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-1β (IL-1β) rs16944 on brain structure in adolescents with BD and healthy control (HC) adolescents. METHODS T1-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-1β rs16944 and the ROIs, controlling for sex, age, and intracranial volume. RESULTS There was an IL-1β rs16944 polymorphism-by-diagnosis interaction effect on the DLPFC; T-carriers with BD had greater surface area compared to non-carriers with BD. Whereas, HC T-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-1β rs16944 polymorphism, whereby T-carriers had greater lateral occipital cortex surface area and volume. CONCLUSIONS The IL-1β 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-1β protein levels.

中文翻译：

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双相情感障碍青少年白细胞介素-1β rs16944基因变异相关结构磁共振成像表型的初步研究。

背景双相情感障碍（BD）是最易遗传的精神疾病之一，与死后大脑中促炎血液标志物和促炎基因表达增加有关。因此，我们检查了促炎单核苷酸多态性白细胞介素 1β (IL-1β) rs16944 对 BD 青少年和健康对照 (HC) 青少年脑结构的影响。方法 获得 38 名 BD 青少年和 32 名 HC 青少年（14-20 岁）的 T1 加权 3-T 磁共振成像数据。使用 FreeSurfer，先验的感兴趣区域分析，检查海马、杏仁核、背外侧前额叶皮层 (DLPFC) 和尾侧前扣带皮层，并辅以探索性全脑顶点分析。一般线性模型评估了 IL-1β rs16944 与 ROI 之间的关联，控制性别、年龄和颅内容量。结果DLPFC存在IL-1βrs16944多态性诊断交互作用；与具有 BD 的非载体相比，具有 BD 的 T 载体具有更大的表面积。然而，与 HC 非载体相比，HC T 载体的 DLPFC 体积更小。在顶点分析中，类似的相互作用在三角部表面积簇和枕外侧皮质体积簇中很明显。全脑分析还产生了 IL-1β rs16944 多态性的主要影响，即 T 载体具有更大的枕叶外侧皮质表面积和体积。结论 IL-1β rs16944 多态性与认知和视觉区域的神经结构表型相关，这些神经结构表型支持功能，包括已知在 BD 中异常的面部识别和反应抑制。