Abnormalities In Schizophrenia Research Articles

Cognitive Mechanisms of Aberrant Self-Referential Social Perception in Psychosis and Bipolar Disorder: Insights From Computational Modeling.

Individuals with schizophrenia (SZ) and bipolar disorder (BD) show disruptions in self-referential gaze perception-a social perceptual process related to symptoms and functioning. However, our current mechanistic understanding of these dysfunctions and relationships is imprecise. The present study used mathematical modeling to uncover cognitive processes driving gaze perception abnormalities in SZ and BD, and how they relate to cognition, symptoms, and social functioning. We modeled the behavior of 28 SZ, 38 BD, and 34 controls (HC) in a self-referential gaze perception task using drift-diffusion models parameterized to index key cognitive components: drift rate (evidence accumulation efficiency), drift bias (perceptual bias), start point (expectation bias), threshold separation (response caution), and nondecision time (encoding/motor processes). Results revealed that aberrant gaze perception in SZ and BD was driven by less efficient evidence accumulation, perceptual biases predisposing self-referential responses, and greater caution (SZ only). Across SZ and HC, poorer social functioning was related to greater expectation biases. Within SZ, perceptual and expectancy biases were associated with hallucination and delusion severity, respectively. These findings indicate that diminished evidence accumulation and perceptual biases may underlie altered gaze perception in patients and that SZ may engage in compensatory cautiousness, sacrificing response speed to preserve accuracy. Moreover, biases at the belief and perceptual levels may relate to symptoms and functioning. Computational modeling can, therefore, be used to achieve a more nuanced, cognitive process-level understanding of the mechanisms of social cognitive difficulties, including gaze perception, in individuals with SZ and BD.

Advances, challenges, and prospects of electroencephalography-based biomarkers for psychiatric disorders: a narrative review.

Owing to a lack of appropriate biomarkers for accurate diagnosis and treatment, psychiatric disorders cause significant distress and functional impairment, leading to social and economic losses. Biomarkers are essential for diagnosing, predicting, treating, and monitoring various diseases. However, their absence in psychiatry is linked to the complex structure of the brain and the lack of direct monitoring modalities. This review examines the potential of electroencephalography (EEG) as a neurophysiological tool for identifying psychiatric biomarkers. EEG noninvasively measures brain electrophysiological activity and is used to diagnose neurological disorders, such as depression, bipolar disorder (BD), and schizophrenia, and identify psychiatric biomarkers. Despite extensive research, EEG-based biomarkers have not been clinically utilized owing to measurement and analysis constraints. EEG studies have revealed spectral and complexity measures for depression, brainwave abnormalities in BD, and power spectral abnormalities in schizophrenia. However, no EEG-based biomarkers are currently used clinically for the treatment of psychiatric disorders. The advantages of EEG include real-time data acquisition, noninvasiveness, cost-effectiveness, and high temporal resolution. Challenges such as low spatial resolution, susceptibility to interference, and complexity of data interpretation limit its clinical application. Integrating EEG with other neuroimaging techniques, advanced signal processing, and standardized protocols is essential to overcome these limitations. Artificial intelligence may enhance EEG analysis and biomarker discovery, potentially transforming psychiatric care by providing early diagnosis, personalized treatment, and improved disease progression monitoring.

Impact of excessive abdominal obesity on brain microstructural abnormality in schizophrenia

Significant evidence links obesity and schizophrenia (SZ), but the brain associations are still largely unclear. 48 people with SZ were divided into two subgroups: patients with lower waist circumference (SZ-LWC: n = 24) and patients with higher waist circumference (SZ-HWC: n = 24). Healthy controls (HC) were included for comparison (HC: n = 27). Using tract-based spatial statistics, we compared fractional anisotropy (FA) of the whole-brain white matter skeleton between these three groups (SZ-LWC, SZ-HWC, HC). Using Free Surfer, we compared whole-brain cortical thickness and the selected subcortical volumes between the three groups. FA of widespread white matter and the mean cortical thickness in the right temporal lobe and insular cortex were significantly lower in the SZ-HWC group than in the HC group. The FA of regional white matter was significantly lower in the SZ-LWC group than in the HC group. There were no significant differences in mean subcortical volumes between the groups. Additionally, the cognitive performances were worse in the SZ-HWC group, who had more severe triglycerides elevation. This study provides evidence for microstructural abnormalities of white matter, cortical thickness and neurocognitive deficits in SZ patients with excessive abdominal obesity.

Generalized Slowing of Resting-State Neural Oscillations in People With Schizophrenia

BackgroundRecent interest in how neural oscillations reflect the flow of information through the brain has led to partitioning electroencephalography (EEG) recordings into periodic (i.e., oscillatory) and aperiodic (i.e., nonoscillatory) components. While both contribute to conventional measures of power within the frequencies that compose EEG recordings, the periodic aspect characterizes true oscillations, the speed of which is thought to be critical to efficient functioning of neural systems. Given evidence of EEG power abnormalities in schizophrenia (SCZ), we sought to determine whether the periodic aspect of EEG was aberrant in people with SCZ and could serve as a general measure of brain efficiency. MethodsResting-state EEGs were gathered from 104 participants with SCZ and 105 healthy control participants. We used the FOOOF toolbox to remove aperiodic neural activity. We computed the cross-correlation between power spectra for individual participants and the mean power spectrum for all participants to quantify the relative speed of neural oscillations. ResultsPeriodic activity in SCZ was shifted toward lower frequencies than control participants during eyes-closed rest. On average, participants with SCZ had a 0.55-Hz shift toward oscillatory slowing across the frequency spectrum that predicted worse perceptual reasoning. Slower neural oscillations were associated with weaker perceptual reasoning in SCZ. ConclusionsSlowed periodic activity at rest is evident in SCZ and may represent inefficient functioning of neural circuits as reflected in worse perceptual reasoning. A slower pace of neural oscillations may be a general limitation on the transmission of information within the brain.

Brain Network Localization of Gray Matter Atrophy and Neurocognitive and Social Cognitive Dysfunction in Schizophrenia

BackgroundNumerous studies have established the presence of gray matter atrophy and brain activation abnormalities during neurocognitive and social cognitive tasks in schizophrenia. Despite a growing consensus that diseases localize better to distributed brain networks than individual anatomical regions, relatively few studies have examined brain network localization of gray matter atrophy and neurocognitive and social cognitive dysfunction in schizophrenia. MethodsTo address this gap, we initially identified brain locations of structural and functional abnormalities in schizophrenia from 301 published neuroimaging studies with 8712 individuals with schizophrenia and 9275 healthy control participants. By applying novel functional connectivity network mapping to large-scale resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to 3 brain abnormality networks of schizophrenia. ResultsThe gray matter atrophy network of schizophrenia comprised a broadly distributed set of brain areas predominantly implicating the ventral attention, somatomotor, and default networks. The neurocognitive dysfunction network was also composed of widespread brain areas primarily involving the frontoparietal and default networks. By contrast, the social cognitive dysfunction network consisted of circumscribed brain regions mainly implicating the default, subcortical, and visual networks. ConclusionsOur findings suggest shared and unique brain network substrates of gray matter atrophy and neurocognitive and social cognitive dysfunction in schizophrenia, which may not only refine the understanding of disease neuropathology from a network perspective but may also contribute to more targeted and effective treatments for impairments in different cognitive domains in schizophrenia.

Functional and structural abnormalities of thalamus in individuals at early stage of schizophrenia

BackgroundThalamic abnormalities in schizophrenia are recognized, alongside cognitive deficits. However, the current findings about these abnormalities during the prodromal period remain relatively few and inconsistent. This study applied multimodal methods to explore the alterations in thalamic function and structure and their relationship with cognitive function in first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, aiming to affirm the thalamus's role in schizophrenia development and cognitive deficits. Methods75 FES patients, 60 UHR individuals, and 60 healthy controls (HC) were recruited. Among the three groups, gray matter volume (GMV) and functional connectivity (FC) were evaluated to reflect the structural and functional abnormalities in the thalamus. Pearson correlation was used to calculate the association between these abnormalities and cognitive impairments. ResultsNo significant difference in GMV of the thalamus was found among the abovementioned three groups. Compared with HC individuals, FES patients had decreased thalamocortical FC mostly in the thalamocortical triple network, including the default mode network (DMN), salience network (SN), and executive control network (ECN). UHR individuals had similar but milder dysconnectivity as the FES group. Furthermore, FC between the left thalamus and right putamen was significantly correlated with execution speed and attention in the FES group. ConclusionsOur findings revealed decreased thalamocortical FC associated with cognitive deficits in FES and UHR subjects. This improves our understanding of the functional alterations in thalamus in prodromal stage of schizophrenia and the related factors of the cognitive impairment of the disease. Trial registrationClinicalTrials.govNCT03965598; https://clinicaltrials.gov/ct2/show/NCT03965598.

Cognitive Mechanisms of Aberrant Self-Referential Social Perception in Psychosis and Bipolar Disorder: Insights from Computational Modeling.

Individuals with schizophrenia (SZ) and bipolar disorder (BD) show disruptions in self-referential gaze perception-a social perceptual process related to symptoms and functioning. However, our current mechanistic understanding of these dysfunctions and relationships is imprecise. The present study used mathematical modeling to uncover cognitive processes driving gaze perception abnormalities in SZ and BD, and how they relate to cognition, symptoms, and social functioning. We modeled the behavior of 28 SZ, 38 BD, and 34 controls (HC) in a self-referential gaze perception task using drift-diffusion models (DDM) parameterized to index key cognitive components: drift rate (evidence accumulation efficiency), drift bias (perceptual bias), start point (expectation bias), threshold separation (response caution), and non- decision time (encoding/motor processes). Results revealed that aberrant gaze perception in SZ and BD was driven by less efficient evidence accumulation, perceptual biases predisposing self-referential responses, and greater caution (SZ only). Across SZ and HC, poorer social functioning was related to greater expectation biases. Within SZ, perceptual and expectancy biases were associated with hallucination and delusion severity, respectively. These findings indicate that diminished evidence accumulation and perceptual biases may underlie altered gaze perception in patients and that SZ may engage in compensatory cautiousness, sacrificing response speed to preserve accuracy. Moreover, biases at the belief and perceptual levels may relate to symptoms and functioning. Computational modeling can, therefore, be used to achieve a more nuanced, cognitive process-level understanding of the mechanisms of social cognitive difficulties, including gaze perception, in individuals with SZ and BD.

Computational analysis of linguistic features in speech samples of first-episode bipolar disorder and psychosis

BackgroundIn recent years, automated analyses using novel NLP methods have been used to investigate language abnormalities in schizophrenia. In contrast, only a few studies used automated language analyses in bipolar disorder. To our knowledge, no previous research compared automated language characteristics of first-episode psychosis (FEP) and bipolar disorder (FEBD) using NLP methods. MethodsOur study included 53 FEP, 40 FEBD and 50 healthy control participants who are native Turkish speakers. Speech samples of the participants in the Thematic Apperception Test (TAT) underwent automated generic and part-of-speech analyses, as well as sentence-level semantic similarity analysis based on SBERT. ResultsBoth FEBD and FEP were associated with the use of shorter sentences and increased sentence-level semantic similarity but less semantic alignment with the TAT pictures. FEP also demonstrated reduced verbosity and syntactic complexity. FEP differed from FEBD in reduced verbosity, decreased first-person singular pronouns, fewer conjunctions, increased semantic similarity as well as shorter sentence and word length. The mean classification accuracy was 82.45 % in FEP vs HC, 71.1 % in FEBD vs HC, and 73 % in FEP vs FEBD. After Bonferroni correction, the severity of negative symptoms in FEP was associated with reduced verbal output and increased 5th percentile of semantic similarity. LimitationsThe main limitation of this study was the cross-sectional nature. ConclusionOur findings demonstrate that both patient groups showed language abnormalities, which were more severe and widespread in FEP compared to FEBD. Our results suggest that NLP methods reveal transdiagnostic linguistic abnormalities in FEP and FEBD.

Short-term antipsychotic treatment reduces functional connectivity of the striatum in first-episode drug-naïve early-onset schizophrenia

BackgroundThe striatum is thought to play a critical role in the pathophysiology and antipsychotic treatment of schizophrenia. Previous studies have revealed abnormal functional connectivity (FC) of the striatum in early-onset schizophrenia (EOS) patients. However, no prior studies have examined post-treatment changes of striatal FC in EOS patients. MethodsWe recruited 49 first-episode drug-naïve EOS patients to have resting-state functional magnetic resonance imaging scans at baseline and after 8 weeks of treatment with antipsychotics, along with baseline scanning of 34 healthy controls (HCs) for comparison purposes. We examined the FC values between each seed in striatal subregion and the rest of the brain. The Positive and Negative Syndrome Scale (PANSS) was applied to measure psychiatric symptoms in patients. ResultsCompared with HCs at baseline, EOS patients exhibited weaker FC of striatal subregions with several brain regions of the salience network and default mode network. Meanwhile, FC between the dorsal caudal putamen (DCP) and left supplementary motor area, as well as between the DCP and right postcentral gyrus, was negatively correlated with PANSS negative scores. Furthermore, after 8 weeks of treatment, EOS patients showed decreased FC between subregions of the putamen and the triangular part of inferior frontal gyrus, middle frontal gyrus, supramarginal gyrus and inferior parietal lobule. ConclusionsDecreased striatal FC is evident, even in the early stages of schizophrenia, and enhance our understanding of the neurodevelopmental abnormalities in schizophrenia. The findings also demonstrate that reduced striatal FC occurs after antipsychotic therapy, indicating that antipsychotic effects need to be accounted for when considering striatal FC abnormalities in schizophrenia.

Resting-state functional connectivity correlates of brain structural aging in schizophrenia.

A large body of research has shown that schizophrenia patients demonstrate increased brain structural aging. Although this process may be coupled with aberrant changes in intrinsic functional architecture of the brain, they remain understudied. We hypothesized that there are brain regions whose whole-brain functional connectivity at rest is differently associated with brain structural aging in schizophrenia patients compared to healthy controls. Eighty-four male schizophrenia patients and eighty-six male healthy controls underwent structural MRI and resting-state fMRI. The brain-predicted age difference (b-PAD) was a measure of brain structural aging. Resting-state fMRI was applied to obtain global correlation (GCOR) maps comprising voxelwise values of the strength and sign of functional connectivity of a given voxel with the rest of the brain. Schizophrenia patients had higher b-PAD compared to controls (mean between-group difference + 2.9 years). Greater b-PAD in schizophrenia patients, compared to controls, was associated with lower whole-brain functional connectivity of a region in frontal orbital cortex, inferior frontal gyrus, Heschl's Gyrus, plana temporale and polare, insula, and opercular cortices of the right hemisphere (rFTI). According to post hoc seed-based correlation analysis, decrease of functional connectivity with the posterior cingulate gyrus, left superior temporal cortices, as well as right angular gyrus/superior lateral occipital cortex has mainly driven the results. Lower functional connectivity of the rFTI was related to worse verbal working memory and language production. Our findings demonstrate that well-established frontotemporal functional abnormalities in schizophrenia are related to increased brain structural aging.

Task-based default mode network connectivity predicts cognitive impairment and negative symptoms in first-episode schizophrenia.

Individuals diagnosed with schizophrenia (SZ) demonstrate difficulty distinguishing between internally and externally generated stimuli. These aberrations in "source monitoring" have been theorized as contributing to symptoms of the disorder, including hallucinations and delusions. Altered connectivity within the default mode network (DMN) of the brain has been proposed as a mechanism through which discrimination between self-generated and externally generated events is disrupted. Source monitoring abnormalities in SZ have additionally been linked to impairments in selective attention and inhibitory processing, which are reliably observed via the N100 component of the event-related brain potential elicited during an auditory paired-stimulus paradigm. Given overlapping constructs associated with DMN connectivity and N100 in SZ, the present investigation evaluated relationships between these measures of disorder-related dysfunction and sought to clarify the nature of task-based DMN function in SZ. DMN connectivity and N100 measures were assessed using EEG recorded from SZ during their first episode of illness (N = 52) and demographically matched healthy comparison participants (N = 25). SZ demonstrated less evoked theta-band connectivity within DMN following presentation of pairs of identical auditory stimuli than HC. Greater DMN connectivity among SZ was associated with better performance on measures of sustained attention (p = .03) and working memory (p = .09), as well as lower severity of negative symptoms, though it was not predictive of N100 measures. Together, present findings provide EEG evidence of lower task-based connectivity among first-episode SZ, reflecting disruptions of DMN functions that support cognitive processes. Attentional processes captured by N100 appear to be supported by different neural mechanisms.

Structural white matter abnormalities in Schizophrenia and associations with neurocognitive performance and symptom severity

Schizophrenia is associated with robust white matter (WM) abnormalities but influences of potentially confounding variables and relationships with cognitive performance and symptom severity remain to be fully determined. This study was designed to evaluate WM abnormalities based on diffusion tensor imaging (DTI) in individuals with schizophrenia, and their relationships with cognitive performance and symptom severity. Data from individuals with schizophrenia (SZ; n=138, mean age±SD=39.02±11.82; 105 males) and healthy controls (HC; n=143, mean age±SD=37.07±10.84; 102 males) were collected as part of the Function Biomedical Informatics Research Network Phase 3 study. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were compared between individuals with schizophrenia and healthy controls, and their relationships with neurocognitive performance and symptomatology assessed. Individuals with SZ had significantly lower FA in forceps minor and the left inferior fronto-occipital fasciculus compared to HC. FA in several tracts were associated with speed of processing and attention/vigilance and the severity of the negative symptom alogia. This study suggests that regional WM abnormalities are fundamentally involved in the pathophysiology of schizophrenia and may contribute to cognitive performance deficits and symptom expression observed in schizophrenia.

Sex-related cortical asymmetry in antipsychotic-naïve first-episode schizophrenia.

Schizophrenia has been considered to exhibit sex-related clinical differences that might be associated with distinctly abnormal brain asymmetries between sexes. One hundred and thirty-two antipsychotic-naïve first-episode patients with schizophrenia and 150 healthy participants were recruited in this study to investigate whether cortical asymmetry would exhibit sex-related abnormalities in schizophrenia. After a 1-yr follow-up, patients were rescanned to obtain the effect of antipsychotic treatment on cortical asymmetry. Male patients were found to show increased lateralization index while female patients were found to exhibit decreased lateralization index in widespread regions when compared with healthy participants of the corresponding sex. Specifically, the cortical asymmetry of male and female patients showed contrary trends in the cingulate, orbitofrontal, parietal, temporal, occipital, and insular cortices. This result suggested male patients showed a leftward shift of asymmetry while female patients showed a rightward shift of asymmetry in these above regions that related to language, vision, emotion, and cognition. Notably, abnormal lateralization indices remained stable after antipsychotic treatment. The contrary trends in asymmetry between female and male patients with schizophrenia together with the persistent abnormalities after antipsychotic treatment suggested the altered brain asymmetries in schizophrenia might be sex-related disturbances, intrinsic, and resistant to the effect of antipsychotic therapy.

Striatum and globus pallidus structural abnormalities in schizophrenia: A retrospective study of the different stages of the disease

BackgroundThe basal ganglia are important structures for the release of dopamine in the limbic circuits of the midbrain, and the striatum and globus pallidus are the major nuclei of the basal ganglia, and the dysfunction of these regions has been the basis of many models that have attempted to explain the underlying mechanisms of schizophrenia symptoms. The purpose of this study was to investigate the changes in the volume of the striatum subregion and globus pallidus in three different stages of schizophrenia, and to analyze whether these volume changes were related to antipsychotic drugs and schizophrenia symptoms. MethodsIn this study, we investigated the volume of the striatum and globus pallidus in patients with schizophrenia at three different stages. The study included 57 patients with first-episode schizophrenia (FSZ), 51 patients with early-stage schizophrenia (ESZ), 86 patients with chronic schizophrenia (CSZ), and 191 healthy controls (HC), all of whom underwent structured magnetic resonance imaging (MRI) scans. Covariance analysis was performed using SPSS 26.0 was used for covariance analysis to determine whether there were significant differences in striatal subregion and globus pallidus volume between groups, and stratified analysis was used to further eliminate the effect of age on brain volume. Finally, the correlation analysis between the region of interest and the cumulative dose of antipsychotic drugs and psychotic symptoms was performed. ResultsThe comparison between the different stages of the illness showed significant volume differences in the left caudate nucleus (lCAU) (F = 2.665, adjusted p = 0.048), left putamen (lPUT) (F = 12.749, adjusted p < 0.001), left pallidum (lPAL) (F = 41.111, adjusted p < 0.001), and right pallidum (rPAL) (F = 14.479, adjusted p < 0.001). Post-hoc analysis with corrections showed that the volume differences in the lCAU subregion disappeared. Further stratified analysis controlling for age showed that compared with the HC, the lPAL (t = 4.347, p < 0.001) was initially significantly enlarged in the FSZ group, the lPUT (t = 4.493, p < 0.001), rPUT (t = 2.190, p = 0.031), lPAL (t = 7.894, p < 0.001), and rPAL (t = 4.983, p < 0.001) volumes were all significantly increased in the ESZ group, and the lPUT (t = 3.314, p = 0.002), lPAL (t = 6.334, p < 0.001), and rPAL (t = 3.604, p < 0.001) subregion volumes were also significantly increased in the CSZ group. Correlation analysis showed that lPUT and bilateral globus pallidus were associated with cumulative dose of antipsychotics, but were not associated with clinical symptoms in each subregion. ConclusionThe findings suggest that different subregions of the striatum and globus pallidus show significant volume differences at different stages of schizophrenia compared to HC. These volume differences may be strong radiographic evidence for schizophrenia. In addition, the lPAL was the only significantly different brain region observed in the FSZ group, suggesting that it may be a sensitive indicator of early brain structural changes in schizophrenia. Finally, our findings support the hypothesis that antipsychotic drugs have an effect on the volume of brain structures.

Subregional thalamic functional connectivity abnormalities and cognitive impairments in first-episode schizophrenia

BackgroundPrevious studies have documented thalamic functional connectivity (FC) abnormalities in schizophrenia, typically examining the thalamus as a whole. The specific link between subregional thalamic FC and cognitive deficits in first-episode schizophrenia (FES) remains unexplored. MethodsUsing data from resting-state functional magnetic resonance imaging, we compared whole-brain FC with thalamic subregions between patients and HCs, and analyzed FC changes in drug-naïve patients separately. We then examined correlations between FC abnormalities with both cognitive impairment and clinical symptoms. ResultsA total of 33 FES patients (20 drug-naïve) and 32 age- and sex-matched healthy controls (HCs) were included. Compared to HCs, FES patients exhibited increased FC between specific thalamic subregions and cortical regions, particularly bilateral middle temporal lobe and cuneus gyrus, left medial superior frontal gyrus, and right inferior/superior occipital gyrus. Decreased FC was observed between certain thalamic subregions and the left inferior frontal triangle. These findings were largely consistent in drug-naïve patients. Notably, deficits in social cognition and visual learning in FES patients correlated with increased FC between certain thalamic subregions and cortical regions involving the right superior occipital gyrus and cuneus gyrus. The severity of negative symptoms was associated with increased FC between a thalamic subregion and the left middle temporal gyrus. ConclusionOur findings suggest FC abnormalities between thalamic subregions and cortical areas in FES patients. Increased FC correlated with cognitive deficits and negative symptoms, highlighting the importance of thalamo-cortical connectivity in the pathophysiology of schizophrenia.

Reduced resting-state gamma-band power correlate with unaltered glutamate + glutamine levels in patients at clinical-high risk of psychosis

IntroductionThere is growing evidence of excitation / inhibition (E/I) balance abnormalities in schizophrenia, which might be associated with abnormal gamma frequency oscillations and glutamate concentrations. However, to the best of our knowledge, only one multimodal study have examined such associations between EEG and metabolite characteristics in patients at clinical-high risk of psychosis (CHR) so far.ObjectivesWe aimed to investigate potential associations between GLX (glutamate + glutamine) levels and resting-state gamma-band power in CHR individuals and healthy controls (HC).MethodsTwenty right-handed male patients (16-27 years, mean age 19.9 ± 2.7) fulfilling CHR criteria and 19 healthy male controls (16-27 years, mean age 21.6 ± 3.6) underwent resting-state EEG (16 leads; 10−20 system) and MR spectroscopy at 3T MRI scanner with voxels of 30×30×30mm located in left and right medial prefrontal cortex. Spectral analysis with estimation of gamma-band power (30-45 Hz) were conducted. MEGA-PRESS acquisitions were analyzed with jMRUi (ver. 5.1 Alpha), levels of GLX were calculated as a ratios to creatine + phosphocreatine (GLX/Cr). Gamma-band (30-45 Hz) spectral power and GLX/Cr were compared between groups. Correlations between EEG and metabolite data were analyzed with regression model including age and chlorpromazine equivalents as covariates.ResultsCompared to healthy controls, patients showed reduced spectral gamma-band power in 6 leads (Table). No alterations in GLX/Cr were detected. Positive correlations between altered gamma-power in all leads (except Cz) and GLX/Cr in left medial prefrontal cortex were revealed in CHR (F3: r=0.51, p=0.006; F8: r=0. 54, p=0.004; C3: r=0.37, p=0.037; Pz: r=0.51, p=0.039; P4: r=0.56, p=0.009). No correlations in HC group were found. Chlorpromazine equivalents did not correlate with GLX/Cr of gamma power in CHR group.Table.Results of between-group comparisons corrected for multiple comparisons Lead CHR Mean±SD HC Mean±SD p -value F Cohen’s d Cohen’s d CI 95%F30.97±0.621.4±0.640.00977.2-0.69-1.22 -0.16F80.84±0.611.45±1.030.00727.8-0.71-1.24 -0.19C30.97±0.551.44±0.640.00269.9-0.79-1.32 -0.27Cz1.03±0.611.42±0.520.00747.7-0.70-1.22 -0.18Pz1.17±0.71.62±0.630.00987.1-0.68-1.2 -0.16P41.04±0.661.53±0.660.00518.5-0.74-1.27 -0.22ConclusionsThe findings suggest that clinical-high risk of psychosis is associated with widespread alterations in resting-state gamma-band power. Positive correlations of such alterations with GLX/Cr and absence of such correlations in HC group are presumably indicative of disturbances in the excitation / inhibition balance in CHR individuals.This study was supported by RFBR grant 19-29-10040Disclosure of InterestNone Declared

Brain Abnormalities in Schizophrenia: A Comparative Imagistic Study.

Background and Objectives: Neuroimaging reveals a link between psychiatric conditions and brain structural-functional changes, prompting a paradigm shift in viewing schizophrenia as a neurodevelopmental disorder. This study aims to identify and compare structural brain changes found during the first schizophrenia episode with those found after more than 5 years of illness. Materials and Methods: This prospective study involved 149 participants enrolled between 1 January 2019 and 31 December 2021. The participants were categorized into three groups: the first comprises 51 individuals with an initial psychotic episode, the second consists of 49 patients diagnosed with schizophrenia for over 5 years, and a control group comprising 50 individuals without a diagnosis of schizophrenia or any other psychotic disorder. All participants underwent brain CT examinations. Results: The study examined all three groups: first-episode schizophrenia (FES), schizophrenia (SCZ), and the control group. The FES group had a mean age of 26.35 years and a mean duration of illness of 1.2 years. The SCZ group, with a mean age of 40.08 years, had been diagnosed with schizophrenia for an average of 15.12 years. The control group, with a mean age of 34.60 years, had no schizophrenia diagnosis. Structural measurements revealed widening of frontal horns and lateral ventricles in the SCZ group compared to FES and the FES group compared to the control group. Differences in the dimensions of the third ventricle were noted between SCZ and FES, while no distinction was observed between FES and the control group. The fourth ventricle had similar measurements in FES and SCZ groups, both exceeding those of the control group. Our results showed higher densities in the frontal lobe in schizophrenia patients compared to FES and the control group, with the control group consistently displaying the lowest densities. Conclusions: In summary, our comparative imaging analysis of schizophrenia patients, first-episode schizophrenia, and control patients revealed distinct ventricular patterns, with SCZ showing greater widening than FES and FES wider than the control group. Frontal lobe density, assessed via cerebral CT scans, indicated a higher density in the SCZ group in both anterior and posterior cortex portions compared to FES and the control group, while the left posterior cortex in FES had the highest density. These findings highlight unique neuroanatomical features across groups, shedding light on structural differences associated with different stages of schizophrenia.

Lifespan development of thalamic nuclei and characterizing thalamic nuclei abnormalities in schizophrenia using normative modeling.

Thalamic abnormalities have been repeatedly implicated in the pathophysiology of schizophrenia and other neurodevelopmental disorders. Uncovering the etiology of thalamic abnormalities and how they may contribute to illness phenotypes faces at least two obstacles. First, the typical developmental trajectories of thalamic nuclei and their association with cognition across the lifespan are largely unknown. Second, modest effect sizes indicate marked individual differences and pose a significant challenge to personalized medicine. To address these knowledge gaps, we characterized the development of thalamic nuclei volumes using normative models generated from the Human Connectome Project Lifespan datasets (5-100+ years), then applied them to an independent clinical cohort to determine the frequency of thalamic volume deviations in people with schizophrenia (17-61 years). Normative models revealed diverse non-linear age effects across the lifespan. Association nuclei exhibited negative age effects during youth but stabilized in adulthood until turning negative again with older age. Sensorimotor nuclei volumes remained relatively stable through youth and adulthood until also turning negative with older age. Up to 18% of individuals with schizophrenia exhibited abnormally small (i.e., below the 5th centile) mediodorsal and pulvinar volumes, and the degree of deviation, but not raw volumes, correlated with the severity of cognitive impairment. While case-control differences are robust, only a minority of patients demonstrate unusually small thalamic nuclei volumes. Normative modeling enables the identification of these individuals, which is a necessary step toward precision medicine.

Aberrant heartbeat-evoked potential in schizophrenia

Self-disturbance is considered a core feature underlying the psychopathology of schizophrenia. Interoception has an important role in the development of a sense of self, leading to increased interest in the potential contribution of abnormal interoception to self-disturbances in schizophrenia. Several neuropsychological studies have demonstrated aberrant interoception in schizophrenia. However, cortical interoceptive processing has not yet been thoroughly investigated. Thus, we sought to examine resting-state heartbeat-evoked potential (HEP) in this population. We hypothesized that patients with schizophrenia would exhibit significant alterations in HEP compared to healthy controls (HCs). In this cross-sectional electroencephalogram (EEG) study, we compared the HEPs between age- and sex-matched groups of patients with schizophrenia and HCs. A 10-min resting-state EEG with eyes closed and an electrocardiogram (ECG) were recorded and analyzed for the time window of 450 ms to 500 ms after an ECG R peak. A positive HEP shift was observed in the frontal-central regions (F [1, 82] = 7.402, p = 0.008, partial η2 = 0.009) in patients with schizophrenia (n = 61) when compared with HCs (n = 31) after adjusting for confounders such as age, sex, and heart rate. A cluster-based correction analysis revealed that the HEP around the right frontal area (Fp2, F4, and F8) showed the most significant group differences (F [1, 82] = 10.079, p = 0.002, partial η2 = 0.021), with a peak at the F4 electrode site (F [1, 82] = 12.646, p < 0.001, partial η2 = 0.069). We observed no correlation between HEP and symptoms in patients with schizophrenia. A positive shift of HEP during the late component could reflect a trait abnormality in schizophrenia. Further research is required to determine the association between the altered cortical interoceptive processing indexed with HEP and self-disturbances in schizophrenia.

Pons-to-Cerebellum Hypoconnectivity Along the Psychosis Spectrum and Associations With Sensory Prediction and Hallucinations in Schizophrenia

BackgroundSensory prediction allows the brain to anticipate and parse incoming self-generated sensory information from externally generated signals. Sensory prediction breakdowns may contribute to perceptual and agency abnormalities in psychosis (hallucinations, delusions). The pons, a central node in a cortico-ponto-cerebellar-thalamo-cortical circuit, is thought to support sensory prediction. Examination of pons connectivity in schizophrenia and its role in sensory prediction abnormalities is lacking. MethodsWe examined these relationships using resting-state functional magnetic resonance imaging and the electroencephalography-based auditory N1 event-related potential in 143 participants with psychotic spectrum disorders (PSPs) (with schizophrenia, schizoaffective disorder, or bipolar disorder); 63 first-degree relatives of individuals with psychosis; 45 people at clinical high risk for psychosis; and 124 unaffected comparison participants. This unique sample allowed examination across the psychosis spectrum and illness trajectory. Seeding from the pons, we extracted average connectivity values from thalamic and cerebellar clusters showing differences between PSPs and unaffected comparison participants. We predicted N1 amplitude attenuation during a vocalization task from pons connectivity and group membership. We correlated participant-level connectivity in PSPs and people at clinical high risk for psychosis with hallucination and delusion severity. ResultsCompared to unaffected comparison participants, PSPs showed pons hypoconnectivity to 2 cerebellar clusters, and first-degree relatives of individuals with psychosis showed hypoconnectivity to 1 of these clusters. Pons-to-cerebellum connectivity was positively correlated with N1 attenuation; only PSPs with heightened pons-to-postcentral gyrus connectivity showed this pattern, suggesting a possible compensatory mechanism. Pons-to-cerebellum hypoconnectivity was correlated with greater hallucination severity specifically among PSPs with schizophrenia. ConclusionsDeficient pons-to-cerebellum connectivity linked sensory prediction network breakdowns with perceptual abnormalities in schizophrenia. Findings highlight shared features and clinical heterogeneity across the psychosis spectrum.