Clinical Correlates and Neural Substrates of P50 Suppression Deficits in Schizophrenia - eScholarship

Published on Jan 1, 2015
The present dissertation evaluated the P50 component of the event-related brain potential (ERP), an index of sensory gating measured during a paired-stimulus paradigm, as an intermediate phenotype between clinical symptoms and neuronal mechanisms that might also contribute to higher-order cognitive dysfunction in schizophrenia. Despite considerable evidence that schizophrenia patients exhibit impaired suppression of the P50 to the second of two identical stimuli, the clinical significance and neural mechanisms associated with the P50 gating deficit remain poorly understood. A series of three related studies sought to more fully define the clinical and neurobiological correlates of P50 suppression deficits in schizophrenia. In Study 1, comparison of 52 schizophrenia patients and 41 healthy participants confirmed a P50 suppression deficit in patients, replicating prior research. Investigation of the clinical correlates of the P50 deficit in patients revealed associations between impaired suppression and clinician ratings of attentional difficulties as well as poor working memory performance. In examining the neural substrates of P50 gating with diffusion tensor imaging, Study 2 found associations between P50 deficits and compromised structural integrity of white matter tracts connecting brain regions previously implicated in the generation of P50 suppression in schizophrenia. Study 3 examined whether P50 impairments are amenable to cognitive training and predictive of treatment outcome. Compared to a control intervention without cognitive targets, patients who completed cognitive remediation demonstrated significant improvements in P50 suppression. Baseline P50 ratios were also predictive of improvement as evidenced by post-treatment clinician ratings and performance on an attention task, thereby indicating that patients with stronger P50 suppression are likely to receive the most benefit from cognitive remediation. All relationships observed in the present set of studies were specific to P50 and did not extend to the N100 component of the ERP. By characterizing the relationship of P50 to clinical symptoms and cognitive dysfunction in schizophrenia, isolating biological mechanisms that might be involved in P50 suppression, and evaluating its amenability to cognitive training, the present dissertation provided support for P50 as a viable biomarker for guiding the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.
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