Do Genetics Influence How Quickly the Brain Recovers From Alcohol Dependence? Research into the Hippocampus of the Brain

After several decades of research on alcohol and the brain, it is widely accepted that alcohol misuse and its associated health effects have a profound impact on the brain, including decreased overall brain volume, and decreased volume and function in the prefrontal cortex, which is crucial to how we organize, sequence, and plan our day to day lives.

Another finding across studies is that alcohol dependent individuals have reduced volume in the hippocampus, which is important to memory formation, and the connection between our memory, emotions, and sensory experiences. In particular, the hippocampus is implicated strongly in visual-spatial processing and memory, seen in day-to-day activities like using a map (or GPS), and understanding that objects become smaller in our visual field as we move further away from them.

However, we know far less about whether and how the hippocampus and its functions recover after someone stops drinking.

Prior research suggests this might be a difficult question to answer for several reasons:

there has not been a clear relationship between markers of alcohol severity, like age of onset for dependence, and smaller hippocampal volume
important factors that typically co-occur with alcohol use disorder, such as cigarette smoking, are also associated with a smaller hippocampus and could impact recovery of this memory-related brain structure
a substance called brain derived neurotrophic factor (BDNF) – which affects brain cell maintenance and production – could impact how the brain recovers from alcohol use disorder. From a genetic perspective, some individuals are born with a variant in the BDNF gene, called “Met carriers” (specifically, the “Val66Met” polymorphism), and prior work shows the brains of Met carriers may not recover as quickly as those without that variation, called Val homozygotes.

Hoefer and colleagues shed some new light on this complex and important issue by studying recovery of the hippocampus and its functions among 121 individuals in recovery from alcohol dependence (ALC) (based on diagnostic criteria from the diagnostic and statistical manual of mental disorders; DSM-IV) and 35 controls (CON) stratified by smoking status and whether or not they were a Met carrier. ALC patients were primarily male and Caucasian, and were recruited from substance use disorder (SUD) treatment programs in San Francisco, CA; controls were recruited from the SUD treatment catchment area.

Those reporting illicit drug misuse or dependence, and those with conditions known to be associated with smaller hippocampal volume (e.g., schizophrenia) were excluded from the study. Tests of ALC participants’ hippocampal volume, measured with magnetic resonance imaging (MRI) and visual-motor functioning, visual processing, and visual memory were administered, on average, about 1 week, 1 month, and 7 months after abstinence initiation. Hippocampal volumes of CON were assessed twice – once at baseline and again about 7 months later.

Authors found that although alcohol dependent individuals had smaller hippocampi than controls, smoking status was unrelated to hippocampus volume.

From a recovery perspective, ALC participants had more growth in their hippocampal volume, though still smaller relatively, compared to CON by the 7-month follow-up. However, the Val homozygotes showed betterrecovery than Met carriers (see figure below pulled from the article). Importantly, there were not clear differences until the 7-month follow-up.

Also, while hippocampal volume generally correlated with tests of visual-spatial processing, and visual-spatial memory, a relationship between increased hippocampal volumes and increases in these functions was only present for the Val homozygotes, but not the Met carriers.

This suggests genetic makeup can effect brain recovery for alcohol dependent individuals in recovery, but this differential growth takes time to observe in brain imaging, and perhaps day to day functioning as well. In addition, alcohol use severity (e.g., drinks per month in the year before treatment entry) was not associated with hippocampal volume.

IN CONTEXT

There is general consensus that alcohol misuse can have durable effects on brain structure and function. This study was unique in that it not only examined recovery of brain structure and function among alcohol dependent patients in recovery, but also considered the influence of cigarette smoking status, and an individual’s unique genetic characteristics

Authors findings’ that the hippocampi of alcohol dependent patients begin to recover after initiating abstinence, but that this recovery is greater for Val homozygotes – implicated in BDNF production – than Met carriers, speaks to the biopsychosocial complexities of addiction recovery, and the value in studying recovery from a multidisciplinary perspective like the one used here.

For example, one implication may be that for Met carriers, who have muted recovery in hippocampal volume, neurocognitive training in visual-spatial processing and memory tasks may be needed to compensate for the genetically-mediated deficit and to maximize recovery benefit and improve day to day functioning.

CITATIONS

Hoefer, M. E., Pennington, D. L., Durazzo, T. C., Mon, A., Abé, C., Truran, D., … & Meyerhoff, D. J. (2014). Genetic and behavioral determinants of hippocampal volume recovery during abstinence from alcohol. Alcohol, 48(7), 631-638.

Blanco, C., Okuda, M., Wang, S., Liu, S. M., & Olfson, M. (2014). Testing the drug substitution switching-addictions hypothesis: A prospective study in a nationally representative sample. JAMA psychiatry, 71(11), 1246-1253.