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Balancing steroidal hormone cascade in treatment-resistant veteran soldiers with PTSD using a fermented soy product (FSWW08): A pilot study

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Abstract

A clinical study was conducted to determine steroidal hormone cascade in the blood to relate them to mental performance with the Clinician-Administered PTSD scale (CAPS), serum lipid concentrations, and steroidal hormones, particularly cortisol, testosterone, estradiol, dehydroepiandrosterone (DHEA), and pregnenolone, in treatment-resistant male veterans with combat-related chronic posttraumatic stress disorder (PTSD) before and after consumption of a special fermented soy formulation (FSWW08). Admitted veterans in the study were resistant to conventional psychological and pharmacological therapies. Ten treatment-resistant soldiers with combat-related PTSD (according to the FSWW08 increased blood levels of steroids, such as testosterone, estradiol, and particularly the adrenal hormones cortisol and androstenediol. Decreased steroidal hormones from the upper part of the hormone cascade, such as cholesterol, DHEA, and pregnenolone were experienced. The arteriosclerotic risk was reduced (cholesterol, 280±35 to 205±22 mmol/L, p

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... It is only recently that the steroidal hormone cascade in the blood of treatment-resistant armed forces veterans suffering from post traumatic stress disorder (PTSD) was investigated [7]. These patients not only suffered from mental disorders, including sleep deprivation, stress, anxiety attacks, and reduced sexual desires, but also suffered from a series of co-pathologies, including metabolic diseases, and immune system aberrations leading to viral infections and inflammation of the joints and/or stomach [7]. ...
... It is only recently that the steroidal hormone cascade in the blood of treatment-resistant armed forces veterans suffering from post traumatic stress disorder (PTSD) was investigated [7]. These patients not only suffered from mental disorders, including sleep deprivation, stress, anxiety attacks, and reduced sexual desires, but also suffered from a series of co-pathologies, including metabolic diseases, and immune system aberrations leading to viral infections and inflammation of the joints and/or stomach [7]. Importantly, they also had an increased risk of diabetes, and an increased risk of stroke and infarction [7]. ...
... These patients not only suffered from mental disorders, including sleep deprivation, stress, anxiety attacks, and reduced sexual desires, but also suffered from a series of co-pathologies, including metabolic diseases, and immune system aberrations leading to viral infections and inflammation of the joints and/or stomach [7]. Importantly, they also had an increased risk of diabetes, and an increased risk of stroke and infarction [7]. Investigation of stressed, traumatized refugee children, who escaped the ordeal but who still refused to speak, showed similar hormone imbalances as those we detected earlier in traumatized soldiers [8]. ...
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Stress was described by Cushing and Selye as an adaptation to a foreign stressor by the anterior pituitary increasing ACTH, which stimulates the release of glucocorticoid and mineralocorticoid hormones. The question is raised whether stress can induce additional steroidal hormone cascade changes in severe mental diseases (SMD), since stress is the common denominator. A systematic literature review was conducted in PubMed, where the steroidal hormone cascade of patients with SMD was compared to the impact of increasing stress on the steroidal hormone cascade (a) in healthy amateur marathon runners with no overtraining; (b) in healthy well-trained elite soldiers of a ranger training unit in North Norway, who were under extreme physical and mental stress, sleep deprivation, and insufficient calories for 1 week; and, (c) in soldiers suffering from post traumatic stress disorder (PTSD), schizophrenia (SI), and bipolar disorders (BD). (a) When physical stress is exposed moderately to healthy men and women for 3–5 days, as in the case of amateur marathon runners, only few steroidal hormones are altered. A mild reduction in testosterone, cholesterol and triglycerides is detected in blood and in saliva, but there was no decrease in estradiol. Conversely, there is an increase of the glucocorticoids, aldosterone and cortisol. Cellular immunity, but not specific immunity, is reduced for a short time in these subjects. (b) These changes are also seen in healthy elite soldiers exposed to extreme physical and mental stress but to a somewhat greater extent. For instance, the aldosterone is increased by a factor of three. (c) In SMD, an irreversible effect on the entire steroidal hormone cascade is detected. Hormones at the top of the cascade, such as cholesterol, dehydroepiandrosterone (DHEA), aldosterone and other glucocorticoids, are increased. However, testosterone and estradiol and their metabolites, and other hormones at the lower end of the cascade, seem to be reduced. 1) The rate and extent of reduction of the androgen metabolites may cause a decrease of cellular and specific immunity which can lead to viral and bacterial infections; joint and stomach inflammation; general pain; and allergic reactions. 2) The decrease in testosterone, and estradiol in SMD may have detrimental effects in cell repair as the estradiol metabolite, 2-methoxy-estradiol (2ME2), helps to transforms stem cells into functional cells. As dopamine and 2ME2 are inversely metabolized via various forms of catechol-O-methyl transferase (COMT), well-being and hypertension may be related. 2ME2 is related to vascular endothelial growth factor (VEGF), which regulates blood capillary growth. Increasing mental and physical stress is related to systematic deviations in the steroidal hormone cascade in the non-psychotic state, which then may cause life threatening co-morbidities in PTSD, SI, and BD.
... However, if mice underwent the stress of chronic social defeat and were treated with Lactobacillus rhamnosus JB-1 or sertraline, there was an increase in both aggressor avoidance and reduced sociability, suggesting a possible detrimental effect [189]. In human subjects, a study by Gocan et al (2012) looked at individuals who developed a combat-related PTSD and monitored symptoms after consumption of fermented soy products. After 6 months of daily ingestion, there was a reduction of anxiety, derealization/detachment, as well as insomnia [190]. ...
... In human subjects, a study by Gocan et al (2012) looked at individuals who developed a combat-related PTSD and monitored symptoms after consumption of fermented soy products. After 6 months of daily ingestion, there was a reduction of anxiety, derealization/detachment, as well as insomnia [190]. Many of the participants were noted to develop flu-like symptoms, skin infections, and even herpes labialis during the beginning of the trial. ...
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Microbial therapeutics, which include gut biotics and fecal transplantation, are interventions designed to improve the gut microbiome. Gut biotics can be considered as the administration of direct microbial populations. The delivery of this can be done through live microbial flora, certain food like fiber, microbial products (metabolites and elements) obtained through the fermentation of food products, or as genetically engineered substances, that may have therapeutic benefit on different health disorders. Dietary intervention and pharmacological supplements with gut biotics aim at correcting disruption of the gut microbiota by repopulating with beneficial microorganism leading to decrease in gut permeability, inflammation, and alteration in metabolic activities, through a variety of mechanisms of action. Our understanding of the pharmacokinetics of microbial therapeutics has improved with in vitro models, sampling techniques in the gut, and tools for the reliable identification of gut biotics. Evidence from human studies points out that prebiotics, probiotics and synbiotics have the potential for treating and preventing mental health disorders, whereas with paraprobiotics, proteobiotics and postbiotics, the research is limited at this point. Some animal studies point out that gut biotics can be used with conventional treatments for a synergistic effect on mental health disorders. If future research shows that there is a possibility of synergistic effect of psychotropic medications with gut biotics, then a gut biotic or nutritional prescription can be given along with psychotropics. Even though the overall safety of gut biotics seems to be good, caution is needed to watch for any known and unknown side effects as well as the need for risk benefit analysis with certain vulnerable populations. Future research is needed before wide spread use of natural and genetically engineered gut biotics. Regulatory framework for gut biotics needs to be optimized. Holistic understanding of gut dysbiosis, along with life style factors, by health care providers is necessary for the better management of these conditions. In conclusion, microbial therapeutics are a new psychotherapeutic approach which offer some hope in certain conditions like dementia and depression. Future of microbial therapeutics will be driven by well-done randomized controlled trials and longitudinal research, as well as by replication studies in human subjects.
... Finally, in the before and after study by Gocan and colleagues (Gocan et al., 2012), 10 participants with combat-related PTSD consumed 120 mL FSWW08 (a fermented soy formulation) daily for 3 months. At follow-up, all participants experienced a reduction of anxiety, derealization/detachment, general infection, headache, loss of appetite, panic, upper GI burning, upper respiratory infection. ...
... 301). Per the authors (Gocan et al., 2012), supplementation resulted in "normalization of the whole steroidal hormone cascade'', as well as improvements in physical and mental functioning (p. 301). ...
Article
Traumatic brain injury (TBI) is highly prevalent among a wide-range of populations, including civilians, military personnel, and Veterans. TBI sequelae may be further exacerbated by symptoms associated with frequently occurring co-morbid psychiatric conditions including posttraumatic stress disorder (PTSD). This is particularly true among the population of military personnel from recent conflicts in Iraq and Afghanistan with a history of mild TBI (mTBI) and PTSD. The need for efficacious treatments for TBI and co-morbid PTSD is significant, and evidence-based interventions for these frequently co-occurring conditions are limited. Based on findings suggesting that inflammation may be an underlying mechanism of both conditions, anti-inflammatory/immunoregulatory agents, including probiotics, may represent a novel strategy to treat TBI and/or PTSD-related symptoms. The focus of this systematic review was to identify and evaluate existing research regarding prebiotic and probiotic interventions for the populations of individuals with a history of TBI and/or PTSD. Only 4 studies were identified (3 severe TBI, 1 PTSD, 0 co-occurring TBI and PTSD). Although findings suggested some promise, work in this area is nascent and results to date do not support some claims within the extensive coverage of probiotics in the popular press.
... Our observation of a relation between homocysteine and HPA-axis activity may provide interesting targets to prevent increased homocysteine. Recently, a pilot study among ten treatment-resistant PTSD patients receiving a specially fermented soy formulation (FSWW08) over a 1-year period, showed a full reduction of PTSD symptoms accompanied with normalization in HPA-axis hormones and homocysteine levels (Gocan et al., 2012). Because trauma-focused psychotherapy for PTSD has been shown to influence HPA-axis activity, this treatment could provide a means of lowering the risk of CVD in PTSD patients (Gerardi et al., 2010;Olff et al., 2007a;Yehuda et al., 2009). ...
... The clinical importance of stress repair mechanism and the difference to chemotherapy may be illustrated by the fact that the fermented soy formulation discussed here in this study caused also a strong and long lasting reduction of mental stress in soldiers suffering from PTSD, the posttraumatic stress disorder [49]: Severe mental stress is a characteristic of PTSD and cellular and mental stress are related [50]. The same fermented soy bean formulation has been shown clinically in humans to stabilize Amyotrophic Lateral Sclerosis, ALS, what is by definition a progressive cell disease [82]: Although no complete normalization was attained, an inhibition of the progressive state was Matrix metalloproteinases (MMP (ref [29]) MMP c-JUN c-JUN seen over several years and for the first time ever. ...
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Introduction: It was suggested that specific plants may reduce cancer's resistance to chemotherapy. Resistance inhibits apoptosis, as well as other fundamental anti-cancer protective mechanisms. Soy bean has been found to reduce cellular stress and repair DNA damage caused by drought or parasites, and can transfer this defense mechanism to other plant species as well. The aim of this study is therefore to conduct a systematic comparison of the effect of soy bean formulation (FSWW08) on gene expression in in vitro human breast cancer cell line, and in in vivo in blood circulating tumor cells (CTC), after oral consumption of FSWW08 by patients suffering from breast-, ovarian-, and prostate cancer. Method: In vitro gene expressions studies were conducted with the human breast cancer cell line BT-474 that was exposed to doxorubicin or FSWW08, either alone or in combination. Ovarian-, prostate-, and breast cancer patients received FSWW08 for 30 days. CTC were extracted from their blood according to an established protocol. Gene expression evaluations were conducted before and after treatment. Results: In vitro, the multi-drug resistance (MDR) protein was reduced by FSWW08, but was increased by doxorubicin. The combination of FSWW08 and doxorubicin, however, showed a protective effect against the increase of MDR in physiologic concentrations, increased, however, also in high experimental concentrations of both agents. The expression of several cancer-related protective genes, such as tumor suppressor factors p21, p38 and p53, was improved by FSWW08 in vitro and in vivo, which helped cell differentiation and new tissue formation. Additionally, the BAX/Bcl2 ratio was improved, in vitro, as well as gene expression of estrogen receptor beta, NF-κB, MAP kinase, c-JUN, and matrix metalloproteinase 9, together with an increase of VEGF expression in vivo in CTC.
... Based on evidence of HPA Axis and immune/inflammatory pathway abnormalities in PTSD, Gocan et al. (2012) prescribed a special fermented soy formulation (FSWW08) for 3 months, with a 6 month extension, to 10 German veterans with PTSD described as resistant to treatment with "standard pharmacologic and psychotherapeutic interventions." The product, FSWW08, had been shown in previous studies to improve immunologic functions and reduce inflammatory cytokines in patients with cancer and Hepatitis B. Increased production of androstenes was described as the key mechanism of FSWW08's proimmune, anti-inflammatory, and improved steroid hormone balance effects. ...
Article
Post-traumatic stress disorder (PTSD) is a serious psychiatric consequence of trauma that occurs in a proportion of individuals exposed to life-threatening events. Trauma-focused psychotherapy is often recommended as first choice for those who do not recover spontaneously. But many individuals require medications. In the US, only paroxetine (PRX) and sertraline (SRT) are FDA approved for PTSD. But response and remission rates with these medications are low, so numerous other pharmacologic interventions have been tried. To date, there has not been a systematic review of the data on what are the best next-step pharmacologic strategies for individuals who fail standard treatments. To that end, we review 167 published trials of medications other than PRX or SRT and provide a detailed analysis of the 88/167 studies that describe alternative pharmacologic interventions in patients refractory to other treatment. We also review clinical factors relevant to treatment-refractory PTSD; the neurobiology of extinction, as well as evidence-based psychotherapy and neuromodulation strategies for this condition.
... Clearly, the strategy to facilitate effects via superfast receptors as a response to stress has its limitation although success has been achieved in the past through insulin delivery and contraception, just to name a few contributions where superfast pharmacology was necessary. We investigated the involvement of innate immunity in the etiology of cancer, reproduction, and severe mental diseases [20,[34][35][36]. This paper provides an overview of treatments exploiting existing gene cascades. ...
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There are two forms of immune defense, the specific or adaptive immune defense and the unspecific innate immune defense. Vaccination is utilized against specific bacteria via the adaptive immune system. The innate immunity DNA stress defense is a non-toxic mechanism developed in yeasts and conserved in mammals and in plants. Although the steroidal hormone cascade has overtaken the stress response and allows superfast response via non-genomic receptors, the old innate immunity response is still mediated via the steroidal hormones cascade. The classical drug/receptor model has provided for many solutions, however, in antibiotics, cancer, and in severe mental diseases this model reaches to certain limits. The NIH/Department of Mental Health has developed a new model that shows severe mental diseases may be immune diseases that can be treated by replacing old diseased nerve cells by new healthy nerve cells, where the old innate immunity may be exploited. This means that severe mental diseases are physical diseases. A newly developed model, where modifications of the steroidal hormone cascade help to understand bipolarity, schizophrenia, and PTSD in men and women can be transferred to gynecological hormone modifications in women, where innate immunity is mediated via the same steroidal hormone cascade. Treatment via immune response via the DNA cascade should be developed in cancer, infections and severe mental disease, because foreign cells or diseased cells may be removed by the unspecific innate immunity.
... One study that assessed the effect of inpatient psychotherapy and clinical management found an increase in TNFconcentration over 6 weeks of treatment (Himmerich et al. 2016). In contrast, daily consumption of a fermented soy formulation resulted in a decrease in TNFconcentrations over the 3-month intervention (Gocan et al. 2012). However, these studies had small samples and did not include a control group. ...
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BACKGROUND: Growing evidence suggests a pathophysiological role of cytokines in post-traumatic stress disorder (PTSD). Tumor necrosis factor (TNF)-α is a key cytokine. Therefore, we performed a systematic review to examine the findings regarding TNF-α derived from both animal and human studies of PTSD. METHODS: Using PRISMA guidelines, we reviewed relevant articles in PubMed from inception until 11th April 2017. Human studies that reported group comparisons and/or longitudinal investigations of TNF-α production/concentration were included. Research reporting on TNF-α levels in animal models of PTSD were also included. RESULTS: Twenty-seven articles were identified. Data from human cross-sectional studies suggests that plasma/serum levels of TNF-α are elevated in those with PTSD, as compared to healthy controls. Longitudinal assessments of TNF-α are limited and data are mixed. Limited data from animal studies suggest an increased TNF-α production in the hippocampus of rats following stress, which can be reversed by immunomodulatory drugs. CONCLUSIONS: Our findings suggest TNF-α may be a potential biomarker and treatment target for PTSD. Findings need to be considered in light of heterogeneous methods for measurement and analysis of TNF-α concentration. Longitudinal research is needed to understand the role of TNF-α in the development and/or maintenance of PTSD.
... Based on evidence of HPA Axis and immune/inflammatory pathway abnormalities in PTSD, Gocan et al. (2012) prescribed a special fermented soy formulation (FSWW08) for 3 months, with a 6 month extension, to 10 German veterans with PTSD described as resistant to treatment with "standard pharmacologic and psychotherapeutic interventions." The product, FSWW08, had been shown in previous studies to improve immunologic functions and reduce inflammatory cytokines in patients with cancer and Hepatitis B. Increased production of androstenes was described as the key mechanism of FSWW08's proimmune, anti-inflammatory, and improved steroid hormone balance effects. ...
... Elevated CRP levels were also associated with exacerbated PTSD symptomatology (Michopoulos et al., 2015b). Furthermore, PTSD symptom improvement has been associated with inflammatory biomarker concentration normalization in female patients diagnosed with PTSD (Gill et al., 2013), male veterans with combat-related PTSD (Gocan et al., 2012), and patients with PTSD who had received evidence-based psychotherapeutic treatment (Morath et al., 2014). ...
Article
The heterogeneity of post-traumatic stress disorder (PTSD) symptoms indicates that multiple neurobiological mechanisms underlie the pathophysiology of the condition. However, no generally accepted PTSD biomarkers in clinical practice currently exist. The sequential responses to recurrent and chronic stress by the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) system are considered to play a significant role in the onset and progression of PTSD. Decreased activity of the HPA axis and parasympathetic nervous system, along with increased activity of the sympathetic nervous system, have been observed in PTSD, which may lead to increased levels of proinflammatory cytokines. Such heightened activity of the immune system may cause alterations in the structure and function of brain regions-for example, the amygdala, hippocampus, medial prefrontal cortex, anterior cingulate cortex, and insula-through changes in levels of serotonin and kynurenine pathway metabolites, and direct neurotoxic effects of cytokines. Although chronic inflammation-induced alterations in brain regions critical in controlling emotional behavior and fear regulation may represent a strong candidate biomarker of PTSD, future studies are necessary to further elucidate inflammation-associated neural biomarkers of PTSD. Continued research on therapeutic methods that involve the normalization of the HPA axis, ANS, and immune system is expected to contribute to the development of novel ways to treat PTSD.
... In a mixed tissue such as peripheral blood, the most likely contributor is the changes in immune cell subtype composition. Changes in immune responses have been reported in PTSD (reviewed by [23]), and symptom normalization may be associated with a change in immune function and cell type proportion [24][25][26]. We attempted to account for this using a bioinformatics deconvolution method for blood cell types from genome-wide methylation data [27] and adding the estimated cell type proportions as covariates. ...
Article
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Background We have previously evaluated the efficacy of the CRF1 receptor antagonist GSK561679 in female PTSD patients. While GSK561679 was not superior to placebo overall, it was associated with a significantly stronger symptom reduction in a subset of patients with probable CRF system hyperactivity, i.e., patients with child abuse and CRHR1 SNP rs110402 GG carriers. Here, we test whether blood-based DNA methylation levels within CRHR1 and other PTSD-relevant genes would be associated with treatment outcome, either overall or in the high CRF activity subgroup. Results Therefore, we measured CRHR1 genotypes as well as baseline and post-treatment DNA methylation from the peripheral blood in the same cohort of PTSD-diagnosed women treated with GSK561679 (N = 43) or placebo (N = 45). In the same patients, we assessed DNA methylation at the PTSD-relevant genes NR3C1 and FKBP5, shown to predict or associate with PTSD treatment outcome after psychotherapy. We observed significant differences in CRHR1 methylation after GSK561679 treatment in the subgroup of patients with high CRF activity. Furthermore, NR3C1 baseline methylation significantly interacted with child abuse to predict PTSD symptom change following GSK561679 treatment. Conclusions Our results support a possible role of CRHR1 methylation levels as an epigenetic marker to track response to CRF1 antagonist treatment in biologically relevant subgroups. Moreover, pre-treatment NR3C1 methylation levels may serve as a potential marker to predict PTSD treatment outcome, independent of the type of therapy. However, to establish clinical relevance of these markers, our findings require replication and validation in larger studies. Trial registration NCT01018992. Registered 6 November 2009. Electronic supplementary material The online version of this article (10.1186/s13148-018-0569-x) contains supplementary material, which is available to authorized users.
... 6.14. Other agents Gocan et al. (2012) found fermented soy oil monotherapy (FSWW08) to provide dramatic long-term symptomatic benefit as well as improvement in a number of metabolic abnormalities (steroid hormones, lipids, C-reactive protein, inflammatory cytokines, thyroid function, leucocyte, lymphocyte and CD-4 count, and plasma homocysteine) in 10 combat veterans whose PTSD had not improved with standard treatments. Unfortunately, this remarkable finding has not been replicated. ...
Article
Recent reviews and treatment guidelines regard trauma-focused cognitive-behavior therapies as the treatments of choice for chronic post-traumatic stress disorder (PTSD). However, many patients do not engage in this treatment when it is available, drop out before completion, or do not respond. Medications remain widely used, alone and in conjunction with psychotherapy, although the limitations of traditional monoamine-based pharmacotherapy are increasingly recognized. This article will review recent developments in psychopharmacology for PTSD, with a focus on current clinical data that apply putative neurobiologic mechanisms to medication use—i.e., a theranostic approach. A theranostic approach however, also requires consideration of timing, pre, peri or post trauma in conjunction with underlying dynamic processes affecting synaptic plasticity, the HPA axis, hippocampal activation, PFC-amygdala circuitry and fear memory.
... Functional GI symptoms were improved in a PD cohort in an RCT on a synbiotic containing multistrain probiotics plus a prebiotic (139). There is limited evidence for ameliorations in microbiota-gut-brain axis signaling in PTSD, with one study showing positive results of a fermented soy drink in a PTSD cohort (140). A recent pilot study has shown some promise for the use of a synbiotic (Bifidobacterium infantis plus oligosaccharides) in ameliorating some of the gut-related comorbidities related to ASD (141). ...
Article
The traditional fields of pharmacology and toxicology are beginning to consider the substantial impact our gut microbiota has on host physiology. The microbiota-gut-brain axis is emerging as a particular area of interest and a potential new therapeutic target for effective treatment of central nervous system disorders, in addition to being a potential cause of drug side effects. Microbiota-gut-brain axis signaling can occur via several pathways, including via the immune system, recruitment of host neurochemical signaling, direct enteric nervous system routes and the vagus nerve, and the production of bacterial metabolites. Altered gut microbial profiles have been described in several psychiatric and neurological disorders. Psychobiotics, live biotherapeutics or substances whose beneficial effects on the brain are bacterially mediated, are currently being investigated as direct and/or adjunctive therapies for psychiatric and neurodevelopmental disorders and possibly for neurodegenerative disease, and they may emerge as new therapeutic options in the clinical management of brain disorders. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 60 is January 6, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... Homocysteine (HCY) levels have been commonly studied in affective disorders and schizophrenia (Delport et al. 2014;Narayan et al. 2014;Chung et al. 2017;Fan et al. 2017), but it was relatively poor investigated in PTSD (Gocan et al. 2012;de Vries et al. 2015). Higher HCY levels were observed in male subjects with PTSD vs. controls (Levine et al. 2008) and non-smoking veterans (Jendricko et al. 2009). ...
Article
Objective: The present exploratory study aimed to investigate relationships between alexithymia, suicide ideation, affective temperaments and homocysteine levels among drug-naïve adult outpatients with Post- Traumatic Stress Disorder (PTSD) in an everyday ‘real world’ clinical setting. Method: Sixty-four adult outpatients with PTSD were evaluated using the Davidson Trauma Scale (DTS), the Toronto Alexithymia Scale (TAS–20), the Scale of Suicide Ideation (SSI), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire. As well, homocysteine levels were measured. Results: Alexithymic subjects showed higher values on all scales but not homocysteine levels. Partial cor- relations showed that almost all studied variables were correlated with each other, except homocysteine levels. Regression analysis showed that higher disorder severity as measured by DTS and TAS-20 ‘Difficulty in Identifying Feelings’ dimension was associated with higher SSI scores. Conclusions: In conclusion, alexithymic PTSD outpatients may be characterised by higher disorder sever- ity and difficulty in identifying feelings that may be linked to increased suicide ideation, regardless of affective temperaments or homocysteine levels. Homocysteine levels were not related to any studied vari- able. However, study limitations are discussed and must be considered. KEYPOINTS � Patients with alexithymia showed increased PTSD severity, a higher score on TEMPS-A subscales, and more severe suicide ideation. � The Difficulty in Identifying Feelings (DIF) dimension of TAS-20 was associated with suicide ideation in patients with PTSD. � Homocysteine did not correlate with any studied variables. � This study was exploratory and cross-sectional: further larger and prospective studies are needed.
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Post-traumatic stress disorder (PTSD) is defined by classic psychological manifestations, although among the characteristics are significantly increased rate of serious somatic comorbidities, such as cardiovascular disease, immune dysfunction and metabolic syndrome. In this review, we assess the evidence for disturbances which may contribute to somatic pathology in inflammation, metabolic syndrome, and circulating metabolites (implicating mitochondrial dysfunction) in individuals with PTSD and in animal models simulating features of PTSD. The clinical and preclinical data highlight probable interrelated features of PTSD pathophysiology including a pro-inflammatory milieu, metabolomic changes (implicating mitochondrial and other processes) and metabolic dysregulation. These data suggest that PTSD may be a systemic illness, or at least has systemic manifestations, albeit the behavioral manifestations being the most easily discerned. Whether somatic pathology precedes the development of PTSD (and thus, may be a risk factor) or follows the development of PTSD (either as a result of shared pathophysiologies or lifestyle adaptations), comorbid PTSD and somatic illness is a potent combination placing affected individuals at increased physical as well as mental health risk. We conclude with directions for future research and novel treatment approaches based on these abnormalities.
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Post-traumatic stress disorder (PTSD) has been associated with an inflammatory state. However, few studies have addressed the mechanisms underlying this immune imbalance that favors inflammation or how this imbalance contributes to PTSD. Whether the immune imbalance influences responsiveness or unresponsiveness of patients to PTSD treatments is currently not known. This review brings forward an immune emphasis to a mental health disorder that is unprecedented in its prevalence among combat Veterans of the ongoing conflicts in Iraq and Afghanistan, and which also afflicts civilians that have undergone extreme traumatic experiences such as following natural disasters, serious accidents or assaults. Included is an overview of the correlative associations in human subjects between PTSD and inflammation, and studies in animal models of PTSD demonstrating causal contributions of inflammation and immune dysregulation to PTSD-like behavior following stress exposure.
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El conocimiento sobre las comunidades microbianas que conviven en simbiosis o apoyo mutuo con el ser humano ha tenido, hasta ahora, muy poco impacto en la medicina y solamente hemos prestado atención a los microorganismos que causan enfermedades, mientras que todos los demás cohabitantes del cuerpo humano se quedaron colectivamente en un limbo donde han permanecido ignorados ante la preocupación por los microbios que podían ser perjudiciales. Esto ha cambiado radicalmente en los últimos años con la caracterización del microbioma humano, secuela científica de la publicación de los primeros borradores del genoma humano los días 15 y 16 de febrero de 2001 en las prestigiosas revistas Nature y Science y que supuso un hito en la historia de la biomedicina. La microbiota es esencial para los seres vivos y la relación que mantenemos con ella es habitualmente mutualista, ya que sus microorganismos nos proporcionan una serie de ventajas que van desde la protección frente a la invasión por agentes patógenos y el desarrollo del sistema inmunitario, a la colaboración en la digestión de componentes de la dieta, la provisión de vitaminas y otros nutrientes esenciales o el desarrollo neurológico en las primeras etapas de la vida. Cada individuo posee una comunidad microbiana peculiar que depende de su genotipo y de la exposición temprana a los microorganismos de su entorno. Un inadecuado desarrollo de nuestra microbiota intestinal durante los primeros meses de vida por el aumento del número de cesáreas, el abandono prematuro de la lactancia materna o, ya en la edad adulta, por el abuso de antibióticos, una dieta inadecuada o el proceso del envejecimiento, nos puede llevar a un estado de disbiosis con una alteración de la microbiota tanto cualitativa (predominio de especies distintas a las habituales) como cuantitativa (menor concentración de bacterias beneficiosas). La consecuencia será la disminución de sus efectos saludables y la aparición de enfermedades de todo tipo: digestivas, ginecológicas, alérgicas, dermatológicas, metabólicas, etc. De hecho, se han descrito más de un centenar de patologías que podrían estar relacionadas con la disbiosis. En los últimos años, se han relacionado muchas enfermedades neurológicas y del campo de la salud mental con una alteración del eje microbiota-intestino-cerebro, comunicación bidireccional, en el que la microbiota intestinal se va a comunicar con los sistemas homeostáticos (el nervioso, el endocrino y el inmunitario) en el intestino y, desde esa localización, a través de diferentes vías, con el cerebro, influyendo en su funcionamiento. Por lo tanto, además de ayudar a mantener las funciones cerebrales, la microbiota intestinal también podría influir en el desarrollo de trastornos neurológicos y con el estrés, como la ansiedad y la depresión, o trastornos del comportamiento, como el autismo. Esta alteración de la microbiota se puede modular con la dieta y el empleo de probióticos y prebióticos. En 2013, Timothy G. Dinan, profesor de Psiquiatría y director del Departamento de Psiquiatría del University College en Cork (Irlanda), en una publicación conjunta con sus colegas Catherine Stanton y John F. Cryan, lanzaron un nuevo concepto: “los psicobióticos”, que eran definidos como aquellos microorganismos vivos que producían un beneficio en la salud de pacientes con trastornos neuropsiquiátricos, es decir, una clase de probióticos capaces de producir y liberar sustancias neuroactivas (GABA, serotonina) que actúan a través del eje microbiota-intestino-cerebro. En un principio, y en base a datos preclínicos, su utilización podría estar indicada en pacientes con patología neurológica (cefaleas, esclerosis múltiple, enfermedad de Parkinson, etc.) o en los trastornos del comportamiento (ansiedad, depresión, autismo, TDAH, enfermedad de Alzheimer, etc.). El grado de evidencia científica de su empleo en muchas de estas patologías todavía es muy limitado, siendo la mayoría de los estudios experimentales en modelos animales, aunque, por la tipología de los pacientes, se han creado muchas expectativas. Con la finalidad de poder encontrar algunas respuestas a muchas patologías neuropsiquiátricas de difícil manejo, y con el objetivo de mejorar la calidad de vida de estos pacientes y, siempre, bajo el mayor rigor científico, tres sociedades científicas: la Sociedad Española de Microbiota, Probióticos y Prebióticos (SEMiPyP), la Sociedad Española de Psiquiatría Biológica (SEPB) y la Sociedad Española de Neurología (SEN), han realizado conjuntamente este Documento de Consenso con la esperanza de que el “mutualismo” entre científicos y clínicos genere más investigaciones relevantes en este campo. Esto permitirá aportar los conocimientos necesarios para nuevas aplicaciones en el tratamiento y prevención de estas enfermedades, reflejo de que estamos ante una de las revoluciones científicas más importantes de la medicina del presente y del futuro.
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Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder and sometimes deadly consequence of exposure to severe psychological trauma. However, there has been little known about the definitive molecular changes involved in determining vulnerability to PTSD. In the current study, we used proteomics to quantify protein changes in the hippocampus of foot shocks rats. A total of 6151 proteins were quantified and 97 proteins were significantly differentially expressed. The protein-protein interaction (PPI) analysis showed that oxidation-reduction process and glutathione homeostasis may be the potential key progress of being vulnerable to PTSD. The Gene Ontology analysis revealed enriched GO terms in the protein groups of Susceptible group vs Control group rats for glutathione binding,oligopeptide binding,modified amino acid binding,and glutathione transferase activity for their molecular functions (MF) and in the process of cellular response to toxic substance,xenobiotic metabolic process, urea metabolic process, and response to drug for the biological process (BP).SIGNIFICANCE:In recent years, there has been a growing interest in mental illness associated with trauma exposure. We found that stress susceptibility was associated with increased expression of arginase 1 indicated as a potential treatment target. Our results also proposed that carbonic anhydrases 3 could be a biomarker for the development of PTSD. This research helps to explain the potential molecular mechanism in PTSD and supply a new method for ameliorating PTSD.
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The rapidly growing field of immunopsychiatry combines expertise and insights from immunology, psychiatry and neuroscience to understand the role of inflammation and other immune processes in causing and treating mental illness. This represents a major shift in mental health science, traditionally focused on psychological and neuronal mechanisms of depression, psychosis and dementia. This book provides the first comprehensive overview of recent, inter-disciplinary research linking disordered function of the immune system to the brain and mental illness. It offers a broad and deep perspective on the implications of immune system involvement in psychiatric disorders, including a balanced focus on basic science and clinical applications. Chapters cover the scientific evidence linking immune processes to major mental illnesses such as schizophrenia, depression, anxiety and dementia. An invaluable guide for graduate students, doctors in training, scientific researchers and others interested in the link between the immune system and mental health.
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The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.
It has been established that carrying a pregnancy to full-term at an early age can protect against contracting cancer by up to 50% in later life. The trophoblast theory of cancer states that trophoblast and cancer tissue are very similar. New findings suggest that the loss of fetal cells during pregnancy resemble those cells responsible for causing metastasis in cancer. Fetal cells and spreading cancer cells are highly proliferative. They are similar to stem cells, exhibiting no or low hormone receptor expression, and require a hormone receptor independent mechanism for control. Control of membrane stability during pregnancy is of vital importance for a successful pregnancy and is mediated by androstenediol and 2-methoxyestradiol. 2-Methoxyestradiol has no hormone receptor affinity and elicits strong anticancer effects particularly against cancer stem cells and fetal cells, for which currently no treatment has yet been established. There is a discussion whether pregnancy reduces cancer stem cells in the breast. Soy isoflavones are structurally similar to both hormones, and elicit strong anticancer effects and antiangiogenesis via inhibition of NF-κB, even in hormone receptor independent breast cancers seen in epidemiologic studies. The trophoblast theory of cancer could help to explain why soy baby nutrition formulas have no effect on baby physiology, other than the nutritional aspect, although soy elicits many effects on the adult immune system. To survive the immune system of the mother, the immune system of the fetus has to be separated; otherwise, the reduction of the immune system in the mother, a necessary feature for the blastocyst to grow, would immediately reduce the immunity for the fetus and endanger its survival. Similar to a fetus, newly born babies show immune insensitive to Th1 and Th2 cytokines, which are necessary and crucial for regulating the immune system of the mother, thus raising the risk of the baby of developing allergies and neurodermatitis. Gene expression studies in vitro as well as in circulating tumor cells from patients consuming a fermented soy product support the antiangiogenic as well as antiproliferative effects of soy.
Many cancer patients do not die due to impaired organ functions, but as a result of reduced general conditions, such as cachexia, sarcopenia, depression, infections, or stress. Reduced general health may be caused by immune modifying cytokines released from the tumor into the body. Improvement of immunity would not only reduce cancer side effects through inhibiting cytokine release from the tumor into the blood, but also, according to a new hypothesis, modify the cancer stem cells (CSC) in the tumor, which are believed to drive cancer growth and metastasis. We reported previously several investigations with a dietary fermented soy formulation (FSWW08) in cancer patients, where we saw a) strong reduction of cancer symptoms, b) broken resistance to chemotherapy, and c) a strong reduction of chemotherapy's toxic side effects, when taken in combination. This publication reports two new findings from a pilot study with postsurgical, treatment resistant patients conducted over four years. First, neither treatment resistance nor side effects were observed. Second, more patients have survived than expected. The improved health and immunity is detected together with increased CSC differentiation, suggesting lower aggressiveness, which was corroborated by increased gene expressions, particularly of steroidal hormones, MAPkinase, NF-κB, and tumor suppressor factor p53, a typical marker of "stemness" or cell differentiation. Although limited by its small, homogenous sample size, the results of this pilot study illustrate the relationship between CSCs differentiation, and the clinical symptoms of immunity, which influence survival outcomes and raise the clinical potential of measuring CSCs in ovarian, prostate, and breast cancers. The improved survival rates are also seen in larger cohort studies, which show similar gene expression profiles, which were induced by FSWW08 in the treatment resistant cancer patients in this study.