Dataset Information

Detection and Treatment of Long-Chain Omega-3 Fatty Acid Deficiency in Adolescents with SSRI-Resistant Major Depressive Disorder.

ABSTRACT: Residual depressive symptoms are commonly observed in adolescents with major depressive disorder (MDD) following treatment with selective serotonin reuptake inhibitors (SSRIs). This study combined a case-control analysis and an open-label fish oil (FO) trial to investigate the relationship between long-chain omega-3 (LCn-3) fatty acid status and residual depressive symptoms in SSRI-resistant adolescent MDD patients. Baseline erythrocyte docosahexaenoic acid (DHA)(-28%, p=0.0003), but not eicosapentaenoic acid (EPA)(-18%, p=0.2), was significantly lower in patients (n=20) compared with healthy controls (n=20). Patients receiving 10-week low-dose (2.4 g/d, n=7) and high-dose (16.2 g/d, n=7) FO exhibited significant increases in erythrocyte EPA and DHA composition. In the intent-to-treat sample, depressive symptoms decreased significantly in the high-dose group (n=7, -40%, p<0.0001), and there was a trend in the low-dose group (n=10, -20%, p=0.06). Symptom remission was observed in 40% of patients in the low-dose group and 100% of patients in the high-dose group. There were no significant changes in vital signs and adverse events were rated as mild or moderate in severity. These preliminary findings demonstrate that adolescents with SSRI-resistant depression exhibit robust DHA deficits, and suggest that adjunctive FO supplementation is well-tolerated and effective for increasing LCn-3 fatty acid status and augmenting SSRI antidepressant effects.

SUBMITTER: McNamara RK

PROVIDER: S-EPMC3998067 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Detection and Treatment of Long-Chain Omega-3 Fatty Acid Deficiency in Adolescents with SSRI-Resistant Major Depressive Disorder.

McNamara Robert K RK Strimpfel Jennifer J Jandacek Ronald R Rider Therese T Tso Patrick P Welge Jeffrey A JA Strawn Jeffrey R JR Delbello Melissa P MP

PharmaNutrition 20140401 2

Residual depressive symptoms are commonly observed in adolescents with major depressive disorder (MDD) following treatment with selective serotonin reuptake inhibitors (SSRIs). This study combined a case-control analysis and an open-label fish oil (FO) trial to investigate the relationship between long-chain omega-3 (LC<i>n</i>-3) fatty acid status and residual depressive symptoms in SSRI-resistant adolescent MDD patients. Baseline erythrocyte docosahexaenoic acid (DHA)(-28%, p=0.0003), but not ...[more]

PMID: 24772386

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Project description:Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (β=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:BackgroundThe prevalence of mood disorders in children is a growing global concern. Omega-3 fatty acids (FA) are emerging as a promising adjuvant therapy for depressive disorder (DD) in paediatric patients. The primary objective of this pilot, single-centre, randomized, double-blind controlled study was to compare the efficacy of an Omega-3 FA fish oil emulsion with a control oil emulsion alongside standard treatment for depressive symptoms in children and adolescents suffering from depressive disorder (DD) and mixed anxiety depressive disorder (MADD).Methods38 children (12 patients were treated and diagnosed for at least 1 month before enrolment, 26 patients were first-time diagnosed as DD) aged 11-17 years were randomised 1:1 to the intervention (Omega-3 FA, 19 patients) or active comparator (Omega-6 FA, 19 patients) groups. Children's depression inventory (CDI) ratings were performed at baseline, every 2 weeks for a 12-week intervention period and at 4-week post-intervention. 35 patients (17 in Omega-3 and 18 in Omega-6 groups) who completed the whole intervention period were evaluated. Patients from Omega-3 group were stratified according to diagnosis into two subgroups (DD-10/17 and mixed anxiety depressive disorder (MADD)-7/17 patients) and in the Omega-6 group into DD-10/18 and MADD-8/18 patients. Groups were evaluated separately. Differences between-groups were tested with the Student´s t test or non-parametric Mann-Whitney U test. Two-way ANOVA with repeated measures and Friedman test were used to analyse the Treatment effect for response in CDI score. p < 0.05 was considered significant in all statistical analyses.ResultsSignificant reductions in CDI scores in 35 analysed patients who completed 12 weeks intervention were observed after 12 weeks of intervention only in the Omega-3 group (p = 0.034). After stratification to depressive disorder and mixed anxiety depressive disorder subgroups, the DD subgroup receiving the Omega-3 FA fish oil showed statistically greater improvement (score reduction after 8 week treatment of -9.1 CDI, p = 0.0001) when compared to the MADD subgroup (score reduction after 8 week treatment -4.24 CDI, p = 0.271).ConclusionsCDI scores were reduced in the Omega-3 group and the depression subgroup had greater improvement than the mixed depressive/anxiety group. An Omega-3 fatty acid rich fish oil emulsion may be an effective adjuvant supplement during the treatment of depressive disorders in children. Trial registration ISRCTN81655012.

Dataset Information

Detection and Treatment of Long-Chain Omega-3 Fatty Acid Deficiency in Adolescents with SSRI-Resistant Major Depressive Disorder.

Publications

Detection and Treatment of Long-Chain Omega-3 Fatty Acid Deficiency in Adolescents with SSRI-Resistant Major Depressive Disorder.

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