TY - JOUR A1 - von Loeffelholz, Christian A1 - Lieske, Stefanie A1 - Neuschaefer-Rube, Frank A1 - Willmes, Diana M. A1 - Raschzok, Nathanael A1 - Sauer, Igor M. A1 - König, Jörg A1 - Fromm, Martin F. A1 - Horn, Paul A1 - Chatzigeorgiou, Antonios A1 - Pathe-Neuschaefer-Rube, Andrea A1 - Jordan, Jens A1 - Pfeiffer, Andreas F. H. A1 - Mingrone, Geltrude A1 - Bornstein, Stefan R. A1 - Stroehle, Peter A1 - Harms, Christoph A1 - Wunderlich, F. Thomas A1 - Helfand, Stephen L. A1 - Bernier, Michel A1 - de Cabo, Rafael A1 - Shulman, Gerald I. A1 - Chavakis, Triantafyllos A1 - Püschel, Gerhard Paul A1 - Birkenfeld, Andreas L. T1 - The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism BT - official journal of the American Association for the Study of Liver Diseases JF - Hepatology N2 - Reduced expression of the Indy ("I am Not Dead, Yet") gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane-associated citrate transporter expressed highly in the liver, protects mice from high-fat diet-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In nonhuman primates, a 2-year high-fat, high-sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription through the IL-6 receptor and activation of the transcription factor signal transducer and activator of transcription 3, and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-signal transducer and activator of transcription 3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx, and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and nonhuman primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 through mINDY. Conclusion: Targeting human mINDY may have therapeutic potential in obese patients with nonalcoholic fatty liver disease. German Clinical Trials Register: DRKS00005450. Y1 - 2017 U6 - https://doi.org/10.1002/hep.29089 SN - 0270-9139 SN - 1527-3350 VL - 66 IS - 2 SP - 616 EP - 630 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Haegele, Claudia A1 - Schlagenhauf, Florian A1 - Rapp, Michael Armin A1 - Sterzer, Philipp A1 - Beck, Anne A1 - Bermpohl, Felix A1 - Stoy, Meline A1 - Stroehle, Andreas A1 - Wittchen, Hans-Ulrich A1 - Dolan, Raymond J. A1 - Heinz, Andreas T1 - Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders JF - Psychopharmacology N2 - A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries. We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment. During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation. Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities. KW - Dimensional KW - fMRI KW - Reward system KW - Ventral striatum KW - Monetary incentive delay task KW - Depressive symptoms Y1 - 2015 U6 - https://doi.org/10.1007/s00213-014-3662-7 SN - 0033-3158 SN - 1432-2072 VL - 232 IS - 2 SP - 331 EP - 341 PB - Springer CY - New York ER - TY - CHAP A1 - Haegele, Claudia A1 - Friedel, Eva A1 - Schlagenhauf, Florian A1 - Sterzer, Philipp A1 - Beck, Anne A1 - Bermpohl, Felix A1 - Rapp, Michael Armin A1 - Stoy, Meline A1 - Stroehle, Andreas A1 - Dolan, Raymond J. A1 - Heinz, Andreas T1 - Reward expectation and affective responses across psychiatric disorders - A dimensional approach T2 - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry KW - dimensional KW - transdiagnostic KW - reward system KW - ventral striatum KW - fMRI Y1 - 2014 SN - 0006-3223 SN - 1873-2402 VL - 75 IS - 9 SP - 91S EP - 92S PB - Elsevier CY - New York ER - TY - GEN A1 - Stroehle, Andreas A1 - Rapp, Michael Armin T1 - Prevention of Cognitive Decline: A Physical Exercise Perspective on Brain Health in the Long Run T2 - Journal of the American Medical Directors Association Y1 - 2016 U6 - https://doi.org/10.1016/j.jamda.2016.02.030 SN - 1525-8610 SN - 1538-9375 VL - 17 SP - 461 EP - 462 PB - Elsevier CY - New York ER - TY - JOUR A1 - Stroehle, Andreas A1 - Schmidt, Dietlinde K. A1 - Schultz, Florian A1 - Fricke, Nina A1 - Staden, Theresa A1 - Hellweg, Rainer A1 - Priller, Josef A1 - Rapp, Michael Armin A1 - Rieckmann, Nina T1 - Drug and Exercise Treatment of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Effects on Cognition in Randomized Controlled Trials JF - The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry N2 - Objective: Demographic changes are increasing the pressure to improve therapeutic strategies against cognitive decline in Alzheimer disease (AD) and mild cognitive impairment (MCI). Besides drug treatment, physical activity seems to be a promising intervention target as epidemiological and clinical studies suggest beneficial effects of exercise training on cognition. Using comparable inclusion and exclusion criteria, we analyzed the efficacy of drug therapy (cholinesterase inhibitors, memantine, and Ginkgo biloba) and exercise interventions for improving cognition in AD and MCI populations. Methods: We searched The Cochrane Library, EBSCO, OVID, Web of Science, and U.S Food and Drug Administration data from inception through October 30, 2013. Randomized controlled trials in which at least one treatment arm consisted of an exercise or a pharmacological intervention for AD or MCI patients, and which had either a non-exposed control condition or a control condition that received another intervention. Treatment discontinuation rates and Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated. Results: Discontinuation rates varied substantially and ranged between 0% and 49% with a median of 18%. Significantly increased discontinuation rates were found for galantamine and rivastigmine as compared to placebo in AD studies. Drug treatments resulted in a small pooled effect on cognition (SMCR: 0.23, 95% CI: 0.20 to 0.25) in AD studies (N = 45, 18,434 patients) and no effect in any of the MCI studies (N = 5, 3,693 patients; SMCR: 0.03, 95% CI: 0.00 to 0.005). Exercise interventions had a moderate to strong pooled effect size (SMCR: 0.83, 95% CI: 0.59 to 1.07) in AD studies (N = 4, 119 patients), and a small effect size (SMCR: 0.20, 95% CI: 0.11 to 0.28) in MCI (N = 6, 443 patients). Conclusions: Drug treatments have a small but significant impact on cognitive functioning in AD and exercise has the potential to improve cognition in AD and MCI. Head-to-head trials with sufficient statistical power are necessary to directly compare efficacy, safety, and acceptability. Combining these two approaches might further increase the efficacy of each individual intervention. Identifier: PROSPERO (2013:CRD42013003910). KW - Alzheimer dementia KW - mild cognitive impairment KW - drug KW - exercise Y1 - 2015 U6 - https://doi.org/10.1016/j.jagp.2015.07.007 SN - 1064-7481 SN - 1545-7214 VL - 23 IS - 12 SP - 1234 EP - 1249 PB - Elsevier CY - New York ER - TY - GEN A1 - Kuhlmann, Stella L. A1 - Tschorn, Mira A1 - Arolt, Volker A1 - Beer, Katja A1 - Brandt, Julia A1 - Grosse, Laura A1 - Haverkamp, Wilhelm A1 - Mueller-Nordhorn, Jacqueline A1 - Rieckmann, Nina A1 - Waltenberger, Johannes A1 - Warnke, Katharina A1 - Hellweg, Rainer A1 - Stroehle, Andreas T1 - Serum brain-derived neurotrophic factor and depressive symptoms in coronary heart disease patients: Role of cognitive functions Reply T2 - Psychoneuroendocrinology Y1 - 2017 U6 - https://doi.org/10.1016/j.psyneuen.2017.02.010 SN - 0306-4530 VL - 79 SP - 175 EP - 176 PB - Elsevier CY - Oxford ER -