Faculty Collaboration Database

Schizophrenia Imaging Signatures and Their Associations With Cognition, Psychopathology, and Genetics in the General Population. Am J Psychiatry 2022 Sep;179(9):650-660

Date

04/13/2022

Pubmed ID

35410495

Pubmed Central ID

PMC9444886

DOI

10.1176/appi.ajp.21070686

Scopus ID

2-s2.0-85137078437 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

OBJECTIVE: The prevalence and significance of schizophrenia-related phenotypes at the population level is debated in the literature. Here, the authors assessed whether two recently reported neuroanatomical signatures of schizophrenia-signature 1, with widespread reduction of gray matter volume, and signature 2, with increased striatal volume-could be replicated in an independent schizophrenia sample, and investigated whether expression of these signatures can be detected at the population level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk.

METHODS: This cross-sectional study used an independent schizophrenia-control sample (N=347; ages 16-57 years) for replication of imaging signatures, and then examined two independent population-level data sets: typically developing youths and youths with psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort (N=359; ages 16-23 years) and adults in the UK Biobank study (N=836; ages 44-50 years). The authors quantified signature expression using support-vector machine learning and compared cognition, psychopathology, and polygenic risk between signatures.

RESULTS: Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youths with psychosis spectrum symptoms than in typically developing youths, whereas signature 2 frequency was similar in the two groups. In both youths and adults, signature 1 was associated with worse cognitive performance than signature 2. Compared with adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2.

CONCLUSIONS: The authors successfully replicated two neuroanatomical signatures of schizophrenia and describe their prevalence in population-based samples of youths and adults. They further demonstrated distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.

Author List

Chand GB, Singhal P, Dwyer DB, Wen J, Erus G, Doshi J, Srinivasan D, Mamourian E, Varol E, Sotiras A, Hwang G, Dazzan P, Kahn RS, Schnack HG, Zanetti MV, Meisenzahl E, Busatto GF, Crespo-Facorro B, Pantelis C, Wood SJ, Zhuo C, Shinohara RT, Shou H, Fan Y, Koutsouleris N, Kaczkurkin AN, Moore TM, Verma A, Calkins ME, Gur RE, Gur RC, Ritchie MD, Satterthwaite TD, Wolf DH, Davatzikos C

Author

Gyujoon Hwang PhD Assistant Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cognition
Cross-Sectional Studies
Gray Matter
Humans
Psychotic Disorders
Schizophrenia