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      Ala54Thr Fatty Acid-Binding Protein 2 ( FABP2) Polymorphism in Recurrent Depression: Associations with Fatty Acid Concentrations and Waist Circumference

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          Abstract

          Background

          Fatty acid (FA)-alterations may mediate the mutual association between Major Depressive Disorder (MDD) and cardiovascular disease (CVD). However, etiology of observed FA-alterations in MDD and CVD remains largely unclear. An interesting candidate may be a mutation in the fatty acid–binding protein 2 (FABP2)-gene, because it regulates dietary FA-uptake. Therefore, we aimed to test the hypotheses that in MDD-patients the FABP2 Ala54Thr-polymorphism would be (I) more prevalent than in sex- and age-matched controls, (II) associated with observed alterations in FA-metabolism, and (III) associated with CVD-risk factor waist circumference.

          Methods

          We measured concentrations of 29 different erythrocyte FAs, FABP2-genotype, and waist circumference in recurrent MDD-patients and matched never-depressed controls.

          Results

          FABP2-genotype distribution did not significantly differ between the 137 MDD-patients and 73 matched controls. However, patients with the Ala54Thr-polymorphism had (I) higher concentrations of especially eicosadienoic acid (C20:2ω6; P=.009) and other 20-carbon FAs, and associated (II) lower waist circumference ( P=.019). In addition, FABP2-genotype effects on waist circumference in patients seemed (I) mediated by its effect on C20:2ω6, and (II) different from controls.

          Conclusions

          Although Ala54Thr-polymorphism distribution was not associated with recurrent MDD, our results indicate that FABP2 may play a role in the explanation of observed FA-alterations in MDD. For Ala54Thr-polymorphism patients, potentially adaptive conversion of increased bioavailable dietary precursors into eicosadienoic acid instead of arachidonic acid might be related to a low waist circumference. Because this is the first investigation of these associations, replication is warranted, preferably by nutrigenetic studies applying lipidomics and detailed dietary assessment.

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          Most cited references28

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          Move over ANOVA: progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry.

          Ralitza Gueorguieva, John Krystal (2004)
          The analysis of repeated-measures data presents challenges to investigators and is a topic for ongoing discussion in the Archives of General Psychiatry. Traditional methods of statistical analysis (end-point analysis and univariate and multivariate repeated-measures analysis of variance [rANOVA and rMANOVA, respectively]) have known disadvantages. More sophisticated mixed-effects models provide flexibility, and recently developed software makes them available to researchers. To review methods for repeated-measures analysis and discuss advantages and potential misuses of mixed-effects models. Also, to assess the extent of the shift from traditional to mixed-effects approaches in published reports in the Archives of General Psychiatry. The Archives of General Psychiatry from 1989 through 2001, and the Department of Veterans Affairs Cooperative Study 425. Studies with a repeated-measures design, at least 2 groups, and a continuous response variable. The first author ranked the studies according to the most advanced statistical method used in the following order: mixed-effects model, rMANOVA, rANOVA, and end-point analysis. The use of mixed-effects models has substantially increased during the last 10 years. In 2001, 30% of clinical trials reported in the Archives of General Psychiatry used mixed-effects analysis. Repeated-measures ANOVAs continue to be used widely for the analysis of repeated-measures data, despite risks to interpretation. Mixed-effects models use all available data, can properly account for correlation between repeated measurements on the same subject, have greater flexibility to model time effects, and can handle missing data more appropriately. Their flexibility makes them the preferred choice for the analysis of repeated-measures data.
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            Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women.

            Cuilin Zhang, Kathryn Rexrode, Rob van Dam … (2008)
            Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent. In a prospective cohort study of 44,636 women in the Nurses' Health Study, associations of abdominal adiposity with all-cause and cause-specific mortality were examined. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. After adjustment for body mass index and potential confounders, the relative risks across the lowest to the highest waist circumference quintiles were 1.00, 1.11, 1.17, 1.31, and 1.79 (95% confidence interval [CI], 1.47 to 1.98) for all-cause mortality; 1.00, 1.04, 1.04, 1.28, and 1.99 (95% CI, 1.44 to 2.73) for CVD mortality; and 1.00, 1.18, 1.20, 1.34, and 1.63 (95% CI, 1.32 to 2.01) for cancer mortality (all P or = 88 cm was 3.02 (95% CI, 1.31 to 6.99) and for waist-to-hip ratio > 0.88 was 3.45 (95% CI, 2.02 to 6.92). After adjustment for waist circumference, hip circumference was significantly and inversely associated with CVD mortality. Anthropometric measures of abdominal adiposity were strongly and positively associated with all-cause, CVD, and cancer mortality independently of body mass index. Elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women.
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              A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression.

              Pao-Yen Lin, Shih-Yi Huang, Kuan-Pin Su (2010)
              On the basis of evidence from studies showing the antidepressant effects of omega-3 polyunsaturated fatty acids and the inverse relation between fish consumption and the prevalence of depression, the phospholipid hypothesis seems promising in ascertaining the etiology and treatment of depression. Although several studies have shown lower levels of omega-3 (n-3) polyunsaturated fatty acids in depressive patients, the results of individual polyunsaturated fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the omega-6 (n-6) polyunsaturated fatty acid arachidonic acid (AA), were inconsistent. We conducted the meta-analyses of 14 studies comparing the levels of polyunsaturated fatty acids between depressive patients and control subjects. The effect size of each study was synthesized by using a random effects model. Compared with control subjects, the levels of EPA, DHA, and total n-3 polyunsaturated fatty acids were significantly lower in depressive patients. There was no significant change in AA or total n-6 polyunsaturated fatty acids. The results showed lower levels of EPA, DHA, and total n-3 polyunsaturated fatty acids in patients with depression, thus implying that n-3 polyunsaturated fatty acids play a role in the pathogenesis of depression. Our findings provide further support to the phospholipid hypothesis of depression and a rationale for using n-3 polyunsaturated fatty acids as an alternative treatment for depression. With these results, future studies examining specific roles of DHA and EPA in different clusters of depressive symptoms are warranted. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Thierry Alquier: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2013
                Publication date (Electronic): 10 December 2013
                Volume: 8
                Issue: 12
                Electronic Location Identifier: e82980
                Affiliations
                [1 ]Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
                [2 ]Program for Mood and Anxiety Disorders, University Center for Psychiatry UMCG, University of Groningen, Groningen, The Netherlands
                [3 ]Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands
                CRCHUM-Montreal Diabetes Research Center, Canada
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AL JA CLHB AHS. Performed the experiments: AL IV CLHB. Analyzed the data: RJTM AL MWJK. Wrote the manuscript: RJTM AL JA MWJK IV HGR CLHB AHS.

                Article
                Publisher ID: PONE-D-13-31590
                DOI: 10.1371/journal.pone.0082980
                PMC ID: 3858331
                PubMed ID: 24340071
                SO-VID: e3bfe026-68fc-461d-afbc-e4abe93434dd
                Copyright statement: Copyright @ 2013
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 31 July 2013
                Date accepted : 29 October 2013
                Funding
                This study has been made possible due to financial aid of the Netherlands Foundation for Mental Health, Utrecht and the Health Research Development Council, Department Prevention Program (ZonMw). HGR is supported by a NWO/ZonMw VENI-Grant #016.126.059. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Uncategorized
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