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Handschuh PA, Murgaš M, Winkler D, Winkler-Pjrek E, Hartmann AM, Domschke K, Baldinger-Melich P, Rujescu D, Lanzenberger R, Spies M. Summer and SERT: Effect of daily sunshine hours on SLC6A4 promoter methylation in seasonal affective disorder. World J Biol Psychiatry 2025:1-11. [PMID: 40114401 DOI: 10.1080/15622975.2025.2477463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/02/2025] [Accepted: 03/05/2025] [Indexed: 03/22/2025]
Abstract
OBJECTIVES Knowledge on how sunlight impacts SERT activity via SLC6A4 promoter methylation in Seasonal Affective Disorder (SAD) remains limited. This study aimed to investigate the effect of daily sunshine duration on SLC6A4 promoter methylation in 28 patients with SAD and 40 healthy controls (HC). METHODS Daily sunlight data for Vienna, Austria (mean of 28 days before blood sampling), were obtained from ©GeoSphere Austria. A general linear model analysed SLC6A4 promoter methylation as the dependent variable, with sunlight hours as the independent variable, and group (SAD, HC), age, sex, and 5-HTTLPR/rs25531 as covariates. Exploratory analyses examined the effects of sunlight hours and methylation on Beck Depression Inventory (BDI) scores. RESULTS Sunlight had a significant effect on SLC6A4 promoter methylation (p = 0.03), with more sunlight hours resulting in lower methylation (r = -0.25). However, the interaction between sunlight and group was non-significant, suggesting a rather general effect across both groups. Sunlight also influenced BDI scores (p < 0.01), with fewer sunlight hours leading to higher scores (r = -0.25), which aligns with previous research. SLC6A4 promoter methylation had no significant effect on BDI scores. CONCLUSIONS Our findings suggest that sunlight influences SLC6A4 methylation without SAD specificity.
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Affiliation(s)
- Patricia A Handschuh
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - Matej Murgaš
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - Dietmar Winkler
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - Edda Winkler-Pjrek
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - Annette M Hartmann
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - Katharina Domschke
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
- Centre for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, Germany
| | - Pia Baldinger-Melich
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - Dan Rujescu
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - Rupert Lanzenberger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - Marie Spies
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
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Jameson AN, Siemann JK, Grueter CA, Grueter B, McMahon DG. Effects of age and sex on photoperiod modulation of nucleus accumbens monoamine content and release in adolescence and adulthood. Neurobiol Sleep Circadian Rhythms 2024; 16:100103. [PMID: 38585223 PMCID: PMC10990739 DOI: 10.1016/j.nbscr.2024.100103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/22/2024] [Accepted: 03/22/2024] [Indexed: 04/09/2024] Open
Abstract
Day length, or photoperiod, is a reliable environmental cue encoded by the brain's circadian clock that indicates changing seasons and induces seasonal biological processes. In humans, photoperiod, age, and sex have been linked to seasonality in neuropsychiatric disorders, as seen in Seasonal Affective Disorder, Major Depressive Disorder, and Bipolar Disorder. The nucleus accumbens is a key locus for the regulation of motivated behaviors and neuropsychiatric disorders. Using periadolescent and young adult male and female mice, here we assessed photoperiod's effect on serotonin and dopamine tissue content in the nucleus accumbens core, as well as on accumbal synaptic dopamine release and uptake. We found greater serotonin and dopamine tissue content in the nucleus accumbens from young adult mice raised in a Short winter-like photoperiod. In addition, dopamine release and clearance were greater in the nucleus accumbens from young adult mice raised in a Long summer-like photoperiod. Importantly, we found that photoperiod's effects on accumbal dopamine tissue content and release were sex-specific to young adult females. These findings support that in mice there are interactions across age, sex, and photoperiod that impact critical monoamine neuromodulators in the nucleus accumbens which may provide mechanistic insight into the age and sex dependencies in seasonality of neuropsychiatric disorders in humans.
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Affiliation(s)
- Alexis N. Jameson
- Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, 37232, USA
| | - Justin K. Siemann
- Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37232, USA
- Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, 37232, USA
| | - Carrie A. Grueter
- Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, 37232, USA
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA
- Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA
| | - BradA. Grueter
- Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37232, USA
| | - Douglas G. McMahon
- Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37232, USA
- Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA
- Department of Biological Sciences, Vanderbilt University, Nashville, TN, 37232, USA
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Dallaspezia S, Cardaci V, Mazza MG, De Lorenzo R, Rovere Querini P, Colombo C, Benedetti F. Higher Seasonal Variation of Systemic Inflammation in Bipolar Disorder. Int J Mol Sci 2024; 25:4310. [PMID: 38673894 PMCID: PMC11049938 DOI: 10.3390/ijms25084310] [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: 01/05/2024] [Revised: 04/08/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Seasonal rhythms affect the immune system. Evidence supports the involvement of immuno-inflammatory mechanisms in bipolar disorder (BD), with the neutrophil to lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII; platelets × neutrophils/lymphocytes) consistently reported to be higher in patients with BD than in HC, but seasonal rhythms of innate and adaptive immunity have never been studied. We retrospectively studied NLR and SII in 824 participants divided into three groups: 321 consecutively admitted inpatients affected by a major depressive episode in course of BD, and 255 consecutively admitted inpatients affected by obsessive-compulsive disorder (OCD; positive psychiatric control), and 248 healthy controls (HC). Patients with BD showed markedly higher markers of systemic inflammation in autumn and winter, but not in spring and summer, in respect to both HC and patients with OCD, thus suggesting a specific effect of season on inflammatory markers in BD, independent of a shared hospital setting and drug treatment. Given that systemic inflammation is emerging as a new marker and as target for treatment in depressive disorders, we suggest that seasonal rhythms should be considered for tailoring antidepressant immuno-modulatory treatments in a precision medicine approach.
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Affiliation(s)
- Sara Dallaspezia
- Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, Italy; (S.D.); (M.G.M.)
| | - Vincenzo Cardaci
- Università Vita-Salute San Raffaele, 20132 Milano, Italy; (V.C.); (P.R.Q.); (C.C.)
| | - Mario Gennaro Mazza
- Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, Italy; (S.D.); (M.G.M.)
| | - Rebecca De Lorenzo
- Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milano, Italy;
| | - Patrizia Rovere Querini
- Università Vita-Salute San Raffaele, 20132 Milano, Italy; (V.C.); (P.R.Q.); (C.C.)
- Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milano, Italy;
| | - Cristina Colombo
- Università Vita-Salute San Raffaele, 20132 Milano, Italy; (V.C.); (P.R.Q.); (C.C.)
- Mood Disorders Unit, IRCCS Ospedale San Raffaele, 20132 Milano, Italy
| | - Francesco Benedetti
- Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milano, Italy; (S.D.); (M.G.M.)
- Università Vita-Salute San Raffaele, 20132 Milano, Italy; (V.C.); (P.R.Q.); (C.C.)
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Karmakar S, Lal G. Role of Serotonergic System in Regulating Brain Tumor-Associated Neuroinflammatory Responses. Methods Mol Biol 2024; 2761:181-207. [PMID: 38427238 DOI: 10.1007/978-1-0716-3662-6_14] [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] [Indexed: 03/02/2024]
Abstract
Serotonin signaling regulates wide arrays of both neural and extra-neural functions. Serotonin is also found to affect cancer progression directly as well as indirectly by modulating the immune cells. In the brain, serotonin plays a key role in regulating various functions; disturbance of the normal activities of serotonin leads to various mental illnesses, including the neuroinflammatory response in the central nervous system (CNS). The neuroinflammatory response can be initiated in various psychological illnesses and brain cancer. Serotonergic signaling can impact the functions of both glial as well as the immune cells. It can also affect the tumor immune microenvironment and the inflammatory response associated with brain cancers. Apart from this, many drugs used for treatment of psychological illness are known to modulate serotonergic system and can cross the blood-brain barrier. Understanding the role of serotonergic pathways in regulating neuroinflammatory response and brain cancer will provide a new paradigm in modulating the serotonergic components in treating brain cancer and associated inflammation-induced brain damages.
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Affiliation(s)
- Surojit Karmakar
- National Centre for Cell Science (NCCS), SPPU Campus, Ganeshkhind, Pune, Maharashtra, India
| | - Girdhari Lal
- National Centre for Cell Science (NCCS), SPPU Campus, Ganeshkhind, Pune, Maharashtra, India.
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Spurny-Dworak B, Reed MB, Handschuh P, Vanicek T, Spies M, Bogner W, Lanzenberger R. The influence of season on glutamate and GABA levels in the healthy human brain investigated by magnetic resonance spectroscopy imaging. Hum Brain Mapp 2023; 44:2654-2663. [PMID: 36840505 PMCID: PMC10028653 DOI: 10.1002/hbm.26236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/22/2023] [Accepted: 02/02/2023] [Indexed: 02/26/2023] Open
Abstract
Seasonal changes in neurotransmitter systems have been demonstrated in imaging studies and are especially noticeable in diseased states such as seasonal affective disorder (SAD). These modulatory neurotransmitters, such as serotonin, are influencing glutamatergic and GABAergic neurotransmission. Furthermore, central components of the circadian pacemaker are regulated by GABA (the suprachiasmatic nucleus) or glutamate (e.g., the retinohypothalamic tract). Therefore, we explored seasonal differences in the GABAergic and glutamatergic system in 159 healthy individuals using magnetic resonance spectroscopy imaging with a GABA-edited 3D-MEGA-LASER sequence at 3T. We quantified GABA+/tCr, GABA+/Glx, and Glx/tCr ratios (GABA+, GABA+ macromolecules; Glx, glutamate + glutamine; tCr, total creatine) in five different subcortical brain regions. Differences between time periods throughout the year, seasonal patterns, and stationarity were tested using ANCOVA models, curve fitting approaches, and unit root and stationarity tests, respectively. Finally, Spearman correlation analyses between neurotransmitter ratios within each brain region and cumulated daylight and global radiation were performed. No seasonal or monthly differences, seasonal patterns, nor significant correlations could be shown in any region or ratio. Unit root and stationarity tests showed stable patterns of GABA+/tCr, GABA+/Glx, and Glx/tCr levels throughout the year, except for hippocampal Glx/tCr. Our results indicate that neurotransmitter levels of glutamate and GABA in healthy individuals are stable throughout the year. Hence, despite the important correction for age and gender in the analyses of MRS derived GABA and glutamate, a correction for seasonality in future studies does not seem necessary. Future investigations in SAD and other psychiatric patients will be of high interest.
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Affiliation(s)
- B Spurny-Dworak
- Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - M B Reed
- Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - P Handschuh
- Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - T Vanicek
- Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - M Spies
- Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
| | - W Bogner
- Department of Biomedical Imaging and Image-Guided Therapy, High Field MR Centre, Medical University of Vienna, Vienna, Austria
| | - R Lanzenberger
- Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria
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Social jetlag and risk of depression: Results from the Korea National Health and Nutrition Examination Survey. J Affect Disord 2023; 323:562-569. [PMID: 36496100 DOI: 10.1016/j.jad.2022.12.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 12/01/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Social jetlag, which is the mismatch between endogenous rhythm and social timing, is prevalent among the working population. Social jetlag may result in mood changes; however, evidence of relationship between social jetlag and depressive disorders has not been fully verified. Hence, this study aimed to investigate the association between social jetlag and depressive symptoms in a representative working population of South Korea. METHODS This study included 5447 Korean employees in the Korea National Health and Nutrition Examination Survey. Social jetlag was calculated as the difference between the midpoint of sleep time on weekdays and free days. Depressive symptoms were assessed using Patient Health Questionnaire-9. Multiple logistic regression was used to estimate the odds ratio after adjusting for confounding factors. Moreover, social jetlag and continuous depression scores were evaluated using linear regression and generalized additive models. RESULTS The proportion of the participants who had >2 h of social jetlag was 10.26 %. Depressive symptoms increased as social jetlag increased. Multiple logistic regression analysis showed that the adjusted OR (95 % confidence interval) for 1 to 2 h of social jetlag was 1.355 (0.891-2.059) and for >2 h was 1.859 (1.084-3.187), which <1 h was reference. LIMITATIONS This study used a cross-sectional design and measurements were based on self-reported scales. CONCLUSION This study found that social jetlag and depressive symptoms were significantly related in the Korean working population.
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Antidepressant Medication Status as a Moderator of Winter Depression Recurrence Following Cognitive-Behavioral Therapy and Light Therapy: Is There Evidence of an Iatrogenic Effect? COGNITIVE THERAPY AND RESEARCH 2022. [DOI: 10.1007/s10608-022-10344-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Benoy A, Wong LW, Ather N, Sajikumar S. Serotonin facilitates late-associative plasticity via synaptic tagging/cross-tagging and capture at hippocampal CA2 synapses in male rats. OXFORD OPEN NEUROSCIENCE 2022; 1:kvac002. [PMID: 38596711 PMCID: PMC10913837 DOI: 10.1093/oons/kvac002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/24/2022] [Accepted: 02/02/2022] [Indexed: 04/11/2024]
Abstract
Synaptic plasticity in the hippocampal Cornu Ammonis (CA) subfield, CA2, is tightly regulated. However, CA2 receives projections from several extra-hippocampal modulatory nuclei that release modulators that could serve to fine-tune plasticity at CA2 synapses. Considering that there are afferent projections from the serotonergic median raphe to hippocampal CA2, we hypothesized that the neuromodulator serotonin (5-hydroxytryptamine; 5-HT) could modulate CA2 synaptic plasticity. Here, we show that bath-application of serotonin facilitates the persistence of long-term depression (LTD) at the CA3 Schaffer collateral inputs to CA2 neurons (SC-CA2) when coupled to a weak low frequency electrical stimulation, in acute rat hippocampal slices. The observed late-LTD at SC-CA2 synapses was protein synthesis- and N-methyl-D-aspartate receptor (NMDAR)-dependent. Moreover, this late-LTD at SC-CA2 synapses paves way for the associative persistence of transient forms of LTD as well as long-term potentiation to long-lasting late forms of plasticity through synaptic tagging and cross-tagging respectively, at the entorhinal cortical synapses of CA2. We further observe that the 5-HT-mediated persistence of activity-dependent LTD at SC-CA2 synapses is blocked in the presence of the brain-derived neurotrophic factor scavenger, TrkB/Fc.
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Affiliation(s)
- Amrita Benoy
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore
- Life Sciences Institute Neurobiology Programme, National University of Singapore, 117456 Singapore
| | - Lik-Wei Wong
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore
- Life Sciences Institute Neurobiology Programme, National University of Singapore, 117456 Singapore
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore
| | - Niha Ather
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore
- Life Sciences Institute Neurobiology Programme, National University of Singapore, 117456 Singapore
| | - Sreedharan Sajikumar
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore
- Life Sciences Institute Neurobiology Programme, National University of Singapore, 117456 Singapore
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore
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Correia AS, Vale N. Antidepressants in Alzheimer's Disease: A Focus on the Role of Mirtazapine. Pharmaceuticals (Basel) 2021; 14:ph14090930. [PMID: 34577630 PMCID: PMC8467729 DOI: 10.3390/ph14090930] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 09/07/2021] [Accepted: 09/14/2021] [Indexed: 12/21/2022] Open
Abstract
Mirtazapine belongs to the category of antidepressants clinically used mainly in major depressive disorder but also used in obsessive-compulsive disorders, generalized anxiety, and sleep disturbances. This drug acts mainly by antagonizing the adrenergic α2, and the serotonergic 5-HT2 and 5-HT3 receptors. Neuropsychiatric symptoms, such as depression and agitation, are strongly associated with Alzheimer’s disease, reducing the life quality of these patients. Thus, it is crucial to control depression in Alzheimer’s patients. For this purpose, drugs such as mirtazapine are important in the control of anxiety, agitation, and other depressive symptoms in these patients. Indeed, despite some contradictory studies, evidence supports the role of mirtazapine in this regard. In this review, we will focus on depression in Alzheimer’s disease, highlighting the role of mirtazapine in this context.
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Affiliation(s)
- Ana Salomé Correia
- OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal;
- Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Nuno Vale
- OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal;
- Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
- Correspondence:
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Ionescu TM, Amend M, Hafiz R, Biswal BB, Maurer A, Pichler BJ, Wehrl HF, Herfert K. Striatal and prefrontal D2R and SERT distributions contrastingly correlate with default-mode connectivity. Neuroimage 2021; 243:118501. [PMID: 34428573 DOI: 10.1016/j.neuroimage.2021.118501] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 07/23/2021] [Accepted: 08/20/2021] [Indexed: 11/28/2022] Open
Abstract
Although brain research has taken important strides in recent decades, the interaction and coupling of its different physiological levels is still not elucidated. Specifically, the molecular substrates of resting-state functional connectivity (rs-FC) remain poorly understood. The aim of this study was elucidating interactions between dopamine D2 receptors (D2R) and serotonin transporter (SERT) availabilities in the striatum (CPu) and medial prefrontal cortex (mPFC), two of the main dopaminergic and serotonergic projection areas, and the default-mode network. Additionally, we delineated its interaction with two other prominent resting-state networks (RSNs), the salience network (SN) and the sensorimotor network (SMN). To this extent, we performed simultaneous PET/fMRI scans in a total of 59 healthy rats using [11C]raclopride and [11C]DASB, two tracers used to image quantify D2R and SERT respectively. Edge, node and network-level rs-FC metrics were calculated for each subject and potential correlations with binding potentials (BPND) in the CPu and mPFC were evaluated. We found widespread negative associations between CPu D2R availability and all the RSNs investigated, consistent with the postulated role of the indirect basal ganglia pathway. Correlations between D2Rs in the mPFC were weaker and largely restricted to DMN connectivity. Strikingly, medial prefrontal SERT correlated both positively with anterior DMN rs-FC and negatively with rs-FC between and within the SN, SMN and the posterior DMN, underlining the complex role of serotonergic neurotransmission in this region. Here we show direct relationships between rs-FC and molecular properties of the brain as assessed by simultaneous PET/fMRI in healthy rodents. The findings in the present study contribute to the basic understanding of rs-FC by revealing associations between inter-subject variances of rs-FC and receptor and transporter availabilities. Additionally, since current therapeutic strategies typically target neurotransmitter systems with the aim of normalizing brain function, delineating associations between molecular and network-level brain properties is essential and may enhance the understanding of neuropathologies and support future drug development.
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Affiliation(s)
- Tudor M Ionescu
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany
| | - Mario Amend
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany
| | - Rakibul Hafiz
- Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ, USA
| | - Bharat B Biswal
- Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ, USA
| | - Andreas Maurer
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany
| | - Bernd J Pichler
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany
| | - Hans F Wehrl
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany
| | - Kristina Herfert
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
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Alkozei A, Dailey NS, Bajaj S, Vanuk JR, Raikes AC, Killgore WDS. Exposure to Blue Wavelength Light Is Associated With Increases in Bidirectional Amygdala-DLPFC Connectivity at Rest. Front Neurol 2021; 12:625443. [PMID: 33841300 PMCID: PMC8032953 DOI: 10.3389/fneur.2021.625443] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 03/03/2021] [Indexed: 11/13/2022] Open
Abstract
Blue wavelength light has been used successfully as a treatment method for certain mood disorders, but, the underlying mechanisms behind the mood enhancing effects of light remain poorly understood. We investigated the effects of a single dose of 30 min of blue wavelength light (n = 17) vs. amber wavelength light (n = 12) exposure in a sample of healthy adults on subsequent resting-state functional and directed connectivity, and associations with changes in state affect. Individuals who received blue vs. amber wavelength light showed greater positive connectivity between the right amygdala and a region within the left dorsolateral prefrontal cortex (DLPFC). In addition, using granger causality, the findings showed that individuals who received blue wavelength light displayed greater bidirectional information flow between these two regions relative to amber light. Furthermore, the strength of amygdala-DLPFC functional connectivity was associated with greater decreases in negative mood for the blue, but not the amber light condition. Blue light exposure may positively influence mood by modulating greater information flow between the amygdala and the DLPFC, which may result in greater engagement of cognitive control strategies that are needed to perceive and regulate arousal and mood.
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Affiliation(s)
- Anna Alkozei
- Social, Cognitive, and Affective Neuroscience Laboratory, Department of Psychiatry, University of Arizona, Tucson, AZ, United States
| | - Natalie S Dailey
- Social, Cognitive, and Affective Neuroscience Laboratory, Department of Psychiatry, University of Arizona, Tucson, AZ, United States
| | - Sahil Bajaj
- Multimodal Clinical Neuroimaging Laboratory (MCNL), Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, United States
| | - John R Vanuk
- Social, Cognitive, and Affective Neuroscience Laboratory, Department of Psychiatry, University of Arizona, Tucson, AZ, United States
| | - Adam C Raikes
- Social, Cognitive, and Affective Neuroscience Laboratory, Department of Psychiatry, University of Arizona, Tucson, AZ, United States
| | - William D S Killgore
- Social, Cognitive, and Affective Neuroscience Laboratory, Department of Psychiatry, University of Arizona, Tucson, AZ, United States
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12
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Shankar A, Williams CT. The darkness and the light: diurnal rodent models for seasonal affective disorder. Dis Model Mech 2021; 14:dmm047217. [PMID: 33735098 PMCID: PMC7859703 DOI: 10.1242/dmm.047217] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
The development of animal models is a critical step for exploring the underlying pathophysiological mechanisms of major affective disorders and for evaluating potential therapeutic approaches. Although most neuropsychiatric research is performed on nocturnal rodents, differences in how diurnal and nocturnal animals respond to changing photoperiods, combined with a possible link between circadian rhythm disruption and affective disorders, has led to a call for the development of diurnal animal models. The need for diurnal models is most clear for seasonal affective disorder (SAD), a widespread recurrent depressive disorder that is linked to exposure to short photoperiods. Here, we briefly review what is known regarding the etiology of SAD and then examine progress in developing appropriate diurnal rodent models. Although circadian disruption is often invoked as a key contributor to SAD, a mechanistic understanding of how misalignment between endogenous circadian physiology and daily environmental rhythms affects mood is lacking. Diurnal rodents show promise as models of SAD, as changes in affective-like behaviors are induced in response to short photoperiods or dim-light conditions, and symptoms can be ameliorated by brief exposure to intervals of bright light coincident with activity onset. One exciting avenue of research involves the orexinergic system, which regulates functions that are disturbed in SAD, including sleep cycles, the reward system, feeding behavior, monoaminergic neurotransmission and hippocampal neurogenesis. However, although diurnal models make intuitive sense for the study of SAD and are more likely to mimic circadian disruption, their utility is currently hampered by a lack of genomic resources needed for the molecular interrogation of potential mechanisms.
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Affiliation(s)
- Anusha Shankar
- Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK 99775, USA
| | - Cory T Williams
- Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK 99775, USA
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Siemann JK, Grueter BA, McMahon DG. Rhythms, Reward, and Blues: Consequences of Circadian Photoperiod on Affective and Reward Circuit Function. Neuroscience 2020; 457:220-234. [PMID: 33385488 DOI: 10.1016/j.neuroscience.2020.12.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 12/07/2020] [Accepted: 12/08/2020] [Indexed: 02/01/2023]
Abstract
Circadian disruptions, along with altered affective and reward states, are commonly associated with psychiatric disorders. In addition to genetics, the enduring influence of environmental factors in programming neural networks is of increased interest in assessing the underpinnings of mental health. The duration of daylight or photoperiod is known to impact both the serotonin and dopamine systems, which are implicated in mood and reward-based disorders. This review first examines the effects of circadian disruption and photoperiod in the serotonin system in both human and preclinical studies. We next highlight how brain regions crucial for the serotoninergic system (i.e., dorsal raphe nucleus; DRN), and dopaminergic (i.e., nucleus accumbens; NAc and ventral tegmental area; VTA) system are intertwined in overlapping circuitry, and play influential roles in the pathology of mood and reward-based disorders. We then focus on human and animal studies that demonstrate the impact of circadian factors on the dopaminergic system. Lastly, we discuss how environmental factors such as circadian photoperiod can impact the neural circuits that are responsible for regulating affective and reward states, offering novel insights into the biological mechanisms underlying the pathophysiology, systems, and therapeutic treatments necessary for mood and reward-based disorders.
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Affiliation(s)
- Justin K Siemann
- Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA; Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN 37235, USA
| | - Brad A Grueter
- Department of Pharmacology, Vanderbilt University, Nashville, TN 37235, USA; Department of Anesthesiology, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37235, USA; Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN 37235, USA
| | - Douglas G McMahon
- Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN 37235, USA; Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN 37235, USA.
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Beyond Haemostasis and Thrombosis: Platelets in Depression and Its Co-Morbidities. Int J Mol Sci 2020; 21:ijms21228817. [PMID: 33233416 PMCID: PMC7700239 DOI: 10.3390/ijms21228817] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 11/18/2020] [Accepted: 11/19/2020] [Indexed: 12/11/2022] Open
Abstract
Alongside their function in primary haemostasis and thrombo-inflammation, platelets are increasingly considered a bridge between mental, immunological and coagulation-related disorders. This review focuses on the link between platelets and the pathophysiology of major depressive disorder (MDD) and its most frequent comorbidities. Platelet- and neuron-shared proteins involved in MDD are functionally described. Platelet-related studies performed in the context of MDD, cardiovascular disease, and major neurodegenerative, neuropsychiatric and neurodevelopmental disorders are transversally presented from an epidemiological, genetic and functional point of view. To provide a complete scenario, we report the analysis of original data on the epidemiological link between platelets and depression symptoms suggesting moderating and interactive effects of sex on this association. Epidemiological and genetic studies discussed suggest that blood platelets might also be relevant biomarkers of MDD prediction and occurrence in the context of MDD comorbidities. Finally, this review has the ambition to formulate some directives and perspectives for future research on this topic.
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Mendoza J. Circadian insights into the biology of depression: Symptoms, treatments and animal models. Behav Brain Res 2019; 376:112186. [PMID: 31473283 DOI: 10.1016/j.bbr.2019.112186] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 08/27/2019] [Accepted: 08/28/2019] [Indexed: 12/22/2022]
Abstract
In depression, symptoms range from loss of motivation and energy to suicidal thoughts. Moreover, in depression alterations might be also observed in the sleep-wake cycle and in the daily rhythms of hormonal (e.g., cortisol, melatonin) secretion. Both, the sleep-wake cycle and hormonal rhythms, are regulated by the internal biological clock within the hypothalamic suprachiasmatic nucleus (SCN). Therefore, a dysregulation of the internal mechanism of the SCN might lead in the disturbance of temporal physiology and depression. Hence, circadian symptoms in mood disorders can be used as important biomarkers for the prevention and treatment of depression. Disruptions of daily rhythms in physiology and behavior are also observed in animal models of depression, giving thus an important tool of research for the understanding of the circadian mechanisms implicated in mood disorders. This review discusses the alterations of daily rhythms in depression, and how circadian perturbations might lead in mood changes and depressive-like behavior in humans and rodents respectively. The use of animal models with circadian disturbances and depressive-like behaviors will help to understand the central timing mechanisms underlying depression, and how treating the biological clock(s) it may be possible to improve mood.
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Affiliation(s)
- Jorge Mendoza
- Institute of Cellular and Integrative Neurosciences, CNRS UPR-3212 University of Strasbourg, 8 allée du Général Rouvillois, 67000, Strasbourg, France.
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Powers JM, Murphy JEJ. Sunlight radiation as a villain and hero: 60 years of illuminating research. Int J Radiat Biol 2019; 95:1043-1049. [PMID: 31157572 DOI: 10.1080/09553002.2019.1627440] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
In the 60 years since the inaugural edition of the International Journal of Radiation Biology, much of our understanding of the biological effects of solar radiation has changed. Earlier in the century, sunlight played a 'hero's' role in reducing disabling rickets, while today debate still continues on the amount of sun required before exposure reveals the 'villainous' side of solar radiation. Although knowledge of the ultra violet (UV) component of sunlight as a carcinogen has become widespread, skin cancer rates are still rising yearly. Twentieth century attitudes have seen an about-face in the field of dermatological sun protection, with sunscreens changing from recipes designed to promote a 'healthy tan' to formulations proven to block both ultraviolet B (UVB) and more recently, ultraviolet A (UVA), to minimize premature sun-aging and skin cancer risk. In the early 1960s, DNA was first found to exist within mitochondria, while recently the connections between mitochondrial changes and UV radiation exposure have been expanded. Sixty years ago, understanding of the endocrine systems of mammals was enjoying its infancy. Early discoveries that light, particularly natural light, could have profound effects on functions such as sleep patterns and hormonal balance were made, while today more advanced knowledge has led to lighting improvements having pronounced effects on human wellbeing. Photosensitization 60 years ago was a health concern for both humans and their domestic animals, while today chemically engineered photosensitizing drugs can be administered along with highly directed light to pinpoint delivery targets for drug action. Life on earth is inextricably bound up with solar radiation. This article attempts to outline many of the ways in which our opinions about solar radiation have changed since the journal's inception.
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Affiliation(s)
- Julia Montelin Powers
- a Cellular Health and Toxicology Research Group, Department of Health and Nutritional Sciences , Institute of Technology Sligo , Sligo , Ireland
| | - James Edward John Murphy
- a Cellular Health and Toxicology Research Group, Department of Health and Nutritional Sciences , Institute of Technology Sligo , Sligo , Ireland
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Cools O, Hebbrecht K, Coppens V, Roosens L, De Witte A, Morrens M, Neels H, Sabbe B. Pharmacotherapy and nutritional supplements for seasonal affective disorders: a systematic review. Expert Opin Pharmacother 2018; 19:1221-1233. [PMID: 30048159 DOI: 10.1080/14656566.2018.1501359] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION A seasonal affective disorder (SAD) is a subtype of unipolar and bipolar major depressive disorders. It is characterized by its annual recurrence of depressive episodes at a particular season, mostly seen in winter and is responsible for 10-20% of the prevalence of major depressive disorders. Some pathophysiological hypotheses, such as the phase delay and the monoamine depletion hypotheses, have been postulated but the exact cause has not been fully unraveled yet. Studies on treatment for SAD in the last decade are lacking. To tackle this chronic disease, attention needs to be drawn to the gaps in this research field. AREAS COVERED In this systematic review, the authors give a broad overview of the pharmacological therapy available for SAD. Also, nutritional substances fitting well with the postulated hypotheses are reviewed for the treatment and prevention of SAD. There is a specific focus on the quality of the currently performed studies. EXPERT OPINION Light therapy and fluoxetine are the only proven and effective acute treatment options for SAD, while bupropion is the only registered drug for prevention of SAD. This area of research is in dire need of valid large-scale and sufficiently reproducible randomized control trials.
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Affiliation(s)
- Olivia Cools
- a Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences , University of Antwerp. Campus Drie Eiken , Antwerpen , Belgium
- b University Department, Psychiatric Hospital Duffel , Duffel , Belgium
| | - Kaat Hebbrecht
- a Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences , University of Antwerp. Campus Drie Eiken , Antwerpen , Belgium
- b University Department, Psychiatric Hospital Duffel , Duffel , Belgium
| | - Violette Coppens
- a Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences , University of Antwerp. Campus Drie Eiken , Antwerpen , Belgium
- b University Department, Psychiatric Hospital Duffel , Duffel , Belgium
| | - Laurence Roosens
- c Toxicological center, Department of Pharmaceutical Sciences , University of Antwerp. Campus Drie Eiken - gebouw S , Antwerpen , Belgium
| | - Andy De Witte
- d Psychiatric Unit of the academic hospital Sint-Vincentius Antwerp , Antwerp , Belgium
| | - Manuel Morrens
- a Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences , University of Antwerp. Campus Drie Eiken , Antwerpen , Belgium
- b University Department, Psychiatric Hospital Duffel , Duffel , Belgium
| | - Hugo Neels
- c Toxicological center, Department of Pharmaceutical Sciences , University of Antwerp. Campus Drie Eiken - gebouw S , Antwerpen , Belgium
| | - Bernard Sabbe
- a Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences , University of Antwerp. Campus Drie Eiken , Antwerpen , Belgium
- b University Department, Psychiatric Hospital Duffel , Duffel , Belgium
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Itzhacki J, Clesse D, Goumon Y, Van Someren EJ, Mendoza J. Light rescues circadian behavior and brain dopamine abnormalities in diurnal rodents exposed to a winter-like photoperiod. Brain Struct Funct 2018; 223:2641-2652. [PMID: 29560509 DOI: 10.1007/s00429-018-1655-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 03/18/2018] [Indexed: 12/17/2022]
Abstract
Seasonal affective disorder (SAD), beyond mood changes, is characterized by alterations in daily rhythms of behavior and physiology. The pathophysiological conditions of SAD involve changes in day length and its first-line treatment is bright light therapy. Animal models using nocturnal rodents have been studied to elucidate the neurobiological mechanisms of depression, but might be ill suited to study the therapeutic effects of light in SAD since they exhibit light-aversive responses. Here Arvicanthis ansorgei, a diurnal rodent, was used to determine behavioral, molecular and brain dopamine changes in response to exposure to a winter-like photoperiod consisting of a light-dark cycle with 8 h of light, under diminished light intensity, and 16 h of darkness. Furthermore, we evaluated whether timed-daily bright light exposure has an effect on behavior and brain physiology of winter-like exposed animals. Arvicanthis under a winter-like condition showed alterations in the synchronization of the locomotor activity rhythm to the light-dark cycle. Moreover, alterations in day-night activity of dopaminergic neurotransmission were revealed in the nucleus accumbens and the dorsal striatum, and in the day-night clock gene expression in the suprachiasmatic nucleus. Interestingly, whereas dopamine disturbances were reversed in animals exposed to daily light at early or late day, altered phase of the daily rhythm of locomotion was reverted only in animals exposed to light at the late day. Moreover, Per2 gene expression in the SCN was also affected by light exposure at late day in winter-like exposed animals. These findings suggest that light induces effects on behavior by mechanisms that rely on both circadian and rhythm-independent pathways influencing the dopaminergic circuitry. This last point might be crucial for understanding the mechanisms of non-pharmacological treatment in SAD.
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Affiliation(s)
- Jacob Itzhacki
- Institute of Cellular and Integrative Neurosciences, CNRS-UPR3212, 5 rue Blaise Pascal, 67084, Strasbourg Cedex, France.,Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
| | - Daniel Clesse
- Laboratoire de Neurosciences Cognitives et Adaptatives, CNRS, UMR 7364 and University of Strasbourg, Strasbourg, France
| | - Yannick Goumon
- Institute of Cellular and Integrative Neurosciences, CNRS-UPR3212, 5 rue Blaise Pascal, 67084, Strasbourg Cedex, France
| | - Eus J Van Someren
- Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.,Department of Integrative Neurophysiology and Psychiatry inGeest, Vrije Universiteit University and Medical Center, Neuroscience Campus, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands
| | - Jorge Mendoza
- Institute of Cellular and Integrative Neurosciences, CNRS-UPR3212, 5 rue Blaise Pascal, 67084, Strasbourg Cedex, France.
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Sarran C, Albers C, Sachon P, Meesters Y. Meteorological analysis of symptom data for people with seasonal affective disorder. Psychiatry Res 2017; 257:501-505. [PMID: 28843193 DOI: 10.1016/j.psychres.2017.08.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 05/19/2017] [Accepted: 08/12/2017] [Indexed: 02/01/2023]
Abstract
It is thought that variation in natural light levels affect people with Seasonal Affective Disorder (SAD). Several meteorological factors related to luminance can be forecast but little is known about which factors are most indicative of worsening SAD symptoms. The aim of this meteorological analysis is to determine which factors are linked to SAD symptoms. The symptoms of 291 individuals with SAD in and near Groningen have been evaluated over the period 2003-2009. Meteorological factors linked to periods of low natural light (sunshine, global radiation, horizontal visibility, cloud cover and mist) and others (temperature, humidity and pressure) were obtained from weather observation stations. A Bayesian zero adjusted auto-correlated multilevel Poisson model was carried out to assess which variables influence the SAD symptom score BDI-II. The outcome of the study suggests that the variable sunshine duration, for both the current and previous week, and global radiation for the previous week, are significantly linked to SAD symptoms.
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Affiliation(s)
| | - Casper Albers
- Heymans Institute for Psychological Research, University of Groningen, Grote Kruisstraat 2/1, 9712 TS Groningen, the Netherlands
| | - Patrick Sachon
- Met Office, Fitzroy Road, Exeter EX1 3PB, United Kingdom
| | - Ybe Meesters
- University Center for Psychiatry, University Medical Center Groningen, Groningen, PO Box 30 001, 9700 RB Groningen, the Netherlands
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Leahy LG. Overcoming Seasonal Affective Disorder. J Psychosoc Nurs Ment Health Serv 2017; 55:10-14. [PMID: 29084340 DOI: 10.3928/02793695-20171016-03] [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: 11/20/2022]
Abstract
Seasonal affective disorder (SAD) significantly impacts the lives of individuals around the world. The mood fluctuations that occur are not only exhibited during the winter months but also during the spring and summer. The key to identifying SAD is the distinct seasonal onset and spontaneous remission of symptoms over the course of a season. Nurses are in a unique position to identify the symptoms of SAD and offer treatment recommendations to reduce the negative impact of these seasonal mood fluctuations. As holistic health care practitioners, nurses provide patient education regarding healthy lifestyle interventions, which can aid in minimizing the disruptive symptoms of SAD. Advanced practice nurses can offer pharmacotherapy interventions to address symptoms contributing to the individual's inability to function across domains-individual, family, and social. Finally, after reading the article, nurses of all disciplines will have a better understanding of the evidence-based bright light therapy (also known as light box therapy) and how to incorporate this treatment when caring for patients with SAD. [Journal of Psychosocial Nursing and Mental Health Services, 55(11), 10-14.].
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Pereira JC, Pradella Hallinan M, Alves RC. Secondary to excessive melatonin synthesis, the consumption of tryptophan from outside the blood-brain barrier and melatonin over-signaling in the pars tuberalis may be central to the pathophysiology of winter depression. Med Hypotheses 2017; 98:69-75. [DOI: 10.1016/j.mehy.2016.11.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 11/27/2016] [Indexed: 12/17/2022]
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Campbell PD, Miller AM, Woesner ME. Bright Light Therapy: Seasonal Affective Disorder and Beyond. THE EINSTEIN JOURNAL OF BIOLOGY AND MEDICINE : EJBM 2017; 32:E13-E25. [PMID: 31528147 PMCID: PMC6746555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Since the first description of Seasonal Affective Disorder (SAD) by Rosenthal et al. in the 1980s, treatment with daily administration of light, or Bright Light Therapy (BLT), has been proven effective and is now recognized as a first-line therapeutic modality. More recently, studies aimed at understanding the pathophysiology of SAD and the mechanism of action of BLT have implicated shifts in the circadian rhythm and alterations in serotonin reuptake. BLT has also been increasingly used as an experimental treatment in non-seasonal unipolar and bipolar depression and other psychiatric disorders with known or suspected alterations in the circadian system. This review will discuss the history of SAD and BLT, the proposed pathophysiology of SAD and mechanisms of action of BLT in the treatment of SAD, and evidence supporting the efficacy of BLT in the treatment of non-seasonal unipolar major depression, bipolar depression, eating disorders, and ADHD.
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Affiliation(s)
- Philip D. Campbell
- Department of Psychiatry & Behavioral Sciences, Albert Einstein College of Medicine, Bronx NY 10461
| | - Ann M. Miller
- Department of Psychiatry & Behavioral Sciences, Albert Einstein College of Medicine, Bronx NY 10461
- Bronx Psychiatric Center, Bronx, NY 10461
| | - Mary E. Woesner
- Department of Psychiatry & Behavioral Sciences, Albert Einstein College of Medicine, Bronx NY 10461
- Bronx Psychiatric Center, Bronx, NY 10461
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Mc Mahon B, Andersen SB, Madsen MK, Hjordt LV, Hageman I, Dam H, Svarer C, da Cunha-Bang S, Baaré W, Madsen J, Hasholt L, Holst K, Frokjaer VG, Knudsen GM. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder. Brain 2016; 139:1605-14. [DOI: 10.1093/brain/aww043] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 01/28/2016] [Indexed: 11/14/2022] Open
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Cocchi M, Sardi L, Tonello L, Martelli G. Do mood disorders play a role in pig welfare? ITALIAN JOURNAL OF ANIMAL SCIENCE 2016. [DOI: 10.4081/ijas.2009.691] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Mouri A, Ikeda M, Koseki T, Iwata N, Nabeshima T. The ubiquitination of serotonin transporter in lymphoblasts derived from fluvoxamine-resistant depression patients. Neurosci Lett 2016; 617:22-6. [PMID: 26845564 DOI: 10.1016/j.neulet.2016.01.064] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 01/06/2016] [Accepted: 01/28/2016] [Indexed: 12/16/2022]
Abstract
There is insufficient serotonergic neuronal function in the pathophysiology of major depressive disorder (MDD). Serotonin transporter (SERT) plays a critical role in terminating the function of serotoninergic neurons. SERT is linked to vulnerability to MDD and is an important target for antidepressants. The expression of SERT in lymphocytes and platelets is associated with their expression in central nervous system. Most of the clinical studies that have analyzed the role of SERT in depression have focused on absolute expression of SERT in the brain or peripheral tissue. Our study has shown that the SERT protein is ubiquitinated, which has been implicated through the SERT stability and depressive behaviors in mice. In our study, we have used lymphoblasts derived from the peripheral blood lymphocytes to quantitatively examine SERT protein expression and ubiquitination in fluvoxamine-responsive and fluvoxamine-resistant MDD patients. We found that the protein levels of SERT were higher in the fluvoxamine-resistant MDD patients. Ubiquitinated protein levels of SERT were lower in the fluvoxamine-resistant MDD patients. The proteasome inhibitor failed to increase the protein levels of SERT in both fluvoxamine-responsive and fluvoxamine-resistant MDD patients. In sum, these findings suggest that the downregulation of the ubiquitination of SERT protein induces insufficient degradation of SERT by proteasome, which resulted in the upregulation of SERT protein in fluvoxamine-resistant MDD patients. Although further studies with various populations will be required to generalize results, SERT protein expression, ubiquitination, and the responsiveness of SERT expression to proteasome inhibitor are potential biomarkers for the diagnosis of MDD and antidepressant efficacy.
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Affiliation(s)
- Akihiro Mouri
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan; Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, Aichi, Japan
| | - Masashi Ikeda
- Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
| | - Takenao Koseki
- Department of Clinical Pharmacy, Fujita Health University School of Medicine, Aichi, Japan
| | - Nakao Iwata
- Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
| | - Toshitaka Nabeshima
- Nabeshima Laboratory, Faculty of Pharmacy, Meijo University, Nagoya, Japan; Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan; Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, Aichi, Japan.
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Fernández-Niño JA, Astudillo-García CI, Bojorquez-Chapela I, Morales-Carmona E, Montoya-Rodriguez AA, Palacio-Mejia LS. The Mexican Cycle of Suicide: A National Analysis of Seasonality, 2000-2013. PLoS One 2016; 11:e0146495. [PMID: 26752641 PMCID: PMC4709116 DOI: 10.1371/journal.pone.0146495] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 12/17/2015] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Suicide is a complex and multifactorial phenomenon with growing importance to public health. An increase in its occurrence has been observed in Mexico over the past 10 years. The present article analyzes the secular trend in suicide at the national level between the years 2000 and 2013. MATERIALS AND METHODS All suicides during the study period (n = 64,298, of which 82.11% were men) were characterized using a spectral decomposition of the time series and a wavelet analysis to evaluate the effect of seasonal changes, type of area (urban versus rural) and sex. RESULTS A seasonal pattern was observed with statistically significant cycles every 12 months, where peaks were identified in May but only for men in urban zones as of the year 2007. In addition, specific days of the year were found to have a higher frequency of suicides, which coincided with holidays (New Year, Mother's Day, Mexican Independence Day and Christmas). CONCLUSION A wavelet analysis can be used to decompose complex time series. To the best of our knowledge, this is the first application of this technique to the study of suicides in developing countries. This analysis enabled identifying a seasonal pattern among urban men in Mexico. The identification of seasonal patterns can help to create primary prevention strategies, increase the dissemination of crisis intervention strategies and promote mental health. These strategies could be emphasized during specific periods of the year and directed towards profiles with a higher risk.
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Affiliation(s)
- Julián Alfredo Fernández-Niño
- Information Center for Decisions in Public Health (CENIDSP), National Institute of Public Health of Mexico, Cuernavaca, Mexico
| | | | | | - Evangelina Morales-Carmona
- Information Center for Decisions in Public Health (CENIDSP), National Institute of Public Health of Mexico, Cuernavaca, Mexico
| | | | - Lina Sofia Palacio-Mejia
- Information Center for Decisions in Public Health (CENIDSP), National Institute of Public Health of Mexico, Cuernavaca, Mexico
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Dietary protein ingested before and during short photoperiods makes an impact on affect-related behaviours and plasma composition of amino acids in mice. Br J Nutr 2015; 114:1734-43. [DOI: 10.1017/s0007114515003396] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AbstractIn mammals, short photoperiod is associated with high depression- and anxiety-like behaviours with low levels of the brain serotonin and its precursor tryptophan (Trp). Because the brain Trp levels are regulated by its ratio to large neutral amino acids (Trp:LNAA) in circulation, this study elucidated whether diets of various protein sources that contain different Trp:LNAA affect depression- and anxiety-like behaviours in C57BL/6J mice under short-day conditions (SD). In the control mice on a casein diet, time spent in the central area in the open field test (OFT) was lower in the mice under SD than in those under long-day conditions (LD), indicating that SD exposure induces anxiety-like behaviour. The SD-induced anxiety-like behaviour was countered by an α-lactalbumin diet given under SD. In the mice that were on a gluten diet before transition to SD, the time spent in the central area in the OFT under SD was higher than that in the SD control mice. Alternatively, mice that ingested soya protein before the transition to SD had lower immobility in the forced swim test, a depression-like behaviour, compared with the SD control. Analysis of Trp:LNAA revealed lower Trp:LNAA in the SD control compared with the LD control, which was counteracted by an α-lactalbumin diet under SD. Furthermore, mice on gluten or soya protein diets before transition to SD exhibited high Trp:LNAA levels in plasma under SD. In conclusion, ingestion of specific proteins at different times relative to photoperiodic transition may modulate anxiety- and/or depression-like behaviours, partially through changes in plasma Trp:LNAA.
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Antidepressant-like effect of bright light is potentiated by l-serine administration in a mouse model of seasonal affective disorder. Brain Res Bull 2015; 118:25-33. [DOI: 10.1016/j.brainresbull.2015.08.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 08/28/2015] [Accepted: 08/29/2015] [Indexed: 12/11/2022]
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Diurnal and seasonal variation of the brain serotonin system in healthy male subjects. Neuroimage 2015; 112:225-231. [DOI: 10.1016/j.neuroimage.2015.03.007] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 02/11/2015] [Accepted: 03/05/2015] [Indexed: 11/20/2022] Open
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Goda R, Otsuka T, Iwamoto A, Kawai M, Shibata S, Furuse M, Yasuo S. Serotonin levels in the dorsal raphe nuclei of both chipmunks and mice are enhanced by long photoperiod, but brain dopamine level response to photoperiod is species-specific. Neurosci Lett 2015; 593:95-100. [PMID: 25797183 DOI: 10.1016/j.neulet.2015.03.035] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 03/13/2015] [Accepted: 03/18/2015] [Indexed: 11/27/2022]
Abstract
Seasonal affective disorder (SAD) is a subtype of major depressive or bipolar disorders associated with the shortened photoperiod in winter. This depressive disorder is integrally tied to the seasonal regulation of the brain's serotonergic system. Recently, we found that C57BL/6J mice subjected to a forced-swim test exhibited immobility, a photoperiod-dependent depression-associated behavior, and suppression of brain serotonin levels. However, mice are nocturnal animals, and it is unclear whether the brain serotonergic system responds similarly to photoperiod in nocturnal and diurnal species. This study compared the responses of brain serotonergic and dopaminergic systems to photoperiod in diurnal chipmunks and nocturnal C57BL/6J mice. In both species, serotonin levels in the dorsal raphe nuclei were higher under long-day conditions than short-day conditions, suggesting a similarity in the photoperiod responses of the serotonergic systems. However, photoperiod affected dopamine levels in various brain regions differently in the two species. Some chipmunk brain regions exhibited stronger photoperiod-induced changes in dopamine levels than those of C57BL/6J mice, and the direction of the changes in the hypothalamus was opposite. In conclusion, photoperiod may regulate the brain serotonergic system through similar mechanisms, regardless of whether the animals are diurnal or nocturnal, but photoperiod-dependent regulation of brain dopamine is species-specific.
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Affiliation(s)
- Ryosei Goda
- Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan
| | - Tsuyoshi Otsuka
- Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan
| | - Ayaka Iwamoto
- Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan
| | - Misato Kawai
- Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan
| | - Satomi Shibata
- Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan
| | - Mitsuhiro Furuse
- Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan
| | - Shinobu Yasuo
- Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan.
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Schaefer A, Burmann I, Regenthal R, Arélin K, Barth C, Pampel A, Villringer A, Margulies DS, Sacher J. Serotonergic modulation of intrinsic functional connectivity. Curr Biol 2014; 24:2314-8. [PMID: 25242032 DOI: 10.1016/j.cub.2014.08.024] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 06/30/2014] [Accepted: 08/13/2014] [Indexed: 10/24/2022]
Abstract
Serotonin functions as an essential neuromodulator that serves a multitude of roles, most prominently balancing mood. Serotonergic challenge has been observed to reduce intrinsic functional connectivity in brain regions implicated in mood regulation. However, the full scope of serotonergic action on functional connectivity in the human brain has not been explored. Here, we show evidence that a single dose of a serotonin reuptake inhibitor dramatically alters functional connectivity throughout the whole brain in healthy subjects (n = 22). Our network-centrality analysis reveals a widespread decrease in connectivity in most cortical and subcortical areas. In the cerebellum and thalamus, however, we find localized increases. These rapid and brain-encompassing connectivity changes linked to acute serotonin transporter blockade suggest a key role for the serotonin transporter in the modulation of the functional macroscale connectome.
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Affiliation(s)
- Alexander Schaefer
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Department of Electrical and Computer Engineering, Clinical Imaging Research Centre & Singapore Insitute for Neurotechnology, National University of Singapore, 117583 Singapore, Singapore
| | - Inga Burmann
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany
| | - Ralf Regenthal
- Division of Clinical Pharmacology, Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, 04107 Leipzig, Germany
| | - Katrin Arélin
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic of Cognitive Neurology, University Hospital Leipzig, 04103 Leipzig, Germany; Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany
| | - Claudia Barth
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany
| | - André Pampel
- Nuclear Magnetic Resonance Unit, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany
| | - Arno Villringer
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic of Cognitive Neurology, University Hospital Leipzig, 04103 Leipzig, Germany; Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany; Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, 04103 Leipzig, Germany; Berlin School of Mind and Brain, Mind and Brain Institute, Charité and Humboldt University, 10099 Berlin, Germany
| | - Daniel S Margulies
- Berlin School of Mind and Brain, Mind and Brain Institute, Charité and Humboldt University, 10099 Berlin, Germany; Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany
| | - Julia Sacher
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic of Cognitive Neurology, University Hospital Leipzig, 04103 Leipzig, Germany; Berlin School of Mind and Brain, Mind and Brain Institute, Charité and Humboldt University, 10099 Berlin, Germany.
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Scharinger C, Rabl U, Kasess CH, Meyer BM, Hofmaier T, Diers K, Bartova L, Pail G, Huf W, Uzelac Z, Hartinger B, Kalcher K, Perkmann T, Haslacher H, Meyer-Lindenberg A, Kasper S, Freissmuth M, Windischberger C, Willeit M, Lanzenberger R, Esterbauer H, Brocke B, Moser E, Sitte HH, Pezawas L. Platelet serotonin transporter function predicts default-mode network activity. PLoS One 2014; 9:e92543. [PMID: 24667541 PMCID: PMC3965432 DOI: 10.1371/journal.pone.0092543] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2012] [Accepted: 02/25/2014] [Indexed: 12/16/2022] Open
Abstract
Background The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. Methods A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA) to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD) activity and platelet Vmax. Results The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN) suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity. Conclusion This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.
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Affiliation(s)
- Christian Scharinger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Ulrich Rabl
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Christian H. Kasess
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Bernhard M. Meyer
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Tina Hofmaier
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
- Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Kersten Diers
- Department of Psychology, Dresden University of Technology, Dresden, Germany
| | - Lucie Bartova
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Gerald Pail
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Huf
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
- Department of Statistics and Probability Theory, Vienna University of Technology, Vienna, Austria
| | - Zeljko Uzelac
- Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Beate Hartinger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Klaudius Kalcher
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
- Department of Statistics and Probability Theory, Vienna University of Technology, Vienna, Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Helmuth Haslacher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Siegfried Kasper
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Michael Freissmuth
- Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Christian Windischberger
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Matthäus Willeit
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Rupert Lanzenberger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Harald Esterbauer
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Burkhard Brocke
- Department of Psychology, Dresden University of Technology, Dresden, Germany
| | - Ewald Moser
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Harald H. Sitte
- Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Lukas Pezawas
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- * E-mail:
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Lavoie J, Illiano P, Sotnikova TD, Gainetdinov RR, Beaulieu JM, Hébert M. The electroretinogram as a biomarker of central dopamine and serotonin: potential relevance to psychiatric disorders. Biol Psychiatry 2014; 75:479-86. [PMID: 23305992 DOI: 10.1016/j.biopsych.2012.11.024] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Revised: 11/26/2012] [Accepted: 11/27/2012] [Indexed: 01/11/2023]
Abstract
BACKGROUND Dysfunctions in brain dopamine and serotonin neurotransmission are believed to be involved in the etiology of psychiatric disorders, and electroretinogram (ERG) anomalies have been reported in psychiatric patients. The goal of this study was to evaluate whether ERG anomalies could result from central dopamine or serotonin dysfunctions or from changes in the retinal bioavailability of these neurotransmitters. METHOD Photopic and scotopic ERGs were recorded in R439H tryptophan hydroxylase 2 knockin (Tph2-KI) mice that have an approximately 80% decrease in brain serotonin and dopamine transporter knockout (DAT-KO) mice showing a fivefold increase in brain extracellular dopamine. Dopamine and serotonin retinal and striatal tissue content were also measured. The role of dopamine D1 receptors (D1R) and D2 receptors (D2R) in the ERG responses was evaluated in D1R-KO and D2R-KO mice. RESULTS An increase in photopic b-wave implicit time was observed in Tph2-KI mice (wildtype = 24.25 msec, KI = 25.22 msec; p = .011). The DAT-KO mice showed a decrease in rod sensitivity (wildtype =-1.97 log units, KO =-1.81 log units; p = .014). In contrast to remarkable alterations in brain levels, no changes in dopamine and serotonin retinal content were found in DAT-KO and Tph2-KI mice, respectively. The D1R-KO mice showed anomalies in photopic and scotopic maximal amplitude, whereas D2R-KO mice showed higher oscillatory potentials relative contribution to the b-wave amplitude. CONCLUSION Alterations in central dopamine and serotonin neurotransmission can affect the ERG responses. The ERG anomalies reported in psychiatric disorders might serve as biomarkers of central monoaminergic dysfunction, thus promoting ERG measurements as a useful tool in psychiatric research.
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Affiliation(s)
- Joëlle Lavoie
- Department of Psychiatry and Neurosciences, Quebec City, Quebec, Canada; Department of Ophthalmology and Otorhinolaryngology, Faculty of Medicine, Université Laval, Quebec City, Quebec, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Quebec, Canada
| | - Placido Illiano
- Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy
| | - Tatyana D Sotnikova
- Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy
| | - Raul R Gainetdinov
- Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy
| | - Jean-Martin Beaulieu
- Department of Psychiatry and Neurosciences, Quebec City, Quebec, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Quebec, Canada
| | - Marc Hébert
- Department of Ophthalmology and Otorhinolaryngology, Faculty of Medicine, Université Laval, Quebec City, Quebec, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, Quebec City, Quebec, Canada.
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How the cerebral serotonin homeostasis predicts environmental changes: a model to explain seasonal changes of brain 5-HTT as intermediate phenotype of the 5-HTTLPR. Psychopharmacology (Berl) 2013; 230:333-43. [PMID: 24150247 DOI: 10.1007/s00213-013-3308-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Accepted: 09/30/2013] [Indexed: 12/23/2022]
Abstract
Molecular imaging studies with positron emission tomography have revealed that the availability of serotonin transporter (5-HTT) in the human brain fluctuates over the course of the year. This effect is most pronounced in carriers of the short allele of the 5-HTT promoter region (5-HTTLPR), which has in several previous studies been linked to an increased risk to develop mood disorders. We argue that long-lasting fluctuations in the cerebral serotonin transmission, which is regulated via the 5-HTT, are responsible for mediating responses to environmental changes based on an assessment of the expected "safety" of the environment; this response is obtained in part through serotonergic modulation of the hypothalamic-pituitary-adrenal (HPA) axis. We posit that the intermediate phenotype of the s-allele may properly be understood as mediating a trade-off, wherein increased responsiveness of cerebral serotonin transmission to seasonal and other forms of environmental change imparts greater behavioral flexibility, at the expense of increased vulnerability to stress. This model may explain the somewhat higher prevalence of the s-allele in some human populations dwelling at geographic latitudes with pronounced seasonal climatic changes, while this hypothesis does not rule out that genetic drift plays an additional or even exclusive role. We argue that s-allele manifests as an intermediate phenotype in terms of an increased responsiveness of the 5-HTT expression to number of daylight hours, which may serve as a stable surrogate marker of other environmental factors, such as availability of food and safety of the environment in populations that live closer to the geographic poles.
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Srivastava S, Donaldson LF, Rai D, Melichar JK, Potokar J. Single bright light exposure decreases sweet taste threshold in healthy volunteers. J Psychopharmacol 2013; 27:921-9. [PMID: 23926241 DOI: 10.1177/0269881113499206] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
INTRODUCTION Bright light exposure can alter circulating serotonin levels, and alteration of available serotonin by acute selective serotonin reuptake inhibition significantly lowers sweet but not salt taste recognition thresholds. We tested the hypothesis that bright light exposure would increase sweet but not salt taste sensitivity in healthy adults. METHODS Fourteen healthy volunteers were exposed to bright (10,000 lux) and dim (<20 lux) light for 30 min each, in counterbalanced order. Measures of taste perception (salt and sweet) and mood were determined at baseline, and before and after each light exposure period. RESULTS Recognition thresholds for sucrose were significantly lower after bright but not dim light exposure. Thresholds for salt were unaffected by either condition. There were no significant changes in taste acuity, intensity or pleasantness for both the taste modalities and on visual analogue scales (VASs) for mood, anxiety, sleepiness and alertness, under either light condition. CONCLUSION Brief bright light exposure reduces sweet but not salt taste recognition thresholds in healthy humans.
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Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR. Transl Psychiatry 2013; 3:e311. [PMID: 24105442 PMCID: PMC3818011 DOI: 10.1038/tp.2013.84] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2013] [Revised: 07/28/2013] [Accepted: 08/01/2013] [Indexed: 11/08/2022] Open
Abstract
Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10(-7)) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.
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Whyte A, Jessen T, Varney S, Carneiro AMD. Serotonin transporter and integrin beta 3 genes interact to modulate serotonin uptake in mouse brain. Neurochem Int 2013; 73:122-6. [PMID: 24083985 DOI: 10.1016/j.neuint.2013.09.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 09/14/2013] [Accepted: 09/19/2013] [Indexed: 01/03/2023]
Abstract
Dysfunctions in serotonin (5-hydroxytryptamine, 5-HT) systems have been associated with several psychiatric illnesses, including anxiety, depression, obsessive-compulsive disorders and autism spectrum disorders. Convergent evidence from genetic analyses of human subjects has implicated the integrin β3 subunit gene (ITGB3) as a modulator of serotonergic systems via genetic interactions with the 5-HT transporter gene (SLC6A4, SERT). While genetic interactions may result from contributions of each gene at several levels, we hypothesize that ITGB3 modulates the 5-HT system at the level of the synapse, through the actions of integrin αvβ3. Here we utilized a genetic approach in mouse models to examine Itgb3 contributions to SERT function both in the context of normal and reduced SERT expression. As integrin αvβ3 is expressed in postsynaptic membranes, we isolated synaptoneurosomes, which maintain intact pre- and post-synaptic associations. Citalopram binding revealed significant Slc6a4-driven reductions in SERT expression in midbrain synapses, whereas no significant changes were observed in hippocampal or cortical projections. Expecting corresponding changes to SERT function, we also measured 5-HT uptake activity in synaptoneurosomal preparations. Itgb3 single heterozygous mice displayed significant reductions in 5-HT Vmax, with no changes in Km, in midbrain preparations. However, in the presence of both Itgb3 and Slc6a4 heterozygozity, 5-HT uptake was similar to wild-type levels, revealing a significant Slc6a4 by Itgb3 genetic interaction in the midbrain. Similar findings were observed in cortical preparations, whereas in the hippocampus, most Vmax changes were driven solely by Slc6a4. Our findings provide evidence that integrin αvβ3 is involved in the regulation of serotonergic systems in some, but not all 5-HT synapses, revealing novel contributions to synaptic specificity within the central nervous system.
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Affiliation(s)
- Alonzo Whyte
- Neuroscience Graduate Program, Vanderbilt Brain Institute, U1205 Medical Research Building III, 465 21st Avenue South, Nashville, TN 37232, United States
| | - Tammy Jessen
- Department of Pharmacology, Vanderbilt University School of Medicine, 215 Light Hall, Nashville, TN 37232, United States
| | - Seth Varney
- Department of Pharmacology, Vanderbilt University School of Medicine, 215 Light Hall, Nashville, TN 37232, United States
| | - Ana M D Carneiro
- Department of Pharmacology, Vanderbilt University School of Medicine, 215 Light Hall, Nashville, TN 37232, United States.
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Visual contrast sensitivity in major depressive disorder. J Psychosom Res 2013; 75:83-6. [PMID: 23751244 DOI: 10.1016/j.jpsychores.2013.03.008] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Revised: 03/12/2013] [Accepted: 03/15/2013] [Indexed: 11/23/2022]
Abstract
OBJECTIVE Through the eyes of those depressed, the world may appear dull and gray. Visual contrast sensitivity has recently been reported to be lower in depressed patients compared to healthy controls. We aimed to examine the consistency of this finding and to explore the underlying retinal electrophysiology. METHODS Twenty subjects with major depressive disorder and 20 matched healthy controls were studied. Pattern electroretinogram (PERG) and subjective visual contrast test were used to assess visual contrast sensitivity. Full-field electroretinography (ffERG) was additionally used to assess retinal neurophysiology. Depression was diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and depression severity was measured using standard psychometric scales. RESULTS Visual contrast sensitivity was significantly lower in depressed patients compared to controls based on the Landolt C visual contrast test, but no difference was found between groups using PERG and ffERG. Greater severity of depressive symptoms correlated (r=0.49, p=0.001) with poorer visual contrast sensitivity. CONCLUSIONS Depressed subjects had reduced visual contrast discrimination performance, but this finding could not be consistently determined using PERG. The neurobiological link between major depressive disorder and visual contrast sensitivity warrants further investigation.
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Williams MS. Platelets and depression in cardiovascular disease: A brief review of the current literature. World J Psychiatry 2012; 2:114-23. [PMID: 24175177 PMCID: PMC3782186 DOI: 10.5498/wjp.v2.i6.114] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2011] [Revised: 09/19/2012] [Accepted: 11/17/2012] [Indexed: 02/05/2023] Open
Abstract
Major depression is an independent risk factor for cardiovascular mortality and morbidity. The exact mechanisms linking depression and increased cardiovascular risk remain poorly understood. Several mechanisms have been proposed including increased platelet reactivity. This review focuses on the current literature that examines the platelet hypothesis of depression. To date studies show increased serotonin response, increased platelet serotonin receptor density, decreased serotonin transporter binding, and decreased platelet serotonin levels in individuals with depression. However other studies have shown no change in serotonin uptake. In addition to platelet serotonin specific pathways, other platelet pathways that have shown significant changes in depressed individuals include blunting of the platelet adenosine response, increased platelet thrombin response, increased glycoprotein Ib expression, increased P-selectin, β thromboglobulin, and platelet factor four, as well as decreased platelet brain derived neurotrophic factor. However there are other studies that show conflicting evidence of increased platelet activation as measured by integrin receptor α2bβ3. Other conflicting data include α adrenergic density and platelet response to augmented serotonin. The direction of future research in platelet functional changes in depression and coronary artery disease should continue to focus on serotonin specific pathways with emphasis on potential mechanisms of specific pathway changes.
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Affiliation(s)
- Marlene S Williams
- Marlene S Williams, Division of Cardiology, Johns Hopkins Bayview Medical Center, The Johns Hopkins University, Baltimore, MD 21224, United States
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Spindelegger C, Stein P, Wadsak W, Fink M, Mitterhauser M, Moser U, Savli M, Mien LK, Akimova E, Hahn A, Willeit M, Kletter K, Kasper S, Lanzenberger R. Light-dependent alteration of serotonin-1A receptor binding in cortical and subcortical limbic regions in the human brain. World J Biol Psychiatry 2012; 13:413-22. [PMID: 22111663 DOI: 10.3109/15622975.2011.630405] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE Climate, in particular sunshine, influences mood and energy levels, creating a positive upswing of mood on bright, sunny days and negative downswing in cold, dark winter seasons. Higher serotonin transporter availability in healthy human subjects in times of lesser light exposure and lower serotonin levels have been shown in winter. METHODS We examined the light-dependent variations in serotonin-1A receptor binding in limbic regions in 36 drug-naive healthy human subjects. Receptor binding was quantified using positron emission tomography and the radioligand [carbonyl-¹¹C]WAY-100635. Binding potential values were related to the amount of individual exposure to sunlight (daily duration of sunshine) and global radiation (total light intensity). RESULTS We found a 20-30% lower serotonin-1A receptor binding in the group exposed to a lower amount of global light radiation. Partial correlation analysis revealed significant positive correlations between the regional postsynaptic serotonin-1A receptor binding and global radiation accumulated over a period of 5 days. CONCLUSIONS Seasonal factors, such as daily amount of sunshine and global radiation, influence serotonin-1A receptor binding in limbic brain regions of healthy human subjects. Combined with recently demonstrated seasonal fluctuations in the serotonin transporter availability, our results underline the importance of seasonal factors in the regulation of the serotonergic transmission.
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Affiliation(s)
- Christoph Spindelegger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
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41
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On the application of light therapy in German-speaking countries. Eur Arch Psychiatry Clin Neurosci 2012; 262:501-5. [PMID: 22228483 DOI: 10.1007/s00406-011-0286-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2011] [Accepted: 12/15/2011] [Indexed: 10/14/2022]
Abstract
Many studies have investigated seasonal affective disorder (SAD; fall-winter-depression) and its treatment with light therapy (LT). However, to the best of our knowledge, no other study has investigated the usage of LT in Europe since 1994. Thus, we performed a survey in hospitals with adult psychiatric departments in German-speaking countries by questionnaire. First, a questionnaire was constructed, considering also recent developments in LT. This questionnaire was sent to all hospitals with adult psychiatric departments listed in the "Deutsches Krankenhaus Adressbuch," which contains hospitals from all German-speaking countries (Germany, Switzerland, and Austria). Non-responders were asked to answer the questionnaire by mail and by phone. We achieved a completion rate of 58%. Data show almost no relevant, non-artificial differences between countries as well as between type of hospital. LT is more frequently used in university and state hospitals than in other types of treatment facilities. Compared to 1994, the major findings are (1) a substantial increase in the use of LT from 13.0 to 69.8% with no differences between Germany, Austria, and Switzerland, (2) this increase is mostly due to treatment for various forms of depression and further possible applications are less often considered, (3) there is a shift in the usage of LT from monotherapy to combination of pharmacotherapy with LT as an adjunctive treatment, and (4) a north-south comparison showed no substantial differences. Considerably higher rates of usage of LT have been found compared to the last survey in German-speaking countries taking place in 1994. Usage almost tripled; however, possible indications for LT other than SAD and non-seasonal depression are not applied to full extent. Further efforts on the propagation of LT should therefore be undertaken, with the same rigorous studies as for pharmacotherapy.
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42
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Vyssoki B, Praschak-Rieder N, Sonneck G, Blüml V, Willeit M, Kasper S, Kapusta ND. Effects of sunshine on suicide rates. Compr Psychiatry 2012; 53:535-9. [PMID: 21821241 DOI: 10.1016/j.comppsych.2011.06.003] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2011] [Revised: 05/30/2011] [Accepted: 06/07/2011] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVES Seasonal spring peaks of suicide are well described in epidemiological studies, but their origin is poorly understood. More recent evidence suggests that this peak may be associated with the increase in the duration of sunshine in spring. We investigated the effect of number of sunshine hours per month on suicide rates in Austria between 1996 and 2006. METHODS Suicide data, differentiated by month of suicide, sex, and method of suicide (violent vs nonviolent methods), were provided by Statistics Austria. Data on the average number of sunshine hours per month were calculated from 39 representative meteorological stations (provided by the Austrian Central Institute for Meteorology and Geodynamics). For statistical analysis, analysis of variance tests, Kruskal-Wallis tests, and Pearson correlation tests were used. RESULTS A total of 16,673 suicides with a median of 126 ± 19.8 suicides per month occurred in the examined period. A clear seasonal pattern was observed, with suicide frequencies being highest between March and May and lowest between November and January (df = 11, F = 5.2, P < .0001) for men (df = 11, F = 4.9, P < .0001) and women (df = 11, F = 2.4, P = .008). The average number of sunshine hours per month was significantly correlated with the number of suicides among both sexes (r = .43, P < .0001), violent methods (r = .48, P < .0001) but not with nonviolent methods (r = .03, P = .707). CONCLUSIONS This study shows that seasonal changes in sunshine account for variations in the number of suicides and especially violent suicides. We propose that sunshine, via interactions with serotonin neurotransmission, may trigger increased impulsivity and promote suicidal acts. However, because of the hypothesis-generating design of this study, more research is needed to further clarify the role of sunshine in triggering neurobiologic changes, which might contribute to suicidal behavior.
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Affiliation(s)
- Benjamin Vyssoki
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
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43
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Praschak-Rieder N, Willeit M. Imaging of seasonal affective disorder and seasonality effects on serotonin and dopamine function in the human brain. Curr Top Behav Neurosci 2012; 11:149-167. [PMID: 22218931 DOI: 10.1007/7854_2011_174] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
According to current knowledge, disturbances in brain monoamine transmission play a major role in many psychiatric disorders, and many of the radioligands used for investigating these disorders bind to targets within the brain monoamine systems. However, a phylogenetically ancient and prevailing function of monoamines is to mediate the adaptation of organisms and cells to rhythmical changes in light conditions, and to other environmental rhythms, such as changes in temperature, or the availability of energy resources throughout the seasons. The physiological systems mediating these changes are highly conserved throughout species, including humans. Here we review the literature on seasonal changes in binding of monoaminergic ligands in the human brain. Moreover, we argue for the importance of considering possible effects of season when investigating brain monoamines in healthy subjects and subjects with psychiatric disorders.
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Affiliation(s)
- Nicole Praschak-Rieder
- Department of Biological Psychiatry, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria,
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44
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45
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Hsu JW, Wang SJ, Lin CL, Hsieh WC, Lirng JF, Shen YC, Liao MH, Chou YH. Short term vs. long term test-retest reproducibility of ¹²³I-ADAM for the binding of serotonin transporters in the human brain. Psychiatry Res 2011; 194:224-229. [PMID: 22079655 DOI: 10.1016/j.pscychresns.2011.04.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2010] [Revised: 04/13/2011] [Accepted: 04/28/2011] [Indexed: 10/15/2022]
Abstract
Previous brain imaging studies have demonstrated a seasonal difference of serotonin transporter (SERT) binding in the human brain. However, the results were somewhat contradictory. We conducted test-retest study with single photon emission computed tomography (SPECT) with ¹²³I-ADAM as ligand in 28 healthy subjects. Ten of the subjects were studied within 1 month, whereas 18 were randomly assigned to be studied over a period of up to 1 year. The primary measure was the specific uptake ratio (SUR). Regions of interest included the midbrain, thalamus, putamen and caudate. The intra-class correlation coefficient (ICC) was 0.52-0.94 across different brain regions over 1 month, whereas the ICC was -0.24-0.63 over a 1-year period. The 1-month variability ranged from 6.5 ± 5.1% to 12.5 ± 10.6% across different brain regions, and the 1-year variability ranged from 16.5 ± 9.6% to 41.9 ± 35.5%. The Kruskal-Wallis test revealed a significant difference of variability across months. The Wilcoxon Signed Ranks Test showed the SUR between test-retest scans was of borderline significance. Curve fitting, using a 4th degree polynomial model, revealed a significant circadian correlation between the variability and interval of test-retest measurements. Our findings demonstrate the test-retest reproducibility of ¹²³I-ADAM in different time periods and suggest that circadian variation of SERT levels in the human brain might exist.
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Affiliation(s)
- Ju-Wei Hsu
- Department of Psychiatry, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan
| | - Shyh-Jen Wang
- Department of Nuclear Medicine, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan
| | - Chun-Lung Lin
- Department of Psychiatry, Taoyuan Armed Forces General Hospital, Taipei, Taiwan
| | - Wen-Chi Hsieh
- Department of Psychiatry, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan
| | - Jiing-Feng Lirng
- Department of Radiology, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan
| | - Yuh-Chiang Shen
- National Research Institute of Chinese Medicine, Taipei, Taiwan
| | - Mei-Hsiu Liao
- Institute of Nuclear Energy Research, Lung-Tan, Taoyuan, Taiwan
| | - Yuan-Hwa Chou
- Department of Psychiatry, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan.
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Pail G, Huf W, Pjrek E, Winkler D, Willeit M, Praschak-Rieder N, Kasper S. Bright-light therapy in the treatment of mood disorders. Neuropsychobiology 2011; 64:152-62. [PMID: 21811085 DOI: 10.1159/000328950] [Citation(s) in RCA: 164] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2009] [Accepted: 08/11/2009] [Indexed: 12/14/2022]
Abstract
Bright-light therapy (BLT) is established as the treatment of choice for seasonal affective disorder/winter type (SAD). In the last two decades, the use of BLT has expanded beyond SAD: there is evidence for efficacy in chronic depression, antepartum depression, premenstrual depression, bipolar depression and disturbances of the sleep-wake cycle. Data on the usefulness of BLT in non-seasonal depression are promising; however, further systematic studies are still warranted. In this review, the authors present a comprehensive overview of the literature on BLT in mood disorders. The first part elucidates the neurobiology of circadian and seasonal adaptive mechanisms focusing on the suprachiasmatic nucleus (SCN), the indolamines melatonin and serotonin, and the chronobiology of mood disorders. The SCN is the primary oscillator in humans. Indolamines are known to transduce light signals into cells and organisms since early in evolution, and their role in signalling change of season is still preserved in humans: melatonin is synthesized primarily in the pineal gland and is the central hormone for internal clock circuitries. The melatonin precursor serotonin is known to modulate many behaviours that vary with season. The second part discusses the pathophysiology and clinical specifiers of SAD, which can be seen as a model disorder for chronobiological disturbances and the mechanism of action of BLT. In the third part, the mode of action, application, efficacy, tolerability and safety of BLT in SAD and other mood disorders are explored.
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Affiliation(s)
- Gerald Pail
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
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Guzmán DC, García EH, Mejía GB, Olguín HJ, Jiménez FT, Soto EB, Del Angel DS, Aparicio LC. Effect of sibutramine on 5-hydroxyindole acetic acid levels and selected oxidative biomarkers on brain regions of female rats in the presence of zinc. Basic Clin Pharmacol Toxicol 2011; 110:421-6. [PMID: 22141426 DOI: 10.1111/j.1742-7843.2011.00829.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
A number of drugs, like sibutramine, which are used clinically in weight control, act on serotonergic metabolism. However, their relation with zinc and free radical (FR) production in central nervous system remains unknown. This study aimed to evaluate the effect of sibutramine and zinc on FR production. Female Wistar rats (about 250 g) were used in this study. The animals received 400 μg/kg of zinc and 10 mg/kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for the measurement of lipid peroxidation thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), hydrogen peroxide (H(2) O(2) ), calcium and 5-hydroxyindole acetic acid (5-HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine group. Zinc given alone and in combination with sibutramine decreased H(2) O(2) concentration in cortex, hemispheres and cerebellum but increased calcium and 5-HIAA concentration in all brain regions. Our results suggest that sibutramine and zinc are associated with weight loss, an effect that was more pronounced in the group treated with both drugs. Reduction in oxidative stress may be involved in these effects.
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Affiliation(s)
- David C Guzmán
- Laboratory of Neurochemistry, National Institute of Pediatrics, Mexico City, Mexico
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Scheid JM, Holzman CB, Jones N, Friderici KH, Jernigan KA, Symonds LL, Sikorskii A, Fisher R. Life stressors and 5-HTTLPR interaction in relation to midpregnancy depressive symptoms among African-American women. Psychiatr Genet 2011; 21:271-80. [PMID: 22030619 PMCID: PMC3205426 DOI: 10.1097/ypg.0b013e32834603e8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE In earlier analyses of nonHispanic White women we found a stronger relation between abuse history and midpregnancy elevated depressive symptoms in women with the serotonin transporter (5-HTTLPR) S/S genotype. Here, we focus on African-American women (N=698). Our inquiry is motivated by racial differences in depression diagnosis/treatment, stressors, and frequency of major 5-HTTLPR alleles (S, LA, LG). MATERIALS AND METHODS Stressful life events (lifetime) and depressive symptoms (current) were ascertained at 15-27 weeks gestation. A Center for Epidemiological Studies Depression Score of more than or equal to 18 was considered 'elevated'. Life events were scored together and separated into six subconstructs. 5-HTTLPR genotypes were grouped as follows: (i) L and S alleles, (ii) S-LG equivalence ('triallelic to biallelic'), and (iii) LA/LA, all others, S/S ('high/intermediate/low'). Odds ratios (OR) for 'elevated' depressive symptoms-life events (total and subconstructs) relations were calculated for each genotype grouping. RESULTS The prevalence of 'elevated' depressive symptoms did not vary by genotype. The relation between stressful life events and 'elevated' depressive symptoms was stronger in S/S compared with LA/LA genotype (interaction P=0.11). Of the six subconstructs, only abuse showed a statistically significant gene-environment interaction. The OR for the abuse-'elevated' depressive symptoms association was greater for S/S vs. LA/LA genotype (interaction P=0.03) and in the 'triallelic to biallelic' grouping (interaction P=0.04). In the 'high/intermediate/low' grouping, 'low' (S/S) had a higher OR (5.5) than both 'intermediate' and 'high' (ORs≤2.3) (interaction P=0.10). CONCLUSIONS These results show the importance of examining racial groups, specific stressful events, and different 5-HTTLPR genotype groupings when exploring gene-environment interactions in depression.
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Affiliation(s)
- Jeanette M Scheid
- Departments of Psychiatry, Michigan State University, East Lansing, Michigan, USA.
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Abnormal hypothalamic response to light in seasonal affective disorder. Biol Psychiatry 2011; 70:954-61. [PMID: 21820647 PMCID: PMC5323254 DOI: 10.1016/j.biopsych.2011.06.022] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2011] [Revised: 06/20/2011] [Accepted: 06/20/2011] [Indexed: 11/20/2022]
Abstract
BACKGROUND Vulnerability to the reduction in natural light associated with fall/winter is generally accepted as the main trigger of seasonal affective disorder (SAD), whereas light therapy is a treatment of choice of the disorder. However, the relationship between exposure to light and mood regulation remains unclear. As compared with green light, blue light was shown to acutely modulate emotion brain processing in healthy individuals. Here, we investigated the impact of light on emotion brain processing in patients with SAD and healthy control subjects and its relationship with retinal light sensitivity. METHODS Fourteen symptomatic untreated patients with SAD (34.5 ± 8.2 years; 9 women) and 16 healthy control subjects (32.3 ± 7.7 years; 11 women) performed an auditory emotional task in functional magnetic resonance imaging during the fall/winter season, while being exposed to alternating blue and green monochromatic light. Scotopic and photopic retinal light sensitivities were then evaluated with electroretinography. RESULTS Blue light enhanced responses to auditory emotional stimuli in the posterior hypothalamus in patients with SAD, whereas green light decreased these responses. These effects of blue and green light were not observed in healthy control subjects, despite similar retinal sensitivity in SAD and control subjects. CONCLUSIONS These results point to the posterior hypothalamus as the neurobiological substrate involved in specific aspects of SAD, including a distinctive response to light and altered emotional responses.
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50
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Interactions of the serotonin and circadian systems: nature and nurture in rhythms and blues. Neuroscience 2011; 197:8-16. [PMID: 21963350 DOI: 10.1016/j.neuroscience.2011.09.036] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2011] [Revised: 09/08/2011] [Accepted: 09/16/2011] [Indexed: 01/31/2023]
Abstract
The serotonin and circadian systems are principal regulatory networks of the brain. Each consists of a unique set of neurons that make widespread neural connections and a defined gene network of transcriptional regulators and signaling genes that subserve serotonergic and circadian function at the genetic level. These master regulatory networks of the brain are extensively intertwined, with reciprocal circuit connections, expression of key genetic elements for serotonin signaling in clock neurons and expression of key clock genes in serotonergic neurons. The reciprocal connections of the serotonin and circadian systems likely have importance for neurobehavioral disorders, as suggested by their convergent contribution to a similar range of mood disorders including seasonal affective disorder (SAD), bipolar disorder, and major depression, and as suggested by their overlapping relationship with the developmental disorder, autism spectrum disorder. Here we review the neuroanatomical and genetic basis for serotonin-circadian interactions in the brain, their potential relationship with neurobehavioral disorders, and recent work examining the effects on the circadian system of genetic perturbation of the serotonergic system as well as the molecular and behavioral effects of developmental imprinting of the circadian system with perinatal seasonal light cycles.
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