Neural roots of alcoholism identified
The physical origin of alcohol addiction has been located by British and Chinese researchers in a network of the human brain that regulates our response to danger. Published in the journal Science Advances, their breakthrough could lead to more effective interventions to tackle the global problem of alcohol abuse, which results in more than 3 million deaths every year.
The medial orbitofrontal cortex (mOFC) at the front of the brain senses an unpleasant or emergency situation, and then sends this information to the dorsal periaqueductal grey (dPAG) at the brain’s core, the latter area processing whether we need to escape the situation. Researchers from the University of Warwick, the University of Cambridge and Fudan University, having noticed that rodent models showed the mOFC and dPAG brain areas could underlie precursors of alcohol dependence, decided to analyse MRI brain scans from the IMAGEN dataset of 2000 individuals from the UK, Germany, France and Ireland, who are helping to advance knowledge of how biological, psychological and environmental factors during adolescence may influence brain development and mental health.
The participants undertook task-based functional MRI scans, and when they did not receive rewards in the tasks (which produced negative feelings of punishment), regulation between the mOFC and dPAG was inhibited more highly in participants who had exhibited alcohol abuse. Equally, in a resting state, participants who demonstrated a more overexcited regulation pathway between the mOFC and dPAG — leading to feelings of needing urgently to escape a situation — also had increased levels of alcohol abuse. The researchers thus concluded that a person is at greater risk of developing alcohol use disorders when the information pathway between the mOFC and the dPAG is imbalanced in two ways.
First, alcohol inhibits the dPAG, so that the brain cannot respond to negative signals or the need to escape from danger — leading a person to only feel the benefits of drinking alcohol, and not its harmful side effects. This is a possible cause of compulsive drinking.
A person with alcohol addiction will also generally have an over-excited dPAG, making them feel that they are in an adverse or unpleasant situation they wish to escape, and they will urgently turn to alcohol to do so. This is the cause of impulsive drinking.
“We have found that the same neural top–down regulation could malfunction in two completely different ways, yet leading to similar alcohol abuse behaviour,” said Dr Tianye Jia from Fudan University.
Professor Jianfeng Feng, from University of Warwick and Fudan University, added, “I was invited to comment on a previous study on mice for the similar purpose: to locate the possible origins of alcohol abuse. It is exciting that we can replicate these murine models in humans, and, of course, go a step further to identify a dual-pathway model that links alcohol abuse to a tendency to exhibit impulsive behaviour.”
Professor Trevor Robbins, from the University of Cambridge, concluded, “It is remarkable that these neural systems in the mouse concerned with responding to threat and punishment have been shown to be relevant to our understanding of the factors leading to alcohol abuse in adolescents.”
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