Shengnan Wei

Neurobiological Commonalities and Distinctions Among Three Major Psychiatric Diagnostic Categories: A Structural MRI Study

BACKGROUND Schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are distinct diagnostic categories in current psychiatric nosology, yet there is increasing evidence for shared clinical and biological features in these disorders. No previous studies have examined brain structural features concurrently in these 3 disorders. The aim of this study was to identify the extent of shared and distinct brain alterations in SZ, BD, and MDD. We examined gray matter (GM) volume and white matter (WM) integrity in a total of 485 individuals (135 with SZ, 86 with BD, 108 with MDD, and 156 healthy controls [HC]) who underwent high-resolution structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at a single site. RESULTS Significant 4-group (SZ, BD, MDD, and HC groups) differences (P < .05, corrected) in GM volumes were found primarily in the paralimbic and heteromodal corticies. Post hoc analyses showed that the SZ, BD, and MDD groups shared GM volume decreases in 87.9% of the total regional volume with significant 4-group differences. Significant 4-group differences in WM integrity (P < .05 corrected) were found in callosal, limbic-paralimbic-hetermodal, cortico-cortical, thalamocortical and cerebellar WM. Post hoc analyses revealed that the SZ and BD groups shared WM alterations in all regions, while WM alterations were not observed with MDD. CONCLUSIONS Our findings of common alterations in SZ, BD, and MDD support the presence of core neurobiological disruptions in these disorders and suggest that neural structural distinctions between these disorders may be less prominent than initially postulated, particularly between SZ and BD.

Sexual dimorphism of the cerebellar vermis in schizophrenia.

Converging lines of evidence implicate structural and functional abnormalities in the cerebellum in schizophrenia (SCZ). The cerebellar vermis is of particular interest given its association with clinical symptoms and cognitive deficits in SCZ and its known connections with cortical regions such as the prefrontal cortex. Prior neuroimaging studies have shown structural and functional abnormalities in the vermis in SCZ. In this study, we examined the cerebellar vermis in 50 individuals with SCZ and 54 healthy controls (HC) using a quantitative volumetric approach. All participants underwent high-resolution structural magnetic resonance imaging (MRI). The vermis was manually traced for each participant, and vermis volumes were computed using semiautomated methods. Volumes for total vermis and vermis subregions (anterior and posterior vermis) were analyzed in the SCZ and HC groups. Significant diagnosis-by-sex interaction effects were found in total vermis and vermis subregion analyses. These effects appeared to be driven by significantly decreased posterior vermis volumes in males with SCZ. Exploratory analyses did not reveal significant effects of clinical variables (FEP status, illness duration, and BPRS total score and subscores) on vermis volumes. The findings herein highlight the presence of neural sex differences in SCZ and the need for considering sex-related factors in studying the disorder.

Amygdala-Prefrontal Cortex Resting-State Functional Connectivity Varies with First Depressive or Manic Episode in Bipolar Disorder.

BACKGROUND Bipolar disorder (BD) is one of the most complex mental illnesses, characterized by interactive depressive and manic states that are 2 contrary symptoms of disease states. The bilateral amygdala and prefrontal cortex (PFC) appear to play critical roles in BD; however, abnormalities seem to manifest differently in the 2 states and may provide further insight into underlying mechanisms. METHODS Sixteen participants with first-episode depressive and 13 participants with first-episode manic states of bipolar disorder as well as 30 healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). Resting-state functional connectivity (rsFC) between the bilateral amygdala and PFC was compared among the 3 groups. RESULTS Compared with depressive state participants of the BD group, manic state participants of the BD group showed a significant decrease in rsFC between the amygdala and right orbital frontal cortex (p<0.05, corrected). In addition, rsFC between the amygdala and left middle frontal cortex was significantly decreased in depressive and manic state participants of the BD group when compared with the HC group (p<0.05, corrected). CONCLUSIONS Our findings suggest that mood state during the first episodes of BD may be related to abnormality in hemispheric lateralization. The abnormalities in amygdala- left PFC functional connectivity might present the trait feature for BD, while deficits in amygdala- right PFC functional connectivity might be specific to manic episode, compared to depressive episode.

Voxel-Based Morphometry in Individuals at Genetic High Risk for Schizophrenia and Patients with Schizophrenia during Their First Episode of Psychosis

Background Understanding morphologic changes in vulnerable and early disease state of schizophrenia (SZ) may provide further insight into the development of psychosis. Method Whole brain voxel-based morphometry was performed to identify gray matter (GM) regional differences in 60 individuals with SZ during their first psychotic episode (FE-SZ), 31 individuals at genetic high risk for SZ (GHR-SZ) individuals, and 71 healthy controls. Results Significant differences were found in several regions including the prefrontal cortex, parietal lobe, temporal lobe, hippocampus, occipital lobe, and cerebellum among the three groups (p<0.05, corrected). Compared to the HC group, the FE-SZ group had significantly decreased GM volumes in several regions including the cerebellum, hippocampus, fusiform gyrus, lingual gyrus, supramarginal gyrus, and superior, middle, and inferior temporal gyri and significantly increased GM volumes in the middle frontal gyrus and inferior operculum frontal gyrus (p<0.05). The GHR-SZ group had significant decreases in GM volumes in the supramaginal gyrus, precentral gyrus, and rolandic operculum and significant increases in GM volumes in the cerebellum, fusiform gyrus, middle frontal gyrus, inferior operculum frontal gyrus, and superior, middle, and inferior temporal gyri when compared to the HC group (p<0.05). Compared to the GHR-SZ group, the FE-SZ group had significant decreases in GM volumes in several regions including the cerebellum, fusiform gyrus, supramarginal gyrus, and superior, middle, and inferior temporal gyri (p<0.05). Conclusions The findings herein implicate the involvement of multisensory integration in SZ development and pathophysiology. Additionally, the patterns of observed differences suggest possible indicators of disease, vulnerability, and resiliency in SZ.

Alteration of cortico-limbic-striatal neural system in major depressive disorder and bipolar disorder

BACKGROUND It is often difficult to differentiate major depressive disorder (MDD) and bipolar disorder (BD) merely according to clinical symptoms. Similarities and differences in neural activity between the two disorders remain unclear. In current study, we use amplitude of low-frequency fluctuations (ALFF) to compare neural activation changes between MDD and BD patients. METHODS One hundred and eighty-three adolescents and young adults (57 MDD, 46 BD and 80 healthy controls, HC) were scanned during resting state. The ALFF for each participant was calculated, and were then compared among all groups using voxel-based analysis. RESULTS There was a significant effect of diagnosis in the core regions of cortico-limbic-striatal neural system. Furthermore, MDD showed left-sided abnormal neural activity while BD showed a bilateral abnormality in this neural system. LIMITATIONS This study was underpowered to consider medications, mood states and neural developmental effects on the neural activation. CONCLUSIONS Differences in lateralization of ALFF alterations were found. Alterations predominated in the left hemisphere for MDD, whereas alterations were bilateral for BD.

Shared and distinct regional homogeneity changes in bipolar and unipolar depression

BACKGROUND Bipolar depression (BD) is easily misdiagnosed as unipolar depression (UD) or major depressive disorder (MDD) because the depressive symptoms can overlap. Regional homogeneity (ReHo), a measure commonly used for analyzing resting-state fMRI data, has been applied to the study of various neuropsychiatric disorders. However, to date, studies directly comparing BD and UD using ReHo have been relatively scarce. Further investigation is needed to study the latent pathophysiological mechanisms of BD and UD. METHODS Fifty-five patients with BD and 76 patients with UD, as well as 113 healthy controls (HC), underwent resting-state functional magnetic resonance imaging (fMRI). We compared the voxel-wise ReHo across the whole brain for subjects in each of the three groups. RESULTS Significant differences were found in the left frontal cluster (LFC) across the three groups. There were differences between BD and UD in the LFC and left temporal cluster (LTC). In addition, differences between UD and HC existed in the LFC and the occipital cluster (OC). When comparing BD subjects with HC subjects, significant differences were found in all three clusters. No correlations were observed between the 17-item Hamilton Depression Rating Scale (HDRS-17) scores or sub-scores and the ReHo values of BD or UD patients. CONCLUSION ReHo values in the LFC differed significantly among BD, UD, and HC subjects. ReHo in the LTC showed significant differences between BD and UD that might serve as neuroimaging markers of BD. Further, BD and UD shared ReHo changes in the cuneus, suggesting that the cuneus might provide a depressive state neuroimaging marker of BD and UD patients.

Similarities and differences of functional connectivity in drug-naïve, first-episode adolescent and young adult with major depressive disorder and schizophrenia

Major depressive disorder (MDD) and schizophrenia (SZ) are considered two distinct psychiatric disorders. Yet, they have considerable overlap in symptomatology and clinical features, particularly in the initial phases of illness. The amygdala and prefrontal cortex (PFC) appear to have critical roles in these disorders; however, abnormalities appear to manifest differently. In our study forty-nine drug-naïve, first-episode MDD, 45 drug-naïve, first-episode SZ, and 50 healthy control (HC) participants from 13 to 30 years old underwent resting-state functional magnetic resonance imaging. Functional connectivity (FC) between the amygdala and PFC was compared among the three groups. Significant differences in FC were observed between the amygdala and ventral PFC (VPFC), dorsolateral PFC (DLPFC), and dorsal anterior cingulated cortex (dACC) among the three groups. Further analyses demonstrated that MDD showed decreased amygdala-VPFC FC and SZ had reductions in amygdala-dACC FC. Both the diagnostic groups had significantly decreased amygdala-DLPFC FC. These indicate abnormalities in amygdala-PFC FC and further support the importance of the interaction between the amygdala and PFC in adolescents and young adults with these disorders. Additionally, the alterations in amygdala-PFC FC may underlie the initial similarities observed between MDD and SZ and suggest potential markers of differentiation between the disorders at first onset.

Shared and Distinct Functional Architectures of Brain Networks Across Psychiatric Disorders

Brain network alterations have increasingly been implicated in schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). However, little is known about the similarities and differences in functional brain networks among patients with SCZ, BD, and MDD. A total of 512 participants (121 with SCZ, 100 with BD, 108 with MDD, and 183 healthy controls, matched for age and sex) completed resting-state functional magnetic resonance imaging at a single site. Four global measures (the clustering coefficient, the characteristic shortest path length, the normalized clustering coefficient, and the normalized characteristic path length) were computed at a voxel level to quantify segregated and integrated configurations. Inter-regional functional associations were examined based on the Euclidean distance between regions. Distance strength maps were used to localize regions with altered distances based on functional connectivity. Patient groups exhibited shifts in their network architectures toward randomized configurations, with SCZ>BD>MDD in the degree of randomization. Patient groups displayed significantly decreased short-range connectivity and increased medium-/long-range connectivity. Decreases in short-range connectivity were similar across the SZ, BD, and MDD groups and were primarily distributed in the primary sensory and association cortices and the thalamus. Increases in medium-/long-range connectivity were differentially localized within the prefrontal cortices among the patient groups. We highlight shared and distinct connectivity features in functional brain networks among patients with SCZ, BD, and MDD, which expands our understanding of the common and distinct pathophysiological mechanisms and provides crucial insights into neuroimaging-based methods for the early diagnosis of and interventions for psychiatric disorders.

Local functional connectivity alterations in schizophrenia, bipolar disorder, and major depressive disorder

BACKGROUND Local functional connectivity (FC) indicates local or short-distance functional interactions and may serve as a neuroimaging marker to investigate the human brain connectome. Local FC alterations suggest a disrupted balance in the local functionality of the whole brain network and are increasingly implicated in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). METHODS We aim to examine the similarities and differences in the local FC across SZ, BD, and MDD. In total, 537 participants (SZ, 126; BD, 97; MDD, 126; and healthy controls, 188) completed resting-state functional magnetic resonance imaging at a single site. The local FC at resting state was calculated and compared across SZ, BD, and MDD. RESULTS The local FC increased across SZ, BD, and MDD within the bilateral orbital frontal cortex (OFC) and additional region in the left OFC extending to putamen and decreased in the primary visual, auditory, and motor cortices, right supplemental motor area, and bilateral thalami. There was a gradient in the extent of alterations such that SZ > BD > MDD. LIMITATIONS This cross-sectional study cannot consider medications and other clinical variables. CONCLUSIONS These findings indicate a disrupted balance between network integration and segregation in SZ, BD, and MDD, including over-integration via increased local FC in the OFC and diminished segregation of neural processing with the weakening of the local FC in the primary sensory cortices and thalamus. The shared local FC abnormalities across SZ, BD, and MDD may shed new light on the potential biological mechanisms underlying these disorders.