title: Brain structure correlates of urban upbringing, an environmental risk factor for schizophrenia.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
authors.forename: Leila
authors.initials: L
authors.lastname: Haddad
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
authors.forename: Axel
authors.initials: A
authors.lastname: Schäfer
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
authors.forename: Fabian
authors.initials: F
authors.lastname: Streit
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
authors.forename: Florian
authors.initials: F
authors.lastname: Lederbogen
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
authors.forename: Oliver
authors.initials: O
authors.lastname: Grimm
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Wüst
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Deuschle
authors.affiliation: Department of Clinical Psychology, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kirsch
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany;
authors.forename: Heike
authors.initials: H
authors.lastname: Tost
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany; a.meyer-lindenberg@zi-mannheim.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D004781:Environmental Exposure; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006179:Gyrus Cinguli / Q000473:pathology*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D009929:Organ Size; D017397:Prefrontal Cortex / Q000473:pathology*; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000473:pathology*; D012931:Social Environment; D013315:Stress, Psychological / Q000473:pathology; D014505:Urban Population / Q000706:statistics & numerical data*; D055815:Young Adult
keywords: cortical volume; environmental risk; schizophrenia; social stress hypothesis; urbanicity; voxel-based morphometry