ADHD: A Precursor to Alcoholism? (Corpus Callosum part 2)

In the previous blog post on ADHD and alcoholism, we investigated some of the signs of overlap between the two disorders. One factor which both disorders appear to share in common is a reduction in volume of specific brain regions, including the corpus callosum, the genu, and the isthmus, when compared to similar individuals who do not exhibit either of the symptoms of ADHD or alcoholism. For a generalized location of these brain regions, please see the diagram below (which is a reprint of the figure from the last blog entry):

The corpus callosum is the tan band located inside of the gyrus cinguli, also known as the cingulate gyrus, a brain region whose role in ADHD we have discussed previously. The isthmus region is relatively small and is not labeled on this diagram. It is located to the right of the label "corpus callosum", and is just to the left of the area labeled "splenium".

**Please note my use of nomenclature here, I am continuing to use the same labeling as I did in the previous post. Here, we are considering the "genu" and "isthmus" as separate, distinct regions from the corpus callosum due, in part, to how they were classified in the studies I have been reviewing. However, many professionals label them all as one entity, with the genu and isthmus serving as sub-sections of the corpus callosum as a whole.

In today's blog, we will discuss the answers to two key questions:

1. Is there a hereditary factor at play for the size abnormalities for these three brain regions?


2. Does the outward expression of symptoms for one of these two disorders predate the other? In other words, is the appearance of ADHD symptoms a warning sign of impending alcohol abuse (or vice versa)?

For the answer to the first question, we turn to a journal article by Venkatasubramanian and coworkers in the journal Psychiatry Research: Neuroimaging. This group found that the relative size of the corpus callosum, genu and isthmus regions of the brain were correlated to an individual being at "high-risk" or "low-risk" for alcohol abuse. In this study, the "high-risk" group had a statistically significant reduction in size of multiple brain regions when compared to the "low-risk" group.

For comparison purposes, the "high-risk" group had approximately:

• a 9% reduction in corpus callosum volume
• a 13% reduction in the volume of the genu, and
• a 17% reduction in isthmus volume when compared to the low-risk group for these brain regions.

**Note: it worth mentioning that the comparative differences in relative brain sizes followed some sort of age-dependent trend. The subjects of study were boys and young men between the ages of 9 and 23. For the age 9-15 group, all three of the above brain regions were smaller. However, for the older group (over 15), only the isthmus region had a statistical size difference between the "high-risk" and "low-risk" groups. This suggests that either the isthmus region follows a much greater developmental delay in individuals identified as being "high-risk" for alcohol dependence than do the corpus callosum or the isthmus region never does fully "catch up" in size to the "low-risk group"

So what exactly constitutes "high" and "low" risk? In this study, the researchers studied males between the ages of 9 and 23 (sampling a relatively even distribution across this age range) who had male parents who both:

1. Developed an alcohol dependence before the age of 25 (average age of dependence around 20)
2. At least two relatives (first-degree), who also had alcohol dependence (average was 3 relatives).

The "low-risk" control group of children and young adults consisted of individuals whose parents were not diagnosed with alcoholism or any other psychological disorders. To ensure that maternal genetic influences were not a factor, none of the mothers of the children (the 9 to 23 year-old group) in the study were diagnosed with alcohol abuse.

This study is of potential interest. While the sample size was small (only 20 "high-risk" and 20 "low-risk"), the choice of following only male parents and male children offered some clear-cut advantages over other similar studies. Among them were:

• It eliminated gender effects. While debatable, some studies have found brain regions like the corpus callosum to be larger in males than in females. Having an all-male study eliminated this potential factor.


• The ages of the two groups (high and low risk) followed similar distribution patterns, to rule out size increases in these brain regions due to aging.


• Since the alcoholism was restricted to the paternal side, physiological effects during pregnancy were eliminated. This is important, as several studies have shown that maternal alcohol consumption during pregnancy can affect the development process including relative sizes of these brain regions. In other words, confounding effects, such as fetal alcohol syndrome were significantly reduced, since none of the mothers in the study suffered from clinical alcohol abuse.


• None of the 9 to 23 year-old test subjects had already developed an alcohol dependence. This eliminates the effects that chronic alcoholism has on reducing the size of the corpus callosum, as reported in recent studies.


• Other than alcoholism for fathers of the "high risk" group, none of the parents of the study participants had any other psychological disorder. This is important, especially due to the effects of comorbidity (disorders or symptoms occurring alongside alcoholism, such as conduct disorders or abuse of other substances) on worsening the symptoms of alcoholism.

So how does ADHD tie in to all of this?

Based on this study's findings, it appears that the expression of ADHD (as well as other "externalizing symptoms", which are symptoms that can be seen outwardly, such as hyper-excitability, conduct disorders, substance abuse, etc.) may be a warning sign of impending alcohol abuse.

For example, it has been postulated that hyperexcitability, which is often seen in individuals with ADHD (especially of the hyperactive-impulsive or combined subtypes) is a genetic precursor to alcohol dependence. In this case, and ADHD-like trait predates alcohol abuse. In other cases, symptoms such as substance abuse, conduct disorders, impulse control problems and other antisocial behaviors have grouped under the umbrella term generalized disinhibitory complex. Here, these numerous symptoms are essentially "clumped together" as one generalized behavior.

Regardless of the "model" one subscribes to, please keep in mind that a reduction in size the corpus callosum, genu and isthmus regions of the brain have been associated with ADHD.

Additionally, the degree of overlap between the two disorders was definitely worth mentioning. Out of the 20 children and young adults of the "high-risk" group, 17 of them were diagnosed with ADHD. Out of the 20 "low-risk" children? Zero.

Keep in mind that the fathers of the high-risk group were not diagnosed with any other disorders, just alcoholism. Additionally, keep in mind that none of the high-risk children had developed an alcohol dependence as of yet. These facts give compelling evidence that fathers who suffer from early-onset alcohol dependence who are not even ADHD themselves, are much more likely to have male children with ADHD, with an onset which precedes alcohol dependence itself.

In essence, this study established a degree of linkage (but not necessarily a direct cause) between the expressed behaviors of ADHD and alcoholism and the physiological features of relative sizes of the isthmus, corpus callosum and genu.

Hopefully this provides evidence that there is in fact a strong underlying hereditary component surrounding both disorders of ADHD and alcoholism. In the next couple of posts, we will investigate some of the individual genes thought to be involved in both of these disorders.