No evidence of DISC1-associated morphological changes in the hippocampus, anterior cingulate cortex, or striatum in major depressive disorder cases and healthy controls

David Stacey; Ronny Redlich; Nils Opel; Dominik Grotegerd; Volker Arolt; Harald Kugel; Walter Heindel; Bernhard T Baune; Udo Dannlowski

doi:10.1016/j.jad.2014.05.001

No evidence of DISC1-associated morphological changes in the hippocampus, anterior cingulate cortex, or striatum in major depressive disorder cases and healthy controls

J Affect Disord. 2014 Sep:166:103-7. doi: 10.1016/j.jad.2014.05.001. Epub 2014 May 11.

Authors

David Stacey¹, Ronny Redlich², Nils Opel², Dominik Grotegerd², Volker Arolt², Harald Kugel³, Walter Heindel³, Bernhard T Baune⁴, Udo Dannlowski⁵

Affiliations

¹ Discipline of Psychiatry, Level 4, Eleanor Harrald Building, Frome Road, School of Medicine, University of Adelaide, SA 5005, Australia. Electronic address: david.stacey@adelaide.edu.au.
² Department of Psychiatry, University of Münster, Germany.
³ Department of Clinical Radiology, University of Münster, Germany.
⁴ Discipline of Psychiatry, Level 4, Eleanor Harrald Building, Frome Road, School of Medicine, University of Adelaide, SA 5005, Australia.
⁵ Department of Psychiatry, University of Münster, Germany; Department of Psychiatry, University of Marburg, Germany.

PMID: 25012417
DOI: 10.1016/j.jad.2014.05.001

Abstract

Background: DISC1 imaging genetics studies in healthy controls, schizophrenia, and bipolar disorder cases have revealed morphological changes in brain regions involved in the pathophysiology of psychiatric disease including the hippocampus, anterior cingulate cortex (ACC), and the striatum. However, many of these studies have yielded discordant findings so there is a need for replication. Furthermore, despite evidence from human genetic studies and animal models implicating DISC1 in major depressive disorder (MDD), a DISC1 imaging genetics study in MDD cases has yet to be published. Thus, using neuroimaging data from MDD cases and a large sample of healthy controls we aimed to identify morphological changes representing neurobiological mechanisms underlying the association between DISC1 and MDD.

Methods: We utilized structural magnetic resonance imaging (sMRI) data from 512 healthy controls and 171 current MDD (SCID interview) cases, each with genotype data for non-synonymous DISC1 SNPs rs3738401, rs6675281, and rs821616.

Results: Region of interest analyses failed to reveal DISC1-associated morphological changes in the hippocampus, ACC, or striatum in MDD patients and healthy controls. Whole brain exploratory analyses identified a nominally significant cluster mapping to the border of the precentral and postcentral gyri associated with rs821616 in healthy controls only (p(uncorrected)<0.001).

Limitations: We focused our analyses exclusively on three, but previously heavily studied, SNPs in DISC1.

Conclusions: Our findings suggest that morphological changes in the hippocampus, ACC, and/or striatum of MDD patients do not represent neurobiological mechanisms underlying the association between DISC1 and MDD. However, we urge replication in independent samples of MDD cases.

Keywords: DISC1; Hippocampus; Imaging genetics; Major depressive disorder.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Case-Control Studies
Corpus Striatum / pathology*
Depressive Disorder, Major / genetics*
Depressive Disorder, Major / pathology*
Female
Gyrus Cinguli / pathology*
Hippocampus / pathology*
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Nerve Tissue Proteins / genetics*
Polymorphism, Single Nucleotide

Substances

DISC1 protein, human
Nerve Tissue Proteins