Three Distinct Pathways to First Episode Mania and Psychosis: Latent Class Analysis of Antecedent Psychopathology

Despite the classic Kraepelinian dichotomy between bipolar disorder (BD) and schizophrenia (SZ), contemporary evidence suggests shared antecedent risk factors and similarities in the early course. This study aimed to identify distinct trajectories leading to first-episode mania (FEM) and first-episode psychosis (FEP) by examining antecedent psychopathology, including psychiatric diagnoses, symptoms, substance use, and psychotropic medication exposure.

Individuals born after 1985 who resided in Olmsted County, Minnesota, USA, and had FEM/FEP were identified through the Rochester Epidemiology Project. Latent class analysis (LCA) was used to identify subgroups based on antecedent psychopathology incorporating 57 dichotomous antecedent measures before FEM/FEP.

A total of 202 individuals (BD n = 73, SZ n = 129; 26.7% female, mean age 20.8 ± 3.7 years) were included. A 3-class LCA model optimally fits the data. Class 1 (Neurodevelopmental, 29.7%) had a high prevalence of neurodevelopmental disorders, behavioral symptoms, and ADHD medication use. Class 2 (Depressive-Anxious, 31.2%) included depressive and anxiety disorders, mood-related symptoms, and SSRI/SNRI use. Class 3 (Minimal Psychiatric Morbidity, 39.1%) had a low prevalence of antecedent diagnoses and symptoms, with comparable substance use to other classes. There were significant diagnostic differences, with SZ being more common in the Neurodevelopmental (71.7%) and Minimal Psychiatric Morbidity (70.9%) classes, while BD was more common in the Depressive-Anxious class (p = 0.007). Neurodevelopmental and Minimal Psychiatric Morbidity classes had higher proportions of males (85.0% and 82.3%, respectively) compared to the Depressive-Anxious class (50.8%, p < 0.001). The Neurodevelopmental class showed an earlier age at first mental health visit (9.5 ± 5.5 years) and a longer antecedent illness duration (10.8 ± 6.1 years) than the other classes (p < 0.001).

This study identified three distinct pathways to FEM and FEP, offering a transdiagnostic perspective on the antecedent illness trajectories of BD and SZ. Future research should validate these categories that are more inclusive than the classic BD versus SZ dichotomy and explore their potential for predicting illness course and guiding personalized early interventions.