Apolipoprotein E Genotype and Odor Identification in Schizophrenia

Twenty-eight patients with a DSM-IV 9 diagnosis of schizophrenia (14 men, 14 women) and 26 healthy volunteers (15 men, 11 women) were recruited from the Schizophrenia Research Center at the University of Pennsylvania Medical Center. Subjects were matched for sex (χ ² =0.32, df=1, p=0.57) and race (χ ² =2.7, df=1, p=0.10). Patients were older than healthy comparison subjects (mean ages of 36.6 [SD=9.1] years and 29.4 [SD=11.2] years, respectively; t=26, df=52, p=0.01). Age was subsequently used as a covariate in all analyses. Due to the fact that schizophrenia adversely affects educational attainment, it was expected that patients attained fewer years of formal education than healthy comparison subjects (t=−2.0, df=52, p=0.04). However, parental education, a more appropriate indicator of preillness educational expectation, revealed no significant difference between groups (Wilks’ λ (2, 51)=0.96, p=0.38). Patients tended to smoke more than comparison subjects (mean pack-years: patients = 7.7 [SD=11.2]; comparison subjects=2.4 [SD=7.4]; t (49)=1.9, p<0.053). All patients met DSM-IV criteria for schizophrenia, with no other concurrent diagnoses. Healthy subjects were free of any Axis I diagnosis, Axis II Cluster A (i.e., schizoptypal, schizoid, or paranoid) personality disorder, and family history of psychiatric illness.

Subjects were excluded if they had a history of neurological disorder, including head trauma with loss of consciousness; a history of substance abuse or dependence (as assessed by history, record review, and serum toxicology); a history of any medical condition that might alter cerebral functioning; or a recent respiratory infection or any other condition that could affect olfactory functioning (e.g., common cold or allergies). Written informed consent was obtained after the procedures had been fully explained.

Apolipoprotein E (ApoE) genotyping was performed on blood using polymerase chain reaction-based methods. 10 ApoE genotypes for each subject were scored independently by two observers who were blind to diagnostic status, and allele frequencies were calculated for each group.

Odor identification skills were assessed with the University of Pennsylvania Smell Identification Test (UPSIT). 11 The UPSIT was administered unilaterally (each nostril separately), with the contralateral naris occluded using a piece of Durapore ^TM tape (3M Corporation, Minneapolis, MN) fitted tightly over the edges of the nostril. This procedure effectively isolated the nostril being examined and prevented retronasal airflow. Two booklets of the test were administered to the left nostril, and two to the right nostril, with the booklets systematically counterbalanced among subjects.

The relationship between ApoE genotype and UPSIT performance was probed in two ways. First, each group was divided into two subgroups based on the presence or absence of at least one ϵ4 allele. These ϵ4-positive and ϵ4-negative subgroups were then contrasted with regard to UPSIT performance using multivariate analysis of covariance (MANCOVA) with age as a covariate. Second, in order to gauge any potential “dose-effect” relationships, each subject’s ApoE genotype was graded on a 5-point scale with the ApoE ϵ2/2 genotype representing the lowest point and ApoE ϵ4/4 the highest point. Employing such a scale incorporated all combinations of the three alleles: 1) the possible protective effects of the ϵ2 allele, 2) presumed neutral effect of the ϵ3 allele, and 3) the putative negative effect of the ϵ4 allele. These relationships were examined using Spearman correlations.