A Neuregulin-1 schizophrenia susceptibility variant causes perihippocampal fiber tract anomalies in healthy young subjects

Thomas Nickl-Jockschat; Tony Stöcker; Axel Krug; Valentin Markov; Ruiwang Huang; Frank Schneider; Ute Habel; Simon B Eickhoff; Klaus Zerres; Markus M Nöthen; Jens Treutlein; Marcella Rietschel; Nadim Jon Shah; Tilo Kircher

doi:10.1002/brb3.203

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A Neuregulin-1 schizophrenia susceptibility variant causes perihippocampal fiber tract anomalies in healthy young subjects

Journal article

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A Neuregulin-1 schizophrenia susceptibility variant causes perihippocampal fiber tract anomalies in healthy young subjects

Thomas Nickl-Jockschat, Tony Stöcker, Axel Krug, Valentin Markov, Ruiwang Huang, Frank Schneider, Ute Habel, Simon B Eickhoff, Klaus Zerres, Markus M Nöthen, …

Brain and behavior, Vol.4(2), pp.215-226

03/2014

DOI: 10.1002/brb3.203

PMCID: PMC3967537

PMID: 24683514

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Abstract

Changes in fiber tract architecture have gained attention as a potentially important aspect of schizophrenia neuropathology. Although the exact pathogenesis of these abnormalities yet remains to be elucidated, a genetic component is highly likely. Neuregulin-1 (NRG1) is one of the best-validated schizophrenia susceptibility genes. We here report the impact of the Neuregulin-1 rs35753505 variant on white matter structure in healthy young individuals with no family history of psychosis. We compared fractional anisotropy in 54 subjects that were either homozygous for the risk C allele carriers (n = 31) for rs35753505 or homozygous for the T allele (n = 23) using diffusion tensor imaging with 3T. Tract-Based Spatial Statistics (TBSS), a method especially developed for diffusion data analysis, was used to improve white matter registration and to focus the statistical analysis to major fiber tracts. Statistical analysis showed that homozygous risk C allele carriers featured elevated fractional anisotropy (FA) in the right perihippocampal region and the white matter proximate to the left area 4p as well as the right hemisphere of the cerebellum. We found three clusters of reduced FA values in homozygous C allele carriers: in the left superior parietal region, the right prefrontal white matter and in the deep white matter of the left frontal lobe. Our results highlight the importance of Neuregulin-1 for structural connectivity of the right medial temporal lobe. This finding is in line with well known neuropathological findings in this region in patients with schizophrenia.

Genetic Predisposition to Disease

Humans

Male

Hippocampus - pathology

Schizophrenia - pathology

Neuregulin-1 - genetics

Cerebellum - pathology

White Matter - pathology

Young Adult

Magnetic Resonance Imaging

Schizophrenia - genetics

Adult

Female

Details

Title: Subtitle: A Neuregulin-1 schizophrenia susceptibility variant causes perihippocampal fiber tract anomalies in healthy young subjects
Creators: Thomas Nickl-Jockschat - Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany ; Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany
Tony Stöcker - Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany ; Institute of Neurosciences and Medicine-4, Juelich Research Center Juelich, Germany
Axel Krug - Department of Psychiatry and Psychotherapy, University of Marburg Marburg, Germany
Valentin Markov - Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany
Ruiwang Huang - Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany ; Institute of Neurosciences and Medicine-4, Juelich Research Center Juelich, Germany
Frank Schneider - Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany ; Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany
Ute Habel - Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany ; Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany
Simon B Eickhoff - Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Germany ; Department of Neuroscience und Medicine, INM-1, Research Center Jülich Jülich, Germany
Klaus Zerres - Institute of Human Genetics, RWTH Aachen University Aachen, Germany
Markus M Nöthen - Department of Genomics, Life and Brain Center, University of Bonn Bonn, Germany
Jens Treutlein - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, Germany
Marcella Rietschel - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, Germany
Nadim Jon Shah - Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany ; Institute of Neurosciences and Medicine-4, Juelich Research Center Juelich, Germany ; Department of Neurology, RWTH Aachen University Aachen, Germany
Tilo Kircher - Department of Psychiatry and Psychotherapy, University of Marburg Marburg, Germany
Resource Type: Journal article
Publication Details: Brain and behavior, Vol.4(2), pp.215-226
DOI: 10.1002/brb3.203
PMID: 24683514
PMCID: PMC3967537
NLM abbreviation: Brain Behav
ISSN: 2162-3279
eISSN: 2162-3279
Publisher: United States
Language: English
Date published: 03/2014
Academic Unit: Psychiatry; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984070876302771

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