Interleukin-1β moderates the relationships between middle frontal-mACC/insular connectivity and depressive symptoms in bipolar II depression

Xiao, Hongqi, Cao, Yuan, Lizano, Paulo, Li, Meng, Sun, Huan, Zhou, Xiaoqin, Deng, Gaoju, Li, Jiafeng, Chand, Tara, Jia, Zhiyun, Qiu, Changjian and Walter, Martin (2024) Interleukin-1β moderates the relationships between middle frontal-mACC/insular connectivity and depressive symptoms in bipolar II depression. Brain, Behavior, and Immunity, 120. pp. 44-53. ISSN 0889-1591

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The functional alterations of the brain in bipolar II depression (BDII-D) and their clinical and inflammatory associations are understudied. We aim to investigate the functional brain alterations in BDII-D and their relationships with inflammation, childhood adversity, and psychiatric symptoms, and to examine the moderating effects among these factors. Using z-normalized amplitude of low-frequency fluctuation (zALFF), we assessed the whole-brain resting-state functional activity between 147 BDII-D individuals and 150 healthy controls (HCs). Differential ALFF regions were selected as seeds for functional connectivity analysis to observe brain connectivity alterations resulting from abnormal regional activity. Four inflammatory cytokines including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) and five clinical scales including Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), and Childhood Trauma Questionnaire (CTQ) were tested and assessed in BDII-D. Partial correlations with multiple comparison corrections identified relationships between brain function and inflammation, childhood adversity, and psychiatric symptoms. Moderation analysis was conducted based on correlation results and previous findings. Compared to HCs, BDII-D individuals displayed significantly lower zALFF in the superior and middle frontal gyri (SFG and MFG) and insula, but higher zALFF in the occipital-temporal area. Only the MFG and insula-related connectivity exhibited significant differences between groups. Within BDII-D, lower right insula zALFF value correlated with higher IL-6, CRP, and emotional adversity scores, while lower right MFG zALFF was related to higher CRP and physical abuse scores. Higher right MFG-mid-anterior cingulate cortex (mACC) connectivity was associated with higher IL-1β. Moreover, IL-1β moderated associations between higher right MFG-mACC/insula connectivity and greater depressive symptoms. This study reveals that abnormal functional alterations in the right MFG and right insula were associated with elevated inflammation, childhood adversity, and depressive symptoms in BDII-D. IL-1β may moderate the relationship between MFG-related connectivity and depressive symptoms.

Item Type: Article
Keywords: Bipolar II depression | Amplitude of low-frequency fluctuation | Functional connectivity | Childhood adversity | Interleukin-1β | Moderation analysis
Subjects: Physical, Life and Health Sciences > Medicine
Social Sciences and humanities > Psychology > General Psychology
Social Sciences and humanities > Psychology > Neuropsychology Psychology
JGU School/Centre: Jindal Institute of Behavioural Sciences
Depositing User: Subhajit Bhattacharjee
Date Deposited: 27 May 2024 07:02
Last Modified: 21 Jun 2024 04:46
Official URL:


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