title: Tryptophan hydroxylase gene and major psychoses.
abstract: Disturbances of the serotoninergic neurotransmitter system have been implicated in the pathogenesis of mood disorders. The tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, has been recently reported to be associated with bipolar disorder. In this study, we investigated TPH A218C gene variants in a sample of subjects affected by major psychoses. One thousand four hundred and twenty-four inpatients affected by bipolar (n=627), major depressive (n=511), schizophrenic (n=210), delusional (n=48) disorder and psychotic disorder not otherwise specified (n=27) (DSM-IV) were included; all patients and 380 controls were typed for the TPH variants using PCR techniques. A sub-sample of 963 patients was assessed using the Operational Criteria for Psychotic Illness (OPCRIT). TPH variants were not associated with major psychoses, but a trend was observed toward an excess of TPH*A/A in bipolar disorder. The analysis of symptomatology factors did not show any significant difference either; however, a trend was observed for males with the TPH*A genotype to have lower depressive symptoms compared with TPH*C subjects. Possible stratification factors such as current age and age of onset did not affect the observed results. TPH A218C variants are not, therefore, a major liability factor for the symptoms of major psychoses to have in the present sample. TPH*A containing variants may be a protective factor for depressive symptoms among male subjects with mood disorders or for a subtype of mood disorders characterized by a mainly manic form of symptomatology.
authors.affiliation: Department of Psychiatry, Vita-Salute University, San Raffaele Institute, Milan, Italy. serreti.alessandro@hsr.it
authors.forename: A
authors.initials: A
authors.lastname: Serretti
authors.forename: R
authors.initials: R
authors.lastname: Lilli
authors.forename: C
authors.initials: C
authors.lastname: Lorenzi
authors.forename: E
authors.initials: E
authors.lastname: Lattuada
authors.forename: C
authors.initials: C
authors.lastname: Cusin
authors.forename: E
authors.initials: E
authors.lastname: Smeraldi
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011618:Psychotic Disorders / Q000201:enzymology* / Q000235:genetics*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012563:Schizophrenia, Paranoid / Q000201:enzymology / Q000235:genetics; D012701:Serotonin / Q000096:biosynthesis; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D014365:Tryptophan Hydroxylase; C015068:1-(3-chlorophenyl)piperazine