Advances towards the understanding of the aetiological mechanisms involved in mood disorders provide interesting yet diverse hypotheses and promising models. In this context, molecular genetics has now been widely incorporated into genetic epidemiological research in psychiatry. Affective disorders and, in particular, bipolar affective disorder have been examined in many molecular genetic studies which have covered a large part of the genome; specific hypotheses such as mutations have also been studied. Most recent studies indicate that several chromosomal regions may be involved in the aetiology of bipolar affective disorder. Other studies have reported the presence of anticipation in bipolar affective disorder (1,2) and in unipolar affective disorder.(3) This phenomenon describes the increase in clinical severity and decrease in age of onset observed in successive generations. This mode of transmission correlates with the presence of specific mutations (trinucleotide repeat sequences) and may represent a genetic factor involved in the transmission of the disorder. (45) Large multicentre and multidisciplinary projects are currently under way in Europe and the United States and hopefully will improve our understanding of the genetic factors involved in affective disorders. In parallel to these new developments in molecular genetics, the classical genetic epidemiology, represented by twin, adoption, and family studies, has provided additional evidence in favour of the genetic hypothesis in mood disorders. Moreover, these methods have been improved through models to test the gene-environment interactions.

In addition to genetic approaches, psychiatric research has focused on the role of psychosocial factors in the emergence of mood disorders. In this approach, psychosocial factors refer to the patient's social life context as well as to personality dimensions. Abnormalities in social behaviour such as impairment in social relationships^7, and 8) and dysfunctional cognitions(9) have been observed during episodes of affective disorders, and implicated in their aetiology. Further, gender and socio-economic status emerged as having a possible impact on the development of affective disorders. Finally, the onset and outcome of affective disorders could also be explained by interactions between the social life context and the individual's temperament and personality. The importance of temperament and personality characteristics in the aetiology of depression has been emphasized in various theories, although disagreement exists with regard to terminology and the aetiology of the characteristics themselves.

While significant advances have been made in these two major fields of research, it appears that integrative models, taking into account the interactions between biological (genetic) factors and social (psychosocial environment) variables, offer the most reliable way to approach the complex mechanisms involved in the aetiology and outcome of mood disorders. This chapter will review some of the most promising genetic and psychosocial hypotheses in mood disorders that can be integrated in interactive models.

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