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Objectives: Whilst reduced signalling and gene expression related to gamma‐aminobutyric acid (GABA) play a role in the presumed pathophysiology of schizophrenia, its origin is unclear. Studying asymptomatic individuals with high genetic liability to schizophrenia (AIs) would provide insights. Therefore, this study aimed to investigate the role of genetic liability in GABAergic dysfunction of schizophrenia by exploring in vivo GABA‐A/benzodiazepine receptor (GABAR) availability in AIs. Methods: A total of 10 AIs with multiple relatives diagnosed as schizophrenia and 11 healthy controls underwent [11C]flumazenil positron emission tomography and neurocognitive function tests. Results: There was no significant difference in [11C]flumazenil availability based on the groups. GABAR availability in caudate nuclei had positive correlations with genetic liability of AIs. GABAR availability in caudate nuclei and verbal memory measures of AIs revealed positive correlations. Only the correlation between right caudate and short‐term verbal memory survived multiple‐comparison correction (p = 0.030). Conclusions: This study, for the first time, reports correlations between the genetic liability of schizophrenia and GABAR availability. Correlations between [11C]flumazenil binding in caudate of individuals with high genetic liability to schizophrenia suggests that the GABAergic dysfunction may arise from shared genetic factors and also that it may be responsible for cognitive impairment of AIs. [ABSTRACT FROM AUTHOR]

Background Emotion dysregulation is crucial to both poor social functioning and psychotic symptom formation in patients with schizophrenia. The efficient use of emotion regulation strategies, such as cognitive reappraisal, has been less frequently observed in the early phases of psychotic disorder. It is unknown whether neurophysiological responses related to emotion regulation by cognitive reappraisal are altered in early psychosis. Methods Fifty-four patients with first-episode psychosis (FEP), 34 subjects at clinical high risk (CHR) for psychosis, and 30 healthy controls (HCs) participated in event-related potential recordings during a validated emotion regulation paradigm to measure the effect of cognitive reappraisal on emotion regulation. Late positive potentials (LPPs), which reflect emotional arousal, were compared across the groups and the 3 conditions (negative, cognitive reappraisal, and neutral). The relationship among LPP modulation by cognitive reappraisal and social/role functioning and severity of psychotic symptoms was investigated in the early psychosis group. Results The FEP and CHR participants showed comparably larger LPP amplitudes in the negative and cognitive reappraisal conditions than in the neutral condition, whereas the HCs presented larger LPPs in the negative condition than in the cognitive reappraisal and neutral conditions. LPP modulation by cognitive reappraisal was negatively correlated with positive symptom severity in the FEP patients and with disorganization severity in the CHR subjects. Conclusions Inefficient use of cognitive reappraisal may be related to the impaired emotion regulation and psychotic symptoms from the very beginning of psychotic disorder. This study provides the first neurophysiological evidence regarding current concepts of emotion regulation in early psychosis. [ABSTRACT FROM AUTHOR]

Objective: The persistent disease burden of psychotic disorders often comes from negative symptoms; however, prognostic biomarkers for negative symptoms have not been fully understood. This study investigated whether the altered functional connectivity of the striatum predicts improvement in negative symptoms and functioning after 1 year of usual treatment in patients with first-episode psychosis. Methods: Resting-state functional magnetic imaging was obtained from 40 first-episode psychosis patients and 40 age- and sex-matched healthy control subjects. Whole-brain functional connectivity maps were generated with subdivisions of the striatum as seed regions and compared between first-episode psychosis patients and healthy controls. In 22 patients with first-episode psychosis, follow-up assessments of negative symptom severity and general functional status were conducted after 1 year of usual treatment. Multiple regression analyses were performed to examine factors predictive of symptomatic or functional improvements over the 1-year period. Results: First-episode psychosis patients showed greater functional connectivity between the left dorsal caudate and left primary motor cortex, as well as between the left ventral rostral putamen and right temporal occipital fusiform cortex, than healthy controls. Lower functional connectivity between the right dorsal rostral putamen and anterior cingulate cortex was observed in the first-episode psychosis patients than in healthy controls. In multiple regression analyses, lower functional connectivity of the left dorsal caudate–left primary motor cortex/right dorsal rostral putamen–anterior cingulate cortex predicted improvement in negative symptoms. In addition, lower right dorsal rostral putamen–anterior cingulate cortex functional connectivity predicted improvement in general functioning. Conclusion: These results suggest that altered striatal functional connectivity can be a potent neurobiological marker in the prognosis prediction of first-episode psychosis. Furthermore, altered striatal functional connectivity may provide a potential target in developing treatments for negative symptoms. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. Methods: Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. Results: Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10− 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10− 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10− 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. Conclusions: Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted. [ABSTRACT FROM AUTHOR]

The objective of the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is to evaluate a set of lab-based behavioral video tracking (VT), electroencephalography (EEG), and eye tracking (ET) measures for use in clinical trials with children with autism spectrum disorder (ASD). Within the larger organizational structure of the ABC-CT, the Data Acquisition and Analytic Core (DAAC) oversees the standardization of VT, EEG, and ET data acquisition, data processing, and data analysis. This includes designing and documenting data acquisition and analytic protocols and manuals; facilitating site training in acquisition; data acquisition quality control (QC); derivation and validation of dependent variables (DVs); and analytic deliverables including preparation of data for submission to the National Database for Autism Research (NDAR). To oversee consistent application of scientific standards and methodological rigor for data acquisition, processing, and analytics, we developed standard operating procedures that reflect the logistical needs of multi-site research, and the need for well-articulated, transparent processes that can be implemented in future clinical trials. This report details the methodology of the ABC-CT related to acquisition and QC in our Feasibility and Main Study phases. Based on our acquisition metrics from a preplanned interim analysis, we report high levels of acquisition success utilizing VT, EEG, and ET experiments in a relatively large sample of children with ASD and typical development (TD), with data acquired across multiple sites and use of a manualized training and acquisition protocol. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) has strong efficacy in patients with treatment refractory schizophrenia. However, access to ECT has been limited by high costs, professional labor, treatment duration, and significant adverse effects. To provide support for the decision to perform ECT, we aimed to predict individual responses to ECT among patients with schizophrenia using machine learning analysis of resting-state electroencephalography (EEG).Methods: Forty-seven patients diagnosed with schizophrenia or schizoaffective disorder with EEG recordings before the course of ECT were treated at Seoul National University Hospital. Among these patients, 29 were responders who showed scores of 3 or less on the Clinical Global Impression Severity scale after the course of ECT. Transfer entropy (TE), which represents information flow, was extracted from baseline EEG data and used as a feature. Feature selection was performed with four methods, including Random Subset Feature Selection (RSFS). The random forest classifier was used to predict individual ECT responses.Results: The averaged TE, especially in frontal regions, was higher in ECT responders than in nonresponders. A predictive model using the RSFS method classified ECT responders and nonresponders with 85.3% balanced accuracy, 85.2% accuracy, 88.7% sensitivity, and 81.8% specificity. The positive predictive value was 82.6%, and the negative predictive value was 88.2%.Conclusions: The results of the current study suggest that higher effective connectivity in frontal areas may be associated with a favorable ECT response. Furthermore, personalized decisions to perform ECT in clinical practice could be augmented by resting-state EEG biomarkers of the ECT response in schizophrenia patients. [ABSTRACT FROM AUTHOR]

Background: Although cognitive dysfunction is a core element of schizophrenia, the neurobiological underpinnings of the pathophysiology are not yet sufficiently understood. Because the resting state is crucial for cognitive functioning and electroencephalography (EEG) can reflect instantaneous neural activity, we investigated theta phase-gamma amplitude coupling (TGC) of resting-state EEG and its relationship with cognitive function in patients with first-episode psychosis (FEP) to reveal the neural correlates of cognitive dysfunction.Methods: A total of 59 FEP patients and 50 healthy controls (HCs) underwent resting-state, eyes-closed EEG recordings and performed the Trail Making Test Part A (TMT-A) and Part B (TMT-B) and California Verbal Learning Test (CVLT). TGC from the source signal of the resting-state EEG in default mode network (DMN)-related brain regions was compared between groups. Correlation analyses were performed between TGC and cognitive function test performance in FEP patients.Results: Mean resting-state TGC was larger for the FEP patients than for the HCs. Patients with FEP showed increased TGC in the left posterior cingulate cortex, which was correlated with better performance on the TMT-A and TMT-B and on immediate and delayed recall in the CVLT.Conclusions: These results suggest that patients with FEP show compensatory hyperactivation of resting-state TGC in DMN-related brain regions, which may be related to the reallocation of cognitive resources to prepare for successful cognitive execution. This study not only highlights the neural underpinnings of cognitive dysfunction in FEP patients but also provides useful background to support the development of treatments for cognitive dysfunction in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Using biological evidence to define subtypes within the heterogeneous population with obsessive–compulsive disorder (OCD) is important for improving treatment response. Based on age at onset, OCD can be clustered into 2 groups, each of which is more homogeneous with respect to clinical and cognitive phenotype. However, the neural bases for these phenotypic differences need to be established to construct evidence-based homogeneous groups. Methods: We compared brain volumes, clinical symptoms, and neurocognitive function for 49 people with early-onset OCD and 52 with late-onset OCD (participants in both groups were unmedicated or drug-naïve), and 103 healthy controls. We performed regression analyses to examine group × volume interaction effects on clinical outcomes or neurocognitive function in people with OCD. Results: We observed larger volumes in the precentral, orbitofrontal, middle frontal, and middle temporal gyri in people with early-onset OCD compared to those with late-onset OCD. Poorer visuospatial construction in early-onset OCD was correlated with a larger left middle frontal gyrus volume. Impaired visuospatial memory in people with early-onset OCD and cognitive inflexibility in people with late-onset OCD were correlated with increased and decreased volume in the left middle frontal gyrus, respectively. We found group × volume interactions for obsessive–compulsive symptom scores in the left middle temporal gyrus of people with OCD. Limitations: Although we divided the subtypes using the commonly adopted criterion of age at onset, this criterion is still somewhat controversial. Conclusion: We provided the neural bases for clinical and neurocognitive differences to demonstrate that biological evidence underlies the distinctions between early- and late-onset OCD. This study suggests that different treatment options should be considered for the OCD subtypes, because their neurobiology differs and is related to distinct phenotypic profiles. [ABSTRACT FROM AUTHOR]

We investigated pharmacotherapy trends for obsessive-compulsive disorder (OCD) patients at a Korean tertiary hospital from 2008 to 2017. Out of 1894 patients, 82.9% received at least one psychotropic medication, with prescription rates increasing over time. The most frequently prescribed drug classes were selective serotonin reuptake inhibitors (SSRIs, 80.5%), anxiolytics (57.5%), antipsychotics (47.2%), other antidepressants (21.1%), and mood stabilizers (18.4%). Combination therapy was administered to 79.7% of medicated patients, with SSRIs, anxiolytics, and antipsychotics being the most common combination. Comorbidities significantly increased the prescription rates of all psychotropic classes (P < 0.001). Our study offers insights that may aid in bridging the gap between OCD treatment guidelines and real-world clinical practice. • Real-world study showed increasing trends in psychotropic prescriptions for OCD patients over time. • SSRIs were the most frequently prescribed drug class, followed by anxiolytics and antipsychotics. • Use of psychotropic drug combinations was common in OCD treatment, with almost 80% of medicated patients. • Psychotropic drug use was higher in OCD patients with comorbidities than those without. • This offers valuable information to enhance understanding of OCD treatment guidelines in real-world practice. [ABSTRACT FROM AUTHOR]