Polyunsaturated fatty acid composition and childhood adversity: Independent correlates of depressive symptom persistence
Introduction
Many ecological and therapeutic studies have demonstrated the importance of polyunsaturated fatty acids (PUFA) to risks for (Lin et al., 2010, Assies et al., 2010, Marx et al., 2015, Horikawa et al., 2016, Beydoun et al., 2015), and recovery from (Mocking et al., 2015, Mocking et al., 2016), depressive disorders. PUFAs are important components of neuronal membranes and particular PUFA deficits adversely affect both the serotonergic and dopaminergic systems (Hibbeln et al., 1998, de la Presa Owens and Innis, 1999). In addition, most PUFAs in the omega-3 series are anti-inflammatory, while those in the omega-6 series are pro-inflammatory (Calder, 2006). A balance in the PUFAs favoring the omega-6 component is therefore associated with increases in pro-inflammatory cytokines and, as an apparent consequence, with increased risks for depressive symptoms (Pascoe et al., 2011).
PUFA measurements at one point reflect not only an individual's concurrent dietary habits, but also that person's activity of desaturases and elongases, enzymes responsible for the interconversion to effector omega-3 and omega-6 fatty acids (Lemaitre et al., 2011). Therefore, a single PUFA measure is likely to predict, at least to some degree, future values and thus to have prognostic weight for the course of depressive illness. Most prospective studies that have examined relationships between baseline dietary omega-3 intake and incident depressive disorder have failed to find them, however (Hakkarainen et al., 2004, Kesse-Guyot et al., 2012, Sanchez-Villegas et al., 2007, Lucas et al., 2011). Another reporter identified a group of adolescents with MDD who had failed to respond to a six-week trial of SSRI antidepressants and found clear deficits in docosahexaenoic acid (DHA) levels relative to those of a nested control group (McNamara et al., 2014). The majority went on to achieve remission of symptoms in a ten-week trial of DHA and eicosapentanoic acid (EPA). Several that did not exclude individuals with depressive disorders at baseline, and that could therefore be considered studies of prevalence rather than incidence, did find association between omega-3 dietary intake and depressive morbidity during follow-up (Beydoun et al., 2015, Astorg et al., 2008, Colangelo et al., 2009). Only two prospective studies have employed direct measures of PUFA composition as potential predictors of depressive morbidity. One found no relationship between baseline serum phospholipid PUFA measures and the occurrence of depressive illness as revealed by records of antidepressant prescriptions (Astorg et al., 2009). In contrast, a much smaller, case-control report found significantly higher ratios of omega-6 to omega-3 concentrations among women who developed post-partum depression in comparison to those who did not (De Vriese et al., 2003).
Several additional prospective studies are germane if suicidal behavior is viewed as a proxy for depressive illness. Sublette (Sublette et al., 2006) found higher ratios of omega-6 to omega-3 composition in patients who attempted suicide during follow-up and Lewis (Lewis et al., 2011) reported lower DHA composition in a large sample of active duty military service members who later committed suicide in comparison to demographically-matched control individuals.
Childhood adversity is a well-established antecedent of depressive illness (Scott et al., 2012, Hovens et al., 2010, Chapman et al., 2004). Moreover, among individuals with depressive disorder, those who have experienced such adversity have poorer outcomes (Hovens et al., 2012, Kim et al., 2013, Klein et al., 2008, Tunnard et al., 2014). While variables such as socio-economic status (SES) may influence both the likelihood of childhood adversity and subsequent dietary habits (Appleton et al., 2007), it may be that PUFA composition and childhood adversity measures are orthogonal in their relationships to the risk for, and course of, depressive illness. If both measures are independently predictive of greater depressive morbidity over time, their combination would be more predictive in at least an additive fashion. Even so, these two factors may share a common pathway in the causal route to depressive illness. A candidate for such a shared intermediary is neuroticism or negative affectivity.
Measures of neuroticism correlate with both the likelihood and the persistence of depressive symptoms. Separate studies have shown significant associations between neuroticism and both low PUFA (Conklin et al., 2007) intake or composition (Evans et al., 2012), and childhood adversity (Hengartner et al., 2015, Allen and Lauterbach, 2007). Notably, at least one study has shown that neuroticism mediated the relationship between cumulative lifetime adversity, inclusive of childhood adversity, and current depressive symptoms (Abravanel and Sinha, 2015). A demonstration that PUFA composition and childhood adversity have independent influences on neuroticism would have important implications for the mechanisms underlying depressive disorders.
Section snippets
Participants
Participants, 15–20 years old, who were within one month of starting a selective serotonin reuptake inhibitor (SSRI) (n = 88), or who were taking no psychotropic medication (n = 92), were enrolled from outpatient and inpatient clinical settings, as well as by e-mail solicitation and word of mouth, into a longitudinal observational study designed to examine the effects of SSRIs on bone mass (Calarge et al., 2014). Of those taking SSRIs, 25 (28.4%) were taking fluoxetine, 25 (28.4%) sertraline, 6
Results
One hundred eighty individuals had baseline PUFA composition data available and, of these, 156 had completed MPQ and ETISR scales. IDS values for all three follow-up visits over the course of one year were available for 103 and 149 had at least one visit. Completers did not differ from the full sample by any of the intake measures used in the present analysis (Table 1).
Partial correlations, controlling for age and sex, revealed positive relationships between baseline IDS scores and both
Discussion
This sample of high school and college students entered a prospective study with depressive symptoms that spanned chiefly the lower end of the severity spectrum. Those who finished one year of follow-up had a mean (SD) IDS score of only 11.5 (9.6), a value at the lower end of the range considered “mild”. Nevertheless, the hypothesized predictors of prospectively observed depressive symptoms performed as expected. Those with higher levels of negative emotionality and of childhood adversity
Disclosures
The authors have no conflict of interest to report.
Results were presented in a poster session. Summaries were not distributed nor were abstracts published in the program.
Acknowledgements
This work was funded by the National Institute of Mental Health (R01MH090072), the National Center for Research Resources (2UL1TR000442-06), and by the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK097820) (AWN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
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