Global and specific neuropsychological impairments over time during the putative prodrome to psychosis

Schizophrenia (SCZ) and related psychotic illnesses are widely considered neurodevelopmental disorders. Although premorbid neuropsychological (NP) impairments are often cited in support of neurodevelopmental models, little is known about the developmental course of these impairments in relation to psychosis onset. Cross-sectional and longitudinal cohort and high risk studies during premorbid and prodromal periods suggest a possible progression of impairment immediately preceding or accompanying illness onset. To evaluate this hypothesis, I conducted three studies examining the nature, timing, and heterogeneity of NP impairments during the premorbid and putatively prodromal stages of psychotic illness. The first study, a meta-analytic review of premorbid IQ in individuals who later developed schizophrenia, identified a moderate and reliable generalized impairment present as early as IQ can be reliably measured and apparently stable prior to symptom onset. The second and third studies assessed NP functioning at baseline and over one year in a sample of help-seeking youth at clinical high risk (CHR) for psychosis relative to well-matched healthy comparison (HC) subjects. CHR status was associated with a moderate generalized impairment, a marked early impairment in olfactory identification, and progressive impairment over time, particularly in executive functions. Those who later developed severe and psychotic level symptoms tended to have greater initial impairments than those who did not, particularly in verbal IQ, verbal memory, and executive functions. Over the course of one year, they not only failed to make expected gains in executive functions and verbal memory, they demonstrated a decline in verbal memory performance from baseline. Degree of risk or presumed proximity to illness onset based on the presence and timing of psychotic level symptoms was associated with a relatively greater discrepancy between expected and observed cognitive functioning. Overall results suggest that IQ, olfactory identification, and verbal memory impairments are present early in the prodrome for individuals presumably at highest risk or closest proximity to acute psychosis. Symptom progression may be associated with impairment in the normal development of executive and verbal memory functions over time. This pattern of initial and progressive impairments supports the presence of both "early" and "late" neurodevelopmental abnormalities in the etiology of psychosis.