Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression

被引:124
作者
Frodl, T
Meisenzahl, EM
Zill, P
Baghai, T
Rujescu, D
Leinsinger, G
Bottlender, R
Schüle, C
Zwanzger, P
Engel, RR
Rupprecht, R
Bondy, B
Reiser, M
Möller, HJ
机构
[1] Univ Munich, Dept Psychiat, D-80336 Munich, Germany
[2] Univ Munich, Dept Radiol, D-80336 Munich, Germany
关键词
D O I
10.1001/archpsyc.61.2.177
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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.
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页码:177 / 183
页数:7
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