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Arch Gen Psychiatry. 2004 Feb;61(2):177-83.

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

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  • 1Department of Psychiatry, Ludwig-Maximilians-University of Munich, Munich, Germany.

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.

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.

[PubMed - indexed for MEDLINE]
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