A
study of nearly 10,000 adolescents funded by the National Institutes of Health
(NIH) has identified
distinct differences in the brain structures of those who used substances
before age 15 compared to those who did not. Many of these structural brain
differences appeared to exist in childhood before any substance use, suggesting
they may play a role in the risk of substance use initiation later in life, in
tandem with genetic, environmental, and other neurological factors.
“This adds to some emerging evidence
that an individual’s brain structure, alongside their unique genetics,
environmental exposures, and interactions among these factors, may impact their
level of risk and resilience for substance use and addiction,” said Nora Volkow
M.D., director of NIDA. “Understanding the complex interplay between the
factors that contribute and that protect against drug use is crucial for
informing effective prevention interventions and providing support for those
who may be most vulnerable.”
Among the 3,460 adolescents who initiated substances before age 15, most
(90.2%) reported trying alcohol, with considerable overlap with nicotine and/or
cannabis use; 61.5% and 52.4% of kids initiating nicotine and cannabis,
respectively, also reported initiating alcohol. Substance initiation was
associated with a variety of brain-wide (global) as well as more regional
structural differences primarily involving the cortex, some of which were
substance-specific. While these data could someday help inform clinical
prevention strategies, the researchers emphasize that brain structure alone
cannot predict substance use during adolescence, and that these data should not
be used as a diagnostic tool.
The study, published in JAMA Network Open, used data from the Adolescent Brain
Cognitive Development Study, (ABCD
Study), the largest longitudinal study of brain development and health in
children and adolescents in the United States, which is supported by the NIH’s
National Institute on Drug Abuse (NIDA) and nine other institutes, centers, and
offices.
Using data from the ABCD Study,
researchers from Washington University in St. Louis assessed MRI scans taken of
9,804 children across the U.S. when they were ages 9 to 11 – at “baseline” –
and followed the participants over three years to determine whether certain
aspects of brain structure captured in the baseline MRIs were associated with
early substance initiation. They monitored for alcohol, nicotine, and/or
cannabis use, the most common substances used in early adolescence, as well as
use of other illicit substances. The researchers compared MRIs of 3,460
participants who reported substance initiation before age 15 from 2016 to 2021
to those who did not (6,344).
They assessed both global and regional
differences in brain structure, looking at measures like volume, thickness,
depth of brain folds, and surface area, primarily in the brain cortex. The
cortex is the outermost layer of the brain, tightly packed with neurons and
responsible for many higher-level processes, including learning, sensation,
memory, language, emotion, and decision-making. Specific characteristics and
differences in these structures – measured by thickness, surface area, and
volume – have been linked to variability in cognitive abilities and
neurological conditions.
The researchers identified five brain
structural differences at the global level between those who reported substance
initiation before the age of 15 and those who did not. These included greater
total brain volume and greater subcortical volume in those who indicated
substance initiation. An additional 39 brain structure differences were found
at the regional level, with approximately 56% of the regional variation
involving cortical thickness. Some brain structural differences also appeared
unique to the type of substance used.
In a post-hoc analysis, the researchers
found that many of these brain differences still held even after removing those
participants who reported substance initiation prior to collection of their
baseline MRIs. The resulting comparison was between those who did not report
any substance use initiation and a subgroup of 1,203 participants in the
substance use initiation group who did not have any substance use experience
when their MRIs were first captured. The results of this secondary analysis
suggest that some of these brain structural differences may exist prior to any
substance use, challenging the interpretation that such differences are only
driven by substance exposure and pointing to an area for further investigation.
While some of the brain regions where
differences were identified have been linked to sensation-seeking and
impulsivity, the researchers note that more work is needed to delineate how
these structural differences may translate to differences in brain function or
behaviors. They also emphasize that the interplay between genetics,
environment, brain structure, the prenatal environment, and behavior influence
affect behaviors.
Another recent analysis of data from
the ABCD study conducted
by the University of Michigan demonstrates this interplay, showing that
patterns of functional brain connectivity in early adolescence could predict
substance use initiation in youth, and that these trajectories were likely
influenced by exposure to pollution.
Future studies will be crucial to
determine how initial brain structure differences may change as children age
and with continued substance use or development of substance use disorder.
“Through the ABCD study, we have a
robust and large database of longitudinal data to go beyond previous
neuroimaging research to understand the bidirectional relationship between
brain structure and substance use,” said Alex Miller, Ph.D., the study’s corresponding
author and an assistant professor of psychiatry at Indiana University. “The
hope is that these types of studies, in conjunction with other data on
environmental exposures and genetic risk, could help change how we think about
the development of substance use disorders and inform more accurate models of
addiction moving forward.”
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