| 1. |
- Zillich, Lea, et al.
(författare)
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Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder
- 2024
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Ingår i: ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH. - : John Wiley & Sons. - 2993-7175. ; 48:2, s. 250-259
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which is strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation and gene expression in neuroinflammation-related pathways in the brain, biological aging represents a potentially important construct for understanding the adverse effects of substance use disorders. Epigenetic clocks have shown accelerated aging in blood samples from individuals with AUD. However, no systematic evaluation of biological age measures in AUD across different tissues and brain regions has been undertaken.MethodsAs markers of biological aging (BioAge markers), we assessed Levine's and Horvath's epigenetic clocks, DNA methylation telomere length (DNAmTL), telomere length (TL), and mitochondrial DNA copy number (mtDNAcn) in postmortem brain samples from Brodmann Area 9 (BA9), caudate nucleus, and ventral striatum (N = 63-94), and in whole blood samples (N = 179) of individuals with and without AUD. To evaluate the association between AUD status and BioAge markers, we performed linear regression analyses while adjusting for covariates.ResultsThe majority of BioAge markers were significantly associated with chronological age in all samples. Levine's epigenetic clock and DNAmTL were indicative of accelerated biological aging in AUD in BA9 and whole blood samples, while Horvath's showed the opposite effect in BA9. No significant association of AUD with TL and mtDNAcn was detected. Measured TL and DNAmTL showed only small correlations in blood and none in brain.ConclusionsThe present study is the first to simultaneously investigate epigenetic clocks, telomere length, and mtDNAcn in postmortem brain and whole blood samples in individuals with AUD. We found evidence for accelerated biological aging in AUD in blood and brain, as measured by Levine's epigenetic clock, and DNAmTL. Additional studies of different tissues from the same individuals are needed to draw valid conclusions about the congruence of biological aging in blood and brain.
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| 2. |
- Ekhtiari, Hamed, et al.
(författare)
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A methodological checklist for fMRI drug cue reactivity studies : development and expert consensus
- 2022
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Ingår i: Nature Protocols. - : Nature Portfolio. - 1754-2189 .- 1750-2799. ; 17:3, s. 567-595
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Tidskriftsartikel (refereegranskat)abstract
- Cue reactivity measured by functional magnetic resonance imaging is used in studies of substance-use disorders. This Consensus Statement is the result of a Delphi process to arrive at parameters that should be reported in describing these studies. Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: Participants Characteristics, General fMRI Information, General Task Information, Cue Information, Craving Assessment Inside Scanner, Craving Assessment Outside Scanner and Pre- and Post-Scanning Considerations. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the General fMRI Information category were reported in 90.5% of the reviewed papers, items in the Pre- and Post-Scanning Considerations category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.
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| 3. |
- Frischknecht, Ulrich, et al.
(författare)
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Screening auf problematischen Alkoholkonsum – Erhebung zur Umsetzung der S3-Leitlinienempfehlungen in der transdisziplinären Versorgung einer Modellregion : [Screening for Problematic Alcohol Consumption – A Survey on Guideline Implementation in Transdisciplinary Health Care of a Model Region]
- 2022
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Ingår i: Das Gesundheitswesen. - : Georg Thieme Verlag KG. - 0941-3790 .- 1439-4421. ; 84:01, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Aim Recording the frequency of screenings for problematic alcohol consumption by professionals involved in the health care of respective patients. The German S3-guideline screening, diagnosis and treatment of alcohol-related disorders recommends the use of questionnaire-based screenings for all patients in all settings.Methods Cross-sectional survey on screening frequency among general practitioners, gynecologists, psychiatrists, child- and adolescent therapists, psychotherapists, social workers and midwives. Logistic regression was used to explore how healthcare professionals' attributes were associated with the implementation of screenings.Results With response rates of about 20%, health care professionals reported using screening instruments for an average of 6.9% of all patients during the previous four weeks. Most of the time, custom-made questions were used instead of the recommended instruments (AUDIT, AUDIT-C). Higher screening rates were reported for patients with newly diagnosed hypertension (21.2%), alcohol-related disorders (43.3%) and mental disorders (39.3%). Knowledge of the guideline was associated with implementation of screenings (OR=4.67; 95% KI 1.94-11.25, p<0.001).Conclusions Comprehensive screening for problematic alcohol use with questionnaire-based instruments in accordance with guidelines is far from being routinely implemented in the studied health care settings. Measures to increase the knowledge of the guidelines are necessary in order to increase the frequency of alcohol screening in health care.
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| 4. |
- Hansson, Anita C., et al.
(författare)
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Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans
- 2018
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Ingår i: Neuropsychopharmacology. - : NATURE PUBLISHING GROUP. - 0893-133X .- 1740-634X. ; 43:6, s. 1235-1246
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Tidskriftsartikel (refereegranskat)abstract
- Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness, and new drugs that can easily be translated into the clinic are warranted. One of those candidates is oxytocin because of its interaction with several alcohol-induced effects. Alcoholdependent rats as well as post-mortem brains of human alcoholics and controls were analyzed for the expression of the oxytocin system by qRT-PCR, in situ hybridizaton, receptor autoradiography ([(125)l]OVTA binding), and immunohistochemistry. Alcohol self administration and cue-induced reinstatement behavior was measured after intracerebroventicular injection of 10 nM oxytocin in dependent rats. Here we show a pronounced upregulation of oxytocin receptors in brain tissues of alcohol dependent rats and deceased alcoholics, primarily in frontal and striatal areas. This upregulation stems most likely from reduced oxytocin expression in hypothalamic nuclei. Pharmacological validaton showed that oxytocin reduced cue-induced reinstatement response in dependent rats-an effect that was not observed in nondependent rats. Finally, a clinical pilot study (German clinical trial number DRKS00009253) using functional magnetic resonance imaging in heavy social male drinkers showed that intranasal oxytocin (24 IU) decreased neural cue-reactivity in brain networks similar to those detected in dependent rats and humans with increased oxytocin receptor expression. These studies suggest that oxytocin might be used as an anticraving medication and thus may positvely affect treatment outcomes in alcoholics.
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| 5. |
- Manthey, Jakob, et al.
(författare)
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Versorgung von Personen mit riskantem Alkoholkonsum und schwerer Alkoholkonsumstörung in Bremen : bedarfsgerecht und leitlinienkonform?
- 2020
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Ingår i: Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. - : Springer Science and Business Media LLC. - 1436-9990 .- 1437-1588. ; 63, s. 122-130
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Tidskriftsartikel (refereegranskat)abstract
- Hintergrund: Riskanter Alkoholkonsum und schwere Alkoholkonsumstörungen sollten wegen gesundheitlichen Folgeschäden rechtzeitig erkannt werden. Die S3-Leitlinie „Screening, Diagnose und Behandlung alkoholbezogener Störungen“ empfiehlt daher die routinemäßige Anwendung von Screeningverfahren, z. B. in Allgemeinarztpraxen. Wird ein riskanter Konsum festgestellt, soll eine Kurzintervention erfolgen. Bei schwerer Alkoholkonsumstörung ist eine Entzugsbehandlung angezeigt, bei Komplikationsrisiken in stationärer Form.Ziel der Arbeit: Schätzung des Anteils von Personen mit riskantem Konsum und schwerer Alkoholkonsumstörung in leitlinienkonformer Versorgung im Bundesland Bremen.Material und Methoden: Die Prävalenz riskanten Konsums (weibl.: ≥12 g/Tag; männl.: ≥24 g/Tag) und schwerer Alkoholkonsumstörungen (weibl.: ≥60 g/Tag; männl.: ≥90 g/Tag) wurde über den Pro-Kopf-Konsum von Reinalkohol geschätzt. Behandlungsraten wurden auf Grundlage von Umfragedaten (für riskanten Konsum) sowie mittels Sekundärdaten vollstationärer Krankenhausaufenthalte (für schwere Alkoholkonsumstörung) geschätzt. Die Schätzungen beziehen sich auf die Bevölkerung ab 15 Jahre im Bundesland Bremen im Jahr 2016.Ergebnisse: Nur 2,9 % aller Personen mit riskantem Alkoholkonsum wurden durch ihre Hausärzt*innen gescreent; die Hälfte davon (1,4 %) erhielt eine Kurzintervention. 7,1 % der Personen mit einer schweren Alkoholkonsumstörung wurden vollstationär behandelt. Stationäre Entzugsbehandlungen wurden bei 14,1 % der Personen mit einer schweren Alkoholkonsumstörung durchgeführt, bei denen ein stationärer Entzug erforderlich ist. Unterdurchschnittliche Behandlungsraten wurden bei 21- bis 39-Jährigen registriert.Diskussion: Riskanter Konsum und schwere Alkoholkonsumstörungen sind in Bremen unzureichend versorgt, insbesondere bei 21- bis 39-Jährigen.
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| 6. |
- Sangchooli, Arshiya, et al.
(författare)
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Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity
- 2024
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Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X.
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Forskningsöversikt (refereegranskat)abstract
- Importance In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.
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| 7. |
- Schulte, Bernd, et al.
(författare)
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Tailored interventions to support the implementation of the German national guideline on screening, diagnosis and treatment of alcohol- related disorders : a project protocol
- 2019
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Ingår i: SUCHT. - : Hogrefe Publishing Group. - 0939-5911 .- 1664-2856. ; 65:6, s. 373-381
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Tidskriftsartikel (refereegranskat)abstract
- Background: The German Guideline on Screening, Diagnosis and Treatment of Alcohol Use Disorders aims to increase the uptake of evidence-based interventions for the early identification, diagnosis, prevention and treatment of alcohol-related disorders in relevant healthcare settings. To date, dissemination has not been accompanied by a guideline implementation strategy. The aim of this study is to develop tailored guideline implementation strategies and to field-test these in relevant medical and psycho-social settings in the city of Bremen, Germany. Methods: The study will conduct an impact and needs assessment of healthcare provision for alcohol use orders in Bremen, drawing on a range of secondary and primary data to: evaluate existing healthcare services; model the potential impact of improved care on public health outcomes; and identify potential barriers and facilitators to implementing evidence-based guidelines. Community advisory boards will be established for the selection of single-component or multi-faceted guideline implementation strategies. The tailoring approach considers guideline, provider and organizational factors shaping implementation. In field tests quality outcome indicators of the delivery of evidence-based interventions will be evaluated accompanied by a process evaluation to examine patient, provider and organizational factors. Outlook: This project will support the translation of guideline recommendations for the identification, prevention and treatment of AUD in routine practice and therefore contributes to the reduction of alcohol-related burden in Germany. The project is running since October 2017 and will provide its main outcomes by end of 2020. Project results will be published in scientific journals and presented at national and international conferences.
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| 8. |
- Sudireddy, B. R., et al.
(författare)
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Development of Robust Metal-Supported SOFCs and Stack Components in EU METSAPP Consortium
- 2017
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Ingår i: Fuel Cells. - : Wiley. - 1615-6846 .- 1615-6854. ; 17:4, s. 508-516
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Tidskriftsartikel (refereegranskat)abstract
- The potential of MS-SOFCs was demonstrated through the previous EU METSOFC project, which concluded that the development of oxidation resistant novel metal-supported solid oxide fule cell (MS-SOFC) design and stack is the requirement to advance this technology to the next level. The following EU METSAPP project has been executed with an overall aim of developing advanced metal-supported cells and stacks based on a robust, reliable and up-scalable technology. During the project, oxidation resistant nanostructured anodes based on modified SrTiO3 were developed and integrated into MS-SOFCs to enhance their robustness. In addition, the manufacturing of metal-supported cells with different geometries, scalability of the manufacturing process was demonstrated and more than 200 cells with an area of approximate to 150 cm(2) were produced. The electrochemical performance of different cell generations was evaluated and best performance and stability combination was observed with doped SrTiO3 based anode designs. Furthermore, numerical models to understand the corrosion behavior of the MS-SOFCs were developed and validated. Finally, the cost effective concept of coated metal interconnects was developed, which resulted in 90% reduction in Cr evaporation, three times lower Cr2O3 scale thickness and increased lifetime. The possibility of assembling these cells into two radically different stack designs was demonstrated.
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