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Clearance of fear memory from the hippocampus through neurogenesis by omega-3 fatty acids: a novel preventive strategy for posttraumatic stress disorder?

Matsuoka Y - Biopsychosoc Med (2011)

Bottom Line: Not only has accidental injury been shown to account for a significant health burden on all populations, regardless of age, sex and geographic region, but patients with accidental injury frequently present with the psychiatric condition of posttraumatic stress disorder (PTSD).Physicians in the field of psychosomatic medicine and critical care medicine have the opportunity to see injured patients in the immediate aftermath of an accident.This article first briefly reviews the prevalence and associated factors of accident-related PTSD, then focuses on a conceptual model of fear memory and proposes a new, rationally hypothesized translational preventive intervention for PTSD through promoting hippocampal neurogenesis by omega-3 fatty acid supplementation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. yutaka@ncnp.go.jp.

ABSTRACT
Not only has accidental injury been shown to account for a significant health burden on all populations, regardless of age, sex and geographic region, but patients with accidental injury frequently present with the psychiatric condition of posttraumatic stress disorder (PTSD). Prevention of accident-related PTSD thus represents a potentially important goal. Physicians in the field of psychosomatic medicine and critical care medicine have the opportunity to see injured patients in the immediate aftermath of an accident. This article first briefly reviews the prevalence and associated factors of accident-related PTSD, then focuses on a conceptual model of fear memory and proposes a new, rationally hypothesized translational preventive intervention for PTSD through promoting hippocampal neurogenesis by omega-3 fatty acid supplementation. The results of an open-label pilot trial of injured patients admitted to the intensive care unit suggest that omega-3 fatty acid supplementation immediately after accidental injury can reduce subsequent PTSD symptoms.

No MeSH data available.


Related in: MedlinePlus

Flow diagram of the planned progress through the phases of a parallel randomized trial of omega-3 fatty acid supplementation for secondary prevention of PTSD after accidental injury.
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Figure 3: Flow diagram of the planned progress through the phases of a parallel randomized trial of omega-3 fatty acid supplementation for secondary prevention of PTSD after accidental injury.

Mentions: Support for the ability of omega-3 fatty acids to minimize subsequent PTSD symptoms comes from one published but preliminary open trial [83]. The author and colleagues [83] recruited 15 consecutive patients admitted to the ICU at a Japanese general hospital immediately following accidental injury (mostly MVA). Patients received omega-3 fatty acid capsules containing 1,470 mg DHA and 147 mg eicosapentaenoic acid, equivalent to 140 g of grilled cololabis saira 'SANMA in Japanese', daily for 12 weeks. The primary efficacy variable was score on the Clinician-Administered PTSD Scale (CAPS). Omega-3 fatty acid supplementation was well tolerated and resulted in a significantly increased DHA concentration in erythrocytes. Compared with the hypothetical mean in our previous cohort study [84], omega-3 fatty acid supplementation resulted in a significantly reduced mean CAPS total score (11 vs. 25, p = 0.03), and over the 12-week period, only one patient (1/15, 6.7%) developed symptoms consistent with a diagnosis of both PTSD and major depression. Regarding the adherence, significant differences in erythrocyte DHA concentrations were confirmed between weeks 0 and 12 (mean % total fatty acids: 5.9 ± 1.4 vs. 8.4 ± 1.7, p < .001). The author and colleagues also investigated the potential role of BDNF as an underlying mechanism of omega-3 fatty acid action for the prevention of PTSD [85]. Serum BDNF was significantly elevated from weeks 0 to 12 (n = 11, 52.4 ± 16.7 vs. 79.8 ± 13.8, p = 0.001), although it was largely unchanged in the two patients who developed PTSD or major depression during the trial. Change in the serum BDNF between weeks 0 to 12 was significantly larger in the non-distress group than in the distress group, who met the criteria for PTSD or major depression (median, 33.5; range, 8.5-56.0 vs. median, 5.4; range, 4.4-6.4, p = 0.037). Recently, Peters and colleagues [86] have reported excellent work that BDNF infused into the infralimbic medial prefrontal cortex (IL mPFC) reduced conditioned fear, even in the absence of extinction training. And they reported that rats failing to learn extinction showed reduced BDNF in hippocampal inputs to the IL mPFC and that augmenting BDNF in this pathway prevented extinction failure. Hence, our observation would be reasonable. Increasing BDNF activity in hippocampal BDNF may prove to be efficacious intervention for PTSD. Because of the open-label design and the lack of controls, however, no definitive conclusion could be drawn from the trial and we must wait for the results of an adequately powered randomized controlled trial (ClinicalTrials.gov Identifier: NCT00671099) (Figure 3). However, this pilot study has provided promising support for our hypothesis that omega-3 fatty acid supplementation started shortly after accidental injury may be efficacious in attenuating PTSD symptoms.


Clearance of fear memory from the hippocampus through neurogenesis by omega-3 fatty acids: a novel preventive strategy for posttraumatic stress disorder?

Matsuoka Y - Biopsychosoc Med (2011)

Flow diagram of the planned progress through the phases of a parallel randomized trial of omega-3 fatty acid supplementation for secondary prevention of PTSD after accidental injury.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045887&req=5

Figure 3: Flow diagram of the planned progress through the phases of a parallel randomized trial of omega-3 fatty acid supplementation for secondary prevention of PTSD after accidental injury.
Mentions: Support for the ability of omega-3 fatty acids to minimize subsequent PTSD symptoms comes from one published but preliminary open trial [83]. The author and colleagues [83] recruited 15 consecutive patients admitted to the ICU at a Japanese general hospital immediately following accidental injury (mostly MVA). Patients received omega-3 fatty acid capsules containing 1,470 mg DHA and 147 mg eicosapentaenoic acid, equivalent to 140 g of grilled cololabis saira 'SANMA in Japanese', daily for 12 weeks. The primary efficacy variable was score on the Clinician-Administered PTSD Scale (CAPS). Omega-3 fatty acid supplementation was well tolerated and resulted in a significantly increased DHA concentration in erythrocytes. Compared with the hypothetical mean in our previous cohort study [84], omega-3 fatty acid supplementation resulted in a significantly reduced mean CAPS total score (11 vs. 25, p = 0.03), and over the 12-week period, only one patient (1/15, 6.7%) developed symptoms consistent with a diagnosis of both PTSD and major depression. Regarding the adherence, significant differences in erythrocyte DHA concentrations were confirmed between weeks 0 and 12 (mean % total fatty acids: 5.9 ± 1.4 vs. 8.4 ± 1.7, p < .001). The author and colleagues also investigated the potential role of BDNF as an underlying mechanism of omega-3 fatty acid action for the prevention of PTSD [85]. Serum BDNF was significantly elevated from weeks 0 to 12 (n = 11, 52.4 ± 16.7 vs. 79.8 ± 13.8, p = 0.001), although it was largely unchanged in the two patients who developed PTSD or major depression during the trial. Change in the serum BDNF between weeks 0 to 12 was significantly larger in the non-distress group than in the distress group, who met the criteria for PTSD or major depression (median, 33.5; range, 8.5-56.0 vs. median, 5.4; range, 4.4-6.4, p = 0.037). Recently, Peters and colleagues [86] have reported excellent work that BDNF infused into the infralimbic medial prefrontal cortex (IL mPFC) reduced conditioned fear, even in the absence of extinction training. And they reported that rats failing to learn extinction showed reduced BDNF in hippocampal inputs to the IL mPFC and that augmenting BDNF in this pathway prevented extinction failure. Hence, our observation would be reasonable. Increasing BDNF activity in hippocampal BDNF may prove to be efficacious intervention for PTSD. Because of the open-label design and the lack of controls, however, no definitive conclusion could be drawn from the trial and we must wait for the results of an adequately powered randomized controlled trial (ClinicalTrials.gov Identifier: NCT00671099) (Figure 3). However, this pilot study has provided promising support for our hypothesis that omega-3 fatty acid supplementation started shortly after accidental injury may be efficacious in attenuating PTSD symptoms.

Bottom Line: Not only has accidental injury been shown to account for a significant health burden on all populations, regardless of age, sex and geographic region, but patients with accidental injury frequently present with the psychiatric condition of posttraumatic stress disorder (PTSD).Physicians in the field of psychosomatic medicine and critical care medicine have the opportunity to see injured patients in the immediate aftermath of an accident.This article first briefly reviews the prevalence and associated factors of accident-related PTSD, then focuses on a conceptual model of fear memory and proposes a new, rationally hypothesized translational preventive intervention for PTSD through promoting hippocampal neurogenesis by omega-3 fatty acid supplementation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. yutaka@ncnp.go.jp.

ABSTRACT
Not only has accidental injury been shown to account for a significant health burden on all populations, regardless of age, sex and geographic region, but patients with accidental injury frequently present with the psychiatric condition of posttraumatic stress disorder (PTSD). Prevention of accident-related PTSD thus represents a potentially important goal. Physicians in the field of psychosomatic medicine and critical care medicine have the opportunity to see injured patients in the immediate aftermath of an accident. This article first briefly reviews the prevalence and associated factors of accident-related PTSD, then focuses on a conceptual model of fear memory and proposes a new, rationally hypothesized translational preventive intervention for PTSD through promoting hippocampal neurogenesis by omega-3 fatty acid supplementation. The results of an open-label pilot trial of injured patients admitted to the intensive care unit suggest that omega-3 fatty acid supplementation immediately after accidental injury can reduce subsequent PTSD symptoms.

No MeSH data available.


Related in: MedlinePlus