Suicidal behavior: relationship between phenotype and serotonergic genotype.
The basis of suicidal behavior (SB) is complex and multifactorial. Numerous risk factors have been identified. Epidemiological genetics studies (family studies, twin studies, adoption studies) suggest that there is a genetic basis to SB and that this genetic basis is specific and independent from the genetic factors implicated in predisposition to psychiatric disorders associated with SB (bipolar disorder, schizophrenia, alcoholism). Recently, new molecular genetics tools have been designed to identify the genetic factors that predispose certain individuals to disorders of complex etiology. Biological psychiatry studies have suggested that the physiopathology of SB involves dysfunctioning of the serotonin system. The first genetic association studies tested candidate genes encoding proteins involved in serotonin metabolism. The results of these studies suggest that the gene coding for the limiting enzyme in the synthesis of serotonin, tryptophan hydroxylase (TPH), and the gene encoding the serotonin transporter are involved in predisposition to SB. Furthermore, it is likely that these genes interact with each other and with environmental factors (early) and that they have different phenotypic consequences. One of the main aims of studies currently underway is to identify the precise phenotypes associated with genes that predispose to SB or intermediate phenotypes (impulsivity, inability to control anger, etc.).
Courtet
Philippe
P
Service de Psychologie Médicale and Psychiatrie, Hôpital Lapeyronie, Montpellier, France. p-courtet@chu-montpellier.fr
Jollant
Fabrice
F
Castelnau
Didier
D
Buresi
Catherine
C
Malafosse
Alain
A
D004644:Emotions / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005826:Genetics, Medical / Q000379:methods; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013405:Suicide; D013406:Suicide, Attempted; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014365:Tryptophan Hydroxylase