Serotonergic genes and suicidality
by
Du L, Faludi G, Palkovits M, Bakish D, Hrdina PD.
Institute of Mental Health Research at
Royal Ottawa Hospital and University of Ottawa,
Ontario, Canada,.
ldu@rohcg.on.ca
Crisis 2001;22(2):54-60


ABSTRACT

Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of depressive illness and suicidal behavior. Studies have shown that the number of brain and platelet serotonin transporter binding sites are reduced in patients with depression and in suicide victims, and that the density of 5-HT2A receptors is increased in brain regions of depressed in suicide victims and in platelets of depressed suicidal patients. Genes that code for proteins, such as tryptophan hydroxylase, 5-HT transporter, and 5-HT2A receptor, involved in regulating serotonergic neurotransmission, have thus been major candidate genes for association studies of suicide and suicidal behavior. Recent studies by our group and by others have shown that genetic variations in the serotonin-system-related genes might be associated with suicidal ideation and completed suicide. We have shown that the 102 C allele in 5-HT2A receptor gene was significantly associated with suicidal ideation (chi2 = 8.5. p < .005) in depressed patients. Patients with a 102 C/C genotype had a significantly higher mean HAMD item #3 score (indication of suicidal ideation) than T/C or T/7 genotype patients. Our results suggest that the 102T/C polymorphism in 5-HT2A receptor gene is primarily associated with suicidal ideation in patients with major depression and not with depression itself. We also found that the 5-HT transporter gene S/L polymorphism was significantly associated with completed suicide. The frequency of the L/L genotype in depressed suicide victims was almost double of that found in control group (48.6% vs. 26.2%). The odds ratio for the L allele was 2.1 (95% CI 1.2-3.7). The association between polymorphism in serotonergic genes and suicidality supports the hypothesis that genetic factors can modulate suicide risk by influencing serotonergic activity.
CRF
LHPA
5-HT1a
5-HT2a
5-HT2c
Serotonin
Anhedonia
Anticonvulsants
Essential fatty acids
Evolution and emotion
The evolution of suicide
Shakespearean suicides
Alcohol, suicide and serotonin
Speech, depression and suicide
Serotonergic genes and suicide
How stress triggers depression
Suicide, serotonin and dopamine
Suicide rates in the antidepressant era
Antidepressants and suicide risk in children


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