Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression.
BACKGROUND
Polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) influence transcription and may play a role in the pathogenesis and course of depression. Recent research demonstrates that specific polymorphisms may be associated with differences in hippocampal volumes in subjects with depression.


OBJECTIVE
To examine associations between 5-HTTLPR genotype and hippocampal volumes in elderly control subjects and elderly subjects classified as having early or late onset of depression.


METHODS
Cohort study examining baseline characteristics.


METHODS
Subjects were community dwelling and 60 years or older. Using a definition of early-onset depression as depression first occurring at 50 years or younger, we examined 72 subjects with early-onset depression, 63 subjects with late-onset depression, and 83 healthy control subjects.


METHODS
All subjects underwent genotyping for the 5-HTTLPR and underwent brain magnetic resonance imaging. Analyses of hippocampal volumes were controlled for total cerebral volume, age, and sex.


RESULTS
The interaction between diagnosis and 5-HTTLPR genotype was statistically significant for the right hippocampus (P = .04). Subjects with late-onset depression who were homozygous for the long (L) allele (L /L genotype) had significantly smaller right hippocampal volumes than did L /L subjects with early-onset depression (P = .046) or L /L control subjects (P = .01). Post hoc analyses showed that later age of depression onset was associated with smaller hippocampal volumes in subjects with the L /L genotype, but earlier age of onset was associated with smaller hippocampal volumes in subjects who were homozygous for the short (S) allele (S/S genotype).


CONCLUSIONS
Subjects with late-onset depression who were homozygous for the L allele exhibited smaller hippocampal volumes than other groups. Genotype also mediated the effect of age of onset on hippocampal volumes. Our findings differ from previous work; however, we examined an older and larger cohort of subjects than previous studies. Possible explanations for these findings include interactions between the serotonergic system and neurotrophic factors or cortisol response to stresses, each of which may affect hippocampal volumes.
Taylor
Warren D
WD
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. taylo006@mc.duke.edu
Steffens
David C
DC
Payne
Martha E
ME
MacFall
James R
JR
Marchuk
Douglas A
DA
Svenson
Ingrid K
IK
Krishnan
K Ranga R
KR
D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D001921:Brain / Q000033:anatomy & histology; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D007839:Functional Laterality; D005838:Genotype; D006624:Hippocampus / Q000033:anatomy & histology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins