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. DESIGN: Baseline investigation of a prospective magnetic resonance imaging study with a 4-year follow-up period. PATIENTS: We examined 40 inpatients with major depression as well as 40 healthy controls matched for age, sex, and handedness. MAIN OUTCOME MEASURES: 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.
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. DESIGN: Baseline investigation of a prospective magnetic resonance imaging study with a 4-year follow-up period. PATIENTS: We examined 40 inpatients with major depression as well as 40 healthy controls matched for age, sex, and handedness. MAIN OUTCOME MEASURES: 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: Marina Boccardi; Rossana Ganzola; Martina Bocchetta; Michela Pievani; Alberto Redolfi; George Bartzokis; Richard Camicioli; John G Csernansky; Mony J de Leon; Leyla deToledo-Morrell; Ronald J Killiany; Stéphane Lehéricy; Johannes Pantel; Jens C Pruessner; H Soininen; Craig Watson; Simon Duchesne; Clifford R Jack; Giovanni B Frisoni Journal: J Alzheimers Dis Date: 2011 Impact factor: 4.472
Authors: Turhan Canli; Maolin Qiu; Kazufumi Omura; Eliza Congdon; Brian W Haas; Zenab Amin; Martin J Herrmann; R Todd Constable; Klaus Peter Lesch Journal: Proc Natl Acad Sci U S A Date: 2006-10-10 Impact factor: 11.205
Authors: Martina Ballmaier; Katherine L Narr; Arthur W Toga; Virginia Elderkin-Thompson; Paul M Thompson; Liberty Hamilton; Ebrahim Haroon; Daniel Pham; Andreas Heinz; Anand Kumar Journal: Am J Psychiatry Date: 2007-11-06 Impact factor: 18.112
Authors: P Cédric M P Koolschijn; Neeltje E M van Haren; Gerty J L M Lensvelt-Mulders; Hilleke E Hulshoff Pol; René S Kahn Journal: Hum Brain Mapp Date: 2009-11 Impact factor: 5.038