22q11.2缺失综合征患者早期慢性肥胖与儿童期冲动性相关,通过剂量依赖性小脑发育异常预测长期精神病轨迹。

IF 4.8
Corrado Sandini, Natacha Reich, Farnaz Delavari, Lara Pajic, Andrea Escelsior, Silas Forrer, Andrea Imparato, Nada Kojovic, Caren Latreche, Valeria Parlatini, Samuele Cortese, Maude Schneider, Stephan Eliez
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引用次数: 0

摘要

背景:最近的流行病学证据将早期肥胖和代谢失调与成年精神病易感性联系起来,尽管因果关系尚不清楚。在高遗传性精神疾病中建立因果关系需要:1)证明早期代谢因素在遗传易感性和精神病轨迹之间起中介作用;2)剖析导致遗传易感性个体早期肥胖的机制;3)阐明将早期肥胖与精神病症状联系起来的下游神经发育途径。方法:在此,我们对184名因22q11.2缺失综合征(22q11DS)而具有精神病高遗传风险的个体和182名神经正常对照进行了一项独特的纵向队列研究,研究了行为、BMI和神经发育轨迹之间的双向通路。我们将重复BMI测量与临床/神经认知表型和神经影像学相结合。我们调查了BMI轨迹与精神病风险之间的关系,并测试了皮质或小脑发育的改变是否可能是这种联系的基础。结果:儿童时期的行为冲动预测了BMI轨迹的早期和进行性偏差,介导了22q11DS易感性对早期肥胖的影响。儿童期表现出的慢性bmi增加预示着随后在青春期晚期/成年早期出现精神病,介导了行为冲动的影响。一种剂量效应关系将bmi状态增加的持续时间与运动和认知障碍的恶化联系起来,运动和认知障碍是精神分裂症的一个关键症状域,这是由后脑-下脑灰质体积进行性减少介导的。结论:这些发现表明,与肥胖相关的代谢失调可能通过影响小脑成熟,将22q11DS的儿童行为冲动与精神病易感性联系起来。这些发现可能支持针对有精神病风险的个体早期代谢轨迹的预防性干预。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chronic early-life obesity linked to childhood impulsivity predicts long-term psychosis trajectory through dose-dependent cerebellar dysmaturation in 22q11.2 Deletion Syndrome.

Background: Recent epidemiological evidence links early-life obesity and metabolic dysregulation to adult psychosis vulnerability, though a causal relationship remains unclear. Establishing causality in highly heritable psychotic disorders requires: 1) demonstrating that early-life metabolic factors mediate between genetic vulnerability and psychosis trajectory, 2) dissecting mechanisms leading to early-life obesity in genetically vulnerable individuals, and 3) clarifying downstream neurodevelopmental pathways linking early-life obesity to psychosis symptoms.

Methods: Here we investigated bidirectional pathways linking behavioral, BMI, and neurodevelopment trajectories in a unique longitudinal cohort of 184 individuals at high genetic risk for psychosis, due to 22q11.2 Deletion Syndrome (22q11DS), and 182 neurotypical controls, followed-up since childhood. We combined repeated BMI measurements with clinical/neurocognitive phenotyping and neuroimaging. We investigated the relationship between BMI trajectories with risk of psychosis and tested whether altered cortical or cerebellar development could underlie this association.

Results: Childhood behavioral impulsivity predicted early and progressive deviations in BMI trajectories, mediating the effects of 22q11DS vulnerability to early-life obesity. Chronic BMI-increases manifesting during childhood predicted the subsequent emergence of psychosis during late-adolescence/early-adulthood, mediating the effects of behavioral impulsivity. A dose effect relationship linked duration of increased BMI-status to worsening of motor and cognitive disorganization, a key schizophrenia symptom domain, which was mediated by progressive gray matter volume reductions in posterior-inferior cerebellum.

Conclusions: These findings suggest that metabolic dysregulation associated with obesity may link childhood behavioral impulsivity to psychosis vulnerability in 22q11DS, by influencing cerebellar maturation. These findings might support preventive interventions targeting early-life metabolic trajectories in individuals at risk of psychosis.

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