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Ding Y, Tian Q, Hou W, Chen Z, Mao Z, Bo Q, Dong F, Wang C. Core of sensory gating deficits in first-episode schizophrenia: attention dysfunction. Front Psychiatry 2023; 14:1160715. [PMID: 37181885 PMCID: PMC10169682 DOI: 10.3389/fpsyt.2023.1160715] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 04/05/2023] [Indexed: 05/16/2023] Open
Abstract
Background Sensory gating deficits are a common feature of schizophrenia and may be indicative of higher-order psychopathological impairments. It has been proposed that incorporating subjective attention components into prepulse inhibition (PPI) measures may improve the accuracy of assessing these deficits. This study aimed to investigate the relationship between modified PPI and cognitive function, with a specific focus on subjective attention, to gain a better understanding of the underlying mechanisms of sensory processing deficits in schizophrenia. Methods Fifty-four unmedicated first-episode schizophrenia (UMFE) patients and 53 healthy controls participated in this study. The modified Prepulse Inhibition paradigm, including Perceived Spatial Separation PPI (PSSPPI) and Perceived Spatial Colocation PPI (PSCPPI), was used to evaluate sensorimotor gating deficits. Cognitive function was assessed in all participants using the Chinese version of the MATRICS Consensus Cognitive Suite Test (MCCB). Results UMFE patients had lower MCCB scores and deficient PSSPPI scores than healthy controls. PSSPPI was negatively correlated with total PANSS scores and positively correlated with the speed of processing, attention/ vigilance, and social cognition. Multiple linear regression analysis showed that the PSSPPI at 60 ms had a significant effect on attentional/ vigilance and social cognition, even after controlling for gender, age, years of education, and smoking. Conclusion The study revealed notable impairments in sensory gating and cognitive function in UMFE patients, best reflected by the PSSPPI measure. Specifically, PSSPPI at 60 ms was significantly associated with both clinical symptoms and cognitive performance, suggesting that PSSPPI at 60 ms may capture psychopathological symptoms related to psychosis.
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Affiliation(s)
- Yushen Ding
- Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Qing Tian
- Suzhou Guangji Hospital, The Affiliated Guangji Hospital of Soochow University, The Institute of Mental Health, Suzhou, China
| | - Wenpeng Hou
- Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Zhenzhu Chen
- Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Zhen Mao
- Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Qijing Bo
- Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Fang Dong
- Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Chuanyue Wang
- Beijing Key Laboratory of Mental Disorders, Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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Li S, Chan SY, Higgins A, Hall MH. Sensory gating, neurocognition, social cognition and real-life functioning: a 2-year follow-up of early psychosis. Psychol Med 2023; 53:2540-2552. [PMID: 37310299 DOI: 10.1017/s0033291721004463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Diminished sensory gating (SG) is a robust finding in psychotic disorders, but studies of early psychosis (EP) are rare. It is unknown whether SG deficit leads to poor neurocognitive, social, and/or real-world functioning. This study aimed to explore the longitudinal relationships between SG and these variables. METHODS Seventy-nine EP patients and 88 healthy controls (HCs) were recruited at baseline. Thirty-three and 20 EP patients completed 12-month and 24-month follow-up, respectively. SG was measured using the auditory dual-click (S1 & S2) paradigm and quantified as P50 ratio (S2/S1) and difference (S1-S2). Cognition, real-life functioning, and symptoms were assessed using the MATRICS Consensus Cognitive Battery, Global Functioning: Social (GFS) and Role (GFR), Multnomah Community Ability Scale (MCAS), Awareness of Social Inference Test (TASIT), and the Positive and Negative Syndrome Scale (PANSS). Analysis of variance (ANOVA), chi-square, mixed model, correlation and regression analyses were used for group comparisons and relationships among variables controlling for potential confounding variables. RESULTS In EP patients, P50 ratio (p < 0.05) and difference (p < 0.001) at 24-month showed significant differences compared with that at baseline. At baseline, P50 indices (ratio, S1-S2 difference, S1) were independently associated with GFR in HCs (all p < 0.05); in EP patients, S2 amplitude was independently associated with GFS (p = 0.037). At 12-month and 24-month, P50 indices (ratio, S1, S2) was independently associated with MCAS (all p < 0.05). S1-S2 difference was a trending predictor of future function (GFS or MCAS). CONCLUSIONS SG showed progressive reduction in EP patients. P50 indices were related to real-life functioning.
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Affiliation(s)
- Shen Li
- Schizophrenia and Bipolar Disorders Program, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
- Psychosis Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
- Department of Psychiatry, College of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Shi Yu Chan
- Schizophrenia and Bipolar Disorders Program, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
- Psychosis Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
- Translational Neurosciences, Singapore Institute for Clinical Sciences 117609, Singapore
| | - Amy Higgins
- Schizophrenia and Bipolar Disorders Program, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
- Psychosis Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
| | - Mei-Hua Hall
- Schizophrenia and Bipolar Disorders Program, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
- Psychosis Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
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P50 sensory gating, cognitive deficits and depressive symptoms in first-episode antipsychotics-naïve schizophrenia. J Affect Disord 2023; 324:153-161. [PMID: 36587903 DOI: 10.1016/j.jad.2022.12.143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 12/21/2022] [Accepted: 12/25/2022] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Sensory gating P50 (SG-P50) may be involved in the pathophysiological mechanisms of impaired cognition in schizophrenia (SCZ). Comorbid depressive symptoms are common in SCZ patients and are also found to be associated with their cognitive impairment. However, it is unclear whether SG-P50 is abnormal in first episode antipsychotics naïve (FEAN) SCZ patients with depressive symptoms. Our aimed to investigate the relationships between SG-P50, depressive symptoms and neurocognition in FEAN-SCZ patients. METHODS We recruited 103 FEAN-SCZ patients (depression: n = 63; non-depression: n = 40) and 55 healthy controls. SG-P50 was measured using the standard auditory dual-click (S1&S2) paradigm. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale-17 (HDRS-17). Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS Compared with non-depressive patients, depressive patients had a significantly larger S2 amplitude (p = 0.005) and a higher S2/S1 ratio at trend level (p = 0.075) after corrected. There were significant differences in the scores of CPT-IP and Mazes (NAB) between depressive and non-depressive FEAN-SCZ patients (both p values < 0.05). For all patients, the SG-P50 S2/S1 ratio was significantly correlated with HDRS-17 score (r = 0.23, p = 0.020) and MCCB-Symbol coding (r = -0.16, p = 0.043). For depressive FEAN-SCZ patients, S2 amplitude was an independent predictor of the MCCB-Mazes (NAB) (β = -0.31, t = -2.52, p = 0.015). CONCLUSIONS SG-P50 deficit may be an informational biomarker for depressive symptoms and neurocognitive impairments in FEAN-SCZ patients.
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Wang S, Li Z, Wang X, Li J, Wang X, Chen J, Li Y, Wang C, Qin L. Cortical and thalamic modulation of auditory gating in the posterior parietal cortex of awake mice. Cereb Cortex 2023:7032934. [PMID: 36757182 DOI: 10.1093/cercor/bhac539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 02/10/2023] Open
Abstract
Auditory gating (AG) is an adaptive mechanism for filtering out redundant acoustic stimuli to protect the brain against information overload. AG deficits have been found in many mental illnesses, including schizophrenia (SZ). However, the neural correlates of AG remain poorly understood. Here, we found that the posterior parietal cortex (PPC) shows an intermediate level of AG in auditory thalamocortical circuits, with a laminar profile in which the strongest AG is in the granular layer. Furthermore, AG of the PPC was decreased and increased by optogenetic inactivation of the medial dorsal thalamic nucleus (MD) and auditory cortex (AC), respectively. Optogenetically activating the axons from the MD and AC drove neural activities in the PPC without an obvious AG. These results indicated that AG in the PPC is determined by the integrated signal streams from the MD and AC in a bottom-up manner. We also found that a mouse model of SZ (postnatal administration of noncompetitive N-methyl-d-aspartate receptor antagonist) presented an AG deficit in the PPC, which may be inherited from the dysfunction of MD. Together, our findings reveal a neural circuit underlying the generation of AG in the PPC and its involvement in the AG deficit of SZ.
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Affiliation(s)
- Shuai Wang
- Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning province 110122, People's Republic of China
| | - Zijie Li
- Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning province 110122, People's Republic of China
| | - Xuejiao Wang
- Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning province 110122, People's Republic of China
| | - Jinhong Li
- Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning province 110122, People's Republic of China
| | - Xueru Wang
- Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning province 110122, People's Republic of China
| | - Jingyu Chen
- Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning province 110122, People's Republic of China
| | - Yingna Li
- Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning province 110122, People's Republic of China
| | - Changming Wang
- Department of Anaesthesiology, The People's Hospital of China Medical University (Liaoning Provincial People's Hospital), No.33 Wenyi Road, Shenhe Area, Shenyang, Liaoning province 110067, People's Republic of China
| | - Ling Qin
- Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning province 110122, People's Republic of China
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Sensory gating deficits and childhood trauma in the onset of first-episode schizophrenia. Asian J Psychiatr 2023; 80:103385. [PMID: 36542893 DOI: 10.1016/j.ajp.2022.103385] [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: 05/02/2022] [Revised: 09/09/2022] [Accepted: 09/20/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Studies have shown sensory gating deficits and severe childhood trauma in patients with schizophrenia; however, their relationship with this condition remains unclear. Here, we hypothesized that sensory gating deficits mediate the effects of childhood trauma on schizophrenia onset. METHODS We recruited 79 patients with first-episode schizophrenia (PFES) and 76 health controls (HC). The auditory conditioning (S1) and testing (S2) stimulus paradigm was used to detect P50 sensory gating. The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma experiences. RESULTS Compared with HC, the PFES group had more severe childhood trauma experiences together with sensory gating deficits. In a partial correlation analysis, sexual abuse was negatively correlated with the P50 S2 latency, physical neglect was negatively correlated with the S1 latency, while emotional neglect was positively correlated with the S2/S1 ratio and negatively correlated with the S1-S2 difference in the PFES group. However, there was no correlation between the CTQ total and each sub-scores and P50 indicators in the HC. The S1-S2 difference was the mediator between emotional neglect and the onset of schizophrenia. CONCLUSION Childhood trauma might be associated with schizophrenia by influencing sensory gating deficits. Early intervention targeting childhood trauma might reduce the incidence of sensory gating deficits and thus schizophrenia.
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Acheson DT, Baker DG, Nievergelt CM, Yurgil KA, Geyer MA, Risbrough VB. Prospective longitudinal assessment of sensorimotor gating as a risk/resiliency factor for posttraumatic stress disorder. Neuropsychopharmacology 2022; 47:2238-2244. [PMID: 36192631 PMCID: PMC9630259 DOI: 10.1038/s41386-022-01460-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 09/02/2022] [Accepted: 09/13/2022] [Indexed: 01/18/2023]
Abstract
Little is understood about cognitive mechanisms that confer risk and resiliency for posttraumatic stress disorder (PTSD). Prepulse Inhibition (PPI) is a measure of pre-attentional response inhibition that is a stable cognitive trait disrupted in many neuropsychiatric disorders characterized by poor behavioral or cognitive inhibition, including PTSD. Differentiating between PTSD-related phenotypes that are pre-existing factors vs. those that emerge specifically after trauma is critical to understanding PTSD etiology and can only be addressed by prospective studies. This study tested the hypothesis that sensorimotor gating performance is associated with risk/resiliency for combat-related PTSD. As part of a prospective, longitudinal study, 1226 active duty Marines and Navy Corpsman completed a PPI test as well as a clinical interview to assess PTSD symptoms both before, and 3 and 6 months after a combat deployment. Participants that developed PTSD 6 months following deployment (N=46) showed lower PPI across pre and post-deployment time points compared to participants who did not develop PTSD (N=1182) . Examination of the distribution of PTSD across PPI performance revealed a lower than expected number of cases in the highest performing quartile compared to the rest of the distribution (p < 0.04). When controlling for other factors that predict PTSD in this population, those in the top 25% of PPI performance showed a >50% reduction in chance to develop PTSD (OR = 0.32). Baseline startle reactivity and startle habituation were not significantly different between PTSD risk and control groups. These findings suggest that robust sensorimotor gating may represent a resiliency factor for development of PTSD following trauma.
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Affiliation(s)
- Dean T Acheson
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA
| | - Dewleen G Baker
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA
| | - Caroline M Nievergelt
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA
| | - Kate A Yurgil
- Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA
- Department of Psychological Sciences, Loyola University New Orleans, New Orleans, LA, USA
| | - Mark A Geyer
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Mental Illness Research, Education and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA
| | - Victoria B Risbrough
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
- Center for Excellence in Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.
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Freedman R, Hunter SK, Law AJ, Clark AM, Roberts A, Hoffman MC. Choline, folic acid, Vitamin D, and fetal brain development in the psychosis spectrum. Schizophr Res 2022; 247:16-25. [PMID: 33838984 PMCID: PMC8494861 DOI: 10.1016/j.schres.2021.03.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 03/17/2021] [Accepted: 03/19/2021] [Indexed: 12/18/2022]
Abstract
Choline, folic acid, and Vitamin D are essential for fetal brain development that may be the first steps in the pathogenesis of the psychotic spectrum. Micronutrient deficiencies have been associated with changes in fetal brain development, manifest as early problems in childhood behavior, and cognition, and later as increased incidence of psychotic and autism spectrum disorders. Micronutrient supplements may not only prevent deficiency, but they may also positively affect brain development in the context of other maternal risk factors, including maternal infection, stress, inflammation, and substance abuse. Many genes associated with later psychotic illness are highly expressed in the fetal brain, where they are responsible for various neurodevelopmental mechanisms. Interaction of micronutrient vitamins with these genetically programmed mechanisms to prevent pathological brain development associated with later psychosis is under active investigation. In addition to their effects on brain development, micronutrient vitamins have effects on other aspects of gestation and fetal development, including the prevention of premature delivery and other developmental abnormalities. Supplemental micronutrient vitamins should be part of good prenatal care, as has already happened for folic acid and Vitamin D and is now advocated by the American Medical Association for choline. The benefits of these micronutrient supplements include protection of brain development and the possibility of decreased risk for future psychotic disorders in those children who are either genetically or environmentally vulnerable. The purpose of this review is to present the current evidence supporting the safety and effectiveness of micronutrients in gestation and to suggest areas for future research.
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Affiliation(s)
- Robert Freedman
- Department of Psychiatry, Division of Maternal and Fetal Medicine, University of Colorado School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045, USA.
| | - Sharon K Hunter
- Department of Psychiatry, Division of Maternal and Fetal Medicine, University of Colorado School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045, USA
| | - Amanda J Law
- Department of Psychiatry, Division of Maternal and Fetal Medicine, University of Colorado School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045, USA; Department of Cell and Developmental Biology, Division of Maternal and Fetal Medicine, University of Colorado School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045, USA; Department of Medicine, Division of Maternal and Fetal Medicine, University of Colorado School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045, USA
| | - Alena M Clark
- Department of Nutrition and Dietetics, Campus Box 93, University of Northern Colorado, Greeley, CO 80639, USA
| | | | - M Camille Hoffman
- Department of Psychiatry, Division of Maternal and Fetal Medicine, University of Colorado School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045, USA; Department of Obstetrics and Gynecology, Division of Maternal and Fetal Medicine, University of Colorado School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045, USA
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Oliveras I, Soria-Ruiz OJ, Sampedro-Viana D, Cañete T, Río-Álamos C, Tobeña A, Fernández-Teruel A. Different maturation patterns for sensorimotor gating and startle habituation deficits in male and female RHA vs RLA rats. Behav Brain Res 2022; 434:114021. [PMID: 35872331 DOI: 10.1016/j.bbr.2022.114021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 05/17/2022] [Accepted: 07/19/2022] [Indexed: 11/28/2022]
Abstract
Neurodevelopmental anomalies are thought to play a crucial role in the emergence of schizophrenia. The Roman high-avoidance (RHA) rats exhibit impaired prepulse inhibition (PPI), as well as other behavioral and cognitive singularities related to schizophrenia syndromes compared to the Roman low-avoidance (RLA) rats. In the present study, we aimed at elucidating whether PPI deficits in the RHA rats take place during prepubescence, adolescence, or adulthood. Thus, we evaluated the levels of PPI of both strains and both sexes during these three developmental phases. Additionally, we also investigated the onset of startle habituation deficits in the same groups. The results showed that male RHA rats exhibit a clear-cut PPI reduction compared to their RLA counterparts in adulthood. In female RHA rats, we observed lower levels of PPI since adolescence and through adulthood. We also found no differences between PPI percentages among the three ages in RHA male rats. Contrarily, in male RLA rats, PPI levels were increased in adults compared to their adolescent and prepubescent counterparts. Finally, a deficit in startle habituation was observed in adulthood of both male and female RHA rats, although in the latter case the disturbance in startle habituation was more profound. These results further the description of the maturational trajectory of cognitive markers relevant to schizophrenia prodrome and they add face validity to the RHA rats as a model of schizophrenia-relevant phenotypes.
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Affiliation(s)
- Ignasi Oliveras
- Medical Psychology Unit, Department of Psychiatry and Forensic Medicine & Institute of Neurosciences, School of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona 08193, Spain.
| | - Oscar J Soria-Ruiz
- Medical Psychology Unit, Department of Psychiatry and Forensic Medicine & Institute of Neurosciences, School of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona 08193, Spain
| | - Daniel Sampedro-Viana
- Medical Psychology Unit, Department of Psychiatry and Forensic Medicine & Institute of Neurosciences, School of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona 08193, Spain
| | - Toni Cañete
- Medical Psychology Unit, Department of Psychiatry and Forensic Medicine & Institute of Neurosciences, School of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona 08193, Spain
| | | | - Adolf Tobeña
- Medical Psychology Unit, Department of Psychiatry and Forensic Medicine & Institute of Neurosciences, School of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona 08193, Spain
| | - Alberto Fernández-Teruel
- Medical Psychology Unit, Department of Psychiatry and Forensic Medicine & Institute of Neurosciences, School of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona 08193, Spain.
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San-Martin R, Zimiani MI, de Ávila MAV, Shuhama R, Del-Ben CM, Menezes PR, Fraga FJ, Salum C. Early Schizophrenia and Bipolar Disorder Patients Display Reduced Neural Prepulse Inhibition. Brain Sci 2022; 12:93. [PMID: 35053836 PMCID: PMC8773710 DOI: 10.3390/brainsci12010093] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/29/2021] [Accepted: 12/29/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Altered sensorimotor gating has been demonstrated by Prepulse Inhibition (PPI) tests in patients with psychosis. Recent advances in signal processing methods allow assessment of neural PPI through electroencephalogram (EEG) recording during acoustic startle response measures (classic muscular PPI). Simultaneous measurements of muscular (eye-blink) and neural gating phenomena during PPI test may help to better understand sensorial processing dysfunctions in psychosis. In this study, we aimed to assess simultaneously muscular and neural PPI in early bipolar disorder and schizophrenia patients. METHOD Participants were recruited from a population-based case-control study of first episode psychosis. PPI was measured using electromyography (EMG) and EEG in pulse alone and prepulse + pulse with intervals of 30, 60, and 120 ms in early bipolar disorder (n = 18) and schizophrenia (n = 11) patients. As control group, 15 socio-economically matched healthy subjects were recruited. All subjects were evaluated with Rating Scale, Hamilton Rating Scale for Depression, and Young Mania Rating Scale questionnaires at recruitment and just before PPI test. Wilcoxon ranked sum tests were used to compare PPI test results between groups. RESULTS In comparison to healthy participants, neural PPI was significantly reduced in PPI 30 and PPI60 among bipolar and schizophrenia patients, while muscular PPI was reduced in PPI60 and PPI120 intervals only among patients with schizophrenia. CONCLUSION The combination of muscular and neural PPI evaluations suggested distinct impairment patterns among schizophrenia and bipolar disorder patients. Simultaneous recording may contribute with novel information in sensory gating investigations.
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Affiliation(s)
- Rodrigo San-Martin
- Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo 09606-045, Brazil; (R.S.-M.); (M.I.Z.)
| | - Maria Inês Zimiani
- Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo 09606-045, Brazil; (R.S.-M.); (M.I.Z.)
| | | | - Rosana Shuhama
- Ribeirão Preto Medical School, Universidade de São Paulo, Ribeirão Preto 14040-900, Brazil; (M.A.V.d.Á.); (R.S.); (C.M.D.-B.)
- Population Mental Health Research Center, Universidade de São Paulo, São Paulo 01246-903, Brazil;
| | - Cristina Marta Del-Ben
- Ribeirão Preto Medical School, Universidade de São Paulo, Ribeirão Preto 14040-900, Brazil; (M.A.V.d.Á.); (R.S.); (C.M.D.-B.)
- Population Mental Health Research Center, Universidade de São Paulo, São Paulo 01246-903, Brazil;
| | - Paulo Rossi Menezes
- Population Mental Health Research Center, Universidade de São Paulo, São Paulo 01246-903, Brazil;
- Department of Preventive Medicine, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-903, Brazil
| | - Francisco José Fraga
- Centro de Engenharia, Modelagem e Ciências Sociais Aplicadas, Universidade Federal do ABC, Santo André 09210-580, Brazil;
| | - Cristiane Salum
- Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo 09606-045, Brazil; (R.S.-M.); (M.I.Z.)
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Hirjak D, Schwarz E, Meyer-Lindenberg A. [Twelve years of research domain criteria in psychiatric research and practice: claim and reality]. DER NERVENARZT 2021; 92:857-867. [PMID: 34342676 DOI: 10.1007/s00115-021-01174-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/13/2021] [Indexed: 12/12/2022]
Abstract
The research domain criteria (RDoC) initiative of the National Institute of Mental Health (NIMH) was presented 12 years ago. The RDoC provides a matrix for the systematic, dimensional and domain-based study of mental disorders that is not based on established disease entities as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases (ICD). The primary aim of RDoC is to understand the nature of mental health and illness in terms of different extents of dysfunction in psychological/biological systems with interconnected diagnoses. This selective review article aims to provide a comprehensive overview of RDoC-based studies that have contributed to a better conceptual organization of mental disorders. Numerous promising and methodologically sophisticated studies on RDoC were identified. The number of scientific studies increased over time, indicating that dimensional research is increasingly being pursued in psychiatry. In summary, the RDoC initiative has a considerable potential to more precisely define the complexity of pathomechanisms underlying mental disorders; however, major challenges (e.g. small and heterogeneous study samples, unclear biomarker definitions and lack of replication studies) remain to be overcome in the future. Furthermore, it is plausible that a diagnostic system of the future will integrate categorical and dimensional approaches to arrive at a stratification that can underpin a precision medical approach in psychiatry.
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Affiliation(s)
- Dusan Hirjak
- Zentralinstitut für Seelische Gesundheit, Klinik für Psychiatrie und Psychotherapie, Medizinische Fakultät Mannheim, Universität Heidelberg, 68159, Mannheim, Deutschland.
| | - Emanuel Schwarz
- Zentralinstitut für Seelische Gesundheit, Klinik für Psychiatrie und Psychotherapie, Medizinische Fakultät Mannheim, Universität Heidelberg, 68159, Mannheim, Deutschland
| | - Andreas Meyer-Lindenberg
- Zentralinstitut für Seelische Gesundheit, Klinik für Psychiatrie und Psychotherapie, Medizinische Fakultät Mannheim, Universität Heidelberg, 68159, Mannheim, Deutschland
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11
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Li W, Mao Z, Bo Q, Sun Y, Wang Z, Wang C. Prepulse inhibition in first-degree relatives of schizophrenia patients: A systematic review. Early Interv Psychiatry 2021; 15:652-661. [PMID: 32567764 DOI: 10.1111/eip.13003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 04/15/2020] [Accepted: 05/24/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Prepulse inhibition (PPI) is a measure of sensorimotor gating used to identify deficits in early-stage information processing and inhibitory function defects. Many studies support the presence of PPI deficits in schizophrenia patients. However, very few studies have explored PPI levels among first-degree relatives (FDR) of schizophrenia patients, and the results have been inconsistent. This review article explored PPI levels in FDR of schizophrenia patients. METHODS We performed a systematic literature review using the PubMed, Cochrane, Embase, EBSCO and Chinese databases from inception to January 2020. A series of related factors (eg, PPI paradigm, heritability and sample characteristics) and outcomes were summarized from the literature that met the inclusion criteria. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. RESULTS A total of eight studies were eligible for systematic review after screening. A meta-analysis of the selected studies was not conducted due to the limitations of quantity and paradigm heterogeneity. A majority of the studies' subjects were siblings of schizophrenia patients and different paradigms were applied. Most of the included studies reported no difference in PPI values between FDR of schizophrenia patients and healthy controls. CONCLUSION Contrary to traditional certainty that unaffected FDR of schizophrenia patients have PPI defects, our review found no sufficient evidence supporting that the PPI level in FDR of schizophrenia patients was lower than in healthy controls. A prospective cohort study focusing on different outcomes such as developing schizophrenia is required to explore PPI levels in FDR of schizophrenia patients.
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Affiliation(s)
- Weidi Li
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Zhen Mao
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Qijing Bo
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Yue Sun
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Zhimin Wang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Chuanyue Wang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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12
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Gil-Miravet I, Fuertes-Saiz A, Benito A, Almodóvar I, Ochoa E, Haro G. Prepulse Inhibition in Cocaine Addiction and Dual Pathologies. Brain Sci 2021; 11:brainsci11020269. [PMID: 33672693 PMCID: PMC7924364 DOI: 10.3390/brainsci11020269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 02/07/2021] [Accepted: 02/16/2021] [Indexed: 12/14/2022] Open
Abstract
Cocaine addiction is frequently associated with different psychiatric disorders, especially schizophrenia and antisocial personality disorder. A small number of studies have used prepulse inhibition (PPI) as a discriminating factor between these disorders. This work evaluated PPI and the phenotype of patients with cocaine-related disorder (CRD) who presented a dual diagnosis of schizophrenia or antisocial personality disorder. A total of 74 men aged 18–60 years were recruited for this research. The sample was divided into four groups: CRD (n = 14), CRD and schizophrenia (n = 21), CRD and antisocial personality disorder (n = 16), and a control group (n = 23). We evaluated the PPI and other possible vulnerability factors in these patients by using different assessment scales. PPI was higher in the CRD group at 30 ms (F(3, 64) = 2.972, p = 0.038). Three discriminant functions were obtained which allowed us to use the overall Hare Psychopathy Checklist Revised score, reward sensitivity, and PPI at 30 ms to predict inclusion of these patients in the different groups with a success rate of 79.7% (42.9% for CRD, 76.2% for CRD and schizophrenia, 100% for CRD and antisocial personality disorder, and 91.3% in the control group). Despite the differences we observed in PPI, this factor is of little use for discriminating between the different diagnostic groups and it acts more as a non-specific endophenotype in certain mental disorders, such as in patients with a dual diagnosis.
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Affiliation(s)
- Isis Gil-Miravet
- TXP Research Group, Universidad Cardenal Herrera-CEU, CEU Universities, 12006 Castellón, Spain; (I.G.-M.); (A.B.); (I.A.); (G.H.)
- Predepartamental Unit of Medicine, Universitat Jaume I, 12071 Castellón, Spain
| | - Alejandro Fuertes-Saiz
- TXP Research Group, Universidad Cardenal Herrera-CEU, CEU Universities, 12006 Castellón, Spain; (I.G.-M.); (A.B.); (I.A.); (G.H.)
- Psychiatry Department, Consorcio Hospitalario Provincial de Castellón, 12002 Castellón, Spain
- Correspondence:
| | - Ana Benito
- TXP Research Group, Universidad Cardenal Herrera-CEU, CEU Universities, 12006 Castellón, Spain; (I.G.-M.); (A.B.); (I.A.); (G.H.)
- Torrente Mental Health Centre, Hospital General Universitario, 46014 Valencia, Spain
| | - Isabel Almodóvar
- TXP Research Group, Universidad Cardenal Herrera-CEU, CEU Universities, 12006 Castellón, Spain; (I.G.-M.); (A.B.); (I.A.); (G.H.)
| | - Enrique Ochoa
- Molecular Biopathology Department, Consorcio Hospitalario Provincial de Castellón, 12002 Castellón, Spain;
| | - Gonzalo Haro
- TXP Research Group, Universidad Cardenal Herrera-CEU, CEU Universities, 12006 Castellón, Spain; (I.G.-M.); (A.B.); (I.A.); (G.H.)
- Psychiatry Department, Consorcio Hospitalario Provincial de Castellón, 12002 Castellón, Spain
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13
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Hedberg M, Imbeault S, Erhardt S, Schwieler L. Disrupted sensorimotor gating in first-episode psychosis patients is not affected by short-term antipsychotic treatment. Schizophr Res 2021; 228:118-123. [PMID: 33434725 DOI: 10.1016/j.schres.2020.12.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 10/23/2020] [Accepted: 12/12/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND Impaired sensorimotor gating, commonly measured as disrupted prepulse inhibition (PPI) of the acoustic startle response, has been widely observed in psychotic diseases. However, most PPI studies published so far involve patients with long illness duration and different drug treatments. Few studies have investigated untreated patients at their first episode of psychotic symptoms. METHOD PPI is an acoustic startle paradigm (30, 60-, 120-ms interstimulus intervals). Startle reactivity and habituation were succesfully assessed in 49 antipsychotic-naïve first-episode psychosis (FEP) patients and compared with 35 age- and gender-matched healthy control subjects. Mean age of patients was 28 years and 27 for controls. Patients treated with antipsychotics more than 30 days were not included in the study and twenty-three out of forty-nine patients received antipsychotic treatment with a mean treatment time of 13 days. RESULTS PPI was significantly lower in FEP patients, compared to healthy controls. The PPI deficiency found in these patients was not due to antipsychotic treatment since PPI did not differ between treated (n=23) and untreated patients n=(26). By using the latent curve modeling we identified a delayed habituation in patients treated with antipsychotics, suggesting that antipsychotic treatment should be considered as a confound when investigating habituation in schizophrenia. CONCLUSIONS Our results suggest that acute pharmacological treatment does not normalize PPI in FEP patients but should be considered as a confound when investigating habituation in these patients.
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Affiliation(s)
- Mikael Hedberg
- Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Sophie Imbeault
- Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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- Dept. of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
| | - Sophie Erhardt
- Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
| | - Lilly Schwieler
- Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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14
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Volkmann P, Stephan M, Krackow S, Jensen N, Rossner MJ. PsyCoP - A Platform for Systematic Semi-Automated Behavioral and Cognitive Profiling Reveals Gene and Environment Dependent Impairments of Tcf4 Transgenic Mice Subjected to Social Defeat. Front Behav Neurosci 2021; 14:618180. [PMID: 33519394 PMCID: PMC7841301 DOI: 10.3389/fnbeh.2020.618180] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/15/2020] [Indexed: 12/14/2022] Open
Abstract
Recently, hundreds of risk genes associated with psychiatric disorders have been identified. These are thought to interact with environmental stress factors in precipitating pathological behaviors. However, the individual phenotypes resulting from specific genotype by environment (G×E) interactions remain to be determined. Toward a more systematic approach, we developed a novel standardized and partially automatized platform for systematic behavioral and cognitive profiling (PsyCoP). Here, we assessed the behavioral and cognitive disturbances in Tcf4 transgenic mice (Tcf4tg) exposed to psychosocial stress by social defeat during adolescence using a "two-hit" G×E mouse model. Notably, TCF4 has been repeatedly identified as a candidate risk gene for different psychiatric diseases and Tcf4tg mice display behavioral endophenotypes such as fear memory impairment and hyperactivity. We use the Research Domain Criteria (RDoC) concept as framework to categorize phenotyping results in a translational approach. We propose two methods of dimension reduction, clustering, and visualization of behavioral phenotypes to retain statistical power and clarity of the overview. Taken together, our results reveal that sensorimotor gating is disturbed by Tcf4 overexpression whereas both negative and positive valence systems are primarily influenced by psychosocial stress. Moreover, we confirm previous reports showing that deficits in the cognitive domain are largely dependent on the interaction between Tcf4 and psychosocial stress. We recommend that the standardized analysis and visualization strategies described here should be applied to other two-hit mouse models of psychiatric diseases and anticipate that this will help directing future preclinical treatment trials.
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Affiliation(s)
- Paul Volkmann
- Department of Psychiatry and Psychotherapy, Laboratory of Molecular Neurobiology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Marius Stephan
- Department of Psychiatry and Psychotherapy, Laboratory of Molecular Neurobiology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.,International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany
| | - Sven Krackow
- Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
| | - Niels Jensen
- Department of Psychiatry and Psychotherapy, Laboratory of Molecular Neurobiology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Moritz J Rossner
- Department of Psychiatry and Psychotherapy, Laboratory of Molecular Neurobiology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
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15
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Rovný R, Besterciová D, Riečanský I. Genetic Determinants of Gating Functions: Do We Get Closer to Understanding Schizophrenia Etiopathogenesis? Front Psychiatry 2020; 11:550225. [PMID: 33324248 PMCID: PMC7723973 DOI: 10.3389/fpsyt.2020.550225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 10/12/2020] [Indexed: 11/13/2022] Open
Abstract
Deficits in the gating of sensory stimuli, i.e., the ability to suppress the processing of irrelevant sensory input, are considered to play an important role in the pathogenesis of several neuropsychiatric disorders, in particular schizophrenia. Gating is disrupted both in schizophrenia patients and their unaffected relatives, suggesting that gating deficit may represent a biomarker associated with a genetic liability to the disorder. To assess the strength of the evidence for the etiopathogenetic links between genetic variation, gating efficiency, and schizophrenia, we carried out a systematic review of human genetic association studies of sensory gating (suppression of the P50 component of the auditory event-related brain potential) and sensorimotor gating (prepulse inhibition of the acoustic startle response). Sixty-three full-text articles met the eligibility criteria for inclusion in the review. In total, 117 genetic variants were reported to be associated with gating functions: 33 variants for sensory gating, 80 variants for sensorimotor gating, and four variants for both sensory and sensorimotor gating. However, only five of these associations (four for prepulse inhibition-CHRNA3 rs1317286, COMT rs4680, HTR2A rs6311, and TCF4 rs9960767, and one for P50 suppression-CHRNA7 rs67158670) were consistently replicated in independent samples. Although these variants and genes were all implicated in schizophrenia in research studies, only two polymorphisms (HTR2A rs6311 and TCF4 rs9960767) were also reported to be associated with schizophrenia at a meta-analytic or genome-wide level of evidence. Thus, although gating is widely considered as an important endophenotype of schizophrenia, these findings demonstrate that evidence for a common genetic etiology of impaired gating functions and schizophrenia is yet unsatisfactory, warranting further studies in this field.
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Affiliation(s)
- Rastislav Rovný
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Dominika Besterciová
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Igor Riečanský
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
- Social, Cognitive and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, Vienna, Austria
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16
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Bigdeli TB, Nuechterlein KH, Sugar CA, Subotnik KL, Kubarych T, Neale MC, Kendler KS, Asarnow RF. Evidence of shared familial factors influencing neurocognitive endophenotypes in adult- and childhood-onset schizophrenia. Psychol Med 2020; 50:1672-1679. [PMID: 31362798 DOI: 10.1017/s0033291719001715] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND The aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormalities, and whether there are differences in the extent of familial transmission for specific domains of cognitive function has not been systematically addressed. METHODS We employed variance components analysis, as implemented in SOLAR-Eclipse, to evaluate the evidence of familial transmission for empirically derived composite scores representing attention, working memory, verbal learning, verbal retention, and memory for faces. We contrast estimates for adult- and childhood-onset schizophrenia families and matched community control pedigrees, and compare our findings to previous reports based on analogous neurocognitive assessments. RESULTS We observed varying degrees of familial transmission; attention and working memory yielded comparable, significant estimates for adult-onset and community control pedigrees; verbal learning was significant for childhood-onset and community control pedigrees; and facial memory demonstrated significant familial transmission only for childhood-onset schizophrenia. Model-fitting analyses indicated significant differences in familiality between adult- and childhood-onset schizophrenia for attention, working memory, and verbal learning. CONCLUSIONS By comprehensively assessing a wide range of neurocognitive domains in adult- and childhood-onset schizophrenia families, we provide additional support for specific neurocognitive domains as schizophrenia endophenotypes. Whereas comparable estimates of familial transmission for certain dimensions of cognitive functioning support a shared etiology of adult- and childhood-onset neurocognitive function, observed differences may be taken as preliminary evidence of partially divergent multifactorial architectures.
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Affiliation(s)
- Tim B Bigdeli
- Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, New York, USA
- Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Keith H Nuechterlein
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
- Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA
| | - Catherine A Sugar
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
- Department of Biostatistics, University of California Los Angeles, Los Angeles, CA, USA
| | - Kenneth L Subotnik
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
| | - Thomas Kubarych
- Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Michael C Neale
- Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Kenneth S Kendler
- Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Robert F Asarnow
- Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
- Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA
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17
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Atagun MI, Drukker M, Hall MH, Altun IK, Tatli SZ, Guloksuz S, van Os J, van Amelsvoort T. Meta-analysis of auditory P50 sensory gating in schizophrenia and bipolar disorder. Psychiatry Res Neuroimaging 2020; 300:111078. [PMID: 32361172 DOI: 10.1016/j.pscychresns.2020.111078] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 03/16/2020] [Accepted: 03/19/2020] [Indexed: 11/15/2022]
Abstract
The ability of the brain to reduce the amount of trivial or redundant sensory inputs is called gating function. Dysfunction of sensory gating may lead to cognitive fragmentation and poor real-world functioning. The auditory dual-click paradigm is a pertinent neurophysiological measure of sensory gating function. This meta-analysis aimed to examine the subcomponents of abnormal P50 waveforms in bipolar disorder and schizophrenia to assess P50 sensory gating deficits and examine effects of diagnoses, illness states (first-episode psychosis vs. schizophrenia, remission vs. episodes in bipolar disorder), and treatment status (medication-free vs. medicated). Literature search of PubMed between Jan 1st 1980 and March 31st 2019 identified 2091 records for schizophrenia, 362 for bipolar disorder. 115 studies in schizophrenia (4932 patients), 16 in bipolar disorder (975 patients) and 10 in first-degree relatives (848 subjects) met the inclusion criteria. P50 sensory gating ratio (S2/S1) and S1-S2 difference were significantly altered in schizophrenia, bipolar disorder and their first-degree relatives. First-episode psychosis did not differ from schizophrenia, however episodes altered P50 sensory gating in bipolar disorder. Medications improve P50 sensory gating alterations in schizophrenia significantly and at trend level in bipolar disorder. Future studies should examine longitudinal course of P50 sensory gating in schizophrenia and bipolar disorder.
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Affiliation(s)
- Murat Ilhan Atagun
- Department of Psychiatry, Ankara Yildirim Beyazit University Medical School, Universities Region, Ihsan Dogramaci Boulevard. No: 6, Bilkent, Cankaya, Ankara Turkey.
| | - Marjan Drukker
- Department of Psychiatry and Neuropsychology, Maastricht University School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands
| | - Mei Hua Hall
- Psychosis Neurobiology Laboratory, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA
| | - Ilkay Keles Altun
- Department of Psychiatry, Bursa Higher Education Training and Education Hospital, Bursa, Turkey
| | | | - Sinan Guloksuz
- Department of Psychiatry and Neuropsychology, Maastricht University School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Jim van Os
- Department of Psychiatry and Neuropsychology, Maastricht University School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; King's Health Partners Department of Psychosis Studies, King's College London, Institute of Psychiatry, London, United Kingdom; Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Thérèse van Amelsvoort
- Department of Psychiatry and Neuropsychology, Maastricht University School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands
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18
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Zhaori G. Professor Robert Freedman and his contributions to psychiatric research. Pediatr Investig 2020; 4:73-76. [PMID: 32851347 PMCID: PMC7331399 DOI: 10.1002/ped4.12201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 05/30/2020] [Indexed: 11/13/2022] Open
Affiliation(s)
- Getu Zhaori
- Editorial OfficePediatric InvestigationBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina
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19
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Martynyuk AE, Ju LS, Morey TE, Zhang JQ. Neuroendocrine, epigenetic, and intergenerational effects of general anesthetics. World J Psychiatry 2020; 10:81-94. [PMID: 32477904 PMCID: PMC7243620 DOI: 10.5498/wjp.v10.i5.81] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 03/18/2020] [Accepted: 03/26/2020] [Indexed: 02/05/2023] Open
Abstract
The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.
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Affiliation(s)
- Anatoly E Martynyuk
- Department of Anesthesiology and the McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Ling-Sha Ju
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Timothy E Morey
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Jia-Qiang Zhang
- Department of Anesthesiology and Perioperative Medicine, Henan Provincial People’s Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
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20
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Togay B, Çıkrıkçılı U, Bayraktaroglu Z, Uslu A, Noyan H, Üçok A. Lower prepulse inhibition in clinical high-risk groups but not in familial risk groups for psychosis compared with healthy controls. Early Interv Psychiatry 2020; 14:196-202. [PMID: 31264797 DOI: 10.1111/eip.12845] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 04/18/2019] [Accepted: 06/09/2019] [Indexed: 10/26/2022]
Abstract
AIM Although the lower level of prepulse inhibition (PPI) of the startle response is well known in schizophrenia, the onset of this difference is not clear. The aim of the present study was to compare PPI in individuals with clinical and familial high risk for psychosis, and healthy controls. METHODS We studied PPI in individuals within three groups: ultra-high risk for psychosis (UHR, n = 29), familial high risk for psychosis (FHR, n = 24) and healthy controls (HC, n = 28). The FHR group was chosen among siblings of patients with schizophrenia, whereas UHR was defined based on the Comprehensive Assessment of At-Risk Mental States (CAARMS). We collected clinical data using the BPRS-E, SANS and SAPS when individuals with UHR were antipsychotic-naïve. A cognitive battery that assessed attention, cognitive flexibility, working memory, verbal learning and memory domains was applied to all participants. RESULTS PPI was lower in the UHR group compared with both the FHR and HC groups. Those with a positive family history for schizophrenia had lower PPI than others in the UHR group. There was no difference in PPI between the FHR and HC groups. We found no relationship between PPI and cognitive performance in the three groups. Startle reactivity was not different among the three groups. Positive and negative symptoms were not related to PPI and startle reactivity in the UHR group. CONCLUSIONS Our findings suggest that clinical and familial high-risk groups for psychosis have different patterns of PPI.
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Affiliation(s)
- Bilge Togay
- University of Health Sciences, Tepecik Training and Research Hospital, Clinic of Psychiatry, Izmir, Turkey
| | | | - Zubeyir Bayraktaroglu
- Istanbul Medipol University, International School of Medicine, Department of Physiology, Beykoz, Istanbul, Turkey.,Istanbul Medipol University, Regenerative and Restorative Medicine Research Center (REMER), Beykoz, Istanbul, Turkey
| | - Atilla Uslu
- Istanbul Faculty of Medicine, Department of Physiology, Istanbul University, Istanbul, Turkey
| | - Handan Noyan
- Institute of Experimental Medicine and Research, Istanbul University, Istanbul, Turkey
| | - Alp Üçok
- Istanbul Faculty of Medicine, Department of Psychiatry, Istanbul University, Istanbul, Turkey
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21
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Freedman R, Olsen-Dufour AM, Olincy A. P50 inhibitory sensory gating in schizophrenia: analysis of recent studies. Schizophr Res 2020; 218:93-98. [PMID: 32061454 PMCID: PMC7299819 DOI: 10.1016/j.schres.2020.02.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 01/22/2020] [Accepted: 02/07/2020] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Inhibitory sensory gating of the P50 cerebral evoked potential to paired auditory stimuli (S1, S2) is a widely used paradigm for the study of schizophrenia and related conditions. Its use to measure genetic, treatment, and developmental effects requires a metric with more stable properties than the simple ratio of the paired responses. METHODS This study assessed the ratio P50S2μV/P50S1μV and P50S2μV co-varied for P50S1μV in all 27 independent published studies that compared schizophrenia patients with healthy controls from 2000 to 2019. The largest study from each research group was selected. The Colorado research group's studies were excluded to eliminate bias from the first report of the phenomenon. RESULTS Across the 27 studies encompassing 1179 schizophrenia patients and 1091 healthy controls, both P50S2μV co-varied for P50S1μV and P50S2μV/P50S1μV significantly separated the patients from the controls (both P < 0.0001). Effect size for P50S2μV co-varied for P50S1μV is d' = 1.23. The normal distribution of P50S2μV co-varied for P50S1μV detected influences of maternal inflammation and effects on behavior in a recent developmental study, an emerging use for the P50 inhibitory gating measure. P50S2μV/P50S1μV was not normally distributed. Results from two multi-site NIMH genetics collaborations also support the use of P50S2μV as a biomarker. CONCLUSION Both methods detect an abnormality of cerebral inhibition in schizophrenia with high significance across multiple independent laboratories. The normal distribution of P50S2μV co-varied for P50S1μV makes it more suitable for studies of genetic, treatment, and other influences on the development and expression of inhibitory deficits in schizophrenia.
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Affiliation(s)
- Robert Freedman
- Department of Psychiatry, University of Colorado Denver School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045, USA.
| | - Amanda M. Olsen-Dufour
- Department of Psychiatry, University of Colorado Denver School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045 USA
| | - Ann Olincy
- Department of Psychiatry, University of Colorado Denver School of Medicine, Anschutz Medical Center, Mail Stop F546, Aurora, CO 80045 USA
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22
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Niemantsverdriet MBA, Slotema CW, van der Veen FM, van der Gaag M, Sommer IEC, Deen M, Franken IHA. Sensory processing deficiencies in patients with borderline personality disorder who experience auditory verbal hallucinations. Psychiatry Res 2019; 281:112545. [PMID: 31536946 DOI: 10.1016/j.psychres.2019.112545] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 08/29/2019] [Accepted: 08/29/2019] [Indexed: 11/25/2022]
Abstract
Auditory verbal hallucinations (AVH) are common in patients with borderline personality disorder (BPD). We examined two candidate mechanisms of AVH in patients with BPD, suggested to underlie sensory processing systems that contribute to psychotic symptoms in patients with schizophrenia; sensory gating (P50 ratio and P50 difference) and change detection (mismatch negativity; MMN). Via electroencephalographic recordings P50 amplitude, P50 ratio, P50 difference and MMN amplitude were compared between 23 borderline patients with and 25 without AVH, and 26 healthy controls. Borderline patients with AVH had a significantly lower P50 difference compared with healthy controls, whereas no difference was found between borderline patients without AVH and healthy controls. The groups did not differ on MMN amplitude. The impaired sensory gating in patients with borderline personality disorder who experience AVH implies that P50 sensory gating deficiencies may underlie psychotic vulnerability in this specific patient group. Patients with borderline personality disorder with or without AVH did not have problems with auditory change detection. This may explain why they are spared from the poor outcome associated with negative symptoms and symptoms of disorganization in patients with chronic schizophrenia.
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Affiliation(s)
- Maria B A Niemantsverdriet
- Department of Personality Disorders, Parnassia Psychiatric Institute, Lijnbaan 4, The Hague, VA, 2512, the Netherlands.
| | - Christina W Slotema
- Department of Personality Disorders, Parnassia Psychiatric Institute, Lijnbaan 4, The Hague, VA, 2512, the Netherlands
| | - Frederik M van der Veen
- Institute of Psychology, Erasmus University Rotterdam, Mandeville Building, Rotterdam, DR, 1738, 3000, the Netherlands
| | - Mark van der Gaag
- Department of Clinical Psychology and Amsterdam Public Health Research Institute, VU University, Van der Boechorststraat 7, Amsterdam, BT, 1081, the Netherlands
| | - Iris E C Sommer
- Department of Neuroscience, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen, AD, 9700, the Netherlands
| | - Mathijs Deen
- Department of Personality Disorders, Parnassia Psychiatric Institute, Lijnbaan 4, The Hague, VA, 2512, the Netherlands
| | - Ingmar H A Franken
- Institute of Psychology, Erasmus University Rotterdam, Mandeville Building, Rotterdam, DR, 1738, 3000, the Netherlands
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23
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Fuertes-Saiz A, Benito A, Mateu C, Carratalá S, Almodóvar I, Baquero A, Haro G. Sensorimotor Gating in Cocaine-Related Disorder with Comorbid Schizophrenia or Antisocial Personality Disorder. J Dual Diagn 2019; 15:243-253. [PMID: 31287382 DOI: 10.1080/15504263.2019.1633489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Objective: Schizophrenia, cocaine-related disorder, antisocial personality disorder, and psychopathy share biological bases, but few studies discriminate between these disorders by means of prepulse inhibition. This work studies the phenotype of patients with cocaine-related disorders who are vulnerable to presenting a dual diagnosis of schizophrenia or antisocial personality disorder, by evaluating their prepulse inhibition, impulsivity and psychopathy personality traits. Methods: The sample (n = 38) was divided into three groups: (1) cocaine-related disorder (8 individuals diagnosed with cocaine-related disorder who did not present any other mental disorder), (2) cocaine-related disorder and schizophrenia (n = 14), and (3) cocaine-related disorder and antisocial personality disorder (n = 16). Results: The prepulse inhibition in the two groups with dual diagnosis was lower than that in the cocaine-related disorder group, F(2, 35) = 6.52, p = .004, while there was no significant differences between the two dual-diagnosis groups. Psychopathy was evaluated with the revised Hare Psychopathy Checklist and showed no correlation with the prepulse inhibition. Secondary psychopathy (impulsivity and poor behavior control), as evaluated with Levenson Self-Report Psychopathy Scale, was related to the prepulse inhibition. Two discriminating functions were obtained that allowed prediction of patient inclusion in the groups using the prepulse inhibition and the revised Hare Psychopathy Checklist with a success rate of 81.6% (cocaine-related disorder = 62.5%; cocaine-related disorder and schizophrenia = 78.6%; cocaine-related disorder and antisocial personality disorder = 93.8%). These results are discussed in regard to the neurobiological implications of prepulse inhibition in dual diagnosis. Conclusions: The results suggest that the prepulse inhibition is a promising dual-diagnosis vulnerability marker in individuals with cocaine addiction, because prepulse inhibition deficits are related both to schizophrenia and antisocial personality disorder. In addition, prepulse inhibition, which is considered a good endophenotype for studies on the genetic and neurobiological basis of cocaine-related disorder and schizophrenia, could be used in the same way in studies on antisocial personality disorder.
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Affiliation(s)
- Alejandro Fuertes-Saiz
- TXP Research Group, Medicine Department, Universidad Cardenal Herrera-CEU, CEU Universities, Castelló, Spain.,Psychiatry Department, Hospital Provincial de Castelló, Castelló, Spain
| | - Ana Benito
- TXP Research Group, Medicine Department, Universidad Cardenal Herrera-CEU, CEU Universities, Castelló, Spain.,Torrente Mental Health Center, Hospital General Universitario, Valencia, Spain
| | - César Mateu
- TXP Research Group, Medicine Department, Universidad Cardenal Herrera-CEU, CEU Universities, Castelló, Spain.,Psychiatry Department, Hospital Arnau de Vilanova, Valencia, Spain
| | - Sonia Carratalá
- TXP Research Group, Medicine Department, Universidad Cardenal Herrera-CEU, CEU Universities, Castelló, Spain.,Neurophysiology Department, Hospital General de Castelló, Castelló, Spain
| | - Isabel Almodóvar
- TXP Research Group, Medicine Department, Universidad Cardenal Herrera-CEU, CEU Universities, Castelló, Spain.,Psychiatry Department, Hospital Provincial de Castelló, Castelló, Spain
| | - Abel Baquero
- TXP Research Group, Medicine Department, Universidad Cardenal Herrera-CEU, CEU Universities, Castelló, Spain.,Proyecto Amigó Foundation, Castelló, Spain
| | - Gonzalo Haro
- TXP Research Group, Medicine Department, Universidad Cardenal Herrera-CEU, CEU Universities, Castelló, Spain.,Psychiatry Department, Hospital Provincial de Castelló, Castelló, Spain
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24
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Abstract
Schizophrenia (SZ) is a severe psychotic disorder that is highly heritable and common in the general population. The genetic heterogeneity of SZ is substantial, with contributions from common, rare, and de novo variants, in addition to environmental factors. Large genome-wide association studies have detected many variants that are associated with SZ, yet the pathways by which these variants influence risk remain largely unknown. SZ is also clinically heterogeneous, with patients exhibiting a broad range of deficits and symptom severity that vary over the course of illness and treatment, which has complicated efforts to identify risk variants. However, the underlying brain dysfunction forms a more stable trait marker that quantitative neurocognitive and neurophysiological endophenotypes may be able to objectively measure. These endophenotypes are less likely to be heterogeneous than the disorder and provide a neurobiological context to detect risk variants and underlying pathways among genes associated with SZ diagnosis. Furthermore, many endophenotypes are translational into animal model systems, allowing for direct evaluation of the neural circuit dysfunctions and neurobiological substrates. We review a selection of the most promising SZ endophenotypes, including prepulse inhibition, mismatch negativity, oculomotor antisaccade, letter-number sequencing, and continuous performance tests. We also highlight recent findings from large consortia that suggest the potential role of genes, particularly in the neuregulin and glutamate pathways, in several of these endophenotypes. Although endophenotypes require additional time and effort to assess, the insight into the underlying neurobiology that they provide may ultimately reveal the underlying genetic architecture for SZ and suggest novel treatment targets.
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25
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Xiang J, Tian C, Niu Y, Yan T, Li D, Cao R, Guo H, Cui X, Cui H, Tan S, Wang B. Abnormal Entropy Modulation of the EEG Signal in Patients With Schizophrenia During the Auditory Paired-Stimulus Paradigm. Front Neuroinform 2019; 13:4. [PMID: 30837859 PMCID: PMC6390065 DOI: 10.3389/fninf.2019.00004] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 01/22/2019] [Indexed: 12/20/2022] Open
Abstract
The complexity change in brain activity in schizophrenia is an interesting topic clinically. Schizophrenia patients exhibit abnormal task-related modulation of complexity, following entropy of electroencephalogram (EEG) analysis. However, complexity modulation in schizophrenia patients during the sensory gating (SG) task, remains unknown. In this study, the classical auditory paired-stimulus paradigm was introduced to investigate SG, and EEG data were recorded from 55 normal controls and 61 schizophrenia patients. Fuzzy entropy (FuzzyEn) was used to explore the complexity of brain activity under the conditions of baseline (BL) and the auditory paired-stimulus paradigm (S1 and S2). Generally, schizophrenia patients showed significantly higher FuzzyEn values in the frontal and occipital regions of interest (ROIs). Relative to the BL condition, the normalized values of FuzzyEn of normal controls were decreased greatly in condition S1 and showed less variance in condition S2. Schizophrenia patients showed a smaller decrease in the normalized values in condition S1. Moreover, schizophrenia patients showed significant diminution in the suppression ratios of FuzzyEn, attributed to the higher FuzzyEn values in condition S1. These results suggested that entropy modulation during the process of sensory information and SG was obvious in normal controls and significantly deficient in schizophrenia patients. Additionally, the FuzzyEn values measured in the frontal ROI were positively correlated with positive scores of Positive and Negative Syndrome Scale (PANSS), indicating that frontal entropy was a potential indicator in evaluating the clinical symptoms. However, negative associations were found between the FuzzyEn values of occipital ROIs and general and total scores of PANSS, likely reflecting the compensation effect in visual processing. Thus, our findings provided a deeper understanding of the deficits in sensory information processing and SG, which contribute to cognitive deficits and symptoms in patients with schizophrenia.
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Affiliation(s)
- Jie Xiang
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Cheng Tian
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Yan Niu
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Ting Yan
- Translational Medicine Research CenterShanxi Medical University, Taiyuan, China
| | - Dandan Li
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Rui Cao
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Hao Guo
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Xiaohong Cui
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Huifang Cui
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Shuping Tan
- Psychiatry Research Center, Beijing Huilongguan Hospital, Peking University, Beijing, China
| | - Bin Wang
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
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26
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Du X, Choa FS, Chiappelli J, Wisner KM, Wittenberg G, Adhikari B, Bruce H, Rowland LM, Kochunov P, Hong LE. Aberrant Middle Prefrontal-Motor Cortex Connectivity Mediates Motor Inhibitory Biomarker in Schizophrenia. Biol Psychiatry 2019; 85:49-59. [PMID: 30126607 PMCID: PMC6289820 DOI: 10.1016/j.biopsych.2018.06.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 05/29/2018] [Accepted: 06/09/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Inhibitory deficits in motor cortex in schizophrenia have been well demonstrated using short-interval intracortical inhibition (SICI) by transcranial magnetic stimulation. However, it remains unknown whether these deficits originate from dysfunction of motor cortex itself or reflect abnormal modulations of motor cortex by other schizophrenia-related brain areas. METHODS The study was completed by 24 patients with schizophrenia spectrum disorders and 30 healthy control subjects. SICI was obtained by delivering transcranial magnetic stimulation over the left motor cortex. Resting-state functional magnetic resonance imaging and diffusion tensor imaging fractional anisotropy were used to measure functional connectivity (FC) and white matter microstructures, respectively. Stimulation sites for SICI at motor cortex were used as the seeds to obtain whole-brain FC maps. Clinical symptoms were assessed with the Brief Psychiatric Rating Scale. RESULTS In schizophrenia, left prefrontal cortex-motor cortex FC was inversely associated with SICI but positively associated with the underlying white matter microstructure at the left corona radiata and also associated with overall symptoms (all corrected p < .05). Mediation analysis showed that the prefrontal-motor cortex FC significantly mediated the corona radiata white matter effects on SICI (p = .007). CONCLUSIONS Higher resting-state left prefrontal-motor cortex FC, accompanied by a higher fractional anisotropy of left corona radiata, predicted fewer inhibitory deficits, suggesting that the inhibitory deficits in motor cortex in schizophrenia may in part be mediated by a top-down prefrontal influence. SICI may serve as a robust biomarker indexing inhibitory dysfunction at anatomic as well as circuitry levels in schizophrenia.
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Affiliation(s)
- Xiaoming Du
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
| | - Fow-Sen Choa
- Department of Electrical Engineering and Computer Science, University of Maryland, Baltimore, Maryland
| | - Joshua Chiappelli
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland
| | - Krista M Wisner
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland
| | - George Wittenberg
- Department of Psychiatry, Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland; Department of Physical Therapy and Rehabilitation Science, University of Maryland School of Medicine, Baltimore, Maryland
| | - Bhim Adhikari
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland
| | - Heather Bruce
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland
| | - Laura M Rowland
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland
| | - Peter Kochunov
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland
| | - L Elliot Hong
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland
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27
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Lucatch AM, Lowe DJE, Clark RC, Kozak K, George TP. Neurobiological Determinants of Tobacco Smoking in Schizophrenia. Front Psychiatry 2018; 9:672. [PMID: 30574101 PMCID: PMC6291492 DOI: 10.3389/fpsyt.2018.00672] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 11/21/2018] [Indexed: 12/22/2022] Open
Abstract
Purpose of review: To provide an overview of the underlying neurobiology of tobacco smoking in schizophrenia, and implications for treatment of this comorbidity. Recent findings: Explanations for heavy tobacco smoking in schizophrenia include pro-cognitive effects of nicotine, and remediation of the underlying pathophysiology of schizophrenia. Nicotine may ameliorate neurochemical deficits through nicotine acetylcholine receptors (nAChRs) located on the dopamine, glutamate, and GABA neurons. Neurophysiological indices including electroencephalography, electromyography, and smooth pursuit eye movement (SPEM) paradigms may be biomarkers for underlying neuronal imbalances that contribute to the specific risk of tobacco smoking initiation, maintenance, and difficulty quitting within schizophrenia. Moreover, several social factors including socioeconomic factors and permissive smoking culture in mental health facilities, may contribute to the smoking behaviors (initiation, maintenance, and inability to quit smoking) within this disorder. Summary: Tobacco smoking may alleviate specific symptoms associated with schizophrenia. Understanding the neurobiological underpinnings and psychosocial determinants of this comorbidity may better explain these potential beneficial effects, while also providing important insights into effective treatments for smoking cessation.
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Affiliation(s)
- Aliya M. Lucatch
- Addictions Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
| | - Darby J. E. Lowe
- Addictions Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
| | - Rachel C. Clark
- Addictions Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Karolina Kozak
- Addictions Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
| | - Tony P. George
- Addictions Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Division and Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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28
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Rovný R, Marko M, Katina S, Murínová J, Roháriková V, Cimrová B, Repiská G, Minárik G, Riečanský I. Association between genetic variability of neuronal nitric oxide synthase and sensorimotor gating in humans. Nitric Oxide 2018; 80:32-36. [PMID: 30096361 DOI: 10.1016/j.niox.2018.08.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 06/15/2018] [Accepted: 08/06/2018] [Indexed: 11/17/2022]
Abstract
Research increasingly suggests that nitric oxide (NO) plays a role in the pathogenesis of schizophrenia. One important line of evidence comes from genetic studies, which have repeatedly detected an association between the neuronal isoform of nitric oxide synthase (nNOS or NOS1) and schizophrenia. However, the pathogenetic pathways linking nNOS, NO, and the disorder remain poorly understood. A deficit in sensorimotor gating is considered to importantly contribute to core schizophrenia symptoms such as psychotic disorganization and thought disturbance. We selected three candidate nNOS polymorphisms (Ex1f-VNTR, rs6490121 and rs41279104), associated with schizophrenia and cognition in previous studies, and tested their association with the efficiency of sensorimotor gating in healthy human adults. We found that risk variants of Ex1f-VNTR and rs6490121 (but not rs41279104) were associated with a weaker prepulse inhibition (PPI) of the acoustic startle reflex, a standard measure of sensorimotor gating. Furthermore, the effect of presence of risk variants in Ex1f-VNTR and rs6490121 was additive: PPI linearly decreased with increasing number of risk alleles, being highest in participants with no risk allele, while lowest in individuals who carry three risk alleles. Our findings indicate that NO is involved in the regulation of sensorimotor gating, and highlight one possible pathogenetic mechanism for NO playing a role in the development of schizophrenia psychosis.
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Affiliation(s)
- Rastislav Rovný
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Martin Marko
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Stanislav Katina
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia; Institute of Mathematics and Statistics, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Jana Murínová
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Veronika Roháriková
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Barbora Cimrová
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Gabriela Repiská
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia
| | - Gabriel Minárik
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, Slovakia
| | - Igor Riečanský
- Department of Behavioural Neuroscience, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia; Social, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna, Austria.
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29
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Messamore E. The niacin response biomarker as a schizophrenia endophenotype: A status update. Prostaglandins Leukot Essent Fatty Acids 2018; 136:95-97. [PMID: 28688777 DOI: 10.1016/j.plefa.2017.06.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 05/03/2017] [Accepted: 06/29/2017] [Indexed: 11/20/2022]
Abstract
Increasingly, it is recognized that the behavioral syndrome of schizophrenia is not a unitary disease with a single underlying cause. Rather, it may have several possible etiologies, and its symptoms may arise from multiple causes. Such heterogeneity could account for some of the difficulties in elucidating its genetics, and may also explain clinical observations of variable medication response in schizophrenia. The ability to categorize schizophrenia using objectively recognizable, physiologically-based subtypes promises to make our understanding of schizophrenia more comprehensive and could provide some clues for more personalized treatment. This paper will review the extent to which an abnormally blunted skin flush response to niacin satisfies the criteria for a schizophrenia endophenotype.
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Affiliation(s)
- Erik Messamore
- Best Practices in Schizophrenia Treatment (BeST) Center, Department of Psychiatry, Northeast Ohio Medical University, Rootstown, OH, USA.
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30
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Quednow BB, Ejebe K, Wagner M, Giakoumaki SG, Bitsios P, Kumari V, Roussos P. Meta-analysis on the association between genetic polymorphisms and prepulse inhibition of the acoustic startle response. Schizophr Res 2018; 198:52-59. [PMID: 29287625 DOI: 10.1016/j.schres.2017.12.011] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 12/13/2017] [Accepted: 12/18/2017] [Indexed: 01/14/2023]
Abstract
Sensorimotor gating measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) has been proposed as one of the most promising electrophysiological endophenotypes of schizophrenia. During the past decade, a number of publications have reported significant associations between genetic polymorphisms and PPI in samples of schizophrenia patients and healthy volunteers. However, an overall evaluation of the robustness of these results has not been published so far. Therefore, we performed the first meta-analysis of published and unpublished associations between gene polymorphisms and PPI of ASR. Unpublished associations between genetic polymorphisms and PPI were derived from three independent samples. In total, 120 single observations from 16 independent samples with 2660 study participants and 43 polymorphisms were included. After correction for multiple testing based on false discovery rate and considering the number of analyzed polymorphisms, significant associations were shown for four variants, even though none of these associations survived a genome-wide correction (P<5∗10-8). These results imply that PPI might be modulated by four genotypes - COMT rs4680 (primarily in males), GRIK3 rs1027599, TCF4 rs9960767, and PRODH rs385440 - indicating a role of these gene variations in the development of early information processing deficits in schizophrenia. However, the overall impact of single genes on PPI is still rather small suggesting that PPI is - like the disease phenotype - highly polygenic. Future genome-wide analyses studies with large sample sizes will enhance our understanding on the genetic architecture of PPI.
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Affiliation(s)
- Boris B Quednow
- Experimental and Clinical Pharmacopsychology, Psychiatric Hospital, University of Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland.
| | - Kenechi Ejebe
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Michael Wagner
- Department for Neurodegenerative Diseases and GeriatricPsychiatry, University Hospital Bonn, Bonn, Germany
| | - Stella G Giakoumaki
- Department of Psychology, Gallos University campus, University of Crete, Rethymno, Greece
| | - Panos Bitsios
- Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, Voutes University campus, University of Crete, Heraklion, Greece
| | - Veena Kumari
- Department of Psychology, Institute of Psychiatry, King's College London, United Kingdom
| | - Panos Roussos
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA; Mental Illness Research, Education, and Clinical Center (VISN 2), James J. Peters VA Medical Center, New York, USA.
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31
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Takahashi H, Kamio Y. Acoustic startle response and its modulation in schizophrenia and autism spectrum disorder in Asian subjects. Schizophr Res 2018; 198:16-20. [PMID: 28578923 DOI: 10.1016/j.schres.2017.05.034] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 05/23/2017] [Accepted: 05/26/2017] [Indexed: 12/28/2022]
Abstract
The acoustic startle response (ASR) and its modulation, including prepulse inhibition (PPI), are considered to be promising neurophysiological indices for translational research in psychiatry. Impairment of the PPI has been reported in several psychiatric disorders, but particularly in schizophrenia, where PPI is considered to be a candidate endophenotype of the disorder. Although the profiles of the ASR differ between races, recent studies of single ethnicity samples in Asia were in accord with a number of studies from Western countries, in reporting that patients with schizophrenia exhibit impaired PPI. The PPI of the ASR is known to develop before 8years of age, and PPI impairment has only been reported in adults (not children) with autism spectrum disorder (ASD), which involves atypical features that are present from early development. Recent Asian studies of children with ASD suggest that comprehensive investigation of the ASR and its modulation, including the startle response to weak startle stimuli, peak startle latency, and PPI, may contribute to an understanding of the impairment of the neural circuitry in children with ASD and its comorbid behavioral problems. In this review, we review recent findings on the ASR and its modulation from Asian countries, and discuss its potential use for studying sensorimotor gating and its relationship to schizophrenia and ASD. In conclusion, the ASR and its modulation can provide a well-established global neurophysiological index for translational research in psychiatric disorders. Future studies investigating the development of sensorimotor gating in early development may contribute to prevention of psychiatric disorders.
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Affiliation(s)
- Hidetoshi Takahashi
- Department of Child and Adolescent Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashicho, Kodaira, Tokyo 187-8553, Japan; Department of Advanced Neuroimaging, Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashicho, Kodaira, Tokyo 187-8551, Japan.
| | - Yoko Kamio
- Department of Child and Adolescent Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashicho, Kodaira, Tokyo 187-8553, Japan.
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Takeuchi N, Sugiyama S, Inui K, Kanemoto K, Nishihara M. New paradigm for auditory paired pulse suppression. PLoS One 2017; 12:e0177747. [PMID: 28542290 PMCID: PMC5436751 DOI: 10.1371/journal.pone.0177747] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 05/02/2017] [Indexed: 11/19/2022] Open
Abstract
Sensory gating is a mechanism of sensory processing used to prevent an overflow of irrelevant information, with some indexes, such as prepulse inhibition (PPI) and P50 suppression, often utilized for its evaluation. In addition, those are clinically important for diseases such as schizophrenia. In the present study, we investigated long-latency paired-pulse suppression of change-related cortical responses using magnetoencephalography. The test change-related response was evoked by an abrupt increase in sound pressure by 15 dB in a continuous sound composed of a train of 25-ms pure tones at 65 dB. By inserting a leading change stimulus (prepulse), we observed suppression of the test response. In Experiment 1, we examined the effects of conditioning-test intervals (CTI) using a 25-ms pure tone at 80 dB as both the test and prepulse. Our results showed clear suppression of the test response peaking at a CTI of 600 ms, while maximum inhibition was approximately 30%. In Experiment 2, the effects of sound pressure on prepulse were examined by inserting prepulses 600 ms prior to the test stimulus. We found that a paired-pulse suppression greater than 25% was obtained by prepulses larger than 77 dB, i.e., 12 dB louder than the background, suggesting that long latency suppression requires a relatively strong prepulse to obtain adequate suppression, different than short-latency paired-pulse suppression reported in previous studies. In Experiment 3, we confirmed similar levels of suppression using electroencephalography. These results suggested that two identical change stimuli spaced by 600 ms were appropriate for observing the long-latency inhibition. The present method requires only a short inspection time and is non-invasive.
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Affiliation(s)
- Nobuyuki Takeuchi
- Neuropsychiatric Department, Aichi Medical University, Nagakute, Japan
| | - Shunsuke Sugiyama
- Department of Psychiatry and Psychotherapy, Gifu University, Gifu, Japan
| | - Koji Inui
- Institute of Human Developmental Research, Aichi Human Service Center, Kasugai, Japan
- Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan
| | - Kousuke Kanemoto
- Neuropsychiatric Department, Aichi Medical University, Nagakute, Japan
| | - Makoto Nishihara
- Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Japan
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Impact of Familial Loading on Prefrontal Activation in Major Psychiatric Disorders: A Near-Infrared Spectroscopy (NIRS) Study. Sci Rep 2017; 7:44268. [PMID: 28295013 PMCID: PMC5353718 DOI: 10.1038/srep44268] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 02/07/2017] [Indexed: 11/08/2022] Open
Abstract
Family history (FH) is predictive of the development of major psychiatric disorders (PSY). Familial psychiatric disorders are largely a consequence of genetic factors and typically exhibit more severe impairments. Decreased prefrontal activity during verbal fluency testing (VFT) may constitute an intermediate phenotype for PSY. We investigated whether familial PSY were associated with a greater severity of prefrontal dysfunction in accordance with genetic loading. We measured prefrontal activity during VFT using near-infrared spectroscopy (NIRS) in patients with schizophrenia (SCZ, n = 45), major depressive disorder (MDD, n = 26) or bipolar disorder (BIP, n = 22) and healthy controls (HC, n = 51). We compared prefrontal activity among patients with or without FH and HC. Patients in the SCZ, MDD and BIP patient groups had lower prefrontal activity than HC subjects. Patients with and without FH in all diagnostic groups had lower prefrontal activity than HC subjects. Moreover, SCZ patients with FH had lower prefrontal activity than SCZ patients without FH. When we included patients with SCZ, MDD or BIP in the group of patients with PSY, the effects of psychiatric FH on prefrontal activity were enhanced. These findings demonstrate the association of substantially more severe prefrontal dysfunction with higher genetic loading in major psychiatric disorders.
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Korostil M, Remington G, McIntosh AR. Practice and Learning: Spatiotemporal Differences in Thalamo-Cortical-Cerebellar Networks Engagement across Learning Phases in Schizophrenia. Front Psychiatry 2017; 7:212. [PMID: 28167919 PMCID: PMC5256117 DOI: 10.3389/fpsyt.2016.00212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 12/22/2016] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Understanding how practice mediates the transition of brain-behavior networks between early and later stages of learning is constrained by the common approach to analysis of fMRI data. Prior imaging studies have mostly relied on a single scan, and parametric, task-related analyses. Our experiment incorporates a multisession fMRI lexicon-learning experiment with multivariate, whole-brain analysis to further knowledge of the distributed networks supporting practice-related learning in schizophrenia (SZ). METHODS Participants with SZ were compared with healthy control (HC) participants as they learned a novel lexicon during two fMRI scans over a several day period. All participants were trained to equal task proficiency prior to scanning. Behavioral-Partial Least Squares, a multivariate analytic approach, was used to analyze the imaging data. Permutation testing was used to determine statistical significance and bootstrap resampling to determine the reliability of the findings. RESULTS With practice, HC participants transitioned to a brain-accuracy network incorporating dorsostriatal regions in late-learning stages. The SZ participants did not transition to this pattern despite comparable behavioral results. Instead, successful learners with SZ were differentiated primarily on the basis of greater engagement of perceptual and perceptual-integration brain regions. CONCLUSION There is a different spatiotemporal unfolding of brain-learning relationships in SZ. In SZ, given the same amount of practice, the movement from networks suggestive of effortful learning toward subcortically driven procedural one differs from HC participants. Learning performance in SZ is driven by varying levels of engagement in perceptual regions, which suggests perception itself is impaired and may impact downstream, "higher level" cognition.
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Affiliation(s)
- Michele Korostil
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Rotman Research Institute of Baycrest Health Sciences, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
| | - Gary Remington
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
| | - Anthony Randal McIntosh
- Rotman Research Institute of Baycrest Health Sciences, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
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Mena A, Ruiz-Salas JC, Puentes A, Dorado I, Ruiz-Veguilla M, De la Casa LG. Reduced Prepulse Inhibition as a Biomarker of Schizophrenia. Front Behav Neurosci 2016; 10:202. [PMID: 27803654 PMCID: PMC5067522 DOI: 10.3389/fnbeh.2016.00202] [Citation(s) in RCA: 142] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 10/04/2016] [Indexed: 01/24/2023] Open
Abstract
The startle response is composed by a set of reflex behaviors intended to prepare the organism to face a potentially relevant stimulus. This response can be modulated by several factors as, for example, repeated presentations of the stimulus (startle habituation), or by previous presentation of a weak stimulus (Prepulse Inhibition [PPI]). Both phenomena appear disrupted in schizophrenia that is thought to reflect an alteration in dopaminergic and glutamatergic neurotransmission. In this paper we analyze whether the reported deficits are indicating a transient effect restricted to the acute phase of the disease, or if it reflects a more general biomarker or endophenotype of the disorder. To this end, we measured startle responses in the same set of thirteen schizophrenia patients with a cross-sectional design at two periods: 5 days after hospital admission and 3 months after discharge. The results showed that both startle habituation and PPI were impaired in the schizophrenia patients at the acute stage as compared to a control group composed by 13 healthy participants, and that PPI but not startle habituation remained disrupted when registered 3 months after the discharge. These data point to the consideration of PPI, but not startle habituation, as a schizophrenia biomarker.
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Affiliation(s)
- Auxiliadora Mena
- Department of Experimental Psychology, University of Seville Seville, Spain
| | - Juan C Ruiz-Salas
- Department of Experimental Psychology, University of Seville Seville, Spain
| | - Andrea Puentes
- Neurosciences Institute, El Bosque University Bogotá, Colombia
| | - Inmaculada Dorado
- Institute of Biomedicine, University Hospital Virgen del Rocío Seville, Spain
| | | | - Luis G De la Casa
- Department of Experimental Psychology, University of Seville Seville, Spain
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