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Updated: Jun 13, 2026
05:42
The Forced Swim Test as a Model of Depressive-like Behavior
Published on: March 2, 2015
Serotonin transporter gene polymorphisms and treatment-resistant depression
Cristian Bonvicini1, Alessandra Minelli, Catia Scassellati
1Genetic Unit, IRCCS San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
Summary
The L(A)L(A) haplotype of the serotonin transporter gene (SLC6A4) may protect against treatment-resistant depression (TRD). This finding suggests lower serotonin transporter transcription alleles are linked to depression resistance.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Major Depressive Disorder (MDD) is a leading cause of disability globally.
- Treatment-resistant depression (TRD) affects about 15% of MDD patients.
- Serotonin transporter gene (SLC6A4) polymorphisms are implicated in MDD, but their role in TRD is unclear.
Purpose of the Study:
- To investigate the association between SLC6A4 polymorphisms and the risk of TRD.
- To analyze the 5-HTTLPR (L/S) polymorphism and the rs25531 (A/G) single nucleotide substitution.
- To examine functional haplotype combinations within the SLC6A4 gene.
Main Methods:
- Genotyping of 310 TRD patients and 284 healthy controls.
- Sequencing analysis to determine the precise location of rs25531 relative to 5-HTTLPR.
- Statistical analysis of allele and haplotype frequencies.
Main Results:
- Significant differences in 5-HTTLPR allele (p=0.04) and L allele carrier (p<0.05) frequencies between groups.
- The L(A)L(A) homozygote haplotype was significantly more prevalent in controls (p=0.01, OR=0.64).
- rs25531 was located immediately outside the 5-HTTLPR segment.
Conclusions:
- The L(A)L(A) haplotype demonstrates a protective effect against TRD.
- This supports the hypothesis linking lower serotonin transporter transcription alleles to depression resistance mechanisms.
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