Biological Psychiatry Laboratory
Biological Psychiatry Laboratory
News Article | May 22, 2017
DALLAS, May 22, 2017 -- Long-term anabolic-androgenic steroid use may reduce the heart's ability to pump blood throughout the body, according to new research in the American Heart Association's journal Circulation. In addition, long-term anabolic-androgenic steroid use damages the heart muscle's ability to relax and may cause atherosclerotic coronary artery disease. Anabolic-androgenic steroids mimic naturally occurring testosterone, a muscle-building hormone that promotes male sexual characteristics. Since illicit use of these steroids became widespread in the American general population in the 1980s, those users are now reaching middle-age and adverse long-term effects are becoming evident. Researchers conducted an observational study of 140 male weightlifters: 86 who used anabolic steroids and 54 non-users. Of the users, 58 were on the drug and 28 were off the drug during evaluations. The off-drug users had last used these steroids an average of 15 months prior to these evaluations. Anabolic steroid users showed higher body- and fat-free mass indexes, consistent with known effects of anabolic steroids. Using two-dimensional ultrasound imaging, researchers found that the left ventricle, the heart's main pumping chamber, was significantly weaker during contraction (systolic function) in those taking anabolic steroids compared to the non-steroid users. Seventy-one percent of the anabolic steroid users who were on-drug at the time of evaluation had a low pumping capacity (less than 52 percent) whereas off-drug users had largely normal pumping capacity. In contrast, researchers found that only two of the non-users had a low pumping capacity. Diastolic function, which is when the left ventricle relaxes and fills with blood, was impaired both for on-drug and off-drug anabolic steroid users. The researchers said this suggests a more permanent heart problem. "Compared to non-users, anabolic steroid users displayed both higher systolic and diastolic blood pressure as well as a higher prevalence of levels of bad (LDL) cholesterol in their blood," said Aaron Baggish, M.D., study co-lead author and associate director of the cardiovascular performance program at Massachusetts General Hospital in Boston. In addition to documenting impairments in heart function, researchers used coronary CT scans to examine the potential link between anabolic steroid use and coronary artery disease. This portion of the study revealed strong associations between the lifetime duration of illicit anabolic steroid use and the amount of plaque build-up in the coronary arteries. "This finding places illicit anabolic steroid use on the list of factors clinicians should consider when caring for men with premature disease of the coronary arteries," Baggish said. Researchers note that it's estimated that between 2.9 million and 4 million Americans have used anabolic steroids. About a million of them, almost all of whom are male, have developed anabolic steroid dependence. "It is critical that clinicians become aware of the long-term risks of anabolic steroid use on the heart. Most people relate anabolic steroids to cheating among athletes and fail to realize that there is a large population of men who have developed dependence upon these drugs, but who are not readily visible. The oldest members of this population are only now reaching middle age," said Harrison Pope, Jr., M.D., the study's other co-lead author and professor of psychiatry at Harvard Medical School. "Clinicians need to know that there may be a marked increase in anabolic steroid-related cardiac pathology as this population moves into later middle-age and beyond," said Pope who is also director of the Biological Psychiatry Laboratory at McLean Hospital, Harvard's largest teaching hospital in psychiatry. Other co-authors are Rory B. Weiner, M.D.; Gen Kanayama, M.D., Ph.D.; James I. Hudson, M.D.; Sc.D.; Michael Lu, M.D.; and Udo Hoffman, M.D., M.P.H. Author disclosures are on the manuscript. A grant from the National Institutes on Drug Abuse funded the study. Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations and health insurance providers are available at http://www. . The American Heart Association is devoted to saving people from heart disease and stroke -- the two leading causes of death in the world. We team with millions of volunteers to fund innovative research, fight for stronger public health policies, and provide lifesaving tools and information to prevent and treat these diseases. The Dallas-based association is the nation's oldest and largest voluntary organization dedicated to fighting heart disease and stroke. To learn more or to get involved, call 1-800-AHA-USA1, visit heart.org or call any of our offices around the country. Follow us on Facebook and Twitter.
Cattaneo A.,Biological Psychiatry Laboratory |
Cattaneo A.,King's College London |
Cattane N.,Biological Psychiatry Laboratory |
Galluzzi S.,Irccs Centro San Giovanni Of Dio Fatebenefratelli |
And 27 more authors.
Neurobiology of Aging | Year: 2017
The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy−) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy− patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy−. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = −9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy− (FC = −7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = −0.48, p < 0.001; rho = −0.25, p = 0.024; rho = −0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation. © 2016
Halpern J.H.,Laboratory for Integrative Psychiatry |
Sherwood A.R.,McLean Hospital |
Sherwood A.R.,Harvard University |
Sherwood A.R.,University of New Mexico |
And 4 more authors.
Addiction | Year: 2011
Aims In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias. Design We compared illicit ecstasy users and non-users while (1) excluding individuals with significant life-time exposure to other illicit drugs or alcohol; (2) requiring that all participants be members of the 'rave' subculture; and (3) testing all participants with breath, urine and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons. Setting Field study. Participants Fifty-two illicit ecstasy users and 59 non-users, aged 18-45 years. Measurements Battery of 15 neuropsychological tests tapping a range of cognitive functions. Findings We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic self-regulation, possibly reflecting increased impulsivity. However, this finding might have reflected a pre-morbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. Conclusions In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.
PubMed | University of Zürich, Biological Psychiatry Laboratory, University of Milan, ETH Zurich and King's College London
Type: | Journal: Cerebral cortex (New York, N.Y. : 1991) | Year: 2016
Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation. Genome-wide transcriptional profiling revealed that prenatal immune activation caused a differential expression of 116 and 251 genes in the medial prefrontal cortex and nucleus accumbens, respectively. A large part of genes that were commonly affected in both brain areas were related to myelin functionality and stability. Subsequent epigenetic analyses indicated that altered DNA methylation of promoter regions might contribute to the differential expression of myelin-related genes. Quantitative relaxometry comparing T
PubMed | Ecole Polytechnique Federale de Lausanne, Neurology Unit, European Foundation Biomedical Research FERB, Biological Psychiatry Laboratory and 11 more.
Type: | Journal: Neurobiology of aging | Year: 2016
The pathway leading from amyloid- deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimers disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n= 40, Amy+) and with no brain amyloidosis (n= 33, Amy-) and also in a group of controls (n= 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E.rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC=-9.6, p < 0.001 and FC=+12.8, p < 0.001, respectively) and to Amy- (FC=-7.7, p < 0.001 and FC=+7.4, p= 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho= 0.60, p < 0.001; rho= 0.57, p < 0.001; and rho= 0.30, p= 0.007, respectively) and a negative correlation with the anti-inflammatory E.rectale (rho=-0.48, p < 0.001; rho=-0.25, p= 0.024; rho=-0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E.rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.
Eitan R.,Biological Psychiatry Laboratory |
Landshut G.,Biological Psychiatry Laboratory |
Lifschytz T.,Biological Psychiatry Laboratory |
Einstein O.,Hebrew University of Jerusalem |
And 2 more authors.
International Journal of Neuropsychopharmacology | Year: 2010
The thyroid hormone triiodothyronine (T3) may accelerate and augment the action of antidepressants. Antidepressants up-regulate neurogenesis in adult rodent hippocampus. We studied the effect of T3 and T3+fluoxetine in enhancement of hippocampal neurogenesis beyond that induced by fluoxetine alone and the correlation with antidepressant behaviour in the novelty suppressed feeding test (NSFT). Rats were administered fluoxetine (5 mg/kg.d), T3 (50 g/kg.d), fluoxetine (5 mg/kg.d)+T3 (50 g/kg.d) or saline, for 21 d. Neurogenesis was studied by doublecortin (DCX) immunohistochemistry in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). In the NSFT, latency to feeding in animals deprived of food was measured. Fluoxetine and fluoxetine+T3 increased the number of doublecortin-positive (DCX+) cells in the SGZ compared to saline (p=0.00005, p=0.008, respectively). There was a trend towards an increased number of DCX+ cells by T3 compared to saline (p=0.06). Combined treatment with fluoxetine+T3 further increased the number of DCX+ cells compared to T3 or fluoxetine alone (p=0.001, p=0.014, respectively). There was no effect of any of the treatments on number of DCX+ cells in the SVZ. In the NSFT, all treatments (T3, fluoxetine+T3 and fluoxetine) reduced latency to feeding compared to saline (p=0.0004, p=0.00001, p=0.00009, respectively). Fluoxetine+T3 further reduced latency to feeding compared to T3 alone (p=0.05). The results suggest that enhancement of antidepressant action by T3 may be related to its effect of increasing hippocampal neurogenesis and that the antidepressant effect of these treatments is specific to the hippocampus and does not represent a general effect on cell proliferation. © 2010 CINP.