Dissecting the impact of complement component 4A in bipolar disorder
Elin Hörbeck1, Lina Jonsson2, Susmita Malwade3
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden.
Brain, Behavior, and Immunity
|December 9, 2023
Summary
Complement component 4A (C4A) gene expression is not altered in bipolar disorder (BD). However, C4A expression is linked to psychotic mood episodes in bipolar I disorder, suggesting a specific role in this symptom dimension.
Area of Science:
- Neurogenetics
- Psychiatric Disorders
Background:
- Schizophrenia (SZ) and bipolar disorder (BD) share significant genetic overlap.
- The extended Major Histocompatibility Complex (MHC) region, particularly complement component 4A (C4A) gene copy number, is a key genetic locus for SZ risk.
Purpose of the Study:
- To investigate the role of C4A expression in the pathophysiology of BD.
- To determine if genetically predicted C4A expression differentiates BD subphenotypes.
Main Methods:
- Analyzed C4A expression in brain tissue from 1,202 BD samples.
- Constructed C4A co-expression networks to assess genetic enrichment in BD.
- Applied C4A expression scores to deep phenotypic data from 4,739 BD cases.
Main Results:
- No significant differences in C4A expression were found in BD brain tissues.
- C4A co-expression networks did not show genetic enrichment for BD.
- A significant association was identified between C4A expression and psychotic mood episodes in bipolar I disorder (BDI).
- No association was observed between C4A expression and non-affective psychosis or other BD subphenotypes.
Conclusions:
- C4A plays a distinct role in BD, specifically associated with the vulnerability to psychotic symptoms during mood episodes in BDI.
- The findings suggest C4A's role in BD is limited to specific symptom dimensions rather than the disorder broadly.
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