Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Department of Internal Medicine (Endocrinology & Metabolism) and Department of Pediatrics (Pediatric Endocrinology), Yale School of Medicine, New Haven, CT, USA.
Neuropsychopharmacology. 2022 Jan;47(2):543-552. doi: 10.1038/s41386-021-01111-5. Epub 2021 Jul 22.
Obesity is a serious medical condition that often co-occurs with stress-related psychiatric disorders. It is recognized that the brain plays a key role in the (patho)physiology of obesity and that there is a bidirectional relationship between obesity and psychopathology, yet molecular mechanisms altered in obesity have not been fully elucidated. Thus, we investigated relationships between obesity and synaptic density in vivo using the radioligand [C]UCB-J (which binds to synaptic glycoprotein SV2A) and positron emission tomography in individuals with obesity, and with or without stress-related psychiatric disorders. Regions of interest were the dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial, amygdala, hippocampus, and cerebellum. Forty individuals with a body mass index (BMI) ≥ 25 kg/m (overweight/obese), with (n = 28) or without (n = 12) psychiatric diagnosis, were compared to 30 age- and sex-matched normal weight individuals (BMI < 25), with (n = 14) or without (n = 16) psychiatric diagnosis. Overall, significantly lower synaptic density was observed in overweight/obese relative to normal weight participants (η = 0.193, F = 2.35, p = 0.042). Importantly, in participants with stress-related psychiatric diagnoses, we found BMI to be negatively correlated with synaptic density in all regions of interest (p ≤ 0.03), but no such relationship observed for mentally healthy controls (p ≥ 0.68). In the stress-related psychiatric groups, dorsolateral prefrontal cortex synaptic density was negatively associated with measures of worry (r = -0.46, p = 0.01), tension/anxiety (r = -0.38, p = 0.04), fatigue (r = -0.44, p = 0.02), and attentional difficulties (r = -0.44, p = 0.02). In summary, the findings of this novel in vivo experiment suggest compounding effects of obesity and stress-related psychopathology on the brain and the associated symptomatology that may impact functioning. This offers a novel biological mechanism for the relationship between overweight/obesity and stress-related psychiatric disorders that may guide future intervention development efforts.
肥胖是一种严重的医学疾病，常与应激相关的精神障碍同时发生。人们认识到大脑在肥胖的（病理）生理学中起着关键作用，肥胖和精神病理学之间存在着双向关系，但肥胖时改变的分子机制尚未完全阐明。因此，我们使用放射性配体 [C]UCB-J（与突触糖蛋白 SV2A 结合）和正电子发射断层扫描（PET），在肥胖者以及有或没有应激相关精神障碍的个体中，研究了肥胖与突触密度之间的关系。感兴趣的区域是背外侧前额叶皮层、眶额皮层、腹内侧、杏仁核、海马体和小脑。将 40 名体重指数（BMI）≥25kg/m2（超重/肥胖）的个体（n=28）或无（n=12）精神障碍诊断的个体与 30 名年龄和性别匹配的正常体重个体（BMI<25）进行比较，其中（n=14）或无（n=16）精神障碍诊断。总体而言，与正常体重参与者相比，超重/肥胖者的突触密度明显较低（η=0.193，F=2.35，p=0.042）。重要的是，在有应激相关精神障碍诊断的参与者中，我们发现 BMI 与所有感兴趣区域的突触密度呈负相关（p≤0.03），但在心理健康对照组中未观察到这种关系（p≥0.68）。在应激相关精神障碍组中，背外侧前额叶皮层的突触密度与担忧（r=-0.46，p=0.01）、紧张/焦虑（r=-0.38，p=0.04）、疲劳（r=-0.44，p=0.02）和注意力困难（r=-0.44，p=0.02）呈负相关。总之，这项新的体内实验研究结果表明，肥胖和应激相关精神障碍对大脑及其相关症状的复合影响可能会影响功能。这为超重/肥胖与应激相关精神障碍之间的关系提供了一种新的生物学机制，可能为未来的干预发展努力提供指导。
