A tryptophan hydroxylase gene marker
for suicidality and alcoholism

by
Nielsen DA, Virkkunen M, Lappalainen J, Eggert M,
Brown GL, Long JC, Goldman D, Linnoila M
Section of Molecular Genetics,
National Institute on Alcohol Abuse and Alcoholism,
National Institutes of Health,
Bethesda, MD, USA.
nielsen@helix.nih.gov
Arch Gen Psychiatry 1998 Jul; 55(7):593-602


ABSTRACT

BACKGROUND: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Low turnover rate of this monoamine neurotransmitter is associated with impaired impulse control. We previously reported that, in Finns, TPH genotype was associated with suicidality, a pathophysiological mechanism that may involve impaired impulse control. METHODS: Association and sib-pair linkage analyses of a polymorphism in intron 7 of the TPH gene with suicidality, alcoholism, and the Karolinska Scales of Personality were conducted in 804 Finnish alcoholic offenders, controls, and their relatives, in a sample that included 369 sib pairs. RESULTS: The association of the TPH 17 779C (L) allele to suicidality in impulsive offenders reported previously was replicated in a new group of Finnish offenders (P=.001, n=122). The intron 7 variant in the TPH gene showed significant evidence for linkage to suicidality (P=.006 in unaffected sib pairs), severe suicide attempts (P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002). CONCLUSIONS: The status of the TPH A779C allele as a marker for suicidality was replicated and linkage with alcoholism and Karolinska Scales of Personality socialization score was also observed. A functional variant(s) in or close to the TPH gene may predispose individuals to suicidality and other behaviors thought to be influenced by serotonin.
MTIP
LHPA
Alcohol
Tryptophan
Ketoconazole
SSRI suicides?
Adenylyl cyclase
CRH-R antagonists
SSRIs for alcoholics
Tryptophan depletion
Ethyl alcohol and suicide
Tryptophan plus fluoxetine
Tryptophan and alcoholism
Suicide: biochemical pathways
Speech, depression and suicide
Suicide, serotonin and dopamine
Tryptophan hydroxylase and anger
Suicide, serotonin and the HPA axis
Serotonin 1A-autoreceptors and suicide
Alcohol, nicotine and the opioid system
Ethyl alcohol and beta-endorphin release
Alcohol, alcoholism and GABA(A) receptors
Alcohol-induced euphoria: exclusion of serotonin


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