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.
Frisch
A
A
Laboratory of Biochemical Genetics, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
Postilnick
D
D
Rockah
R
R
Michaelovsky
E
E
Postilnick
S
S
Birman
E
E
Laor
N
N
Rauchverger
B
B
Kreinin
A
A
Poyurovsky
M
M
Schneidman
M
M
Modai
I
I
Weizman
R
R
D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003866:Depressive Disorder / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005060:Europe / Q000208:ethnology; D005260:Female; D005838:Genotype; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D011985:Receptors, Serotonin / Q000235:genetics; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D014365:Tryptophan Hydroxylase / Q000235:genetics
D002352:Carrier Proteins; C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D002394:Catechol O-Methyltransferase; D004298:Dopamine