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Background and Hypothesis: Obesity is a common comorbidity in individuals with schizophrenia and is associated with poor clinical outcomes. At present, there are limited effective approaches for addressing this issue. We conducted a double-blind, randomized, sham-controlled clinical trial to investigate the efficacy of noninvasive magnetic stimulation techniques in reducing obesity in individuals with schizophrenia., Study Design: Forty overweight individuals with schizophrenia were recruited and randomly assigned to receive either the active or sham intervention. The active group received 50 accelerated continuous theta burst stimulation (cTBS) sessions over the left primary motor area (M1), while the sham group received sham stimulation. The primary outcomes were the change in body weight and body mass index (BMI), and the secondary outcomes were the psychiatric symptoms, eating behavior scales, metabolic measures, and electrophysiological to food picture stimuli., Study Results: The study demonstrated a significant decrease in body weight and BMI after the intervention selectively in the active group (mean = -1.33 kg, P = .002), and this improvement remained at the 1-month follow-up (mean = -2.02 kg, P = .008). The score on the Barratt Impulsivity Scale (mean = -1.78, P = 0.036) decreased in the active group and mediated the effect of accelerated cTBS on body weight. In the food picture cue electroencephalograph task, the late positive potential component, which is related to motivated attention and emotional processing, decreased in frontal brain regions and increased in posterior regions after the active intervention., Conclusions: The accelerated cTBS may offer a promising approach for treating obesity in individuals with schizophrenia. Further research with a larger sample size or individualized stimulation protocol should be promising., Trial Registration: Clinical trial registered with clinicaltrials.gov (NCT05086133)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Recent genetic evidence implicates glutamatergic-receptor variations in schizophrenia. Glutamatergic excess during early life in people with schizophrenia may cause excitotoxicity and produce structural deficits in the brain. Cortical thickness and gyrification are reduced in schizophrenia, but only a subgroup of patients exhibits such structural deficits. We delineate the structural variations among unaffected siblings and patients with schizophrenia and study the role of key glutamate-receptor polymorphisms on these variations., Methods: Gaussian Mixture Model clustering was applied to the cortical thickness and gyrification data of 114 patients, 112 healthy controls, and 42 unaffected siblings to identify subgroups. The distribution of glutamate-receptor (GRM3, GRIN2A, and GRIA1) and voltage-gated calcium channel (CACNA1C) variations across the MRI-based subgroups was studied. The comparisons in clinical symptoms and cognition between patient subgroups were conducted., Results: We observed a "hypogyric," "impoverished-thickness," and "supra-normal" subgroups of patients, with higher negative symptom burden and poorer verbal fluency in the hypogyric subgroup and notable functional deterioration in the impoverished-thickness subgroup. Compared to healthy subjects, the hypogyric subgroup had significant GRIN2A and GRM3 variations, the impoverished-thickness subgroup had CACNA1C variations while the supra-normal group had no differences., Conclusions: Disrupted gyrification and thickness can be traced to the glutamatergic receptor and voltage-gated calcium channel dysfunction respectively in schizophrenia. This raises the question of whether MRI-based multimetric subtyping may be relevant for clinical trials of agents affecting the glutamatergic system.

Background: Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cognitive dysfunction in schizophrenia., Methods: Both n-back working memory (WM) task-fMRI and resting-state fMRI data were collected from 172 patients with SCZ and 103 healthy control subjects (HC). A replication sample with 49 SCZ and 48 HC was independently obtained. Sixteen thalamic subdivisions were employed as seeds for the analysis., Results: During both task-performance and rest, SCZ showed thalamic hyperconnectivity with sensorimotor cortices, but hypoconnectivity with prefrontal-cerebellar regions relative to controls. Higher sensorimotor-thalamic connectivity and lower prefronto-thalamic connectivity both relate to poorer WM performance (lower task accuracy and longer response time) and difficulties in discriminating target from nontarget (lower d' score) in n-back task. The prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity were anti-correlated both in SCZ and HCs; this anti-correlation was more pronounced with less cognitive demand (rest>0-back>2-back). These findings replicated well in the second sample. Finally, the hypo- and hyper-connectivity patterns during resting-state positively correlated with the hypo- and hyper-connectivity during 2-back task-state in SCZ respectively., Conclusions: The thalamocortical imbalance reflected by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity is present both at rest and during task engagement in SCZ and relates to working memory performance. The frontal reduction, sensorimotor enhancement pattern of thalamocortical imbalance is a state-invariant feature of SCZ that affects a core cognitive function., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Thalamic circuit imbalance characterized by increased sensorimotor-thalamic connectivity and decreased prefrontal-thalamic connectivity has been consistently observed in adult-onset schizophrenia (AOS), although it is unclear whether this pattern is also a feature of early-onset schizophrenia (EOS). If this is the case, thalamic circuit imbalance can be considered as a core mechanistic defect in schizophrenia, unconfounded by the age of onset., Method: A total of 116 adolescents with EOS (63 drug-naive EOS) and 55 matched healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging scans. To define the specific location of the thalamic subregions in thalamocortical circuit, 16 atlas-based thalamic subdivisions were used in functional connectivity analysis., Results: The EOS group showed increased sensorimotor-thalamic connectivity and decreased prefrontal-cerebello-thalamic connectivity, consistent with AOS. Sensorimotor-thalamic hyperconnectivity was more prominent than prefrontal-thalamic hypoconnectivity, which was circumscribed to the medial prefrontal cortex (mPFC), in EOS. Of note, the EOS group specifically exhibited strengthened thalamic connectivity with the salience network (SN). In addition, the EOS showed a more prominent disruption of the lateral thalamic nuclear connectivity., Conclusion: Thalamic dysconnectivity observed in the EOS extends the observations from adult patients. Sensorimotor-thalamic hyperconnectivity is critical for the expression of schizophrenia phenotype irrespective of the age of onset, raising the possibility of aberrant but accelerated functional network maturation in EOS. The specific thalamocortical dysconnectivity involving the SN and mPFC may underlie the distinctive features of multi-modal hallucinations and heightened emotional valence of psychosis seen in EOS., (Copyright © 2020 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The Medication Adherence Rating Scale (MARS) is a fast, non-intrusive way of measuring adherence to medication in order to improve the management of patients with schizophrenia. The current cross-sectional study evaluated the reliability of the Chinese (Mandarin) version of the MARS and explored clinical and demographic correlates to medication adherence in a large sample of patients affected by schizophrenia with an episodic course in China. 1198 patients were recruited from 37 different hospitals in 17 provinces/municipalities of China and evaluated with the Medication Adherence Rating Scale (MARS), Clinical Global Impression-Severity of Illness (CGI-SI) and Sheehan Disability Scale-Chinese version (SDS-C). The MARS showed good internal consistency; Cronbach's alpha of total MARS was 0.83. Among the cohort of patients affected by schizophrenia with an episodic course, 28.5 % met the criteria of good adherence to antipsychotic medication; age, steady income, and severity of illness had significant effects on medication adherence. Medication adherence of patients affected by schizophrenia in mainland China was found to be relatively low, calling for urgent attention and intervention. Risk factors for non-adherence to medication among patients affected by schizophrenia with an episodic course include older age, unsteady income, being in the acute period of the disease, and severity of illness., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Working memory (WM) deficit is a key feature of schizophrenia that relates to a generalized neural inefficiency of extensive brain areas. To date, it remains unknown how these distributed regions are systemically organized at the connectome level and how the disruption of such organization brings about the WM impairment seen in schizophrenia., Methods: We used graph theory to examine the neural efficiency of the functional connectome in different granularity in 155 patients with schizophrenia and 96 healthy controls during a WM task. These analyses were repeated in another independent dataset (81 patients and 54 controls). Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. A machine-learning approach was adopted to study the ability of multivariate connectome features from one dataset to discriminate patients from controls in the second dataset., Results: Small-worldness of the whole-brain connectome was significantly increased in schizophrenia during the WM task; this increase is related to better (though subpar) WM accuracy in patients with more severe negative symptom burden. There was a shift in the degree distribution to a more homogeneous form in patients. The machine-learning approach classified a new set of patients from controls with 84.3% true-positivity rate for schizophrenia and 71.6% overall accuracy., Conclusions: We demonstrate a putative mechanistic link between connectome topology, hub redistribution, and impaired n-back performance in schizophrenia. The task-dependent modulation of the connectome relates to, but remains inefficient in, improving the performance above par in the presence of severe negative symptoms., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: While transnational migration has been shown to be a risk factor for schizophrenia, studies have not examined whether massive internal rural-to-urban migration in China in recent years has increased the risk of hospitalization for schizophrenia, or schizophrenia symptom severity among migrants., Method: In a sample of patients acutely hospitalized with schizophrenia in Changsha, Hunan Province, China (N=334), the proportion of past migrant workers among patients was compared to the proportion of past migrant workers in the general adult population of Hunan. Past migrants were also compared to non-migrants on age of onset, and on symptom severity using the Positive and Negative Syndrome Scale (PANSS). The risk ratio for being a migrant among those hospitalized for schizophrenia was stratified by age and gender subgroups. Multiple regression analysis was used to evaluate group differences in age of onset and symptoms., Results: Of 334 patients diagnosed with schizophrenia hospitalized for <180days, 150 (44.9%) were identified as having been migrant workers compared to 31.0% in the general adult population of Hunan for a risk ratio of 1.45, a risk that was higher for women (2.19) than for men (1.09). Migrant workers also had higher scores than others on total PANSS symptoms., Conclusion: Migrant workers appear to be at greater risk of hospitalization for schizophrenia than other residents of Hunan and showed more severe psychopathology. These findings may reflect specific lack of health insurance coverage for workers migrating to non-native provinces in China, thereby delaying access to treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In the last two decades there has been an increase on task and resting-state functional Magnetic Resonance Imaging (fMRI) studies that explore the brain's functional changes in schizophrenia. However, it remains unclear as to whether the brain's functional changes during the resting state are sensitive to the same brain regions during task fMRI. Therefore, we conducted a systematic literature search of task and resting-state fMRI studies that investigated brain pathological changes in first-episode schizophrenia (Fleischhacker et al.). Nineteen studies met the inclusion criteria; seven were resting state fMRI studies with 371 FES patients and 363 healthy controls and twelve were task fMRI studies with 235 FES patients and 291 healthy controls. We found overlapping task and resting-state fMRI abnormalities in the prefrontal regions, including the dorsal lateral prefrontal cortex, the orbital frontal cortex and the temporal lobe, especially in the left superior temporal gyrus (STG). The findings of this systematic review support the frontotemporal hypothesis of schizophrenia, and the disruption in prefrontal and STG might represent the pathophysiology of schizophrenia disorder at a relatively early stage., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Several resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patient's genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia., Methods: 27 pairs of schizophrenia patients and their unaffected siblings, as well as 27 healthy controls, were scanned using gradient-echo echo-planar imaging at rest. By using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (Reho), we investigated the intensity and synchronization of local spontaneous neuronal activity in three groups., Results: We observed that increased amplitude and reduced synchronization (coherence) of spontaneous neuronal activity were shared by patients and their unaffected siblings. The key brain regions with this abnormal neural pattern in both patients and siblings included the middle temporal, orbito-frontal, inferior occipital and fronto-insular gyrus., Conclusions: This abnormal neural pattern of excessive and incoherent neuronal activity shared by schizophrenia patients and their healthy siblings may improve our understanding of neuropathology and genetic predisposition in schizophrenia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortex when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro-pathological role of inefficient DMN suppression in cognitive deficits of first-episode schizophrenia.

Background: Schizophrenia (SZ) and bipolar I disorder (BD) share many overlapping clinical features, confounding the current diagnostic systems. Recent studies suggest the posterior cingulate (PCC) and medial prefrontal (MPFC) cortices that are involved in SZ and BD pathophysiology. However, the roles of PCC and MPFC in providing specific distinctive and shared neural substrates between these two disorders remain largely unknown. Examining the neurophysiologic mechanism of these diseases may help explain the clinical observations and differentiate the two disorders., Methods: We used the Dynamic Casual Modeling (DCM), which is capable of eliciting hidden neuronal dynamics and reveal cross-regulation of multiple neuronal systems, to characterize the pattern of disrupted effective connectivity in the left PCC-MPFC circuit during working memory tasks in 36 SZ and 20 BD patients as well as 29 healthy controls., Results: Compared to the healthy controls, both SZ and BD patient groups exhibited significant negative effective connectivity from the left MPFC to PCC. The negative effective connectivity was more remarkable in schizophrenic patients. Only patients with BD differed from healthy controls with positive effective connectivity from the left PCC to MPFC., Conclusions: Whole brain analysis revealed deactivation of the left PCC and MPFC across all patient groups. This study provides new insight that changes in effective connectivity of the left MPFC to left PCC circuit during working memory processing may be a core pathophysiological feature distinguishing SZ from BD., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: There is an increasing interest in the patterns of mental health care of people with serious mental illnesses in China, where outpatient and community-based care are not fully developed and long-term hospitalization is still not uncommon. Comparison of sociodemographic and clinical characteristics of long-term and short-term inpatients diagnosed with schizophrenia can be informative about pattern of treatment and their relationship to services needs., Methods: Seventy-three long-term schizophrenia inpatients (current length of stay of more than 5 years) were compared to 116 short-term schizophrenia inpatients (current length of stay of 30 days or less) assessed with the Individual Background Questionnaire, the Positive and Negative Syndrome Scale (PANSS) and the Social Support Rating Scale (SSRS)., Results: There was no significant difference between the groups on the total PANSS symptom score but the short-term inpatients scored significantly higher than their long-term counterparts on the Positive Syndrome sub-scale and the SSRS and lower on the Negative Syndrome sub-scale., Discussion: Differences in symptomatology and social functioning may be related to better medication adherence and more extended social isolation among long-term inpatients while the increased positive symptoms are likely to reflect more acute disease process in short-term inpatients, and possibly poorer medication adherence. These differences may be especially pronounced in developing countries like China in which community-based services need to be more fully developed to facilitate medication adherence and prevent relapse, and to support community adjustment of socially isolated patients who otherwise require hospitalization., (Copyright © 2012 Wiley Publishing Asia Pty Ltd.)

Aim: There has been considerable interest in identifying and addressing the specific needs of early-episode patients diagnosed with schizophrenia in the hope that by addressing such needs early, chronic disabilities can be avoided., Methods: One hundred twenty-eight early-episode and 571 chronic patients were compared on socio-demographic characteristics, clinical symptoms and history of childhood trauma. Symptoms were measured with the Positive and Negative Syndrome Scale (PANSS), and trauma with the short version of the Childhood Trauma Questionnaire., Results: First-episode patients scored 9.3% higher than chronic patients on the PANSS positive symptom scale and 16.3% lower on the negative symptom scale. More first episode patients reported childhood sexual abuse (P = 0.033); however, fewer reported childhood emotional neglect (P = 0.01). Childhood trauma was associated with positive symptoms, specifically with hallucinations in first-episode patients (r = 0.174; P = 0.049). Moreover, fewer parents of first episode patients were living alone (P = 0.008). On multiple logistic regression, the first-episode patients were younger (odds ratio = 0.92), had higher PANSS positive symptom scores (odds ratio 1.04) and lower negative symptom scores (odds ratio 0.948 recalculate)., Conclusions: More positive symptoms, fewer negative symptoms, less isolated parents and greater risk of childhood sexual abuse might warrant attention in first episode schizophrenia and perhaps should be a focus for the development of targeted interventions., (© 2012 Wiley Publishing Asia Pty Ltd.)

Schizophrenia and bipolar disorder share some common clinical features and are both characterized by aberrant resting-state functional connectivity (FC). However, little is known about the common and specific aberrant features of the dynamic FC patterns in these two disorders. In this study, we explored the differences in dynamic FC among schizophrenia patients (n = 66), type I bipolar disorder patients (n = 53), and healthy controls (n = 66), by comparing temporal variabilities of FC patterns involved in specific brain regions and large-scale brain networks. Compared with healthy controls, both patient groups showed significantly increased regional FC variabilities in subcortical areas including the thalamus and basal ganglia, as well as increased inter-network FC variability between the thalamus and sensorimotor areas. Specifically, more widespread changes were found in the schizophrenia group, involving increased FC variabilities in sensorimotor, visual, attention, limbic and subcortical areas at both regional and network levels, as well as decreased regional FC variabilities in the default-mode areas. The observed alterations shared by schizophrenia and bipolar disorder may help to explain their overlapped clinical features; meanwhile, the schizophrenia-specific abnormalities in a wider range may support that schizophrenia is associated with more severe functional brain deficits than bipolar disorder. Together, these findings highlight the potentials of using dynamic FC as an objective biomarker for the monitoring and diagnosis of either schizophrenia or bipolar disorder. [ABSTRACT FROM AUTHOR]