A growing number of epidemiological studies have suggested an association between mental health and reduced dietary intake of omega-3 fatty acids, essential fatty acids that humans cannot synthesize de novo. Recent clinical trials are supportive of omega-3 fatty acid supplementation in reducing depressive symptoms, although it reduces anxiety symptoms only slightly [
43,
44]. Based on the animal research to date, omega-3 fatty acids are the most promising candidate for dietary intervention in the aftermath of a traumatic event to facilitate adult hippocampal neurogenesis. Animal studies have revealed that short-term augmentation of dietary omega-3 fatty acids relative to omega-6 fatty acids up-regulated adult neurogenesis [
45], and that dietary omega-3 fatty acids elevated levels of brain-derived neurotrophic factor (BDNF) which promotes neuronal survival and growth [
46,
47]. Further, docosahexaenoic acid (DHA, 22:6
n-3), a 22-carboned omega-3 fatty acid, promoted the development of hippocampal neurons in vitro by increasing neurite extension and branching [
48] as well as the maturation of neurons and hippocampal neurogenesis in adult rats [
49]. Venna and colleagues have shown that the increase in newborn hippocampal cells by polyunsaturated fatty acids occurred in parallel with an increase in hippocampal volume and over-expression of BDNF mRNA and protein in the hippocampus [
50]. BDNF influences the survival of existing neurons and the growth and differentiation of new neurons, and is also implied in the regulation of various neurotransmitter systems [
51,
52]. Moreover, BDNF infused directly into the dorsal hippocampus of rats significantly increased the granule cell layer, indicating neurogenesis [
53]. Wu and Gomez-Pinilla have indicated that DHA dietary supplementation enhanced the effects of exercise on cognition and BDNF-related synaptic plasticity [
47]. Evidence has accumulated that omega-3 fatty acids have an influence on hippocampal neurogenesis by increasing BDNF. In addition, Watanabe and colleagues have revealed that brain fatty acid binding-protein 7 (
Fabp7) which preferentially binds DHA, plays a significant role in neurogenesis, most likely thorough maintenance of neural stem/progenitor cells [
54].
The possible effects of omega-3 fatty acids on brain structures are also highlighted by clinical observation. A significant correlation was found between omega-3 fatty acid consumption and gray matter volume of the amygdala, hippocampus and anterior cingulate gyrus in healthy adults [
55]. Conversely, a selective deficit of DHA was reported in the postmortem frontal cortex of patients with depressive disorder [
56]. Hippocampal volume appears to be diminished in PTSD in some [
57‐
70] but not all studies [
71‐
77]. The author and colleagues have reported smaller volumes of the amygdala and hippocampus in a cohort of breast cancer survivors experiencing intrusive recollections of traumatic memory, compared to survivors without intrusive recollections [
78,
79]. Furthermore, a significant negative correlation has been shown between script-driven enhanced emotional memory about MVA and urgent surgery and hippocampal volume in healthy women [
80]. Two studies have suggested that hippocampal volume might increase following treatment with antidepressants [
81,
82]. While the origin of small hippocampal volume is unknown, the result of one twin study suggested that small hippocampal volume might be a familial risk factor for developing PTSD [
60]. As well, the nutritional environment, including omega-3 fatty acids, may contribute to hippocampal volume.