title: Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression.
abstract: BACKGROUND
  Substantial evidence supports a role for dysfunction of the serotonin transporter in the pathogenesis of major depression. Several studies have found reciprocal interactions between the serotonergic system and both brain-derived neurotrophic factor and glutamate, which are known to modulate or affect hippocampal morphologic characteristics.
  
  
  OBJECTIVE
  To examine the influence of a polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene on hippocampal volumes in patients with major depression and healthy controls.
  
  
  METHODS
  Baseline investigation of a prospective magnetic resonance imaging study with a 4-year follow-up period.
  
  
  METHODS
  We examined 40 inpatients with major depression as well as 40 healthy controls matched for age, sex, and handedness.
  
  
  METHODS
  Subjects underwent high-resolution magnetic resonance imaging. Furthermore, genotyping for the 5-HTTLPR biallelic polymorphism was performed, which consists of a 44-base pair insertion (L allele) or deletion (S allele).
  
  
  RESULTS
  Patients with the L/L homozygous genotype had significantly smaller hippocampal gray matter (left hemisphere: P=.003; right hemisphere: P=.01) and white matter volumes (left hemisphere: P=.001; right hemisphere: P=.002) than controls with this genotype. No significant differences were found between patients and controls with the L/S or S/S genotype. Moreover, patients with the L/L genotype had significantly smaller hippocampal white matter volumes than those with the L/S or S/S genotype (P=.03).
  
  
  CONCLUSIONS
  These findings suggest that homozygosity for the L allele is associated with decreased hippocampal volumes in patients with major depression but not in healthy controls. A possible explanation is that the interaction between the serotonergic system and neurotrophic factors as well as excitatory amino acid neurotransmission may affect hippocampal morphologic characteristics.
authors.affiliation: Department of Psychiatry, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frodl
authors.forename: Eva M
authors.initials: EM
authors.lastname: Meisenzahl
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Thomas
authors.initials: T
authors.lastname: Baghai
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Gerda
authors.initials: G
authors.lastname: Leinsinger
authors.forename: Ronald
authors.initials: R
authors.lastname: Bottlender
authors.forename: Cornelius
authors.initials: C
authors.lastname: Schüle
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Rolf R
authors.initials: RR
authors.lastname: Engel
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
authors.forename: Maximilian
authors.initials: M
authors.lastname: Reiser
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000033:anatomy & histology / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin