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Su C, Huang T, Zhang M, Zhang Y, Zeng Y, Chen X. Glucocorticoid receptor signaling in the brain and its involvement in cognitive function. Neural Regen Res 2025; 20:2520-2537. [PMID: 39248182 PMCID: PMC11801288 DOI: 10.4103/nrr.nrr-d-24-00355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/07/2024] [Accepted: 07/06/2024] [Indexed: 09/10/2024] Open
Abstract
The hypothalamic-pituitary-adrenal axis regulates the secretion of glucocorticoids in response to environmental challenges. In the brain, a nuclear receptor transcription factor, the glucocorticoid receptor, is an important component of the hypothalamic-pituitary-adrenal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity. The glucocorticoid receptor influences cognitive processes, including glutamate neurotransmission, calcium signaling, and the activation of brain-derived neurotrophic factor-mediated pathways, through a combination of genomic and non-genomic mechanisms. Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor, thereby affecting the hypothalamic-pituitary-adrenal axis and stress-related cognitive functions. An appropriate level of glucocorticoid receptor expression can improve cognitive function, while excessive glucocorticoid receptors or long-term exposure to glucocorticoids may lead to cognitive impairment. Patients with cognitive impairment-associated diseases, such as Alzheimer's disease, aging, depression, Parkinson's disease, Huntington's disease, stroke, and addiction, often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression. This review provides a comprehensive overview of the functions of the glucocorticoid receptor in the hypothalamic-pituitary-adrenal axis and cognitive activities. It emphasizes that appropriate glucocorticoid receptor signaling facilitates learning and memory, while its dysregulation can lead to cognitive impairment. This provides clues about how glucocorticoid receptor signaling can be targeted to overcome cognitive disability-related disorders.
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Affiliation(s)
- Chonglin Su
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Taiqi Huang
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Meiyu Zhang
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Yanyu Zhang
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Yan Zeng
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
| | - Xingxing Chen
- Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
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2
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Martinez MX, Mahler SV. Potential roles for microglia in drug addiction: Adolescent neurodevelopment and beyond. J Neuroimmunol 2025; 404:578600. [PMID: 40199197 DOI: 10.1016/j.jneuroim.2025.578600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 03/14/2025] [Accepted: 03/27/2025] [Indexed: 04/10/2025]
Abstract
Adolescence is a sensitive period for development of addiction-relevant brain circuits, and it is also when people typically start experimenting with drugs. Unfortunately, such substance use may cause lasting impacts on the brain, and might increase vulnerability to later-life addictions. Microglia are the brain's immune cells, but their roles in shaping neural connectivity and synaptic plasticity, especially in developmental sensitive periods like adolescence, may also contribute to addiction-related phenomena. Here, we overview how drugs of abuse impact microglia, and propose that they may play poorly-understood, but important roles in addiction vulnerability and progression.
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Affiliation(s)
- Maricela X Martinez
- Department of Neurobiology and Behavior, University of California, 2221 McGaugh Hall, Irvine, CA 92697, USA.
| | - Stephen V Mahler
- Department of Neurobiology and Behavior, University of California, 2221 McGaugh Hall, Irvine, CA 92697, USA
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3
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Cornejo NE, McNeely EC, Yates TQ, Kaneko M, Leong KC. Oxytocin attenuates yohimbine-induced responding for oral oxycodone under a progressive ratio schedule in male and female rats. Behav Brain Res 2025; 488:115598. [PMID: 40268056 DOI: 10.1016/j.bbr.2025.115598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 04/07/2025] [Accepted: 04/18/2025] [Indexed: 04/25/2025]
Abstract
Opioid Use Disorder (OUD) has become an epidemic in the United States, with oxycodone (OXY) being one of the most widely misused opioids. Stress plays a key role in triggering opioid use, which can lead to addiction and relapse, underscoring the urgent need for effective therapeutic interventions. Recent studies suggest that the neuropeptide oxytocin (OXT) may reduce addiction-related behaviors and possess anxiolytic properties. The present study investigates the effect of peripheral administration of OXT on attenuating stress-induced motivation to seek oral OXY, as measured by progressive ratio (PR) responding in both male and female rats. Animals were first trained in an operant conditioning paradigm to orally self-administer a sucrose solution by pressing an active lever for access to the solution. As responding stabilized, subjects were switched to an OXY-sucrose solution, with sucrose concentration reduced overtime, until subjects were self-administering oral OXY alone. To test the effect of stress on OXY responding the pharmacological stressor, yohimbine (YOH), was administered prior to a progressive ratio test in which animals were required to produce increasingly higher responses to receive a single exposure to OXY. Through a within subjects design, when OXT was concurrently administered, this YOH-induced enhancement of OXY reward strength was attenuated in both male and female rats. These results suggest that OXT may serve as a potential therapeutic remedy to mitigate the deleterious effects of stress on OXY addiction in both sexes.
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Affiliation(s)
- Natalie E Cornejo
- Department of Psychology, Trinity University, San Antonio, TX 78212, USA
| | | | - Taylor Q Yates
- Department of Psychology, Trinity University, San Antonio, TX 78212, USA
| | - Moe Kaneko
- Department of Psychology, Trinity University, San Antonio, TX 78212, USA
| | - Kah-Chung Leong
- Department of Psychology, Trinity University, San Antonio, TX 78212, USA.
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4
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Sommer WH, Canals S. Alcohol-Induced Changes in Brain Microstructure: Uncovering Novel Pathophysiological Mechanisms of AUD Using Translational DTI in Humans and Rodents. Curr Top Behav Neurosci 2025. [PMID: 40360929 DOI: 10.1007/7854_2025_585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
Alcohol use disorder (AUD) induces significant structural alterations in both gray and white matter, contributing to cognitive and functional impairments. This chapter presents a translational neuroimaging approach using diffusion-weighted MRI in humans and rodents to uncover novel pathophysiological mechanisms underlying AUD. Our studies demonstrate that increased mean diffusivity (MD) in gray matter reflects microglial reactivity and reduced extracellular space tortuosity, leading to enhanced volume neurotransmission. In white matter, fractional anisotropy (FA) reductions indicate progressive deterioration of key tracts, particularly the fimbria/fornix, linked to impaired cognitive flexibility. Importantly, longitudinal analyses reveal that white matter degeneration continues during early abstinence, suggesting that neuroinflammation and demyelination persist beyond alcohol cessation. Finally, we discuss how neuromodulatory interventions, such as transcranial magnetic stimulation (TMS), may promote recovery by enhancing myelin plasticity. These findings provide crucial insights into AUD's neurobiological underpinnings and highlight potential therapeutic targets for improving treatment outcomes.
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Affiliation(s)
- Wolfgang H Sommer
- Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- German Center for Mental Health (DZPG), partner site Mannheim/Heidelberg/Ulm, Mannheim, Germany.
| | - Santiago Canals
- Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Miguel Hernandez (UMH), Sant Joan d'Alacant, Spain.
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5
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Kirsch D, Nemeroff CM, Lippard ETC. Early Life Stress and Substance Use Disorders: Underlying Neurobiology and Pathways to Adverse Outcomes. FOCUS (AMERICAN PSYCHIATRIC PUBLISHING) 2025; 23:221-238. [PMID: 40235604 PMCID: PMC11995910 DOI: 10.1176/appi.focus.25023013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/17/2025]
Abstract
Early life stress (ELS) has been established as a major risk factor for a multitude of psychiatric and medical disorders. ELS is highly prevalent in the general population and constitutes a major public health concern. The current review will focus on the clinical literature that suggests a link between adverse early life experiences and vulnerability for adolescent and adult substance use disorders. It will investigate the characteristics of ELS that appear to increase risk for disorder onset and a more severe disease course, characterized by earlier onset, greater risk of relapse, and treatment resistance. The authors explore how ELS may increase risk for adverse substance use outcomes through long-lasting changes in the HPA axis and development of stress, reward, and executive control brain systems. The review will also discuss potential pathways to substance use disorder following ELS, with a focus on the role of comorbid mood and anxiety disorders and other modifiable traits. Finally, the authors will discuss how the current body of work presents the potential for prevention and intervention strategies to reduce the psychosocial consequences following early life stress and minimize adverse substance use outcomes. Reprinted from Advers Resil Sci 2020; 1:29-47, with permission from Springer. Copyright © 2020.
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Affiliation(s)
- Dylan Kirsch
- Department of Psychiatry, Dell Medical School, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Institute for Neuroscience, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Department of Psychology, University of Texas, Austin, TX, USA (Lippard); Institute of Early Life Adversity Research, University of Texas, Austin, TX, USA (Nemeroff, Lippard); Mulva Clinic for Neuroscience, Dell Medical School, University of Texas, Austin, TX, USA (Nemeroff, Lippard)
| | - Charles M Nemeroff
- Department of Psychiatry, Dell Medical School, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Institute for Neuroscience, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Department of Psychology, University of Texas, Austin, TX, USA (Lippard); Institute of Early Life Adversity Research, University of Texas, Austin, TX, USA (Nemeroff, Lippard); Mulva Clinic for Neuroscience, Dell Medical School, University of Texas, Austin, TX, USA (Nemeroff, Lippard)
| | - Elizabeth T C Lippard
- Department of Psychiatry, Dell Medical School, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Institute for Neuroscience, University of Texas, Austin, TX, USA (Kirsch, Nemeroff, Lippard); Department of Psychology, University of Texas, Austin, TX, USA (Lippard); Institute of Early Life Adversity Research, University of Texas, Austin, TX, USA (Nemeroff, Lippard); Mulva Clinic for Neuroscience, Dell Medical School, University of Texas, Austin, TX, USA (Nemeroff, Lippard)
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Smith MD, Wesselbaum D. Global evidence on the prevalence of and risk factors associated with stress. J Affect Disord 2025; 374:179-183. [PMID: 39805499 DOI: 10.1016/j.jad.2025.01.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 01/07/2025] [Accepted: 01/09/2025] [Indexed: 01/16/2025]
Abstract
BACKGROUND Stress is a major public health issue linked to physical and mental health disorders, economic burdens, and social challenges. Understanding its prevalence and determinants across demographic and economic groups is essential for effective intervention. METHODS This study uses data from the Gallup World Poll, with over 300,000 participants across 131 countries. We apply linear probability regression models to examine the relationships between stress and factors such as demographics, socioeconomic status, and health. RESULTS Overall, 35.1 % of respondents report experiencing stress, with higher prevalence among females (36.1 %) compared to males (33.6 %) (p < .001). Stress is more common in high-income countries (36 %) than in low- and middle-income countries, but differences are small (2.3 percentage points). Key stress correlates include income instability (p < .01), health issues (p < .01), and food insecurity (p < .01). Gender differences are pronounced in high-income countries, where women report more stress. CONCLUSIONS Addressing stress requires gender-sensitive interventions and economic policies that target income stability and job creation. Tailored programs can mitigate the health impacts of stress, reduce health disparities, and support progress toward UN SDG 3 on health and well-being.
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Affiliation(s)
- Michael D Smith
- U.S.G.A.O. U.S. Government Accountability Office, Applied Research and Methods, Center for Economics, Washington, DC, USA..
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Michael A, Onisiforou A, Georgiou P, Koumas M, Powels C, Mammadov E, Georgiou AN, Zanos P. (2R,6R)-hydroxynorketamine prevents opioid abstinence-related negative affect and stress-induced reinstatement in mice. Br J Pharmacol 2025. [PMID: 40155780 DOI: 10.1111/bph.70018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/09/2025] [Accepted: 02/05/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND AND PURPOSE Opioid use disorder (OUD) is a pressing public health concern marked by frequent relapse during periods of abstinence, perpetuated by negative affective states. Classical antidepressants or the currently prescribed opioid pharmacotherapies have limited efficacy to reverse the negative affect or prevent relapse. EXPERIMENTAL APPROACH Using mouse models, we investigated the effects of ketamine's metabolite (2R,6R)-hydroxynorketamine (HNK) on reversing conditioning to sub-effective doses of morphine in stress-susceptible mice, preventing conditioned-place aversion and alleviating acute somatic abstinence symptoms in opioid-dependent mice. Additionally, we evaluated its effects on anhedonia, anxiety-like behaviours and cognitive impairment during protracted opioid abstinence, while mechanistic studies examined cortical EEG oscillations and synaptic plasticity markers. KEY RESULTS (2R,6R)-HNK reversed conditioning to sub-effective doses of morphine in stress-susceptible mice and prevented conditioned-place aversion and acute somatic abstinence symptoms in opioid-dependent mice. In addition, (2R,6R)-HNK reversed anhedonia, anxiety-like behaviours and cognitive impairment emerging during protracted opioid abstinence plausibly via a restoration of impaired cortical high-frequency EEG oscillations, through a GluN2A-NMDA receptor-dependent mechanism. Notably, (2R,6R)-HNK facilitated the extinction of opioid conditioning, prevented stress-induced reinstatement of opioid-seeking behaviours and reduced the propensity for enhanced morphine self-consumption in mice previously exposed to opioids. CONCLUSIONS AND IMPLICATIONS These findings emphasize the therapeutic potential of (2R,6R)-HNK, which is currently in Phase II clinical trials, in addressing stress-related opioid responses. Reducing the time and cost required for development of new medications for the treatment of OUDs via drug repurposing is critical due to the opioid crisis we currently face.
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Affiliation(s)
- Andria Michael
- Department of Psychology, University of Cyprus, Nicosia, Cyprus
- Center for Applied Neuroscience (CAN), University of Cyprus, Nicosia, Cyprus
| | - Anna Onisiforou
- Department of Psychology, University of Cyprus, Nicosia, Cyprus
- Center for Applied Neuroscience (CAN), University of Cyprus, Nicosia, Cyprus
| | - Polymnia Georgiou
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA
| | - Morfeas Koumas
- Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus
| | - Chris Powels
- Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, Maryland, USA
| | - Elmar Mammadov
- Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, Maryland, USA
| | - Andrea N Georgiou
- Department of Psychology, University of Cyprus, Nicosia, Cyprus
- Center for Applied Neuroscience (CAN), University of Cyprus, Nicosia, Cyprus
| | - Panos Zanos
- Department of Psychology, University of Cyprus, Nicosia, Cyprus
- Center for Applied Neuroscience (CAN), University of Cyprus, Nicosia, Cyprus
- Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, Maryland, USA
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Gugula A, Sambak P, Trenk A, Drabik S, Nogaj A, Soltys Z, Gundlach AL, Blasiak A. Early-life adversity alters adult nucleus incertus neurons: implications for neuronal mechanisms of increased stress and compulsive behavior vulnerability. Neuropsychopharmacology 2025:10.1038/s41386-025-02089-0. [PMID: 40114019 DOI: 10.1038/s41386-025-02089-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 02/27/2025] [Accepted: 03/07/2025] [Indexed: 03/22/2025]
Abstract
Early-life stress (ELS) arising from physical and emotional abuse disrupts normal brain development and impairs hypothalamic-pituitary-adrenal axis function, increasing the risk of psychopathological disorders and compulsive behaviors in adulthood. However, the underlying neural mechanisms remain unclear. The brainstem nucleus incertus (NI) is a highly stress-sensitive locus, involved in behavioral activation and stress-induced reward (food/alcohol) seeking, but its sensitivity to ELS remains unexplored. We used neonatal maternal separation stress in rats as a model for ELS and examined its impact on stress-related mRNA and neuropeptide expression in the NI, using fluorescent in situ hybridization and immunohistochemistry, respectively. Using whole-cell, patch-clamp recordings we determined the influence of ELS on the synaptic activity, excitability, and electrophysiological properties of NI neurons. Using c-Fos protein expression we also assessed the impact of ELS on the sensitivity of NI neurons to acute restraint stress in adulthood. ELS weakened the acute stress responsiveness of NI neurons, and caused dendritic shrinkage, impaired synaptic transmission and altered electrophysiological properties of NI neurons in a cell-type-specific manner. Additionally, ELS increased the expression of mRNA encoding corticotropin-releasing hormone receptor type 1 and the nerve-growth factor receptor, TrkA in adult NI. The multiple, cell-type specific changes in the expression of neuropeptides and molecules associated with stress and substance abuse in the NI, as well as impairments in NI neuron morphology and electrophysiology caused by ELS and observed in the adult brain, may contribute to the increased susceptibility to stress and compulsive behaviors observed in individuals with a history of ELS.
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Affiliation(s)
- Anna Gugula
- Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, Poland.
| | - Patryk Sambak
- Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, Poland
- Doctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland
| | - Aleksandra Trenk
- Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, Poland
| | - Sylwia Drabik
- Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, Poland
- Doctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland
| | - Aleksandra Nogaj
- Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, Poland
- Doctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland
| | - Zbigniew Soltys
- Laboratory of Experimental Neuropathology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, Poland
| | - Andrew L Gundlach
- The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, and Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia
| | - Anna Blasiak
- Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, Poland.
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Muchomba FM, Teitler JO, Fox C, Reichman NE. Racialized Police Use of Force and Maternal Health. Am J Prev Med 2025; 68:535-544. [PMID: 39617107 DOI: 10.1016/j.amepre.2024.11.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 01/12/2025]
Abstract
INTRODUCTION There are large racial disparities in maternal health that cannot be explained by education, income, or other individual-level risk factors. This cross-sectional study estimated associations between racial inequity in police use of force at the community level and health outcomes of Black and White women. METHODS Birth records were linked to maternal hospital discharge records and municipal police department data for 326,240 births occurring between January 1, 2012, and December 31, 2016, to Black and White women in the state of New Jersey. Outcomes, identified using diagnosis and procedure codes, were substance use (any/tobacco/alcohol/other), mental health disorders (any/depression/anxiety/other), asthma, obesity, hypertension (pre-existing/gestational), diabetes (pre-existing/gestational), severe maternal morbidity, other cardiovascular diseases, and preterm labor. Data were analyzed in 2024. RESULTS For Black women, living in a community with 1% greater racially-disproportionate police use of force was associated with higher odds of any mental health disorder (by 0.18%; 95% CI=0.08, 0.28), depression (0.19%; 95% CI=0.05, 0.33), anxiety (0.25%; 95% CI=0.09, 0.41), other mental health disorder (0.17%; 95% CI=0.07, 0.27), any substance use (0.26%; 95% CI=0.14, 0.38), tobacco use (0.31%; 95% CI=0.16, 0.46), other substance use (0.17%; 95% CI=0.04, 0.30), asthma (0.12%; 95% CI=0.04, 0.21), and preterm labor (0.17%; 95% CI=0.05, 0.29) in adjusted models. There were no robust associations with the other outcomes for Black women or with any of the outcomes for White women. CONCLUSIONS Racially-disproportionate police use of force was significantly associated with mental illness, substance use, asthma, and preterm labor of Black women. Results underscore the potential importance of institutionalized racism as a fundamental cause of health disparities.
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Affiliation(s)
- Felix M Muchomba
- Rutgers, The State University of New Jersey, New Brunswick, New Jersey.
| | | | - Carolyn Fox
- Rutgers University, Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Nancy E Reichman
- Rutgers University, Robert Wood Johnson Medical School, New Brunswick, New Jersey
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10
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Perry TW, Carvour HM, Reichert AN, Sneddon EA, Roemer CAEG, Gao YY, Schuh KM, Shand NA, Quinn JJ, Radke AK. Early life stress paired with adolescent alcohol consumption reduces two-bottle choice alcohol consumption in mice. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2025; 49:678-691. [PMID: 39887902 PMCID: PMC11926665 DOI: 10.1111/acer.70004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 01/15/2025] [Indexed: 02/01/2025]
Abstract
BACKGROUND In humans, early life stress (ELS) is associated with an increased risk for developing both alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). We previously used an infant footshock model in rats that produces stress-enhanced fear learning (SEFL) and increases aversion-resistant alcohol drinking to explore this shared predisposition. The goal of the current study was to test the viability of this procedure as a model of comorbid PTSD and AUD in male and female C57BL/6J mice. METHODS Acute ELS was induced using 15 footshocks on postnatal day (PND) 17. In adulthood, alcohol drinking behavior was tested in one of three two-bottle choice drinking paradigms. In continuous access, mice were given 24 h access to 5% and 10% ethanol and water for five consecutive drinking sessions each. In limited access drinking in the dark, mice were given 2 h of access to 15% ethanol and water across 15 sessions 3 h into the dark cycle. In intermittent access, mice were presented with 20% ethanol and water Monday, Wednesday, and Friday, for four consecutive weeks. In a fifth week of intermittent access drinking, increasing concentrations of quinine (10, 100, and 200 mg/L) were added to the ethanol to test aversion-resistant drinking. Intermittent access drinking was tested with and without a period of adolescent drinking (PND 35). RESULTS Infant footshock did not alter drinking in the continuous or limited access tasks. In the intermittent access task, adult consumption and preference were lower in shocked mice when adolescent drinking was included. Aversion resistance was greater in females following infant footshock and adolescent drinking. CONCLUSIONS Our results demonstrate that ELS, in the form of infant footshock on PND 17, must be followed by a period of adolescent drinking to affect adult alcohol consumption in mice.
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Affiliation(s)
- Thomas W. Perry
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
| | - Harrison M. Carvour
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
| | - Amanda N. Reichert
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
| | - Elizabeth A. Sneddon
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
| | | | - Ying Ying Gao
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
| | - Kristen M. Schuh
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
| | - Natalie A. Shand
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
| | - Jennifer J. Quinn
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
| | - Anna K. Radke
- Department of Psychology and Center for Neuroscience and BehaviorMiami UniversityOxfordOhioUSA
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11
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Amano Y, Koizumi K, Takizawa H, Tasaka S, Hamaguchi T. Effectiveness of Attentional Bias Modification Combined With Cognitive Behavioral Therapy in Reducing Relapse Risk and Cravings in Male Patients With Alcohol Use Disorder: A Quasi-Randomized Controlled Trial. Neuropsychopharmacol Rep 2025; 45:e70002. [PMID: 39907051 PMCID: PMC11795173 DOI: 10.1002/npr2.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 01/06/2025] [Accepted: 01/13/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Alcohol use disorder (AUD) is characterized by severe dependence on alcohol, poor impulse control, and heightened attention to alcohol-related cues. Attention bias modification (ABM) retrains individuals to distract attention from alcohol-related cues. This study investigates the effect of combining ABM with cognitive behavioral therapy (CBT) to reduce relapse risk and cravings in male patients with AUD. METHODS A quasi-randomized controlled trial was conducted among male inpatients diagnosed with AUD. Participants were divided into an intervention group receiving ABM in addition to CBT and a control group receiving CBT with a placebo intervention. The primary outcomes-risk of relapse and craving levels-were measured using the Alcohol Relapse Risk Scale (ARRS) and a visual analog scale (VAS), respectively. Participants underwent weekly sessions over 6 weeks, and outcomes were analyzed using generalized linear models (GLMs). RESULTS The analysis did not reveal significant interactions between the intervention group and time for ARRS scores and craving levels. Both groups experienced a reduction in relapse risk and cravings. However, there was no significant difference between the ABM + CBT and CBT-only groups. CONCLUSIONS Although the combined ABM and CBT intervention did not result in statistically significant reductions in relapse risk and cravings compared to CBT alone, the overall reduction in these outcomes in both groups highlights the effectiveness of CBT in treating AUD. Future studies should use naturalistic settings and tailor the intervention to individual cognitive profiles.
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Affiliation(s)
- Yoshifumi Amano
- Narimasu Kousei HospitalItabashi WardTokyoJapan
- Department of Rehabilitation, Graduate School of Health ScienceSaitama Prefectural UniversityKoshigaya CitySaitama PrefectureJapan
| | - Kohei Koizumi
- Department of Rehabilitation, Graduate School of Health ScienceSaitama Prefectural UniversityKoshigaya CitySaitama PrefectureJapan
| | - Hirokazu Takizawa
- Department of Rehabilitation, Graduate School of Health ScienceSaitama Prefectural UniversityKoshigaya CitySaitama PrefectureJapan
| | - Shota Tasaka
- Department of Rehabilitation, Graduate School of Health ScienceSaitama Prefectural UniversityKoshigaya CitySaitama PrefectureJapan
| | - Toyohiro Hamaguchi
- Department of Rehabilitation, Graduate School of Health ScienceSaitama Prefectural UniversityKoshigaya CitySaitama PrefectureJapan
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12
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Munroe C, Surace A, Martinez P. "My Health Is More Important than Drinking": A Qualitative Analysis of Alcohol Use During COVID-19. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2025; 22:224. [PMID: 40003450 PMCID: PMC11855319 DOI: 10.3390/ijerph22020224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/24/2025] [Accepted: 01/31/2025] [Indexed: 02/27/2025]
Abstract
(1) Background: Although alcohol use increased overall in the US during the COVID-19 pandemic, approximately 16% of people decreased their drinking. Understanding reasons for decreasing or discontinuing alcohol use during a time of crisis could inform alcohol messaging during future crises. (2) Methods: We conducted hour-long interviews with 26 participants who reported drinking above NIAAA guidelines at the second wave of the National Alcohol Survey COVID Cohort (a longitudinal study of alcohol use during the COVID-19 pandemic). Data were analyzed using codebook thematic analysis. (3) Results: Many participants reported decreasing use after a period of heavy drinking. Four themes emerged as reasons for doing so: (1) health conditions attributed to or worsened by drinking, (2) concerns about developing the same alcohol problems as a family member, (3) life demands and transitions that limited drinking opportunities, and (4) disliking the side- and after-effects of drinking (e.g., hangovers). (4) Conclusions: Concerns about negative health consequences from heavy alcohol use and limited opportunities to use alcohol due to competing life demands were salient reasons for reducing or abstaining from alcohol use during COVID-19. Incorporating themes about health and life obligations into messaging to reduce alcohol use during crises may improve message relevance.
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Affiliation(s)
- Cat Munroe
- Department of Psychology, Purchase College SUNY, Purchase, NY 10577, USA
- Alcohol Research Group, Public Health Institute, Emeryville, CA 94608, USA; (A.S.); (P.M.)
| | - Anthony Surace
- Alcohol Research Group, Public Health Institute, Emeryville, CA 94608, USA; (A.S.); (P.M.)
- School of Public Health, University of California, Berkeley, Berkeley, CA 94720, USA
| | - Priscilla Martinez
- Alcohol Research Group, Public Health Institute, Emeryville, CA 94608, USA; (A.S.); (P.M.)
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13
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Hinds NM, Wojtas ID, Pulley DM, McDonald SJ, Spencer CD, Sudarikov M, Hubbard NE, Kulick-Soper CM, de Guzman S, Hayden S, Debski JJ, Patel B, Fox DP, Manvich DF. Fos expression in the periaqueductal gray, but not the ventromedial hypothalamus, is correlated with psychosocial stress-induced cocaine-seeking behavior in rats. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.22.634146. [PMID: 39896664 PMCID: PMC11785129 DOI: 10.1101/2025.01.22.634146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Psychosocial stressors are known to promote cocaine craving and relapse in humans but are infrequently employed in preclinical relapse models. Consequently, the underlying neural circuitry by which these stressors drive cocaine seeking has not been thoroughly explored. Using Fos expression analyses, we sought to examine whether the ventromedial hypothalamus (VMH) or periaqueductal gray (PAG), two critical components of the brain's hypothalamic defense system, are activated during psychosocial stress-induced cocaine seeking. Adult male and female rats self-administered cocaine (0.5 mg/kg/inf IV, fixed-ratio 1 schedule, 2 h/session) over 20 sessions. On sessions 11, 14, 17, and 20, a tactile cue was present in the operant chamber that signaled impending social defeat stress (n=16, 8/sex), footshock stress (n=12, 6/sex), or a no-stress control condition (n=12, 6/sex) immediately after the session's conclusion. Responding was subsequently extinguished, and rats were tested for reinstatement of cocaine seeking during re-exposure to the tactile cue that signaled their impending stress/no-stress post-session event. All experimental groups displayed significant reinstatement of cocaine seeking, but Fos analyses indicated that neural activity within the rostrolateral PAG (rPAGl) was selectively correlated with cocaine-seeking magnitude in the socially-defeated rats. rPAGl activation was also associated with active-defense coping behaviors during social defeat encounters and with Fos expression in prelimbic prefrontal cortex and orexin-negative cells of the lateral hypothalamus/perifornical area in males, but not females. These findings suggest a potentially novel role for the rPAGl in psychosocial stress-induced cocaine seeking, perhaps in a sex-dependent manner.
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Affiliation(s)
- Nicole M. Hinds
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Ireneusz D. Wojtas
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Desta M. Pulley
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Stephany J. McDonald
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Colton D. Spencer
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Milena Sudarikov
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Nicole E. Hubbard
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Colin M. Kulick-Soper
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Samantha de Guzman
- College of Liberal Arts, Temple University, 1114 West Berks Street, Philadelphia, PA 19122
| | - Sara Hayden
- College of Liberal Arts, Temple University, 1114 West Berks Street, Philadelphia, PA 19122
| | - Jessica J. Debski
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Bianca Patel
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Douglas P. Fox
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
| | - Daniel F. Manvich
- Department of Cell Biology and Neuroscience, Rowan-Virtua School of Osteopathic Medicine, 42 East Laurel Road, Suite 2200, Stratford, NJ 08084
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14
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Floyd LJ, Brown K. Perceived neighborhood disorder as a moderator of the relationship between marijuana use and disinhibition in a sample of emerging adult African American females. J Ethn Subst Abuse 2025; 24:188-202. [PMID: 37270673 PMCID: PMC10694336 DOI: 10.1080/15332640.2023.2195691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Disinhibition is associated with myriad risk-taking behaviors and adverse outcomes. Both marijuana use and poor neighborhood conditions have been associated with disinhibition. However, the extent to which neighborhood disorder interacts with marijuana use to influence disinhibition has not been studied, extensively. A better understanding of these relationships has implications for designing more effective tailored place-based interventions that aim to reduce risk taking behaviors and related adverse social and health outcomes associated with marijuana use. Thus, the purpose of this study was to examine the interactive effects of perceived neighborhood disorder and marijuana use on disinhibition. The sample included 120 African American female residents of disadvantaged neighborhoods (Mage = 23.6 ± 3.46). We employed hierarchical linear regression analysis to examine the interactive effects of marijuana use and perceived neighborhood disorder on disinhibition, while controlling for age and education. The interaction term was marginally significant (b = 5.66; t(109) = 1.72, p = .08). Next, the conditional effects were explored. Results indicated the association of marijuana use with disinhibition was stronger for females in the higher neighborhood disorder group, compared to those in the lower neighborhood disorder group (10.40 and 4.51, respectively). Our findings support the need for more research on the potential of neighborhood disorder to amplify the effects of marijuana use on disinhibition and related neurobehavioral traits. The identification of contextual moderators and high-risk sub-groups will aid in the design of more tailored place-based interventions that aim to reduce risk-taking behavior among those most vulnerable.
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15
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Buttrick N, Yang S, Okada S. Mass shootings durably increase the sale of alcohol in American communities. PNAS NEXUS 2025; 4:pgae570. [PMID: 39840222 PMCID: PMC11748128 DOI: 10.1093/pnasnexus/pgae570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 11/20/2024] [Indexed: 01/23/2025]
Abstract
Mass shootings are devastating events. Communities can cope with the ensuing trauma in a number of ways, including changing their behavioral patterns. Using point-of-sale data from 35,000 individual retailers, including more than half of all American grocery and drugstore purchases, and all American mass shootings from 2006 to 2019, we find, in a set of two-way fixed-effects counterfactual analyses, that a mass shooting in a given community (the area covered by the ZIP-3 code) predicts a significant increase in the sales of alcohol that lasts at least 2 years past the shooting. The effect is especially strong for the subset of mass shootings that take place in public settings, whereas we find no evidence for an increase in alcohol sales in the aftermath of mass shootings that take place in private homes or residences. As alcohol is an accelerant for violence, especially firearm-related violence, we suggest the importance of whole-community approaches to addressing the trauma of mass shootings.
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Affiliation(s)
- Nicholas Buttrick
- Department of Psychology, University of Wisconsin-Madison, 1202 W Johnson St, Madison, WI 53706, USA
| | - Shiyu Yang
- Department of Psychology, University of Wisconsin-Madison, 1202 W Johnson St, Madison, WI 53706, USA
| | - Sosuke Okada
- Department of Psychology, University of Wisconsin-Madison, 1202 W Johnson St, Madison, WI 53706, USA
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16
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Morel C, Parise LF, Van der Zee YY, Issler O, Cai M, Browne CJ, Blando A, LeClair KB, Aubry AV, Haynes S, Williams RW, Mulligan MK, Russo SJ, Nestler EJ, Han MH. Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure. Sci Rep 2024; 14:30785. [PMID: 39730457 PMCID: PMC11680947 DOI: 10.1038/s41598-024-80767-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 11/21/2024] [Indexed: 12/29/2024] Open
Abstract
Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions-specifically gene x chronic stress-here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J. Utilizing the chronic social defeat stress (CSDS) and chronic variable stress (CVS) paradigms, we first showed sexual dimorphism in social and exploratory behaviors between the mouse strains. Further, we observed an interaction between genetic background and vulnerability to prolonged exposure to non-social stressors. Finally, we found that DBA/2J and C57BL/6J mice pre-exposed to stress displayed differences in morphine sensitivity. Our results support the hypothesis that genetic variation influences chronic stress-induced behavioral outcomes such as social and approach-avoidance behaviors, reward responses, as well as morphine sensitivity, and is likely to modulate the development of drug addiction.
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Affiliation(s)
- Carole Morel
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Lyonna F Parise
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Yentl Y Van der Zee
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Orna Issler
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Min Cai
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Caleb J Browne
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Anthony Blando
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Katherine B LeClair
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Antonio V Aubry
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sherod Haynes
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Robert W Williams
- Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Megan K Mulligan
- Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Scott J Russo
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Eric J Nestler
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Ming-Hu Han
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Friedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology (SIAT), and Department of Mental Health and Public Health, Faculty of Life and Health Sciences, Shenzhen University of Advanced Technology (SUAT), Chinese Academy of Sciences, Shenzhen, Guangdong, People's Republic of China.
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17
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de Ternay J, Nohales L, Fort E, Pelloux S, Coste C, Leblanc P, Wallon M, Fassier JB, Rolland B. Impact of Working Conditions and Other Determinants on the Risk of Substance Misuse among Healthcare Residents: Results of a Cross-Sectional Study. Eur Addict Res 2024; 30:390-401. [PMID: 39631377 DOI: 10.1159/000542592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/29/2024] [Indexed: 12/07/2024]
Abstract
INTRODUCTION Substance misuse significantly impairs psychosocial functioning and correlates with many environmental factors, including working conditions. We investigated the influence of working conditions and other determinants on the risk of substance misuse among healthcare residents of Lyon, France. METHODS We conducted an online survey among medicine, dentistry and pharmacy residents of Lyon from May 30, 2022, to July 15, 2022. Participants reported their age, sex, residency specialty, and living conditions and completed the French Job Content Questionnaire, the Alcohol Use Disorder Identification Test - consumption, and questions exploring their current tobacco, alcohol, and illicit drug use. We constructed directed acyclic graphs to model the effect of working conditions on substance misuse and used them to perform multivariable logistic regressions. RESULTS Among the 1,936 residents of the Lyon subdivision, 904 (46.7%) completed the survey. Among these, 54.0% exhibited alcohol misuse, 23.7% reported tobacco misuse, and 34.5% reported illicit drug misuse. Working more than 48 h per week was not associated with any substance misuse. Low social support at work predicted the use of illicit drugs (aOR: 1.49, 95% CI: [1.04; 2.13]). Compared with general medicine residents, psychiatric residents had greater odds of reporting tobacco misuse (aOR: 2.28, 95% CI: [1.14; 4.58]) and illicit drug misuse (aOR: 2.51, 95% CI: [1.33; 4.74]). Pediatric and pharmacy residents had lower odds of reporting alcohol misuse (aOR: 0.42, 95% CI: [0.21; 0.84] and OR: 0.53, 95% CI: [0.28; 0.98], respectively). CONCLUSIONS Social support at work significantly impacts the risk of substance misuse among healthcare residents, as do other factors, such as residents' health specialty. These findings contribute to the development of appropriate institutional policies and support programs to improve the well-being of healthcare residents.
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Affiliation(s)
- Julia de Ternay
- Service Universitaire d'Addictologie de Lyon (SUAL), Groupement Hospitalier Centre, Hospices Civils de Lyon, Lyon, France
- Research on Healthcare Performance (RESHAPE), INSERM U1290, University Claude Bernard Lyon 1, Lyon, France
| | - Ludivine Nohales
- Occupational Health Unit - CRPPE, Groupement Hospitalier Centre, Hospices Civils de Lyon, Lyon, France
- University Lyon, University Gustave Eiffel, University Claude Bernard Lyon 1, UMRESTTE UMR T 9405, Lyon, France
| | - Emmanuel Fort
- University Lyon, University Gustave Eiffel, University Claude Bernard Lyon 1, UMRESTTE UMR T 9405, Lyon, France
| | - Sophie Pelloux
- Service de Santé Universitaire (SSU), University Claude Bernard Lyon 1, Lyon, France
| | - Clio Coste
- Department of Radiotherapy, University Claude Bernard Lyon 1, Lyon, France
- Department of Radiotherapy, Léon Bérard Cancer Center, Lyon, France
| | - Pierre Leblanc
- Research on Healthcare Performance (RESHAPE), INSERM U1290, University Claude Bernard Lyon 1, Lyon, France
- Direction Qualité Usagers et Santé Populationnelle, Hospices Civils de Lyon, Lyon, France
| | - Martine Wallon
- Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France
- Waking Team INSERM U1028 - CNRS UMR 5292 CRNL, University Claude Bernard Lyon 1, Bron, France
| | - Jean-Baptiste Fassier
- University Lyon, University Gustave Eiffel, University Claude Bernard Lyon 1, UMRESTTE UMR T 9405, Lyon, France
| | - Benjamin Rolland
- Service Universitaire d'Addictologie de Lyon (SUAL), Groupement Hospitalier Centre, Hospices Civils de Lyon, Lyon, France
- Service Universitaire d'Addictologie de Lyon (SUAL), CH Le Vinatier, Pôle MOPHA, Bron, France
- Inserm U1028, CNRS UMR, CRNL, University Claude Bernard Lyon 1, Bron, France
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18
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Wyckmans F, Chatard A, Kornreich C, Gruson D, Jaafari N, Noël X. Impact of provoked stress on model-free and model-based reinforcement learning in individuals with alcohol use disorder. Addict Behav Rep 2024; 20:100574. [PMID: 39659897 PMCID: PMC11629551 DOI: 10.1016/j.abrep.2024.100574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 11/06/2024] [Accepted: 11/22/2024] [Indexed: 12/12/2024] Open
Abstract
Background From both clinical and theoretical perspectives, understanding the functionality of evaluative reinforcement learning mechanisms (Model-Free, MF, and Model-Based, MB) under provoked stress, particularly in Alcohol Use Disorder (AUD), is crucial yet underexplored. This study aims to evaluate whether individuals with AUD who do not seek treatment show a greater tendency towards retrospective behaviors (MF) rather than prospective and deliberative simulations (MB) compared to controls. Additionally, it examines the impact of induced social stress on these decision-making processes. Methods A cohort comprising 117 participants, including 55 individuals with AUD and 62 controls, was examined. Acute social stress was induced through the socially evaluated cold pressor task (SECPT), followed by engagement in a Two-Step Markov task to assess MB and MF learning tendencies. We measured hypothalamic-pituitary-adrenal axis stress response using salivary cortisol levels. Results Both groups showed similar baseline cortisol levels and responses to the SECPT. Our findings indicate that participants with AUD exhibit a reduced reliance on MB strategies compared to those without AUD. Furthermore, stress decreases reliance on MB strategies in healthy participants, but this effect is not observed in those with AUD. Conclusion An atypical pattern of stress modulation impacting the balance between MB and MF reinforcement learning was identified in individuals with AUD who are not seeking treatment. Potential explanations for these findings and their clinical implications are explored.
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Affiliation(s)
- Florent Wyckmans
- Laboratoire de Psychologie Médicale et d’Addictologie, Université Libre de Bruxelles (ULB), place Van Gehuchten 4, 1020 Brussels, Belgium
| | - Armand Chatard
- Faculty of Psychology, Université de Poitiers, MSHS Bat A5 - 5, rue Théodore Lefebvre, 86073 Poitiers, France
| | - Charles Kornreich
- Laboratoire de Psychologie Médicale et d’Addictologie, Université Libre de Bruxelles (ULB), place Van Gehuchten 4, 1020 Brussels, Belgium
| | - Damien Gruson
- Cliniques Universitaires St-Luc, Av. Hippocrate 10, 1200 Brussels, Belgium
| | - Nemat Jaafari
- Centre Hospitalier Henri Laborit, 370 Avenue Jacques Cœur, Pavillon Toulouse, Université de Poitiers, France
| | - Xavier Noël
- Laboratoire de Psychologie Médicale et d’Addictologie, Université Libre de Bruxelles (ULB), place Van Gehuchten 4, 1020 Brussels, Belgium
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Paliarin F, Duplantis C, Doré E, Basavanhalli S, Weiser E, Jones TW, Maiya R. BLA KOR inputs to the BNST regulate social stress-escalated alcohol consumption. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.11.07.622470. [PMID: 39574601 PMCID: PMC11581013 DOI: 10.1101/2024.11.07.622470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/01/2024]
Abstract
Background Aversive social experiences can lead to escalated drug consumption and increase the risk of relapse to drug seeking. Individuals who consume alcohol to alleviate the effects of social stress are more likely to develop an alcohol use disorder (AUD). Repeated social defeat stress (SDS) enhances the rewarding and reinforcing effects of alcohol. However, the neural mechanisms that underlie social stress-escalated alcohol drinking are not well understood. Here we explored the role of the dynorphin/kappa opioid receptor (Dyn/KOR) system in regulating social stress-escalated alcohol consumption. Methods Male and female mice were subjected to repeated SDS for 10 days following which they were left undisturbed in their home cages. They were then subject to intermittent access (IA) two-bottle choice alcohol consumption procedure. The effects of systemic and BNST-specific KOR antagonism using the selective KOR antagonist NorBNI on stress-escalated drinking were evaluated. Using chemogenetic approaches in Oprk1-Cre mice, we examined the role of KOR expressing cells in the basolateral amygdala (BLA KORs ) and BLA KOR -BNST pathway in social stress-escalated alcohol consumption. Results Repeated SDS increased alcohol consumption and preference in both males and females. Systemic KOR antagonism attenuated SDS-escalated alcohol consumption in both males and females. BNST -specific KOR antagonism also attenuated stress-escalated drinking in males. Finally, selective chemogenetic activation of BLA KORs and BKA KOR -BNST pathway attenuated social stress-escalated alcohol consumption in both sexes. Conclusion Our results suggest a significant role for BLA KOR projections to the BNST in regulating social stress-escalated alcohol consumption. Our results provide further evidence that the Dyn/KOR system maybe a viable target for medications development to tareat comorbid stress and AUD.
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Affiliation(s)
- Franciely Paliarin
- Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112
| | - Chelsea Duplantis
- Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112
| | - Evan Doré
- Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112
| | - Samhita Basavanhalli
- Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112
| | - Emma Weiser
- Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112
| | - Tameka W. Jones
- Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112
| | - Rajani Maiya
- Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112
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20
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Kale S, Lopresti A, Suri R, Garg N, Langade D. Safety and Efficacy of Ashwagandha Root Extract on Cognition, Energy and Mood Problems in Adults: Prospective, Randomized, Placebo-Controlled Study. J Psychoactive Drugs 2024:1-13. [PMID: 39498904 DOI: 10.1080/02791072.2024.2424279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 08/17/2024] [Accepted: 08/19/2024] [Indexed: 11/07/2024]
Abstract
This prospective, randomized, placebo-controlled study assessed the effects of Ashwagandha root extract (ARE) on cognition, energy, and mood in adults with self-reported cognitive and energy problems. Healthy subjects aged 30-75 years were randomized to receive ashwagandha (Withania somnifera) root extract (ARE) 600 mg/day (n = 60)/identical placebo (n = 60) orally for 8 weeks. Cognitive function was assessed at baseline and week 8 using a Computerized Mental Performance Assessment System (COMPASS). Secondary outcomes were Profile of Mood States Abbreviated Version (POMS-A), Mental Fatigue Scale (MFS) and Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) for effects on mood, mental fatigue and executive function, respectively, assessed at baseline, week 4 and 8. Greater improvement (p < .05) from baseline scores were seen with ARE as against placebo for COMPASS items episodic memory, working memory and accuracy of attention. ARE also improved the POMS-A, MFS and BRIEF-A scores from baseline suggesting an improvement in mood, vigor, and an increase in the executive functioning respectively with ARE. The herb was well tolerated and had a good patient compliance with no serious adverse events reported in either of the groups. This study suggests that a dose of 600 mg a day can improve cognition, energy, and mood in adults with self-reported cognitive and energy problems.
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Affiliation(s)
- Sanjiv Kale
- Psychiatry, D Y Patil University School of Medicine, Nerul, Navi Mumbai, Maharashtra, India
| | - Adrian Lopresti
- Clinical Psychology, Clinical Research Australia, Duncraig, WA, Australia
| | - Ravleen Suri
- Psychiatry, D Y Patil University School of Medicine, Nerul, Navi Mumbai, Maharashtra, India
| | - Neha Garg
- Psychiatry, D Y Patil University School of Medicine, Nerul, Navi Mumbai, Maharashtra, India
| | - Deepak Langade
- Pharmacology, D Y Patil University School of Medicine, Nerul, Navi Mumbai, Maharashtra, India
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Meade CS, Towe SL. Accentuate the positive: Cultivating positive affect during treatment for stimulant use disorder can regulate the immune system. Brain Behav Immun 2024; 122:566-567. [PMID: 39218232 DOI: 10.1016/j.bbi.2024.08.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 08/29/2024] [Indexed: 09/04/2024] Open
Affiliation(s)
- Christina S Meade
- Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.
| | - Sheri L Towe
- Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA
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22
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Walker LC, Huckstep KL, Becker HC, Langmead CJ, Lawrence AJ. Targeting muscarinic receptors for the treatment of alcohol use disorders: Opportunities and hurdles for clinical development. Br J Pharmacol 2024; 181:4385-4398. [PMID: 37005377 DOI: 10.1111/bph.16081] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 03/28/2023] [Accepted: 03/30/2023] [Indexed: 04/04/2023] Open
Abstract
Emerging evidence suggests muscarinic acetylcholine receptors represent novel targets to treat alcohol use disorder. In this review, we draw from literature across medicinal chemistry, molecular biology, addiction and learning/cognition fields to interrogate the proposition for muscarinic receptor ligands in treating various aspects of alcohol use disorder, including cognitive dysfunction, motivation to consume alcohol and relapse. In support of this proposition, we describe cholinergic dysfunction in the pathophysiology of alcohol use disorder at a network level, including alcohol-induced adaptations present in both human post-mortem brains and reverse-translated rodent models. Preclinical behavioural pharmacology implicates specific muscarinic receptors, in particular, M4 and M5 receptors, as potential therapeutic targets worthy of further interrogation. We detail how these receptors can be selectively targeted in vivo by the use of subtype-selective allosteric modulators, a strategy that overcomes the issue of targeting a highly conserved orthosteric site bound by acetylcholine. Finally, we highlight the intense pharma interest in allosteric modulators of muscarinic receptors for other indications that provide an opportunity for repurposing into the alcohol use disorder space and provide some currently unanswered questions as a roadmap for future investigation.
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Affiliation(s)
- Leigh C Walker
- Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
- Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
| | - Kade L Huckstep
- Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
- Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
| | - Howard C Becker
- Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
- Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Christopher J Langmead
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
- Neuromedicines Discovery Centre, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Andrew J Lawrence
- Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
- Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
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23
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Schmid AM, Thomas TA, Blümel S, Erdal NK, Müller SM, Merz CJ, Wolf OT, Brand M, Müller A, Steins-Loeber S. Transfer from goal-directed behavior to stimulus-response habits and its modulation by acute stress in individuals with risky gaming behavior. Sci Rep 2024; 14:26015. [PMID: 39472683 PMCID: PMC11522379 DOI: 10.1038/s41598-024-73899-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 09/23/2024] [Indexed: 11/02/2024] Open
Abstract
Habitual responses towards addiction-related cues play a relevant role in the development and maintenance of addictions. Such automatic responses may be more likely under stress, as stress has been shown to induce a shift from goal-directed to habitual behavior. The current study investigated these mechanisms in risky gaming behavior. Individuals with risky gaming behavior (n = 68), as established by a structured clinical interview, and a matched control group (n = 67) completed a Pavlovian-to-Instrumental Transfer (PIT) paradigm with gaming-related cues and rewards. After the Pavlovian training, participants underwent a stress (Trier Social Stress Test) or control condition before performing the instrumental training and the transfer phase of the PIT paradigm. To assess habitual behavior, the gaming-related rewards were devalued after half of the transfer phase. In both groups, gaming-related cues enhanced the choice of the gaming-related reward and this gaming PIT effect was reduced, however, not eliminated by the devaluation. Unexpectedly, stress did not significantly increase responding for the gaming-related reward in participants aware of the stimulus-outcome associations, however seemed to enhance habitual responding in unaware participants. Our findings underline the relevance of gaming-related cues in triggering habitual responses, which may undermine attempts to change a problematic gaming behavior.
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Affiliation(s)
- Anna M Schmid
- Department of Clinical Psychology and Psychotherapy, Otto-Friedrich-University of Bamberg, Bamberg, Germany.
| | - Tobias A Thomas
- Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Stefan Blümel
- Department of Clinical Psychology and Psychotherapy, Otto-Friedrich-University of Bamberg, Bamberg, Germany
| | - Nicolas K Erdal
- Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Silke M Müller
- General Psychology: Cognition, Faculty of Computer Science, University of Duisburg-Essen, Duisburg, Germany
- Center for Behavioral Addiction Research (CeBAR), Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen, Germany
| | - Christian J Merz
- Department of Cognitive Psychology, Institute of Cognitive Neuroscience, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany
| | - Oliver T Wolf
- Department of Cognitive Psychology, Institute of Cognitive Neuroscience, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany
| | - Matthias Brand
- General Psychology: Cognition, Faculty of Computer Science, University of Duisburg-Essen, Duisburg, Germany
- Center for Behavioral Addiction Research (CeBAR), Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen, Germany
| | - Astrid Müller
- Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Sabine Steins-Loeber
- Department of Clinical Psychology and Psychotherapy, Otto-Friedrich-University of Bamberg, Bamberg, Germany
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24
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Clay JM, Badariotti JI, Kozhushko N, Parker MO. HPA activity mediates the link between trait impulsivity and boredom. Physiol Behav 2024; 284:114637. [PMID: 38997097 DOI: 10.1016/j.physbeh.2024.114637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 07/03/2024] [Accepted: 07/09/2024] [Indexed: 07/14/2024]
Abstract
Boredom, a complex emotional state with implications for mental health and well-being, has garnered attention across disciplines, yet remains relatively understudied in psychiatric research. Here, we explored the intricate relationship between trait-impulsivity, stress, and boredom across two studies. Participants completed self-report measures of trait-impulsivity and boredom and boredom-inducing tasks. Study 1, involving 80 participants (42 women and 38 men, aged 20-63), replicates previous findings, by demonstrating that impulsive individuals report greater boredom following a boring task. Study 2 then extends this, using 20 participants (9 women and 12 men, aged 18-24), to show that hypothalamic-pituitary-adrenal (HPA) axis activity, specifically heightened salivary cortisol responses, mediate the link between impulsivity and boredom following a boring task. Collectively, these results demonstrate that HPA axis activity may underline the relationship between trait-impulsivity and boredom by extending previous work and offering a novel insight into potential mechanisms. These findings offer promise for personalised interventions, designed for high impulsivity individuals, to alleviate the negative impacts of boredom and potentially break the identified feedback loop.
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Affiliation(s)
- James M Clay
- Department of Psychology, University of Portsmouth, UK; Canadian Institute for Substance Use Research, University of Victoria, Victoria, Canada; Department of Community Health and Epidemiology, Dalhousie University, Halifax, Canada
| | | | - Nikita Kozhushko
- School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, UK
| | - Matthew O Parker
- Surrey Sleep Research Centre, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
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25
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Kroll SL, Meier P, Mayo LM, Gertsch J, Quednow BB. Endocannabinoids and related lipids linked to social exclusion in individuals with chronic non-medical prescription opioid use. Neuropsychopharmacology 2024; 49:1630-1639. [PMID: 38773316 PMCID: PMC11319498 DOI: 10.1038/s41386-024-01881-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 04/10/2024] [Accepted: 04/29/2024] [Indexed: 05/23/2024]
Abstract
Opioid-related overdose deaths are still on the rise in North America, emphasizing the need to better understand the underlying neurobiological mechanisms regarding the development of opioid use disorder (OUD). Recent evidence from preclinical and clinical studies indicate that the endocannabinoid system (ECS) may play a crucial role in stress and reward, both involved in the development and maintenance of substance use disorders. Animal models demonstrate a specific crosstalk between the ECS and the endogenous opioid system. However, translational studies in humans are scarce. Here, we investigated basal plasma levels of the endocannabinoids anandamide (AEA) and 2-arachidonoyglycerol (2-AG), and eight endocannabinoid-related lipids, including oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), as well as whole blood fatty acid amide hydrolase (FAAH) activity in chronic non-medical prescription opioid users (NMPOU; n = 21) compared to opioid-naïve healthy controls (n = 29) considering age, sex, and cannabis use as potential confounders. Additionally, the association of endocannabinoids and related lipids with the participants' response to experimentally induced social exclusion was examined. We found significantly elevated basal AEA, OEA, and PEA levels in NMPOU compared to controls, but no differences in FAAH activity, 2-AG, or other endocannabinoid-related lipids. Within NMPOU, higher AEA levels were associated with lower perception of social exclusion. Robust positive correlations within N-acylethanolamines (i.e., AEA, OEA, and PEA) indicate strong metabolic associations. Together with our recent findings of elevated basal 2-AG levels in dependent cocaine users, present results indicate substance-specific alterations of the ECS that may have implications in the search for novel therapeutic interventions for these populations.
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Affiliation(s)
- Sara L Kroll
- Social and Affective Neuropsychopharmacology, Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
- Experimental and Clinical Pharmacopsychology, Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
- Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland.
| | - Philip Meier
- Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
| | - Leah M Mayo
- Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, and Department of Psychiatry, University of Calgary, Calgary, AB, Canada
| | - Jürg Gertsch
- Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
| | - Boris B Quednow
- Experimental and Clinical Pharmacopsychology, Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
- Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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26
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Sun C, Li H, Wang X, Shao Y, Huang X, Qi H, Zhang Z, Su G. Self-control as mediator and social support as moderator in stress-relapse dynamics of substance dependency. Sci Rep 2024; 14:19852. [PMID: 39191931 PMCID: PMC11349877 DOI: 10.1038/s41598-024-70884-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 08/22/2024] [Indexed: 08/29/2024] Open
Abstract
Substance Use Disorders (SUDs) present a significant challenge to global public health, with prolonged drug use not only impairing individual health but also hindering social development. Despite various interventions aimed at addressing drug abuse and dependence, a high relapse rate remains a prominent issue. In light of this, this study aims to explore the impact of perceived stress on the relapse of individuals with SUDs, as well as the mediating role of self-control and the moderating role of social support, in hopes of providing new perspectives for interventions to reduce the risk of relapse among individuals with SUDs. By utilizing a convenience sampling method, 420 male individuals with SUDs were recruited from detoxification centers in Guangxi, China. They completed questionnaires on perceived stress, self-control, social support, and tendencies towards relapse. A total of 401 valid datasets were obtained and analyzed using the SPSS Process plugin to conduct a moderated mediation model analysis. Results: (1) Perceived stress had a positive impact on the relapse of individuals with SUDs, (2) Self-control played a partial mediating role between perceived stress and the relapse, (3) The direct effect of perceived stress on the relapse and its first half of the indirect effect were moderated by social support. The research emphasize the critical importance of learning stress management strategies, enhancing self-control, and receiving comprehensive social support in the prevention and treatment of substance dependence. By strengthening self-control and social support as both internal and external resources, the likelihood of relapse among individuals with SUDs can be reduced, contributing to more effective and comprehensive drug rehabilitation strategies.
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Affiliation(s)
- Chao Sun
- School of Psychology, Beijing Sport University, Beijing, 100084, China
| | - Haojie Li
- School of Exercise and Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Xiaojun Wang
- China Wushu School, Beijing Sport University, Beijing, 100084, China.
| | - Yongcong Shao
- School of Psychology, Beijing Sport University, Beijing, 100084, China.
| | - Xuetong Huang
- China Wushu School, Beijing Sport University, Beijing, 100084, China
| | - Huanhuan Qi
- China Wushu School, Beijing Sport University, Beijing, 100084, China
| | - Zhuolin Zhang
- China Wushu School, Beijing Sport University, Beijing, 100084, China
| | - Guobai Su
- Department of Physical Education, Tianjin Medical University, Tianjin, 300070, China.
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27
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Perry TW, Carvour HM, Reichert AN, Sneddon EA, Roemer CAEG, Gao YY, Schuh KM, Shand NA, Quinn JJ, Radke AK. Effects of early life stress paired with adolescent alcohol consumption on two-bottle choice alcohol drinking behaviors in mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.01.21.524642. [PMID: 36711856 PMCID: PMC9882357 DOI: 10.1101/2023.01.21.524642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Background In humans, early life stress (ELS) is associated with an increased risk for developing both alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). We previously used an infant footshock model that produces stress-enhanced fear learning (SEFL) in rats and mice and increases aversion-resistant alcohol drinking in rats to explore this shared predisposition. The goal of the current study was to extend this model of comorbid PTSD and AUD to male and female C57BL/6J mice. Methods Acute ELS was induced using 15 footshocks on postnatal day (PND) 17. In adulthood, alcohol drinking behavior was tested in one of three two-bottle choice drinking paradigms. In continuous access, mice were given 24 h access to 5% or 10% ethanol and water for five consecutive drinking sessions each. In limited access drinking in the dark, mice were given 2 h of access to 15% ethanol and water across 15 sessions 3 h into the dark cycle. In intermittent access, mice were presented with 20% ethanol and water Monday, Wednesday, and Friday, for four consecutive weeks. In a fifth week of intermittent access drinking, increasing concentrations of quinine (10 mg/L, 100 mg/L, and 200 mg/L) were added to the ethanol to test aversion-resistant drinking. Intermittent access drinking was tested with and without a period of adolescent drinking (PND 35). Results Infant footshock did not alter drinking in the continuous or limited access tasks. Adult consumption and preference were lower in the intermittent access task when adolescent drinking was included and there were ELS-induced differences in consumption of quinine-adulterated ethanol in females. Conclusions Our results demonstrate that infant footshock followed by a period of adolescent drinking is a viable model of comorbid PTSD and AUD in rats and mice.
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Affiliation(s)
- Thomas W Perry
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Harrison M Carvour
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Amanda N Reichert
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Elizabeth A Sneddon
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Charlotte A E G Roemer
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Ying Ying Gao
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Kristen M Schuh
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Natalie A Shand
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Jennifer J Quinn
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
| | - Anna K Radke
- Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA
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28
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Sinha R. Stress and substance use disorders: risk, relapse, and treatment outcomes. J Clin Invest 2024; 134:e172883. [PMID: 39145454 PMCID: PMC11324296 DOI: 10.1172/jci172883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2024] Open
Abstract
Stress has long been associated with substance misuse and substance use disorders (SUDs). The past two decades have seen a surge in research aimed at understanding the underlying mechanisms driving this association. This Review introduces a multilevel "adaptive stress response" framework, encompassing a stress baseline, acute reaction, and recovery with return-to-homeostasis phase that occurs at varying response times and across domains of analysis. It also discusses evidence showing the disruption of this adaptive stress response in the context of chronic and repeated stressors, trauma, adverse social and drug-related environments, as well as with acute and chronic drug misuse and with drug withdrawal and abstinence sequelae. Subjective, cognitive, peripheral, and neurobiological disruptions in the adaptive stress response phases and their link to inflexible, maladaptive coping; increased craving; relapse risk; and maintenance of drug intake are also presented. Finally, the prevention and treatment implications of targeting this "stress pathophysiology of addiction" are discussed, along with specific aspects that may be targeted in intervention development to rescue stress-related alterations in drug motivation and to improve SUD treatment outcomes.
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29
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Carreiro S, Ramanand P, Taylor M, Leach R, Stapp J, Sherestha S, Smelson D, Indic P. Evaluation of a digital tool for detecting stress and craving in SUD recovery: An observational trial of accuracy and engagement. Drug Alcohol Depend 2024; 261:111353. [PMID: 38917718 PMCID: PMC11260438 DOI: 10.1016/j.drugalcdep.2024.111353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 05/13/2024] [Accepted: 05/30/2024] [Indexed: 06/27/2024]
Abstract
BACKGROUND Digital health interventions offer opportunities to expand access to substance use disorder (SUD) treatment, collect objective real-time data, and deliver just-in-time interventions: however implementation has been limited. RAE (Realize, Analyze, Engage) Health is a digital tool which uses continuous physiologic data to detect high risk behavioral states (stress and craving) during SUD recovery. METHODS This was an observational study to evaluate the digital stress and craving detection during outpatient SUD treatment. Participants were asked to use the RAE Health app, wear a commercial-grade wrist sensor over a 30-day period. They were asked to self-report stress and craving, at which time were offered brief in-app de-escalation tools. Supervised machine learning algorithms were applied retrospectively to wearable sensor data obtained to develop group-based digital biomarkers for stress and craving. Engagement was assessed by number of days of utilization, and number of hours in a given day of connection. RESULTS Sixty percent of participants (N=30) completed the 30-day protocol. The model detected stress and craving correctly 76 % and 69 % of the time, respectively, but with false positive rates of 33 % and 28 % respectively. All models performed close to previously validated models from a research grade sensor. Participants used the app for a mean of 14.2 days (SD 10.1) and 11.7 h per day (SD 8.2). Anxiety disorders were associated with higher mean hours per day connected, and return to drug use events were associated with lower mean hours per day connected. CONCLUSIONS Future work should explore the effect of similar digital health systems on treatment outcomes and the optimal dose of digital interventions needed to make a clinically significant impact.
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Affiliation(s)
- Stephanie Carreiro
- Department of Emergency Medicine, Division of Medical Toxicology, University of Massachusetts Chan Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
| | - Pravitha Ramanand
- Department of Electrical and Computer Engineering, University of Texas at Tyler, 3900 University Blvd, Tyler, TX 75799, USA
| | - Melissa Taylor
- Department of Emergency Medicine, Division of Medical Toxicology, University of Massachusetts Chan Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
| | - Rebecca Leach
- Department of Emergency Medicine, Division of Medical Toxicology, University of Massachusetts Chan Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
| | - Joshua Stapp
- Department of Electrical and Computer Engineering, University of Texas at Tyler, 3900 University Blvd, Tyler, TX 75799, USA; RAE Health, 13 Devoe Raod, Bristol, ME 04539, USA
| | - Sloke Sherestha
- Department of Electrical and Computer Engineering, University of Texas at Tyler, 3900 University Blvd, Tyler, TX 75799, USA
| | - David Smelson
- Department of Medicine, University of Massachusetts Chan Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
| | - Premananda Indic
- Department of Electrical and Computer Engineering, University of Texas at Tyler, 3900 University Blvd, Tyler, TX 75799, USA
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30
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Cuthbertson C, Billington A, Rudolphi J. Substance Use Among Illinois Farmers. Subst Use Misuse 2024; 59:1812-1819. [PMID: 39091097 DOI: 10.1080/10826084.2024.2383594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
BACKGROUND People in agriculture face unique stressors and occupational hazards, and relatively little is known about substance use in this population. The purpose of this study was to describe substance use among farmers in Illinois. METHODS We conducted a mail survey of Illinois farmers that included the Brief ASSIST to assess substance use for lifetime and past three-month use of ten different substances. The survey also included questions about farming characteristics, mental health, stress, coping, social support, and demographic characteristics. We used chi-square and non-parametric tests to assess group differences. RESULTS Alcohol, tobacco, cannabis, and sedatives were most reported as used for a lifetime and in the past three months. About three-quarters of the sample had recently used alcohol. Recent tobacco use was associated with not being married, less education, and less concern about climate-related farm stress. Recent sedative use was associated with greater concern about isolation-related farm stress. People who reported multiple substance use were at a greater risk for suicide and were more likely to meet the criteria for generalized anxiety disorder. None of the participants reported recent use of cocaine, heroin, inhalants, or hallucinogens. CONCLUSION Specific social and cultural aspects of farming and farm communities may contribute to substance use among people working in agriculture. Future research can help to better understand this intersection and make recommendations for programs and resources to promote adaptive coping strategies.
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Affiliation(s)
- Courtney Cuthbertson
- Department of Human Development and Family Studies, University of Illinois, Urbana, IL, USA
| | - Alyssa Billington
- Department of Human Development and Family Studies, University of Illinois, Urbana, IL, USA
| | - Josie Rudolphi
- Department of Agricultural and Biological Engineering, University of Illinois, Urbana, IL, USA
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31
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Turfe A, Westbrook SR, Lopez SA, Chang SE, Flagel SB. The effect of corticosterone on the acquisition of Pavlovian conditioned approach behavior in rats is dependent on sex and vendor. Horm Behav 2024; 164:105609. [PMID: 39083878 DOI: 10.1016/j.yhbeh.2024.105609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 07/02/2024] [Accepted: 07/19/2024] [Indexed: 08/02/2024]
Abstract
Cues in the environment become predictors of biologically relevant stimuli, such as food, through associative learning. These cues can not only act as predictors but can also be attributed with incentive motivational value and gain control over behavior. When a cue is imbued with incentive salience, it attains the ability to elicit maladaptive behaviors characteristic of psychopathology. We can capture the propensity to attribute incentive salience to a reward cue in rats using a Pavlovian conditioned approach paradigm, in which the presentation of a discrete lever-cue is followed by the delivery of a food reward. Upon learning the cue-reward relationship, some rats, termed sign-trackers, develop a conditioned response directed towards the lever-cue; whereas others, termed goal-trackers, approach the food cup upon lever-cue presentation. Here, we assessed the effects of systemic corticosterone (CORT) on the acquisition and expression of sign- and goal-tracking behaviors in male and female rats, while examining the role of the vendor (Charles River or Taconic) from which the rats originated in these effects. Treatment naïve male and female rats from Charles River had a greater tendency to sign-track than those from Taconic. Administration of CORT enhanced the acquisition of sign-tracking behavior in males from Charles River and females from both vendors. Conversely, administration of CORT had no effect on the expression of the conditioned response. These findings demonstrate a role for CORT in cue-reward learning and suggest that inherent tendencies towards sign- or goal-tracking may interact with this physiological mediator of motivated behavior.
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Affiliation(s)
- Alexandra Turfe
- Michigan Neuroscience Institute, University of Michigan, Ann Arbor 48109, United States of America
| | - Sara R Westbrook
- Michigan Neuroscience Institute, University of Michigan, Ann Arbor 48109, United States of America
| | - Sofia A Lopez
- Neuroscience Graduate Program, University of Michigan, Ann Arbor 48109, United States of America
| | - Stephen E Chang
- Michigan Neuroscience Institute, University of Michigan, Ann Arbor 48109, United States of America
| | - Shelly B Flagel
- Michigan Neuroscience Institute, University of Michigan, Ann Arbor 48109, United States of America; Department of Psychiatry, University of Michigan, Ann Arbor 48109, United States of America.
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32
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Cruz-Vespa I, Dembling SJ, Han BH, Inagaki TK. Associations between vicarious racism and psychoactive substance use depend on strength of ethnic identity. Sci Rep 2024; 14:17217. [PMID: 39060300 PMCID: PMC11282253 DOI: 10.1038/s41598-024-67202-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Racism is a pervasive threat to health with differential impact based on race and ethnicity. Considering the continued perpetration and visibility of racism online and in the news, vicarious racism, or "secondhand" racism when hearing about or witnessing racism being committed against members of one's ethnic or racial group, is a particularly urgent threat in the context of such disparities and their subsequent health consequences. The current study examines if frequency of exposure to vicarious racism and the emotional impact of those experiences are linked to psychoactive substance use, and explores the role of ethnic identity in moderating these relationships. In a cross-sectional survey, 504 adult participants aged 18-78 (M age = 30.15, SD = 11.52, 52.6% female) identifying as Black/African American or Latine reported on their experiences with vicarious racism and alcohol, marijuana, and tobacco use over the past 30 days. Logistic regression was utilized to test hypotheses. Primary findings indicate that greater emotional impact of vicarious racism was associated with a 50% increase in odds of alcohol consumption and that ethnic identity moderated the association between vicarious racism and marijuana use. Greater emotional impact of vicarious racism was related to more marijuana use for those lower on ethnic identity, whereas there was no association for those higher on ethnic identity. Vicarious racism was not related to tobacco use. Results suggest that ethnic identity might be protective in the association of vicarious racism on substance use. Further research on this topic is needed as vicarious racism becomes an increasingly common experience among marginalized populations.
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Affiliation(s)
| | - Sarah J Dembling
- Department of Psychology, San Diego State University, San Diego, USA
- SDSU-UC San Diego Joint Doctoral Program, San Diego, USA
| | | | - Tristen K Inagaki
- Department of Psychology, San Diego State University, San Diego, USA
- SDSU-UC San Diego Joint Doctoral Program, San Diego, USA
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Ward RN, Erickson AJ, Carlson KJ, Yalch MM. The role of unit cohesion and perceived resilience in substance use disorder. MILITARY PSYCHOLOGY 2024; 36:403-409. [PMID: 38913766 PMCID: PMC11197915 DOI: 10.1080/08995605.2023.2189861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 02/28/2023] [Indexed: 03/17/2023]
Abstract
Soldiers have high rates of substance use disorders (SUD), often in the aftermath of stressors experienced during military deployments. There are several factors that protect against SUD. For example, individual factors like perceived resilience and group factors such as unit cohesion may make someone less likely to abuse substances. However, there is little research on the differential influence of these resilience factors on SUD over and above deployment stressors. In this study, we examined the relative effects of perceived resilience, unit cohesion, and deployment stressors on SUD in a sample of 21,449 active duty and reserve soldiers from the U.S. Army (primarily White and male, mean age = 28.66, SD = 7.41) using structural equation modeling. We found that unit cohesion (ß = -.17) and perceived resilience (ß = -.16) had negative effects on SUD over and above deployment stressors. The study findings clarify research on resilience to SUD and have implications for addressing substance use in the military, specifically regarding the importance of building unit cohesion.
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Affiliation(s)
- Rachel N. Ward
- Department of Psychology, Palo Alto University, Palo Alto, California
| | - Alexander J. Erickson
- Department of Psychology, Palo Alto University, Palo Alto, California
- Geriatric Research, Education, and Clinical Center, Veterans Affairs (VA) Greater Los Angeles Healthcare System, Los Angeles, California
| | - Katie J. Carlson
- Department of Psychology, Palo Alto University, Palo Alto, California
| | - Matthew M. Yalch
- Department of Psychology, Palo Alto University, Palo Alto, California
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van Dijk W, Oosterman M, de Vente W, Jansen I, Blankers M, Huizink AC. Smoking cessation in pregnant women: A randomized controlled trial investigating the effectiveness of an eHealth intervention including heart rate variability-biofeedback training. Addict Behav 2024; 154:108005. [PMID: 38513327 DOI: 10.1016/j.addbeh.2024.108005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 02/16/2024] [Accepted: 03/01/2024] [Indexed: 03/23/2024]
Abstract
BACKGROUND Prenatal smoking and stress are associated with adverse health effects for women themselves and are risk factors for adverse outcomes of the child. Effective interventions are needed to support women with smoking cessation and reducing stress. The aims were (1) to test the effectiveness of an 8-week eHealth intervention targeting stress reduction and smoking cessation; (2) to examine whether stress reduction mediated the intervention effect on smoking behavior; (3) to test motivation to quit as a moderator; and (4) to investigate a dose-response effect of program usage. METHODS Pregnant women were included if they were >18 years of age, < 28 weeks pregnant at recruitment, and currently smoking. In total, 156 consenting participants were randomly assigned to the intervention or active control condition. Study outcomes on smoking (yes/no, frequency, and quantity) were collected via online questionnaires at pre-intervention (baseline; t0), post-intervention (8 weeks after t0; t1), and follow up at two weeks (t2) and three months (t3) after birth. RESULTS Smoking and stress reduced over the 8-week period in both conditions. The intervention effect on smoking was not mediated by stress reduction. Motivation to quit was found to moderate the intervention effect (smoking frequency and quantity) and a dose-response effect was found for program usage in the intervention for the reduction on smoking frequency and quantity. CONCLUSION Program usage and motivation to quit are important for smoking reduction in pregnant women. Further research is needed to examine how the intervention could be improved to increase treatment effectiveness.
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Affiliation(s)
- Willeke van Dijk
- Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands.
| | - Mirjam Oosterman
- Department of Clinical Child and Family Studies, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands.
| | - Wieke de Vente
- Research Institute of Child Development and Education, University of Amsterdam, Amsterdam Roeterseilandcampus, Building D, Nieuwe Achtergracht 127, 1018 WS Amsterdam, the Netherlands.
| | - Imke Jansen
- Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands; Institute for Brain and Behavior Amsterdam (IBBA), Van der Boechorststraat 1, Transitorium Room 1B-78, 1081 BT Amsterdam, the Netherlands.
| | - Matthijs Blankers
- Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Da Costakade 45, 3521 VS Utrecht, the Netherlands; Arkin Mental Health Care, Klaprozenweg 111, 1033 NN Amsterdam, the Netherlands; Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
| | - Anja C Huizink
- Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands.
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Forbes PA, Nitschke JP, Hochmeister N, Kalenscher T, Lamm C. No effects of acute stress on monetary delay discounting: A systematic literature review and meta-analysis. Neurobiol Stress 2024; 31:100653. [PMID: 38933285 PMCID: PMC11201353 DOI: 10.1016/j.ynstr.2024.100653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 05/06/2024] [Accepted: 05/30/2024] [Indexed: 06/28/2024] Open
Abstract
Many everyday decisions, including those concerning our health, finances and the environment, involve choosing between a smaller but imminent reward (e.g., €20 now) and a later but larger reward (e.g., €40 in a month). The extent to which an individual prefers smaller imminent rewards over larger delayed rewards can be measured using delay discounting tasks. Acute stress induces a cascade of biological and psychological responses with potential consequences for how individuals think about the future, process rewards, and make decisions, all of which can impact delay discounting. Several studies have shown that individuals focus more on imminent rewards under stress. These findings have been used to explain why individuals make detrimental choices under acute stress. Yet, the evidence linking acute stress to delay discounting is equivocal. To address this uncertainty, we conducted a meta-analysis of 11 studies (14 effects) to systematically quantify the effects of acute stress on monetary delay discounting. Overall, we find no effect of acute stress on delay discounting, compared to control conditions (SMD = -0.18, 95% CI [-0.57, 0.20], p = 0.32). We also find that neither the gender/sex of the participants, the type of stressor (e.g., physical vs. psychosocial) nor whether monetary decisions were hypothetical or incentivized (i.e. monetary decisions were actually paid out) moderated the impact of acute stress on monetary delay discounting. We argue that establishing the effects of acute stress on the separate processes involved in delay discounting, such as reward valuation and prospection, will help to resolve the inconsistencies in the field.
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Affiliation(s)
- Paul A.G. Forbes
- Comparative Psychology, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Germany
- Social, Cognitive, and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, Austria
| | - Jonas P. Nitschke
- Social, Cognitive, and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, Austria
| | - Nicole Hochmeister
- Social, Cognitive, and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, Austria
| | - Tobias Kalenscher
- Comparative Psychology, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Germany
| | - Claus Lamm
- Social, Cognitive, and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, Austria
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Haeny AM, Schick MR, McKenley C, Chowdhary A, Bellamy CD, O'Malley SS, Sinha R. Evidence that personalized racial stress procedures elicit a stress response and increases alcohol craving among Black adults with alcohol use disorder: A laboratory pilot study. Drug Alcohol Depend 2024; 260:111312. [PMID: 38749311 PMCID: PMC11991899 DOI: 10.1016/j.drugalcdep.2024.111312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 04/15/2024] [Accepted: 04/16/2024] [Indexed: 06/16/2024]
Abstract
BACKGROUND The objective of this study was to pilot test newly developed personalized imagery procedures to investigate the impact of racial stress on alcohol craving and emotional and physiological response in Black adults with alcohol use disorder (AUD). METHODS Twenty Black adults (45% women, meanage=37.05, SDage=13.19) with AUD participated in two sessions. In the first, participants described a stressful personal event involving their race and a neutral relaxing situation and these descriptions were used to develop scripts for the subsequent laboratory exposure session. The second session was an experimental provocation session in which participants reported on alcohol craving and emotional response before and after imagined exposure to stress and neutral conditions using personalized racial stress and neutral/relaxing scripts. Conditions were randomized and counterbalanced across subjects, and heart rate and blood pressure were assessed before and after each image. RESULTS Alcohol craving and negative emotions significantly increased, and positive emotions decreased following the racial stress script relative to the neutral/relaxing script. We found no differences in physiological response. Exploratory analyses found that increase in alcohol craving was correlated with racial identity exploration but not racial identity commitment, men reported greater reductions in anger than women in the neutral condition only, and income was correlated with fear in the racial stress condition only. CONCLUSIONS This study provides evidence that personalized racial stress procedures elicit a stress response and increases alcohol craving and emotional response but not physiological response among Black adults with AUD. These findings warrant replication in a larger study.
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Affiliation(s)
- Angela M Haeny
- Yale School of Medicine, Department of Psychiatry, New Haven, CT 06519, USA; Racial Equity and Addiction Lab at Yale, New Haven, CT 06519, USA.
| | - Melissa R Schick
- Yale School of Medicine, Department of Psychiatry, New Haven, CT 06519, USA; Racial Equity and Addiction Lab at Yale, New Haven, CT 06519, USA
| | - Claudia McKenley
- Yale School of Medicine, Department of Psychiatry, New Haven, CT 06519, USA; Racial Equity and Addiction Lab at Yale, New Haven, CT 06519, USA
| | - Aishwarya Chowdhary
- Yale School of Medicine, Department of Psychiatry, New Haven, CT 06519, USA; Racial Equity and Addiction Lab at Yale, New Haven, CT 06519, USA; Yale Stress Center, New Haven, CT 06511, USA
| | - Chyrell D Bellamy
- Yale School of Medicine, Department of Psychiatry, New Haven, CT 06519, USA
| | | | - Rajita Sinha
- Yale School of Medicine, Department of Psychiatry, New Haven, CT 06519, USA; Yale Stress Center, New Haven, CT 06511, USA
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Mao S, Chou T, D'Orsogna MR. A probabilistic model of relapse in drug addiction. Math Biosci 2024; 372:109184. [PMID: 38582296 DOI: 10.1016/j.mbs.2024.109184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 03/25/2024] [Indexed: 04/08/2024]
Abstract
More than 60% of individuals recovering from substance use disorder relapse within one year. Some will resume drug consumption even after decades of abstinence. The cognitive and psychological mechanisms that lead to relapse are not completely understood, but stressful life experiences and external stimuli that are associated with past drug-taking are known to play a primary role. Stressors and cues elicit memories of drug-induced euphoria and the expectation of relief from current anxiety, igniting an intense craving to use again; positive experiences and supportive environments may mitigate relapse. We present a mathematical model of relapse in drug addiction that draws on known psychiatric concepts such as the "positive activation; negative activation" paradigm and the "peak-end" rule to construct a relapse rate that depends on external factors (intensity and timing of life events) and individual traits (mental responses to these events). We analyze which combinations and ordering of stressors, cues, and positive events lead to the largest relapse probability and propose interventions to minimize the likelihood of relapse. We find that the best protective factor is exposure to a mild, yet continuous, source of contentment, rather than large, episodic jolts of happiness.
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Affiliation(s)
- Sayun Mao
- Department of Computational Medicine, UCLA, Los Angeles, 90095-1766, CA, USA.
| | - Tom Chou
- Department of Computational Medicine, UCLA, Los Angeles, 90095-1766, CA, USA.
| | - Maria R D'Orsogna
- Department of Computational Medicine, UCLA, Los Angeles, 90095-1766, CA, USA; Department of Mathematics, California State University at Northridge, Los Angeles, 91330, CA, USA.
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Assari S. Racial Differences in Biopsychosocial Pathways to Tobacco and Marijuana Use Among Youth. J Racial Ethn Health Disparities 2024:10.1007/s40615-024-02035-8. [PMID: 38807026 DOI: 10.1007/s40615-024-02035-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/13/2024] [Accepted: 05/16/2024] [Indexed: 05/30/2024]
Abstract
BACKGROUND The influence of socioeconomic disparities and multidimensional stressors on youth tobacco and marijuana use is recognized; however, the extent of these effects varies among different racial groups. Understanding the racial differences in the factors influencing substance use is crucial for developing tailored interventions aimed at reducing disparities in tobacco and marijuana use among adolescents. AIMS This study aims to explore the differential effects of socioeconomic disparities and multidimensional stressors on tobacco and marijuana use between Black and White adolescents. METHODS Utilizing longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study, this research includes a cohort of pre-youth, monitored from the age of 9-10 years for a period of up to 36 months. We examined the impact of various socioeconomic status (SES) indicators and multidimensional stressors, including trauma, financial stress, racial discrimination, and family stress, alongside baseline average cortical thickness and the subsequent initiation of tobacco and marijuana use over the 36-month follow-up. RESULTS Overall, 10,777 participants entered our analysis. This included 8263 White and 2514 Black youth. Our findings indicate significant differences in the pathways from SES indicators through stress types to cortical thickness between Black and White youths. Notably, cortical thickness's impact on the future initiation of tobacco and marijuana use was present in both groups. CONCLUSION The study suggests that compared to White adolescents, Black adolescents' substance use and associated cortical thickness are less influenced by stress and SES indicators. This discrepancy may be attributed to the compounded effects of racism, where psychosocial mechanisms might be more diminished for Black youth than White youth. These findings support the theory of Minorities' Diminished Returns rather than the cumulative disadvantage or double jeopardy hypothesis, highlighting the need for interventions that address the unique challenges faced by Black adolescents.
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Affiliation(s)
- Shervin Assari
- Department of Internal Medicine, Charles R Drew University of Medicine and Science, 1731 E. 120th St., Los Angeles, CA, 90059, USA.
- Department of Family Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA.
- Department of Urban Public Health, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA.
- Marginalization-Related Diminished Returns, Los Angeles, CA, USA.
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Brown CH, Johnson KA, Hills HA, Vermeer W, Clarke DL, Barnett JT, Newman RT, Burns TL, Pellan WA. Overdose deaths before and during the COVID-19 pandemic in a US county. Front Public Health 2024; 12:1366161. [PMID: 38859894 PMCID: PMC11163089 DOI: 10.3389/fpubh.2024.1366161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/23/2024] [Indexed: 06/12/2024] Open
Abstract
Introduction Globally, overdose deaths increased near the beginning of the COVID-19 pandemic, which created availability and access barriers to addiction and social services. Especially in times of a crisis like a pandemic, local exposures, service availability and access, and system responses have major influence on people who use drugs. For policy makers to be effective, an understanding at the local level is needed. Methods This retrospective epidemiologic study from 2019 through 2021 compares immediate and 20-months changes in overdose deaths from the pandemic start to 16 months before its arrival in Pinellas County, FL We examine toxicologic death records of 1,701 overdoses to identify relations with interdiction, and service delivery. Results There was an immediate 49% increase (95% CI 23-82%, p < 0.0001) in overdose deaths in the first month following the first COVID deaths. Immediate increases were found for deaths involving alcohol (171%), heroin (108%), fentanyl (78%), amphetamines (55%), and cocaine (45%). Overdose deaths remained 27% higher (CI 4-55%, p = 0.015) than before the pandemic through 2021.Abrupt service reductions occurred when the pandemic began: in-clinic methadone treatment dropped by two-thirds, counseling by 38%, opioid seizures by 29%, and drug arrests by 56%. Emergency transport for overdose and naloxone distributions increased at the pandemic onset (12%, 93%, respectively) and remained higher through 2021 (15%, 377%,). Regression results indicate that lower drug seizures predicted higher overdoses, and increased 911 transports predicted higher overdoses. The proportion of excess overdose deaths to excess non-COVID deaths after the pandemic relative to the year before was 0.28 in Pinellas County, larger than 75% of other US counties. Conclusions Service and interdiction interruptions likely contributed to overdose death increases during the pandemic. Relaxing restrictions on medical treatment for opioid addiction and public health interventions could have immediate and long-lasting effects when a major disruption, such as a pandemic, occurs. County level data dashboards comprised of overdose toxicology, and interdiction and service data, can help explain changes in overdose deaths. As a next step in predicting which policies and practices will best reduce local overdoses, we propose using simulation modeling with agent-based models to examine complex interacting systems.
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Affiliation(s)
- C. Hendricks Brown
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Kimberly A. Johnson
- Department of Mental Health Law and Policy (MHC 2636), College of Behavioral and Community Sciences, University of South Florida, Tampa, FL, United States
| | - Holly A. Hills
- Department of Mental Health Law and Policy (MHC 2636), College of Behavioral and Community Sciences, University of South Florida, Tampa, FL, United States
| | - Wouter Vermeer
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | | | - Joshua T. Barnett
- Department of Human Services, Pinellas County Government, Clearwater, FL, United States
| | - Reta T. Newman
- Pinellas County Forensic Lab, District Six Medical Examiner Office, Largo, FL, United States
| | - Tim L. Burns
- Department of Human Services, Pinellas County Government, Clearwater, FL, United States
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Barbosa-Méndez S, Salazar-Juárez A. Evaluation of multitarget drugs on the expression of cocaine-induced locomotor sensitization in male rats: A comparative study. Heliyon 2024; 10:e29979. [PMID: 38726128 PMCID: PMC11079035 DOI: 10.1016/j.heliyon.2024.e29979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 04/17/2024] [Accepted: 04/18/2024] [Indexed: 05/12/2024] Open
Abstract
Purpose - Cocaine use disorder (CUD) is a complex disease. Several studies have shown the efficacy of multitarget drugs used to treat CUD. Here we compare the efficacy of mirtazapine (MIR), pindolol (PIN), fluoxetine (FLX), risperidone (RIS), trazodone (TRZ), ziprasidone (ZPR), ondansetron (OND), yohimbine (YOH), or prazosin (PRZ), to reduce long-term cocaine-induced locomotor activity and the expression of cocaine-induced locomotor sensitization in rats. Methods - The study consists of four experiments, which were divided into four experimental phases. Induction (10 days), cocaine withdrawal (30 days), expression (10 days), and post-expression phase (10 days). Male Wistar rats were daily dosed with cocaine (10 mg/kg; i.p.) during the induction and post-expression phases. During drug withdrawal, the MIR, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ were administered 30 min before saline. In the expression, the multitarget drugs were administered 30 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min.During the agonism phase, in experiment four, 8-OH-DPAT, DOI, CP-809-101, SR-57227A, or clonidine (CLO) was administered 30 min before MIR and 60 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min. Results -MIR, FLX, RIS, ZPR, OND, or PRZ attenuated the cocaine-induced locomotor activity and cocaine locomotor sensitization. PIN, TRZ, and YOH failed to decrease cocaine locomotor sensitization. At the optimal doses used, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ failed to attenuate long-term cocaine locomotor activation. MIR generated a decrease in cocaine-induced locomotor activity of greater magnitude and duration than the other multitarget drugs evaluated. Conclusion - At the optimal doses of multitarget drugs evaluated, MIR was the multitarget drug that showed the greatest long-term cocaine-induced behavior effects compared to other multitarget drugs.
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Affiliation(s)
- Susana Barbosa-Méndez
- Subdirección de Investigaciones Clínicas. Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental. Instituto Nacional de Psiquiatría. Ciudad de México, 14370, Mexico
| | - Alberto Salazar-Juárez
- Subdirección de Investigaciones Clínicas. Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental. Instituto Nacional de Psiquiatría. Ciudad de México, 14370, Mexico
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Muniz FB, Kalina E, Patock-Peckham JA, Berberian S, Fulop B, Williams J, Leeman RF. A Test of the Self-Medication Hypothesis Using a Latent Measurement Model: Are Stress and Impaired Control over Alcohol Mediating Mechanisms of Parenting Styles on Heavy Episodic Drinking and Alcohol-Related Problems among University Students? Behav Sci (Basel) 2024; 14:384. [PMID: 38785875 PMCID: PMC11117968 DOI: 10.3390/bs14050384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 04/29/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024] Open
Abstract
INTRODUCTION The self-medication hypothesis (SMH) suggests that individuals consume alcohol to alleviate stressful emotions. Still, the underlying mechanisms between stress and heavy episodic drinking remain to be explored. Impaired control over drinking (IC) reflects a failure of self-regulation specific to the drinking context, with individuals exceeding self-prescribed limits. Parenting styles experienced during childhood have a lasting influence on the stress response, which may contribute to IC. METHOD We examined the indirect influences of parenting styles (e.g., permissive, authoritarian, and authoritative) on heavy episodic drinking and alcohol-related problems through the mediating mechanisms of stress and IC. We fit a latent measurement model with 938 (473 men; 465 women) university students, utilizing bootstrap confidence intervals, in Mplus 8.0. RESULTS Higher levels of authoritative parenting (mother and father) were indirectly linked to fewer alcohol-related problems and less heavy episodic drinking through less stress and IC. Maternal permissiveness was indirectly linked to more alcohol-related problems and heavy episodic drinking through more stress and, in turn, more IC. Impaired control appeared to be a mediator for stress and alcohol-related problems. CONCLUSIONS Maternal permissiveness contributes to the use of alcohol to alleviate stress. Thus, reducing stress may reduce problematic heavy drinking and alcohol problems among emerging adults with high IC who may also have experienced permissive parenting. Stress may exacerbate behavioral dysregulation of drinking within self-prescribed limits.
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Affiliation(s)
- Felix B. Muniz
- Department of Psychology, Arizona State University, Tempe, AZ 85287-1104, USA; (J.A.P.-P.); (S.B.)
| | - Elena Kalina
- Department of Health Education and Behavior, University of Florida, Gainesville, FL 32611, USA;
| | - Julie A. Patock-Peckham
- Department of Psychology, Arizona State University, Tempe, AZ 85287-1104, USA; (J.A.P.-P.); (S.B.)
| | - Sophia Berberian
- Department of Psychology, Arizona State University, Tempe, AZ 85287-1104, USA; (J.A.P.-P.); (S.B.)
| | - Brittney Fulop
- Department of Psychology, Arizona State University, Tempe, AZ 85287-1104, USA; (J.A.P.-P.); (S.B.)
| | - Jason Williams
- RTI International, Research Triangle Park, NC 27709, USA;
| | - Robert F. Leeman
- Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA;
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Le AB, Urban-Wojcik E, Seewald M, Mezuk BR. The Relationship Between Workplace Drug Policies, Opioid Misuse, and Psychological Distress: Evidence From the 2020 National Survey on Drug Use and Health. New Solut 2024; 34:22-37. [PMID: 38332622 PMCID: PMC11003197 DOI: 10.1177/10482911241231523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2024]
Abstract
Background: This study, using a nationally representative dataset of the U.S. workforce, examines how punitive workplace drug policies relate to opioid use/misuse and psychological distress. Methods: The sample included adults aged ≥18 years who participated in the National Survey on Drug Use and Health and were employed in 2020. Hierarchical multivariate logistical models were constructed to address the research questions. Results: The weighted, design-based estimates indicate that of 147 831 081 workers, 3.38% reported misusing opioids in the last 12 months. Having a punitive workplace policy was associated with higher rates of opioid use/misuse among workers aged ≤ 34 compared to their same-aged counterparts in nonpunitive workplaces, and among workers identifying as Black, Indigenous, or Person of Color who also experienced severe psychological distress the past year. Conclusion: Some employers may think drug testing policies are net-beneficial to worker well-being; these findings indicate such policies may interact in harmful ways with psychological distress.
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Affiliation(s)
- Aurora B. Le
- Department of Health Behavior, School of Public Health, Texas A&M University, College Station, TX, USA
| | - Emily Urban-Wojcik
- Eisenberg Family Depression Center, University of Michigan, Ann Arbor, MI, USA
| | - Meghan Seewald
- Eisenberg Family Depression Center, University of Michigan, Ann Arbor, MI, USA
| | - Briana R. Mezuk
- Eisenberg Family Depression Center, University of Michigan, Ann Arbor, MI, USA
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
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Marziali ME, Prins SJ, Gutkind S, Martins SS. Partner incarceration, maternal substance use, and the mediating role of social support: A longitudinal analysis using the future of families and child wellbeing study. Soc Sci Med 2024; 349:116896. [PMID: 38653185 PMCID: PMC11097120 DOI: 10.1016/j.socscimed.2024.116896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 04/11/2024] [Accepted: 04/15/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION The United States is responsible for the highest incarceration rate globally. This study aimed to explore the impact of partner incarceration on maternal substance use and whether social support mediates the relationship between partner incarceration and maternal substance use. METHODS Using data from the Future of Families and Child Wellbeing Study, a longitudinal cohort following new parents and children, this analysis quantifies the relationship between paternal incarceration and maternal substance use (N = 2823). We analyzed maternal responses in years 3 (2001-2003), 5 (2003-2006), 9 (2007-2010), and 15 (2014-2017). We explored the role of financial support and emergency social support as potential mediators. Confirmatory factor analysis (CFA) was employed to construct support-related mediators. We modeled the impact of partner incarceration and maternal substance use using generalized estimating equations (GEE) to account for repeated measures, adjusting for appropriate confounders (age of mother at child's birth, race, education, employment, and history of intimate partner violence). RESULTS Nearly half (44.2%, N = 1247) of participants reported partner incarceration. Among mothers who experienced partner incarceration, the odds of reporting substance use were 110% greater than those who reported no partner incarceration (adjusted Odds Ratio [aOR]: 2.10; 95% Confidence Interval (CI):1.67-2.63). Financial support at year 5 accounted for 19.5% (95% CI: 6.03-33.06%) of the association between partner incarceration at year 3 and substance use at year 9; emergency social support at year 5 accounted for 6.4% (95% CI: 0.51-12.25%) of the association between partner incarceration and substance use at year 9. Neither financial nor emergency social support at year 9 were significant mediators between partner incarceration at year 3 and substance use at year 15. CONCLUSIONS These findings demonstrate that partner incarceration impacts maternal substance use. Financial and emergency support may partially mediate this relationship in the short term, which has important implications for families disrupted by mass incarceration.
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Affiliation(s)
- Megan E Marziali
- Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, New York, NY, 10032, USA.
| | - Seth J Prins
- Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, New York, NY, 10032, USA
| | - Sarah Gutkind
- Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, New York, NY, 10032, USA
| | - Silvia S Martins
- Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St, New York, NY, 10032, USA
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Das P, Das T, Roy TB. Investigating key latent factors influencing alcohol consumption among the tribal male adolescents in Dooars region, West Bengal. J Ethn Subst Abuse 2024:1-24. [PMID: 38613768 DOI: 10.1080/15332640.2024.2340540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/15/2024]
Abstract
BACKGROUND Alcohol consumption among tribal male adolescents in India is a significant social concern. Tribal adolescents are particularly vulnerable and tend to lean toward alcohol addiction. Therefore, it is crucial to introduce some necessary footsteps to reduce alcohol consumption. The primary objective of this study is to investigate the association of various latent factors with the alcohol-drinking behavior of tribal adolescents. METHODS The study collected data from 600 tribal adolescents from the Dooars region, with 241 of them reported consuming alcohol. The study aimed to confirm the theoretical development of hypotheses regarding peer pressure, parental discord, stress, attitude toward alcohol, and food insecurity as exogenous latent factors influencing the alcohol-drinking behavior of tribal adolescents. In this context, the study adopted both measurement and structural models using Partial Least Squares-Structural Equation Modeling (PLS-SEM). RESULTS The findings revealed a significant path relationship between alcohol drinking behavior and various exogenous factors like peer pressure (β = 0.214, p = .000), parental discord (β = 0.121, p = .009), stress (β = 0.170, p = .000), attitude toward alcohol (β = 0.110, p = .004), and food insecurity (β = 0.510, p = .000). This study developed a reflective measurement model, and the evaluation of reflective measurement models was conducted, assessing internal consistency, convergent validity, and discriminant validity, yielding satisfactory results. CONCLUSION To tackle alcohol issues among tribal adolescents in the Dooars region, effective strategies should be employed. These include educating in schools, highlighting tribal role models, aiding peers with alcohol dependence, providing life skills training, and addressing parental discord and food insecurity through awareness campaigns, workshops, and better infrastructure.
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Affiliation(s)
| | - Tanu Das
- Raiganj University, Raiganj, India
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Martinez CA, Pantazopoulos H, Gisabella B, Stephens ET, Garteiser J, Del Arco A. Choice impulsivity after repeated social stress is associated with increased perineuronal nets in the medial prefrontal cortex. Sci Rep 2024; 14:7093. [PMID: 38528075 PMCID: PMC10963730 DOI: 10.1038/s41598-024-57599-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 03/20/2024] [Indexed: 03/27/2024] Open
Abstract
Repeated stress can predispose to substance abuse. However, behavioral and neurobiological adaptations that link stress to substance abuse remain unclear. This study investigates whether intermittent social defeat (ISD), a stress protocol that promotes drug-seeking behavior, alters intertemporal decision-making and cortical inhibitory function in the medial prefrontal cortex (mPFC). Male long evans rats were trained in a delay discounting task (DDT) where rats make a choice between a fast (1 s) small reward (1 sugar pellet) and a large reward (3 sugar pellets) that comes with a time delay (10 s or 20 s). A decreased preference for delayed rewards was used as an index of choice impulsivity. Rats were exposed to ISD and tested in the DDT 24 h after each stress episode, and one- and two-weeks after the last stress episode. Immunohistochemistry was performed in rat's brains to evaluate perineuronal nets (PNNs) and parvalbumin GABA interneurons (PV) labeling as markers of inhibitory function in mPFC. ISD significantly decreased the preference for delayed large rewards in low impulsive, but not high impulsive, animals. ISD also increased the density of PNNs in the mPFC. These results suggest that increased choice impulsivity and cortical inhibition predispose animals to seek out rewards after stress.
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Affiliation(s)
| | - Harry Pantazopoulos
- Department of Psychiatry and Human Behavior, Medical School, University of Mississippi Medical Center, Jackson, MS, USA
| | - Barbara Gisabella
- Department of Psychiatry and Human Behavior, Medical School, University of Mississippi Medical Center, Jackson, MS, USA
| | - Emily T Stephens
- Department of Psychiatry and Human Behavior, Medical School, University of Mississippi Medical Center, Jackson, MS, USA
| | - Jacob Garteiser
- Department of Psychiatry and Human Behavior, Medical School, University of Mississippi Medical Center, Jackson, MS, USA
| | - Alberto Del Arco
- HESRM, School of Applied Sciences, University of Mississippi, Oxford, MS, USA.
- Department of Psychiatry and Human Behavior, Medical School, University of Mississippi Medical Center, Jackson, MS, USA.
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Turfe A, Westbrook SR, Lopez SA, Chang SE, Flagel SB. The effect of corticosterone on the acquisition of Pavlovian conditioned approach behavior is dependent on sex and vendor. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.03.20.586009. [PMID: 38562896 PMCID: PMC10983933 DOI: 10.1101/2024.03.20.586009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Cues in the environment become predictors of biologically relevant stimuli, such as food, through associative learning. These cues can not only act as predictors but can also be attributed with incentive motivational value and gain control over behavior. When a cue is imbued with incentive salience, it attains the ability to elicit maladaptive behaviors characteristic of psychopathology. We can capture the propensity to attribute incentive salience to a reward cue in rats using a Pavlovian conditioned approach paradigm, in which the presentation of a discrete lever-cue is followed by the delivery of a food reward. Upon learning the cue-reward relationship, some rats, termed sign-trackers, develop a conditioned response directed towards the lever-cue; whereas others, termed goal-trackers, approach the food cup upon lever-cue presentation. Here, we assessed the effects of systemic corticosterone (CORT) on the acquisition and expression of sign- and goal-tracking behaviors in male and female rats, while examining the role of the vendor (Charles River or Taconic) from which the rats originated in these effects. Male and female rats from Charles River had a greater tendency to sign-track than those from Taconic. Administration of CORT enhanced the acquisition of sign-tracking behavior in males from Charles River and females from both vendors. Conversely, administration of CORT had no effect on the expression of the conditioned response. These findings demonstrate a role for CORT in cue-reward learning and suggest that inherent tendencies towards sign- or goal-tracking may interact with this physiological mediator of motivated behavior. Highlights Male and female rats from Charles River exhibit more sign-tracking relative to those from Taconic.Corticosterone increases the acquisition of sign-tracking in male rats from Charles River.Corticosterone increases the acquisition of sign-tracking in female rats, regardless of vendor.There is no effect of corticosterone on the expression of sign-tracking behavior in either male or female rats.
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Morel C, Parise LF, Van der Zee Y, Issler O, Cai M, Browne C, Blando A, Leclair K, Haynes S, Williams RW, Mulligan MK, Russo SJ, Nestler EJ, Han MH. Male and female variability in response to chronic stress and morphine in C57BL/6J, DBA/2J, and their BXD progeny. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.02.23.581795. [PMID: 38464110 PMCID: PMC10925176 DOI: 10.1101/2024.02.23.581795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and thereby more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions-specifically gene x chronic stress -here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J. Utilizing the chronic social defeat stress (CSDS) and chronic variable stress (CVS) paradigms, we first showed sexual dimorphism in the behavioral stress response between the mouse strains. Further, we observed an interaction between genetic background and vulnerability to prolonged exposure to non-social stressors. Finally, we found that DBA/2J and C57BL/6J mice pre-exposed to stress displayed differences in morphine sensitivity. Our results support the hypothesis that genetic variation in predisposition to stress responses influences morphine sensitivity and is likely to modulate the development of drug addiction.
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Barré T, Cherikh F, Carrieri P, Marcellin F. A call for mindfulness-based interventions for cannabis-use disorders. L'ENCEPHALE 2024; 50:118-120. [PMID: 37604715 DOI: 10.1016/j.encep.2023.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 06/14/2023] [Indexed: 08/23/2023]
Abstract
Cannabis use is being increasingly liberalized worldwide, and an increasing prevalence of cannabis-use disorder (CUD) is observed. The few current therapeutic options for CUD are only modestly effective. Mindfulness-based interventions offer promising prospects for the management of substance-use disorders. However, despite proliferating literature on mindfulness and substance use, few studies have explored mindfulness in terms of cannabis use and CUD. There are many possibilities for the implementation of mindfulness-based interventions for cannabis use reduction, especially for younger users, who are more vulnerable to cannabis-related harms. Accordingly, large controlled trials are needed to reliably assess the potential of such interventions.
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Affiliation(s)
- Tangui Barré
- Inserm, IRD, Sciences économiques et sociales de la santé et traitement de l'information médicale (SESSTIM), ISSPAM, Aix-Marseille université, Marseille, France.
| | - Faredj Cherikh
- Inserm, IRD, Sciences économiques et sociales de la santé et traitement de l'information médicale (SESSTIM), ISSPAM, Aix-Marseille université, Marseille, France; Addictology Unit, University Hospital of Nice, Archet 2 Hospital, Nice, France.
| | - Patrizia Carrieri
- Inserm, IRD, Sciences économiques et sociales de la santé et traitement de l'information médicale (SESSTIM), ISSPAM, Aix-Marseille université, Marseille, France.
| | - Fabienne Marcellin
- Inserm, IRD, Sciences économiques et sociales de la santé et traitement de l'information médicale (SESSTIM), ISSPAM, Aix-Marseille université, Marseille, France.
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Bach P, Zaiser J, Zimmermann S, Gessner T, Hoffmann S, Gerhardt S, Berhe O, Bekier NK, Abel M, Radler P, Langejürgen J, Tost H, Lenz B, Vollstädt-Klein S, Stallkamp J, Kirschbaum C, Kiefer F. Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder. Biol Psychiatry 2024; 95:245-255. [PMID: 37678541 DOI: 10.1016/j.biopsych.2023.08.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 08/24/2023] [Accepted: 08/25/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Stress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. METHODS Neural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. RESULTS Compared with both control conditions, psychosocial stress elicited higher alcohol cue-induced activation in the left anterior insula (familywise error-corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate-corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate-corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate-corrected p = .046). CONCLUSIONS Results indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.
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Affiliation(s)
- Patrick Bach
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany; Feuerlein Center on Translational Addiction Medicine, University of Heidelberg, Heidelberg, Germany.
| | - Judith Zaiser
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany
| | - Sina Zimmermann
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany
| | - Tatjana Gessner
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany
| | - Sabine Hoffmann
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany; Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Sarah Gerhardt
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany
| | - Oksana Berhe
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
| | - Nina Kim Bekier
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany
| | - Martin Abel
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany
| | - Philipp Radler
- Fraunhofer Institute for Manufacturing Engineering and Automation Institute for Production Technology and Automation, Mannheim, Germany
| | - Jens Langejürgen
- Fraunhofer Institute for Manufacturing Engineering and Automation Institute for Production Technology and Automation, Mannheim, Germany
| | - Heike Tost
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
| | - Bernd Lenz
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany
| | - Sabine Vollstädt-Klein
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany; Mannheim Center for Translational Neurosciences, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany
| | - Jan Stallkamp
- Mannheim Institute for Intelligent Systems in Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
| | - Clemens Kirschbaum
- Department of Psychology, Technical University Dresden, Dresden, Germany
| | - Falk Kiefer
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany; Feuerlein Center on Translational Addiction Medicine, University of Heidelberg, Heidelberg, Germany; Mannheim Center for Translational Neurosciences, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany
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Davis JP, Prindle J, Saba SK, Castro CA, Hummer J, Canning L, Pedersen ER. Longitudinal associations between insomnia, cannabis use and stress among US veterans. J Sleep Res 2024; 33:e13945. [PMID: 37243415 PMCID: PMC10676445 DOI: 10.1111/jsr.13945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 05/02/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023]
Abstract
Insomnia is highly prevalent among military veterans, with rates nearly double that of civilian populations. Insomnia typically co-occurs with other psychological problems, including substance use (e.g. cannabis) and perceived stress. Much of the research focused on insomnia, stress and cannabis use explores cannabis as a sleep aid and a mechanism for stress relief. However, recent theoretical and empirical evidence suggests a dynamic interplay between insomnia, cannabis use and perceived stress, yet few longitudinal studies exist. Using a sample of 1105 post-9/11 veterans assessed over four time points across 12 months, we used latent difference score modelling to examine proportional change between insomnia, perceived stress and cannabis use. Results revealed a complex interplay between all three constructs. In particular, we show that higher prior levels of insomnia are associated with greater increases in perceived stress, and greater prior levels of stress are associated with greater increases in cannabis use. Perhaps more importantly, our results also point to cannabis use as a catalyst for greater increases in both stress and insomnia severity. Our results suggest there may be both benefits and costs of cannabis use among veterans. Specifically, for veterans who experience chronic sleep problems, perceived stress may become overwhelming, and the benefit of stress reduction from increased cannabis use may come at the cost of increasing insomnia symptomology.
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Affiliation(s)
- Jordan P. Davis
- University of Southern California, Suzanne Dworak-Peck School of Social Work
| | - John Prindle
- University of Southern California, Suzanne Dworak-Peck School of Social Work
| | - Shaddy K. Saba
- University of Southern California, Suzanne Dworak-Peck School of Social Work
| | - Carl A. Castro
- University of Southern California, Suzanne Dworak-Peck School of Social Work
| | | | - Liv Canning
- University of Southern California, Suzanne Dworak-Peck School of Social Work
| | - Eric R. Pedersen
- University of Southern California, Keck School of Medicine, Department of Psychiatry and Behavioral Sciences
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