@article{vonLoeffelholzLieskeNeuschaeferRubeetal.2017, author = {von Loeffelholz, Christian and Lieske, Stefanie and Neuschaefer-Rube, Frank and Willmes, Diana M. and Raschzok, Nathanael and Sauer, Igor M. and K{\"o}nig, J{\"o}rg and Fromm, Martin F. and Horn, Paul and Chatzigeorgiou, Antonios and Pathe-Neuschaefer-Rube, Andrea and Jordan, Jens and Pfeiffer, Andreas F. H. and Mingrone, Geltrude and Bornstein, Stefan R. and Stroehle, Peter and Harms, Christoph and Wunderlich, F. Thomas and Helfand, Stephen L. and Bernier, Michel and de Cabo, Rafael and Shulman, Gerald I. and Chavakis, Triantafyllos and P{\"u}schel, Gerhard Paul and Birkenfeld, Andreas L.}, title = {The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism}, series = {Hepatology}, volume = {66}, journal = {Hepatology}, number = {2}, publisher = {Wiley}, address = {Hoboken}, issn = {0270-9139}, doi = {10.1002/hep.29089}, pages = {616 -- 630}, year = {2017}, abstract = {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.}, language = {en} } @article{HaegeleSchlagenhaufRappetal.2015, author = {Haegele, Claudia and Schlagenhauf, Florian and Rapp, Michael Armin and Sterzer, Philipp and Beck, Anne and Bermpohl, Felix and Stoy, Meline and Stroehle, Andreas and Wittchen, Hans-Ulrich and Dolan, Raymond J. and Heinz, Andreas}, title = {Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders}, series = {Psychopharmacology}, volume = {232}, journal = {Psychopharmacology}, number = {2}, publisher = {Springer}, address = {New York}, issn = {0033-3158}, doi = {10.1007/s00213-014-3662-7}, pages = {331 -- 341}, year = {2015}, abstract = {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.}, language = {en} } @inproceedings{HaegeleFriedelSchlagenhaufetal.2014, author = {Haegele, Claudia and Friedel, Eva and Schlagenhauf, Florian and Sterzer, Philipp and Beck, Anne and Bermpohl, Felix and Rapp, Michael Armin and Stoy, Meline and Stroehle, Andreas and Dolan, Raymond J. and Heinz, Andreas}, title = {Reward expectation and affective responses across psychiatric disorders - A dimensional approach}, series = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, volume = {75}, booktitle = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, number = {9}, publisher = {Elsevier}, address = {New York}, issn = {0006-3223}, pages = {91S -- 92S}, year = {2014}, language = {en} } @misc{StroehleRapp2016, author = {Stroehle, Andreas and Rapp, Michael Armin}, title = {Prevention of Cognitive Decline: A Physical Exercise Perspective on Brain Health in the Long Run}, series = {Journal of the American Medical Directors Association}, volume = {17}, journal = {Journal of the American Medical Directors Association}, publisher = {Elsevier}, address = {New York}, issn = {1525-8610}, doi = {10.1016/j.jamda.2016.02.030}, pages = {461 -- 462}, year = {2016}, language = {en} } @article{StroehleSchmidtSchultzetal.2015, author = {Stroehle, Andreas and Schmidt, Dietlinde K. and Schultz, Florian and Fricke, Nina and Staden, Theresa and Hellweg, Rainer and Priller, Josef and Rapp, Michael Armin and Rieckmann, Nina}, title = {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}, series = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry}, volume = {23}, journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry}, number = {12}, publisher = {Elsevier}, address = {New York}, issn = {1064-7481}, doi = {10.1016/j.jagp.2015.07.007}, pages = {1234 -- 1249}, year = {2015}, abstract = {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).}, language = {en} } @misc{KuhlmannTschornAroltetal.2017, author = {Kuhlmann, Stella L. and Tschorn, Mira and Arolt, Volker and Beer, Katja and Brandt, Julia and Grosse, Laura and Haverkamp, Wilhelm and Mueller-Nordhorn, Jacqueline and Rieckmann, Nina and Waltenberger, Johannes and Warnke, Katharina and Hellweg, Rainer and Stroehle, Andreas}, title = {Serum brain-derived neurotrophic factor and depressive symptoms in coronary heart disease patients: Role of cognitive functions Reply}, series = {Psychoneuroendocrinology}, volume = {79}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2017.02.010}, pages = {175 -- 176}, year = {2017}, language = {en} }