Showing posts with label metabolic disorders. Show all posts
Showing posts with label metabolic disorders. Show all posts

Wednesday, March 26, 2014

Abuse Alters Hormones in Kids, Hikes Risk of Metabolic Disorders

We have known for quite a while that children who experience abuse and/or neglect in childhood are more likely to have metabolic disorders as adults (i.e., be overweight, have type-II diabetes, high blood pressure, and so on). The mechanisms of action have not been clear, other than an awareness that it involves inflammation.

The researchers looked at the weight-regulating hormones leptin, adiponectin, and irisin (as well as the inflammatory marker C-reactive protein) in the blood of adults who endured physical, emotional, or sexual abuse or neglect as children. They found that early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin.


Abuse Alters Hormones in Kids, Hikes Risk of Metabolic Disorders

By Rick Nauert PhD Senior News Editor
Reviewed by John M. Grohol, Psy.D. on March 21, 2014


 
A new endocrinology investigation suggests childhood abuse or neglect can lead to long-term hormone impairment that raises the risk of developing obesity, diabetes, or other metabolic disorders in adulthood.

The study is published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

For the study, researchers examined levels of the weight-regulating hormones leptin, adiponectin, and irisin in the blood of adults who endured physical, emotional, or sexual abuse or neglect as children.

Leptin is involved in regulating appetite and is linked to body-mass index (BMI) and fat mass. The hormone irisin is involved in energy metabolism. Adiponectin reduces inflammation in the body, and obese people tend to have lower levels of the hormone.

Researchers found that these important hormones were out of balance in people who had been abused or neglected as children.

“This study helps illuminate why people who have dealt with childhood adversity face a higher risk of developing excess belly fat and related health conditions,” said one of the study’s authors, Christos S. Mantzoros, M.D., D.Sc., Ph.D.

“The data suggest that childhood adversity places stress on the endocrine system, leading to impairment of important hormones that can contribute to abdominal obesity well into adulthood.”

The cross-sectional study examined hormone levels in the blood of 95 adults ages 35 to 65. Using questionnaires and interviews, each participant was assigned a score based on the severity of the abuse or neglect experienced during childhood.

Researchers divided the participants into three groups and compared hormone levels in people with the highest adversity scores to the other two-thirds of the participants.

Participants with the highest adversity scores tended to have higher levels of leptin, irisin, and the inflammatory marker C-reactive protein in their blood. All of these markers are linked to obesity.

In addition, the group of people who suffered the most adversity tended to have lower levels of adiponectin, another risk factor for obesity.

Even after researchers adjusted for differences in diet, exercise, and demographic variables among the participants, high levels of leptin and irisin continued to be associated with childhood adversity.

“What we are seeing is a direct correlation between childhood adversity and hormone impairment, over and above the impact abuse or neglect may have on lifestyle factors such as diet and education,” Mantzoros said.

“Understanding these mechanisms could help health care providers develop new and better interventions to address this population’s elevated risk of abdominal obesity and cardiometabolic risk later in life.”

Source:
The Endocrine Society

* * * * *



Early-life adversity, defined as physical, emotional, or sexual abuse and neglect before 18 years of age, is associated with metabolic syndrome, obesity, and type 2 diabetes mellitus in adult life. However, the underlying mechanism is not fully understood, and whether adipomyokines are associated with early-life adversity independent of other factors such as body mass index, psychosocial risks, and health behaviors is not known.

The objective of the study was to evaluate the association between early-life adversity and circulating the levels of the adipomyokines such as leptin, adiponectin, and irisin and the inflammatory marker, C-reactive protein (CRP).

This study was a cross-sectional study of 95 adults at a university-based research center. We collected venous blood from participants and analyzed serum for leptin, adiponectin, irisin, and CRP.

Circulating leptin, irisin, and CRP levels were significantly higher in the highest adversity tertile group compared with low and middle tertile groups (P < .001 for leptin, P = .01 for irisin, and P = .02 for CRP). Adiponectin levels were lower in the highest tertile group compared with the low and middle tertile groups (P = .03). After adjusting for demographic variables, physical activity, diet, current mental health, and body mass index, the associations between early-life adversity leptin, irisin, and did not change. However, adiponectin and CRP levels were no longer significantly related to early life adversity.

Early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin. These findings suggest that these adipomyokines may play a role in the pathogenesis of metabolic abnormality in a population with significant early life adversity.

Thursday, October 24, 2013

Sleep and Immunity / Insufficient Sleep - Health Matters (UCTV)


By now, most of us have heard that getting insufficient sleep can cause weight gain, likely due to the increase in stress hormones. New research also shows that lack of sleep harms the immune system and trigger an inflammatory response.

Below are two different perspectives on the same issue. First up is a video of a talk from Sean P.A. Drummond, PhD, director of the Behavioral Sleep Medicine Program and Cognitive Behavioral Interventions Program in the VA San Diego Healthcare System on how insufficient sleep is damaging to our health.

Below that is a research review of a new article from PLOS ONE on the ways insufficient sleep harms not only our metabolic system, but also damages our immune system and causes inflammation (linked to nearly all diseases).

Insufficient Sleep - Health Matters (UCTV)


Published on Oct 23, 2013 
(Visit: http://www.uctv.tv/)


The CDC has declared insufficient sleep to be a national health epidemic. Why are we not getting enough and how can we change our behaviors? Sean P.A. Drummond, PhD, director of the Behavioral Sleep Medicine Program and Cognitive Behavioral Interventions Program in the VA San Diego Healthcare System, joins host Dr.David Granet to discuss the ramifications of insufficient sleep and ways to improve your sleep health. Series: "Health Matters" [10/2013]
 * * * * *

Here is an excellent overview of a new article from the open access journal PLOS ONE

New biological links between sleep deprivation and the immune system discovered

Posted By News On October 23, 2013
 
Population-level studies have indicated that insufficient sleep increases the risk of cardiovascular diseases and type 2 diabetes. These diseases are known to be linked to inflammatory responses in the body.

University of Helsinki researchers have now shown what kinds of biological mechanisms related to sleep loss affect the immune system and trigger an inflammatory response. They identified the genes which are most susceptible to sleep deprivation and examined whether these genes are involved in the regulation of the immune system. The study was published in the journal PLOS ONE on 23 October 2013.

Conducted at the sleep laboratory of the Finnish Institute of Occupational Health, the study restricted the amount of sleep of a group of healthy young men to four hours per night for five days, imitating the schedule of a normal working week. Blood samples were taken before and after the sleep deprivation test. White blood cells were isolated from the samples, and the expression of all genes at the time of the sampling was examined using microarrays. The results were compared with samples from healthy men of comparable age who had been sleeping eight hours per night for the week.

"We compared the gene expression before and after the sleep deprivation period, and focused on the genes whose behaviour was most strongly altered," explains researcher Vilma Aho. "The expression of many genes and gene pathways related to the functions of the immune system was increased during the sleep deprivation. There was an increase in activity of B cells which are responsible for producing antigens that contribute to the body's defensive reactions, but also to allergic reactions and asthma. This may explain the previous observations of increased asthmatic symptoms in a state of sleep deprivation."

The amount of certain interleukins, or signalling molecules which promote inflammation, increased, as did the amount of associated receptors such as Toll-like receptors (TLR). On the gene level, this was apparent in the higher-than-normal expression of the TLR4 gene after sleep loss. CRP level was also elevated, indicating inflammation.


Sleep loss causes changes to the system that regulates our immune defence. Some of these changes appear to be long-term, and may contribute to the development of cardiovascular diseases and type 2 diabetes. (Photo Credit: Vilma Aho / Univ. of Helsinki)

The researchers also wanted to examine the impact that long-term sleep deprivation could have on the immune system. For this follow-up study, they used material from the national FINRISKI health survey. Participants in this population study underwent blood tests but also answered questions about their health, for example whether they were getting enough sleep.

The researchers compared participants who believed they were sleeping sufficiently with those who felt that they were not sleeping enough. Some of the gene-level changes observed in the experimental working week sleep restriction study were repeated in the population sample. These results may help explain the connection between shorter sleep and the development of inflammatory diseases, such as cardiovascular disease and diabetes, which has been established in epidemiological studies.

"These results corroborate the idea that sleep does not only impact brain function, but also interacts with our immune system and metabolism. Sleep loss causes changes to the system that regulates our immune defence. Some of these changes appear to be long-term, and may contribute to the development of diseases that have been linked to sleep deprivation in epidemiological research," Aho states.

"Our results corroborate the idea that sleep does not only impact brain function, but also interacts with our immune system and metabolism", researcher Vilma Aho states. (Photo Credit: Linda Tammisto / University of Helsinki)
* * * * *

Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans

Vilma Aho equal contributor, Hanna M. Ollila equal contributor, Ville Rantanen, Erkki Kronholm, Ida Surakka, Wessel M. A. van Leeuwen, Maili Lehto, Sampsa Matikainen, Samuli Ripatti, Mikko Härmä, Mikael Sallinen, Veikko Salomaa, Matti Jauhiainen, Harri Alenius, Tiina Paunio, Tarja Porkka-Heiskanen

Abstract


Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-κB signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.

Full Citation:

Aho V, Ollila HM, Rantanen V, Kronholm E, Surakka I, et al. (2013, Oct 23). Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans. PLoS ONE 8(10): e77184. doi:10.1371/journal.pone.0077184

Saturday, October 19, 2013

Dr. Robert Lustig - Fat Chance: Fructose 2.0

 

Dr. Robert Lustig is a professor in the UC San Francisco Division of Pediatric Endocrinology, and he has previously been featured on UCTV with his talk, Sugar: The Bitter Truth, of which this talk is an update. He argues that fructose (too much) and fiber (not enough) appear to be cornerstones of the obesity epidemic through their effects on insulin.



A little background from Wikipedia:
[Dr. Lustig] practices in the field of neuroendocrinology, with an emphasis on the regulation of energy balance by the central nervous system.[2] He also has a special interest in childhood obesity.[2]

Lustig came to public attention through his efforts to establish that fructose can have serious deleterious effects on human (especially children's) health if consumed in too large amounts.[3] On May 26, 2009, he delivered a lecture called "Sugar: The Bitter Truth" which was posted on YouTube the following July and "went viral" with some 3.47 million viewings (as of Apr 28, 2013).[3] In his lecture, Lustig calls fructose a "poison" and equates its metabolic effects with those of ethanol.

Lustig is the author of Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease (2012).

Fat Chance: Fructose 2.0


Published on Oct 18, 2013

Dr. Robert Lustig, UCSF Division of Pediatric Endocrinology, updates his very popular video "Sugar: The Bitter Truth." He argues that sugar and processed foods are driving the obesity epidemic, which in turn affects our endocrine system. Series: "UCSF Osher Center for Integrative Medicine presents Mini Medical School for the Public" [10/2013]

(Visit: UCTV)

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, Carrà, 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.



ABSTRACT

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.

Wednesday, October 24, 2012

This Is Your Brain on Food - Research Update


This brief review article presents small summaries of new research presented at the Society for Neuroscience annual conference in New Orleans last week. The summary provides some good bullet point information, then below that are the abstracts informing the bullet points.

This is your brain on food: Studies reveal how diet affects brain functions

Posted On: October 16, 2012

NEW ORLEANS — Studies released today explore the neurological component of dietary disorders, uncovering evidence that the brain's biological mechanisms may contribute to significant public health challenges — obesity, diabetes, binge eating, and the allure of the high-calorie meal. The findings were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

Scientists are ultimately searching for new ways to treat diet-related disorders while raising awareness that diet and obesity affect mental as well as physical health.

Today's new findings show that:
  • Being obese appears to affect cognitive function, requiring more effort to complete a complex decision-making task (Timothy Verstynen, PhD, abstract 802.20, see attached summary).
  • Brain images suggest that when people skip breakfast, the pleasure-seeking part of the brain is activated by pictures of high-calorie food. Skipping breakfast also appears to increase food consumption at lunch, possibly casting doubt on the use of fasting as an approach to diet control (Tony Goldstone, MD, PhD, abstract 798.02, see attached summary).
  • A study in rats suggests they may be able to curb binge-eating behavior with medication used to keep substance abusers clean and sober (Angelo Blasio, PhD, abstract 283.03, see attached summary).
Other recent findings discussed show that:
  • Amidst growing concern that diet-related metabolic disorders such as diabetes impair brain function, an animal study reports that a high-sugar diet may affect insulin receptors in the brain and dull spatial learning and memory skills. But omega-3 supplements may at least partially offset this effect (Rahul Agrawal, PhD, see attached summary).
  • Evidence from a rat study suggests that a new compound under development to treat compulsive eating disorders and obesity may be effective at blocking a specific receptor in the brain that triggers food cravings and eating when activated by "food related cues," such as pictures or smells, irrespective of the body's energy needs (Chiara Giuliano, PhD, see attached summary).
"These are fascinating studies because they show the brain is an often overlooked yet significant organ in an array of dietary disorders," said press conference moderator Paul Kenny, PhD, of The Scripps Research Institute in Florida, an expert on addiction and obesity. "Many of these findings have the potential to lead to new interventions that can help reduce the ranks of the obese, helping those who struggle daily with dietary decisions reassert control over what they eat."

Source: Society for Neuroscience

Here are the abstracts that went into this press release:

Abstract 802.20 Summary
Lead author: Timothy Verstynen, PhD
Carnegie Mellon University
Pittsburgh, Penn.
412-624-1194
timothyv@andrew.cmu.edu

Scientists Find Obesity Associated with Changes in Brain Connections


Study suggests obesity may affect how hard the brain works to process information

A new study finds that being obese appears to affect cognitive function, underscoring the important link between diet and brain health. The research was presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.

Timothy Verstynen, PhD, of Carnegie Mellon University, the study’s lead author and his colleagues at the University of Pittsburgh used functional magnetic resonance imaging to image the brains of 29 adults all considered neurologically healthy, but with Body Mass Index scores that ranged from normal to obese. When compared with brain images of leaner participants the images of individuals in the overweight and obese range reflected hyper-connectivity in brain pathways that are critical to cognitive functions, suggesting reduced communication efficiency in these pathways, according to the scientists. Moreover, obese individuals also required more effort to perform a complex decision-making task.

“As people put on unhealthy amounts of weight, the body’s energy systems begin to degrade and you can start to see the negative effect on brain circuitry, particularly areas that are important for controlling impulsive behaviors,” Verstynen said.

Research was supported by the Defense Advanced Research Projects Agency, the Pittsburgh Claude D. Pepper Older Americans Independence Center, the University of Pittsburgh Alzheimer’s Disease Research Center, and the National Institutes of Health.

Scientific Presentation: Wednesday, Oct. 17, 11 a.m.–12 p.m., Hall F-J

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802.20, Altered cortico-basal ganglia connectivity with obesity predicts inefficient executive control processing


T. D. VERSTYNEN, R. LECKIE, A. WEINSTEIN, J. JACKIC, D. ROFEY, K. ERICKSON; Dept. of Psychology, Dept. of Hlth. and Physical Activity, Univ. of Pittsburgh, Pittsburgh, PA; Dept. of Psychology, Carnegie Mellon Univ., Pittsburgh, PA; Weight Mgmt. and Wellness Ctr., Univ. of Pittsburgh Med. Ctr., Pittsburgh, PA

TECHNICAL ABSTRACT: Many cognitive functions, including executive control, saliency and reward processing, share a common circuitry through the cortico-basal ganglia network. Several of these abilities have recently been shown to be impaired in individuals with chronic obesity. Obesity has also been linked to altered basal ganglia dynamics, particularly reward processing in the striatum. In this experiment we tested the hypothesis that the obesity-linked changes to cognitive processing are directly associated with dysfunctional cortico-basal ganglia dynamics. We used resting state fMRI (Siemens Verio 3T, TE=20 ms; TR=1500 ms; Flip Angle=90°, 3.2 mm x 3.2 mm x 4 mm voxels, 30 slices) to determine how increased body mass index (BMI), a common measure of obesity, is correlated with changes in the dynamics of the cortico-basal ganglia networks and how these changes correlate to cognitive processing. In otherwise neurologically healthy adults (N=29, 7 male, mean age 38 years, BMI range = 18.5=45.7) BMI correlated with global connectivity changes in bilateral regions of the orbitofrontal cortex and caudate nucleus. Using these as seed regions, we found a hyper-connectivity of reward and saliency sub-networks of the cortico-basal ganglia system, in subjects with high BMI values. Using a task-evoked fMRI paradigm, we then probed cortical dynamics during the color-word Stroop task and found that these responses were stronger in obese individuals (BMI > 30) than lean controls (BMI < 25). Most importantly, the BMI-associated changes in resting state cortico-basal ganglia connectivity predicted the exaggerated evoked responses in the Stroop task. These results highlight how obesity-linked changes to saliency and reward networks may also influence subsequent executive control processing.

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Abstract 798.02 Summary
Lead author: Tony Goldstone, MD, PhD
MRC Clinical Sciences Centre, Imperial College
London, England
(20) 331-358-56
tony.goldstone@imperial.ac.uk

Good Breakfast and Good Diet: New Findings Support Common Sense


Brain scans of breakfast-skippers show circuits may be primed for poor eating

A new study that compared participants’ brain scans and eating patterns — both after breakfast and when they are fasting —may show why eating the first meal of the day may be a good way to avoid subsequent over-eating and poor dietary choices. The findings were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.

Scientists lead by Tony Goldstone, MD, PhD, from the MRC Clinical Science Centre at London’s Imperial College, obtained multiple magnetic resonance images (MRIs) of 21 volunteers who had not eaten anything before arriving for the tests. On one visit they were first given a 750-calorie breakfast before the scans began; on another visit they received no breakfast. Lunch was always served after the scans.

“Through both the participants’ MRI results and observations of how much they ate at lunch, we found ample evidence that fasting made people hungrier, and increased the appeal of high-calorie foods and the amount people ate,” said Goldstone.

In the MRIs of those who had not eaten breakfast, the scientists discovered a variation in the pattern of activity in the orbitofrontal cortex —the area right above the eyes that can affect decisions regarding the pleasantness and reward value of food. The scientists reported that when fasting participants were shown pictures of high-calorie food, this brain area was “activated,” a reaction less strong when they had eaten breakfast.

Moreover, Goldstone and colleagues noted their ability to use brain MRIs to predict which individuals appear primed to respond strongly to high-calorie foods. This suggests the orbitofrontal cortex may play a vital role in determining how people make dietary choices. They said the study also adds to previous research that indicates fasting may be a poor way to lose weight as it seems to create a “bias” in the brain toward seeking a high-calorie food reward.

Research was supported by the UK Medical Research Council, European Union Marie Curie Fellowship, Imperial College Healthcare Charity, and the National Institute for Health Research.
Scientific Presentation: Wednesday, Oct. 17, 9–10 a.m., Hall F-J

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798.02, Salience resting state network integrity in the orbitofrontal cortex predicts task activation to viewing high-calorie foods when fasted


A.P. GOLDSTONE, C. G. PRECHTL, J. A. STARKE, S. SCHOLTZ, N. CHHINA, A. MIRAS, G. DURIGHEL, R. LEECH, D. J. SHARP, C. F. BECKMANN, G. S. FROST, J. D. BELL; Metabolic and Mol. Imaging Group, MRC Clin. Sci. Ctr., Robert Steiner MRI Unit, Computational, Cognitive and Clin. Neuroimaging Lab., Div. of Diabetes, Endocrinol. and Metabolism, Imperial Col. London, London, United Kingdom

TECHNICAL ABSTRACT: Background: Fasting increases appetite, food intake and hedonics, and activation of brain reward systems to food cues. Changes in brain activity in the resting state (i.e. in the absence of a task) are also functionally relevant. A number of resting state networks (RSN) have been identified including a salience network (SALN) involving the insula, ventral anterior cingulate (vACC) and orbitofrontal (OFC) cortex, regions also activated by food cues. We hypothesised that functional integrity within the SALN at rest may predict activation in the same regions during a food evaluation fMRI task and that this relationship may be influenced by food category and feeding state.
Methods: 21 healthy, non-obese subjects (16 male, mean ± SD age 25.4 ± 7.5yrs, BMI 24.1 ± 2.7 kg/m) attended after an overnight fast. After a first visit [Initial], at subsequent visits subjects either remained fasted [Fasted], or received a 730kCal breakfast at t=0min [Fed], in a randomised cross-over design. At +85min subjects had a 10min resting state fMRI scan (3T, 186 vol, TR 3sec), followed by a food picture fMRI task during which they rated the appeal of high-calorie or low-calorie foods or household objects (2x10min runs, 60 pictures each). Independent component analysis in FSL was used to identify regions of interest (ROI) within the SALN from the Initial resting fMRI scan: insula, vACC and OFC. ROIs for activation to food pictures (vs. objects) in the same sub-regions were also determined from the Initial task fMRI scan (FDR P<0.05). Network integrity within each SALN ROI was correlated with task BOLD activation within each ROI at the Fasted and Fed visits.

Results: Fasting increased hunger, appeal of high-calorie foods and food intake at lunch after scanning (P<0.05). BOLD activation to high-calorie foods was greater at the Fasted than Fed visit in the OFC (P<0.05), but not in the vACC or insula. At the Fasted visit, resting SALN integrity in the OFC was positively correlated with task OFC activation to high-calorie foods (r=+0.52, P=0.02). However this correlation was not significant for low-calorie foods (r=+0.31, P=0.18), nor for the vACC or insula (P=0.30-0.98). At the Fed visit, there were no significant correlations between resting SALN integrity and task activation for any ROI (P=0.10-0.89).

Conclusion: OFC network integrity at rest predicted subsequent OFC activation during a picture evaluation task for high-calorie foods. Furthermore this relationship was seen when fasted but not when fed, supporting previous work that fasting biases OFC responses towards high-calorie foods. This highlights the interaction between feeding status and OFC function in encoding reward value and salience.

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Abstract 283.03 Summary
Lead author: Angelo Blasio, PhD
Boston University School of Medicine
Boston, Mass.
(617) 894-9723
blasio@bu.edu

Drug Used in Addiction Treatment May Block Impulse to Binge on Food


Effect on sugar-craving rats could prompt hunt for medications for diet disorder

Often portrayed as a behavior akin to drug addiction, new research in rats offers evidence that binging on junk food — a psychiatric illness that affects 15 million Americans — might be inhibited by a medication now used to help sustain recovery from alcohol and drug abuse. The findings were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.

Lead author Angelo Blasio, PhD, of the Laboratory of Addictive Disorders at Boston University School of Medicine, and his colleagues found that when they used the drug naltrexone to block receptors in a part of the brain involved in seeking rewards and making decisions, rats curbed their excessive consumption of highly palatable foods.

“These results may open new avenues of investigation toward developing pharmacological treatments for Binge Eating Disorder in humans,” Blasio said. “People who engage in this behavior often describe it as a compulsive loss of control and our work shows there may be medications that can help them regain control.”

Blasio and his colleagues, including Pietro Cottone, PhD, director of the laboratory and senior author of the study, allowed a group of rats to develop into binge eaters by providing them with a chocolate-flavored, high-sugar diet for one hour every day. Within two weeks the rats were exhibiting binge-eating behavior. Meanwhile, a second group of rats was offered a normal, healthy diet. Both groups were then given naltrexone injections at two different sites in the brain.

The drug reduced the amount of food consumed in both groups, except when it was injected directly into the prefrontal cortex — an area of the brain just behind the forehead. There, the drug modified the eating behavior only of the binging rats. The researchers also discovered that the binging rats had undergone genetic changes in the proteins know as opioid receptors, which are located in the prefrontal cortex. When activated by opiates like heroin, these receptors stimulate areas of the brain involved in pleasure and reward; scientists suspect the receptors respond to certain foods in much the same way.

Research was supported by the National Institute on Drug Abuse, National Institute of Mental Health, National Institute on Alcohol Abuse and Alcoholism, and the Peter Paul Career Development Professorship.

Scientific Presentation: Sunday, Oct. 14, 3–4 p.m., Hall F-J

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283.03, Title: Blockade of opioid receptors in the prefrontal cortex decreases binge-like eating


A. BLASIO, L. STEARDO, V. SABINO, P. COTTONE; Pharmacol. & Exptl. Therapeut., Boston Univ. Sch. of Med., Boston, MA; Dept. of Physiol. and Pharmacol., Univ. of Rome La Sapienza, Rome, Italy

TECHNICAL ABSTRACT: Binge eating disorder is an addiction-like disorder characterized by rapid, excessive and uncontrollable food consumption of highly palatable foods, which occurs within discrete periods of time. The central opioidergic system is highly involved in the modulation of both homeostatic and hedonic feeding. Numerous studies have suggested that subcortical regions, such as the Nucleus Accumbens (NAcc), are involved in the modulation of hedonic feeding. However, the role of the opioid receptor system of the Prefrontal Cortex (PFC) in food intake is poorly understood. The present study examined the effect of opioid receptor blockade in a rat model of binge-like eating. Male Wistar rats were allowed to nosepoke to obtain either a sugary highly-palatable diet (Palatable rats) or a regular chow diet (Chow control rats) 1 hour a day, using an operant FR1 schedule of reinforcement. Following stabilization of performance, subjects were systemically administered the non-selective opioid receptor antagonist naltrexone (0.03, 0.1, 0.3 mg/kg, s.c.). Naltrexone was also microinfused in the PFC and the NAcc (10, 50 ug). Finally, differences in opioid receptors gene expression in PFC and NAcc were assessed in Palatable rats and Chow control rats, using RT-PCR. Palatable rats rapidly developed binge-like eating, escalating the 1-hour intake by 4 times.

Naltrexone, administered both systemically and intra-NAcc, dose-dependently reduced responding for food in both Chow and Palatable rats. Interestingly, site-specific administration of naltrexone in the PFC reduced responding for food selectively in Palatable rats, without affecting responding in the Chow group. RT-PCR results showed differential changes in gene expression of opioid receptors in Palatable rats compared to Chow control rats. Our data suggest that neuroadaptations in the opioid receptor system of the PFC occur following intermittent access to highly palatable food, which may be responsible for the development of binge-like eating.

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Speaker’s Summary
Speaker: Rahul Agrawal, PhD
University of California, Los Angeles
Los Angeles, Calif.
(310) 825-1788
ragrawalcdri@rediffmail.com

Metabolic Syndrome in the Brain: How the Balance between Sugars and Omega-3 Fatty Acid Determines Cognitive Plasticity (726.13)


Nanosymposium Session: Metabolism and Brain Function
Wednesday, Oct. 17, 8–11:15 a.m., Room 288

There is growing concern that high sugar consumption is a causative factor for the rise of metabolic syndrome (MetS), the collection of obesity-related risk factors associated with insulin resistance. The concept of MetS has mostly been associated with the body; here we provide novel evidence for the consequences of metabolic disturbances on brain function. Metabolic disorders such as diabetes and obesity increase the vulnerability to mental illness; however, the mechanisms that link cellular metabolism and mental health are poorly understood. We induced metabolic syndrome by high fructose intake (15%) in drinking water and assessed the capacity of dietary n-3 fatty acids (deficient Vs 1.2% DHA) to modulate the vulnerability for MetS. The peripheral occurrence of MetS was confirmed by an increase in insulin resistance index, insulin and triglycerides levels in blood. The effects of MeS in brain were expressed by a decrease in hippocampal insulin receptor signaling in fructose treated animals exposed to the n-3 deficient diet. These changes were concurrent with reductions in memory functions in Barnes maze test. The same dietary treatment resulted in disruption of membrane homeostasis as evidenced by an increase in levels of the lipid peroxidation marker 4-hydroxynonenal (4-HNE), and an increase in ratio of n-6/n-3. A disturbance in energy metabolic pathways was manifested by a reduction in AMPK and LKB1 phosphorylation as well as a decrease in Sir2 levels. The changes observed in LKB1 phosphorylation varied in direct proportion to the n-3 fatty acid docosohexaenoic (DHA) level, and in inverse proportion to the level of the n-6 fatty acid arachidonic (AA), suggesting that a decline in the ratio n-6/n-3 contributes to maintain energy homeostasis. The promoting effect of the fructose/DHA deficiency on dysfunctional synaptic plasticity was evidenced by a decrease in phosphorylation of CREB, synapsin I and a synaptophysin (SYP) levels. The deficiency of dietary n-3 increases vulnerability to impaired cognitive functions and intake of high fructose diet exacerbates this condition. It is encouraging that the presence of n-3 diet was sufficient to buffer the effects of metabolic dysfunction. This study provides a potential mechanism for the deleterious effects of high sugar diets on cognitive function and the possibility to counteract these effects via other healthy components in the diet such as DHA.

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Speaker’s Summary
Speaker: Chiara Giuliano, PhD
University of Cambridge
Cambridge, England
44 (776) 050-5405
Cg451@cam.ac.uk

Attenuation of Highly Palatable Food, Heroin and Cocaine Seeking By GSK1521498, a Novel μ-Opioid Receptor Antagonist, Compared to Naltrexone (362.08)


Poster Session: CNS Depressants, Neuropeptides, and Behavior
Monday, Oct. 15, 11 a.m.–12 p.m., Hall F-J

Evidence has implicated the endogenous opioids and in particular μ-opioid receptors in emotional behaviour, memory and the regulation of reward circuits, especially in the context of heroin addiction and hedonic responses to ingestive rewards. The μ-opioid receptor antagonist naltrexone (NTX) has been reported to be effective in preventing relapse to alcoholism and in reducing alcohol and cocaine craving during abstinence. The aim of the present experiments was to investigate the effects of a novel selective μ-opioid receptor antagonist GSK1521498 on food, cocaine and heroin seeking and the primary reinforcement of self-administration behaviour. Rats were first trained to self-administer food, or cocaine, or heroin and then to seek the reward over prolonged periods of time under a second-order schedule of reinforcement, in which responding is maintained by contingent presentation of a reward-associated conditioned reinforcer. After stable seeking behaviour had been acquired, animals were treated with either GSK1521498 (0.1, 1 and 3mg/kg; IP) or naltrexone (NTX 0.1, 1 and 3mg/kg; SC) before each test session. GSK1521498 dose-dependently reduced food seeking both before and after food ingestion, whereas NTX reduced food seeking only after food ingestion. Thus, whilst both drugs affected the post-ingestional value of the preferred food, GSK1521498 also directly decreased incentive motivation for chocolate. In addition, cocaine seeking was dose-dependently decreased following GSK1521498 treatment. However, the same treatment had no effect on cocaine self-administration under a continuous reinforcement schedule. Treatment with NTX had a less pronounced, but similar effect. GSK1521498, but not NTX, also dose-dependently reduced heroin seeking both before and after infusion of the drug although both increased heroin self-administration under continuous reinforcement. These data suggest that GSK1521498, by reducing opioid transmission at the μ-opioid receptor, may have therapeutic potential to reduce maladaptive, palatability-driven eating behaviour, but also the propensity to seek cocaine or heroin. In addition, it may diminish the consequence of an initial relapse to heroin taking.