Linkage analysis of manic depression in an Irish family using H-ras 1 and INS DNA markers.

Linkage analysis of manic depression in an Irish family using H-ras 1 and INS DNA markers Manic depression (bipolar affective disorder) is one of the major psychiatric illnesses.It is distinguished from unipolar major depression by the occurrence of manic episodes, symptoms of which show a variable combination of heightened and expansive mood, restlessness, irritability, pressure of speech, disinhibition, increased energy, and grandiose ideas or delusions.It has a lifetime risk of slightly less than 1% in most populations studied.A large genetic component has been shown using twin and adoption studies.Egeland et all have shown linkage between the manic depressive phenotype in one North American pedigree and two polymorphic DNA markers on the tip of the short arm of chromosome 11.Other studies2 ' have failed to show this linkage in Icelandic and other North American pedigrees.We have ruled out tight linkage between these DNA markers and the manic depressive phenotype, assuming that the disorder is segregating as an autosomal dominant trait in a large Irish pedigree.A single, unilateral source of the manic depression is likely but cannot be proven. The diagnoses were based on the Research Diagnostic Criteria of Spitzer et al,4 compiled using a combination of interviews, a review of the case notes, and the Schizophrenia and Affective Disorders Schedule-Lifetime Version (SADS-L).All cases were of bipolar affective disorder, apart from one case of unipolar depression.Of the unaffected subjects only those over the age of 55 were used to minimise the risk of false negative phenotype assignment.The pedigree is shown in the figure.DNA samples from members of the pedigree were