Amygdala-Prefrontal Function and Clinical Course among Adolescents and Young Adults at Clinical High Risk for Psychosis
- Author(s): Gee, Dylan
- Advisor(s): Cannon, Tyrone D
- Tottenham, Nim
- et al.
Emotion processing deficits are core features of schizophrenia, and patients display abnormalities in emotion processing at the neural level. However, the extent to which these deficits are present prior to the onset of psychosis and the role that they might play in its development are not well understood. Given the severity of psychotic illness and limitations of extant treatments, research has increasingly focused on the early detection of risk for psychosis to elucidate mechanisms underlying risk progression and facilitate early intervention. Integrating biological markers derived through neuroimaging into predictive algorithms represents a promising avenue to improve risk detection. Based on prior findings of amygdala-prefrontal abnormalities in schizophrenia, the present study investigated whether alterations in amygdala-prefrontal circuitry predate the onset of psychosis and predict clinical outcomes. Participants were adolescents and young adults at clinical high risk (CHR) for psychosis and healthy controls who completed an emotional faces fMRI task at baseline and received follow-up clinical assessments through the North American Longitudinal Prodrome Study. Findings revealed differential activation and functional connectivity at baseline among CHR participants who recovered symptomatically within six months or who converted to psychosis. Compared with non-converting CHR participants and healthy controls, converters exhibited reduced activation in the amygdala and prefrontal cortex (PFC) during emotion processing. Converters showed positive amygdala-PFC connectivity, compared with the expected pattern of negative connectivity in this regulatory circuit. In contrast, the recovery group resembled controls and showed increased amygdala and PFC activation, as well as stronger negative amygdala-prefrontal functional connectivity. Behaviorally, CHR participants who converted to psychosis also performed with lower accuracy during the emotional faces task at baseline, compared with CHR participants who recovered from the at-risk state. The present findings suggest that the extent to which amygdala-prefrontal circuitry is abnormal or typical among individuals at risk for psychosis may relate to the severity of clinical course. Taken together, these results provide novel insight into the nature of emotion processing deficits in the development of psychosis and may enhance early identification of risk for psychosis.