Exercise training induces depot-specific adaptations to white and brown adipose tissue

Exercise affects whole-body metabolism through adaptations to various tissues, including adipose tissue (AT). Recent studies investigated exercise-induced adaptations to AT, focusing on inguinal white adipose tissue (WAT), perigonadal WAT, and interscapular brown adipose tissue (iBAT). Although these AT depots play important roles in metabolism, they account for only ∼50% of the AT mass in a mouse. Here, we investigated the effects of 3 weeks of exercise training on all 14 AT depots. Exercise induced depot-specific effects in genes involved in mitochondrial activity, glucose metabolism, and fatty acid uptake and oxidation in each adipose tissue (AT) depot. These data demonstrate that exercise training results in unique responses in each AT depot; identifying the depot-specific adaptations to AT in response to exercise is essential to determine how AT contributes to the overall beneficial effect of exercise11425439This work was supported by National Institutes of Health grants R01-HL138738 and K01-DK105109 (to K.I.S.), R01-DK099511 (to L.J.G.), and 5P30 DK36836 (Joslin Diabetes Center DRC). The authors thank Nathan Makarewicz for editorial contribution

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R 2) at the optimal p-value threshold is reported. Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R 2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R 2 = 8.18%, p = .0013), Belgium (R 2 = 6.83%, p = .016), and the Netherlands (R 2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R 2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R 2 = 4.42%, p = .0024) and unipolar MDE only (R 2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry

Access and allocation in earth system governance: Water and climate change compared

A significant percentage of the global population does not yet have access to safe drinking water, sufficient food or energy to live in dignity. There is a continuous struggle to allocate the earth's resources among users and uses. This article argues that distributional problems have two faces: access to basic resources or ecospace; and, the allocation of environmental resources, risks, burdens, and responsibilities for causing problems. Furthermore, addressing problems of access and allocation often requires access to social processes (science, movements and law). Analysts, however, have tended to take a narrow, disciplinary approach although an integrated conceptual approach may yield better answers. This article proposes a multi-disciplinary perspective to the problem of access and allocation and illustrates its application to water management and climate change. © The Author(s) 2010

Antipsychotic medications and cognitive functioning in bipolar disorder: moderating effects of COMT Val^108/158 Met genotype

Abstract Background There is a negative association between the use of antipsychotics and cognitive functioning in bipolar patients, which may be mediated by altered dopamine signaling in selected brain areas, and moderation thereof by genetic sequence variation such as COMT Val108/158Met. The interaction between antipsychotic drug use and the COMT Val108/158Met genotype on two-year cognitive functioning in bipolar patients was examined. Methods Interaction between the COMT Val108/158Met and antipsychotics on a composite cognitive measure was examined in 51 bipolar patients who were assessed 12 times at two-monthly intervals over a period of two years (379 observations). Results There was a significant negative effect of the interaction between antipsychotic medications and Val allele load on the composite cognitive measure in bipolar patients (p  Conclusions The negative effects of antipsychotics on cognitive functioning in bipolar disorder may be moderated by the COMT Val 108/158 Met genotype, with a negative effect of Val allele load. If replicated, the results may be indicative of pharmacogenetic interactions in bipolar disorder.</p

Antipsychotic medications and cognitive functioning in bipolar disorder: moderating effects of COMT Val(108/158) Met genotype

BACKGROUND: There is a negative association between the use of antipsychotics and cognitive functioning in bipolar patients, which may be mediated by altered dopamine signaling in selected brain areas, and moderation thereof by genetic sequence variation such as COMT Val(108/158)Met. The interaction between antipsychotic drug use and the COMT Val(108/158)Met genotype on two-year cognitive functioning in bipolar patients was examined. METHODS: Interaction between the COMT Val(108/158)Met and antipsychotics on a composite cognitive measure was examined in 51 bipolar patients who were assessed 12 times at two-monthly intervals over a period of two years (379 observations). RESULTS: There was a significant negative effect of the interaction between antipsychotic medications and Val allele load on the composite cognitive measure in bipolar patients (p < 0.001). CONCLUSIONS: The negative effects of antipsychotics on cognitive functioning in bipolar disorder may be moderated by the COMT Val (108/158) Met genotype, with a negative effect of Val allele load. If replicated, the results may be indicative of pharmacogenetic interactions in bipolar disorder

The Immune System and Electroconvulsive Therapy for Depression

Background: Electroconvulsive therapy (ECT) remains the most effective and fast-acting treatment option for several psychiatric conditions, including treatment-resistant depression. Although ECT has been in use for 75 years, the mechanism of action is unknown. There is emerging evidence that modulation of the hypothalamic-pituitary-adrenal axis may mediate, in part, the therapeutic action of ECT. A growing body of evidence points to links between disturbances in the immune system and depression. However, the impact of ECT on immune functioning and the possible role of alterations in the immune system as a mechanism of action of ECT remain elusive. Objectives: To provide a literature overview on the effects of ECT on the immune system. Methods: Relevant articles and abstracts in English were retrieved from PubMed/Medline using search terms related to ECT, inflammation, and immune system. The results of studies examining ECT-induced changes in immune functioning as well as the degree to which these represent possible mechanisms mediating the therapeutic action of ECT were summarized. Results: Our search identified only a limited number of studies. The findings suggest that a single session of ECT induces an acute, transient immune activation, whereas repetitive ECT treatment results in long-term down-regulation of immune activation. However, inconsistency in findings and methodological issues, including sample size and lack of consideration of confounding factors affecting cytokine concentrations, precludes definitive conclusion. Conclusions: To elucidate the possible role of immunological changes mediating the effect of ECT, more prospective controlled studies with larger sample sizes are required