IL-1beta moderated the relations of MFG-insula/mACC connectivity and depressive symptoms in BDII-D

539 

Abstract Submission 

Yuan Cao¹, Paulo Lizano², Hongqi Xiao³, Meng Li¹, Zhiyun Jia⁴, Changjian Qiu³, Martin Walter¹

¹Jena University Hospital, Jena, Germany, ²Beth Israel Deaconess Medical Center of Harvard Medical School, Boston, MA, ³Mental Health Center of West China Hospital, Chengdu, China, ⁴Sichuan University West China Hospital, Chengdu, Sichuan

Yuan Cao  
Jena University Hospital
Jena, Germany

Paulo Lizano  
Beth Israel Deaconess Medical Center of Harvard Medical School
Boston, MA

Hongqi Xiao  
Mental Health Center of West China Hospital
Chengdu, China

Meng Li  
Jena University Hospital
Jena, Germany

Zhiyun Jia  
Sichuan University West China Hospital
Chengdu, Sichuan

Changjian Qiu  
Mental Health Center of West China Hospital
Chengdu, China

Martin Walter  
Jena University Hospital
Jena, Germany

Bipolar disorder depression (BDD) is a chronic and challenging mental health condition characterized by profound mood disturbances, cognitive impairment, and a higher risk of suicide [1]. Approximately 60% of bipolar disorder (BD) experience their first mood episode as depression, and 17% of BDD individuals were diagnosed with unipolar depression in primary care [2,3]. Our previous study has unveiled the relationships between reduced gray matter volumes (GMVs) of the middle frontal gyrus (MFG), superior frontal gyrus (SFG), middle temporal pole, cerebellum, insula, and caudate and inflammation, childhood adversity, and psychiatric symptoms in BDII-D [4]. Additionally, our previous indicated that higher interleukin (IL)-1β levels were related to greater depressive symptoms and smaller volumes of MFG [4,5]. Whether alterations in brain structure correspondingly usher in impairments in brain function, whether there is a link between such brain functional alterations and inflammation, childhood adversity, and psychiatric symptoms, and whether IL-1β plays a moderate role between brain functional alterations and psychiatric symptoms, are aspects that need to be explored but have not yet been fully revealed.

Using the CONN toolbox, we assessed brain activity and functional connectivity in 147 BDII-D individuals and 150 healthy controls (HCs). Partial correlation with multiple comparison correction identified significant relationships between brain functional alterations and inflammation, childhood adversity, and psychiatric symptoms. Moderated analysis delved into the role of IL-1β.

Compared to HCs, BDII-D individuals displayed significantly lower amplitude of low-frequency fluctuation (ALFF) in the frontal and insular regions but higher ALFF in the occipital-temporal area. Significant differences in FC were observed in the seed regions of MFG and insula. Within BDII-D, lower ALFF of the right insula was significantly correlated with higher IL-6 level (r = -0.316, q = 0.0021), CRP level (r = -0.448, q < 0.001), emotional abuse scores (r = -0.376, q = 0.002), and emotional neglect scores (r = -0.304, q = 0.004). Lower ALFF of the MFG significantly related to higher CRP (r = -0.309, q = 0.002) and childhood physical abuse score (r = -0.256, q = 0.027). For seeds derived from ALFF results, we observed higher MFG-mACC FC was significantly related to higher IL-1β (r = 0.289, q = 0.016). Moreover, there were positive relationships between higher HAMD score and higher FC value between the right MFG and right insula (r = 0.22, q = 0.036) and higher FC value between the right MFG and medial anterior cingulate cortex (mACC) (r = 0.327, q < 0.001). . Moreover, IL-1β moderated associations between higher MFG-mACC (β = 2.68, 95%CI 0.60-4.77, p = 0.01) and MFG-insula (β = 3.53, 95%CI 1.085-5.968, p = 0.005) connectivity and greater depressive symptoms.

Our study reveals abnormal function alterations in the right MFG, and insula associated with elevated inflammation, childhood adversity, and depressive symptoms in BDII-D. Importantly, IL-1β plays a moderated role in the relationship between MFG-related FC and depressive symptoms.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

fMRI Connectivity and Network Modeling ²

Affective Disorders

Astrocyte

Blood

FUNCTIONAL MRI

Psychiatric Disorders