title: No evidence of DISC1-associated morphological changes in the hippocampus, anterior cingulate cortex, or striatum in major depressive disorder cases and healthy controls.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Stacey
authors.affiliation: Department of Psychiatry, University of Münster, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Redlich
authors.affiliation: Department of Psychiatry, University of Münster, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Opel
authors.affiliation: Department of Psychiatry, University of Münster, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Grotegerd
authors.affiliation: Department of Psychiatry, University of Münster, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Clinical Radiology, University of Münster, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Kugel
authors.affiliation: Department of Clinical Radiology, University of Münster, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Heindel
authors.affiliation: Discipline of Psychiatry, Level 4, Eleanor Harrald Building, Frome Road, School of Medicine, University of Adelaide, SA 5005, Australia.
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: Department of Psychiatry, University of Münster, Germany; Department of Psychiatry, University of Marburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Dannlowski
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000473:pathology*; D003865:Major Depressive Disorder / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins
keywords: DISC1; Hippocampus; Imaging genetics; Major depressive disorder