Memory Impairments and Psychosis Prediction: A Scoping Review and Theoretical Overview

Impairments in memory functions are among the most robust correlates of schizophrenia and of poor functional outcomes in individuals with psychotic disorders. Prospective, longitudinal studies are crucial to determining the meaning of these deficits in relation to mechanisms associated with the onset and course of these disorders.The objective of this review is to examine the literature concerning premorbid memory impairments during the prodromal phase of psychosis to address three primary questions 1) are memory impairments present among individuals with a clinical high risk syndrome? 2) are memory deficits in clinical high risk cases predictive of future conversion to psychosis? and 3) what are the underlying neural correlates of memory impairment in clinical high risk individuals and are they also predictive of future conversion?PubMed and Google Scholar databases were systematically searched. The primary inclusion criteria were to select studies that 1) were original research articles published in a peer-reviewed journal in the past 25 years, 2) studied subjects at clinical high risk for psychosis or in the prodromal phase of illness, and 3) included examinations into verbal memory performance in those at clinical high risk for psychosis.64 articles were identified and screened for eligibility. The review included 34 studies investigating verbal memory impairment in clinical high risk individuals compared to controls. The average effect size of verbal learning total recall was .58, indicating a moderate level of impairment in verbal learning among individuals at clinical high risk for psychosis as compared to healthy controls. Of studies that predicted time to conversion, indices of memory, particularly declarative and verbal working memory, were especially predictive of future conversion. Finally, when examining investigations of the neural correlates of memory dysfunction in the clinical high risk state, findings suggest altered activation and functional connectivity among medial temporal lobe regions may underlie differences in memory performance between clinical high risk individuals and healthy controls.Findings to date strongly indicate that memory impairments are present during the premorbid phase of psychosis and that verbal memory impairment in particular is predictive of future conversion to psychosis. Evidence from fMRI studies is fairly consistent in showing greater activation of memory-related regions during retrieval among clinical high risk cases who convert, with less consistent evidence of altered functional connectivity in the encoding phase. These findings support the use of verbal learning and memory measures in the psychosis prediction and prevention field.