Zentralinstitut für Seelische Gesundheit

MONTBONNOT, France, June 7, 2023 /PRNewswire/ -- While several effective treatments (benzodiazepines) are currently available for the treatment of alcohol withdrawal syndrome, there is an unmet medical need in the abstinence maintenance phase. With its broad mechanism of action on the brain's reward system, sodium oxybate has shown very positive new results confirming its efficacy in the treatment of alcohol dependence and which are presented in the PhD thesis of Julien Guiraud that was carried out at the faculty of medicine of the University of Amsterdam. These new studies included 1,082 patients and were conducted by Julien Guiraud and a group of international experts under the supervision of renowned professors in the field of addiction treatment: Prof. W. van den Brink: Professor of Psychiatry and Addictology at the University of Amsterdam Medical School (Netherlands) Prof. A.E. Goudriaan: Professor of Addictology, specialist in the neurobiology of addiction, University of Amsterdam Medical School (Netherlands) Prof. R. Spanagel: Professor, Scientific Director of the Institute of Psychopharmacology, Central Institute of Mental Health. Mannheim Medical School, University of Heidelberg (Germany) The thesis is based on double-blind randomized trials and meta-analyses of eight studies that investigate the heterogeneity of within- and across-study results. These trials and meta-analyses confirm the efficacy, the good tolerance and the safety of sodium oxybate in the maintenance of abstinence, particularly in severe alcohol-dependent patients. Sodium oxybate has a broad mechanism of action, acting on several neurobiological systems within the brain's reward system. At therapeutic doses, sodium oxybate mimics the mechanism of action of alcohol, without its toxicity in the body, and without the problem of transfer of dependence. Alcohol dependence currently affects 3.4% of the general population aged 18 to 64 in the European Union (EU). It is one of the main causes of morbidity (mental health conditions, cardiovascular disease, cancers, etc.) and mortality (49,000 deaths per year attributed to alcohol dependence in France)1. In addition, the social cost of alcohol in France is estimated at 120 billion euros per year2. For 30 years, Italy and Austria have been successfully using sodium oxybate to help many patients overcome alcohol dependence. Given the urgency of the ever-growing medical need, these studies can be used to extend the marketing authorization of sodium oxybate to other EU countries, such as France, where alcohol dependence remains a major public health issue. 1. Source : Santé publique France 2. Source : OFDT About D&A Pharma: D&A Pharma is a pharmaceutical company founded in 2006 by Patrice Debrégeas. The company's mission is to help people live better without their addictions. Since 2007, D&A Pharma has been developing treatments for addictions and orphan diseases. Since 2015, D&A Pharma has been developing a sodium oxybate-based drug for the treatment of alcohol dependence. D&A Pharma has provided a financial support to Julien Guiraud for the conduct of his PhD thesis and has sponsored several studies presented in the thesis () Logo - Gildas de la Monneraye, [email protected] SOURCE D&A Pharma

Genes influence different structures and the function of the brain. These in turn explain differences in behavior. Analyzing all three aspects at once is a challenge -- but has now been achieved. Intelligence is partly heritable. There are studies that show that certain genetic variations are linked to better performance in intelligence tests. Other studies show that a variety of brain characteristics, such as network efficiency, are related to intelligence. For the first time, researchers have now studied all three parameters -- genes, different brain characteristics and behaviour -- simultaneously. Using gene analyses, magnetic resonance imaging and intelligence tests, the team demonstrated which brain characteristics form the link between genes and behaviour. The results are described by a team around Dorothea Metzen from the Department of Biopsychology at Ruhr University Bochum, Germany, and Dr. Erhan Genç, formerly at Ruhr University, now at the Leibniz Research Centre for Working Environment and Human Factors in Dortmund (IfADo), in the journal Human Brain Mapping, published online on 4 April 2023. In addition to the IfADo and various institutions of Ruhr University, the Humboldt-Universität Berlin, the Central Institute of Mental Health in Mannheim, the Medical School Hamburg and the University of Luxembourg were involved. At Ruhr University, the biopsychology, human genetics and genetic psychology teams cooperated. Genes, brain, behaviour -- a unique data set The team included 557 subjects aged between 18 and 75 years in the study. Using saliva samples, they analysed which individuals possessed how many gene variations associated with high intelligence. "There are thousands of genes that contribute to intelligence," explains Dorothea Metzen. "We calculated a summary score for each person that reflects the genetic predisposition for high intelligence." In addition, all subjects took part in brain scans, which the researchers used to determine not only the thickness and surface area of the cerebral cortex, but also how efficiently the structural and functional networks in the brain are organized. All participants also completed an intelligence test. "The broadness and detailed recording of various data in this study is, as far as I am aware, unprecedented," emphasises Erhan Genç. "For the first time, we looked at the triad of genes, different brain characteristics and behavioural traits as a whole." Specifically, the group analysed which differences in genetic variations are related to differences in brain characteristics and differences in behaviour. Interplay of genes, brain characteristics and intelligence in a few brain regions When the team only looked at the connection between genetic variations and brain characteristics -- that is, disregarding intelligence test results -- they found numerous associations in many regions distributed across the entire brain. Significantly fewer associations were apparent when the researchers investigated which brain characteristics were associated with intelligence test performance. When they considered all three parameters at once -- genes, brain characteristics and intelligence test performance -- an association was only found in few brain areas in the frontal, parietal and visual cortex. This means that there are only specific areas in the brain where gene variations influence brain characteristics, and these characteristics simultaneously affect intelligence. The decisive brain characteristics were the size of the brain surface and the efficiency of structural connectivity. The researchers found very few such connections between genes, brain and behaviour when they examined the thickness of the cerebral cortex and the efficiency of functional connectivity. Method also transferable to other areas With their study, the researchers hope to have proposed a method that can also be transferred to other areas. This is because it allows the interplay of genes, brain and behaviour to be studied not only for intelligence, but also for other traits. "It would also be interesting if such methods were used in the future with larger cohorts of thousands or tens of thousands of test subjects," says Erhan Genç, because that would improve the quality of the results. "Studying the impact of age would also be an interesting future research project," adds Genç.

An interdisciplinary research team has found important clues about the functioning of the sensorimotor cortex. The new findings on neuronal activities in this brain area could be helpful for the further development and use of so-called neuroprostheses. These have an interface with the nervous system and are intended to help compensate for neuronal dysfunctions. An interdisciplinary research team at the University of Freiburg has found important clues about the functioning of the sensorimotor cortex. The new findings on neuronal activities in this brain area could be helpful for the further development and use of so-called neuroprostheses. These have an interface with the nervous system and are intended to help compensate for neuronal dysfunctions. "Our results will contribute to the improvement of neuroprosthetic approaches while shortening the training period of patients with prostheses," says neurobiologist Prof. Dr. Ilka Diester from the Faculty of Biology at the University of Freiburg. The results have just been published in the journal Nature Communications. Understanding the brain under more natural conditions The research project also involved the working groups of computer scientist Prof. Dr. Thomas Brox from the University of Freiburg and neuroscientist Prof. Dr. Daniel Durstewitz from the Central Institute of Mental Health in Mannheim. The team found evidence of conserved structures of neuronal activity in the sensorimotor cortex of freely moving rats. The electrophysiological recordings across the entire bilateral sensorimotor cortex allow conclusions about the respective contributions of the premotor, motor and sensory areas. In particular, the researchers found a clear gradient for a contralateral bias, i.e. for movements of the opposite half of the body, from anterior to posterior regions. Previous findings on sensorimotor cortex are mostly based on highly constrained, stereotyped movements in a laboratory setting. The current work uses recordings on freely moving subjects using 3D tracking and addresses the question of the transferability of knowledge about neural control of movements from constrained behavior to a freely moving condition, a prerequisite for understanding the brain under more natural conditions as well as for the further development of neuroprosthetic devices. Categories of behavior across individuals The team used a dimensionality reduction and neural data alignment method. Thus, the high-dimensional neuronal patterns were reduced to a low-dimensional representation by means of their similarity to other patterns, resulting in geometric structures in the visual representation. These geometric patterns were then automatically aligned with each other, similar to the image of holding a magnet to a pack of nails. These then align themselves in a certain direction. Based on such aligned geometric structures, the researchers were able to decipher behavioral categories across recording sessions and even across individuals, and find corresponding evidence of conserved structures of neural activity.