UCLA

Early-onset psychosis (EOP), or onset of overt psychosis prior to age 18, is associated with particularly severe neurocognitive and social impairment, and poor prognosis (Frangou, 2010; Vyas & Gogtay, 2012). While significant impairments have been documented in specific cognitive domains (Fioravanti, Carlone, Vitale, Cinti, & Clare, 2005; Heinrichs & Zakzanis, 1998), working memory (WM) in particular is an area that has been theorized to represent a reliable cognitive endophenotype of schizophrenia. However, the majority of literature to date has focused on adult-onset schizophrenia, in which relevant developmental processes have already unfolded. Adolescence provides a privileged opportunity to understand how psychosis-related abnormalities in the structure and function of neural networks affect the relationships between social cognition, neurocognition and functioning, as well as an opportunity to define biomarkers for development of treatments to improve functional outcomes.

As such, the first study examined the relationship between individual WM capacity and task-based neural activation and functional connectivity. Results indicated that, relative to typically developing controls, patients with EOP have poorer WM performance, lower overall WM capacity, reduced neural activity in WM-associated brain regions, and reduced coupling of WM-associated regions. Additionally, EOP patients evidenced greater neural activation and connectivity with increasing age, suggesting an atypical developmental trajectory along with general inefficiency of WM circuitry.

Additional insight into the neurodevelopmental processes relevant to psychosis can come from examining genetically defined high-risk cohorts, such as 22q11.2 deletion syndrome (22q11DS). The second study evaluated the phenotypic overlap between EOP and 22q11DS by investigating the profile of neurocognitive and social cognitive impairment in individuals with EOP relative to 22q11DS patients and healthy controls. Despite greater overall cognitive impairment in the 22q11DS group (with the exception of verbal fluency, for which EOP patients evidenced greater impairment), patients with EOP and 22q11DS had comparable deficits in processing speed. 22q11DS and EOP patients also evidenced similar patterns of relationships between cognitive measures and psychotic symptoms. However, neurocognition and social cognition largely did not predict future functioning among the groups.

The third and final study examined plasticity-based cognitive training (CT) as a potential intervention for such cognitive impairments in EOP. Results from the feasibility study indicated that slightly over half of participants were able to complete at least 10 hours of CT; dropout was primarily due to finding training boring. However, patients completing training showed higher post- versus pre-CT social functioning, and pre- to post-CT reductions in general and anxiety symptoms. This investigation into neurocognitive and social cognitive dysfunction in EOP, which incorporates perspectives from an fMRI paradigm and a comparison to a genetic high-risk cohort, has the potential to generate knowledge on a clinically significant and understudied area, and potentially produce new treatment targets for EOP.