Substantial evidence supports a role for dysfunction of brain serotonergic (5-HT) systems in the pathogenesis of major affective disorder, both unipolar (recurrent major depression) and bipolar. 1 Modification of serotonergic neurotransmission is pivotally implicated in the mechanism of action of antidepressant drugs 2 and also in the action of mood stabilizing agents, particularly lithium carbonate. 3 Accordingly, genes that code for the multiple subtypes of serotonin receptors that have been cloned and are expressed in brain, 4 are strong candidates for a role in the genetic etiology of affective illness. We examined a structural variant of the serotonin 2C (5-HT2C) receptor gene (HTR2C) that gives rise to a cysteine to serine substitution in the N terminal extracellular domain of the receptor protein (cys23ser), 5 in 513 patients with recurrent major depression (MDD-R), 649 patients with bipolar (BP) affective disorder and 901 normal controls. The subjects were drawn from nine European countries participating in the European Collaborative Project on Affective Disorders. There was significant variation in the frequency of the HT2CR ser23 allele among the 10 population groups included in the sample (from 24.6% in Greek control subjects to 9.2% in Scots, 2 = 20.9, df 9, P = 0.01). Logistic regression analysis demonstrated that over and above this interpopulation variability, there was a significant excess of HT2CR ser23 allele carriers in patients compared to normal controls that was demonstrable for both the MDD ( 2 = 7.34, df 1, P = 0.006) and BP ( 2 = 5.45, df 1, P = 0.02) patients. These findings support a possible role for genetically based structural variation in 5-HT2C receptors in the pathogenesis of major affective disorder. Molecular Psychiatry (2001) 6, 579-585.It is widely accepted that the genetic basis of affective disorders, both unipolar (recurrent major depression) and bipolar (manic depressive illness) is complex and is likely to involve several genes and also environmental factors. 6,7 A principal aim of the European Collaborative Project on Affective Disorders (ECPAD) is to harness the statistical power potentially provided by the large numbers of subjects who can be recruited by the participating centers in order to elucidate the role of candidate genes and environmental factors in the pathogenesis of affective illness. 8 In the course of the project a very large sample has been recruited and clinically evaluated, with blood samples obtained for DNA extraction. The method of recruitment of patients has been described in detail by Souery et al 8 and is summarized below in the Methods section. Subjects were genotyped for the HT2CR cys23ser polymorphism in the participating laboratories according to a standardized protocol (see below). Clinical and genotype data were centralized in the ECPAD database in Brussels and were electronically transferred to BL and FM for statistical analysis. After removal of subjects whose geographical origin was unclear, whose genotype data were ambiguous or contrad...

For centuries, scientists are intrigued by the differences in personality between individuals. As early as in the ancient Greek civilization, people tried to formulate theories to systematize this diversity. With the increased interest in behavior genetics, personality was also considered a challenging phenotype. From the early start, studies suggested a heritable component in personality. After the successes of molecular genetic studies in unraveling the genetic basis of (mostly) monogenic diseases, the focus shifted towards complex traits, including psychiatric disorders. It was observed in several studies that personality measures differed between patients with psychiatric disorders and healthy controls. Therefore, normal personality was considered a viable endophenotype in the search for genes involved in psychiatric disorders such as affective disorders, ADHD and substance dependence. Genes that were to be found in studies on personality could be candidate genes for particular psychiatric disorders. In the course of time, however the study of genes for personality turned out to be at least as hard as the search for genes involved in other complex disorders. In this review, past studies, present problems and future directions concerning the study of personality genetics are discussed.

The aim of this study was to validate a zygosity questionnaire that can be administered over the telephone. Mothers of same-sexed twins of known zygosity and chronicity between 2 and 31 years of age were interviewed on a nine-item questionnaire. From the answers one unweighted and four weighted indices were computed. As single questions, the mother's opinion and the "two peas in a pod" question differentiated best between monozygotic and dizygotic twins. One independent well-trained observer assessed the zygosity based on the questionnaire and made the correct diagnosis in 96% of the cases. A weighted index of eight similarity questions yielded an accuracy of 98%. This study shows that the zygosity of same-sexed twins more than 2 years old and without gross physical malformation can reliably be determined by a telephone questionnaire with a high accuracy.

Cancer results from the expansion of cell clones that progressively lose control of proliferation, differentiation, and death, owing to accumulation of mutational events in genes that control the cell cycle and apoptosis. Nuclear protein p53 is thought to play a major role in malignancy, since it induces genes that determine apoptosis and cell-cycle arrest, interacts with proteins employed in DNA repair, and binds to DNA strand breaks. As expected, somatic mutations in p53 are found in a variety of human cancers. Mutations are predominantly inactivating, thus eliminating the "guardian of the genome" from the proliferating cells. Germ-line mutations