Schizophrenia is often conceptualized as a brain network disorder, yet the organizational principles and heterogeneity underlying widespread cortical abnormalities remain poorly understood. Leveraging multisite MRI data from 3,958 individuals diagnosed with schizophrenia and 5,489 neurotypical individuals, we studied the cortical organization and its subtyping by analyzing individualized cortical network similarity. We used eigenvector decompositions to study spatial patterning of the gradients and graph theory to study small-world topology. Individuals with schizophrenia showed widespread alterations of gradient loadings, which followed inferior-superior and frontal-temporal axes. Alterations in small-world topology were localized in key network hubs, including the insula and anterior cingulate cortex. Brain-symptom association analyses identified a latent dimension linking disorganization symptoms to topological alterations. Finally, clustering cortical alterations identified two robust subtypes, characterized by divergent anterior cingulate (S1) versus temporoparietal (S2) thickness differences aligned with the intrinsic gradient-topology patterns. Both subtypes were present early in the illness and stable across disease stages and age groups. These findings reveal systematic disruptions of cortical organization in schizophrenia, providing a network-level framework for macroscale brain organization and inter-individual heterogeneity.

Positive and negative schizotypy reflect distinct patterns of subclinical traits in the general population associated with neurodevelopmental and schizophrenia-spectrum pathologies. Yet, a comprehensive characterization of the unique and shared neuroanatomical signatures of these schizotypy dimensions is lacking. Leveraging 3D brain MRI data from 2730 unmedicated healthy individuals, we identified neuroanatomical profiles of positive and negative schizotypy and systematically compared them with disorder-specific, microarchitectural, neurotransmitter-level, and connectome measures. Positive and negative schizotypy were associated with distinct cortical signatures, of predominantly thinner frontal and thicker paralimbic cortical areas, respectively. These cortical signatures of positive and negative schizotypy were differentially linked to brain-wide cortical patterns of schizophrenia-spectrum (clinical high-risk for psychosis, schizophrenia) and neurodevelopmental conditions (ADHD, autism spectrum disorder and 22q11.2 deletion syndrome). Additionally, the positive and negative schizotypy-related cortical profiles mapped onto different local attributes of gene expression, cortical myelination, D1, and histamine receptor distributions. Network models further showed that positive and negative schizotypy cortical signatures were spatially associated with cortical hubs, suggesting that highly interconnected regions are more vulnerable to the morphological differences associated with both schizotypy dimensions. Finally, predominantly sensorimotor-to-association and paralimbic areas emerged as epicenters with connectivity profiles significantly linked to the schizotypy-related cortical patterns. Collectively, this study identified cortical signatures of positive and negative schizotypy traits that are embedded along multiple scales of cortical organization and neuropsychiatric pathologies. Our work yields novel insights into how neurobiology and brain architecture may guide neuroanatomical vulnerability and resilience to psychopathology in the general population.

Abstract Elucidating the neurobiological basis of neurodevelopmental and psychiatric conditions (NDPCs) remains challenging because brain alterations vary within diagnoses and overlap across them. Whether diverse alterations follow a systematic organization that may reflect shared vulnerabilities remains unknown. Here, we assembled 10,135 individuals with schizophrenia, autism, bipolar, obsessive-compulsive, generalized anxiety, and major depressive disorders, and 11,998 reference participants across six continents through the ENIGMA consortium. Using normative modeling, we quantified individual deviations in cortical thickness, surface area, and subcortical volumes relative to lifespan reference trajectories (5 to 80 years). We show that structural deviations converged along cortical axes reflecting connectome organization, maturation, and cytoarchitectonic diversity. These axes mirrored typical population variation, but their expression differed across diagnoses and partly scaled with symptom severity. Even rare and highly individualized extreme deviations followed this organization, concentrating in densely connected regions. Finally, brain structural deviations overlapped substantially across diagnoses, while differences between them increased toward the association cortex. Together, we provide large-scale evidence that structural deviations across NDPCs are systematically constrained by the brain’s intrinsic architecture. This shared organization provides a framework for reconciling individual variability with transdiagnostic similarities and motivates an integrative, systems-level understanding of mental health.

The structural MRI of the cortex, subcortical structures, hippocampal subfields, and brainstem regions in patients with persecutory delusions in schizophrenia (ICD-10 code: F20) and delusional disorder (ICD-10 code: F22.0) were analyzed. Patients demonstrated multiple regions of decreased cortical gray matter thickness, reduced volumes of the left thalamus and some hippocampal sub-fields compared to mentally healthy subjects. No alterations in brainstem structures were found. The results were analyzed within the framework of the transnosological model of delusions.

It is hypothesised that structural brain abnormalities in individuals with schizophrenia are associated with aggressive behaviour, but this has not been tested directly. We pooled magnetic resonance imaging and clinical data from 2095 patients and 2861 healthy control subjects across 20 sites of the ENIGMA-Schizophrenia Working Group. Using normative modelling, we quantified individual-level deviations from controls (z-scores) for global and regional grey matter volume and white matter microstructural integrity. Ordinal regression models were used to estimate the associations between these deviations and concurrent aggression (odds ratios [ORs] with 99

Brain network architecture is anticipated to influence future grey matter loss in individuals at Clinical High Risk (CHR) for psychosis. However, existing studies on grey matter structural network properties in CHR are scarce and constrained by small sample sizes. Here, we examined network topology differences comparing a) CHR versus healthy controls (HC); b) CHR who transitioned to psychosis (CHR-T) versus those who did not (CHR-NT); and c) different subsyndromes. We included structural scans from 1842 CHR individuals and 1417 HC individuals from 31 sites within the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. At the global level, CHR individuals exhibited lower structural covariance (q < 0.001; Cohen’s d = 0.164) and less optimal structural network configuration than HC (lower global efficiency and clustering coefficient, d = 0.100,0.087, qs <= 0.027). Though no global difference between CHR-T and CHR-NT, network distinctiveness of the frontal and temporal surface area networks was higher in CHR-T than CHR-NT (d = 0.223,0.237) and HC (d = 0.208,0.219) (qs < 0.001). Network distinctiveness of the frontal cortical thickness network was lower in CHR-T (d = 0.218, q < 0.001) than CHR-NT and HC (d = 0.165, q < 0.001). Importantly, higher network distinctiveness was associated with worse positive symptoms in CHR-NT (frontal surface area, q = 0.008, R2 = 0.013) and at trend with worse negative symptoms in CHR-T (frontal thickness, q = 0.063, R2 = 0.049). Further, the brief intermittent psychotic syndrome subgroup showed more severe network alterations. Together, brain structural networks inform symptoms and the risk of transition to psychosis in CHR individuals.

Objectives. To compare the clinical outcome and tolerability of transcranial magnetic stimulation (rTMS) using different stimulation protocols and to determine the dynamics of neurophysiological indexes of the functional state of the brain. Materials and methods. The study included 28 patients (mean age 23.5 ± 4.4 years) diagnosed with psychometrically confirmed F21 or F31–F34 and clinically significant depression (mean score on the Hamilton Depression Rating Scale (HDRS) 21.7 ± 5.6). Treatment included combined medication and rTMS of the left dorsolateral prefrontal cortex using two different protocols: 10 Hz (n = 16) and intermittent θ-burst stimulation (n = 12), which were randomly assigned. EEG recordings were made in all patients, both EEG and fMRI were made in patients undergoing θ-burst stimulation. The treatment efficacy criterion was a ≥25

Background: studies allowing to explore the neurobiological characteristics of the long-term schizophrenic process are of high significance for both clinical practice and biological psychiatry. Objective: to examine morphometric brain characteristics in chronic schizophrenia patients with different types of functional outcomes. Patients and methods: morphometric MRI characteristics of the cerebral cortex and subcortical structures are analysed in 46 patients with schizophrenia with a long disease durations (20.5 ± 6.7 years), and in 35 mentally healthy subjects matched by sex and age. Results and discussion: the whole group of patients showed decreased gray matter thickness in some cerebral cortex regions. When outcome was assessed using clinical-psychopathologic, clinical-catamnestic, and clinical-epidemiologic methods, bilateral increases in pallidum and putamen volumes were found to be a presumptive marker of worse functional outcome and remission poor quality. At the same time, when outcome was assessed on the basis of the current psychometric measures of social functioning and clinical symptomatology, patients with an unfavorable outcome were characterized by decreased gray matter thickness in the two cingulate cortex regions compared to both healthy controls and patients with a good outcome. However, the absence of correlations with clinical scales and functioning doesn’t allow a conclusion on the specificity of this decrease as a marker of outcome. Conclusion: the results may only presume beforehand the existence of different neuroanatomical subtypes (biotypes) associated with different functional outcomes in patients with chronic schizophrenia.

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia’s alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

One of the informative and widely used approaches to understanding the pathogenetic (including neurobiological) mechanisms of schizophrenia is the study of patients with clinically high risk (CHR) for the disease. The power and topography of the theta rhythm event-related synchronization (ERS) related to peripheral stimulus that must be remembered (memory-guided saccades/antisaccades paradigm) have been studied in the groups of 20 mentally healthy subjects and 20 patients with CHR. The analysis was carried out according to the Pfurtscheller method. Based on the saccades latency value and the error numbers, the task performance was decreased in patients with CHR compared to healthy subjects. Intergroup differences by theta rhythm ERS magnitude and topography were found for three consecutive delay period intervals (900 ms each) before saccades to the right and antisaccades to the left. The findings are considered as being the reflection of violations of the spatial attention and working memory maintaining in CHR patients that has a certain interhemispheric asymmetry. It has been suggested an activation of the compensatory processes and the cognitive control reorganization of the fronto-parietal networks with predominantly right hemisphere preservation at the early stage of schizophrenia development.

Background: the dorsolateral prefrontal cortex (DLPFC) is one of the latest brain structures to mature during the ontogeny, and its structural and functional abnormalities play an important role in the pathogenesis of schizophrenia. As schizophrenia spectrum disorders usually start before the complete brain maturation and their earlier onset is coupled with worse prognosis, we suggested that earlier illness onset is related to more pronounced aberrations of the DLPFC. The aim of study was to analyze the associations of the onset age of schizophrenia spectrum disorders with structural and functional characteristics of the DLPFC that differentiated patients with schizophrenia spectrum disorders from healthy controls. Patients and methods: male patients with a diagnosis of schizophrenia spectrum disorders (n = 82) and healthy controls (n = 86) underwent structural MRI and functional resting-state fMRI. Cortical thickness and whole-brain functional connectivity of the DLPFC as well as local coherence and amplitude of low-frequency fluctuations of haemodynamic signal in the DLPFC were analyzed. Results: patients demonstrated a decreased gray matter thickness in the DLPFC bilaterally along with aberrant (predominantly decreased) functional connectivity of the DLPFC with other brain structures in each hemisphere. These measures were not associated with the age of illness onset. Conclusions: structural and functional abnormalities revealed in this study coincide with conventional view on the DLPFC as one of the key regions in schizophrenia spectrum disorders pathogenesis, however, these aberrations were not related to the age of psychosis onset. Possible interpretations of our results and limitations of the study are discussed in the article.

Background Despite the high clinical role of delusions as a transnosological psychopathological phenomenon, the number of experimental studies on the different types of delusions across schizophrenia spectrum is still relatively small, and their results are somehow inconsistent. We aimed to understand the current state of knowledge regarding the structural and functional brain alterations in delusions to determine whether particular types of delusions are associated with specific brain changes and to identify common alterations underlying the formation and persistence of delusions regardless of their content. Methods For this systematic review, we followed PRISMA guidelines to search in PubMed for English papers published between 1953 and September 30, 2023. The initial inclusion criteria for screening purposes were articles that investigated delusions or subclinical delusional beliefs in schizophrenia spectrum disorders, high clinical or genetic risk for schizophrenia using fMRI, sMRI or/and dwMRI methods. Exclusion criteria during the screening phase were articles that investigated lesion-induced or substance-induced delusions, delusions in Alzheimer's disease and other neurocognitive disorders, single case studies and non-human studies. The publication metadata were uploaded to the web-tool for working on systematic reviews, Rayyan. For each of the studies, a table was filled out with detailed information. Results We found 1752 records, of which 95 full-text documents were reviewed and included in the current paper. Both nonspecific and particular types of delusions were associated with widespread structural and functional alterations. The most prominent areas affected across all types of delusions were the superior temporal cortex (predominantly left language processing areas), anterior cingulate/medial prefrontal cortex and insula. The most reproducible findings in paranoia may be alterations in the functioning of the amygdala and its interactions with other regions. Somatic delusions and delusional infestation were mostly characterized by alterations in the insula and thalamus. Discussion The data are ambiguous; however, in general the predictive processing framework seems to be the most widely accepted approach to explaining different types of delusions. Aberrant prediction errors signaling during processing of social, self-generated and sensory information may lead to inaccuracies in assessing the intentions of others, self-relevancy of ambiguous stimuli, misattribution of self-generated actions and unusual sensations, which could provoke delusional ideation with persecutory, reference, control and somatic content correspondingly. However, currently available data are still insufficient to draw conclusions about the specific biological mechanisms of predictive coding account of delusions. Thus, further studies exploring more homogeneous groups and interaction of diagnoses by types of delusions are needed. There are also some limitations in this review. Studies that investigate delusions induced by lesions, substance abuse or neurodegeneration and studies using modalities other than fMRI, sMRI or dwMRI were not included in the review. Due to the relatively small number of publications, we systematized them based on a certain type of delusions, while the results could also be affected by the diagnosis of patients, the presence and type of therapy, illness duration etc.

Objectives . To identify the structural features of the gray matter of the cerebral cortex in patients with depression at clinical high risk of psychosis. Materials and methods . Nineteen right-handed male patients with juvenile depression who met the criteria for a high risk of psychosis, along with 20 sex- and age-matched mentally healthy subjects as a control group, underwent clinical and MRI investigations. T1-weighted images were processed in FreeSurfer 7.1.1 to obtain average cortical gray matter thickness, subcortical volume, and amygdalar nucleus volume for each subject. Between-group comparisons were made and correlations with psychometric measures (SOPS, HDRS) were calculated. Results . Lower cortical thickness was found in patients in the left ( p = 0.002) and right ( p = 0.003) postcentral gyrus, along with greater thickness in the right posterior cingulate cortex ( p = 0.003) and the anterior part of the anterior cingulate cortex ( p = 0.001). Conclusions . This picture may reflect changes in the cerebral cortex at the early stages of the endogenous process, including reductions in gray matter in some areas and changes in the opposite direction in others (a relationship between the latter and altered ontogenesis and/or certain compensatory changes cannot be excluded).

Thanks to the development of structural and functional magnetic resonance imaging (MRI) methods, in recent decades there has been a lot of research aimed at elucidating brain abnormalities caused by amblyopia. In the cases of this prevalent visual disorder, the anomalies causing decreased visual acuity and other visual disabilities cannot be determined by standard ophthalmologic examination. Since there are several types of this disorder that are fundamentally different in etiology, it is natural to suggest the presence of different types of corresponding brain abnormalities. In this regard, before obtaining a general picture of the pathogenesis of amblyopia, studies conducted on groups of specially selected similar patients are very important. This paper presents the results of a study of school-age children with left-sided anisometropic amblyopia. In the patients investigated, MRI data revealed interhemispheric differences in the thickness of the lateral occipital cortex, and resting-state fMRI revealed interhemispheric differences in the local coherence of the hemodynamic signal within 17 Brodmann area and in the functional connectivity between 17 and 18+19 Brodmann areas. The data obtained contribute to the creation of a general MRI database on the pathophysiology of amblyopia, help clarify some controversial issues and indicate the advisability of using resting-state fMRI in ophthalmology.

With the aim of systematizing scientific data in the current Russian and foreign literature on the efficacy of biofeedback (BF) in the treatment of patients with depressive disorders and the clinical efficacy and prospects for use of BF in psychiatric practice, the MEDLINE/PubMed and eLibrary databases were searched with the keywords “biofeedback,” “depression,” “therapy for depression,” “electroencephalogram,” and “non-drug methods for treating depression” and scientific publications from 2013 to 2023 were analyzed along with relevant references cited in the articles analyzed. The BF method has definite therapeutic potential for the treatment of depression. The method can be used to augment therapy when therapeutic effects are insufficient, when patient compliance is low, when tolerance of psychopharmacotherapy is poor, and when residual symptoms are present after pharmacological treatment. The method provides correction of psychoemotional state, improves the balance between the parasympathetic and sympathetic branches of the autonomic nervous system, and contributes to a more sustainable clinical effect. At the same time, further studies are needed with larger patient cohorts from a variety of nosological groups and with analysis of the comparability of the effects of different BF protocols.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS + individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1,165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1,029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-includingthose from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS + from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS + in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Background: brain structural peculiarities in different mental disorders are neurobiological indicators that are extremely important both for understanding of the diseases’ pathogenesis and for identifying potentially valid prognostic markers. The aim of this pilot study was to identify the range of brain morphometric parameters in the group of patients with schizotypal disorders with catatonia syndrome. Patients and methods: 33 patients with schizotypal disorder and 33 age-matched mentally healthy subjects underwent high-resolution structural MRI on a 3T Philips Ingenia scanner. Results: there were found widely distributed intergroup differences in form of the smaller gray matter thickness. In this spectrum, a morphometric abnormality of the precentral gyrus, an area of the primary motor cortex localization, previously not noted in the literature on schizotypal disorder, drew special attention. In addition, smaller volume of the nuclei accumbens (included in the processes of choosing actions) was found. Conclusions: this pilot study allowed to reveal some brain elements of the mosaic presumably associated with the manifestation of catatonia syndrome in schizotypal disorder.

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.

Background: despite a significant progress of psychopharmacology, treatment-resistant schizophrenia (TRS) remains a challenge for clinicians. The etiology and pathogenesis of TRS probably differ from schizophrenia susceptible to therapy, which underlies the non-respondence to most antipsychotics.Objective: to establish morphometric gray matter brain structural features in TRS as well as to analyze the association of these parameters with the clinical characteristics of patients.Patients and methods: 21 right-handed male patients diagnosed with paranoid schizophrenia and meeting criteria for treatment resistance and 21 matched healthy controls underwent MRI and clinical examination. T1-weighted images were processed via FreeSurfer 7.1.1. For each subject average values for the cortex thickness and area, volumes of subcortical structures, brain stem structures, and separately volumes of the amygdala nuclei and hippocampal subregions were obtained. Intergroup comparisons and correlations with clinical scales (PANSS, CDSS) and antipsychotic dosage in chlorpromazine equivalent were calculated. Results: TRS patients showed decreased gray matter thickness in frontal, temporal, parietal, occipital, cingulate and insular regions, volumes of the amygdala, hippocampus and nucleus accumbens, as well as a number of amygdala nuclei and hippocampal subregions bilaterally. The volume of the right globus pallidus, on the contrary, was increased.Conclusion: the widespread gray matter thinning in TRS confirmed the other researchs, which described resistance as a more severe form of schizophrenia that affects brain structures worse. The increase of globus pallidus volume is a surprising result, which is not yet clearly explained.

Based on the concept of clinical high risk for psychosis, we aimed to reveal characteristics of brain functioning (resting-state fMRI) and neurocognition in 27 patients with non-psychotic mental disorders with attenuated schizophrenia symptoms who did not transit to psychosis for a long period of observation, in contrast to 24 patients with first-episode schizophrenia and 27 mentally healthy subjects. The main group was characterized by higher local coherence of BOLD signal in the right visual cortex and higher functional connectivity between the occipital component of the visual network and the right prefrontal component of the salience network (as compared to patients with schizophrenia). In both patient groups, a decreased productivity in verbal fluency tests was found. The neuroimaging and neuropsychological findings in the main group can be considered via the dichotomy of protective and pathological mechanisms in patients with high risk for psychosis.