Coplan Jeremy D, Fathy Hassan M, Abdallah Chadi G, Ragab Sherif A, Kral John G, Mao Xiangling, Shungu Dikoma C, Mathew Sanjay J
Department of Psychiatry, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Neuroimage Clin. 2014 Jan 9;4:326-35. doi: 10.1016/j.nicl.2013.12.014. eCollection 2014.
We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis - a form of neuroplasticity - and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS).
We combined two previously studied cohorts of GAD and control subjects. Using proton magnetic resonance spectroscopy imaging ((1)H MRSI) in medication-free patients with GAD (n = 29) and a matched healthy control group (n = 22), we determined hippocampal concentrations of (1) NAA (2) choline containing compounds (CHO), and (3) Creatine + phosphocreatine (CR). Data were combined from 1.5 T and 3 T scans by converting values from each cohort to z-scores. Overweight and GAD diagnosis were used as categorical variables while the Penn State Worry Questionnaire (PSWQ) and Anxiety Sensitivity Index (ASI) were used as dependent variables.
Overweight subjects (BMI ≥ 25) exhibited lower NAA levels in the hippocampus than normal-weight subjects (BMI < 25) (partial Eta-squared = 0.14) controlling for age, sex and psychiatric diagnosis, and the effect was significant for the right hippocampus in both GAD patients and control subjects. An inverse linear correlation was noted in all subjects between right hippocampal NAA and BMI. High scores on the PSWQ predicted low hippocampal NAA and CR. Both BMI and worry were independent inverse predictors of hippocampal NAA.
Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted.
我们之前证明了齿状回神经发生（一种神经可塑性形式）与抗凋亡基因标志物BCL-2的表达以及成年猕猴体重之间存在负相关关系。因此，我们探讨了在人类中体重指数（BMI）与海马体N-乙酰天门冬氨酸（NAA）（一种神经元完整性标志物，推测也是神经可塑性标志物）之间是否存在类似的负相关关系。我们还研究了在广泛性焦虑障碍（GAD）患者和对照组（CS）中，一种潜在的神经毒性过程——担忧，与海马体NAA之间的关系。
我们合并了两个之前研究过的GAD患者队列和对照组。使用质子磁共振波谱成像（（1）H MRSI）对未服用药物的GAD患者（n = 29）和匹配的健康对照组（n = 22）进行检测，我们测定了海马体中（1）NAA、（2）含胆碱化合物（CHO）和（3）肌酸+磷酸肌酸（CR）的浓度。通过将每个队列的值转换为z分数，将来自1.5T和3T扫描的数据合并。超重和GAD诊断用作分类变量，而宾夕法尼亚州立大学担忧问卷（PSWQ）和焦虑敏感性指数（ASI）用作因变量。
在控制年龄、性别和精神诊断的情况下，超重受试者（BMI≥25）海马体中的NAA水平低于正常体重受试者（BMI<25）（偏η² = 0.14），并且该效应在GAD患者和对照组的右侧海马体中均显著。在所有受试者中，右侧海马体NAA与BMI之间存在负线性相关。PSWQ得分高预示着海马体NAA和CR水平低。BMI和担忧都是海马体NAA的独立负向预测因素。
超重与海马体中NAA浓度降低相关，效应量较大。未来有必要进行机制研究。
