UCLA

Psychotic disorders are severe psychiatric disorders, characterized by hallucinations and delusions, which occur in about 1-2% of the general population. While these disorders are highly disabling, increasing evidence suggests that psychotic experiences occur on a spectrum. Around 10% of children and adolescents from community samples endorse psychotic experiences, which are associated with greater risk of developing a full-blown psychotic disorder in adulthood. Psychotic disorders are often preceded by a prodromal period, with declines in work, school, and in social functioning, years before the onset of psychosis. Moreover, reducing the duration of untreated psychosis is associated with better response to medication, lower suicide rate, and better functional outcomes. As such, increasing research on psychosis focuses on understanding its neural precursors, with the goals of understanding its etiology and early intervention. Cognitive deficits are a core feature of schizophrenia. Against a backdrop of generalized cognitive deficit, attention is one of the most significantly impaired domains in schizophrenia. In individuals who later develop schizophrenia, attention deficits are detected as early as they can be assessed, long before psychotic symptoms typically emerge (ages 18-25) in those who later develop schizophrenia. Moreover, attentional impairments in schizophrenia likely have genetic underpinnings, as they are also observed first-degree relatives. Notably, current medications for schizophrenia do not address generalized cognitive or attention deficits, which are associated with worse psychosocial functioning and ability to live independently. Thus, understanding the neurobiology of attention deficits in the psychosis spectrum may ultimately identify novel avenues for early intervention for psychosis. Further introduction can be found in Chapter 1. Yet, relationships between the brain and everyday attention problems in typically developing youth are not fully understood. Building on highly cited work establishing links between anticorrelated functional networks and attention in adults, Chapter 1 replicates and extends these findings in typically developing youth aged 9-10 in a manuscript published in Biological Psychiatry: Global Open Science. In Chapter 2, we evaluate whether the same anticorrelated functional networks, lab-based assessments of attention, and broad genetic liability related to attention are associated with psychotic-like experiences in early adolescence, in the general population. Lastly, in Chapter 3, we leverage a longitudinal, multi-site study of youth at clinical high risk for psychosis and typically developing youth and find that alterations in neural oscillations that support attentional control precede the onset of a full-blown psychotic disorder. In sum, the dissertation work herein focuses on attention in typical development and in the psychosis spectrum via a multi-modal investigation across genetic, neural, and behavioral levels of study, and in a risk period for psychosis and mental illness broadly.