The COMT Val108/158Met polymorphism and medial temporal lobe volumetry in patients with schizophrenia and healthy adults

Stefan Ehrlich; Eric M Morrow; Joshua L Roffman; Stuart R Wallace; Melissa Naylor; H. Jeremy Bockholt; Antonia Lundquist; Anastasia Yendiki; Beng-Choon Ho; Tonya White; Dara S Manoach; Vincent P Clark; Vince D Calhoun; Randy L Gollub; Daphne J Holt

doi:10.1016/j.neuroimage.2009.12.046

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The COMT Val108/158Met polymorphism and medial temporal lobe volumetry in patients with schizophrenia and healthy adults

Journal article

Peer reviewed

The COMT Val108/158Met polymorphism and medial temporal lobe volumetry in patients with schizophrenia and healthy adults

Stefan Ehrlich, Eric M Morrow, Joshua L Roffman, Stuart R Wallace, Melissa Naylor, H. Jeremy Bockholt, Antonia Lundquist, Anastasia Yendiki, Beng-Choon Ho, Tonya White, …

NeuroImage (Orlando, Fla.), Vol.53(3), pp.992-1000

11/15/2010

DOI: 10.1016/j.neuroimage.2009.12.046

PMCID: PMC2888809

PMID: 20026221

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https://www.ncbi.nlm.nih.gov/pmc/articles/2888809View

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Abstract

Abnormalities of the medial temporal lobe have been consistently demonstrated in schizophrenia. A common functional polymorphism, Val108/158Met, in the putative schizophrenia susceptibility gene, catechol-O-methyltransferase (COMT), has been shown to influence medial temporal lobe function. However, the effects of this polymorphism on volumes of medial temporal lobe structures, particularly in patients with schizophrenia, are less clear. Here we measured the effects of COMT Val108/158Met genotype on the volume of two regions within the medial temporal lobe, the amygdala and hippocampus, in patients with schizophrenia and healthy control subjects. We obtained MRI and genotype data for 98 schizophrenic patients and 114 matched controls. An automated atlas-based segmentation algorithm was used to generate volumetric measures of the amygdala and hippocampus. Regression analyses included COMT met allele load as an additive effect, and also controlled for age, intracranial volume, gender and acquisition site. Across patients and controls, each copy of the COMT met allele was associated on average with a 2.6% increase in right amygdala volume, a 3.8% increase in left amygdala volume and a 2.2% increase in right hippocampus volume. There were no effects of COMT genotype on volumes of the whole brain and prefrontal regions. Thus, the COMT Val108/158Met polymorphism was shown to influence medial temporal lobe volumes in a linear-additive manner, mirroring its effect on dopamine catabolism. Taken together with previous work, our data support a model in which lower COMT activity, and a resulting elevation in extracellular dopamine levels, stimulates growth of medial temporal lobe structures.

Schizophrenia

Dopamine

COMT Val108/158Met Polymorphism

Structural MRI

Amygdala

Hippocampus

Details

Title: Subtitle: The COMT Val108/158Met polymorphism and medial temporal lobe volumetry in patients with schizophrenia and healthy adults
Creators: Stefan Ehrlich - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Eric M Morrow - Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
Joshua L Roffman - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Stuart R Wallace - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Melissa Naylor - Harvard School of Public Health, Department of Biostatistics, Boston, MA, USA
H. Jeremy Bockholt - The Mind Research Network, Albuquerque, NM, USA
Antonia Lundquist - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Anastasia Yendiki - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Beng-Choon Ho - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Tonya White - Department of Psychiatry and the Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA
Dara S Manoach - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Vincent P Clark - The Mind Research Network, Albuquerque, NM, USA
Vince D Calhoun - The Mind Research Network, Albuquerque, NM, USA
Randy L Gollub - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Daphne J Holt - MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
Resource Type: Journal article
Publication Details: NeuroImage (Orlando, Fla.), Vol.53(3), pp.992-1000
DOI: 10.1016/j.neuroimage.2009.12.046
PMID: 20026221
PMCID: PMC2888809
NLM abbreviation: Neuroimage
ISSN: 1053-8119
eISSN: 1095-9572
Publisher: Elsevier Inc
Grant note: name: NIH/NCRR, award: P41RR14075; name: Department of Energy, Mental Illness and Neuroscience Discovery (MIND) Research Network, Morphometry Biomedical Informatics Research Network (mBIRN), award: 1U24, RR021382A; name: Function BIRN, award: U24RR021992; name: NIMH K23, award: MH076054; name: NIMH K23, award: MH080954; name: National Alliance for Research in Schizophrenia and Depression, award: M01-RR-01066; DOI: 10.13039/100000861, name: Burroughs Wellcome Fund; DOI: 10.13039/100012138, name: Nellie Ball Research Trust; DOI: 10.13039/501100001659, name: Deutsche Forschungsgemeinschaft
Language: English
Date published: 11/15/2010
Academic Unit: Psychiatry
Record Identifier: 9984004079102771

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