Associations Between Premorbid Trajectory-defined Subgroups of Schizophrenia and Clinical and Neuroanatomic Features

Abstract

Different trajectories of premorbid functioning in schizophrenia spectrum disorder (SSD) have been associated with differences in clinical presentation and neuroanatomy; however, previous studies have largely focused on IQ-based premorbid cognitive trajectories, which discount non-cognitive domains of functioning and are unable to capture differential slopes of functional trajectories prior to psychosis onset. The present study utilized latent class mixture modeling of Premorbid Adjustment Scale (PAS) data from a multi-site sample of individuals with SSD (n=720), identifying four latent class psychosocial functioning trajectory subgroups. SSD premorbid trajectory groups differed in age of psychosis onset and likelihood of having a narrow schizophrenia or schizophreniform diagnosis versus broader SSD diagnosis. When the SSD-derived latent class model was applied to a larger sample including 253 SSD relatives, 1221 individuals at clinical high risk for psychosis who did not develop a psychotic disorder within 2 years (CHR nonconverters), and 710 controls, premorbid functioning trajectory groups also differed in estimates of current IQ and cannabis use. However, while narrowly defined SSD subjects differed from other diagnostic categories in age-normalized global cortical thickness (CT) and cross-regional CT similarity to idiopathic schizophrenia, there were no significant differences between premorbid trajectory groups on these metrics within SSD nor in the full sample. Results highlight differences in premorbid functioning and current clinical profile between schizophrenia and other psychotic disorders. These findings additionally suggest weaker associations with current cognition and neuroanatomy for measures of broader premorbid psychosocial functioning compared to premorbid measures narrowly focused on cognition.