The discovery centres on a brain receptor related to the chemical dopamine, which has a complex role in addictive behaviours.

Using brain scans and a novel chemical probe developed in CAMH’s Research Imaging Centre, CAMH scientists found that the probe had high levels of binding to the dopamine D3 receptor in some people with methamphetamine addiction, compared with those who had no addiction. Higher levels of D3 were also linked to participants’ reported motivation to take drugs.

“This is the first time, to our knowledge, that anyone has shown that D3 receptor levels are high in people with an active addiction to methamphetamine,” says Dr. Isabelle Boileau, a scientist in the Research Imaging Centre, part of the new Campbell Family Research Institute at CAMH. Boileau led the study that appears in the January 25, 2012 issue of The Journal of Neuroscience.

Using positron emission tomography (PET), Boileau’s team looked at D3 levels in 16 people who were dependent on methamphetamine. Participants abstained from methamphetamine use for 14 days prior to brain scans. Their results were compared with scans from 16 participants with no addiction. On a separate day after scanning, participants were given a low dose of amphetamine, and they had to report how much they wanted to use drugs.

D3 receptors appear to have a role in craving, but it is not fully established how they are related to drug-related behaviours. The new chemical probe developed at CAMH, called 11C-(+)-PHNO, binds to dopamine D3 receptors. This probe allows researchers to study D3 in people for the first time, using PET scans, in order to answer questions about its role in stimulant addiction.

Understanding the role of brain receptors in addiction has enabled researchers to develop treatment medications, such as nicotine replacement therapy for smoking. So far, therapeutic strategies for stimulant addiction have focused on increasing activity with D2 receptors, where binding levels have been low.

“We can now suggest that any therapeutic approach aimed at increasing activity with D2 receptors should consider being selective at targeting D2, and not increasing D3 levels,” says Boileau. “Our finding also supports the idea that D3 should be considered another target for anti-craving medications.”

Boileau is also looking at the role of D3 in different types of addictions, including cocaine and gambling.

Building on CAMH’s record of innovation and discovery, the Campbell Family Mental Health Research Institute will be accelerating discoveries in the areas of mood disorders, addictions, schizophrenia and cognitive impairment.

CAMH’s Research Imaging Centre is the first of its kind in Canada where positron emission tomography (PET), magnetic resonance imaging (MRI), and imaging-genetics are dedicated to the study of mental illness and addictions.

This new discovery is an example of the innovative brain science at CAMH’s new Research Imaging Centre, the first of its kind in Canada where positron emission tomography (PET), magnetic resonance imaging (MRI), and genetic imaging are dedicated to the study of mental illness and addictions.

“Research shows there is a spike in alcohol-related consequences that occur in the first few weeks of the semester, especially with college freshmen,” said Michael J. Cleveland, research associate at the Prevention Research Center and the Methodology Center. “If you can buffer that and get beyond that point and safely navigate through that passage, you reduce the risk of later problems occurring.”

The researchers tested two different methods of intervention on incoming freshmen — parent-based intervention and peer-based intervention. Cleveland and his colleagues found that students who were non-drinkers before starting college, and who received the parent-based intervention, were unlikely to escalate to heavy drinking when surveyed again during the fall semester of their first year.

Students who were heavy drinkers during the summer before college were more likely to transition out of that group if they received either parent-based intervention or peer-based intervention. However, if a heavy-drinker received both interventions, there was no enhanced effect.

Cleveland reported online in Psychology of Addictive Behaviors that 8 percent of the incoming freshmen were heavy drinkers the summer before starting college. The researchers surveyed the students again during the fall semester and found 28 percent of the freshmen now drank heavily.

The results of the study were based on a study of 1,275 high-risk matriculating college students originally conducted in 2006 by Rob Turrisi, professor of biobehavioral health. Turrisi and his colleagues randomly assigned students to one of four intervention groups — parent-based intervention only, peer-based intervention only, both parent- and peer-based intervention or no intervention — and then surveyed the students on their drinking behaviors the summer before they entered college and then again during their first fall semester.

The parent-based intervention involved parents receiving a 35-page handbook outlining how to discuss the issue of alcohol and how to relate to their college student. Parents were asked to fill out an evaluation of the booklet, which also served as a measure to determine how many parents read the material. All parents completed the evaluations.

For peer-based intervention, subjects met one-on-one with a trained peer facilitator once within the first two weeks on campus. The meetings were 45 to 60 minutes long and included “perceived and actual descriptive norms for drinking, drinking consequences, alcoholic caloric consumption and hours of exercise required to burn those calories,” the researchers report.

All students included in the survey were former high school athletes, chosen because this group is considered at high risk for heavy alcohol use and its consequences, which include risky sex, driving drunk and personal injury or death.

In the new investigation, Cleveland and his colleagues approached the study differently. Rather than focusing on average levels of drinking — peak blood alcohol content, drinks per weekend and drinks per week — Cleveland reanalyzed the data using a person-centered approach to determine students’ patterns of drinking as well as how the students responded to intervention. This allowed the researchers to examine how drinking patterns varied throughout the week as well as how the interventions could be linked to students’ transitions from one sub-group to another.

“We found four sub-groups of drinkers, which is an important advance to understanding different types of drinking that were present in this college sample,” said Cleveland.

The sub-groups included non-drinkers, who did not report drinking alcohol at all; weekend non-bingers, who tended to only consume alcohol socially on Fridays and Saturdays; weekend bingers, who were likely to report binge drinking and getting drunk in the past month on Fridays and Saturdays; and heavy drinkers, who reported drinking every day of the week, most notably Thursdays.

Although neither intervention strategy appeared to influence the weekend drinkers, whether bingers or non-bingers, the intervention effects on the nondrinkers and heavy drinkers were promising, said Cleveland.

“From here we may be able to tailor the intervention to different types of students, identifying those students who are at different types of risk,” said Cleveland. “By figuring out a way to match the intervention to the individual you can also maximize your resources for intervention.”

Cleveland is continuing this work by replicating the results among another sample of college students and is also using the same methods to study the drinking behaviors of young adults who are not attending college.

A new brain imaging study by Yale School of Medicine researchers suggests stress robustly activates areas of the brain associated with craving in cocaine-dependent women, while drug cues activate similar brain regions in cocaine-dependent men. The study, expected to be published online Jan. 31 in the American Journal of Psychiatry, suggests men and women with cocaine dependence might benefit more from different treatment options.

“There are differences in treatment outcomes for people with addictions who experience stress-induced drug cravings and those whose cravings are induced by drug cues,” said Marc Potenza, professor of psychiatry, child study, and neurobiology and first author of the study. “It is important to understand the biologic mechanisms that underlie these cravings.”

The researchers conducted functional magnetic resonance imaging scans of 30 cocaine-dependent individuals and 36 control subjects who were recreational drinkers. While undergoing brain scans, researchers then presented subjects with personalized cues (situations or events) the participants had indicated were personally stressful and other cues involving cocaine or alcohol.

As expected, cocaine-dependent individuals showed greater activation in broad regions of the brain linked to addiction and motivation than the control subjects. Patterns of activation between the groups, however, differed markedly in men and women when presented with stress or drug cues.

Potenza said the findings suggest that women with cocaine dependence might benefit from stress-reduction therapies that specifically target these cravings. Men, on the other hand, might derive more benefit from elements of cognitive behavioral therapy or 12-step programs based on the principles of Alcoholics Anonymous.

From a clinical point of view the Authors of this study were interested in the predictive value of alexithymia at baseline on recovery. They hypothesized a negative relation of alexithymia with outcomes, which would be a strong argument for addressing alexithymia at intake and adjusting therapy for highly alexithymic patients. A total of 187 abstinent SUD inpatients were assessed at baseline by the Dutch version of the Toronto Alexithymia Scale (TAS-20) and the European ASI (EuropASI) at baseline and 3-month follow-up after an inpatient CBT as usual (CBT-TAU group) or CBT with shared decision making intervention (SDMI) (CBT-SDMI group).

All patients have been diagnosed according to the DSM-IV-TR as having 1 or more substance-related disorders. The mean score on the TAS-20 at baseline was 55.7 (SD = 11.3). According to the cutoff score, 36.9% were highly alexithymic and 33.2% were low scoring alexithymics. Highly alexithymic patients had fewer years of education [p =0.05] and were more often unemployed [p = 0.05] than low-scoring alexithymics.

Highscoring alexithymics showed more problems in the ‘work, income and education’ [p= 0.04] and ‘psychiatry’ domains [p<0.001]. The mean time of treatment (in days) for highly alexithymic patients (116.0, SD = 58.9) was not different from that for low scoring alexithymics [p = 0.26], and also the rate of completers was similar between high- (50.7%) and low-scoring alexithymics [p=0.41]. Fifty-four percent of the high-scoring, and 45.7% of the low-scoring alexithymics were abstinent at follow-up [p=0.41].

As concerns the Europ-ASI, differences between baseline high- and low-scoring alexithymic patients were found for the ‘work, income and education’ domain in the CBT-SDMI group, and for the ‘family and social relations’ and ‘drugs’ domains in the CBT-TAU group.

Overall, highly alexithymic patients improved on the EuropASI change scores at least equally well as low-scoring alexithymic patients, and alexithymia as a continuous score was predominantly positively associated with these change scores.

The results of this study show that highly alexithymic SUD patients can profit from CBT with or without SDMI, and that the degree of alexithymia is not negatively related to resulting outcomes. Limitations of this study were the absence of systematic urine or blood samples to confirm abstinence, and not having performed multimethod alexithymia assessments with an observer scale included.

However, in answering the question on whether a highly alexithymic SUD patient should be treated differently at the beginning of treatment, the Authors made use of the two extremes of categorical classification of alexithymia. As highly alexithymic SUD patients performed very well and alexithymia was associated with the treatment outcomes, CBT may be used in this population even if patients present alexithymic features at intervention entry.

For every three months during the study, participants drank an average of 8 percent fewer drinks on their heaviest drinking days.

They also had fewer instances of delirium tremens, a life-threatening form of alcohol withdrawal.

The American Journal of Public Health published the findings Jan. 19.

Housing for chronically homeless people usually comes with many conditions, including abstinence from drugs and alcohol and compliance with psychiatric and substance abuse treatment. But such requirements can become barriers to staying in housing.

“These individuals have multiple medical, psychiatric and substance abuse problems, and housing that requires them to give up their belongings, adhere to curfews, stop drinking and commit to treatment all at once is setting them up to fail. The result is that we are relegating some of the most vulnerable people in our community to a life on the streets,” said Susan Collins, lead author and University of Washington research assistant professor of psychiatry and behavioral sciences.

Because they are unable to cope with the rules, they often do not qualify for housing or are asked to leave. Once back on the street, they cost taxpayers’ money through use of emergency room visits, shelter and sobering center stays, arrests and jail bookings.

In response, an approach called project-based Housing First has been developed by the Downtown Emergency Service Center, a Seattle-based housing agency. Project-based Housing First provides immediate, permanent and supportive housing to chronically homeless people within a single housing project. It is considered “low-barrier” because it removes some of the traditional barriers to housing, such as abstinence from alcohol.

The idea behind it is that if chronically homeless people are provided with stable, permanent housing, then their medical, psychiatric and substance abuse problems will become more manageable.

Downtown Emergency Service Center’s 1811 Eastlake housing project is the first project-based Housing First model in the United States to be scientifically studied. Residents agree to spend 30 percent of their income – if they have any – on rent, and in return they are provided with permanent housing and social services.

An earlier study published in the Journal of the American Medical Association found that, in its first year of operation, this housing project saved Seattle taxpayers more than $4 million in costs from publicly funded services. The new study shows that drinking also decreases.

“A lot of people believe in the ‘enabling hypothesis’ – that allowing homeless, alcohol-dependent individuals to drink in their homes will enable them to drink more, and their drinking will spiral out of control,” Collins said. “But instead what we found are across-the-board decreases in alcohol consumption and problems.”

Health also improved. Residents reporting recent bouts of delirium tremens dropped by more than half over the two-year study, from 65 percent to 23 percent.

In the study:

• 94 percent of the 95 participants were men and most were white (40 percent) or American Indian/Alaska Native (27 percent).
• The average number of drinks consumed on the heaviest drinking day of the month decreased from 40 to 26 across two years, a decrease of 35 percent.
• The median number of drinks, a more accurate view of drinking patterns for this study’s participants, showed a change from 20 to 12 drinks per typical drinking day – a 40 percent drop.
• By the end of one year, 80 percent of participants remained in the study. That was reduced to 79 percent after 18 months and 61 percent after two years. Severity of drinking and demographic variables were ruled out as reasons why participants left the study.

Collins said that she and her team witnessed the resilience of the residents. “When they were on the streets, they were in dire straits and did what they needed to do to survive,” Collins said. But with steady housing, they were able to have a more normal existence. “Participants in the study told us that they’re happy to have a home, and happy that they no longer have to drink to stay warm or to put themselves to sleep or to forget that they’re on the streets.”

People tend to think that chronically homeless people with severe alcohol problems are unable to control themselves or monitor their drinking, Collins said, but instead this study shows that they are “human beings who are capable of change if they are given the same chance as the rest of us.”

Christine Sheffer, associate medical professor at CCNY’s Sophie Davis School of Biomedical Education, tracked smokers from different socioeconomic backgrounds after they had completed a statewide smoking cessation program in Arkansas.

Whether rich or poor, participants managed to quit at about the same rate upon completing a program of cognitive behavioral therapy, either with or without nicotine patches. But as time went on, a disparity between the groups appeared and widened.

Those with the fewest social and financial resources had the hardest time staving off cravings over the long run.  “The poorer they are, the worse it gets,” said Professor Sheffer, who directed the program and was an assistant professor with the University of Arkansas for Medical Sciences at the time.

She found that smokers on the lowest rungs of the socioeconomic ladder were 55 percent more likely than those at the upper end to start smoking again three months after treatment. By six months post-quitting, the probability of their going back to cigarettes jumped to two-and-a-half times that of the more affluent smokers. The research will be published in the March 2012 issue of the “American Journal of Public Health” and will appear ahead-of-print online under the journal’s “First Look” section.

In their study, Professor Sheffer and her colleagues noted that overall, Americans with household incomes of $15,000 or less smoke at nearly three times the rate of those with incomes of $50,000 or greater. The consequences are bleak. “Smoking is still the greatest cause of preventable death and disease in the United States today,” noted Professor Sheffer. “And it’s a growing problem in developing countries.”

Harder to Stay Away

Professor Sheffer suggested reasons it may be harder for some to give up tobacco forever.

Smoking relieves stress for those fighting nicotine addiction, so it is life’s difficulties that often make them reach for the cigarette pack again. Unfortunately, those on the lower end of the socioeconomic scale suffer more hardships than those at the top – in the form of financial difficulties, discrimination, and job insecurity, to name a few. And for those smokers who started as teenagers, they may have never learned other ways to manage stress, said Professor Sheffer.

For people with lower socioeconomic status (SES), it can be tougher to avoid temptation as well. “Lower SES groups, with lower paying jobs, aren’t as protected by smoke-free laws,” said Sheffer, so individuals who have quit can find themselves back at work and surrounded by smokers. Also fewer of them have no-smoking policies in their homes.

These factors are rarely addressed in standard treatment programs. “The evidence-based treatments that are around have been developed for middle-class patients,” Professor Sheffer pointed out. “So (in therapy) we talk about middle-class problems.”

Further research would help determine how the standard six sessions of therapy might be altered or augmented to help. “Our next plan is to take the results of this and other studies and apply what we learned to revise the approach, in order to better meet the needs of poor folks,” she said. “Maybe there is a better arrangement, like giving ‘booster sessions’. Not everybody can predict in six weeks all the stresses they will have later on down the road.”

“Some people say [quitting] is the most difficult thing in their life to do,” said Sheffer. “If we better prepare people with more limited resources to manage the types of stress they have in their lives, we’d get better results. “

The finding is the result of a year-long effort by a team of researchers led by associate professor of Molecular and Cellular Biology Naoshige Uchida to examine a brain process known as reward prediction error. Thought to be a key component of learning, prediction error was long believed to be the product of dopamine neurons firing in response to an unexpected “reward,” thus reinforcing the behavior that led to the reward.

But Uchida and colleagues from Harvard and Beth Israel Deaconess Medical Center report in the Jan. 18 issue of Nature that reward prediction error is actually the product of a complex interplay between two classes of neurons – one that relies on dopamine and an inhibitory class of neuron that uses the neurotransmitter GABA.

“Until now, no one knew how these GABA neurons were involved in the reward and punishment cycle,” Uchida said. “What we believe is happening is that they are inhibiting the dopamine neurons, so the two are working together to make the reward error computation.”

Before Uchida and his team could prove that GABA neurons are involved in the computation, however, they had to be sure what type of cells they were observing.

The challenge in studying either dopamine or GABA neurons is that the two cell types are intermingled in a relatively small area of the brain, making it difficult for researchers to definitively know which type they are observing. Ultimately, researchers developed an elegant solution to the problem.

Researchers genetically altered the neurons in two groups of mice – one for the dopamine neurons, the other for GABA neurons – to fire when hit by a pulse of laser light. Once researchers were certain they were measuring the correct type of neuron, they used electrodes to measure whether and when the neurons fired in response to expected and actual rewards.

The results, Uchida said, showed that while firing of dopamine neurons signaled reward prediction error, firing of GABA neurons signaled an expected reward. Taken together, GABA neurons help dopamine neurons calculate reward prediction error.

The finding is particularly important, Uchida said, because it sheds new light on how behaviors can be reinforced, either through normal brain function, or by damaging the way the two types of neurons interact.

“What happens with drug abuse is that many drugs, such as opioids and cannabinoids, target the GABA neurons,” he said. “What we are hypothesizing is that, by inhibiting those GABA neurons, you can lose this feedback cycle, so you keep getting reinforcing signals from the dopamine neurons.

“This is a new way of thinking about addiction in general,” Uchida continued. “Based on this theory, I believe you may be able to develop new theories or treatments for addiction.”

Results will be published in the April 2012 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“This study was designed to address two challenges in FAS studies,” said Haruna Sawada Feldman, a post-doctoral student in the department of pediatrics under the mentorship of professor Christina Chambers at the University of California, San Diego. “The first challenge concerned obtaining accurate alcohol exposure history from maternal reports that might involve social stigma and recall bias. This study collected information during pregnancy when women were unaware of their pregnancy outcome. The data were also collected by trained counseling specialists who had built a rapport with the woman and guaranteed confidentiality while collecting sensitive information. Finally, data were collected with specific details about timing in gestation, dose and pattern.”

The second challenge concerned the quality of information on specific physical features of FAS. “These alcohol-related features are often subtle, and a non-expert examiner may miss or misclassify features, and/or can be biased by subjectivity, especially if he/she suspects or knows about prenatal alcohol exposure (PAE),” said Feldman. “This study used an exposure-blinded expert dysmorphologist to look for these features. Furthermore, potential bias due to subjectivity was reduced because these examinations were conducted in the context of a larger study of more than 70 agents of interest, only one of which was alcohol.”

“Research that links the quantity, frequency and timing of alcohol consumption during pregnancy among humans is virtually non-existent,” added Philip A. May, a research professor in the Gillings School of Global Public Health at The University of North Carolina. “While animal data exist, studies like this one in humans are greatly needed, because extrapolation of concepts from animal models to humans is fraught with complications and problems of translation.”

Feldman and her colleagues used data gathered on 992 women and their singleton infants in California between 1978 and 2005, examining patterns of drinking and timing of alcohol exposure in relation to selected FAS features. Structural features were assessed by a dysmorphologist who performed a blinded physical examination of all infants. Patterns of drinking were evaluated by drinks per day, number of binge episodes, and maximum number of drinks. Timing of exposure was evaluated zero to six weeks post-conception, six to 12 weeks post-conception, and during the first, second, and third trimesters.

“Higher PAE in every pattern we examined was significantly associated with an increased risk for having an infant born with reduced birth length or weight or having a smooth philtrum or thin vermillion border or microcephaly,” said Feldman. “The most significant associations were seen during the second half of the first trimester; for every one drink increase in the average number of drinks consumed daily, there was a 25 percent increased risk for smooth philtrum, a 22 percent increased risk for thin vermillion border, a 12 percent increased risk for microcephaly, a 16 percent increased risk for reduced birth weight, and an 18 percent increased risk for reduced birth length.”

“This paper clearly illustrates that drinking alcohol, especially binge drinking, during the first seven to 12 weeks of gestation is associated with four of the most important facial features characteristic of FAS as well as reductions in birth length and weight that are also characteristic of infants and children with FAS,” said May. “This study also illustrates clearly that there is no threshold that triggers these features of FAS. Instead there is variability from woman to woman in the level of drinking that produces these features.”

Feldman added that the lack of associations found during first-half of the first trimester between alcohol and outcomes should not be interpreted to mean that alcohol consumption during this time period is somehow safe. “Due to the study design, we were only able to include women who gave birth to live infants,” she said. “Therefore, we did not include women who may have had miscarriages or stillbirths. It is important to know that alcohol-exposed infants who would have exhibited alcohol-related minor malformations might also be more likely to be lost to miscarriage following exposure during the first six-week window.”

Both Feldman and May believe these findings reinforce the warning that there is no “safe” level of alcohol consumption during pregnancy. “Clinicians should continue to follow the recommendations to encourage women who are planning a pregnancy or have the potential to become pregnant to avoid alcohol, and to advise women who become pregnant to stop alcohol consumption,” said Sawada. “These new findings can also help clinicians quantify the importance of discontinuing alcohol as early as possible.”

Results will be published in the April 2012 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“People in low to middle-income countries are experiencing a lot of stress due to rapid industrialization and urbanization and are therefore likely to use substances more to relieve their stress,” explained Hae Kook Lee, associate professor at the Catholic University of Korea and corresponding author for the study. “Furthermore, westernization might weaken the taboo for female drinking, especially in Eastern countries.”

“Cross-cultural epidemiologic studies like this one are extremely valuable,” added Howard B. Moss, associate director for clinical and translational research at NIAAA. “Despite over thirty years of research emphasizing the biopsychosocial nature of a wide variety of mental disorders, we see an over-emphasis of the neurobiological underpinnings of addictive disorders. Of course alcohol and other drugs of abuse do significantly impact upon brain processes through mechanisms of reward, plasticity, and adaptation leading from use, intoxication, and tolerance to physical dependence. However, the human process of addiction is much more complex than dopamine release in the reward pathways of the brain or the binding occupancy of the endogenous opiate receptors. Cross-cultural studies like this one reveal that we should also appreciate that the personal distress felt by addicted patients, and their frequently challenging illness behaviors, are manifestations of complex psychological processes that may be culturally bound and exist within a sociocultural paradigm. Thus, research like this reminds the scientific community of the complexity of alcoholism and comorbid conditions.”

Lee and his colleagues used nationally representative samples of the U.S. and South Korean general populations to compare rates of AUDs, ND, and mood and anxiety disorders between the two countries. Study authors also examined the rates and comorbidity patterns among individuals with AUDs who sought treatment in the preceding 12 months.

“Results showed that the prevalence of AUDs among Americans was substantially greater than among South Koreans,” said Lee. More specifically, the 12-month prevalences of AUDs, ND, and any mood and any anxiety disorders were 9.7, 14.4, 9.5 and 11.9 percent among Americans, compared to 7.1, 6.6, 2.0, and 5.2 percent among South Koreans. “The differences in overall prevalence of AUD rates between the two countries was largely due to prevalence among females, that is, drinking by women has historically been tempered by Confucian culture in Korea even though it is increasing rapidly now.”

“America has a longer cultural history with alcohol than do South Koreans,” added Moss. “At the time of the colonization of North America, most European colonists came from countries with strong cultural ties to regular and heavy alcohol consumption. While the Korean people historically used alcohol, its use was limited during the colonial period. Alcohol use was then stimulated in 1986 by a government policy to identify and support culturally important Korean alcoholic beverages. While Prohibition, in theory, limited American access to legal drinking for 13 years, Americans did not have a prolonged abstinence period that shifted cultural norms as occurred in Korea.”

“Even though we found a greater prevalence of alcoholism, mood and anxiety disorders among Americans in comparison to South Koreans,” said Lee, “alcohol-dependent Americans were four times more likely to seek treatment compared to their Korean counterparts, which may indicate the influence of a social stigma toward substance-abuse or mental-health problems despite national health insurance in Korea.”

While Moss agreed that it is clear that South Koreans are less likely to seek treatment for their alcohol problems than Americans, he questioned that this is because of stigma and saving face. “Americans with alcohol dependence and psychiatric comorbidity are more likely to seek treatment than those with alcohol dependence alone,” he observed. “I think seeking treatment has more to do with the degree of discomfort and suffering experienced by the individual, perhaps combined with issues of stigma and face-saving.”

Another finding, comorbidity of mood and anxiety disorders and alcohol use disorders, is the norm rather than the exception, added Lee. “These patterns were similar among American and Korean alcoholics,” he said. “Further, socio-cultural factors might also affect treatment seeking and rates of comorbidity as the higher social stigma of psychiatric treatment might make the patients with mood disorders drink more to relieve their symptoms.”

However, added Moss, the patterns of comorbid psychiatric disorders were different among Korean smokers versus American smokers as American smokers displayed more comorbid mood and anxiety disorders than did Korean smokers.

“Fundamentally,” said Moss, “I think this study forces us to think more about cultural and environmental influences on the etiology of alcohol dependence in conjunction with the neurobiology and genetics of addiction. This study reminds us that neither biological determinism nor social determinism is the whole story. Human behavior is extremely complex, and reductionism of any sort is, more often than not, incorrect.”

Results will be published in the April 2012 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“We know that a familial history of alcoholism is a significant risk factor for future alcohol abuse,” said Bonnie J. Nagel, assistant professor of psychiatry and behavioral neuroscience at Oregon Health & Science University as well as corresponding author for the study. “We were interested in determining whether adolescents at heightened risk for alcohol use made more risky decisions during a laboratory task compared to their lower-risk peers. Additionally, we wanted to examine whether differences in brain responses when making risky decisions were present in these two groups. We wanted to investigate pre-morbid neural risk factors during decision making in FHP youth, as opposed to differences in brain response due to heavy alcohol use itself.”

“This is the first study to examine the neural substrates of risk-taking in FHP adolescents who are substance naïve,” added Megan Herting, a PhD candidate in behavioral neuroscience at Oregon Health & Science University. “A previous study looked at young adults who were drinkers, therefore, it is hard to say if the differences found were purely a pre-existing neural risk factor for alcohol use. Alcohol use may also differentially impact the brains of those with and without a family history of alcoholism. Thus, the current study is a very novel and important piece of work showing that the brain is doing something different during risky decision making in substance-naïve FHP adolescents.”

Study authors recruited 31 youth – 18 FHP (12 males, 6 females) and 13 FHN (8 males, 5 females) – between 13 and 15 years of age from the local community. All of the youth had little to no alcohol involvement prior to their participation in the study. Functional magnetic resonance imaging (fMRI) was used to examine brain responses of the youth during a Wheel of Fortune (WOF) decision-making task, which presented risky versus safe probabilities of winning different amounts of money.

“While our study found that FHP adolescents did not perform significantly differently on the WOF task compared to the FHN adolescents,” said Nagel, “we found two areas of the brain that responded differently. These areas were in the prefrontal cortex and cerebellum, both of which are important for higher-order day-to-day functioning, such as decision-making. In these brain regions, FHP adolescents showed weaker brain responses during risky decision-making compared to their FHN peers. We believe that weaker activation of these brain areas, known to be important for optimal decision-making, may confer vulnerability towards risky decisions with regards to future alcohol use in adolescents already at risk for alcoholism.”

Herting noted that higher-order or executive functioning is also important for things like attention, working memory, and inhibition. “Therefore, differences in brain activity may impact the ability of FHP individuals to make good decisions in many contexts, and in particular may facilitate poor decision-making in regards to alcohol use,” she said. “Taken together with other studies on FHP youth, these results suggest that atypical brain structure and function exist prior to any substance use, and may contribute to an increased vulnerability for alcoholism in these individuals.”

Both Nagel and Herting believe these findings can help to develop better prevention programs based on familial risk factors. “These findings may suggest a neurobiological marker that helps to explain how family history of alcoholism confers risk,” said Nagel. “Furthermore, our research may aid clinicians who work with high-risk youth to develop effective prevention strategies for these adolescents to promote healthy decision-making.”

However, they both added, having a familial history of alcoholism is just one of many different factors involved in future alcohol abuse. “While having a family history of alcoholism may put one at greater risk for alcohol abuse, personality and behavioral risk factors are also important to consider,” said Nagel. “The combination of genetic and environmental factors is very different for everyone, so some individuals may be at higher risk than others, and certainly there are genetic and environmental factors that can also protect against alcohol abuse. Future research will need to determine the relative influence of these traits on alcohol abuse risk to be able to design specific prevention strategies for different high-risk populations.”