The Nature of the Familial Risk for Psychosis in Bipolar Disorder.

Background And Hypothesis: To clarify whether the familial liability to psychosis associated with bipolar disorder (BD) is nonspecific or has a greater effect on risk for psychosis in cases with prominent mood symptoms and/or a remitting course.

Study Design: We examined, in 984 809 offspring raised in intact families in Sweden, born 1980-1996 and followed-up through 2018, by multivariable Cox proportional hazards regression, risk in offspring of parents with BD for 7 psychotic disorders: Psychotic MD (PMD), psychotic BD (PBD), schizoaffective disorder (SAD), acute psychoses, psychosis NOS, delusional disorder (DD) and schizophrenia (SZ). Diagnoses were obtained from national registers.

Study Results: In the offspring of BD parents, the hazard ratios (HR) for these 7 disorders formed an inverted U-shaped curve, rising from 2.98 for PMD, to peak at 4.49 for PBD and 5.25 for SAD, and then declining to a HR of 3.48 for acute psychoses and 3.22 for psychosis NOS, to a low of 2.19 for DD and 2.33 for SZ. A similar pattern of risks was seen in offspring of mothers and fathers affected with BD and in offspring predicted from age at onset in their BD parent.

Conclusions: The BD-associated risk for psychosis impacts most strongly on mood disorders, moderately on episodic psychotic syndromes, and least on chronic psychotic disorders. These results support prior clinical studies suggesting a qualitative difference in the familial substrate for psychosis occurring in BD and SZ.