Heavy Drinking Linked to Decreased Grey Matter in Young Adults

Batya Swift Yasgur, MA, LSW

July 04, 2018

Heavy drinking in young adults is tied to changes in metabolite profile, which in turn, may be correlated with reduced brain grey matter volume, new research suggests.

Investigators studied young adults with a 10-year history of alcohol consumption, comparing the moderate-to-heavy and light drinkers by measuring metabolite concentrations and assessing brain grey matter volumes.

They found alterations in amino acid and energy metabolism, notably in creatine and mehtylhistamine, in the moderate-to-heavy drinkers compared with the light drinkers. In particular, the mehtylhistamine change was correlated with reduced grey matter volumes, especially in young women.

"Although the participants in our study didn't fulfill the criteria for alcohol addiction or even harmful use of alcohol according to ICD-10, the moderate-to-heavy drinking participants had changes in their metabolic profile and brain structure," lead author Noora Heikkinen, MSSc, a PhD candidate and researcher at the University of Eastern Finland, told Medscape Medical News.

"The production of histamine seems to be increased in the brains of heavy-drinking adolescents, which could cause brain atrophy manifested as reduced grey matter volume," she said.

The study was published online May 31 in Alcohol.

"Normative" Adolescent Use

Alcohol use "dramatically increases" during late adolescence, and heavy drinking is particularly detrimental to adolescent brain development, the authors write.

Neuroimaging studies have demonstrated that heavy alcohol consumption is connected to smaller grey matter volume in adults, and pathology studies have linked heavy alcohol use with white matter atrophy and focal neuronal loss.

Changes in amino acid and energy metabolism (for example, decreased amounts of glutamine and citrulline) are associated with alcohol consumption in both human and animal models.

It is likely that changes in metabolic processes and brain structure are linked but no previous studies have combined brain morphometry and metabolic profile analysis in humans, the writers note.

"There are several studies that have focused on the brain changes among adult alcoholics, however many adolescents and young adults engage in binge drinking," Heikkinen said.

"As the brain continues to develop throughout adolescence and even young adulthood, we thought it would be interesting to see if the so-called 'normative' adolescent use during this period of life could be seen as an altered metabolomics profile or changed brain structure," she reported.

The research was conducted as part of the Adolescents and Alcohol Study, which focuses on Finnish adolescent health and alcohol use.

The original cohort (n = 4127) was studied between 2001 and 2005, when participants were aged 13 to 17 years (time point 1).

All participants completed a questionnaire that included a shortened version of the Alcohol Use Disorders Identification Test (AUDIT-C).

They completed the same questionnaire in 2010–2011 (time point 2). Participants in the current study were selected from this group in 2013–2015 (time point 3).

Moderate-to-heavy use was defined as an AUDIT-C score of 4 or higher in males and 3 or higher in females, while light-drinking controls had scores of  2 or lower.

Age-, gender-, and education-matched light-drinking controls were recruited to correspond with the moderate-to-heavy alcohol users.

Exclusion criteria were a history of a head injury requiring medical treatment, neurological or severe mental illness, regular use of other intoxicating substances, and pregnancy.

The final number of participants included in the analysis were 35 moderate-to-heavy drinkers (20 females and 15 males) and 27 light-drinking controls (15 females and 12 males).

Researchers used liquid chromatography mass spectrometry to perform the metabolomics analysis of serum samples, and brain imaging was conducted using 3-T MRI.

Histamine Release

Researchers identified 100 metabolites from the samples, of which several differed between the moderate-to-heavy drinking participants and light-drinking controls. However, after adjustment, only the increased concentration of 1-methylhistamine in the moderate-to-heavy drinking participants was significant versus controls (P = .0011).

Compared with light-drinking controls, the moderate-to-heavy drinkers had higher concentrations of creatine and arginine.

Moderate-to-heavy drinkers also had significantly decreased brain grey matter volumes compared with the light-drinking controls (mean ± SD, 675.7 ± 51.2 mL vs 712.3 ± 51.4 mL; P = .007).

Researchers conducted a Pearson's correlation analysis between grey matter volume and metabolite abundance in the whole group.

They found significant inverse correlations between grey matter volume and creatine (r = -0.582; P < .0001) and 1-methylhistamine (r = -0.346; P = .0059). When researchers analyzed the genders separately, these correlations remained significant in females (r = -0.52, P = .0012; and r = -0.48, P = .0038; respectively) but not males (r = -0.25, P = .216; and r = -0.20, P = .316, respectively).

"The metabolites were measured from peripheral venous blood; however, 1-mehtylhistamine, which was discovered to be inversely correlated with brain grey matter volume in females, is produced in the brain from histamine," Heikkinen explained.

"Histamine release is part of the neuroimmune response and has been considered to be one of the reasons for alcohol-induced brain damage," she continued

She cautioned that, because the MRI scans were only performed at the end of the 10-year follow-up, "we cannot talk about causalities, as we cannot be sure whether the metabolic and brain changes would be in fact premorbid in heavy-drinking participants."

Toxic to Developing Brains

Commenting on the study for Medscape Medical News, Joseph Lee, MD, medical director for youth services, Hazelden Betty Ford Foundation, Center City, Minnesota, who was not involved with the study, said that it "challenges social norms like binge drinking in college and often anticlimactic birthday memes, potentially outdated rites of passage that do not cater to the best interests of our youth in an ever-competitive society."

Lee, who is a spokesperson for the American Academy of Child and Adolescent Psychiatry, noted that "previously touted health benefits of alcohol are now being challenged and it appears that even moderate levels of alcohol can be detrimental to one's health — this is another study in a similar vein."

He concluded, "Alcohol is simply toxic for developing brains. While the study doesn't aim to show functional practical deficits in young adults who drink moderately to heavily, the deterioration of grey matter volumes and suspected neuroinflammatory metabolites raise concern."

Heikkinen added, "There is some evidence that at least part of the changes in the brain structure are reversible if drinking is discontinued."

However, she cautioned, "more should be known about the exact mechanisms by which alcohol is connected to metabolic and brain structural changes to better understand when the changes might become permanent."

The study was supported by the Yrjö Jahnsson Foundation, Finnish Foundation for Alcohol Studies, Finnish Medical Foundation, and Paulo Foundation. Heikkinen reports receiving funding from Alko and the Olvi Foundation. Lee has reported no relevant financial relationships.

Alcohol. Published online May 31, 2018. Abstract

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