title: Impact of monoamine-related gene polymorphisms on hippocampal volume in treatment-resistant depression.
abstract: OBJECTIVE
  In major depressive disorder (MDD), single nucleotide polymorphisms (SNPs) in monoaminergic genes may impact disease susceptibility, treatment response, and brain volume. The objective of this study was to examine the effect of such polymorphisms on hippocampal volume in patients with treatment-resistant MDD and healthy controls. Candidate gene risk alleles were hypothesised to be associated with reductions in hippocampal volume.
  
  
  METHODS
  A total of 26 outpatients with treatment-resistant MDD and 27 matched healthy controls underwent magnetic resonance imaging and genotyping for six SNPs in monoaminergic genes [serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), serotonin 1A and 2A receptors (HTR1A and HTR2A), catechol-O-methyltransferase (COMT), and brain-derived neurotrophic factor (BDNF)]. Hippocampal volume was estimated using an automated segmentation algorithm (FreeSurfer).
  
  
  RESULTS
  Hippocampal volume did not differ between patients and controls. Within the entire study sample irrespective of diagnosis, C allele-carriers for both the NET-182 T/C [rs2242446] and 5-HT1A-1019C/G [rs6295] polymorphisms had smaller hippocampal volumes relative to other genotypes. For the 5-HTTLPR (rs25531) polymorphism, there was a significant diagnosis by genotype interaction effect on hippocampal volume. Among patients only, homozygosity for the 5-HTTLPR short (S) allele was associated with smaller hippocampal volume. There was no association between the 5-HT2A, COMT, and BDNF SNPs and hippocampal volume.
  
  
  CONCLUSIONS
  The results indicate that the volume of the hippocampus may be influenced by serotonin- and norepinephrine-related gene polymorphisms. The NET and 5-HT1A polymorphisms appear to have similar effects on hippocampal volume in patients and controls while the 5-HTTLPR polymorphism differentially affects hippocampal volume in the presence of depression.
authors.affiliation: 1University of Ottawa Institute of Mental Health Research,Ottawa,Canada.
authors.forename: Jennifer Lynne
authors.initials: JL
authors.lastname: Phillips
authors.affiliation: 1University of Ottawa Institute of Mental Health Research,Ottawa,Canada.
authors.forename: Lisa Ann
authors.initials: LA
authors.lastname: Batten
authors.affiliation: 1University of Ottawa Institute of Mental Health Research,Ottawa,Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Tremblay
authors.affiliation: 1University of Ottawa Institute of Mental Health Research,Ottawa,Canada.
authors.forename: Fahad
authors.initials: F
authors.lastname: Aldosary
authors.affiliation: 1University of Ottawa Institute of Mental Health Research,Ottawa,Canada.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Du
authors.affiliation: 1University of Ottawa Institute of Mental Health Research,Ottawa,Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
mesh_terms: D000328:Adult; D000465:Algorithms; D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D061218:Depressive Disorder, Treatment-Resistant / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C583518:HTR1A protein, human; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; C579455:BDNF protein, human; D002394:Catechol O-Methyltransferase
keywords: hippocampal volume; magnetic resonance imaging; major depressive disorder; single nucleotide polymorphism