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Apolipoprotein E-?4 allele predicts escalation of psychotic symptoms in late adulthood.

ABSTRACT: BACKGROUND:Research on a putative link between apolipoprotein-?4 allele (APOE-?4) and schizophrenia has been inconclusive. However, prior studies have not investigated the association between APOE-?4 and symptom trajectories, nor has the existing literature taken into account the potentially moderating effect of age in genetic association studies. METHODS:The association between APOE-?4 and four symptom dimensions was investigated in a longitudinal study of 116 individuals with schizophrenia initially assessed during their first admission for psychosis and evaluated five times over the following 20years. A meta-analysis identified 29 case-control studies of APOE-?4 allele frequency in schizophrenia, which were analyzed using random-effects meta-regression to test the potentially moderating effect of age. RESULTS:Longitudinal models identified a specific association between APOE-?4 and symptom trajectories, showing that APOE-?4 portends worsening severity of hallucinations and delusions in late adulthood among people with schizophrenia, at a rate of a 0.46 standard deviation increase per decade. Meta-analysis showed a significant effect of age: the association between APOE-?4 and schizophrenia was not detectable in younger people but became pronounced with age, such that APOE-?4 increased the odds of diagnosis by 10% per decade. CONCLUSIONS:Taken together, the meta-analysis and longitudinal analysis implicate APOE-?4 as an age-related risk factor for worsening hallucinations and delusions, and suggest APOE-?4 may play an age-mediated pathophysiological role in schizophrenia. The presence of an APOE-?4 allele may also identify a subgroup of patients who require intensive monitoring and additional targeted interventions, especially in mid-to late-life.

SUBMITTER: Jonas K

PROVIDER: S-EPMC6525644 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Apolipoprotein E-ε4 allele predicts escalation of psychotic symptoms in late adulthood.

Jonas Katherine K Clouston Sean S Li Kaiqiao K Fochtmann Laura J LJ Lencz Todd T Malhotra Anil K AK Cicero David D Perlman Greg G Bromet Evelyn J EJ Kotov Roman R

Schizophrenia research 20181221

<h4>Background</h4>Research on a putative link between apolipoprotein-ε4 allele (APOE-ε4) and schizophrenia has been inconclusive. However, prior studies have not investigated the association between APOE-ε4 and symptom trajectories, nor has the existing literature taken into account the potentially moderating effect of age in genetic association studies.<h4>Methods</h4>The association between APOE-ε4 and four symptom dimensions was investigated in a longitudinal study of 116 individuals with sc ...[more]

PMID: 30584027

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Project description:Theoretical background: The Apolipoprotein E (APOE) ε4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ε4 allele status has been associated with brain structural alterations and lower cognitive ability in non-demented subjects. However, it remains unclear to what extent the visuospatial cognitive domain is affected, from what age onward changes are detectable and if alterations may interact with cognitive deficits in major depressive disorder (MDD). The current work investigated the effect of APOE ε4 homozygosity on visuospatial working memory (vWM) capacity, and on hippocampal morphometry. Furthermore, potential moderating roles of age and MDD were assessed. Methods: A sample of n = 31 homozygous ε4 carriers was contrasted with n = 31 non-ε4 carriers in a cross-sectional design. The sample consisted of non-demented, young to mid-age participants (mean age = 34.47; SD = 13.48; 51.6% female). Among them were n = 12 homozygous ε4 carriers and n = 12 non-ε4 carriers suffering from MDD (39%). VWM was assessed using the Corsi block-tapping task. Region of interest analyses of hippocampal gray matter density and volume were conducted using voxel-based morphometry (CAT12), and Freesurfer, respectively. Results: Homozygous ε4 carriers showed significantly lower Corsi span capacity than non-ε4 carriers did, and Corsi span capacity was associated with higher gray matter density of the hippocampus. APOE group differences in hippocampal volume could be detected but were no longer present when controlling for total intracranial volume. Hippocampal gray matter density did not differ between APOE groups. We did not find any interaction effects of age and MDD diagnosis on hippocampal morphometry. Conclusion: Our results point toward a negative association of homozygous ε4 allele status with vWM capacity already during mid-adulthood, which emerges independently of MDD diagnosis and age. APOE genotype seems to be associated with global brain structural rather than hippocampus specific alterations in young- to mid-age participants.

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Apolipoprotein E-?4 allele predicts escalation of psychotic symptoms in late adulthood.

Publications

Apolipoprotein E-ε4 allele predicts escalation of psychotic symptoms in late adulthood.

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