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This study aimed to identify neural biomarkers for schizophrenia (SZ) and bipolar disorder (BP) by analyzing multimodal neuroimaging. Utilizing data from structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI), multiclass classification models were created for SZ, BP, and healthy controls (HC). A total of 113 participants (BP: 31, SZ: 39, and HC: 43) were recruited under strict enrollment control, from which 272, 200, and 1875 features were extracted from sMRI, DTI, and rs-fMRI data, respectively. A support vector machine (SVM) with recursive feature elimination (RFE) was employed to build the models using a one-against-one approach and leave-one-out cross-validation, achieving a classification accuracy of 70.8%. The most discriminative features were primarily from rs-fMRI, along with significant findings in sMRI and DTI. Key biomarkers identified included the increased thickness of the left cuneus cortex and decreased regional functional connectivity strength (rFCS) in the left supramarginal gyrus as shared indicators for BP and SZ. Additionally, decreased fractional anisotropy in the left superior fronto-occipital fasciculus was suggested as specific to BP, while decreased rFCS in the left inferior parietal area might serve as a specific biomarker for SZ. These findings underscore the potential of multimodal neuroimaging in distinguishing between BP and SZ and contribute to the understanding of their neural underpinnings., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Cognitive deficits are core symptoms of schizophrenia (SZ) and are associated with impaired resilience to stress. Different cognitive functions appeared to be interrelated, and the mechanism may involve neural alterations. The disrupted topological organization indicated abnormalities in the segregation and integration of brain networks that support various cognitive processes in SZ patients. Therefore, this study aimed to assess the direct and indirect effects of resilience on cognitive functions. We hypothesized that topological properties would moderate these associations., Methods: Forty-nine SZ patients and fifty-two healthy controls (HCs) were recruited in this study. The Connor-Davidson Resilience Scale and the MATRICS Consensus Cognitive Battery were used to examine resilience and cognitive functions, respectively, and a graph theory approach was used to assess white matter topological organization., Results: Compared to HCs, SZ patients showed lower levels of resilience and cognitive functions in multiple domains as well as abnormal global properties and nodal metrics. In addition, shorter characteristic path length was associated with a stronger indirect effect of resilience on working memory through processing speed in SZ patients., Conclusion: Characteristic path length might moderate the mediating effects of processing speed in the relationship between resilience and working memory in schizophrenia patients., Competing Interests: Declaration of Competing Interest We declare that the work described in this paper had no financial or personal relationships with other people or organizations. All authors reported no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Schizophrenia (SZ) and bipolar disorder with psychosis (BDP) can be clinically confusing. The specific connectomic changes in SZ compared with BDP may lead to a deeper comprehension of the pathophysiological core of SZ. Therefore, this study explored the common and distinct white matter (WM) structural connectomic alterations between these two diseases., Method: Diffusion tensor imaging data were collected from 19 drug-naïve patients with first episode SZ, 19 drug-naïve patients with BDP, and 19 healthy controls (HC). A graph theoretical approach was used to assess the brain WM network properties., Results: Except for the clustering coefficients, no significant differences in the global parameters was found between SZ and BDP. Five brain regions, the right precentral, right post-cingulum, right insula, left superior occipital, and left inferior temporal gyri, showed specific differences in the nodal parameters in SZ compared with BDP and HC. Nine brain regions, the left rectus, left lingual, right inferior parietal, left superior temporal, right precentral, right postcentral, bilateral middle frontal, and right post-cingulum gyri, showed specific differences in the nodal parameters in BDP. Significant correlations between clinical symptoms and connectomic changes were detected in the right insula and left superior occipital gyrus in patients with SZ but in the left lingual gyrus in patients with BDP., Conclusions: Identifying shared and distinct WM structural networks between SZ and BDP may improve the understanding of the neuroanatomy of mental diseases. Specifically, the insula, the inferior temporal, superior temporal, and the lingual gyri may help to distinguish between SZ and BDP., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Schizophrenia (SCZ) is a highly heritable disorder associated with brain connectivity changes. Although the mechanism of disease expression and vulnerability of SCZ have been reported by previous studies, the mechanism of resilience to SCZ based on the brain structural connectivity is poorly understood. The goal of the present study was to identify the structural brain connectivity related with the resilience to SCZ, which is defined here as the capacity to avoid or delay the onset of SCZ in unaffected siblings of SCZ probands., Method: We collected diffusion tensor imaging (DTI) data of 49 medication-naive, first-episode SCZ (FE-SCZ) patients, 56 unaffected siblings of SCZ probands (SIB-SCZ), and 90 healthy controls. Then we used graph theoretical approach to calculate the topological properties of the brain structural network, including global, subnetwork, and regional parameters. Finally, we compared the parameters between the three groups, and identified the brain structural network related to the resilience, vulnerability and disease expression to SCZ., Results: With respect to resilience, only the SIB-SCZ showed significantly increased connectivity in the subnetworks of the left cuneus-precuneus and left posterior cingulate gyrus-precuneus, and in brain areas of right supramarginal gyrus and right inferior temporal gyrus. With respect to vulnerability, both the FE-SCZ and SIB-SCZ had decreased cluster coefficients and local efficiency, and decreased nodal efficiency in the right medial superior frontal gyrus and right medial orbital superior frontal gyrus compared with the healthy controls. With respect to disease expression, only the FE-SCZ group showed decreased or increased global, subnetwork, and nodal connectivity in broader brain regions compared with the healthy controls., Conclusion: Difference in the topological properties of brain structural connectivity not only reflect the underlying mechanism of vulnerability but also that of resilience to schizophrenia. Alteration in the brain structural connectivity associating with resilience and disease expression may contribute to the onset of SCZ., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The effects of ZNF804A rs1344706, a prominent susceptibility gene for schizophrenia, on gray matter (GM) structure in unmedicated schizophrenia (SZ) patients are still unknown, although several previous studies investigated the effects in medicated SZ patients and healthy controls (HC). Analyzing cortical thickness, surface area, and GM volume simultaneously may provide a more precise and complete picture of the effects. We genotyped 59 unmedicated first episode SZ patients and 60 healthy controls for the ZNF804A single nucleotide polymorphism (SNP) rs1344706, and examined between-group differences in cortical thickness, surface area, and cortical volume using a full-factorial 2 × 2 analysis of variance (ANOVA). We found the risk allele (T) in ZNF804A rs1344706, compared to the non-risk allele (G), was associated with thinner cortex in the bilateral precuneus, left precentral gyrus, and several other regions, associated with a smaller cortical surface area in the left superior parietal, precuneus cortex and left superior frontal, and associated with a lower cortical volume in the left superior frontal, left precentral, and right precuneus in SZ patients. In contrast, in the controls, the T allele was associated with the increased cortical measurements compared to the G allele in the same regions as those mentioned above. ZNF804A rs1344706 has significant, but different, effects on cortical thickness, surface area, and cortical volume in multiple regions of the brain cortex. Our findings suggest that ZNF804A rs1344706 may aggravate the risk for schizophrenia by exerting its effects on cortical thickness, surface area, and cortical volume in these brain regions., (© 2015 Wiley Periodicals, Inc.)

Previous studies suggested that the topological properties of brain anatomical networks may be aberrant in schizophrenia (SCZ), and most of them focused on the chronic and antipsychotic-medicated SCZ patients which may introduce various confounding factors due to antipsychotic medication and duration of illness. To avoid those potential confounders, a desirable approach is to select medication-naïve, first-episode schizophrenia (FE-SCZ) patients. In this study, we acquired diffusion tensor imaging datasets from 30 FE-SCZ patients and 34 age- and gender-matched healthy controls. Taking a distinct gray matter region as a node, inter-regional connectivity as edge and the corresponding streamline counts as edge weight, we constructed whole-brain anatomical networks for both groups, calculated their topological parameters using graph theory, and compared their between-group differences using nonparametric permutation tests. In addition, network-based statistic method was utilized to identify inter-regional connections which were impaired in the FE-SCZ patients. We detected only significantly decreased inter-regional connections in the FE-SCZ patients compared to the controls. These connections were primarily located in the frontal, parietal, occipital, and subcortical regions. Although small-worldness was conserved in the FE-SCZ patients, we found that the network strength and global efficiency as well as the degree were significantly decreased, and shortest path length was significantly increased in the FE-SCZ patients compared to the controls. Most of the regions that showed significantly decreased nodal parameters belonged to the top-down control, sensorimotor, basal ganglia, and limbic-visual system systems. Correlation analysis indicated that the nodal efficiency in the sensorimotor system was negatively correlated with the severity of psychosis symptoms in the FE-SCZ patients. Our results suggest that the network organization is changed in the early stages of the SCZ disease process. Our findings provide useful information for further understanding the brain white matter dysconnectivity of schizophrenia.

Objective: To detect the changes of cortical thickness and cortical surface area in untreated patients of first-episode schizophrenia., Methods: Fifty-seven untreated patients of first-episode schizophrenia (SCZ) hospitalized from September 2009 to March 2012 at Department of Psychiatry, Third Affiliated Hospital, SUN Yat-sen University and 57 healthy controls (HC) recruited by advertising during the same period underwent a high resolution three-dimensional magnetic resonance imaging of brain structures. And cortical-surface based technique was used to analyze the cortical thickness and cortical surface area. The general linear model (GLM) was employed to detect the differences of cortical thickness and cortical surface area between two groups., Results: were corrected for multiple comparisons by the Monte Carlo simulation method., Results: As compared with HC, the cortical thickness of left superior frontal, left caudal middle cingulate, left lateral occipital, right superior frontal, right superior temporal and right fusiform regions in SCZ decreased by 6.0%, 7.2%, 8.2%, 5.2%, 7.1% and 6.0% respectively. And the largest reductions occurred in left lateral occipital regions. Cortical surface area of each brain regions in SCZ had no significant difference with HC., Conclusion: Cortical thickness reductions exist in multiple brain regions in schizophrenia. It may be the neuropathological mechanisms of schizophrenia.

Altered brain connectivity has been widely considered as a genetic risk mechanism for schizophrenia. Of the many susceptibility genes identified so far, ZNF804A (rs1344706) is the first common genetic variant associated with schizophrenia on a genome-wide level. Previous fMRI studies have found that carriers of rs1344706 exhibit altered functional connectivity. However, the relationship between ZNF804A and white matter structural connectivity in patients of schizophrenia remains unknown. In this study, 100 patients with schizophrenia and 69 healthy controls were genotyped at the single nucleotide polymorphism rs1344706. Diffusion tensor imaging (DTI) was conducted and analyzed with tract-based spatial statistics. Systematic statistical analysis was conducted on multiple diffusion indices, including fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. Unpaired two-sample t-test revealed significant differences in fractional anisotropy and diffusivity between schizophrenia and control groups. A two-way ANOVA analysis was conducted to assess the main effects of and the interaction between schizophrenia and ZNF804A. Although significant main effects of the diagnosis of schizophrenia were found on radial diffusivity, no association between the ZNF804A (rs1344706) and white matter connectivity was found in the entire group of subjects or in a selected subgroup of age-matched subjects (n=72)., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To explore the diffusion tensor imaging (DTI) features of white matter in healthy siblings of schizophrenics., Methods: Twenty healthy siblings of schizophrenics and 45 healthy controls without a family history of mental disorder. They responded to advertised recruitment during December 2009 and March 2012. All participants underwent diffusion weighted magnetic resonance images with a single-shot echo planar imaging (EPI) sequence aligned to straight axial plane. The fractional anisotropy (FA) images of two groups underwent two-sample t-test with SPM5 software., Results: The healthy siblings of schizophrenics demonstrated a significant decrease of regional white matter FA values in right anterior cingulated (MNI: x = 9, y = 43, z = 4; cluster = 106)., Conclusion: Reduced white matter integrity in right anterior cingulated may be a risk actor of schizophrenia.

Schizophrenia is thought to arise in part from abnormal gray matter (GM), which are partly shared by the relatives of the probands. DISC1 is one of the most promising susceptibility genes of schizophrenia and a SNP rs821597 (A) in the gene was associated with schizophrenia in Han Chinese population. In this study, 61 healthy controls and 72 with schizophrenic patients were genotyped at rs821597, and underwent T1-weighted MRI for the density of GM. The results showed that the risk allele (A) carriers had higher GM density in regional left parahippocampal gyrus and right orbitofrontal cortex in schizophrenic patients, but had reduced GM density of these brain regions in healthy controls. The DISC1 variant rs821597 may confer risk for schizophrenia by its effects on the regional GM in left parahippocampal gyrus and right orbitofrontal cortex with other risk factors for schizophrenia., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To explore the roles of diffusion tensor imaging (DTI) of white matter at an early stage of schizophrenia., Methods: The participants were 20 first-episode, medication-naïve schizophrenics at an early stage (1 - 6 months) and 20 healthy controls adjusted in gender and age during December 2009 and October 2010. They underwent diffusion weighted magnetic resonance imaging with a single-shot echo planar imaging (EPI) sequence aligned to straight axial plane. The fractional anisotropy (FA) images of two groups underwent two-sample paired t-test with SPM5 software., Results: The schizophrenics at an early stage demonstrated a significant decrease of regional white matter FA values in right anterior cingulated (MNI: x = 12, y = 24, z = -10; cluster = 145) and right middle occipital lobe (MNI: x = 36, y = -76, z = -2; cluster = 135)., Conclusion: The altered white matter DTI in right anterior cingulated and middle occipital lobe may contribute to an early detection of schizophrenia.

Background: ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients., Methods: 69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2×2 analysis of variance., Results: 1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers. 2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group., Limitation: The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated., Conclusions: The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To compare the regional white matter integrity of schizophrenics with impulsive behaviors versus those without., Methods: Seventeen patients with first-episode-schizophrenia impulsive behaviors and 24 patients with first-episode-schizophrenia non-impulsive behaviors underwent diffusion weighted magnetic resonance imaging with a single-shot echo planar imaging (EPI) sequence aligned to straight axial plane. The fractional anisotropy (FA) images of two groups received two-sample t-test with SPM5 software., Results: The patients with impulsive behaviors demonstrated a significant decrement of white matter FA values in left precentral gyrus (MNI: x = -28.00, y = -28.72, z = -54.71; cluster = 79 voxels), left cerebellum anterior lobe (MNI: x = -22, y = -56, z = -28; cluster = 130 voxels) and left occipital lobe (MNI: x = -6, y = -72, z = 6; cluster = 54 voxels)., Conclusion: The altered white matter integrity of left precentral gyrus, cerebellum anterior lobe and occipital lobe may be involved in the neural mechanism of impulsive behaviors in schizophrenia.

Objective: To investigate the integrity of white matters in first-episode and chronic schizophrenics., Methods: For this study, 39 first-episode and 38 chronic schizophrenics, 69 healthy controls (age, gender and years of received education no significantly different from those of the patients) underwent diffusion weighted images with a single-shot echo planar imaging (EPI) sequence aligned to the straight axial plane. The fractional anisotropy (FA) images of three groups underwent one-way ANOVA with the methods of voxel-based morphometric (VBM) analysis., Results: (1) There were three brain regions where the FA values of white matter were different among three groups: right caudate nucleus (MNI: 20, 12, 14; cluster = 432 voxels; FA value: 0.36 ± 0.18 vs 0.35 ± 0.24 vs 0.38 ± 0.17), left insula (MNI: -32, 18, 2; cluster = 204 voxels; FA value: 0.35 ± 0.31 vs 0.33 ± 0.24 vs 0.36 ± 0.21) and right anterior cingulate (MNI: 16, 36, 12; cluster = 132 voxels; FA value: 0.35 ± 0.29 vs 0.34 ± 0.31 vs 0.37 ± 0.25). (2) The mean FA values of the three brain regions of two patients groups decreased versus those of healthy controls (P < 0.05). (3) The mean FA values of left insular region in chronic patients decreased versus those of the first-episode patients (P < 0.05)., Conclusion: The reduced integrity of white matter may play an etiological role in schizophrenia and the changes are probably progressive.

Objective: To investigate the value of diffusion tenser image (DTI) in identifying subtle abnormalities in the corpus callosum and bilateral middle cerebellar peduncles in patients with the initial onset of schizophrenia., Methods: Twenty patients with the first episode of schizophrenia and 18 healthy subjects were examined by DTI. Fractional anisotropy (FA) and averaged diffusion coefficient (ADC) were measured in the bilateral middle cerebellar peduncles, genu and splenium of the corpus callosum. Independent-sample t test was used to compare the value of FA and ADC between the two groups., Result: The FA of the bilateral middle cerebellar peduncles was significantly lower in the schizophrenic patients than in the healthy subjects (P<0.05), but that in the genu and splenium of the corpus callosum were comparable between the two groups (P>0.05). The ADC values showed no significant difference in all the above regions between the two groups (P>0.05)., Conclusion: Subtle abnormal changes occur in the cerebrum-cerebellumto circuit in schizophrenic patients, and may trigger the onset of the symptoms in the early stages of schizophrenia.