The following is a summary of “Relationship of Family Genetic Risk Score With Diagnostic Trajectory in a Swedish National Sample of Incident Cases of Major Depression, Bipolar Disorder, Other Nonaffective Psychosis, and Schizophrenia,” published in the January 2023 issue of Psychiatry by Kendler, et al.

Diagnostic stability and familial/genetic risk have long been two of the most significant psychiatric nosologic validators, dating back to Kraepelin’s development of the field in the contemporary period. For a study, researchers sought to evaluate the connections between the family genetic risk score (FGRS) and the stability or change of the diagnosis of schizophrenia, bipolar disorder (BD), other nonaffective psychosis (ONAP), and major depression (MD).

The longitudinal population-based cohort (N = 4,171,120) included individuals with incident cases of MD (n = 235,095), BD (n = 11,681), ONAP (n = 16,009), and schizophrenia (n = 6,302) who had at least 1 additional diagnosis of the 4 disorders during follow-up, as assessed from Swedish national medical registries, observed over a mean (SD) of 13.1 (5.9) years until a mean (SD) of 48.4 (12.3) years. Between August and September 2022, data that were gathered from January 1973 to December 2018 were evaluated.

Out of the 269,097 individuals included in the study, 64.3% (173,061) were female, and their mean age at first registration was 35.1 years with a standard deviation of 11.9 years. The study found that diagnostic stability was highest for MD, with 91.4% (214,794) of cases remaining stable, followed by schizophrenia, BD, and ONAP, with stability rates of (4621) 73.2%, (7428) 63.6%, and (6738) 42.1%, respectively. The second most common final diagnosis for each of these disorders was BD for MD (15,506 [6.6%]), ONAP (1,110 [17.6%]), MD(2,681 [23.0%]), and schizophrenia (4,401 [27.5%]). The study also found that individuals with a high familial genetic risk score (FGRS) for their incident diagnosis had a higher likelihood of diagnostic stability, while those with a high FGRS for their final diagnosis and a low FGRS for their incident diagnosis were more likely to experience diagnostic change. In multivariate models, individuals in the upper 5% of genetic risk had an odds ratio of 1.75 or greater for certain diagnostic transitions. For instance, those with a high MD FGRS had higher odds of transitioning from ONAP to MD (OR, 1.91; 95% CI, 1.59-2.29) and from schizophrenia to MD (OR, 2.45; 95% CI, 1.64-3.68). Similarly, those with a high BD FGRS had higher odds of transitioning from MD to BD (OR, 2.60; 95% CI, 2.47-2.73), from ONAP to BD (OR, 2.16; 95% CI, 1.85-2.52), and from schizophrenia to BD (OR, 2.20; 95% CI, 1.39-3.49). Those with a high ONAP FGRS had higher odds of transitioning from MD to ONAP (OR, 1.80; 95% CI, 1.62-2.02), from MD to schizophrenia (OR, 1.95; 95% CI, 1.58-2.41), and from BD to schizophrenia (OR, 1.89; 95% CI, 1.39-2.56). Lastly, those with a high schizophrenia FGRS had higher odds of transitioning from MD to schizophrenia (OR, 1.80; 95% CI, 1.46-2.23) and from BD to schizophrenia (OR, 1.75; 95% CI, 1.25-2.45). Finally, the study found that FGRS profiles for incident cases confirmed at final diagnosis were more homogeneous than genetic profiles for those who changed diagnoses.

The genetic risk factors for MD, BD, ONAP, and schizophrenia were substantially and systematically linked to the course of these 4 illnesses’ diagnoses in a sizable population-based longitudinal cohort. Clinical diagnosis and genetic risk profiles converged more and more over time, providing genetic confirmation for these diagnostic frameworks. Diagnostically unstable incident cases had higher levels of genetic heterogeneity than those with stable diagnoses throughout time.

Reference: jamanetwork.com/journals/jamapsychiatry/article-abstract/2800309