Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia

Thomas H Wassink; Eric A Epping; Danielle Rudd; Michael Axelsen; Stephen Ziebell; Frank W Fleming; Eric Monson; Beng Choon Ho; Nancy C Andreasen

doi:10.1001/archgenpsychiatry.2011.2116

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Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia

Journal article

Open access

Peer reviewed

Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia

Thomas H Wassink, Eric A Epping, Danielle Rudd, Michael Axelsen, Stephen Ziebell, Frank W Fleming, Eric Monson, Beng Choon Ho and Nancy C Andreasen

Archives of general psychiatry, Vol.69(9), pp.885-892

09/2012

DOI: 10.1001/archgenpsychiatry.2011.2116

PMCID: PMC3852666

PMID: 22945618

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Abstract

CONTEXT The single-nucleotide polymorphism rs1344706 in the gene ZNF804a has been associated with schizophrenia and with quantitative phenotypic features, including brain structure volume and the core symptoms of schizophrenia. OBJECTIVE To evaluate associations of rs1344706 with brain structure and the core symptoms of schizophrenia. DESIGN Case-control analysis of covariance. SETTING University-based research hospital. PARTICIPANTS Volunteer sample of 335 individuals with schizophrenia spectrum disorders (306 with core schizophrenia) and 198 healthy volunteers. MAIN OUTCOME MEASURES Cerebral cortical gray matter and white matter (WM) volumes (total and frontal, parietal, temporal, and occipital lobes), lateral ventricular cerebrospinal fluid volume, and symptom severity from the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms divided into 3 domains: psychotic, negative, and disorganized. RESULTS The rs1344706 genotype produced significant main effects on total, frontal, and parietal lobe WM volumes (F = 3.98, P = .02; F = 4.95, P = .007; and F = 3.08, P = .05, respectively). In the schizophrenia group, rs1344706 produced significant simple effects on total (F = 3.93, P = .02) and frontal WM volumes (F = 7.16, P < .001) and on psychotic symptom severity (F = 6.07, P = .003); the pattern of effects was concordant with risk allele carriers having larger volumes and more severe symptoms of disease than nonrisk homozygotes. In the healthy volunteer group, risk allele homozygotes had increased total WM volume compared with nonrisk allele carriers (F = 4.61, P = .03), replicating a previously reported association. CONCLUSIONS A growing body of evidence suggests that the risk allele of rs1347706 is associated with a distinctive set of phenotypic features in healthy volunteers and individuals with schizophrenia. Our study supports this assertion by finding that specific genotypes of the polymorphism are associated with brain structure volumes in individuals with schizophrenia and healthy volunteers and with symptom severity in schizophrenia.

Gene Frequency - genetics

Genetic Predisposition to Disease - genetics

Humans

Cerebral Cortex - pathology

Image Interpretation, Computer-Assisted

Genotype

Male

Organ Size - physiology

Reference Values

Schizophrenic Psychology

Case-Control Studies

Young Adult

Homozygote

Magnetic Resonance Imaging

Phenotype

Psychiatric Status Rating Scales

Schizophrenia - genetics

Schizophrenia - diagnosis

Alleles

Polymorphism, Single Nucleotide - genetics

Adult

Female

Kruppel-Like Transcription Factors - genetics

Genetic Carrier Screening

Details

Title: Subtitle: Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia
Creators: Thomas H Wassink - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. thomas-wassink@uiowa.edu
Eric A Epping
Danielle Rudd
Michael Axelsen
Stephen Ziebell
Frank W Fleming
Eric Monson
Beng Choon Ho
Nancy C Andreasen
Resource Type: Journal article
Publication Details: Archives of general psychiatry, Vol.69(9), pp.885-892
DOI: 10.1001/archgenpsychiatry.2011.2116
PMID: 22945618
PMCID: PMC3852666
NLM abbreviation: Arch Gen Psychiatry
ISSN: 0003-990X
eISSN: 1538-3636
Publisher: American Medical Association; United States
Grant note: MH68380 / NIMH NIH HHS R01 MH080128 / NIMH NIH HHS MH31593 / NIMH NIH HHS MH40856 / NIMH NIH HHS R01 MH031593 / NIMH NIH HHS R01 MH040856 / NIMH NIH HHS T32 GM007337 / NIGMS NIH HHS P30 MH043271 / NIMH NIH HHS R37 MH031593 / NIMH NIH HHS MH43271 / NIMH NIH HHS K23 MH068380 / NIMH NIH HHS MH080128 / NIMH NIH HHS
Language: English
Date published: 09/2012
Academic Unit: Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984004193202771

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