Does the use of psychoactive substances alter brain structure, or does brain structure predispose individuals to use these substances?

The use of psychoactive substances is significantly associated with an increased risk of developing brain structure disorders, particularly during adolescence when the brain undergoes substantial development, along with other adverse consequences later in life.

However, are the changes observed in the brains of individuals who use psychoactive substances a result of the substance use itself, or are they an inherent predisposition of certain individuals with specific neuroanatomical traits?

In the study "Neuroanatomical Variability and the Onset of Psychoactive Substance Use in Late Childhood and Early Adolescence," published in JAMA Network Open, researchers conducted a long-term study of behavioral and biological development from mid-childhood to young adulthood, tracking psychoactive substance use and brain structure.

A total of 11,875 children aged 8.9 to 11 years were selected at baseline from 22 research centers across the United States. The final analysis included 9,805 children who participated in 3-year follow-up assessments as part of the ongoing Adolescent Brain Cognitive Development (ABCD) Study.

Self-reports of the onset of psychoactive substance use (alcohol, nicotine, cannabis, or other substances) were recorded alongside baseline data from magnetic resonance imaging (MRI) assessing brain structures.

The researchers examined 297 phenotypes obtained through imaging, including measures of overall brain volume, volume, thickness, surface area of the cortex and subcortex, as well as the depth of sulci. The variable parameters included age, sex, puberty status, family relationships, prenatal exposure to psychoactive substances, and MRI scanner models.

In the statistical analysis, the brain structure of participants who began using psychoactive substances before the age of 15 was compared to those who did not use psychoactive substances. To identify differences in brain structure that preceded the onset of psychoactive substance use, participants who reported substance use at baseline were excluded from the analysis. Corrections for multiple testing were applied to validate the findings.

The results indicate that structural differences in the brain, including a larger overall brain volume and regionally thinner prefrontal cortex, may predispose adolescents to initiate use of substances such as alcohol, nicotine, and cannabis before the age of 15. These structural differences were observed prior to the onset of psychoactive substance use, suggesting that they reflect an already existing condition, potentially serving as risk factors rather than consequences of psychoactive substance exposure.

Among the participants, 3,460 individuals (35.3%) reported the onset of psychoactive substance use before the age of 15, with alcohol being the most common (90.2% of cases).

The differences in brain structure included:

– Significant signs of thinner cortical areas in the prefrontal cortex, particularly in the central frontal gyrus. Increased cortical thickness in the occipital, parietal, and temporal lobes.

– A larger total brain volume, cortical volume, and subcortical volume were associated with the onset of psychoactive substance use, including a larger volume of the hippocampus and globus pallidus.

– Cannabis use was uniquely associated with a reduction in the volume of the right tail. Subsequent specialized analyses confirmed most findings when compared to children who do not use psychoactive substances, suggesting that structural differences precede psychoactive substance use.

The researchers emphasize the importance of the study for rethinking the causal premises in models of brain diseases related to addiction.

They believe that the large sample size, long-term design, and genetically informative components of the ABCD study (family study design, nested twin subsamples, and DNA collection) are key to improving qualitative conclusions about neural risk factors.