Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways

Major depressive disorder (MDD) is a severe psychiatric disorder with a lifetime prevalence of about 15%.1 The importance of the genetic component is well accepted,2 but the mode of inheritance is complex and non-Mendelian. A line of evidence suggests the involvement of serotonin and dopamine neurotransmitters in the pathophysiology of depression. In the present study, 102 unipolar MDD patients and 172 healthy controls were genotyped for polymorphisms in four serotonergic and three dopaminergic candidate genes [tryptophan hydroxylase (TPH), serotonin receptor 2A (HTR2A), serotonin receptor 2C (HTR2C), serotonin transporter promoter region (5-HTTLPR), dopamine receptor D4 (DRD4), dopamine transporter (DAT1) and catechol-O-methyl transferase (COMT)]. There were no statistical differences between MDD patients and healthy controls in the genotypic and allelic distribution of all polymorphisms investigated. Thus, our study does not support a major role for these polymorphisms in contributing to susceptibility to MDD, although it does not preclude minor effects.

[1]  X Li,et al.  Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. , 1992, Genomics.

[2]  M. Dean,et al.  Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism. , 1992, American journal of human genetics.

[3]  K. Lesch,et al.  Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region , 1996, Science.

[4]  E. Paykel,et al.  No association of the tryptophan hydroxylase gene with bipolar affective disorder, unipolar affective disorder, or suicidal behaviour in major affective disorder. , 1998, American journal of medical genetics.

[5]  M. Jakovljevič,et al.  Analysis of the tyrosine hydroxylase and dopamine D4 receptor genes in a Croatian sample of bipolar I and unipolar patients. , 1997, American journal of medical genetics.

[6]  R Kucherlapati,et al.  Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. , 1996, American journal of medical genetics.

[7]  Kevin S. Chen,et al.  Serotonin2A receptor gene polymorphism in mood disorders , 1997, Biological Psychiatry.

[8]  R. Murray,et al.  A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. , 1996, Molecular psychiatry.

[9]  J. Macher,et al.  Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders. , 1998, American journal of medical genetics.

[10]  J. Fink,et al.  An MspI polymorphism in the hyman serotonin receptor gene (HTR2): detection by DGGE and RFLP analysis. , 1992, Human molecular genetics.

[11]  S. Nanko,et al.  Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder , 1997, Molecular Psychiatry.

[12]  N. Craddock,et al.  Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT) , 1997, Molecular Psychiatry.

[13]  F. Bloom,et al.  Psychopharmacology: The Fourth Generation of Progress , 1995 .

[14]  D. Goldman,et al.  Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C). , 1995, Genomics.

[15]  K. Ohara,et al.  Low activity allele of catechol‐o‐methyltransferase gene and Japanese unipolar depression , 1998, Neuroreport.

[16]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[17]  S. Kanba,et al.  Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders. , 1996, Journal of affective disorders.

[18]  Francois Mai,et al.  Synopsis of Psychiatry. , 1992 .

[19]  K K Kidd,et al.  A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. , 1993, Human molecular genetics.

[20]  N. Martin,et al.  Sources of individual differences in depressive symptoms: analysis of two samples of twins and their families. , 1994, The American journal of psychiatry.

[21]  M. Owen,et al.  Association studies in psychiatric genetics , 1997, Molecular Psychiatry.

[22]  D. Easton,et al.  Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders. , 1998, American journal of medical genetics.