Sunday, October 06, 2013

Post-Traumatic Stress Disorder Increases Risk of Metabolic Syndrome

Based on my own experience, I can generalize that PTSD does indeed increase the risk for metabolic syndrome, as well as gastrointestinal issues, diabetes, cardiovascular disease, and some form of cancers. This based on observations of the client population where I work as well as research I have seen over the years that connects early childhood trauma (in particular) with a whole host of health issues.

The bottom line, in my opinion, is that PTSD is post-traumatic STRESS disorder, and nearly all disease can be traced to stress responses in the body, especially metabolic disorders (stress hormones disrupt insulin function, which leads to weight gain and higher cholesterol). [It must be noted that some stress - stress that is short-term and manageable - is actually good for the immune system.]
[Chronic stress] raises catecholamine and suppressor T cells levels, which suppress the immune system. This suppression, in turn raises the risk of viral infection. Stress also leads to the release of histamine, which can trigger severe broncho-constriction in asthmatics. Stress increases the risk for diabetes mellitus, especially in overweight individuals, since psychological stress alters insulin needs. Stress also alters the acid concentration in the stomach, which can lead to peptic ulcers, stress ulcers or ulcerative colitis. Chronic stress can also lead to plaque buildup in the arteries (atherosclerosis), especially if combined with a high-fat diet and sedentary living. The correlation between stressful life events and psychiatric illness is stronger than the correlation with medical or physical illness. The relationship of stress with psychiatric illness is strongest in neuroses, which is followed by depression and schizophrenia. There is no scientific evidence of a direct cause-and-effect relationship between the immune system changes and the development of cancer. However, recent studies found a link between stress, tumour development and suppression of natural killer (NK) cells, which is actively involved in preventing metastasis and destroying small metastases. (Salleh, 2008)
The research summary (below) discusses the findings of a new meta-analysis that found there is an increased risk of metabolic syndrome for those with PTSD. However, the same journal (Metabolic Syndrome and Related Disorders) that published the review article also published a review that questions the findings of the original review article.

The juxtaposition of the two perspectives makes for interesting reading. While I agree with their finding in general, their meta-analysis is deeply flawed. Five of the six studies included in their review did not provide data on antipsychotic or other drugs used for PTSD treatment, substances which are well-known to cause weight-gain, reduced insulin sensitivity leading to high blood sugar levels (hyperglycemia), and increased cholesterol and fat content in the blood (dyslipidemia).

Post-traumatic stress disorder increases risk of metabolic syndrome

Article Date: 05 Oct 2013

People suffering from post-traumatic stress disorder (PTSD) face a greater risk of cardiovascular disease and death. A new study involving a comprehensive review of the medical literature shows that PTSD also increases an individual's risk of metabolic syndrome. What links these two disorders is not clear, according to a study published in Metabolic Syndrome and Related Disorders, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Metabolic Syndrome and Related Disorders website.

Francesco Bartoli and coauthors from University of Milano-Bicocca, Italy, University College London, UK, and San Gerardo Hospital, Monza, Italy, conducted a systematic review and meta-analysis and, based on their findings, propose that the increased risk of metabolic syndrome may result from neurological and hormonal responses to chronic stress. Their study is entitled "Metabolic Syndrome in People Suffering from Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis."

In an accompanying Editorial, "Posttraumatic Stress Disorder and Metabolic Syndrome: More Questions than Answers," authors Dawn Schwenke, PhD, VA Health Care System and Arizona State University, Phoenix, and David Siegel, MD, Northern California Health Care System (Mather) and University of California, Davis, suggest that more research is needed to determine whether the relationship between PTSD and metabolic syndrome is independent of other factors such as socioeconomic status, diet, physical activity, smoking, alcohol consumption, and insomnia.

"While Bartoli and colleagues conclude from their meta-analysis that PTSD confers a greater risk for metabolic syndrome, Schwenke and Siegel in their editorial suggest caution, explaining that it is not a simple relationship and many confounding factors could explain this," says Ishwarlal (Kenny) Jialal, MD, PhD, Editor-in-Chief of the Journal and Distinguished Professor of Pathology and Laboratory Medicine and Internal Medicine (Endocrinology, Diabetes and Metabolism), Robert E. Stowell Endowed Chair in Experimental Pathology, Director of the Laboratory for Atherosclerosis and Metabolic Research, Director Special Chemistry and Toxicology, Davis Medical Center (Sacramento). "In agreement with the latter, I believe this is a fertile area for further investigation before any definite conclusions can be drawn."
Full Citation:
Bartoli, F, CarrĂ , G, Crocamo, C, Carretta, D, and Clerici, M. (2013, Jun 11). Metabolic Syndrome in People Suffering from Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis. Metabolic Syndrome and Related Disorders; October, 11(5): 301-308. doi:10.1089/met.2013.0010.

The full article is available online at the above link. Here is the abstract, followed by the editorial response.


Background: Previous reports showed a high prevalence of obesity, diabetes, hypertension, and dyslipidemia among people suffering from posttraumatic stress disorder (PTSD). However, there is a lack of reviews that systematically analyze the relationship between PTSD and metabolic syndrome. We conducted a systematic review and meta-analysis aimed at estimating the association between PTSD and metabolic syndrome.

Methods: We systematically searched PubMed, Embase, and Web of Science. We included observational studies assessing the prevalence of metabolic syndrome in a sample with PTSD and in a comparison group without PTSD. Data were analyzed using Review manager 5.1. Odds ratios (OR) with 95% confidence intervals were used as an association measure for pooled analysis, based on a random-effects model.

Results: Six articles were eligible according to the inclusion criteria, for an overall number of 528 individuals suffering from PTSD and 846 controls without PTSD. The pooled OR for metabolic syndrome for people with PTSD was 1.37 (1.03–1.82). Statistical heterogeneity between the included studies was low (I2=22%).

Conclusions: Despite some limitations, the findings of this systematic review and meta-analysis confirmed our hypothesis that individuals suffering from PTSD have a greater risk of metabolic syndrome. The potential role of unknown factors or mediators that might clarify the nature of this association needs further research.

Dawn C. Schwenke PhD, MS and David Siegel, MD, MPH wrote a lengthy response to the review article.

Schwenke, DC, and Siegel, D. (2013, Jul 31). Posttraumatic Stress Disorder and Metabolic Syndrome: More Questions Than Answers. Metabolic Syndrome and Related Disorders; October, 11(5): 297-300. doi:10.1089/met.2013.1504.  

Posttraumatic Stress Disorder and Metabolic Syndrome: More Questions Than Answers
The criteria for metabolic syndrome as identified by the modified National Cholesterol Education Panel–Adult Treatment Panel (NCEP–ATP III) include abdominal obesity, an atherogenic dyslipidemia manifest as elevated levels of triglycerides (TGs) and low levels of high density lipoprotein-cholesterol (HDL-C), raised blood pressure, and impaired fasting glucose.[1] The importance of metabolic syndrome is that it confers at least a two-fold increased risk of cardiovascular disease and at least five-fold increased risk for subsequent diabetes.[2–5]

In their report in Metabolic Syndrome and Related Disorders, Bartoli et al.[6] study the association of posttraumatic stress disorder (PTSD) and metabolic syndrome. The authors found six studies that met their criteria for inclusion in their meta-analysis involving 528 subjects with PTSD and 846 comparison patients; 5 of these had at least a trend toward a positive association. The studies included both men and women (although two of the studies were exclusively and one 92% men) with mean ages of 43.7–61 years of age (one study reported age as <40 or ≥40 years of age). Four studies were of war veterans, one was of police officers, and one was of subjects recruited from the waiting rooms of primary care clinics at a busy inner city hospital. Four papers were from the United States and two were from Europe (Bosnia and Herzegovina). Individuals suffering from PTSD were more likely (36%) than the general population (28%) to have dyslipidemia, hypertension, diabetes, and obesity. The pooled odds ratio [95% confidence intervals (CI)] for metabolic syndrome in people suffering from PTSD was 1.37 (1.03–1.82) compared with those without PTSD.

The findings in this meta-analysis are of interest, but several questions remain. Much remains to be learned concerning whether the relationship between PTSD and metabolic syndrome is independent of other factors that have been associated with metabolic syndrome or metabolic syndrome components. For example, lower socioeconomic class,[7] poor dietary quality,[8] physical inactivity/increased sedentary behavior,[9] active smoking,[10] increased alcohol consumption,[11] and specific symptoms of insomnia, including difficulty falling asleep and unrefreshing sleep,[12] have been associated with metabolic syndrome or metabolic syndrome components in individuals without psychiatric disorders. One of the most commonly reported symptoms of PTSD is insomnia.[13] PTSD is also associated with poor dietary quality, physical inactivity, higher rates of smoking, and increased alcohol consumption.[14] Importantly, several behavioral factors that are more prevalent in individuals with PTSD, including poor dietary quality,[15] active smoking,[10] and higher alcohol consumption[11] are prospectively associated with metabolic syndrome/metabolic syndrome components incidence. Among Iraq combat veterans, worsening insomnia during deployment predicted worsening PTSD symptoms, whereas worsening PTSD did not predict worsening insomnia,[16] suggesting that insomnia may play a causative role in PTSD. This notion is supported by a report in civilians experiencing traumatic injury that found sleep disturbance in the period immediately before a traumatic event to predict the subsequent development of a posttraumatic psychiatric disorder.[17] Thus, it remains to be clarified whether the association between PTSD and metabolic syndrome is independent of recognized risk factors for metabolic syndrome. Indeed, given the limitations of the available data, it is not clear whether metabolic syndrome might increase risk of PTSD.

How does the prevalence of metabolic syndrome and patterns of metabolic syndrome components compare between those with PTSD and those with other mental illnesses? In one longitudinal study, 75 patients with bipolar disorder (BPAD) and 53 patients with schizophrenia were evaluated for metabolic syndrome and then followed up for a period of 6 months.[18] The prevalence of metabolic syndrome at baseline was 40% in the BPAD group and 32% in the schizophrenia group. Over 6 months of follow-up, the prevalence of metabolic syndrome increased by 8% and 9.4% in the BPAD and the schizophrenia groups, respectively. Another 28%–32% of patients in the BPAD group also fulfilled two criteria, and 13%–17% fulfilled at least one criterion of metabolic syndrome at different points of assessment. Similarly, 19%–26% of the patients with schizophrenia met at least two criteria and 23%–26% of the patients fulfilled at least one criterion of metabolic syndrome. The prevalence of metabolic syndrome in these patients is close to the 36% of PTSD patients with metabolic syndrome reported by Bartoli et al.[6] Thus, it remains unclear whether PTSD confers any special risk for metabolic syndrome when compared with other psychiatric disorders.

Is the association of PTSD and metabolic syndrome independent of medical treatments that PTSD patients may receive, including antipsychotic and other prescribed medications as well as self-medication with substances such as alcohol, tobacco, marijuana, and cocaine? These medications and practices may have independent effects on the components of metabolic syndrome, and it may be difficult to separate these effects from the hypothesized direct effects of PTSD on metabolic syndrome components. The pharmacotherapy of PTSD is aimed at the hallmarks of the disorder, which include intrusive thoughts and images, phobic avoidance, pathological hyperarousal, hypervigilance, irritability and anger, and depression. Treatment of PTSD thus encompasses a wide range of medications including selective serotonin reuptake inhibitors (SSRIs) and other antidepressants, atypical antipsychotics, alpha-adrenergic receptor blockers, benzodiazepines, and mood stabilizers, including anticonvulsants. While alpha-adrenergic receptor blockers used to treat PTSD, i.e., prazosin, will decrease blood pressure, treatment with atypical antipsychotics is associated with weight gain, hyperglycemia, and dyslipidemia.[19–21] In one study, 26 children and adolescents (21 males, 5 females) aged 7–15.5 years with a diagnosis of schizophrenia received risperidone from 1 mg/day to a maximum of 6 mg/day. There was a statistically significant link between a prescription for risperidone and 6-month increases of body mass index (BMI) and sex- and age-adjusted BMI percentile.[22] In addition to the studies noted above, excessive alcohol use, smoking, low physical exercise, low self-care, and excessive calorie intake may contribute to increased risk of cardiovascular and metabolic diseases in PTSD patients.[14] Unfortunately, five of the six studies in this meta-analysis did not provide data on antipsychotic or other drugs used for PTSD treatment.6 Therefore, the authors were unable to investigate the influence of these medications on the components of metabolic syndrome. Hopefully, future studies will include this information.

How similar are the patterns of metabolic abnormalities in persons with metabolic syndrome with and without PTSD? Prevalence of metabolic syndrome/metabolic syndrome characteristics and values for metabolic syndrome characteristics have been described for a number of population-based samples recruited without regard to occupation or presence or absence of PTSD.[7,23–25] Prevalence of metabolic syndrome differs according to age,[7, 23–25] race/ethnic background,[23,24] and sex,[7,23–25] although the directionality of the sex difference varies between countries. Other literature suggests that individuals of the same or similar race/ethnic background can have differing prevalence of metabolic syndrome and patterns of metabolic syndrome characteristics.[26] In the US population, both ATP III criteria[23] and International Diabetes Federation (IDF) criteria[24] are concordant and indicate the most prevalent metabolic syndrome characteristic to be central obesity for each of non-Hispanic white, Mexican-American, and African-American adult women. For US men, ATP III and IDF criteria both indicate central obesity to be the most prevalent metabolic syndrome criteria for Mexican-American and African-American adult men, whereas for adult non-Hispanic white men, ATP III and IDF, respectively, indicate low HDL and central obesity to be the most prevalent metabolic syndrome characteristics.[23,24] Unfortunately, none of the reports concerning PTSD and metabolic syndrome summarized in the report of Bartoli et al.[6] reported on the prevalence of individual metabolic syndrome characteristics. Thus, it is uncertain whether the pattern of metabolic abnormalities in individuals with PTSD and metabolic syndrome differs from that for individuals of the same age, sex, race/ethnicity, and community background with metabolic syndrome but without PTSD.

Is the relationship between PTSD and metabolic syndrome influenced by the age at which trauma is experienced or the age of onset of PTSD? Conceivably, children with PTSD could either be unusually susceptible to metabolic syndrome compared with children not affected by PTSD or could enjoy protection from metabolic syndrome due to factors related to the very low prevalence of metabolic syndrome observed in young children selected without consideration of history of trauma.[27] One study reported metabolic syndrome characteristics in adults with and without chronic current PTSD who experienced trauma as children. Study participants were born between 1933 and 1940 and traumatized as children when they were displaced from their homes in the former German eastern territories at ages 5–12 years during/after World War II.[28] In this study, concentrations of fasting glucose and HDL-C, systolic and diastolic blood pressure, and waist circumference did not differ significantly between participants with and without PTSD, whereas serum TG concentrations were significantly lower for individuals with PTSD compared with those without PTSD (104.4±7.2 standard error (SE) versus 134.9±12.8, P<0.05). Current PTSD in subjects classified as having current PTSD was verified by scores on a Structured Diagnostic Interview according the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). While prevalence of metabolic syndrome was not reported in this study, the lack of evidence for more adverse values for metabolic syndrome characteristics suggests that metabolic syndrome was not increased in these individuals with continuing PTSD due to trauma experienced as children. Future work is needed to both characterize the relationship between PTSD and metabolic syndrome across a broad range of ages at which trauma is experienced/age of onset of PTSD and to investigate the potential for moderation of the association of PTSD with metabolic syndrome by age of trauma/age of PTSD onset.

Does the relationship between PTSD and metabolic syndrome differ according to the setting in which the trauma that is the source of PTSD is experienced? PTSD can occur in war veterans,[29–32] police officers,[33] and the general population. Among more general populations not selected by vocation, PTSD or PTSD-like symptoms can develop subsequent to trauma experienced in a variety of settings, including being the victim of[34] or witnessing[35,36] violence in areas subject to armed conflict[36] or terrorist attack,[35] experiencing an automobile accident[37] or other accidents,[38] experiencing sexual and/or physical abuse,[36,39] race-related stress,[40] natural disasters,[41] and serious medical conditions.[42,43] Family members and professionals providing care for injured or severely ill persons may also experience PTSD.[43,44] Data for metabolic syndrome and metabolic syndrome characteristics appear to be limited to few reports for veterans,[29–32] one in police officers,[33] one in impoverished individuals of whom only about 1/5 were employed,[45] the report concerning war refugees discussed above,[28] and other reports that included information for only a subset of metabolic syndrome characteristics.[42] The minimal overlap of data included in these studies precludes any conclusions concerning how the setting in which the trauma that is the source of PTSD is experienced might influence the relationship between PTSD and metabolic syndrome. Thus, it remains to be clarified whether the relationship between PTSD and metabolic syndrome differs according to the setting in which the trauma that is the source of PTSD is experienced.

Is the relationship between PTSD and metabolic syndrome independent of any physical trauma that might have been part of the psychological trauma that resulted in PTSD? Potentially, any traumatic experience that was associated with physical injury compromising function of the endocrine organs could have adverse effects on metabolic syndrome characteristics and the development of metabolic syndrome. Additionally, traumatic experience co-incident with physical damage to the central nervous system centers responsible for impulse control and executive functioning, such as might occur in traumatic brain injury, might have adverse effects on metabolic syndrome characteristics and development of metabolic syndrome through poor lifestyle. Similarly, in children and adolescents, any physical injury to critical areas of the brain that adversely affected development of impulse control or executive functioning might be expected to adversely affect development of metabolic syndrome. Unfortunately, it does not appear that any prior investigation of separate and joint effects of PTSD and physical injury on metabolic syndrome/metabolic syndrome components has been conducted.

In summary, the report by Bartoli et al.[6] in this journal provides limited evidence that PTSD is associated with metabolic syndrome. However, this report leaves unanswered many questions that have received little attention and are worthy of future research.
References are available at the journal site.

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