Bipolar manic-depressive psychoses: Results of a genetic investigation

Summary Ninety-five patients with bipolar manicdepressive disorders were followed from 1959 to 1975, and their first-degree relatives (N=617) were studied. In the search for heterogeneity of bipolar illness the patients were subclassified according to various criteria: sex, age at onset, number of episodes, and longitudinal syndrome subtypes (Dm, MD, Md), and the genetic findings were used as an external criterion.The first-degree relatives of female probands showed a higher morbidity risk for psychiatric disorders than the relatives of male probands, and the highest morbidity risk was found in the female relatives of female probands. Early onset and late-onset patients did not differ from a genetic point of view. Patients with ten episodes or more showed slightly higher family morbidity than those with less than ten episodes.The three subtypes of bipolar disorders preponderantly depressed (Dm), nuclear type (MD), and preponderantly manic (Md), showed significant genetic differences. The families of type Dm had the highest morbidity, and families of type Md, the lowest! The type MD took an intermediate position. The results are surprising and not compatible with current hypotheses of multifactorial heredity assuming a continuum from depression to mania with distinct thresholds for the manifestation of unipolar depression, bipolar psychosis, and pure mania. The findings also do not suggest the existence of a drug-induced hypomania.Father-son transmission was frequent, and this fact excludes a substantial amount of X-chromosomal inheritance.Parents, siblings, and children exhibited roughly the same morbidity risk. If a proband had an affected parent, the morbidity risk for his siblings and children was nearly twice as high as without such a parent (38% vs 21%). The analysis of the intrafamilial distribution of diagnoses supported the assumption that neurotic depression belongs to the true spectrum of affective psychoses.