Dataset Information

ApoE alleles, depression and positive affect in multiple sclerosis.

ABSTRACT: The role of apolipoprotein E (ApoE) alleles has received recent attention in depressive disorders, the ApoE epsilon4 conferring greater risk for poorer outcomes, and the ApoE epsilon2 allele providing some protective effects. Depression is common in multiple sclerosis (MS) and the role of ApoE alleles is unknown.To evaluate ApoE alleles in relation to symptoms of depression in a cohort of patients with MS participating in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka Study). To examine risk and protection, depressed mood and positive affect were each investigated with respect to the ApoE epsilon4 and ApoE epsilon2 alleles, respectively.Of the total 101 participants, 22.8% were ApoE epsilon2 carriers and 21.8% were ApoE epsilon4 carriers. Hierarchical linear regression analyses suggested that after controlling for demographics, disease duration, and disability, ApoE epsilon2 significantly predicted increased positive affect (R2Delta=0.05, F(1,94)=5.44, P=0.02) and was associated with decreased severity of depressive symptoms, although this did not reach statistical significance (R2Delta=0.03, F(1,94)=3.44, P=0.06). ApoE epsilon4 did not significantly predict depression status.The presence of the ApoE epsilon2 allele in this study is suggested to be protective against depressive symptoms in our subsample of patients recruited from the Slifka Study. These findings are consistent with reports in psychiatric populations linking ApoE epsilon2 with decreased incidence of depressive disorders. Further investigation would be warranted to understand the role of ApoE genotypes and risk for depressive symptoms.

SUBMITTER: Julian LJ

PROVIDER: S-EPMC3045528 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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ApoE alleles, depression and positive affect in multiple sclerosis.

Julian L J LJ Vella L L Frankel D D Minden S L SL Oksenberg J R JR Mohr D C DC

Multiple sclerosis (Houndmills, Basingstoke, England) 20090301 3

<h4>Background</h4>The role of apolipoprotein E (ApoE) alleles has received recent attention in depressive disorders, the ApoE epsilon4 conferring greater risk for poorer outcomes, and the ApoE epsilon2 allele providing some protective effects. Depression is common in multiple sclerosis (MS) and the role of ApoE alleles is unknown.<h4>Aims</h4>To evaluate ApoE alleles in relation to symptoms of depression in a cohort of patients with MS participating in the Sonya Slifka Longitudinal Multiple Scl ...[more]

PMID: 19244396

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Project description:Depression is among the most common comorbidities in multiple sclerosis and has severe psychosocial consequences. Alterations in neural emotion regulation in amygdala and prefrontal cortex have been recognized as key mechanism of depression but never been investigated in multiple sclerosis depression. In this cross-sectional observational study, we employed a functional MRI task investigating neural emotion regulation by contrasting regulated versus unregulated negative stimulus perception in 16 persons with multiple sclerosis and depression (47.9 ± 11.8 years; 14 female) and 26 persons with multiple sclerosis but without depression (47.3 ± 11.7 years; 14 female). We tested the impact of depression and its interaction with lesions in amygdala-prefrontal fibre tracts on brain activity reflecting emotion regulation. A potential impact of sex, age, information processing speed, disease duration, overall lesion load, grey matter fraction, and treatment was taken into account in these analyses. Patients with depression were less able (i) to downregulate negative emotions than those without (t = -2.25, P = 0.012, β = -0.33) on a behavioural level according to self-report data and (ii) to downregulate activity in a left amygdala coordinate (t = 3.03, P Family-wise error [FWE]-corrected = 0.017, β = 0.39). Moreover, (iii) an interdependent effect of depression and lesions in amygdala-prefrontal tracts on activity was found in two left amygdala coordinates (t = 3.53, pFWE = 0.007, β = 0.48; t = 3.21, pFWE = 0.0158, β = 0.49) and one right amygdala coordinate (t = 3.41, pFWE = 0.009, β = 0.51). Compatible with key elements of the cognitive depression theory formulated for idiopathic depression, our study demonstrates that depression in multiple sclerosis is characterized by impaired neurobehavioural emotion regulation. Complementing these findings, it shows that the relation between neural emotion regulation and depression is affected by lesion load, a key pathological feature of multiple sclerosis, located in amygdala-prefrontal tracts.

Project description:Background: Since APOE alleles represent the most impactful genetic risk factors for Alzheimer's disease (AD), their differential mechanism(s) of action are under intense scrutiny. APOE4 is robustly associated with increased AD risk compared to the neutral APOE3 and protective APOE2. APOE alleles have also been associated with differential inflammation and gastrointestinal recovery after insult in human and murine studies, leading us to hypothesize that APOE alleles impact the gut microbiome. Methods: To assess this hypothesis, we compared 16S ribosomal RNA gene amplicon-based microbiome profiles in a cohort of mice that were homozygous for APOE2, APOE3, or APOE4, and included both males and females as well as carriers and non-carriers of five familial AD (5xFAD) mutations. Fecal samples were analyzed from mice at 4 and 6 months of age. APOE genotype, as well as sex and 5xFAD status, was then tested for influence on alpha diversity (Shannon H index) and beta diversity (principal coordinate analyses and PERMANOVA). A Random Forest analysis was used to identify features that predicted APOE, sex and 5xFAD status. Results: The richness and evenness (alpha diversity) of the fecal microbiome was not robustly associated with APOE genotype, 5xFAD status or sex. In contrast, microbial community composition (beta-diversity) was consistently and strongly associated with APOE genotype. The association between beta-diversity and sex or 5xFAD status was less consistent and more modest. Comparison of the differences underlying APOE effects showed that the relative abundance of multiple bacterial taxa was significantly different as a function of APOE genotype. Conclusions: The structure of the gut microbiome was strongly and significantly associated with APOE alleles in this murine model. Further evaluation of these findings in humans, as well as studies evaluating the impact of the APOE-associated microbiota on AD-relevant phenotypes in murine models, will be necessary to determine if alterations in the gut microbiome represent a novel mechanism whereby APOE genotype impacts AD.

Dataset Information

ApoE alleles, depression and positive affect in multiple sclerosis.

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ApoE alleles, depression and positive affect in multiple sclerosis.

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