Research paperEffects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: A randomized, double-blind, placebo-controlled trial
Introduction
Psychophysiological symptoms were considered a prominent feature of post-traumatic stress disorder (PTSD) (Kardiner, 1941; Mott, 1919) even before its diagnostic criteria was first established in 1980 (American Psychiatric Association, 1980). A recent quantitative meta-analytic review confirmed that people with PTSD clearly displayed increased heart rate (HR) and skin conductance (SC) not only as a response to trauma-related cues but also at baseline, even in the absence of obvious traumatic stimuli (Pole, 2007). However, little is known about the effectiveness of drugs for the secondary prevention of these psychophysiological symptoms. To our knowledge, only one published clinical trial (Pitman et al., 2002) has reported a positive preventive effect on psychophysiological responses of beta-blockers administered immediately after a traumatic event. Obviously, effective agents other than beta-blockers must be explored.
As for possible alternatives, a leading candidate is omega-3 polyunsaturated fatty acids (PUFAs). Docosahexaenoic acid (DHA; 22:6) and eicosapentaenoic acid (EPA; 20:5), found in fish oil, and α-linolenic acid (18:3) are omega-3 PUFAs, essential fatty acids. They are involved in wide ranges of vital activities. Several possible mechanisms underlie the prevention of psychophysiological symptoms with omega-3 PUFAs. First, fish oil can facilitate fear-extinction learning by facilitating hippocampal neurogenesis (Beltz et al., 2007, Calderon and Kim, 2004, Kitamura et al., 2009, Matsuoka, 2011). In addition, omega-3 PUFAs maintain endocannabinoid-mediated neuronal functions (Lafourcade et al., 2011, Yamada et al., 2014) that facilitates extinction of fear memories (Marsicano et al., 2002). Such actions against fear memory are similar to those of beta-blockers (Brunet et al., 2008, Pitman et al., 2002). Second, fish oil can reduce sympathetic nerve activity (Ginty and Conklin, 2012, Hamazaki et al., 2005, Matsumura et al., 2012, Spence et al., 2003) that possibly plays a pivotal role in the development of PTSD (Charney et al., 1993). Third, intervention studies have shown effectiveness of fish oil in other psychiatric disorders (Freeman et al., 2006, Lin and Su, 2007). However, no evidence yet exists concerning psychophysiological symptoms.
In the present study, we examined the effectiveness of post-trauma supplementation of omega-3 PUFAs on reducing subsequent psychophysiological symptoms of PTSD in Japanese accident survivors. We adapted a script-driven imagery protocol (Brunet et al., 2008, McNally et al., 2004, Pitman et al., 2002) to measure psychophysiological symptoms in a randomized, double-blind, placebo-controlled trial. We hypothesized that patients who supplemented with omega-3 PUFAs would show reduced psychophysiological responses to trauma-related stimuli and/or decreased resting psychophysiological levels compared to those who supplemented with placebo.
Section snippets
Study design
This study was a single-center, stratified (gender, age, sense of threat), randomized (allocation ratio=1:1), double-blind, placebo-controlled, parallel-group trial. This study was conducted as part of the TPOP (Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid) trial (registered at ClinicalTrials.com as NCT00671099). The full protocol is available as a published paper (Matsuoka et al., 2013).
Participants
Participants were a total of 83 severely
Participant flow
Among 1386 patients, 1026 were excluded by exclusion criteria, early discharge before screening, inclusion criteria, and other reasons. The remaining 360 patients continued to the next stage of psychoeducation. Among these, 250 were excluded by exclusion criteria, no will to participate, frequent fish consumption, and other reasons. Although the remaining 110 patients consented to participate and were randomized, 25 were lost to follow-up and two were excluded on technical grounds due to
Discussion
Results of the present study partially support our hypothesis that post-trauma omega-3 PUFAs reduce subsequent psychophysiological PTSD symptoms. Namely, 12-week supplementation of omega-3 PUFAs following accidental injury reduced HR during both rest and imagery periods that were performed 3-months after the event, although we observed no group difference in SC. The HR-reducing action of omega-3 PUFAs has potential benefits for those at high risk of PTSD, aside from the psychophysiological
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2022, Epigenetics of Stress and Stress DisordersThe effects of eicosapentaenoic acid dietary supplementation on behavioral parameters and expression of hippocampal brain-derived neurotrophic factor in an animal model of post-traumatic stress disorder
2019, European Journal of PharmacologyCitation Excerpt :To establish the proper animal model of PTSD, exclusion of learning effects will be needed in future studies to observe hypervigilant/hyperarousal behaviors. Many clinical studies have reported the effectiveness of supplemental EPA administration on both prevention (Su et al., 2015; Matsumura et al., 2017; Zhang XW et al., 2016ab) and treatment (Mocking et al., 2016; Su et al., 2018) of psychiatric disorders including major depression, anxiety symptoms, PTSD, and cognitive impairment. Considering that PTSD has an etiological trigger of life-threatening event and EPA comes from natural food of oily fish without apparent side effects, amelioration of PTSD psychiatric symptoms by EPA supplementation started just after traumatization is quite promising.
Theranostic pharmacology in PTSD: Neurobiology and timing
2019, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Unfortunately, this remarkable finding has not been replicated. Matsumura et al. (2017) found omega-3 fatty acid supplementation reduced spontaneous and script-driven imagery associated heart rate in Japanese accident survivors with PTSD. We note that to date there is still no published RCT of lithium.
Mechanisms underlying the effects of n-3 polyunsaturated fatty acids on fear memory processing and their hypothetical effects on fear of cancer recurrence in cancer survivors
2018, Prostaglandins Leukotrienes and Essential Fatty AcidsCitation Excerpt :n-3 PUFAs can also influence vagus nerve signaling. Matsumura et al. found that 12 weeks of n-3 supplementation for traumatized severely accident-injured survivors reduced heart rate both at rest and in a “recall period” when the participants remembered the traumatic experience using a script summarizing their experience [98]. Previous work also reported that the consumption of n-3 PUFAs is related to a reduced heart rate and improved heart rate variability [99].