Anticipation with phenotypic variation in three father-son pairs with affective disorder: a case series.

Anticipation is a phenomenon in which successive generations within a family experience an earlier age of onset and a more severe form of a given illness. It has been observed in various neurological and psychiatric conditions, including bipolar disorder. The molecular basis of anticipation involves trinucleotide repeat expansions in genes, but this has not been conclusively demonstrated in bipolar disorder. The histories of 3 father-son pairs are presented. In each pair, the son presented with an early-onset bipolar disorder, and the father developed severe depression after the age of 50 years. No female relatives were affected. The implications of these observations are discussed. Genetic, epigenetic, and environmental mechanisms that may have contributed to this phenomenon are briefly described. The study of such patients may throw light on the "extended phenotype" of mood disorders, as well as the genetic and epigenetic mechanisms involved in the phenomena of anticipation and phenotypic variation.

A 5-year course of predominantly obsessive vs. mixed subtypes of obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is considered a heterogeneous disorder. One of the traditional approaches to subtype OCD is based on the predominance of obsessions, compulsions or both. Some studies suggest that the "predominantly obsessive" subtype of OCD may have poor outcome, whereas few other studies suggest that "mixed" OCD is associated with poor outcome. Therefore, it is not clear if the long-term course of "predominantly obsessive" subjects is different from those with "mixed" OCD. In the establishment of diagnostic validity of psychiatric conditions, differential course is an important validating factor. AIM: This study compares the 5-6 year course of the "predominantly obsessive" subtype with that of the "mixed" subtype of OCD with the objective of determining if the course of OCD differs according to subtypes and whether course could be a validating factor for subtyping OCD based on predominance of obsessions, compulsions or both. SETTING AND DESIGN: Tertiary hospital, institutional setting. The study has a retrospective cohort design. MATERIALS AND METHODS: Fifty-four subjects with "predominantly obsessions" and an equal number of the "mixed" subtype of OCD were recruited from the database of a specialty OCD clinic of a major psychiatric hospital. They were followed up after 5-6 years. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) checklist and severity rating scale was used for assessing OCD. The course of OCD was determined according to predefined criteria. STATISTICS: The Chi-square/Fisher's exact test and the independent samples "t" test were used to compare categorical and continuous variables, respectively. Correlations were tested using the Pearson's correlation analysis. RESULTS: Thirty-eight "predominantly obsessive" (70%) and 39 "mixed" (72%) OCD subjects could be traced and evaluated. The course of illness was similar in the two subtypes. A majority of the sample (72%) did not have clinical OCD at follow-up. CONCLUSIONS: "Predominantly obsessive" subjects have a course similar to those with "mixed" OCD. Clinically, it is reassuring to know that obsessive subjects do not have an unfavorable course as was suggested by some previous studies. In this sample, course did not validate the subtyping method employed, but it would be premature to conclude that the subtyping method employed is incorrect based on the course alone. Prospective study of the course in larger samples and neurobiological and family-genetic data may help further validation.