What Factors Predict Conversion from Bipolar Disorder to Schizophrenia?

The strongest predictors of conversion from bipolar disorder to schizophrenia are earlier years of birth, younger age at bipolar disorder onset, low genetic risk for bipolar disorder, and being unmarried at bipolar disorder onset, according to study results published in Schizophrenia Bulletin.

Previous research has established that both bipolar disorder and schizophrenia are associated with diagnostic instability, as diagnosis at first presentation can often change over the course of illness. Accordingly, investigators from Virginia Commonwealth University in the United States and Lund University in Sweden conducted a study to evaluate predictors of diagnostic conversion from bipolar disorder to schizophrenia and vice versa.

The investigators used data from national registers in Sweden to determine the frequency of bipolar disorder and schizophrenia conversion and whether these conversions could be predicted. Individuals born in Sweden to Swedish-born parents between 1950 and 1995 were evaluated for a first diagnosis of schizophrenia or bipolar disorder and for their final diagnosis at least 10 years later.

A total of 4,068,052 individuals were included in the present analysis, 8449 of whom had a baseline diagnosis of schizophrenia and 8438 had a baseline diagnosis of bipolar disorder. Individuals a first diagnosis of bipolar disorder and schizophrenia had a mean (SD) age of 32.1 (10.0) and 29.7 (8.3) years at diagnosis and 41.8% and 65.9% were men, respectively.

After a mean follow-up of 22.9 to 25.7 years, 4.5% of those initially diagnosed with schizophrenia converted to bipolar disorder and 10.1% of those with an initial diagnosis of bipolar disorder converted to schizophrenia. Overall, the survival curve for the conversion from schizophrenia to bipolar disorder was linear whereas the curve for bipolar disorder to schizophrenia had a steeper slope at 2 to 3 years.

Conversion from schizophrenia to bipolar disorder significantly predicted by being married at schizophrenia onset (hazard ratio [HR], 2.80; P <.0001), having a history of psychotic (HR, 2.68; P <.05) or nonpsychotic (HR, 1.69; P <.001) major depression prior to schizophrenia onset, female sex (HR, 1.59; P <.0001), high familial genetic risk score (FGRS) for bipolar disorder (HR, 1.16; P <.0001), birth year (HR, 1.02; P <.01), age at schizophrenia onset (HR, 0.97; P <.01), and high FGRS for other nonaffective psychoses (HR, 0.92; P <.01).

Conversion from bipolar disorder to schizophrenia was significantly predicted by schizotypal personality disorder prior to bipolar disorder onset (HR, 8.01; P <.0001), bipolar disorder type 1 at diagnosis (HR, 3.05; P <.0001), drug use disorder prior to bipolar disorder onset (HR, 1.95; P <.0001), male sex (HR, 1.33; P <.0001), high FGRS for other nonaffective psychoses (HR, 1.06; P <.0001), high FGRS for schizophrenia (HR, 1.04; P <.0001), age at bipolar disorder onset (HR, 0.95; P <.0001), birth year (HR, 0.95; P <.0001), high FGRS for major depression (HR, 0.93; P <.05), high FGRS for bipolar disorder (HR, 0.90; P <.0001), nonpsychotic MD prior to bipolar disorder onset (HR, 0.74; P <.01), and being previously married (HR, 0.70; P <.05) or married (HR, 0.32; P <.0001) at bipolar disorder onset.

Using these predictors, conversion from schizophrenia to bipolar disorder at 5 years could be predicted with an area under to curve (AUC) of 0.65 and from bipolar disorder to schizophrenia with an AUC of 0.78.

These findings indicate that diagnostic conversion between bipolar disorder and schizophrenia is not rare and should be considered in future studies of this disorder. The investigators concluded, “[I]n studies that seek to investigate the differences between schizophrenia and bipolar disorder… studying new-onset cases will likely result in less clear-cut findings than cases followed over a sufficient period of time to confirm the accuracy of the original diagnosis.”

These findings may not be generalizable to a more diverse population.

This article originally appeared on Psychiatry Advisor