Effects of serotonin transporter promoter polymorphisms on serotonin function.
The serotonin transporter promoter polymorphism (5-HTTLPR) has been associated with vulnerability to stress-induced depressive symptoms and with the speed and rate of response to antidepressant treatment. The goal of the present study was to evaluate the association between the 5-HTTLPR and the functional response of the serotonin system as measured by the neuroendocrine and cerebral metabolic response to intravenous administration of the selective serotonin reuptake inhibitor citalopram in normal control subjects. Genotyping was performed for 5-HTTLPR insertion/deletion polymorphism long (l) and short (s) variant alleles. The ll genotype was compared with the combined sl+ss and with the ss genotype alone. Citalopram plasma concentrations did not differ significantly between groups. The s allele was associated with a less of an increase in prolactin and cortisol than the ll genotype. The s allele was associated with greater decreases in left frontal, precentral and middle temporal gyri compared to the ll genotype. The ll genotype was associated with greater decreases in right frontal, insula and superior temporal gyrus compared to the ss genotype. These findings suggest that 5-HTTLPR is associated with an altered functional response of the serotonin system, which may represent a neurobiologic substrate for the differential response to antidepressant treatment in late life and the emergence of neuropsychiatric symptoms in neurodegenerative disorders.
Smith
Gwenn S
GS
Department of Psychiatry, the Zucker Hillside Hospital, Glen Oaks, NY 11004, USA. gsmith@lij.edu
Lotrich
Francis E
FE
Malhotra
Anil K
AK
Lee
Annette T
AT
Ma
Yilong
Y
Kramer
Elisse
E
Gregersen
Peter K
PK
Eidelberg
David
D
Pollock
Bruce G
BG
D000328:Adult; D000368:Aged; D000483:Alleles; D019540:Area Under Curve; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009490:Neurosecretory Systems / Q000187:drug effects; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography / Q000379:methods; D011388:Prolactin / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors
D015283:Citalopram; D006854:Hydrocortisone; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011388:Prolactin; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human