Research article summary (published 29 Apr 2009):

Neural mechanisms of a genome-wide supported psychosis variant.

Full Abstract

Schizophrenia is a devastating, highly heritable brain disorder of unknown etiology. Recently, the first common genetic variant associated on a genome-wide level with schizophrenia and possibly bipolar disorder was discovered in ZNF804A (rs1344706). We show, by using an imaging genetics approach, that healthy carriers of rs1344706 risk genotypes exhibit no changes in regional activity but pronounced gene dosage-dependent alterations in functional coupling (correlated activity) of dorsolateral prefrontal cortex (DLPFC) across hemispheres and with hippocampus, mirroring findings in patients, and abnormal coupling of amygdala. Our findings establish disturbed connectivity as a neurogenetic risk mechanism for psychosis supported by genome-wide association, show that rs1344706 or variation in linkage disequilibrium is functional in human brain, and validate the intermediate phenotype strategy in psychiatry.

Author information

Author/s: Esslinger, Christine (C); Walter, Henrik (H); Kirsch, Peter (P); Erk, Susanne (S); Schnell, Knut (K); Arnold, Claudia (C); Haddad, Leila (L); Mier, Daniela (D); Opitz von Boberfeld, Carola (C); Raab, Kyeon (K); Witt, Stephanie H (SH); Rietschel, Marcella (M); Cichon, Sven (S); Meyer-Lindenberg, Andreas (A);

Affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, J5, 68159 Mannheim, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Science (New York, N.Y.) (Science), published in United States. (Language: eng)

Reference: 2009-May; vol 324 (issue 5927) : pp 605

Dates: Created 2009/05/01; Completed 2009/05/13;

PMID: 19407193, status: MEDLINE (last retrieval date: 5/13/2009, IMS Date: 13 May 2009 00:00:00)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Affective Symptoms - genetics; physiopathology Bipolar Disorder - genetics; physiopathology Brain Mapping Female Genetic Predisposition to Disease Genome-Wide Association Study Genotype Hippocampus - physiology

Humans Kruppel-Like Transcription Factors - genetics Magnetic Resonance Imaging Male Mental Processes Phenotype Polymorphism, Single Nucleotide Prefrontal Cortex - physiology Schizophrenia - genetics; physiopathology

Associated Chemicals: Kruppel-Like Transcription Factors (0) ; ZNF804A protein, human (0)

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