Abstract
Background: Dimensional psychopathology and its neurobiological underpinnings could provide important insight into the major psychiatric disorders (MPDs), including major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). In this study, we examined depressive symptoms and their relationship with functional connectivity (FC) and leptin across MPDs. Methods: A total of 728 participants [healthy controls (HC), n = 325; MDD, n = 153; BPD, n = 123; SCZ, n = 127] underwent resting state functional magnetic resonance imaging at a single site. Plasma leptin levels and depressive symptom measures (Hamilton Depression Rating Scale, HAMD) were obtained within 24 hours of scan. Factor analyses were used to identify HAMD factor scores. Regional FC and plasma leptin levels were compared between MPDs and HC. Mediational analyses were performed to determine the relationship between regional FC, plasma leptin levels, and HAMD factor scores. Findings: We found that depressive symptoms were associated with regional FC decreases in primary sensory and association cortices and thalamus, regional FC increases in the prefrontal cortex and angular gyrus, and elevated leptin levels across MPDs, compared to HC. Mediation analyses showed that plasma leptin level mediates the relationship between regional FC alterations in primary somatosensory cortex and somatic depressive symptoms. Interpretation: Our findings support a role of the primary somatosensory cortex in depressive symptoms across MPDs. Further, leptin appears to be an important link between brain connectivity alterations in this region and somatic depressive symptoms, suggesting a potential therapeutic target for depressive symptoms in patients with MPDs. Funding: This study was funded by National Science Fund for Distinguished Young Scholars (81725005 to F.W.), National Natural Science Foundation of China (81571311 to Y.T., 81571331 to F.W.), National Key Research and Development Program (2018YFC1311604 to Y.T., 2016YFC1306900 to Y.T., 2016YFC0904300 to F.W.), National High Tech Development Plan (863) (2015AA020513 to F.W.), Liaoning Science and Technology Project (2015225018 to Y.T.), Liaoning Education Foundation (Pandeng Scholar to F.W.), Innovation Team Support Plan of Higher Education of Liaoning Provience (LT2017007 to F.W.), and Major Special Construction plan of China Medical University (3110117059 to F.W.). Declaration of Interest: The authors report no biomedical financial interests or potential conflicts of interest. Ethical Approval: The study was approved by the Institutional Review Board of the China Medical University and was conducted in accordance with the Declaration of Helsinki. Participants provided written informed consent. All the experiments and methods were carried out in accordance with approved regulations and guidelines.
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