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Low omega-3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder.
Cussotto, S, Delgado, I, Oriolo, G, Kemper, J, Begarie, D, Dexpert, S, Sauvant, J, Leboyer, M, Aouizerate, B, Martin-Santos, R, et al
Depression and anxiety. 2022
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Plain language summary
Major depressive disorder (MDD) is a leading cause of disability, and antidepressant drug treatment is only effective in over half of patients with a high prevalence of treatment resistance. The importance of nutrition in mental health is gaining recognition. Omega-3 is an essential polyunsaturated fatty acid (PUFA) vital for anti-inflammatory processes and brain integrity. In the absence of the body's ability to make Omega-3, it or its precursors must be acquired from the diet. Yet altered metabolic pathways can hamper the process and the adequate balance with PUFA Omega‐6 is also crucial, as elevated levels of Omega-6 are linked to several diseases. An extensive amount of research suggests that higher Omega-3 levels reduce the occurrence of depression. Yet results using just Omega-3s for depression have been varied. This European-wide study sought to investigate how the PUFA status could affect the clinical response to treatment with antidepressants. 60-adults with an average age of 41 with major depressive disorders received antidepressive treatment. Their red blood cell fatty acids content was determined, and at the end of the 8-week trial treatment responders and non-responders were identified. Findings affirmed the existing knowledge that depressive symptoms are strongly associated with PUFA status. Patients who did not respond to treatment showed low levels of Omega-3 and an unfavourable ratio of Omega-3 to Omega-6 at the start of treatment. Higher levels of Omega-3 fatty acid of DHA seemed to produce a better clinical response to treatments than the Omega-3 of EPA. The authors discussed some potential mechanisms and suggested that PUFA intake and metabolism could be a potential tool for the management of treatment-unresponsive patients with depression. This review highlights the clinical importance of considering PUFA status and metabolism in the support of major depressive disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Healthy eating such as that with low omega-6 diets has more than a physiological result on the human body and carries significant biochemical consequences when the omega-6 to omega-3 ratio is deemed to be ‘high’.
- The result of this research has pharmaceutical implications - if the findings could be imparted to the general public in layman’s terms, practitioners could empower individuals to take greater control of their mental health through more naturalistic means, i.e., optimised nutrition.
- There are wider cognitive considerations of healthy eating beyond that of treating Major Depressive Disorder due to implicated blood-brain-barrier effects, as concluded in this study.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Sixty adults suffering from major depressive disorder (MDD) were recruited into a multicenter study assessing the impact of baseline polyunsaturated (PUFA) levels on responsiveness to antidepressants. Neuropsychiatric evaluations producing MADRS (Montgomery Åsberg Depression Rating Scale) scores at baseline, four weeks and again at eight weeks, were performed. The pre-recorded baseline PUFA levels were then used as an associative and predictive indicator when viewing the end point scoring of participants, thus categorising into responsive and nonresponsive strata.
Of those with low omega-3 and high omega-6 to omega-3 ratio at baseline, there was increased association with ‘non-responsive’ classification at end point (week 8). Participants were deemed ‘non-responsive’ to anti-depressant treatment when scores at week 8 failed to demonstrate ≥50% reduction in MADRS scoring.
Clinical practice applications:
- Clinicians could monitor MDD within at-risk-groups, such as those who are overweight (mean BMI of ALL study participants was 24.20 kg/m2 with a standard deviation of 4.21) or those experiencing an inflammatory state with blood-brain-barrier involvement, as part of a mental ill-health prevention programme.
- When presenting with symptoms of major depressive disorder and prescribing antidepressants, clinicians could recommend increasing consumption of foods high in omega-3 and/or querying the patient about their dietary habits.
- Article supports recommendations for an increase in the consumption of omega-3 rich foods amongst the general population to prevent or intervene in cases of major depressive disorder.
- Wider cognitive implications beyond major depressive disorder in the presence of low omega-3, such as cognitive decline as seen with dementia, theorised due to altered blood-brain-barrier (Cussotto et al., 2022; Gustafson et al., 2020).
Considerations for future research:
- Repeated studies, with normalised distribution of antidepressant and sample size by country, with greater geographic inclusion, along with age categorisation. The broader geographic inclusion is necessary to rule out cultural diets as a confounding variable. An example of how different cultural diets could influence the results, which has potentially been highlighted in this study, is the more predominant consumption of a Mediterranean diet which may have been the case for the participants from Spain or, as could also be the case, an underlying vitamin D deficiency of the participants from Germany.
- Novel studies for assessing diet against mood could be beneficial to fully apply the findings of this study to clinical practice applications and that of the practice of nutritional therapists. The thinking here is the potential for anti-inflammatory foods inducing better mood results through gut-brain axis links and resultant influence on microbiome.
Abstract
BACKGROUND Major depressive disorder (MDD) is characterized by a high rate of treatment resistance. Omega (ω)-3 polyunsaturated fatty acids (PUFAs) were shown to correlate with depressive phenotype both in rodents and in humans. However, few studies to date have investigated the role of PUFAs in antidepressant response. The primary aim of this study was to assess the link between baseline PUFA composition and changes in depressive symptoms as well as antidepressant response in a multicenter study of depressed patients. METHODS Sixty depressed adults who met criteria for MDD according to DSM-IV-TR were recruited. Neuropsychiatric evaluations occurred at baseline and after 4 and 8 weeks of treatment with standard antidepressants, including escitalopram (N = 45), sertraline (N = 13) and venlafaxine (N = 2). At study endpoint, patients were stratified into responders (R) or non-responders (NR) based on their MADRS (Montgomery-Åsberg Depression Rating Scale) score. Baseline PUFA levels were assessed and their association with clinical response was determined. RESULTS Lower ω-3 PUFA levels were associated to worse baseline symptomatology. Baseline levels of PUFAs were significantly different between R and NR, with R exhibiting lower docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and ω-3 index; and higher ω-6/ω-3 ratio than NR before the start of antidepressant treatment. DHA levels as well as the ω-3 index and ω-6/ω-3 ratio significantly predicted response to antidepressants at study endpoint. CONCLUSIONS These results show that baseline levels of PUFAs predict later response to standard antidepressants in depressed subjects. They suggest that PUFA intake and/or metabolism represent a novel modifiable tool for the management of unresponsive depressed patients.
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Association of Migraine with Its Comorbidities and Food Specific Immunoglobulin G Antibodies and Inflammatory Cytokines: Cross-Sectional Clinical Research.
Zhao, Z, Jin, H, Yin, Y, Hou, Y, Wang, J, Tang, C, Fu, J
Journal of pain research. 2021;14:2359-2368
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Plain language summary
Migraine is a chronic, multifactorial headache with multiple comorbid conditions. Previous studies have shown a correlation between food-specific IgG antibodies and chronic inflammation in migraineurs. IgG antibody detection may therefore be a biomarker for migraine since it plays a crucial role in the pathogenesis of the disease. This cross-sectional clinical trial investigated the relationship between IgG antibodies against food antigens and headaches, gastrointestinal symptoms, anxiety, depression, sleep disorders, dermatosis and inflammatory cytokines such as IL-6, TNFα, and IL-10. In this study, migraine patients who had positive food-specific IgG antibodies had severe migraine, anxiety, gastrointestinal symptoms, and elevated levels of proinflammatory cytokines such as IL-6 and TNFα, indicating a causal relationship. However, further studies are required to determine the immune reaction to food antigens and the effect of eliminating IgG positive foods on migraine and its associated comorbidities. Nevertheless, this study can help healthcare professionals understand how food-specific antibodies play a role in diagnosing and treating migraine.
Abstract
PURPOSE The relationship between food allergy caused by food specific IgG antibodies and migraine has received increased attention in recent years. Here, we aimed to evaluate the effects of food specific IgG antibodies on headache, gastrointestinal symptoms, anxiety, depression, sleep disorders, dermatosis, and serum inflammatory cytokines in migraine patients, and to quantitatively assess the effect of IgG levels on the severity of headache and its comorbidities. METHODS Of 89 migraine patients, those who had one or more food specific IgG antibodies ≥50 U/mL were classified into the IgG positive group, which was then further divided into subgroups based on differing numbers of food allergens. All other subjects were classified into the IgG negative group. We compared the frequency and severity of migraine, anxiety, depression, sleep disorders, dermatosis, and inflammatory cytokines between groups. A regression model was performed to further assess the effect of overall positive IgG concentration and the mediation effect of inflammatory cytokines. RESULTS Participants in the positive IgG group (n = 67) were more likely to have longer time elapsed since diagnosis, more frequent and severe migraine, a higher risk of developing anxiety and gastrointestinal symptoms, along with higher IL-6 and TNF-α. Subgroups with more food allergens generally had worse conditions as well. After adjusting for the inflammatory cytokines, the effect of IgG was reduced. CONCLUSION Migraine patients with positive food specific IgG antibodies had worse migraine, anxiety, and gastrointestinal symptoms. Inflammatory cytokines partially mediate the causal pathway between food specific IgG antibodies, migraine, and migraine comorbidities.
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Psychological, pharmacological, and combined treatments for binge eating disorder: a systematic review and meta-analysis.
Ghaderi, A, Odeberg, J, Gustafsson, S, Råstam, M, Brolund, A, Pettersson, A, Parling, T
PeerJ. 2018;6:e5113
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Plain language summary
It is estimated that between 1% and 4% of the population suffer from binge eating disorder (BED), which is characterised by episodes of binge eating and a lack of control over eating. People with BED tend to have lower mental wellbeing and are more likely to be overweight or obese, leading to increased risk of related diseases such as type 2 diabetes. Treatments for BED include psychological treatments such as cognitive behavioural therapy (CBT), and medication such as selective serotonin re-update inhibitors (SSRIs) and weight-loss medication, as well as medications that are normally prescribed for attention deficit disorders, addictions and epilepsy. The aim of this review was to evaluate previous trials on the effectiveness of a range of psychological, pharmacological and combined treatments for BED. The authors looked at 45 trials which included over 4,000 participants. They found moderate support for the effectiveness of CBT and guided self-help for the treatment of BED in stopping or reducing the frequency of binge eating. Overall, there was a lack of long-term follow-ups, with no data on the long-term effect of medications. Interesting, the use of SSRIs did not have a significant impact on depressed mood in people with BED and lisdexamfetamine was the only intervention associated with a reduction in BMI (an expected finding as this medication is associated with some loss of appetite). There were very few studies that directly compared psychological treatments with medication, and a lack of evidence on the effectiveness of treatment in younger adults and teenagers. The authors concluded that more long-term studies are needed in the treatment of BED (included exploring quality of life), standardised assessments of BED and people from underrepresented populations (e.g. adolescents).
Abstract
OBJECTIVE To systematically review the efficacy of psychological, pharmacological, and combined treatments for binge eating disorder (BED). METHOD Systematic search and meta-analysis. RESULTS We found 45 unique studies with low/medium risk of bias, and moderate support for the efficacy of cognitive behavior therapy (CBT) and CBT guided self-help (with moderate quality of evidence), and modest support for interpersonal psychotherapy (IPT), selective serotonin reuptake inhibitors (SSRI), and lisdexamfetamine (with low quality of evidence) in the treatment of adults with BED in terms of cessation of or reduction in the frequency of binge eating. The results on weight loss were disappointing. Only lisdexamfetamine showed a very modest effect on weight loss (low quality of evidence). While there is limited support for the long-term effect of psychological treatments, we have currently no data to ascertain the long-term effect of drug treatments. Some undesired side effects are more common in drug treatment compared to placebo, while the side effects of psychological treatments are unknown. Direct comparisons between pharmaceutical and psychological treatments are lacking as well as data to generalize these results to adolescents. CONCLUSION We found moderate support for the efficacy of CBT and guided self-help for the treatment of BED. However, IPT, SSRI, and lisdexamfetamine received only modest support in terms of cessation of or reduction in the frequency of binge eating. The lack of long-term follow-ups is alarming, especially with regard to medication. Long-term follow-ups, standardized assessments including measures of quality of life, and the study of underrepresented populations should be a priority for future research.