Preliminary Study of Structural Magnetic Resonance Imaging Phenotypes Related to Genetic Variation in Interleukin-1β Rs16944 in Adolescents with Bipolar Disorder.

Background: Bipolar disorder (BD), among the most heritable psychiatric conditions, is associated with increased pro-inflammatory blood markers and pro-inflammatory gene expression in post-mortem brain. We therefore examined the effects of pro-inflammatory single nucleotide polymorphism interleukin-1 beta (IL-1 beta) rs16944 on brain structure in adolescents with BD and healthy control (HC) adolescents. Methods: T-1-weighted 3-T magnetic resonance imaging data were acquired for 38 adolescents with BD and 32 HC adolescents (14-20 years). Using FreeSurfer, a priori regions of interest analyses, examining hippocampus, amygdala, dorsolateral prefrontal cortex (DLPFC), and caudal anterior cingulate cortex, were complemented by exploratory whole-brain vertex-wise analyses. General linear models assessed the association between IL-1 beta rs16944 and the ROIs, controlling for sex, age, and intracranial volume. Results: There was an IL-1 beta rs16944 polymorphism-by-diagnosis interaction effect on the DLPFC; T-carriers with BD had greater surface area compared to non-carriers with BD. Whereas, HCT-carriers had smaller DLPFC volume compared to HC non-carriers. In vertex-wise analyses, similar interactions were evident in a pars triangularis surface area cluster and a lateral occipital cortex volume cluster. Whole-brain analyses also yielded a main effect of IL-1 beta rs16944 polymorphism, whereby T-carriers had greater lateral occipital cortex surface area and volume. Conclusions: The IL-1 beta rs16944 polymorphism is associated with neurostructural phenotypes in cognitive and visual regions that subserve functions, including facial recognition and response inhibition, which are known to be aberrant in BD. Future studies are warranted to evaluate whether the observed rs16944-related structural differences are relevant to neurocognitive function, functional neuroimaging phenotypes and IL-1 beta protein levels.