Clinical research to date has primarily focused on the emotional symptoms of depression, while problems with cognition can equally impact everyday functioning and quality of life, especially in children and adolescents, and meta-analyses have reported moderate cognitive impairments in depressed adults.
Nutritional patterns in Western societies have shifted toward foods containing more omega-6 (n-6) compared to omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and n-3 PUFA deficiency has been associated with depression with eicosapentaenoic acid (EPA) status specifically being negatively associated with depression severity.
Meta-analytic evidence has further suggested beneficial effects of n-3 PUFA supplementation on depression symptoms, especially with high doses of EPA. Some meta-analyses have also suggested beneficial effects of EPA rather than docosahexaenoic acid (DHA). In youths, however, only four randomised controlled trials (RCTs) have been carried out.
While several studies link n-3 PUFA intake with cognitive function, it is less clear how n-3 PUFAs might affect cognition in depressed individuals.
Researchers from Switzerland therefore conducted the current investigation to dig deeper into the associations between EPA and DHA statuses and cognitive performance in depressed children and adolescents.
The team used data from the “The Omega-3-pMDD trial”, a multi-centre placebo-controlled trial aiming to investigate the efficacy of omega-3 fatty acid supplementation in moderately to severely depressed children and adolescents aged 8–17 years. Participants were recruited from seven different in- and outpatient services across Switzerland.
During the lead-in phase, all participants received a placebo in a single blinded fashion and psychopathological, cognitive, and bloodwork baseline data were collected. Assessment of the inclusion and exclusion criteria was repeated at the end of this phase, after which patients were randomized to a treatment arm in a double-blind fashion. At the time of analysis, the sample consisted of 107 patients that met all of the inclusion and no exclusion criteria at screening and had analyzed PUFA blood sample data.
The current report investigated this sub-sample in a cross-sectional manner using single cognitive and psychopathological assessments from the lead-in phase of the trial, to compare RBC EPA and DHA levels, as well as depression severity in relation to memory performance.
The report indicates that, over 20% of the patients (compared to an expected 15.9% in a healthy population) achieved below average normative scores. These results indicate a tendency toward impaired verbal memory in depressed youths. However, they did not find any significant differences in verbal memory performance between moderately and severely depressed patients.
Most importantly, the researchers looked at the data from the short-term memory trials of a verbal list learning test. They found that, compared to patients with a moderate or low EPA status, those with a high EPA status seemed to remember more words faster.
However, they found no significant differences concerning EPA status between moderately and depressed patients.
The researchers were not able to find a significant effect of DHA on any verbal memory parameter. In fact, surprisingly, the data revealed a higher DHA and total omega-3 status in severely depressed patients, compared to the moderately depressed. One explanation the researchers suggest for this is altered nutritional patterns.
These results are in line with previous findings from meta-analyses that suggested beneficial effects of EPA but not DHA on cognitive functioning and effects in clinical rather than healthy populations.
The report concludes: "Our results further contribute to previous findings that reported some impairment considering cognitive functions and especially memory performance in depressed youths.
"Although the reported analyses with EPA and DHA only contributed associations between RBC levels and verbal memory rather than effects of supplementation, they further corroborate evidence from meta-analyses that confirmed the beneficial supplementation effects of EPA, but not DHA.
"Thus, our findings suggest that an increased dietary intake of EPA might prove beneficial for cognitive improvement or even remission in depressed youths. Based on our findings, future RCTs should investigate the effects of EPA compared to DHA supplementation in depressed children and adolescents to potentially establish a recommendation for a natural and easily accessible intervention for cognitive improvement or remission in depressed youths.
"The supplementation advantages of EPA over DHA have yet to be explained, considering EPA is found in much smaller concentrations within the brain compared to DHA. The researchers also note there is a lack of understanding about the actual absorption and utilization of both EPA and DHA, so it's important to investigate the moderating effects of, for example, the microbiome, as these might explain differential effects in different populations."
n-3 PUFAs and Depression
The anti-inflammatory properties of n-3 PUFAs are believed to be responsible for their beneficial effects in relation to depression as proinflammatory cytokines have been shown to play a role in depression, and hence n-3 PUFAs have been discussed to counteract these inflammatory processes.
Many studies have shown n-3 PUFAs are vital for normal brain development. Several studies in youths have reported positive associations between reported dietary n-3 PUFA intake and cognitive performance.
In a study by Montgomery et al., low blood n-3 PUFA status was associated with poorer reading abilities and working memory performance in children. Similarly, Wurff et al. reported better performance on an attention task for adolescents with higher n-3 PUFA status.
Drechsler. R. et al
"Verbal Memory Performance in Depressed Children and Adolescents: Associations with EPA but Not DHA and Depression Severity"