Volume 13, Issue 2
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Spring 2021
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https://www.spectrum.niaaa.nih.gov
FEATURE
BRAIN RESEARCH: A FOCUS ON CHILDHOOD
TRAUMA AND ALCOHOL MISUSE
News reports of college
drinking tragedies, and
concerns about increased
access to alcohol in the home
during the pandemic, make
clear that COVID-19 has
provided no reprieve from
the problems of underage
drinking. A perennial public
health priority, alcohol
misuse by young people
increases the likelihood of myriad serious consequences, including altered
brain development, academic problems, unsafe sexual behavior, physical and
sexual assault, traffic crashes, injuries, overdoses, and alcohol use disorder
(AUD).
To be sure, efforts to reduce underage drinking have seen success in recent
decades. Epidemiological data from the annual Monitoring the Future survey,
funded by the National Institute on Drug Abuse, show that by 2020,
proportional declines in the prevalence of binge drinking, following recent
peaks reached in the 1990s, were 66 percent, 60 percent, and 47 percent for
grades 8, 10, and 12, respectively.
George. F. Koob, Ph.D., Director of the National Institute on Alcohol Abuse
and Alcoholism (NIAAA), notes “We are indeed making progress at
reducing alcohol misuse among adolescents and young adults; however, the
declines have been larger among males than females, and trends in serious
alcohol-related harms have not matched the trends in drinking prevalence.
Also, drinking to cope with stress is a growing concern.”
Recent and ongoing studies supported by NIAAA indicate that investigations
of the relationship between childhood trauma and alcohol misuse, and the
neural substrates through which that relationship is mediated, will provide
important avenues for continued progress against underage drinking, its
subsequent problems, and their potential treatment. Many of these studies
include examination of emotional stress and mental health problems, such as
post-traumatic stress disorder (PTSD), that frequently co-occur with AUD.
IN THIS ISSUE
FEATURE
1
Brain Research: A Focus on
Childhood Trauma and
Alcohol Misuse
NEWS FROM THE FIELD
3
Emotional Responses to
Alcohol May Predict
Alcohol-Related Problems
4
Insights on Alcohol-
Related Brain
Inflammation, and Hints
About How To Reduce It
NOTEWORTHY
5
NIAAA Announces New
Extramural Research
Division
6
NIAAA Intramural Scientists
Named to Cell Mentor’s List
of Inspiring Black Scientists
in America
SPOTLIGHT
7
NIAAA Expands Its Social
Media Presence to Facebook
8 Racial Equity and Inclusion
in Biomedical Research—
and the NIH UNITE
Program
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For example, in a 2020 study led by scientists at Arizona State University, researchers found that recollections of
childhood trauma (such as sexual and emotional abuse) may contribute to PTSD symptoms and impaired control
over drinking among college students. The researchers found that reducing PTSD symptoms may help individuals
regain control over their drinking. Also last year, researchers at Virginia Commonwealth University reported that
young adults with a history of childhood maltreatment may use alcohol to cope with trauma-related negative
emotions. The study’s findings suggest that targeting emotional distress in people exposed to trauma in childhood
may be helpful in preventing and treating alcohol-related problems in this vulnerable population. In a recent
analysis conducted by the NIAAA-
showed that having a family history of AUD and exposure to trauma during adolescence may be associated with
increased PTSD and AUD symptoms and poor problem-solving abilities in adulthood.
NIAAA supports the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), a
major research initiative established to determine the effects of alcohol misuse on the developing adolescent brain
and to examine brain characteristics that predict AUD. In a recent study, researchers used NCANDA data to
investigate the relationships among childhood trauma, functional brain connectivity, impaired executive function,
and future binge drinking during adolescence. Led by scientists at the University of California San Diego, the
study found that functional brain networks, particularly from regions important for cognitive and sensorimotor
control, explain the relationship between childhood trauma and impaired executive function and are important for
predicting binge drinking. Age, severity of childhood trauma, extent of executive function deficits, and functional
brain connectivity together were useful in accurately predicting binge drinking 1–4 years after research
participants were initially assessed for alcohol misuse.
Another NCANDA study recently demonstrated that adolescent alcohol misuse and early-life trauma led to
increased hippocampus growth and decreased amygdala growth with age. The hippocampus and amygdala are
brain regions that regulate goal-directed behaviors, inhibition, memory, anxiety, and fear responses. NCANDA
investigators have also demonstrated that non-drinking or low-drinking adolescents who reported experiencing
trauma and symptoms of post-traumatic stress escalated their alcohol intake during a 4-year followup period more
quickly than adolescents who did not experience trauma. Taken together, these NCANDA findings demonstrate a
relationship between early adverse experiences, brain development, and alcohol misuse, and suggest that
interventions that target trauma may be beneficial in preventing future alcohol misuse and AUD.
NIAAA-supported research continues to build a solid foundation for the development of unique strategies for
treating alcohol problems that arise during the developmentally risky period of adolescence. Recently, NIAAA
issued a Notice of Special Interest to expand research on how treatment strategies can be tailored for adolescents.
These strategies include behavioral treatments that take into account the developmental, biological,
neurocognitive, psychological, emotional, and social needs of youth, as well as intervention approaches that
account for comorbidity, cultural, and other factors.
“Prevention and treatment strategies grounded in a developmental framework that takes into account early life
stress will help us maximize the odds that individuals make it into young adulthood cognitively and emotionally
prepared for the rigors of adult life,” says Dr. Koob.
He adds that the unprecedented stressors experienced by young people during the COVID-19 pandemic will
linger to some degree, even as society begins to contemplate the potential end of the pandemic. “Current public
health measures, and the uncertainties and anxieties they engender about the future, lost income, and social
isolation, will be with us for a while longer. And the transition to a post-pandemic reality will itself be a likely
source of new stressors and anxieties as society adjusts to a new ‘normal,’ underscoring the importance of
ongoing NIAAA investigations into the relationship between stress and alcohol misuse.”
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References:
Patock-Peckham, J.A.; Belton, D.A.; D’Ardenne, K.; Tein, J-Y.; Bauman, D.C.; Infurna, F.J.; Sanabria, F.; Curtis, J.; Morgan-Lopez, A.A.; and McClure, S.M.
Dimensions of childhood trauma and their direct and indirect links to PTSD, impaired control over drinking, and alcohol-related-problems. Addictive
Behaviors Reports 12:100304, 2020. PMID: 33364313
Shin, S
.H.; Jiskrova, G.K.; Yoon, S.H.; and Kobulsky, J.M. Childhood maltreatment, motives to drink and alcohol-related problems in young adulthood.
Child Abuse & Neglect 108:104657, 2020. PMID: 32854053
Subbie-Saen
z de Viteri, S.; Pandey, A.; Pandey, G.; Kamarajan, C.; Smith, R.; Anokhin, A.; Bauer, L.; Bender, A.; Chan, G.; Dick, D.; Edenberg, H.;
Kinreich, S.; Kramer, J.; Schuckit, M.; Zang, Y.; McCutcheon, V.; Bucholz, K.; Porjesz, B.; and Meyers, J.L. Pathways to post-traumatic stress disorder and
alcohol dependence: Trauma, executive functioning, and family history of alcoholism in adolescents and young adults. Brain and Behavior
10(11):e01789, 2020. PMID: 32990406
Silveir
a, S.; Shah, R.; Nooner, K.B.; Nagel, B.J.; Tapert, S.F.; De Bellis, M.D.; and Mishra, J. Impact of childhood trauma on executive function in
adolescence—Mediating functional brain networks and prediction of high-risk drinking. Biological Psychiatry: Cognitive Neuroscience and
Neuroimaging 5(5):499–509, 2020. PMID: 32299789
Phillips
, R.D.; De Bellis, M.D.; Brumback, T.; Clausen, A.N.; Clarke-Rubright, E.K.; Haswell, C.C.; and Morey, R.A. Volumetric trajectories of hippocampal
subfields and amygdala nuclei influenced by adolescent alcohol use and lifetime trauma. Translational Psychiatry 11(1):154, 2021. PMID: 33654086
NEWS FROM THE FIELD
EMOTIONAL RESPONSES TO ALCOHOL MAY PREDICT ALCOHOL-
RELATED PROBLEMS
Alcohol can induce temporary positive feelings such as
elation and happiness and reduce negative feelings like
distress. These emotional responses to alcohol are
believed to contribute to drinking behaviors that lead to
alcohol use disorder or that make abstaining from
drinking more difficult for some people. A new study
funded by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) now sheds more light on the link
between emotional responses to alcohol and drinking
behaviors. It also reveals that emotional responses may
be a predictor of alcohol-related problems.
To examine alcohol’s effects on emotions and drinking
behaviors over time, Catharine Fairbairn, Ph.D., and
Walter James Venerable, III, M.S., at the University of
Illinois at Urbana-Champaign, combined laboratory
and real-world assessments that measured emotional responses to alcohol with long-term followup surveys of
alcohol consumption. In the study, 60 young adults who engaged in heavy drinking attended two beverage-
administration sessions in a laboratory, in which they consumed their beverages in social groups, designed to
mirror real-world drinking conditions. They also completed surveys that measured their anxiety and positive and
negative moods, such as cheerful and upbeat or annoyed and sad, respectively. In one session, participants
received an alcoholic beverage, and in the other session they received a nonalcoholic beverage. A subset of
participants also participated in a real-world, or ambulatory, assessment for 7 days to evaluate their alcohol
consumption and mood in everyday contexts. This group wore transdermal alcohol monitors and responded to
Catharine Fairbairn, Ph.D., and Walter James Venerable, III, M.S., led the
University of Illinois at Urbana-Champaign project assessing emotional responses
to alcohol.
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random survey prompts about their mood six times per day. They also provided daily reports of their alcohol
consumption. The researchers followed up with participants 18 months later.
The researchers found that participants who experienced a greater degree of positive mood after alcohol
administration in the laboratory study were more likely to binge drink regularly and experience drinking problems
at the 18-month followup. Similarly, participants who experienced greater reductions in negative mood were more
likely to have drinking problems 18 months later. In the ambulatory study, alcohol-related reductions in negative
mood measured in everyday contexts significantly predicted drinking problems at followup.
The results of the study support prior research demonstrating that emotional responses contribute to problematic
drinking and that alcohol’s ability to enhance positive mood and reduce negative mood may predict problematic
drinking patterns later on.
Note:
NIAAA defines heavy drinking as follows:
•
•
For men, consuming more than 4 drinks on any day or more than 14 drinks per week
For women, consuming more than 3 drinks on any day or more than 7 drinks per week
Reference:
Venerable, W.J.; and Fairbairn, C.E. A multimodal, longitudinal investigation of alcohol’s emotional rewards and drinking over time in young adults.
Psychology of Addictive Behaviors 34(5):601–612, 2020.
PMID: 32118462
NEWS FROM THE FIELD
INSIGHTS ON ALCOHOL-RELATED BRAIN INFLAMMATION, AND
HINTS ABOUT HOW TO REDUCE IT
Research suggests that long-term alcohol exposure leads to
inflammation and damage to tissue in the brain and other
organs—and inflammation could also potentially be involved in
alcohol use disorder (AUD). A recently published mouse study
supported by the National Institute on Alcohol Abuse and
Alcoholism suggests a mechanism that contributes to this
process: the migration and recruitment of blood-circulating
immune cells to the brain. The study also shows that blocking
one step along this pathway reduces this immune cell
recruitment—opening a door to a potential therapeutic target for
reducing inflammation-related damage in the brain.
Pr
evious research suggests that immune cells from the body can infiltrate the brain following long-term alcohol
exposure. The immune cells in question—monocytes—can wreak havoc if they are recruited to an organ such as
the brain or liver. In the brain, monocytes transform into a type of immune cell called macrophages, which can
play a role in kicking off a chain reaction of inflammation and tissue damage.
In
the current study, the researchers found that feeding mice alcohol over the course of 6 weeks increased the
number of macrophages in the brain. Once in the brain, macrophages contribute to signs of brain injury, such as
the activation of brain-specific immune cells known as microglia, and the release of cytokines (a cell-signaling
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molecule). This increase in macrophages was particularly noticeable in the hippocampus (compared to the
cerebellum or cortex).
The r
esearchers then tested whether they could reduce neuroinflammation after chronic alcohol use by blocking
the CCR2/CCR5 pathway via administration of a drug called cenicriviroc (CVC). Previous research suggested
that the CCR2/CCR5 pathway is involved in monocyte recruitment to tissues like the brain following long-term
alcohol exposure. For example, there is evidence that alcohol exposure ramps up the amount of the protein—
CCL2—that binds to the CCR2 receptor protein and promotes the recruitment of monocytes. The researchers
showed that CVC is effective in reducing the recruitment of monocytes to the brain after long-term alcohol
exposure. CVC also decreased certain signs of alcohol-induced brain inflammation. This finding complements
results of ongoing research with CVC aimed at reducing inflammation in the liver, suggesting CVC could reduce
inflammatory damage in multiple organ systems.
Taken
together, this research reveals a potential molecular target to curb brain and liver inflammation due to long-
term alcohol consumption, such as in individuals with AUD and alcohol-associated liver disease.
References:
Lowe, P.P.; Morel, C.; Ambade, A.; Iracheta-Vellve, A.; Kwiatkowski, E.; Satishchandran, A.; Furi, I.; Cho, Y.; Gyongyosi, B.; Catalano, D.; Lefebvre, E.;
Fischer, L.; Seyedkazemi, S.; Schafer, D.P.; and Szabo, G. Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral
macrophage infiltration and microglia alterations. Journal of Neuroinflammation 17(1):296, 2020.
PMID: 33036616
Lefebvre, E.; Moyle, G.; Reshef, R.; Richman, L.P.; Thompson, M.; Hong, F.; Chou, H-L.; Hashiguchi, T.; Plato, C.; Poulin, D.; Richards, T.; Yoneyama, H.;
Jenkins, H.; Wolfgang, G.; and Friedman, S.L. Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney
fibrosis. PLoS One 11(6):e0158156, 2016.
PMID: 27347680
NOTEWORTHY
NIAAA ANNOUNCES NEW EXTRAMURAL RESEARCH DIVISION
T
he Med
ications Development Branch oversees the development of medications for AUD by translating
neuroscience discoveries into promising compounds and advancing them through the medications
development pipeline. This includes funding studies to enable investigators to obtain Investigational New
Drug status from the U.S. Food and Drug Administration for compounds that show promise, and conducting
and supporting alcohol interaction, human laboratory, and Phase II clinical trials. The Medications
Development Branch also seeks to:
The National Institute on Alcohol Abuse and Alcoholism
(NIAAA) recently introduced the Division of Treatment and
Recovery (DTR), formed from the merger of the Institute’s
Division of Medications Development and Division of
Treatment and Recovery Research. The new division
focuses on identifying and improving pharmacological and
behavioral treatments for alcohol use disorder (AUD),
enhancing methods for sustaining recovery, and increasing
the use of evidence-based treatments in real-world practice.
DTR is led by Raye Litten, Ph.D., Acting Director, and
Joanne Fertig, Ph.D., Acting Deputy Director, and is
composed of a Medications Development Branch and a
Treatment, Services, and Recovery Branch.
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•
•
•
•
Identify new targets for AUD medications in collaboration with the Division of Neuroscience and
Behavior and Division of Metabolism and Health at NIAAA,
Develop screening models that predict a high probability of clinical efficacy and safety,
Engage pharmaceutical and biotechnical companies in medications development for AUD, and
Facilitate the use of alcohol treatment medications in clinical practice.
The Treatment, Services, and Recovery Branch supports a broad portfolio of behavioral treatment and
recovery research. This includes:
•
•
•
•
•
Developing and improving behavioral interventions for AUD,
Increasing the use of evidence-based behavioral treatments in a wide range of practice settings,
Improving treatments for individuals with AUD and co-occurring psychiatric and substance use
disorders,
Gaining a better understanding of the dynamics of recovery, and
Developing innovative methods and technologies for AUD treatment and recovery.
The Treatment, Services, and Recovery Branch is also interested in advancing research on topics focusing on
special-emphasis and underserved populations, including minority populations, adolescents and young adults,
older adults, individuals with fetal alcohol spectrum disorders, and persons living with HIV/AIDS. Together
both branches will facilitate the overall goals of the Division of Treatment and Recovery to advance precision
medicine in the treatment of AUD and promote and facilitate treatment of AUD across all groups in our
diverse society.
NOTEWORTHY
NIAAA INTRAMURAL SCIENTISTS NAMED TO CELL MENTOR’S
LIST OF INSPIRING BLACK SCIENTISTS IN AMERICA
The Cell Mentor website (http://crosstalk.cell.com/en/cell-mentor) is a dedicated resource provided by Cell Press
to help individuals build the skills necessary for a successful career in science. Cell Mentor collects blog posts,
video interviews, experimental tutorials, handbooks, and Cell Press journal articles to empower and inspire early
career researchers. On December 28, 2020, Cell Mentor posted a list of 1,000 inspiring Black scientists in
America.
Included in the Cell Mentor list were two National Institute on Alcohol Abuse and Alcoholism (NIAAA)
intramural scientists:
Michelle Antoine, Ph.D., Chief of the Section on Neural Circuits. Dr. Antoine joined
NIAAA in 2020 as an Earl Stadtman Tenure-Track Investigator and is currently an
NIH Distinguished Scholar. Her laboratory focuses on genetic and environmental
factors that impair neurocircuit activity, leading to neurodevelopmental disorders.
Her recent work on neuron signal activity led to important new insights into autism
spectrum disorder. At NIAAA, Dr. Antoine is applying her basic research experience
in neurocircuit function to neurodevelopmental comorbidities commonly seen in fetal
alcohol spectrum disorders.
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Paule Valery Joseph, CRNP, Ph.D., Chief of the Section of Sensory Science and
Metabolism. A Lasker Clinical Research Scholar and an NIH Distinguished Scholar,
Dr. Joseph leads a research group conducting preclinical, clinical, and translational
studies that aims to improve the diagnosis, prevention, and management of
chemosensory disorders and symptoms (taste and smell alterations). A focus of
Dr. Joseph’s research at NIAAA is to explore, at the neurobiological level, how
senses such as smell and taste are involved in cues that trigger craving for alcohol, a
diagnostic feature of alcohol use disorder.
Congratulations to Dr. Joseph and Dr. Antoine!
SPOTLIGHT
NIAAA EXPANDS ITS SOCIAL MEDIA PRESENCE TO FACEBOOK
The National Institute on Alcohol Abuse and Alcoholism
(NIAAA) recently launched a new Facebook page. This
expansion of the Institute’s social media footprint allows NIAAA
to reach the rich diversity of Facebook users—particularly
individuals, families, educators, and other adults who could
benefit from NIAAA’s resources and health messages. Follow us
on Facebook today at
https://www.facebook.com/NIAAAgov.
Alcohol affects the lives of many Americans. According to the
2019 National Survey on Drug Use and Health, 54.9 percent of
adults reported that they drank alcohol sometime in the past
month and 25.8 percent reported binge drinking in the past
month. Through Facebook, NIAAA will be able to provide users
of this platform with valuable information about how alcohol
misuse affects human health and development, and about the
work of NIAAA.
Learn more about NIAAA’s social media efforts and other ways to stay connected.
CONTACT US
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SPOTLIGHT
RACIAL EQUITY AND INCLUSION IN BIOMEDICAL RESEARCH—
AND THE NIH UNITE PROGRAM
This past March, the National Institutes of Health (NIH) launched the
UNITE initiative to address structural racism at NIH, NIH-supported
institutions, and anywhere NIH research activities take place. The
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Director George F. Koob, Ph.D., announced his enthusiastic support
of UNITE and his commitment to equity, diversity, and inclusion at
NIAAA and in the alcohol research enterprise.
The UNITE program aligns with the efforts that NIAAA has made—
and continues to make—to promote equity, diversity, and inclusion.
For example, NIAAA recently established an Equity, Diversity, and
Inclusion Steering Committee to inform its efforts. To make the foundational changes that are needed, NIAAA
will focus on the following domains: improving the NIAAA intramural and extramural workplace and culture,
increasing diversity and equity in the scientific and administrative workforce, and enhancing the NIAAA
intramural and extramural scientific research portfolio.
Looking ahead, NIAAA is dedicated to expanding career opportunities for researchers, clinicians, and
administrators from diverse and underserved communities. “Because our alcohol research community is so
focused and we know that diversity enriches our efforts in every way, we can dedicate ourselves to engaging
diversity to sustain our field. As such, I believe we have a unique opportunity to expand opportunities for future
alcohol researchers and administrators. Let’s remember, a focus on equity does not apply solely to those who
work on our purely scientific endeavors, but to all of us who support this critical biomedical enterprise dedicated
to the diagnosis, prevention, and treatment of alcohol misuse,” says Dr. Koob.
ABOUT US
NIAAA Spectrum is NIAAA’s webzine. With engaging
feature articles, short news updates, and colorful graphics, NIAAA
Spectrum offers accessible and relevant information on NIAAA and
the alcohol research field.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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P.O. Box 10686, Rockville, MD 20849-0686
888–MY–NIAAA (888–696–4222)