Liam Davenport

September 06, 2017

PARIS ― Long-term, heavy alcohol use during adolescence affects male and female brains differently, with males at greater risk for functional alterations that could lead to brain changes in later life, a new Finnish study suggests.

Investigators at the University of Eastern Finland found that transcranial magnetic stimulation (TMS) to the motor cortex evoked electrical changes in the brains of alcohol users that were suggestive of alterations in gamma-aminobutyric acidergic (GABAergic) function and that electrical activity was increased and more widespread in the brains of male alcohol users than in their female counterparts.

This finding of greater changes in brain electrical activity in men "was a surprise, as we expected it would be the other way around," Outi Kaarre, MD, University of Eastern Finland and Kuopio University Hospital, said in a statement.

"This means that male brain electrical functioning is changed more than female brains by long-term alcohol use," said Dr Kaare.

The findings were presented here at the 30th European College of Neuropsychopharmacology (ECNP) Congress.

Calming Brain Activity

Previous studies have shown that the long-term effects of alcohol on the brain are mediated by alterations in GABAergic neurotransmission and that the EEG potentials N45 and N100, evoked by TMS stimulation of the motor cortex, reflect GABA-A-ergic and GABA-B-ergic function, respectively.

To examine whether long-term alcohol use affects cortical activity differently in men than in women, the researchers obtained TMS-EEG measurements in 27 young adults (11 men) who had used alcohol heavily during adolescence and a control group of 25 participants (12 men) who had little or no history of alcohol use.

The participants, aged 23 to 28 years at the time of the study, underwent 150 TMS stimuli targeted to the motor cortex at 90% of the resting motor threshold of the abductor pollicis braves muscle. Brain activity was assessed using 61-channel EEG.

Statistical analysis showed that total EEG, as measured by global-mean field power (GMFP), was significantly increased in male alcohol users vs control participants between 52 ms and 77 ms (P < .05). There were no significant differences in GMFP between female alcohol users and control persons.

The investigators found that compared with the control group, there was a significant increase in N45 amplitude frontally in both male and female alcohol users (P < .001 and P = .003, respectively), indicating alterations in GABA-A-ergic functioning.

Male alcohol users also showed significant increases in N100 amplitude compared with male control-group members (P < .001), suggesting altered GABA-B-ergic functioning. There were no significant differences observed between female alcohol users and control participants.

Danger to Developing Brain

Dr Kaare told Medscape Medical News that the participants "were considered 'normal' alcohol users, so they were doing well in their life.

"They weren't considered problem drinkers, and even then, we found these changes. So, for me, it is an issue, and it should be also to others. I don't think we pay enough attention to how dangerous it is to use alcohol, especially when you are young and your brain is developing very fast."

Dr Kaare pointed out that it is already known that alcohol affects brain development and is associated with thinning of the cortex in alcohol users. It is also associated with poorer performance on neuropsychological tests that measure attention, working memory, and executive function.

She said she believes electrical changes observed in the current study may occur before the structural and neurophysiologic changes are seen, "so these might be first signs that alcohol causes dangerous effects on the brain.

"But it also could be that these changes are compensatory, meaning that the brain tries to compensate for the adverse effects of the alcohol." In other words, the increased electrical activity indicates that the brain "is trying to work normally, even though the alcohol is effecting it already," she said.

Dr Kaare said it is not possible to say at this stage which of these theories is correct. She noted that genetics and environmental vulnerabilities may also play a role.

She added that the investigators are still trying to determine the meaning of the results, but noted that "GABA is a pretty fundamental neurotransmitter in the inhibition of many brain and central nervous systems functions. It's involved in many neurological systems and is important in anxiety and depression. Generally, it seems to calm down brain activity."

She noted that it's important to find out how these differences manifest themselves.

"It may be that we need to look at tightening regulations on youth drinking, since none of our study participants met the diagnostic criteria for alcohol use disorders, and still these significant changes in brain functioning were found," she said.

Treatment Implications?

Wim van den Brink, MD, PhD, professor of psychiatry and addiction at the Academic Medical Center, University of Amsterdam, the Netherlands, said in a release that the findings were interesting, "especially since young women are catching up with young men when it comes to drinking and heavy drinking in Europe.

"This may also mean that a different group of women is getting involved in early heavy alcohol use than used to be the case. In other words, when heavy drinking occurs more frequently and tends to become the norm, women do not need to have some aberrant personal characteristic to become an early heavy user of alcohol," said Dr van den Brink, who was not involved with the research.

While noting that the study did not investigate preexisting neurobiological differences between the groups, "the finding of a different EEG pattern in male and female early heavy drinkers may indeed have important consequences for the treatment of male and female patients with an alcohol use disorder," he said.

"One of the most recent new medications for the treatment of alcohol dependence is the GABA-B agonist baclofen, which has shown mixed results, which may be explained by this work."

The study was supported by the Finnish Psychiatric Association, the Finnish Association of Adolescent Psychiatry, the Finnish Medical Society Duodecim, the Finnish Foundation for Alcohol Studies, the Paulo Foundation, and state research funding. The investigators have disclosed no relevant financial relationships.

30th European College of Neuropsychopharmacology (ECNP) Congress. Poster P.6.b.008, presented September 4, 2017.

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