Probiotic treatment improves post-traumatic stress disorder outcomes in mice.

Post-traumatic stress disorder (PTSD) is a mental disorder resulting from traumatic events which are characterized primarily by anxiety and depressive disorder. In this study, we determine the role of gut bacteria in PTSD. PTSD-like symptoms were produced by single prolonged stress (SPS). SPS animals showed increased levels of anxiety as measured by the elevated plus maze test, while depressive behaviour was confirmed using sucrose preference, force swim, and tail suspension tests. Gut dysbiosis was confirmed in PTSD animals by next-generation sequencing of 16 s RNA of faecal samples, while these animals also showed increased intestinal permeability and altered intestinal ultrastructure. Probiotic treatment increases beneficial microbiota, improves intestinal health and reduces PTSD-associated anxiety and depression. We also found a decrease in cortical BDNF levels in PTSD animals, which was reversed after probiotic administration. Here, we establish the link between gut dysbiosis and PTSD and show that probiotic treatment may improve the outcome of PTSD like symptoms in mice.

Diet, Stress and Mental Health.

INTRODUCTION: There has long been an interest in the effects of diet on mental health, and the interaction of the two with stress; however, the nature of these relationships is not well understood. Although associations between diet, obesity and the related metabolic syndrome (MetS), stress, and mental disorders exist, causal pathways have not been established. METHODS: We reviewed the literature on the relationship between diet, stress, obesity and psychiatric disorders related to stress. RESULTS: Diet and obesity can affect mood through direct effects, or stress-related mental disorders could lead to changes in diet habits that affect weight. Alternatively, common factors such as stress or predisposition could lead to both obesity and stress-related mental disorders, such as depression and posttraumatic stress disorder (PTSD). Specific aspects of diet can lead to acute changes in mood as well as stimulate inflammation, which has led to efforts to assess polyunsaturated fats (PUFA) as a treatment for depression. Bidirectional relationships between these different factors are also likely. Finally, there has been increased attention recently on the relationship between the gut and the brain, with the realization that the gut microbiome has an influence on brain function and probably also mood and behavior, introducing another way diet can influence mental health and disorders. Brain areas and neurotransmitters and neuropeptides that are involved in both mood and appetite likely play a role in mediating this relationship. CONCLUSIONS: Understanding the relationship between diet, stress and mood and behavior could have important implications for the treatment of both stress-related mental disorders and obesity.

Supplementation with Robuvit® in post-traumatic stress disorders associated to high oxidative stress.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated to recurrent, obsessive recollection of severe traumatic events. This condition is still not completely understood. Elective treatment of PTSD is psychotherapy. Standardized supplements, used for improving chronic fatigue syndrome (i.e. Robuvit®, Horphag Research Ltd) can also be used to control some of the symptoms associated to PTSD, as well as to control the associated increased oxidative stress, present in many of these patients. The aim of this open registry was to evaluate the effects of supplementary Robuvit® 300 mg/day, added to standard management (SM), in subjects with PTSD over a period of 4 weeks, both on the psychological and the inflammatory level. METHODS: Otherwise healthy individuals with a diagnosis of PTSD were included in this registry. A clear main traumatic event occurred with different modalities in all subjects during or just after major earthquakes in Central Italy. SM included exposure therapy and psychotherapy. Supportive psychotherapy was used in all affected subjects. Subjects autonomously decided which group to enter (either SM or SM + Robuvit®), without any pre-defined group allocation or randomization. No placebo was used. RESULTS: The two groups were comparable: 18 subjects (11 females; age range 25-49) were included in the SM group, and 16 subjects (8 females; age range 26-52) using SM in combination with Robuvit® supplementation. BMI of all subjects was below 25 kg/m2. After 4 weeks, the percentages of subjects with recurrent memories and dreams, transient walking-dissociative states and reactive flashbacks/hallucinations, alarm reactions and intense emotional distress, emotional numbness, social disinterest and detachment were significantly lower in the subjects treated with Robuvit® (P<0.05%). Sleeping problems, irritability, and fatigue were also significantly reduced with supplementation. CONCLUSIONS: The results of our preliminary, pilot registry show that symptoms of PTSD as well as the high oxidative stress-related to the condition can be controlled and improved using Robuvit® as a supplementary management. The improvement with Robuvit® is faster and larger than that seen with standard management only. Supplementation is safe and well tolerated and may represent an important option in PTSD treatment.

Remote Healing of Bipolar Disorder, Eating Disorder Not Otherwise Specified, Posttraumatic Stress Disorder, Fibromyalgia, and Irritable Bowel Syndrome Through Lifestyle Change.

This case report illustrates the relationship between gut, hormonal, and brain function in that dietary change, mindfulness interventions, and detoxification led to resolution of disabling psychiatric symptoms. In this case, a single Caucasian female resolved her symptoms of bipolar disorder (BD) including psychotic features and suicidality, posttraumatic stress disorder symptoms from childhood torture, disordered eating, fibromyalgia, and irritable bowel syndrome through lifestyle interventions. This patient survived a severe trauma history only to develop alcohol dependence, disordered eating, and depressive symptoms, which were treated with a polypharmaceutical psychiatric approach. She was formally diagnosed with BD after being treated with antidepressants and went on to be treated with up to 15 medications in the ensuing years. Disabled by the side effects of her treatment, she worked with her treating psychiatrist to taper off of 4 medications before she learned of nutritional change through a book authored by the author. After completing 1 mo of these recommendations including dietary change, detox, and meditation, she enrolled in the author's online program and went on to resolve her symptoms, physical and psychiatric, to the extent that BD has been removed from her medical record. She has been symptom free for 1 y. This case is evidence of the potential for self-directed healing and resolution of chronic illness.

The Anti-Inflammatory Effects of Blueberries in an Animal Model of Post-Traumatic Stress Disorder (PTSD).

Post-traumatic stress disorder (PTSD) is a trauma and stressor-related disorder that results in a prolonged stress response. It is associated with increased oxidative stress and inflammation in the prefrontal cortex (PFC) and hippocampus (HC). The only approved therapy for PTSD is selective serotonin re-uptake inhibitors (SSRIs), but their efficacy is marginal. Recently, we demonstrated that over-production of norepinephrine (NE) as the possible reason for the lack of efficacy of SSRIs. Hence, there is a need for novel therapeutic approaches for the treatment of PTSD. In this study, we investigated the anti-inflammatory role of blueberries in modulating inflammatory markers and neurotransmitter levels in PTSD. Rats were fed either a blueberry enriched (2%) or a control diet. Rats were exposed to cats for one hour on days 1 and 11 of a 31-day schedule to simulate traumatic conditions. The rats were also subjected to psychosocial stress via daily cage cohort changes. At the end of the study, the rats were euthanized and the PFC and HC were isolated. Monoamines were measured by high-performance liquid chromatography. Reactive oxygen species (ROS), gene and protein expression levels of inflammatory cytokines were also measured. In our PTSD model, NE levels were increased and 5-HT levels were decreased when compared to control. In contrast, a blueberry enriched diet increased 5-HT without affecting NE levels. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also studied and they confirmed our findings. The enhanced levels free radicals, gene and protein expression of inflammatory cytokines seen in the PTSD group were normalized with a blueberry enriched diet. Decreased anxiety in this group was shown by improved performance on the elevated plus-maze. These findings indicate blueberries can attenuate oxidative stress and inflammation and restore neurotransmitter imbalances in a rat model of PTSD.

The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors.

Numerous studies have linked severe stress to the development of major depressive disorder (MDD) and suicidal behaviors. Furthermore, recent preclinical studies from our laboratory and others have demonstrated that in rodents, chronic stress and the stress hormone cortisol cause oxidative damage to mitochondrial function and membrane lipids in the brain. Mitochondria play a key role in synaptic neurotransmitter signaling by providing adenosine triphosphate (ATP), mediating lipid and protein synthesis, buffering intracellular calcium, and regulating apoptotic and resilience pathways. Membrane lipids are similarly essential to central nervous system (CNS) function because cholesterol, polyunsaturated fatty acids, and sphingolipids form a lipid raft region, a special lipid region on the membrane that mediates neurotransmitter signaling through G-protein-coupled receptors and ion channels. Low serum cholesterol levels, low antioxidant capacity, and abnormal early morning cortisol levels are biomarkers consistently associated with both depression and suicidal behaviors. In this review, we summarize the manner in which nutrients can protect against oxidative damage to mitochondria and lipids in the neuronal circuits associated with cognitive and affective behaviors. These nutrients include ω3 fatty acids, antioxidants (vitamin C and zinc), members of the vitamin B family (Vitamin B12 and folic acid), and magnesium. Accumulating data have shown that these nutrients can enhance neurocognitive function, and may have therapeutic benefits for depression and suicidal behaviors. A growing body of studies suggests the intriguing possibility that regular consumption of these nutrients may help prevent the onset of mood disorders and suicidal behaviors in vulnerable individuals, or significantly augment the therapeutic effect of available antidepressants. These findings have important implications for the health of both military and civilian populations.

ß-Alanine supplemented diets enhance behavioral resilience to stress exposure in an animal model of PTSD.

This study investigated the effects of ß-alanine (BA) ingestion on the behavioral and neuroendocrine response of post-traumatic stress disorder (PTSD) in a murine model. Animals were fed a normal diet with or without (PL) BA supplementation (100 mg kg(-1)) for 30 days. Animals were then exposed to a predator-scent stress (PSS) or a sham (UNEX). Behaviors were evaluated using an elevated plus maze (EPM) and acoustic startle response (ASR) 7 days following exposure to the PSS. Corticosterone concentrations (CS), expression of brain-derived neurotrophic factor (BDNF), and brain carnosine concentrations were analyzed a day later. Animals in PSS+PL spent significantly less time in the open arms and in the number of entries in the EPM than PSS+BA, UNEX+BA, or UNEX+PL. Animals in PSS+BA had comparable scores to UNEX+BA. Anxiety index was higher (p < 0.05) in PSS+PL compared to PSS+BA or animals that were unexposed. ASR and freezing were greater (p < 0.05) in animals exposed to PSS compared to animals unexposed. CS expression was higher (p < 0.05) in animals exposed to PSS compared to unexposed animals. Brain carnosine concentrations in the hippocampus and other brain sections were significantly greater in animals supplemented with BA compared to PL. BDNF expression in the CA1 and DG subregions of the hippocampus was lower (p < 0.05) in animals exposed and fed a normal diet compared to animals exposed and supplemented with BA, or animals unexposed. In conclusion, BA supplementation in rats increased brain carnosine concentrations and resulted in a reduction in PTSD-like behavior, which may be mediated in part by maintaining BDNF expression in the hippocampus.

A diet enriched with curcumin impairs newly acquired and reactivated fear memories.

Curcumin, a yellow-pigment compound found in the popular Indian spice turmeric (Curcuma longa), has been extensively investigated for its anti-inflammatory, chemopreventative, and antidepressant properties. Here, we examined the efficacy of dietary curcumin at impairing the consolidation and reconsolidation of a Pavlovian fear memory, a widely studied animal model of traumatic memory formation in posttraumatic stress disorder (PTSD). We show that a diet enriched with 1.5% curcumin prevents the training-related elevation in the expression of the immediate early genes (IEGs) Arc/Arg3.1 and Egr-1 in the lateral amygdala (LA) and impairs the 'consolidation' of an auditory Pavlovian fear memory; short-term memory (STM) is intact, whereas long-term memory (LTM) is significantly impaired. Next, we show that dietary curcumin impairs the 'reconsolidation' of a recently formed auditory Pavlovian fear memory; fear memory retrieval (reactivation) and postreactivation (PR)-STM are intact, whereas PR-LTM is significantly impaired. Additional experiments revealed that dietary curcumin is also effective at impairing the reconsolidation of an older, well-consolidated fear memory. Furthermore, we observed that fear memories that fail to reconsolidate under the influence of dietary curcumin are impaired in an enduring manner; unlike extinguished fear memories, they are not subject to reinstatement or renewal. Collectively, our findings indicate that a diet enriched with curcumin is capable of impairing fear memory consolidation and reconsolidation processes, findings that may have important clinical implications for the treatment of disorders such as PTSD that are characterized by unusually strong and persistently reactivated fear memories.

Treatment of post traumatic stress disorder symptoms in emotionally distressed individuals.

Older individuals with emotional distress and a history of psychologic trauma are at risk for post traumatic stress disorder (PTSD) and major depression. This study was an exploratory, secondary analysis of data from the study "Prevention of Depression in Older African Americans". It examined whether Problem Solving Therapy-Primary Care (PST-PC) would lead to improvement in PTSD symptoms in patients with subsyndromal depression and a history of psychologic trauma. The control condition was dietary education (DIET). Participants (n=60) were age 50 or older with scores on the Center for Epidemiologic Studies-Depression scale of 11 or greater and history of psychologic trauma. Exclusions stipulated no major depression and substance dependence within a year. Participants were randomized to 6-8 sessions of either PST-PC or DIET and followed 2 years with booster sessions every 6 months; 29 participants were in the PST-PC group and 31 were in the DIET group. Mixed effects models showed that improvement of PTSD Check List scores was significantly greater in the DIET group over two years than in the PST-PC group (based on a group time interaction). We observed no intervention⁎time interactions in Beck Depression Inventory or Brief Symptom Inventory-Anxiety subscale scores.

[Advances of selenium supplementation in posttraumatic stress disorder risk group patients].

Posttraumatic stress disorder (PTSD) is a complex of symptoms developed in a patient after traumatic event. The basis of PTSD pathophysiology is hyper activation of neurones under stress factors influence, so-called excitotoxicity, followed by oxidative stress (OS) because of an accumulation of free radicals. Lipid peroxidation can lead to neurons damage. Neurons are especially susceptible to OS, changing signal transduction and information processing mechanisms. Clinically excitotoxicity preforms as different acute and/or chronic stress reactions and can cause PTSD. Selenium (Se) is involved on different stages of transport and metabolism of Glutamate. Research aim: to access PTSD incidence, OS parameters and their adjustment advances using organic Se in PTSD risk group patients. PTSD symptomatic severity (in PCL-M points) reduced for 5.85% to baseline, Prevalence Rate reduced for 46.03% to baseline in Se group patients. We can conclude that: 1) there is a statistically reliable correlations between the incidence of PTSD and OS parameters, between PTSD symptomatic severity and OS parameters; 2) the use of Se during the mission can reduce the OS parameters, minimize the incidence of PTSD and reduce the PTSD symptomatic severity.

Attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among disaster medical assistance team members after the Great East Japan Earthquake: the APOP randomized controlled trial.

BACKGROUND: On March 11, 2011, a magnitude 9.0 earthquake, the most powerful ever recorded in Japan, and a massive tsunami struck off the coast of the Sanriku region. A Disaster Medical Assistance Team, a mobile medical team with specialized training that is deployed during the acute phase of a disaster, was dispatched to areas with large-scale destruction and multiple injured and sick casualties. Previous studies have reported critical incident stress (i.e. posttraumatic stress disorder symptoms and depressive symptoms) among rescue workers as well as the need for screening and prevention for posttraumatic stress disorder. So far we have shown in an open trial that posttraumatic stress disorder symptoms in critically injured patients can be reduced by taking omega-3 fatty acids intended to stimulate hippocampal neurogenesis. METHOD/DESIGN: This study is designed to determine the effectiveness of attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among Disaster Medical Assistance Team members after the Great East Japan Earthquake, and is named the APOP randomized controlled trial which is currently ongoing. First, we will provide psycho-education on posttraumatic distress, which is common in responders to the Disaster Medical Assistance Team members deployed to the disaster area. Second, observational research will be conducted to evaluate critical incident stress following the completion of medical activities. Third, team members who provide consent to participate in the intervention research will be randomly divided into a group given an omega-3 fatty acid supplement and a group not given the supplements. Outcome will be evaluated at 12 weeks after the supplements are shipped to the team members. DISCUSSION: Measures that address critical incident stress in disaster responders are important, but there is no substantial evidence that links such measures with prevention of posttraumatic stress disorder. Thus, any confirmation through this study that the intake of omega-3 fatty acid supplements serves as a simple preventative measure for critical incident stress will be of great significance. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000005367.