SCZ Group Research Articles

Fixational eye movements and their associated evoked potentials during natural vision are altered in schizophrenia

BackgroundVisual exploration is abnormal in schizophrenia; however, few studies have investigated the physiological responses during selecting objectives in more ecological scenarios. This study aimed to demonstrate that people with schizophrenia have difficulties observing the prominent elements of an image due to a deficit mechanism of sensory modulation (active sensing) during natural vision. MethodsAn electroencephalogram recording with eye tracking data was collected on 18 healthy individuals and 18 people affected by schizophrenia while looking at natural images. These had a prominent color element and blinking produced by changes in image luminance. ResultsWe found fewer fixations when all images were scanned, late focus on prominent image areas, decreased amplitude in the eye-fixation-related potential, and decreased intertrial coherence in the SCZ group. ConclusionsThe decrease in the visual attention response evoked by the prominence of visual stimuli in patients affected by schizophrenia is generated by a reduction in endogenous attention mechanisms to initiate and maintain visual exploration. Further work is required to explain the relationship of this decrease with clinical indicators.

Abnormal Serum Biochemical Results and Mitochondrial Damage of Lymphocytes in Patients with Schizophrenia and SARS-CoV-2 Infection: A Retrospective Study.

In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to provide assistance to the treatment and management of COVID-19 positive patients with schizophrenia. We undertook an exploratory, retrospective review of patient data from Dec. 6, 2022, to Jan. 31, 2023. A total of 1696 inpatients with psychosis (921 schizophrenia patients and 775 diagnosed with other mental diseases) during this period were identified. Finally, 60 schizophrenia patients were enrolled in our study, and 20 of them were infected with syndrome coronavirus 2 (SARS-CoV-2). The serum biochemical levels and single-cell mitochondrial mass (SCMM) of the T lymphocytes of all schizophrenia patients were analyzed. The serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine (Cr) and lactate dehydrogenase (LDH) were significantly higher in schizophrenia patients with COVID-19 (SCZ-C) group. In addition, the SCZ-C group showed lower CD3+, CD3+CD4+ and CD3+CD8+ cell counts and higher SCMM of T lymphocytes compared to SCZ group. Furthermore, positive correlations were found between the T-cell subpopulation counts and positive symptom scores on the Positive and Negative Syndrome Scale (PANSS). Our study findings showed that schizophrenia patients with COVID-19 have a phenotype of mitochondrial damage in T lymphocytes and higher serum levels of AST, ALP, Cr and LDH, which might provide evidence for treating individuals with schizophrenia during subsequent spread of infectious disease.

Fractal dimension analysis of resting state functional networks in schizophrenia from EEG signals.

Fractal dimension (FD) has been revealed as a very useful tool in analyzing the changes in brain dynamics present in many neurological disorders. The fractal dimension index (FDI) is a measure of the spatiotemporal complexity of brain activations extracted from EEG signals induced by transcranial magnetic stimulation. In this study, we assess whether the FDI methodology can be also useful for analyzing resting state EEG signals, by characterizing the brain dynamic changes in different functional networks affected by schizophrenia, a mental disorder associated with dysfunction in the information flow dynamics in the spontaneous brain networks. We analyzed 31 resting-state EEG records of 150 s belonging to 20 healthy subjects (HC group) and 11 schizophrenia patients (SCZ group). Brain activations at each time sample were established by a thresholding process applied on the 15,002 sources modeled from the EEG signal. FDI was then computed individually in each resting-state functional network, averaging all the FDI values obtained using a sliding window of 1 s in the epoch. Compared to the HC group, significant lower values of FDI were obtained in the SCZ group for the auditory network (p < 0.05), the dorsal attention network (p < 0.05), and the salience network (p < 0.05). We found strong negative correlations (p < 0.01) between psychopathological scores and FDI in all resting-state networks analyzed, except the visual network. A receiver operating characteristic curve analysis also revealed that the FDI of the salience network performed very well as a potential feature for classifiers of schizophrenia, obtaining an area under curve value of 0.83. These results suggest that FDI is a promising method for assessing the complexity of the brain dynamics in different regions of interest, and from long resting-state EEG signals. Regarding the specific changes associated with schizophrenia in the dynamics of the spontaneous brain networks, FDI distinguished between patients and healthy subjects, and correlated to clinical variables.

Social cognition and real-life functioning in patient samples with 22q11.2 deletion syndrome with or without psychosis, compared to a large sample of patients with schizophrenia only and healthy controls.

Patients with the 22q11.2 deletion syndrome (DS) show an increased risk of developing a psychotic illness lifetime. 22q11.2DS may represent a reliable model for studying the neurobiological underpinnings of schizophrenia. The study of social inference abilities in a genetic condition at high risk for psychosis, like 22q11.2DS, may shed light on the relationships between neurocognitive processes and patients' daily general functioning. The study sample consisted of 1736 participants, divided into four groups: 22q11.2DS patients with diagnosis of psychotic disorder (DEL SCZ, N = 20); 22q11.2DS subjects with no diagnosis of psychosis (DEL, N = 43); patients diagnosed with schizophrenia without 22q11.2DS (SCZ, N = 893); and healthy controls (HC, N = 780). Social cognition was assessed through The Awareness of Social Inference Test (TASIT) and general functioning through the Specific Levels of Functioning (SLoF) scale. We analysed data through regression analysis. The SCZ and DEL groups had similar levels of global functioning; they both had significantly lower SLoF Total scores than HC (p < .001); the DEL SCZ group showed significantly lower scores compared to the other groups (SCZ, p = .004; DEL, p = .003; HC, p < .001). A significant deficit in social cognition was observed in the three clinical groups. In the DEL SCZ and SCZ groups, TASIT scores significantly predicted global functioning (p < .05). Our findings of social cognition deficit in psychosis-prone patients point to the possible future adoption of rehabilitation programmes, like Social Skills Training and Cognitive Remediation, during premorbid stages of psychosis.

Psychosis among individuals with methamphetamine use disorder is associated with elevated rates of hospitalizations and emergency department visits across an academic health care system

IntroductionMethamphetamine (MA) is increasingly available in the United States and manufactured with increasing potency. Although psychosis is a known harm related to MA use, we know little about the clinical outcomes and prognosis of individuals who use MA and experience psychosis. Some evidence exists that psychosis among people who use methamphetamine leads to a high utilization of emergency and acute inpatient services, but the extent of this use is unclear. MethodsUsing an electronic health record (EHR) database, this study assessed acute care visits of individuals receiving diagnostic codes of the following disorders: methamphetamine use disorder with undifferentiated psychosis (MUDp), schizophrenia (MUDs) and no history of psychosis (MUD) in addition to individuals without MUD diagnosis but with diagnoses of either undifferentiated psychosis (Psy) or schizophrenia (Scz) from 2006 to 2019. The study explored potential clinical risk factors associated with rate of acute care visits. ResultsReceiving diagnoses of psychotic disorders and MUD were both associated with high rates of acute care utilization. The incidence rate ratio (IRR) was highest in the MUDp group 6.30 (95% CI: 5.73, 6.93) followed by the MUDs group 4.03 (95% CI: 3.87, 4.20), the Psy group 3.77 (95% CI: 3.45, 4.11), the Scz group 3.11 (95% CI: 2.99, 3.23), and the MUD group 2.17 (95% CI: 2.09, 2.25). Receiving another SUD diagnosis was identified as a risk factor for acute care visits in the MUDp group, and mood and anxiety disorder diagnoses were a risk factor in the MUDs group. ConclusionsIn a general health care system, individuals receiving diagnoses of MUD and co-occurring psychotic disorders were observed to have particularly high rates of acute care service utilization, suggesting a high degree of disease burden and the need for development of targeted treatment interventions with both MUD and psychosis.

The Relationship between Motor Symptoms, Signs, and Parkinsonism with Facial Emotion Recognition Deficits in Individuals with 22q11.2 Deletion Syndrome at High Genetic Risk for Psychosis

Background. The 22q11.2 Deletion Syndrome (22q11.2DS) is a genetic condition at high risk of developing both psychosis and motor disorders. Social Cognition (SC) deficits have been associated not only with schizophrenia but also with Parkinson’s disease (PD). The present study assessed SC deficits in 22q11.2DS and investigated the interaction between motor symptoms and deficits in Facial Emotion Expressions (FEE) recognition and in Theory of Mind (ToM) tasks in people with 22q11.2DS. Methods. We recruited 38 individuals with 22q11.2DS without psychosis ( N = 38 , DEL) and 18 with 22q11.2DS and psychosis ( N = 18 , DEL_SCZ). The Positive And Negative Syndrome Scale (PANSS), Ekman’s 60 Faces Test (EK-60F), the Awareness of Social Inference Test (TASIT EmRec), and the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (UPDRS III) were administered. Correlations were sought between UPDRS III and both TASIT EmRec and EK-60F scores. Analyses were conducted separately for each psychopathological subgroup. Results. Higher UPDRS III ( p = 0.04 ) and lower EK-60F ( p = 0.025 ) scores were observed in the DEL_SCZ group. We found inverse correlations between UPDRS III and both TASIT EmRec ( r = − 0.289 , p = 0.031 ) and EK-60F ( r = − 0.387 , p = 0.006 ) scores in the whole sample. Correlations were no longer significant in the DEL_SCZ group (UPDRS III-TASIT EmRec p = 0.629 ; UPDRS III-EK60F p = 0.933 ) whilst being stronger in the DEL group (TASIT EmRec, r = − 0.560 , p &lt; 0.001 ; EK60F, r = − 0.542 , p &lt; 0.001 ). Analyses were adjusted for CPZ Eq and IQ. Conclusions. A modulation between FEE recognition deficits and motor symptoms and signs was observed in the 22q11.2DS group, likely affecting patients’ quality of life.

Neural Correlates of Variation in Personal Space and Social Functioning in Schizophrenia and Healthy Individuals.

BackgroundChanges in the regulation of interpersonal distance, or “personal space” (PS), have been repeatedly observed in schizophrenia and, in some studies, linked to negative symptoms. However, the neurobiological basis of these impairments is poorly understood.MethodsPersonal space measurements, functional connectivity of a brain network sensitive to intrusions into PS, and symptoms of social withdrawal and anhedonia were assessed, and associations among these outcomes measured, in 33 individuals with a psychotic disorder (primarily schizophrenia [SCZ]) and 36 control subjects (CON).ResultsPersonal space size was significantly higher (P = .002) and PS permeability (reflecting the capacity to tolerate intrusions into PS) was significantly lower (P = .021) in the SCZ relative to the CON group, and both measures were significantly correlated with social anhedonia and withdrawal in the full sample (all P < .007). Moreover, functional connectivity between the PS and default mode (DM) networks was significantly correlated with the permeability, but not the size, of PS in the full sample and in the SCZ and CON groups separately, and with social withdrawal in the SCZ group. Lastly, the association between PS-DM network connectivity and social withdrawal in the SCZ group was fully mediated by PS permeability.DiscussionNeural and behavioral aspects of PS regulation are linked to social motivation in both healthy individuals and those with psychotic disorders, suggesting that measurements of PS could serve as transdiagnostic markers of social functioning.

Quantitative detection of methylated SOCS-1 in schizophrenia and bipolar disorder considering SOCS-1 -1478 CA/del polymorphism and clinical parameters

IntroductionSuppressor of cytokine signaling (SOCS) proteins are the critical negative regulators of immune responses that exert their effects by inhibiting the Jak/Stat signaling pathway.ObjectivesTo investigate quantitative detection of methylated SOCS-1 in schizophrenia and bipolar disorder considering SOCS-1 -1478CA/del polymorphism and clinical parameters.Methods 114 patients with SCZ, 86 patients with BD, and 80 healthy volunteers were included in the case-control study. The patients were consecutively admitted to the outpatient clinic for three months and were evaluated with some scales for clinical parameters. To measure the methylation level of the SOCS-1 gene, bisulfite-converted DNA samples were analyzed using the real-time quantitative methylation-specific PCR method. SOCS-1 -1478CA/del gene polymorphism was evaluated by using the PCR-RFLP.ResultsThe SOCS-1 promoter methylation levels of SCZ (p = .001) and BD (p = .024) were found to be significantly different from the control group. SOCS-1 methylation was significantly different between SCZ groups due to the age of onset (p = .009). Again, SOCS-1 methylation was significantly different between BD groups due to YMRS scale scores (p = .027). While the SOCS-1 genotype distributions of SCZ patients were not found to be statistically different from the control group, a significant difference in genotype distribution between BD patients and healthy controls was found (p = .013).ConclusionsThe methylated SOCS-1 quantity in DNA samples of both SCZ and BD patients was significantly lower than in control samples. Whereas the SOCS-1 -1478CA/del polymorphism was not related to SCZ, it may be associated with the BD.DisclosureNo significant relationships.

Association of acute psychosocial stress with oxidative stress: Evidence from serum analysis

Growing evidence implicates an association between psychosocial stress and oxidative stress (OxSt) although there are not yet reliable biomarkers to study this association. We used a Trier Social Stress Test (TSST) and compared the response of a healthy control group (HC; N=10) against the response of a schizophrenia group (SCZ; N=10) that is expected to have higher levels of OxSt. Because our previous study showed inconsistent changes in conventional molecular markers for stress responses in the neuroendocrine and immune systems, we analyzed the same serum samples using a separate reducing capacity assay that provides a more global measurement of OxSt. This assay uses the moderately strong oxidizing agent iridium (Ir) to probe a sample's reducing capacity. Specifically, we characterized OxSt by this Ir-reducing capacity assay (Ir-RCA) using two measurement modalities (optical and electrochemical) and we tuned this assay by imposing an input voltage sequence that generates multiple output metrics for data-driven analysis. We defined five OxSt metrics (one optical and four electrochemical metrics) and showed: (i) internal consistency among each metric in the measurements of all 40 samples (baseline and post TSST for N=20); (ii) all five metrics were consistent with expectations of higher levels of OxSt for the SCZ group (three individual metrics showed statistically significant differences); and (iii) all five metrics showed higher levels of OxSt Post-TSST (one metric showed statistically significant difference). Using multivariant analysis, we showed that combinations of OxSt metrics could discern statistically significant increases in OxSt for both the SCZ and HC groups 90 min after the imposed acute psychosocial stress.

Brain dysfunction of methamphetamine-associated psychosis in resting state: Approaching schizophrenia and critical role of right superior temporal deficit.

Methamphetamine (MA)-associated psychosis (MAP) is highly debilitating and common among individuals who use the drug, yet the underlying neural mechanism is not clear. This study compared brain functions between patients with MAP and those with schizophrenia during resting state and investigated the effect of brain alteration on the association between MA use and psychosis in patients with MAP. Three groups, including 24 patients with MAP, 17 with schizophrenia in first-episode (SCZ) and 31 healthy controls (HCs), were included after receiving a resting-state functional MRI scan. The severity of psychosis was assessed with Positive and Negative Syndrome Scale (PANSS). Imaging data were analysed using regional homogeneity (ReHo) to measure individual's brain function. Compared with the HC subjects, the MAP and SCZ groups had significantly lower ReHo in the cortical regions including left postcentral cortex, right superior temporal gyrus and right rolandic operculum, while had higher ReHo in the left putamen, with brain dysfunctions being more pronounced in the SCZ group. Among the MAP subjects, a mediating effect of ReHo in the right superior temporal gyrus was found on the association between MA use frequency and PANSS positive score. MAP and schizophrenia had a common trend of brain alteration, with the dysfunction being more pronounced in schizophrenia. This finding implicated that MAP might be a condition with neuropathology approaching schizophrenia. The observed critical role of right superior temporal deficit between MA use and psychosis proposed a potential target for interventions.

Comparison of inflammatory, nutrient, and neurohormonal indicators in patients with schizophrenia, bipolar disorder and major depressive disorder

Psychiatric disorders are severe, debilitating conditions with unknown etiology and are commonly misdiagnosed, when based solely on clinical interviews, because of overlapping symptoms and similar familial patterns. Until now, no valid and objective biomarkers have been used to diagnose and differentiate between psychiatric disorders. We compared clinically tested serum indicators in terms of inflammation (C-reactive protein, complement proteins C3 and C4, and serum Immunoglobulins A, M, and G), nutrients (homocysteine, folate, and vitamin B12), and neurohormones (adrenocorticotropic hormone and cortisol) in patients with schizophrenia (SCZ, n = 1659), bipolar disorder (BD, n = 1901), and major depressive disorder (MDD, n = 1521) to investigate potential biomarkers. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of these analytes. We found that compared with MDD, serum levels of C-reactive protein, C3, C4, and homocysteine were higher in SCZ and BD groups, and folate and vitamin B12 were lower in SCZ and BD groups. In contrast with BD, adrenocorticotropic hormone and cortisol increased in patients with MDD. Although ROC analysis suggested that they were not able to effectively distinguish between the three, these biological indicators showed different patterns in the three disorders. As such, more specific biomarkers should be explored in the future.

Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1β levels in patients with schizophrenia spectrum disorder and their siblings

ObjectiveThere is evidence suggesting that tryptophan (TRP)-kynurenine (KYN) pathway dysregulation is involved in the pathophysiology of schizophrenia and is regulated by inflammatory cytokines. The study investigate for the first time whether this dysregulation occurs in advanced stages of the disease as a byproduct or emerges as one of the early and inherited manifestations of schizophrenia. MethodSera of 148 patients with schizophrenia spectrum disorders (SCZ), 139 unaffected siblings (SIB) and 210 controls were investigated. Serum interleukin (IL)-1β levels were measured by ELISA, and TRP, KYN and kynurenic acid (KYNA) levels were measured by a high-performance liquid chromatography system. Also, we collected clinical data by applying Comprehensive Assessment of Symptoms and History in SCZ, and SIS-R in SIB and control groups. ResultsCompared to controls, SCZ and SIB groups had lower TRP and higher KYNA levels. TRP levels showed significant differences only between SCZ and controls (p < 0.01). KYNA levels of both SCZ (p ≤ 0.001) and SIB (p < 0.05) were higher than controls. No statistical significance was found for KYN levels across groups. SCZ and SIB groups had higher serum IL-1β levels than controls (p ≤ 0.001). ConclusionsPatients with SCZ and their siblings exhibited similar clinical features and TRP metabolite levels suggesting that TRP-KYN dysregulation may be an inherited component of the disease putatively conferring increased risk to schizophrenia. Elevation of IL-1β is one of the factors promoting overconsumption of the TRP-KYN pathway leading to increased production of neuroregulatory KYNA and presumably to neurodegeneration.

Jumpstarting metabolomics and the next generation of clinically useful gut-brain microbiome research

Using 1H NMR-based metabolomics in association to chemometrics analysis, we analyzed here the metabolic differences between schizophrenia patients (SCZ) compared to healthy controls (HCs). HCs and SCZ patients underwent clinical interview using the Structured Clinical Interview for DSM Disorders (SCID). SCZ patients were further assessed by Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning Scale (GAF), and Clinical Global Impressions Scale (CGI). Using the principal component analysis (PCA) and supervised partial least-squares discriminate analysis (PLS-DA) in obtained NMR data, a clear group separation between HCs and SCZ patients was achieved. Interestingly, all metabolite compounds identified as exclusively present in the SCZ group, except for the gamma-aminobutyric acid (GABA), were never previously associated with mental disorders. Although the initial perception of an absence of obvious biological link among the different key molecules exclusively observed in each group, and no identification of any specific pathway yet, the present work represents an important contribution for the identification of potential biomarkers to inform diagnosis, as it was possible to completely separate the affected SCZ patients from HCs, with no outliers or exceptions. In addition, the data presented here reinforced the role of the modulation of glycolysis pathway and the loss of GABA interneuron/hyperglutamate hypothesis in SCZ.

The machine learning algorithm for the diagnosis of schizophrenia on the basis of gene expression in peripheral blood

BackgroundSchizophrenia (SCZ) is a highly heritable mental disorder with a substantial disease burden. Machine learning (ML) method can be used to identify individuals with SCZ on the basis of blood gene expression data with high accuracy. MethodsThis study aimed to differentiate patients with SCZ from healthy individuals by using the messenger RNA expression level in peripheral blood of 48 patients with SCZ and 50 controls via ML algorithms, namely, artificial neural networks, extreme gradient boosting, support vector machine (SVM), decision tree, and random forest. The expression of six mRNAs was detected using quantitative real-time polymerase chain reaction (qRT-PCR). ResultsThe relative expression levels of GNAI1 (P < 0.001), PRKCA (P < 0.001), and PRKCB (P = 0.021) increased in the SCZ group, whereas those of FYN (P < 0.001), LYN (P = 0.022), and YWHAZ (P < 0.001) decreased in the SCZ group. We generated models with various combinations of genes based on five ML algorithms. The SVM model with six factors (GNAI1, FYN, PRKCA, YWHAZ, PRKCB, and LYN genes) was the best model for distinguishing patients with SCZ from healthy individuals (AUC = 0.993, sensitivity = 1.000, specificity = 0.895, and Youden index = 0.895). ConclusionsThis study suggested that the combination of genes using the ML method is better than the use of a single gene to discriminate patients with SCZ from healthy individuals. The combination of GNAI1, FYN, PRKCA, YWHAZ, PRKCB, and LYN under the SVM model can be used as a diagnostic biomarker for SCZ.

Disrupted Intersubject Variability Architecture in Functional Connectomes in Schizophrenia.

Schizophrenia (SCZ) is a highly heterogeneous disorder with remarkable intersubject variability in clinical presentations. Previous neuroimaging studies in SCZ have primarily focused on identifying group-averaged differences in the brain connectome between patients and healthy controls (HCs), largely neglecting the intersubject differences among patients. We acquired whole-brain resting-state functional MRI data from 121 SCZ patients and 183 HCs and examined the intersubject variability of the functional connectome (IVFC) in SCZ patients and HCs. Between-group differences were determined using permutation analysis. Then, we evaluated the relationship between IVFC and clinical variables in SCZ. Finally, we used datasets of patients with bipolar disorder (BD) and major depressive disorder (MDD) to assess the specificity of IVFC alteration in SCZ. The whole-brain IVFC pattern in the SCZ group was generally similar to that in HCs. Compared with the HC group, the SCZ group exhibited higher IVFC in the bilateral sensorimotor, visual, auditory, and subcortical regions. Moreover, altered IVFC was negatively correlated with age of onset, illness duration, and Brief Psychiatric Rating Scale scores and positively correlated with clinical heterogeneity. Although the SCZ shared altered IVFC in the visual cortex with BD and MDD, the alterations of IVFC in the sensorimotor, auditory, and subcortical cortices were specific to SCZ. The alterations of whole-brain IVFC in SCZ have potential implications for the understanding of the high clinical heterogeneity of SCZ and the future individualized clinical diagnosis and treatment of this disease.

Chemosensory Anhedonia in Patients With Schizophrenia and Individuals With Schizotypy: A Questionnaire Study.

Anhedonia, the loss or decline of the ability to enjoy pleasure, is an important clinical characteristic of schizophrenia. Schizotypal traits refer to the appearance of subclinical symptoms of schizophrenia across normal people. Still, few studies have investigated chemosensory anhedonia in schizophrenia patients and schizotypy individuals. Seventy-one schizophrenia patients (SCZ), 162 schizotypy individuals (SCT) as selected by the Schizotypal Personality Questionnaire (SPQ), and 182 healthy controls (HC) participated in our study. We used the Positive and Negative Syndrome Scale (PANSS) to measure the clinical symptoms of schizophrenia patients. All participants completed the Chemosensory Pleasure Scale (CPS), which was used to assess participants’ smell and taste hedonic capacities. We found that the three groups differed in chemosensory anhedonia. The SCZ group presented more severe chemosensory anhedonia than the SCT group, and the SCT group presented more severe chemosensory anhedonia than the HC group. We also found that chemosensory hedonic capacity was negatively correlated with negative schizotypal traits in the SCT group. Our results suggested that chemosensory anhedonia is an important characteristic of schizophrenia spectrum disorders.

Altered Signaling in CB1R-5-HT2AR Heteromers in Olfactory Neuroepithelium Cells of Schizophrenia Patients is Modulated by Cannabis Use.

Schizophrenia (SCZ) has been associated with serotonergic and endocannabinoid systems dysregulation, but difficulty in obtaining in vivo neurological tissue has limited its exploration. We investigated CB1R-5-HT2AR heteromer expression and functionality via intracellular pERK and cAMP quantification in olfactory neuroepithelium (ON) cells of SCZ patients non-cannabis users (SCZ/nc), and evaluated whether cannabis modulated these parameters in patients using cannabis (SCZ/c). Results were compared vs healthy controls non-cannabis users (HC/nc) and healthy controls cannabis users (HC/c). Further, antipsychotic effects on heteromer signaling were tested in vitro in HC/nc and HC/c. Results indicated that heteromer expression was enhanced in both SCZ groups vs HC/nc. Additionally, pooling all 4 groups together, heteromer expression correlated with worse attentional performance and more neurological soft signs (NSS), indicating that these changes may be useful markers for neurocognitive impairment. Remarkably, the previously reported signaling properties of CB1R-5-HT2AR heteromers in ON cells were absent, specifically in SCZ/nc treated with clozapine. These findings were mimicked in cells from HC/nc exposed to clozapine, suggesting a major role of this antipsychotic in altering the quaternary structure of the CB1R-5-HT2AR heteromer in SCZ/nc patients. In contrast, cells from SCZ/c showed enhanced heteromer functionality similar to HC/c. Our data highlight a molecular marker of the interaction between antipsychotic medication and cannabis use in SCZ with relevance for future studies evaluating its association with specific neuropsychiatric alterations.

Global and Specific Cortical Volume Asymmetries in Individuals With Psychosis Risk Syndrome and Schizophrenia: A Mixed Cross-sectional and Longitudinal Perspective.

Cortical volumetric asymmetry (CVA) has been widely observed in individuals with psychosis, and is associated with etiological risk factors (e.g., genetics, neuromaturation) and treatment response. However, it is unclear whether CVA abnormalities emerge before psychotic illness onset. Understanding whether CVA manifests in clinical high-risk (CHR)-compared with healthy controls and schizophrenia patients (SCZ)-over time may inform our understanding of pathogenic factors. A total of 233 individuals: 73 CHR, 112 healthy controls, and 48 SCZ underwent an MRI and clinical interviews. Ninety-four individuals including healthy volunteers (HV) (n = 49) and CHR (n = 45), completed another scan at 12-months. CVA was compared by lobe in a repeated-measure design across groups, then nested by time in a longitudinal model. CHR and SCZ groups showed reduced global CVA compared with the healthy control groups but the CHR and SCZ group did not differ from each other. A group by lobe interaction indicated the presence of lobe specific reductions in frontal and cingulate CVA. Cingulate CVA was reduced in CHR and SCZ groups compared to HC groups but did not differ from each other. Frontal CVA was reduced in the older healthy controls compared with younger-HC and CHR, but did not differ from the similarly aged SZ group. CVA is similarly impacted in SCZ and CHR groups, potentially reflecting pathogenic processes. Longitudinal analyses provided further support for the neurodevelopmental hypothesis as CHR exhibited longitudinal changes in opposite directions from normative neuromaturation in HV, which was related to increasing risk for psychosis in the CHR.

The latent structure of depressive symptoms across clinical high risk and chronic phases of psychotic illness

Depressive symptoms are highly prevalent in psychotic populations and result in significant functional impairment. Limited knowledge of whether depressive symptoms are invariant across stages of illness curtails our ability to understand how these relate to illness progression. Clarifying the latent structure of depressive symptoms across stages of illness progression would aid etiological conceptualizations and preventive models. In the present study, one-factor (including all items) and two-factor (depression/hopelessness and guilt/self-depreciation) solutions were specified through confirmatory factor analysis (CFA). Measurement invariance analyses were undertaken across schizophrenia (SCZ; n = 312) and clinical high-risk (CHR; n = 175) groups to estimate whether the same construct is being measured across groups. Clinical correlates of the factors were examined. Results indicated that CHR individuals had a greater proportion of mood disorder diagnoses. Metric invariance held for the one-factor solution, and scalar invariance held for the two-factor solution. Notably, negative symptoms did not correlate with depressive symptoms in the SCZ group, though strong correlations were observed in CHR individuals. Positive symptoms were comparably associated with depressive symptoms in both groups. Results suggest depressive symptoms are more prevalent in CHR individuals. Targeting these symptoms may aid future efforts to identify risk of conversion. Further, some depressive symptoms may be systematically more endorsed in CHR individuals. Separating into depression/hopelessness and guilt/self-depreciation scores may aid comparability across stages of illness progression, though this issue deserves careful attention and future study.

Altered expression of the CSMD1 gene in the peripheral blood of schizophrenia patients

BackgroundSchizophrenia (SCZ) is a heritable, refractory, and devastating psychiatric disorder. Previous studies have shown that the variants of CUB and sushi multiple domains 1 (CSMD1) demonstrate significant genome-wide association with SCZ. However, few studies have been conducted on the effect of antipsychotics on the expression levels of CSMD1. This study explored whether a change occurs in the expression of the CSMD1 gene before and after antipsychotic treatment in SCZ patients.MethodsThe study population comprised Han Chinese patients from eastern China, including 32 SCZ patients and 48 healthy controls. The expression of CSMD1 before and after treatment in the SCZ group and between the two groups was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR).ResultsThe expression levels of the CSMD1 gene in the peripheral blood mononuclear cells (PBMCs) of SCZ patients were lower than those in the healthy controls. The expression levels of the CSMD1 gene in the PBMCs of the SCZ patients after antipsychotic treatment were higher than those in the baseline SCZ patients (all P < 0.05).ConclusionsOur results showed that the expression levels of CSMD1 are correlated with the development and treatment of SCZ, providing further evidence for the involvement of CSMD1 in SCZ.