Genetic polymorphisms in the serotonergic system and symptom clusters of major depressive disorder

• Published in: Journal of Affective Disorders Vol. 135; no. 1-3; pp. 374 - 376
• Main Authors: Kamata, Mitsuhiro, Suzuki, Akihito, Yoshida, Keizo, Takahashi, Hitoshi, Higuchi, Hisashi, Otani, Koichi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.12.2011; Elsevier BV; Elsevier
• Subjects: 5HT2A; Adult; Adult and adolescent clinical studies; Alleles; Biological and medical sciences; Carrier Proteins; Carrier Proteins - genetics; Depression; Depressive Disorder; Depressive Disorder - genetics; Depressive Disorder, Major; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - genetics; Depressive Disorder, Major - psychology; Depressive personality disorders; Female; Genetic polymorphism; Genotype; Humans; Japan; MADRS; Major depressive disorder; Male; Medical sciences; Middle Aged; Mood disorders; Polymorphism, Genetic; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2A - genetics; Serotonin Plasma Membrane Transport Proteins; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin receptors; Serotonin transporter; Symptoms; Tryptophan; Tryptophan Hydroxylase; Tryptophan Hydroxylase - genetics; Tryptophan hydroxylase; MADRS; Serotonin transporter; 5HT2A; Major depressive disorder; Genetic polymorphism; Mood disorder; Enzyme; Depression; Genetic determinism; Symptomatology; Tryptophan 5-monooxygenase; Genetics; Oxidoreductases; Polymorphism
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2011.08.027

It has been suggested that the symptoms of major depressive disorder (MDD) are composed of some clusters, which are linked to distinct genetic mechanisms. The purpose of this study was to examine the associations of genetic polymorphisms in the serotonergic system with three factors of the Montgomery-Åsberg Depression Rating Scale (MADRS), i.e., dysphoria, retardation, and vegetative symptoms. The subjects were 132 Japanese patients of MDD. The genotypes of tryptophan hydroxylase 218A/C, serotonin transporter gene-linked polymorphic region (5HTTLPR), and 5HT2A receptor -1438G/A polymorphisms were determined by PCR methods. Statistical analyses were performed by the multiple regression analysis. The A allele of 5HT2A polymorphism was associated with higher vegetative scores (p=0.001) and total MADRS scores (p=0.005), while the S allele of 5HTTLPR was related to higher dysphoric scores (p=0.012). The tryptophan hydroxylase genotype was not related to any factor scores or total MADRS scores. The sample size was relatively small, and the subjects were composed of Japanese only. This study suggests that the genetic polymorphisms in 5HT2A receptor and serotonin transporter are linked to discrete symptom clusters of MDD.