Apolipoprotein E-ε4 allele predicts escalation of psychotic symptoms in late adulthood.
Apolipoprotein E
Delusions
Hallucinations
Psychosis
Schizophrenia
Journal
Schizophrenia research
ISSN: 1573-2509
Titre abrégé: Schizophr Res
Pays: Netherlands
ID NLM: 8804207
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
18
09
2018
revised:
14
11
2018
accepted:
07
12
2018
pubmed:
26
12
2018
medline:
14
5
2020
entrez:
26
12
2018
Statut:
ppublish
Résumé
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. The association between APOE-ε4 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-ε4 allele frequency in schizophrenia, which were analyzed using random-effects meta-regression to test the potentially moderating effect of age. Longitudinal models identified a specific association between APOE-ε4 and symptom trajectories, showing that APOE-ε4 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-ε4 and schizophrenia was not detectable in younger people but became pronounced with age, such that APOE-ε4 increased the odds of diagnosis by 10% per decade. Taken together, the meta-analysis and longitudinal analysis implicate APOE-ε4 as an age-related risk factor for worsening hallucinations and delusions, and suggest APOE-ε4 may play an age-mediated pathophysiological role in schizophrenia. The presence of an APOE-ε4 allele may also identify a subgroup of patients who require intensive monitoring and additional targeted interventions, especially in mid-to late-life.
Sections du résumé
BACKGROUND
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.
METHODS
The association between APOE-ε4 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-ε4 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-ε4 and symptom trajectories, showing that APOE-ε4 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-ε4 and schizophrenia was not detectable in younger people but became pronounced with age, such that APOE-ε4 increased the odds of diagnosis by 10% per decade.
CONCLUSIONS
Taken together, the meta-analysis and longitudinal analysis implicate APOE-ε4 as an age-related risk factor for worsening hallucinations and delusions, and suggest APOE-ε4 may play an age-mediated pathophysiological role in schizophrenia. The presence of an APOE-ε4 allele may also identify a subgroup of patients who require intensive monitoring and additional targeted interventions, especially in mid-to late-life.
Identifiants
pubmed: 30584027
pii: S0920-9964(18)30698-4
doi: 10.1016/j.schres.2018.12.010
pmc: PMC6525644
mid: NIHMS1517318
pii:
doi:
Substances chimiques
Apolipoprotein E4
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
82-88Subventions
Organisme : NIMH NIH HHS
ID : R01 MH117646
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH104964
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH094398
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085548
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH123451
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110434
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH044801
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085542
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.
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