TPH gene polymorphism and aging: Indication of combined effect on the predisposition to violent suicide

Findings relating serotonin to suicidal behavior suggest the role of genes for tryptophan hydroxylase (TPH) in the genetic substrate of this disorder. Association of Tph1 gene and suicidality, despite considerable research efforts, remains controversial. Polymorphism A218C in intron 7 of Tph1 gene was studied in violent suicide victims (N = 247) and controls (N = 320) of Slavic (Croatian) origin, with specific consideration of the influence of subjects' age. The frequency of, allegedly less active, CC genotype was increased in older (above 65 years) victims as compared to controls (P = 0.0126 and 0.0008, for comparison with age‐specific and integral control samples, respectively), while there were no differences between victims under 65 years and controls. Excess of the CC genotype in elderly victims of violent suicide points to the possible combined effect of the respective genetic factor and physiological changes during aging on the predisposition to this disorder. © 2006 Wiley‐Liss, Inc.

[1]  J. Škavić,et al.  Variability of the tryptophan hydroxylase gene: Study in victims of violent suicide , 2005, Psychiatry Research.

[2]  David A. Schwartz,et al.  Loss-of-Function Mutation in Tryptophan Hydroxylase-2 Identified in Unipolar Major Depression , 2005, Neuron.

[3]  H. Möller,et al.  Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase Isoform (TPH2) gene in suicide victims , 2004, Biological Psychiatry.

[4]  Ajit K. Shah,et al.  Psychotropic Prescriptions and Elderly Suicide Rates , 2004, Medicine, science, and the law.

[5]  A. Mitra,et al.  Effect of reactive oxygen species on the metabolism of tryptophan in rat brain: Influence of age , 2004, Molecular and Cellular Biochemistry.

[6]  P. Patel,et al.  Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal gland , 2004, Biological Psychiatry.

[7]  J. Škavić,et al.  Intronic polymorphism of tryptophan hydroxylase and serotonin transporter: indication for combined effect in predisposition to suicide , 2004, Journal of Neural Transmission.

[8]  P. Blenkiron.  The timing of deliberate self harm behaviour , 2003, Irish Journal of Psychological Medicine.

[9]  J. Mann.  Neurobiology of suicidal behaviour , 2003, Nature Reviews Neuroscience.

[10]  Michael Bader,et al.  Synthesis of Serotonin by a Second Tryptophan Hydroxylase Isoform , 2003, Science.

[11]  P. Linkowski,et al.  Molecular genetics in the analysis of suicide , 2003, Annals of medicine.

[12]  B. Müller-Oerlinghausen,et al.  Concretism in Biological Suicide Research - Are We Eating the Menu Instead of the Meal? , 2002, Pharmacopsychiatry.

[13]  D. Trichopoulos,et al.  A Role of Sunshine in the Triggering of Suicide , 2002, Epidemiology.

[14]  H. Ono,et al.  Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls , 2002, Molecular Psychiatry.

[15]  A. Roy.  Genetic influences on suicide risk , 2001, Clinical Neuroscience Research.

[16]  M. Åsberg,et al.  Excess Tryptophan Hydroxylase 17 779C Allele in Surviving Cotwins of Monozygotic Twin Suicide Victims , 2001, Neuropsychobiology.

[17]  J. Lonnqvist,et al.  Attempted and completed suicide in older subjects: results from the WHO/EURO multicentre study of suicidal behaviour , 2001, International journal of geriatric psychiatry.

[18]  M. Alda,et al.  TPH and suicidal behavior: a study in suicide completers , 2001, Molecular Psychiatry.

[19]  H. Ono,et al.  Tryptophan hydroxylase gene polymorphisms are not associated with suicide. , 2000, American journal of medical genetics.

[20]  M. Palkovits,et al.  Tryptophan hydroxylase gene 218A/C polymorphism is not associated with depressed suicide. , 2000, The international journal of neuropsychopharmacology.

[21]  A. Mitra,et al.  Effect of aging on tryptophan hydroxylase in rat brain: implications on serotonin level. , 2000, Drug metabolism and disposition: the biological fate of chemicals.

[22]  W. McMahon,et al.  Tryptophan hydroxylase polymorphisms in suicide victims , 2000, Psychiatric genetics.

[23]  K. Stefanisko,et al.  Sequence, splice site and population frequency distribution analyses of the polymorphic human tryptophan hydroxylase intron 7. , 1997, Brain research. Molecular brain research.

[24]  G. Hochbaum.  Suicide by the elderly. , 1992, American journal of public health.

[25]  J. Launay,et al.  Complete coding sequence of human tryptophan hydroxylase. , 1990, Nucleic acids research.

[26]  F. Reinoso-suárez,et al.  Changes in biogenic amines in rat hippocampus during development and aging. , 1988, Life sciences.

[27]  D. Sparks,et al.  Age-associated alteration of serotonergic synaptic neurochemistry in rat rostral hypothalamus , 1985, Neurobiology of Aging.

[28]  M. Åsberg,et al.  5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? , 1976, Archives of general psychiatry.

[29]  N. S. Patel.  Attempted and completed suicide. , 1974, Medicine, science, and the law.