Verbal memory improvement in first-episode psychosis APOE-ε4 carriers: a pleiotropic effect?

Abstract

Fidel Vila-Rodriguez,1 Donna J Lang,2 Heather Baitz,3 Kristina Gicas,3 Allen E Thorton,3 Thomas S Ehmann,1 Geoff N Smith,1 Alasdair M Barr,4 Ivan J Torres,1 Lili C Kopala,1 G William MacEwan,1 Daniel J Müller,5 James L Kennedy,5 William G Honer11Department of Psychiatry, 2Division of Neuroradiology, Department of Radiology, The University of British Columbia, Vancouver, 3Department of Psychology, Simon Fraser University, Burnaby, 4Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC, 5Department of Psychiatry, Centre for Mental Health and Addictions, University of Toronto, Toronto, ON, CanadaBackground: Verbal memory impairment is a core feature in schizophrenia even at early stages of the disease, but its etiopathogenesis is not fully understood. The APOE-ε4 is the main genetic risk factor for late-onset Alzheimer’s disease. Our primary goal was to ascertain whether APOE-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, APOE 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-APOE-ε4 carriers and FEP-APOE-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; F[1, 119.7]=42.97; P<0.001) as well as an APOE-ε4 by group by time (F[4, 116.2]=2.73, P=0.033) interaction with only FEP-APOE-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 APOE-ε4 carriers and replicates the prominent verbal memory deficits present in FEP. Our work provides further evidence pointing to an antagonistic pleiotropic effect of APOE-ε4 in neuropsychiatric disorders. Our results merit further research into antagonistic pleiotropic effects in schizophrenia. Keywords: APOE, verbal memory, antagonistic pleiotropy, first-episode psychosis, schizophrenia

Keywords

• APOE
• verbal memory
• antagonistic pleiotropy
• first episode psychosis
• schizophrenia