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Background: Schizophrenia, bipolar disorder and major depressive disorder are increasingly being conceptualized as a transdiagnostic continuum. Disruption of white matter is a common alteration in these psychiatric disorders, but the molecular mechanisms underlying the disruption remain unclear. Neuregulin 1 (NRG1) is genetically linked with susceptibility to schizophrenia, bipolar disorder and major depressive disorder, and it is also related to white matter. Methods: Using a transdiagnostic approach, we aimed to identify white matter differences associated with NRG1 and their relationship to transdiagnostic symptoms and cognitive function. We examined the white matter of 1051 participants (318 healthy controls and 733 patients with major psychiatric disorders: 254 with schizophrenia, 212 with bipolar disorder and 267 with major depressive disorder) who underwent diffusion tensor imaging. We measured the plasma NRG1-[beta]1 levels of 331 participants. We also evaluated clinical symptoms and cognitive function. Results: In the patient group, abnormal white matter was negatively associated with NRG1-[beta]1 levels in the genu of the corpus callosum, right uncinate fasciculus, bilateral inferior fronto-occipital fasciculus, right external capsule, fornix, right optic tract, left straight gyrus white matter and left olfactory radiation. These NRG1-associated white matter abnormalities were also associated with depression and anxiety symptoms and executive function in patients with a major psychiatric disorder. Furthermore, across the 3 disorders we observed analogous alterations in white matter, NRG1-[beta]1 levels and clinical manifestations. Limitations: Medication status, the wide age range and our cross-sectional findings were limitations of this study. Conclusion: This study is the first to provide evidence for an association between NRG1, white matter abnormalities, clinical symptoms and cognition in a transdiagnostic psychiatric cohort. These findings provide further support for an understanding of the molecular mechanisms that underlie the neuroimaging substrates of major psychiatric disorders and their clinical implications., Introduction Schizophrenia, bipolar disorder and major depressive disorder have been separate diagnoses since the time of Kraepelin in the 1920s. (1) However, diagnostic categories based on presenting signs and symptoms [...]

Aims: Neurodevelopmental impairments are closely linked to the basis of adolescent major psychiatric disorders (MPDs). The visual cortex can regulate neuroplasticity throughout the brain during critical periods of neurodevelopment, which may provide a promising target for neuromodulation therapy. This cross‐species translational study examined the effects of visual cortex repetitive transcranial magnetic stimulation (rTMS) on neurodevelopmental impairments in MPDs. Methods: Visual cortex rTMS was performed in both adolescent methylazoxymethanol acetate (MAM) rats and patients with MPDs. Functional magnetic resonance imaging (fMRI) and brain tissue proteomic data in rats and fMRI and clinical symptom data in patients were analyzed. Results: The regional homogeneity (ReHo) analysis of fMRI data revealed an increase in the frontal cortex and a decrease in the posterior cortex in the MAM rats, representing the abnormal neurodevelopmental pattern in MPDs. In regard to the effects of rTMS, similar neuroimaging changes, particularly reduced frontal ReHo, were found both in MAM rats and adolescent patients, suggesting that rTMS may reverse the abnormal neurodevelopmental pattern. Proteomic analysis revealed that rTMS modulated frontal synapse‐associated proteins, which may be the underpinnings of rTMS efficacy. Furthermore, a positive relationship was observed between frontal ReHo and clinical symptoms after rTMS in patients. Conclusion: Visual cortex rTMS was proven to be an effective treatment for adolescent MPDs, and the underlying neural and molecular mechanisms were uncovered. Our study provides translational evidence for therapeutics targeting the neurodevelopmental factor in MPDs. [ABSTRACT FROM AUTHOR]

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., Introduction Psychiatric nosology arose in central Europe toward the end of the 19th century. In particular, Kraepelin made the foundational distinction between dementia praecox (schizophrenia) and manic depression. (1) The [...]

Background: The association between executive dysfunction, brain dysconnectivity, and inflammation is a prominent feature across major psychiatric disorders (MPDs), schizophrenia, bipolar disorder, and major depressive disorder. A dimensional approach is warranted to delineate their mechanistic interplay across MPDs. Methods: This single site study included a total of 1543 participants (1058 patients and 485 controls). In total, 1169 participants underwent diffusion tensor and resting-state functional magnetic resonance imaging (745 patients and 379 controls completed the Wisconsin Card Sorting Test). Fractional anisotropy (FA) and regional homogeneity (ReHo) assessed structural and functional connectivity, respectively. Pro-inflammatory cytokine levels [interleukin (IL)-1 β , IL-6, and tumor necrosis factor- α ] were obtained in 325 participants using blood samples collected with 24 h of scanning. Group differences were determined for main measures, and correlation and mediation analyses and machine learning prediction modeling were performed. Results: Executive deficits were associated with decreased FA, increased ReHo, and elevated IL-1 β and IL-6 levels across MPDs, compared to controls. FA and ReHo alterations in fronto-limbic-striatal regions contributed to executive deficits. IL-1 β mediated the association between FA and cognition, and IL-6 mediated the relationship between ReHo and cognition. Executive cognition was better predicted by both brain connectivity and cytokine measures than either one alone for FA-IL-1 β and ReHo-IL-6. Conclusions: Transdiagnostic associations among brain connectivity, inflammation, and executive cognition exist across MPDs, implicating common neurobiological substrates and mechanisms for executive deficits in MPDs. Further, inflammation-related brain dysconnectivity within fronto-limbic-striatal regions may represent a transdiagnostic dimension underlying executive dysfunction that could be leveraged to advance treatment. [ABSTRACT FROM AUTHOR]

The olfactocentric paralimbic cortex plays a critical role in the regulation of emotional and neurovegetative functions that are disrupted in core features of bipolar disorder. Adolescence is thought to be a critical period in both the maturation of the olfactocentric paralimbic cortex and in the emergence of bipolar disorder pathology. Together, these factors implicate a central role for the olfactocentric paralimbic cortex in the development of bipolar disorder and suggest that abnormalities in this cortex may be expressed by adolescence in the disorder. We tested the hypothesis that differences in olfactocentric paralimbic cortex structure are a morphological feature in adolescents with bipolar disorder. Subjects included 118 adolescents (41 with bipolar disorder and 77 healthy controls). Cortical grey matter volume differences between adolescents with and without bipolar disorder were assessed with voxel-based morphometry analyses of high-resolution structural magnetic resonance imaging scans. Compared with healthy comparison adolescents, adolescents with bipolar disorder demonstrated significant volume decreases in olfactocentric paralimbic regions, including orbitofrontal, insular and temporopolar cortices. Findings in these regions survived small volume correction (P less than 0.05, corrected). Volume decreases in adolescents with bipolar disorder were also noted in inferior prefrontal and superior temporal gyri and cerebellum. The findings suggest that abnormalities in the morphology of the olfactocentric paralimbic cortex may contribute to the bipolar disorder phenotype that emerges in adolescence. The morphological development of the olfactocentric paralimbic cortex has received little study. The importance of these cortices in emotional and social development, and support for a central role for these cortices in the development of bipolar disorder, suggest that study of the development of these cortices in health and in bipolar disorder is critically needed.

Dynamic functional connectivity (DFC) analysis can capture time‐varying properties of connectivity. However, studies on large samples using DFC to investigate transdiagnostic dysconnectivity across schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are rare. In this study, we used resting‐state functional magnetic resonance imaging and a sliding‐window method to study DFC in a total of 610 individuals (150 with SZ, 100 with BD, 150 with MDD, and 210 healthy controls [HC]) at a single site. Using k‐means clustering, DFCs were clustered into three functional connectivity states: one was a more frequent state with moderate positive and negative connectivity (State 1), and the other two were less frequent states with stronger positive and negative connectivity (State 2 and State 3). Significant 4‐group differences (SZ, BD, MDD, and HC groups; q <.05, false‐discovery rate [FDR]‐corrected) in DFC were nearly only in State 1. Post hoc analyses (q <.05, FDR‐corrected) in State 1 showed that transdiagnostic dysconnectivity patterns among SZ, BD and MDD featured consistently decreased connectivity within most networks (the visual, somatomotor, salience and frontoparietal networks), which was most obvious in both range and extent for SZ. Our findings suggest that there is more common dysconnectivity across SZ, BD and MDD than we previously expected and that such dysconnectivity is state‐dependent, which provides new insights into the pathophysiological mechanism of major psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Previous studies of atypical antipsychotic effects on cortical structures in schizophrenia (SZ) and bipolar disorder (BD) have findings that vary between the short and long term. In particular, there has not been a study exploring the effects of atypical antipsychotics on age-related cortical structural changes in SZ and BD. This study aimed to determine whether mid- to long-term atypical antipsychotic treatment (mean duration = 20 months) is associated with cortical structural changes and whether age-related cortical structural changes are affected by atypical antipsychotics. Methods: Structural magnetic resonance imaging images were obtained from 445 participants consisting of 88 medicated patients (67 with SZ, 21 with BD), 84 unmedicated patients (50 with SZ, 34 with BD), and 273 healthy controls (HC). Surface-based analyses were employed to detect differences in thickness and area among the three groups. We examined the age-related effects of atypical antipsychotics after excluding the potential effects of illness duration. Results: Significant differences in cortical thickness were observed in the frontal, temporal, parietal, and insular areas and the isthmus of the cingulate gyrus. The medicated group showed greater cortical thinning in these regions than the unmediated group and HC; furthermore, there were age-related differences in the effects of atypical antipsychotics, and these effects did not relate to illness duration. Moreover, cortical thinning was significantly correlated with lower symptom scores and Wisconsin Card Sorting Test (WCST) deficits in patients. After false discovery rate correction, cortical thinning in the right middle temporal gyrus in patients was significantly positively correlated with lower HAMD scores. The unmedicated group showed only greater frontotemporal thickness than the HC group. Conclusion: Mid- to long-term atypical antipsychotic use may adversely affect cortical thickness over the course of treatment and ageing and may also result in worsening cognitive function. [ABSTRACT FROM AUTHOR]