Ullamari Pesonen

Two naturally occurring amino acid substitutions of the 5-HT2A receptor: Similar prevalence in patients with seasonal affective disorder and controls

We screened the 5-HT2A receptor gene coding region in 50 patients with seasonal affective disorder (SAD) using a single strand conformational polymorphism analysis and estimated the frequencies of two synonymous and two non-synonymous substitutions we detected in 70 Centre dEtude du Polymorphism Humain (CEPH) population controls and 62 normal controls. Both of the amino acid substitutions: Ala447-Val447 and His452-Tyr452, were located within the cytoplasmic. C-terminal tail of the receptor. Rarer allele frequencies in CEPH were 0.7% and 9.3% for Val447 and Tyr452, respectively. Allele frequencies of all four polymorphisms, including the two amino acid substitutions, were not significantly different in SAD patients as compared to CEPH and normal controls. Lack of association of Val447 and Tyr452 to SAD is consistent with observations showing normal 5-HT2A receptor Ca2+ response in platelets with this disorder, however, the two 5-HT2A amino acid substitutions may lead to differences in behavioral phenotypes.

Mutation screening of the 5-hydroxytryptamine7 receptor gene among Finnish alcoholics and controls

Impaired central serotonin neurotransmission has been associated with increased aggression, impaired impulse control and diurnal activity rhythm disturbances among humans. Neuroanatomic distribution and pharmacological properties of the serotonin 5-HT7 receptor suggest that it may play a role in psychiatric disorders and in circadian rhythm regulation. In this study a point mutation causing proline279 --> leucine amino acid substitution in the 5-hydroxytryptamine7 (5-HT7) receptor gene was discovered. This 5-HT7Leu279 variant was observed in six of 825 individuals, all of whom are heterozygous for the substitution. Three of them are alcoholic offenders (3/255), two are relatives of an offender without the 5-HT7Leu279 allele (2/255) and one is a healthy control without any psychiatric diagnosis (1/248). The allele frequency of the 5-HT7Leu279 variant is 0.004 (6/758) among Finns. Although the 5-HT7Leu279 variant is approximately three times more common among alcoholic offenders than among healthy controls, it is not significantly associated with alcoholism or impulsivity in the present study. The 5-HT7Leu279 allele may, however, be a predisposing allele in a subgroup of alcoholic offenders with multiple behavioral problems.

Molecular genetics of impaired impulse control and early onset alcoholism

s DlOL PSYCUIATRY 1996;39:500-666 561 pcl5on:aIHy, distinguishing four dimensions of temperament that are 50% heritable and indeplmdent of one another. This genetic architecture for pcrsomdil) has now been independently replicmcd also. In tum, PcIllon· ailly was n:lated to sllsceptibility to a!c:oholism and to underlying variation in monoaminergic neurotronsmission. Recent results predicting susceptibility to alcoholism and other psychopathology wlll be described in terms of the non-llneardyn.amics of personality development, which is relevant to both hum:an and .animal research. Finally, current findings about Ihe neurobiological correlates of personality in the general popu· 13tion and in a alcoholics will be summarized. 212. MOLECULAR GENETICS OF IMPAIRED IMPULSE CONTROL AND EARLY ONSET