Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
Douglas Research Centre, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Appetite. 2025 Jan 1;204:107762. doi: 10.1016/j.appet.2024.107762. Epub 2024 Nov 7.
Insulin receptors, located in brain regions associated with reward sensitivity and decision-making, facilitate insulin action in the brain, modulating intracellular signaling cascades, gene expression, and neural activity. Here, we tested if variations in the expression of the insulin receptor gene network in the prefrontal cortex (PFC) and striatum (STR) moderate the association between early life adversity and eating behaviour in childhood and if this moderation is sex-specific. Participants from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and Basal Influences on the Baby's Development (BIBO) were included as two independent cohorts. A biologically-informed polygenic score reflecting functional variation of the mesocorticolimbic insulin receptor gene network was created by using insulin receptor co-expression data from the PFC and STR in mice, and validated in humans through filtering by homologous expression in PFC using well-known databases. Early life adversity exposure was measured as a composite score. Eating behaviour was characterized using the Child Eating Behaviour Questionnaire administered to mothers of children aged 4 and 6 years in MAVAN, and 6 years in BIBO. We found that only in those with high expression of the mesocorticolimbic insulin receptor gene network a higher early adversity score associated with a higher desire to drink in 4-year boys and 6-year girls, as well as a higher food approach score and food approach/food avoidance ratio in 4-year girls. Also, a higher early life adversity was associated with higher food responsiveness, food approach score and food approach/food avoidance ratio at 6 years in the MAVAN full sample. The moderation observed on desire to drink was partially replicated in BIBO children aged 6 years. Identifying individual differences in response to early adversity may help to prioritize individuals at high risk for long-term disease and design suitable interventions.
胰岛素受体位于与奖励敏感性和决策相关的脑区，促进胰岛素在大脑中的作用，调节细胞内信号级联、基因表达和神经活动。在这里，我们测试了前额叶皮层（PFC）和纹状体（STR）中胰岛素受体基因网络表达的变化是否调节了童年早期生活逆境与饮食行为之间的关联，以及这种调节是否具有性别特异性。Maternal Adversity，Vulnerability and Neurodevelopment（MAVAN）和Basal Influences on the Baby's Development（BIBO）的参与者被纳入两个独立的队列。通过使用来自小鼠 PFC 和 STR 的胰岛素受体共表达数据创建了一个反映中边缘胰岛素受体基因网络功能变异的生物信息多基因评分，并通过使用 PFC 中的同源表达在人类中通过过滤进行验证已知数据库。早期生活逆境暴露被测量为一个综合分数。饮食行为特征使用儿童饮食行为问卷（Child Eating Behaviour Questionnaire）进行评估，该问卷由 MAVAN 的 4 岁和 6 岁儿童的母亲以及 BIBO 的 6 岁儿童的母亲填写。我们发现，只有在中边缘胰岛素受体基因网络高表达的情况下，较高的早期逆境评分才与 4 岁男孩和 6 岁女孩的更高的饮水欲望相关，以及 4 岁女孩的更高的食物接近评分和食物接近/食物回避比。此外，在 MAVAN 全样本中，较高的早期生活逆境与 6 岁时更高的食物反应性、食物接近评分和食物接近/食物回避比相关。在 BIBO 6 岁儿童中，部分复制了对饮水欲望的调节。识别对早期逆境的个体差异可能有助于优先考虑处于长期疾病高风险的个体，并设计合适的干预措施。
