Marine Omega-3 Fatty Acid Supplementation for Borderline Personality Disorder: A Meta-Analysis.

OBJECTIVE: Several promising studies investigated marine omega-3 fatty acids (ie, fish oil) in borderline personality disorder (BPD), but overall effects remain unclear. The aim of this study was to obtain estimates of effectiveness of omega-3 fatty acids in BPD using meta-analysis, with a priori differentiation of affective, impulsive, and cognitive-perceptual symptom domains. DATA SOURCES: We performed a literature search in PubMed, EMBASE, PsycINFO, and MEDLINE, using terms related to BPD and omega-3 fatty acids. Publication date was not a restriction. STUDY SELECTION: We included randomized controlled trials (RCTs) that compared omega-3 fatty acids to placebo or any active comparator and pooled data using meta-analysis. Five studies were included in the meta-analysis, describing 4 RCTs testing effects of omega-3 fatty acids in 137 patients with BPD or BPD-related behavior. DATA EXTRACTION: Using a pre-piloted data extraction form, we obtained data including intervention dose, duration, and BPD symptom scale scores, differentiating affective, impulsive, and cognitive-perceptual symptom domains. RESULTS: Random effects meta-analysis showed an overall significant decreasing effect of omega-3 fatty acids on overall BPD symptom severity (0.54 standardized difference in means [SDM]; 95% CI = 0.91 to 0.17; Z = 2.87; P = .0041), without heterogeneity (I2 = 0.00; Q = 2.63; P = .45). A priori differentiation of relevant symptom domains showed significant effects on affect dysregulation (0.74 SDM; 95% CI = 1.21 to 0.27; Z = 3.11; P = .002) and impulsive behavior (0.45 SDM; 95% CI = 0.84 to 0.059; Z = 2.26; P = .024). However, effects on cognitive-perceptual symptoms did not reach the significance threshold. CONCLUSIONS: Available data indicate that marine omega-3 fatty acids improve symptoms of BPD, particularly impulsive behavioral dyscontrol and affective dysregulation. Marine omega-3 fatty acids could be considered as add-on therapy.

Omega-3 Fatty Acid Supplementation for Perinatal Depression: A Meta-Analysis.

OBJECTIVE: Several randomized controlled trials (RCTs) investigated omega-3 polyunsaturated fatty acids (PUFAs) (ie, fish oil) in perinatal depression, but their efficacy remains unclear. We performed a meta-analysis of RCTs on omega-3 PUFAs for perinatal depression, comparing a priori defined subgroups: pregnant women vs postpartum women and prevention vs treatment of perinatal depression. METHODS: We searched Web of Science, Embase, PsycINFO, and the Cochrane Library, combining omega-3 PUFAs and perinatal depression terms and including publications up to February 18, 2019, for RCTs on omega-3 PUFAs compared to placebo or any active comparator. RESULTS: Data from 18 RCTs on 4,052 participants showed an overall significant small beneficial effect of omega-3 PUFAs on depressive symptoms compared to placebo (-0.236 standardized difference in means [SDM]; 95% CI = -0.463 to -0.009; P = .042). Heterogeneity was considerable (I² = 88.58; P < .001), with significant subgroup differences explaining 55% of between-study variance (P = .001). In depressed women, omega-3 PUFAs showed a medium effect (SDM = -0.545; 95% CI = -1.182 to 0.093; P = .094) vs no effect in nondepressed women (SDM = -0.073). Moreover, the effect was medium to large in postpartum women (SDM = -0.656; 95% CI = -1.690 to 0.378; P = .214) compared to a negligible effect during pregnancy (SDM = -0.071). RCTs specifically studying postpartum depression showed the largest effect (SDM = -0.886; 95% CI = -2.088 to 0.316; P = .149). CONCLUSIONS: Omega-3 PUFAs have an overall significant small beneficial effect on perinatal depression, with important subgroup differences. We advise against prescribing omega-3 PUFAs for the treatment or prevention of depressive symptoms during pregnancy, given a lack of effect with low heterogeneity. In contrast, omega-3 PUFA supplementation may be a promising (add-on) treatment for postpartum depression.

Biological effects of add-on eicosapentaenoic acid supplementation in diabetes mellitus and co-morbid depression: a randomized controlled trial.

BACKGROUND: Eicosapentaenoic acid (EPA) may reduce increased risks for (cardiovascular) morbidity and mortality in patients with diabetes mellitus (DM) and comorbid major depressive depression (MDD). Yet, effects of EPA-supplementation on biological risk factors for adverse outcomes have not been studied in DM-patients with MDD. METHODS: We performed a randomized, double-blind trial (n = 25) comparing add-on ethyl-EPA-supplementation to placebo on (I) oxidative stress, (II) inflammatory, (III) hypothalamic-pituitary-adrenal (HPA)-axis, (IV) one-carbon-cycle, (V) fatty acid metabolism and (VI) lipoprotein parameters during 12-weeks' follow-up. RESULTS: Besides increases in supplemented α-tocopherol [estimate (95% CI); 3.62 (1.14-6.11) µmol/l; p = 0.006] and plasma and erythrocyte EPA, the intervention did not influence other oxidative stress, inflammatory or one-carbon-cycle parameters compared to placebo. HPA-axis reactivity significantly decreased in the EPA-group (N = 12) [AUC(i): -121.93 (-240.20--3.47) min×nmol/l; p = 0.045], not in the placebo-group (N = 12). Furthermore, EPA-supplementation increased erythrocyte and plasma docosapentaenoic acid, and decreased plasma arachidonic acid (AA) concentrations [-1.61 (-3.10--0.11) %; p = 0.036]. Finally, EPA had a multivariate influence on lipoprotein concentrations (p = 0.030), reflected by relative increases in high density lipoprotein [HDL; 0.30 (0.02-0.58) mmol/l; p = 0.039] and total cholesterol concentrations [1.01 (0.29-1.72) mmol/l; p = 0.008]. CONCLUSION: Overall, add-on EPA-supplementation had limited effects on biological risk factors for adverse outcome in this sample of DM-patients with comorbid MDD. Besides increases in concentrations of supplemented α-tocopherol and EPA, AA decreased, and inconclusive effects on HPA-axis (re)activity and lipoprotein concentrations were observed. Therefore, further studies on the alleged beneficial effects of EPA-supplementation on biological risk factors for adverse outcome in DM-patients with comorbid MDD seem warranted, preferably using clinical outcomes such as (cardiovascular) DM-complications.

Sustained medically unexplained physical symptoms in euthymic patients with recurrent depression: predictive value for recurrence and associations with omega 3- and 6 fatty acids and 5-HTTLPR?

BACKGROUND: Identification of potentially modifiable risk factors for recurrence in recurrent depression could provide opportunities to improve preventive interventions. In this study we aimed to examine the predictive value of medically unexplained physical symptoms (MUPS) on time to recurrence in recurrent depression. Additionally, to elucidate pathophysiological mechanisms that could explain the relations between MUPS and depression, we investigate the association between a sustained high level of MUPS, and (I) omega (ω)-3 and -6 fatty acid (FA)-status and (II) functional polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR). METHODS: Based on three Physical Symptom Checklist (PCS) scores over 12 months, we defined two groups of remitted recurrently depressed patients: 41 patients with a sustained high number of MUPS and 34 patients with a sustained low number or no MUPS. Patients were followed-up for 3.5 years while recurrence of their depression was monitored. In addition, we analyzed patients' erythrocyte's FA-profiles and triallelically genotyped their 5-HTTLPR. RESULTS: A sustained high level of MUPS predicted consecutive depression recurrence over 3.5 years (adjusted relative risk 2.8). FA-status and distribution of 5-HTTLPR variant frequencies did not differ between patients with sustained high compared to low/absent MUPS-levels. LIMITATIONS: Our sample was relatively small. CONCLUSION: Remitted recurrently depressed patients with sustained MUPS have a considerably increased risk of recurrence. Having sustained MUPS is not associated with either erythrocyte ω-3 or -6 FA-levels or 5-HTTLPR polymorphism. Recognition and reducing MUPS in an early state could prevent a (depressive) relapse.