title: The influence of 5-HTTLPR and Val66Met polymorphisms on cortical thickness and volume in limbic and paralimbic regions in depression: a preliminary study.
abstract: BACKGROUND
  Structural brain abnormalities have been investigated in multi-genetic and complex disorders such as major depressive disorder (MDD). Among the various candidate genes implicated in MDD, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and 5-HT transporter gene linked polymorphism (5-HTTLPR) have garnered the most attention due to their putative roles in neural plasticity and antidepressant response. However, relatively few studies have assessed the influence of these polymorphysims on cortical thickness or brain volume in para-limbic and limbic regions in MDD, which was the aim of this study.
  
  
  METHODS
  Forty-three adults with MDD and 15 healthy controls (HC) underwent structural magnetic resonance imaging (MRI). Cortical thickness was assessed in frontal, cingulate and temporal regions. Volumetric measures were carried out in the thalamus, caudate, putamen, pallidum, hippocampus and amygdala. Participants were genotyped to determine their 5-HTTLPR (tri-allelic) and Val66Met polymorphisms.
  
  
  RESULTS
  In the combined sample (MDD + HC), smaller right pallidum volumes were found in LA/S (LA/S & LA/LG) heterozygotes compared to S/S (S/S, LG/S & LG/LG) homozygotes, though the effect was modest. In the MDD group, larger left thalamus and putamen volumes were observed in LA/LA homozygotes. No Val66Met or 5-HTTLPR genotype effects existed on cortical thickness and no main effects of the Val66Met polymorphism were observed.
  
  
  CONCLUSIONS
  Our preliminary results suggest that the 5-HTTLPR polymorphism is associated with morphometric changes in regions known to play an important role in emotional and reward processing in depression. A larger sample size is required to replicate these findings and to potentially reveal subtle morphometric changes.
authors.affiliation: Department of Psychiatry, McGill University, Montreal, PQ, Canada.|Department of Psychiatry, Mathison Centre for Mental Health Research & Education, University of Calgary, #4D64 TRW Building, 3280 Hospital Drive NW, Calgary, AB, T2N4Z6, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Jaworska
authors.affiliation: Department of Psychiatry, Mathison Centre for Mental Health Research & Education, University of Calgary, #4D64 TRW Building, 3280 Hospital Drive NW, Calgary, AB, T2N4Z6, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.|Child & Adolescent Imaging Research (CAIR) Program, Alberta Children's Hospital Research Institute for Child & Maternal Health, Calgary, AB, Canada.
authors.forename: Frank P
authors.initials: FP
authors.lastname: MacMaster
authors.affiliation: Department of Psychiatry & Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Foster
authors.affiliation: Department of Psychiatry, Mathison Centre for Mental Health Research & Education, University of Calgary, #4D64 TRW Building, 3280 Hospital Drive NW, Calgary, AB, T2N4Z6, Canada. rramasub@ucalgary.ca.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. rramasub@ucalgary.ca.
authors.forename: Rajamannar
authors.initials: R
authors.lastname: Ramasubbu
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014633:Valine
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C579455:BDNF protein, human; D008715:Methionine; D014633:Valine
keywords: 5-HTTLPR; Cortical thickness; Depression; Polymorphism; Structural volume; Val66Met