Recent Cohort Study Assesses Genetic Relationships Between Psychotic Disorders
From a genetic perspective, delusional disorder (DD), acute psychoses (AP), psychosis otherwise not specified (PNOS), and schizoaffective disorder (SAD) do not appear to be subtypes of schizophrenia (SZ), bipolar disorder (BD), or major depression (MD), according to a cohort study published in JAMA Psychiatry.
“For DD, AP, and SAD, repeated debates have arisen as to whether they are distinct clinical entities or subforms of SZ, BD, or MD,” wrote Kenneth S. Kendler, MD, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, and study coauthors. “Building on an earlier report of a subset of these diagnoses, we here seek to address more definitively than has hitherto been possible the genetic relationship between DD, AP, SAD, and PNOS and the classical syndromes of SZ, BD, and MD.”
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To do so, the researchers assessed the levels of family genetic risk scores (FGRS) for SZ, BD, and MD in individuals with DD, AP, PNOS, and SAD diagnoses in a cohort of all individuals born in Sweden to Swedish-born parents between 1950 and 2000.
Within the cohort, 667,012 patients had MD, 58,385 had BD, 17,465 had SZ, 16,315 had AP, 27,127 had PNOS, 7597 had SAD, and 11,560 had DD. The researchers calculated the FGRS using morbidity risks observed in first-through-fifth degree relatives while accounting for cohabitation effects and created 2-dimensional “genetic maps” to depict the corresponding mean genetic risks for each disorder.
Researchers found that the genetic map positions of DD, AP, PNOS, and SAD were distinct from the positions of SZ, BD, and MD. SAD was the only disorder that showed high genetic risks for both SZ and BD, but was clearly distinct from psychotic BD. The position of DD showed half of the genetic risk for SZ compared with SZ cases and had similar levels of BD and MD risks. The genetic profiles of AP and PNOS were similar, with levels of SZ FGRS that mirrored those of DD, but higher risk for MD and BD.
The authors also subdivided psychoses by psychiatric and social outcomes, which produced minimal effects on the DD genetic profile, moderate effects on the AP and PNOS genetic profiles, and large effects on the SAD genetic profile. Good social outcomes were associated with decreased SZ FGRS and increased BD FGRS, while good psychiatric outcomes were associated with decreased risk for both disorders.
The authors acknowledged several limitations of their research methods, which relied heavily on the quality of the diagnoses in the Swedish registries. Still, the researchers emphasized how clarifying the genetic profiles of DD, PNOS, AP, and SAD may improve broader understanding of psychotic disorders. “While generating much less clinical and research attention than SZ, BD, and MD, the syndromes of DD, AP, PNOS, and SAD likely have much to teach about the relationship between dimensions of genetic risk and the clinical presentation and course of psychotic illness,” they concluded.