Haddad Leila, Schäfer Axel, Streit Fabian, Lederbogen Florian, Grimm Oliver, Wüst Stefan, Deuschle Michael, Kirsch Peter, Tost Heike, Meyer-Lindenberg Andreas
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
Schizophr Bull. 2015 Jan;41(1):115-22. doi: 10.1093/schbul/sbu072. Epub 2014 Jun 3.
Urban upbringing has consistently been associated with schizophrenia, but which specific environmental exposures are reflected by this epidemiological observation and how they impact the developing brain to increase risk is largely unknown. On the basis of prior observations of abnormal functional brain processing of social stress in urban-born humans and preclinical evidence for enduring structural brain effects of early social stress, we investigated a possible morphological correlate of urban upbringing in human brain. In a sample of 110 healthy subjects studied with voxel-based morphometry, we detected a strong inverse correlation between early-life urbanicity and gray matter (GM) volume in the right dorsolateral prefrontal cortex (DLPFC, Brodmann area 9). Furthermore, we detected a negative correlation of early-life urbanicity and GM volumes in the perigenual anterior cingulate cortex (pACC) in men only. Previous work has linked volume reductions in the DLPFC to the exposure to psychosocial stress, including stressful experiences in early life. Besides, anatomical and functional alterations of this region have been identified in schizophrenic patients and high-risk populations. Previous data linking functional hyperactivation of pACC during social stress to urban upbringing suggest that the present interaction effect in brain structure might contribute to an increased risk for schizophrenia in males brought up in cities. Taken together, our results suggest a neural mechanism by which early-life urbanicity could impact brain architecture to increase the risk for schizophrenia.
城市成长环境一直与精神分裂症相关联，但这种流行病学观察反映了哪些具体的环境暴露因素，以及它们如何影响发育中的大脑从而增加患病风险，目前很大程度上尚不清楚。基于此前对城市出生人群大脑处理社会压力时功能异常的观察，以及早期社会压力对大脑结构产生持久影响的临床前证据，我们研究了城市成长环境在人类大脑中可能存在的形态学关联。在一个由110名健康受试者组成的样本中，我们采用基于体素的形态测量法进行研究，发现早年城市生活程度与右侧背外侧前额叶皮质（DLPFC，布罗德曼区9）的灰质（GM）体积之间存在强烈的负相关。此外，我们仅在男性中检测到早年城市生活程度与膝周前扣带回皮质（pACC）的GM体积呈负相关。此前的研究已将DLPFC体积减小与接触心理社会压力联系起来，包括早年的压力经历。此外，在精神分裂症患者和高危人群中已发现该区域存在解剖学和功能改变。此前的数据将社会压力期间pACC的功能亢进与城市成长环境联系起来，这表明目前在大脑结构方面的交互作用可能会增加城市中成长男性患精神分裂症的风险。综上所述，我们的研究结果表明了一种神经机制，通过该机制早年城市生活程度可能会影响大脑结构，从而增加患精神分裂症的风险。
