Association between serotonin transporter polymorphisms (5-HTTLPR) and the MADRS Dysphoria, Retardation, and Vegetative Subscale scores in the treatment of depression

Hitoshi Takahashi,¹ Hisashi Higuchi,² Kazuhiro Sato,³ Mitsuhiro Kamata,³ Keizo Yoshida,⁴ Katsuji Nishimura<sup>1

1</sup>Department of Neuropsychiatry, Tokyo Women’s Medical University School of Medicine, Shinjuku-ku, ²Suzuki Jikoh Hospital, Ome-shi, Tokyo, ³Akita Kaiseikai Hospital, Akita-shi, ⁴Health Care Promotion Division, DENSO Corporation, Kariya-shi, Aichi, Japan

Objective: We investigated the association between serotonin- or 5-hydroxytryptamine (5-HT)-related gene polymorphisms and response to antidepressant treatment in a specific symptom cluster of major depression by using the three-factor model of the Montgomery–Åsberg Depression Rating Scale (MADRS), ie, dysphoria (items of sadness, pessimistic thoughts, and suicidal thoughts), retardation (items of lassitude, inability to feel, apparent sadness, and concentration difficulties), and vegetative symptoms (items of reduced sleep, reduced appetite, and inner tension).
Methods: This study was an open-label and nonrandomized trial. A total of 160 patients with baseline MADRS scores of ≥21, who were treated with fluvoxamine or milnacipran for 6 weeks, were included in the statistical analysis. Polymorphisms within a 5-HT transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the second intron of the 5-HTT gene (5-HTTVNTR), and 5HT2A receptor (1438G/A) were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results: The 5-HTTLPR polymorphisms affected the MADRS score change in dysphoria, but not in retardation, vegetative, or total symptoms. Dysphoria scores significantly decreased in patients with the S/S genotype compared to those in patients with the short (S)/long (L) + L/L genotype. However, 5-HTTVNTR and 1438G/A polymorphisms were not significantly associated with the treatment response to any cluster of depressive symptoms. When a Bonferroni correction was made, however, our results did not reach the criteria for statistical significance.
Conclusion: The use of a single total depression rating scale may not be sufficient to accurately estimate the clinical response to antidepressants. Analyzing a subset of symptoms in psychological scales could be important when performing pharmacogenetic studies.

Keywords: serotonin transporter polymorphism, dysphoria score, antidepressants, MADRS