Associations between hemispheric asymmetry and schizophrenia-related risk genes in people with schizophrenia and people at a genetic high risk of schizophrenia.

BACKGROUND: Schizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear. AIMS: To investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes. METHOD: A total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic-neural association, bioinformatics enrichment was explored. RESULTS: There were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network. CONCLUSIONS: The shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic-neural pathological underpinnings of schizophrenia.

Spontaneous low-frequency fluctuations in the neural system for emotional perception in major psychiatric disorders: amplitude similarities and differences across frequency bands

Background: Growing evidence indicates both shared and distinct features of emotional perception in schizophrenia, bipolar disorder and major depressive disorder. In these disorders, alterations in spontaneous low-frequency fluctuations have been reported in the neural system for emotional perception, but the similarities and differences in the amplitude of low-frequency fluctuation (ALFF) across the 3 disorders are unknown. Methods: We compared ALFF and its signal balance in the neural system for emotional perception at 2 frequency bands (slow-5 and slow-4) in 119 participants with schizophrenia, 100 with bipolar disorder, 123 with major depressive disorder and 183 healthy controls. We performed exploratory Pearson partial correlation analyses to determine the relationship between ALFF signal balance and clinical variables. Results: We observed commonalities in ALFF change patterns across the 3 disorders for emotional perception neural substrates, such as increased ALFF in the anterior cerebrum (including subcortical, limbic, paralimbic and heteromodal cortical regions) and decreased ALFF in the posterior visual cortices. Schizophrenia, bipolar disorder and major depressive disorder showed significantly decreased ALFF signal balance in the neural system for emotional perception at both slow-5 and slow-4 frequency bands, with the greatest alterations for schizophrenia, followed by bipolar disorder and major depressive disorder. We found a negative correlation between ALFF signal balance and negative/disorganized symptoms in slow-4 across the 3 disorders. Limitations: The relatively broad age range in our sample and the cross-sectional study design may not account for our findings. Conclusion: The extent of the commonalities we observed further support the concept of core neurobiological disruptions shared among the 3 disorders; ALFF signal balance could be an important neuroimaging marker for the diagnosis and treatment of schizophrenia, bipolar disorder and major depressive disorder.

Alterations in gray matter volumes and intrinsic activity in the prefrontal cortex are associated with suicide attempts in patients with bipolar disorder.

Bipolar disorder (BD) is associated with increased suicidal behavior. Understanding the neural features of suicide attempts (SA) in patients with BD is critical to preventing suicidal behavior. The prefrontal cortex (PFC) is a key region related to SA. In this study, forty BD patients with a history of SA (BD+SA), 70 BD patients without a history of SA (BD-SA), and 110 individuals in a healthy control (HC) group underwent structural magnetic resonance imaging (MRI) and resting-state functional MRI. We used voxel-based morphometry (VBM) and amplitude of low frequency fluctuations (ALFF) techniques to examine the gray matter volumes (GMVs) and ALFF values in the PFC. Compared with the HC group, both the BD+SA and BD-SA groups had lower GMVs and higher ALFF values in the medial PFC (MPFC), ventral PFC (VPFC), and dorsolateral PFC (DLPFC). The ALFF values in the MPFC, VPFC, and DLPFC in the BD+SA group were significantly higher than those in the BD-SA group. These findings suggest that BD patients with SA have intrinsic activity abnormalities in PFC regions. This provides potentially identifiable neuroimaging markers in BD patients with SA that could be used to increase our understanding of suicidal behavior.

Structural alterations associated with suicide attempts in major depressive disorder and bipolar disorder: A diffusion tensor imaging study.

BACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BD) are major affective disorders associated with high risk for suicide. Neural mechanisms underlying suicide attempts are poorly understood in MDD and BD but likely relate to the structural abnormalities in brain regions. In this study, we explored structural alterations in MDD and BD with prior suicide attempts (SA) using diffusion tensor imaging (DTI). METHODS: Participants consisted of 27 MDD patients with prior SA (men: 9; age means±sd: 28.04 ± 11.06 years), 49 MDD patients without prior SA (men: 11; age means±sd: 30.03 ± 0.91 years), 25 BD patients with prior SA (men: 7, age means±sd: 27.08 ± 8.40 years), 49 BD patients without prior SA (men: 26, means±sd: 27.69 ± 9.97 years)，and 49 healthy controls (HC) (men: 18, means±sd: 31.12 ± 9.95 years). All participants underwent DTI to examine fractional anisotropy (FA) in brain regions. RESULTS: FA in several major white matter (WM) bundles including bilateral inferior fronto-occipital fasciculus (IFOF), bilateral uncinate fasciculus (UF), and the corpus callosum (CC) was shown in MDD with prior SA, compared to MDD without prior SA and HC. Decreased FA was also found in bilateral IFOF, bilateral UF, and CC, as well as other WM bundles, in BD with prior SA, compared to BD without prior SA and HC. Significant diagnostic group by SA effects were shown in bilateral thalami with lowest mean FA values in MDD with prior SA. CONCLUSIONS: Our findings support the involvement of structural alterations in suicide attempts in major affective disorders. Shared and distinct structural alterations were shown in MDD and BD with prior SA, suggesting common and differential neural pathways for suicide among major affective disorder.

Structural and Functional Abnormities of Amygdala and Prefrontal Cortex in Major Depressive Disorder With Suicide Attempts.

Finding neural features of suicide attempts (SA) in major depressive disorder (MDD) may be helpful in preventing suicidal behavior. The ventral and medial prefrontal cortex (PFC), as well as the amygdala form a circuit implicated in emotion regulation and the pathogenesis of MDD. The aim of this study was to identify whether patients with MDD who had a history of SA show structural and functional connectivity abnormalities in the amygdala and PFC relative to MDD patients without a history of SA. We measured gray matter volume in the amygdala and PFC and amygdala-PFC functional connectivity using structural and functional magnetic resonance imaging (MRI) in 158 participants [38 MDD patients with a history of SA, 60 MDD patients without a history of SA, and 60 healthy control (HC)]. MDD patients with a history of SA had decreased gray matter volume in the right and left amygdala (F = 30.270, P = 0.000), ventral/medial/dorsal PFC (F = 15.349, P = 0.000), and diminished functional connectivity between the bilateral amygdala and ventral and medial PFC regions (F = 22.467, P = 0.000), compared with individuals who had MDD without a history of SA, and the HC group. These findings provide evidence that the amygdala and PFC may be closely related to the pathogenesis of suicidal behavior in MDD and implicate the amygdala-ventral/medial PFC circuit as a potential target for suicide intervention.