Verbal Memory Improvement in First-episode Psychosis -ε4 Carriers: a Pleiotropic Effect?

Background: Verbal memory impairment is a core feature in schizophrenia even at early stages of the disease, but its etiopathogenesis is not fully understood. The -ε4 is the main genetic risk factor for late-onset Alzheimer's disease. Our primary goal was to ascertain whether -ε4 status had a pleiotropic effect in early stages of the illness.

Participants And Methods: A total of 86 first-episode psychosis (FEP) outpatients and 39 healthy volunteers were recruited. Demographic and clinical data, genotyping, and a neuropsychological test battery including the California Verbal Learning Test - second edition (CVLT-II) were administered and assessed at study entry and at 1-year follow-up. Data were analyzed using mixed-model repeated measures, where the dependent variable was verbal memory indexed by California Verbal Learning Test (CVLT) Trials 1-5 total recall score.

Results: FEP--ε4 carriers and FEP--ε4 noncarriers had similar symptom severity, clinical outcomes, premorbid and current intelligence quotient, and exposure to antipsychotics. There was a main effect of group on CVLT 1-5 (FEP =43.30 vs control =58.25; [1, 119.7]=42.97; <0.001) as well as an -ε4 by group by time ([4, 116.2]=2.73, =0.033) interaction with only FEP--ε4 carriers showing improved verbal memory at follow-up.

Conclusion: Our study is the first to report improvement in verbal memory in persons afflicted by FEP who are -ε4 carriers and replicates the prominent verbal memory deficits present in FEP. Our work provides further evidence pointing to an antagonistic pleiotropic effect of -ε4 in neuropsychiatric disorders. Our results merit further research into antagonistic pleiotropic effects in schizophrenia.