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1.  Executive functioning among young people in relation to alcohol use 
Current opinion in psychiatry  2013;26(4):305-309.
Purpose of review
This article reviews recent findings regarding neurobehavioral factors which may be associated with risk for alcohol misuse, as well as those which may occur as a result of alcohol misuse during adolescence and emerging adulthood.
Recent findings
Current research extends previous findings by engaging multiple assessment methods and integrating behavioral and imaging technologies. These efforts reinforce previous findings regarding alcohol-related changes in macrostructure while demonstrating alterations in brain connectivity previously underappreciated. Longitudinal work now being reported suggests problem use during adolescence may be associated with persistent neurobehavioral aberrations.
For many years, little attention was directed to the neurobehavioral consequences of alcohol use across adolescence and emerging adulthood or to the neurobehavioral factors which might predispose youth to alcohol misuse. Recent work provides critical insights regarding the underpinnings of the deficits in executive function often observed in those at risk for alcohol dependence and those who develop alcohol use disorders. These studies suggest that, even when behavioral deficits are not evident, changes in brain connectivity and microstructure may be observed. Programmatic, longitudinal research must be conducted to determine the relevance of these alterations to use trajectories and long-term adaptation.
PMCID: PMC4241361  PMID: 23695532
alcohol; executive functions; neurobehavior; risk; youth
2.  Nicotine Effects on Immediate and Delayed Verbal Memory After Substance Use Detoxification 
Decrements in verbal memory are commonly reported by detoxified treatment-seeking individuals. Although acute nicotine has been shown to improve attentional performance, its effects on verbal memory in substance abusers have not been addressed. Treatment-seeking alcohol dependent (ALCS N=29; 14 male), illicit stimulant (predominantly cocaine) dependent (STIMS N = 25; 15 male) and alcohol and illicit stimulant dependent (ALC/STIMS N = 50; 35 male) participants with co-morbid nicotine dependence were studied. Subjects had been abstinent from their drugs of choice for 41(±18) days and were in short-term abstinence from tobacco (~8–10 hours). Subjects received double-blind administration of either transdermal nicotine (High dose: 21/14 mg for men and women, respectively or Low dose: 7 mg) or placebo. The Logical Memory (LM) subtest from the Wechsler Memory Scale -Revised (WMS-R) was used to assess immediate and delayed verbal memory recall. Results indicated that STIMS receiving the high dose of nicotine recalled more words at immediate recall than STIMS who received placebo. Trend level differences were also noted at delayed recall between STIM nicotine and placebo doses. Nicotine failed to impact either recall in alcoholic subgroups. Although not the primary focus, results also revealed differences in the forgetting rates between the groups with the ALC/STIMS demonstrating the steepest forgetting slope. In summary, this study suggests that nicotine effects may be differentially experienced by substance using subgroups; that nicotine may have a direct effect on memory and, that considering neurocognitive processes (e.g., encoding vs. retrieval) underlying endpoint indicators (e.g. correct recall) may be critical in predicting outcomes.
PMCID: PMC3146969  PMID: 21526444
Available evidence suggests women may be more vulnerable to the effects of chronic alcohol consumption than men. The few investigations of gender differences in treatment-seeking populations have often involved study samples restricted by selection criteria (e.g., age, education). The current study examined gender differences in a heterogeneous sample of individuals seeking treatment for a substance use disorder. We examined alcohol drinking levels, age at drinking milestones (e.g., first drink, first intoxication), and progression from milestones to alcohol problems or treatment. Additionally, family history, spousal alcoholism, and nicotine use were analyzed.
Participants included men (n=274) and women (n=257) in substance abuse treatment facilities. Participants completed inventories quantifying affect, intellectual ability, and drinking consequences. A family tree for substance use and personal histories for alcohol and nicotine use, including chronicity, frequency, and regularity, were collected.
Telescoping was not observed when progression from drinking milestones to alcoholism or alcohol problems was compared between men and women. In contrast, when considered as progression to treatment, marked telescoping effects were detected, with women entering treatment more rapidly by approximately four years. Familial differences included a greater proportion of women reporting alcoholic parents (73% women; 61% men) and alcoholic spouses (58% women; 38% men). Smoking behaviors were similar between genders, however men reporting higher levels of alcohol consumption reported greater intensity of chronic smoking. Smoking and drinking behaviors were correlated among men, but not women. Rates of pre-treatment drug problems were equivalent between genders.
When contrasted with the available literature, our data were only partially supportive of gender-contingent telescoping. While women did not experience alcohol problems or alcoholism earlier than men, they progressed to treatment more quickly. These results highlight the importance of carefully considering the sample and specific outcome variables when interpreting gender differences.
PMCID: PMC3855552  PMID: 23930695
Gender Differences; Alcohol; Telescoping; Psychosocial Correlates
4.  Interactive Effects of Chronic Cigarette Smoking and Age on Hippocampal Volumes 
Drug and alcohol dependence  2013;133(2):10.1016/j.drugalcdep.2013.08.020.
Previous cross-sectional MRI studies with healthy, young-to-middle-aged adults reported no significant differences between smokers and non-smokers on total hippocampal volume. However, these studies did not specifically test for greater age-related volume loss in the total hippocampus or hippocampal subregions in smokers, and did they did not examine relationships between hippocampal and subfield volumes and episodic learning and memory performance.
Healthy, young-to-middle-aged (45 ± 12 years of age) smokers (n = 39) and non-smokers (n = 43) were compared on total hippocampal and subfield volumes derived from high-resolution 4 Tesla MRI, emphasizing testing for greater age-related volume losses in smokers. Associations between hippocampal volumes and measures of episodic learning and memory were examined.
Smokers showed significantly smaller volumes, as well as greater volume loss with increasing age than non-smokers in the bilateral total hippocampus and multiple subfields. In smokers, greater pack-years were associated with smaller volumes of the total hippocampus, presubiculum, and subiculum. In the entire cohort, performance on measures of learning and memory was related to larger total hippocampal and several subfield volumes, predominately in the left hemisphere.
Chronic cigarette smoking in this young-to-middle aged cohort was associated with smaller total hippocampal and subfield volumes, which were was exacerbated by advancing age. Findings also indicated an adverse smoking dose/duration response (i.e., pack-years) with total hippocampal and select subfield volumes. These hippocampal volume abnormalities in smokers may be related to the deficiencies in episodic learning and memory in young-to-middle-aged smokers reported in previous studies.
PMCID: PMC3870586  PMID: 24051060
cigarette smoking; MRI; hippocampus; hippocampal subfields; learning and memory; aging
Nearly 40% of adults aged 65 and older in the United States consume alcohol. Research in older adults has largely examined potential health effects of a moderate drinking lifestyle. Examination of acute effects in this population is generally lacking. To investigate alcohol-induced alteration of electrophysiological correlates of attention in this population, we employed a covert attentional task. We hypothesized that moderate alcohol administration as well as older age would reduce P3 amplitude and increase latency. We anticipated an interaction such that, relative to their age-matched controls, older adults receiving alcohol would be more affected than their younger counterparts.
Participants included healthy older (aged 50–67; n = 20; 9 men) and younger (aged 25–35; n = 12; 5 men) moderate drinkers. Participants received either a moderate dose of alcohol (breath alcohol concentration [BrAC] ~50 mg/dl) or a placebo beverage. Following absorption, the task was administered and neurophysiological measures were obtained. P3 amplitude and latency were separately subjected to ANOVA across cue conditions using age and dose as independent variables.
As predicted, P3 amplitude in older adults was significantly lower than younger adults across cue conditions. An age by alcohol interaction was detected, revealing that older adults receiving alcohol showed lower P3 amplitudes than any other group. An age effect for P3 latency was found, with older adults having longer latencies than their younger counterparts. A significant age by alcohol interaction for P3 latency was detected, revealing that older adults receiving alcohol displayed delayed P3 latencies relative to older adults receiving placebo. In contrast, younger adults receiving alcohol had reduced latency compared to those receiving placebo although this effect did not reach significance.
Results suggest that older adults demonstrated alcohol related shifts in P3 characteristics during an intentional attention task, whereas younger adults failed to demonstrate this pattern.
PMCID: PMC3620967  PMID: 23278355
moderate alcohol; aging; attention; neurophysiology; P3
6.  Cognitive flexibility during breath alcohol plateau is associated with previous drinking measures 
Alcohol (Fayetteville, N.Y.)  2013;47(4):10.1016/j.alcohol.2013.01.007.
Although the biphasic effects of acute alcohol during ascending and descending Breath Alcohol Concentrations (BrACs) are well described, the plateau period between peak and steadily descending BrACs is generally unrecognized and under-studied by researchers. Naturalistic examinations indicate such periods persist for substantial intervals, with a time frame of onset suggesting BrAC plateaus may co-occur with potentially risky behaviors (e.g., driving). The current pilot study examined neurocognitive performance during this period. Participants were healthy, community-residing moderate drinkers (n= 18). In the first phase of the study, the Digit Symbol Substitution and Trail Making Tasks were administered during BrAC plateau (M = 62 mg/dL). BrACs were negatively correlated with Digit Symbol performance but unrelated to other tasks. In contrast, performance on a derived Trail Making measure of set-shifting was positively associated with the maximum alcohol doses consumed in the preceding 6 months. Phase 2 analyses demonstrated that relationships between previous alcohol experience and cognitive performance were absent among individuals receiving placebo beverages. Taken together, these data suggest a relationship worthy of investigation between previous drinking experiences and cognitive flexibility during the plateau phase.
PMCID: PMC3809826  PMID: 23597416
Alcohol; BAC; Acute administration; Alcohol use history; Digit Symbol Substitution Task; Trail Making Task
7.  Lifetime Psychiatric and Substance Use Disorders Among Impaired Physicians in a Physicians Health Program: Comparison to a General Treatment Population 
Journal of addiction medicine  2013;7(2):108-112.
The prevalence of substance abuse and other psychiatric disorders among physicians is not well-established. We determined differences in lifetime substance use, and abuse/dependence as well as other psychiatric disorders, comparing physicians undergoing monitoring with a general population that had sought treatment for substance use.
Participants were 99 physicians referred to a Physician's Health Program (PHP) due to suspected impairment, who were administered the Computerized Diagnostic Interview Schedule Version IV (CDIS-IV) to assess the presence of psychiatric disorders. Referred physicians were compared to an age, gender, and education status-matched comparison group from National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Wave 1, in a 1:1 ratio.
While referred physicians did not differ from their counterparts on lifetime use of alcohol, opiates, or sedatives, they did have significantly higher conditional odds of meeting criteria for alcohol, opiate, and sedative DSM-IV abuse/dependence disorders. Physicians referred to the PHP had significantly lower odds of obsessive compulsive disorder, major depression, and specific phobia compared to their counterparts.
Physicians referred to a PHP have significantly higher odds of abuse/dependence disorders for cannabinoids, and cocaine/crack, compared to a matched general population sample that had ever sought treatment for substance use, even though physicians were less likely to report use of those substances. Although the rate of alcohol use was similar between the two populations, physicians had higher odds of abuse/dependence for opiates, sedatives, and alcohol. More research is needed to understand patterns of use, abuse/dependence and psychiatric morbidity among physicians.
PMCID: PMC3618571  PMID: 23412081
Physician impairment; psychopathology; substance abuse; epidemiology; MDs; drug abuse
Studies exploring differential effects of acute alcohol consumption on younger and older adults are lacking within the field of alcohol research, especially those using moderate doses. Previous studies addressing this question have tended to use complex behavioral tasks too broad to isolate specific neurocognitive processes affected by both alcohol and aging. Compromises in cognitive efficiency (i.e. the ability to respond both quickly and accurately) have previously been identified in both elderly and acutely intoxicated individuals.
The present study employed a visual-spatial, two-choice reaction time task to evaluate the interactive effects of aging and alcohol on cognitive efficiency. Our primary outcome measure was an efficiency ratio derived from each participant’s response accuracy (ACC) and mean reaction time (RT) (%correct/RT). Younger (25 – 35; n=22) and older (55 – 74; n=37) participants were randomly assigned to receive either a placebo or moderate alcohol dose intended to produce a peak BrAC of 0.04%. Participants performed the task at peak alcohol levels.
A significant interaction between age group and dose assignment was observed (F3,55=4.86, p=.03) for the efficiency ratio. Younger participants who received alcohol performed significantly better than did their older counterparts regardless of alcohol condition and despite no differences in performance between the two age groups in the placebo condition. Additional correlation analyses between ACC and RT suggested that moderately intoxicated older adults become more accurate as response times increase. This relationship was not observed in older adults in the placebo condition.
These data suggest that healthy individuals exhibit a differential susceptibility to the effects of alcohol depending on their age. Unfortunately, due to the presumed safety of moderate alcohol doses and a lack of studies investigating the interactive effects of acute alcohol consumption and aging, most individuals are unlikely to be aware of this relationship between alcohol consumption and age.
PMCID: PMC3424337  PMID: 22591190
Alcohol; aging; cognition; speed-accuracy trade-off
9.  A Comprehensive Assessment of Neurocognition in Middle-Aged Chronic Cigarette Smokers 
Drug and Alcohol Dependence  2011;122(1-2):105-111.
The majority of studies investigating the neurocognitive consequences of chronic smoking have been conducted with adults 60 years and older. Therefore, the scope of neurocognitive dysfunction associated with chronic cigarette smoking in middle age (i.e., 30–60 age range) has not been fully delineated.
Twenty-seven (44±9 years of age; 4 females) non-smoking and 30 smoking (49±8 years of age; 4 females) participants completed a comprehensive neurocognitive battery and measures of fine motor dexterity and postural stability. All participants were free of biomedical or psychiatric conditions that may have influenced neurocognitive and motor function.
Smokers performed significantly worse than non-smokers on the following domains: auditory-verbal and visuospatial learning, visuospatial memory, cognitive efficiency, executive skills, general intelligence, processing speed, fine motor dexterity and postural stability. The differences between smokers and non-smokers evidenced moderate to strong effect sizes and were not mediated by age, education, vocational level, estimated verbal intelligence or alcohol consumption. In smokers, a greater number of lifetime years of smoking was related to poorer performance on measures of cognitive efficiency, processing speed and visuospatial skills.
Results from this middle-aged cohort replicated previous research and provides novel findings indicating that chronic smoking was associated with inferior performance on measures of general intelligence, visuospatial learning and memory and fine motor dexterity. Research that relates measures of neurobiological function/integrity to neurocognition is needed to better understand the mechanisms contributing to the poorer performance across multiple domains demonstrated by smokers.
PMCID: PMC3258460  PMID: 21992872
cigarette smoking; cognition; neurocognition; assessment; middle-age
Addictive behaviors  2011;36(12):1344-1348.
Current literature suggests that acute nicotine administration provides a compensatory mechanism by which alcoholics might alleviate attentional deficits. In contrast, chronic smoking is increasingly recognized as negatively affecting neurobehavioral integrity. These opposing effects have not been simultaneously examined. Thus, we sought to a) extend previous work by exploring the effects of acute nicotine effects on vigilance components of attention and replicate previous findings suggesting that treatment-seeking alcoholics experience benefit to a greater extent than do other groups; and b) to examine the impact of chronic smoking on these tasks and across subgroups.
Substance abusing participants (N=86) were recruited and subgrouped on the basis of dependency criteria as either alcoholics, alcoholics with co-morbid stimulant dependence, or stimulant dependent individuals. Groups of cigarette-smoking (N=17) and non-smoking (N=22) community controls were recruited as comparison groups. Smoking subjects were assigned a placebo, low, or high dose nicotine patch in a double-blind placebo controlled fashion. Non-smoking controls were administered either a placebo or low dose. Testing occurred after dose stabilization.
General linear models indicated greater sensitivity to acute nicotine administration among alcoholics than other groups when controlling for the effect of intensity of smoking history, as reflected by pack-years. Pack-years correlated negatively with performance measures in alcoholics but not stimulant abusing subgroups or smoking controls. Finally, regression analyses demonstrated that pack-years predicted poorer performance only for the alcoholic subgroup.
These results support previous work finding a compensatory effect of acute nicotine administration on attentional performance in alcoholics and reinforce the consideration of recent nicotine use as a confound in neurocognitive studies of alcoholics. Of particular interest is the finding that smoking history as reflected in pack-years predicted poorer performance, but only among alcoholics. Further systematic study of these opposing effects among alcoholics and other groups using a broader array of tasks is needed.
PMCID: PMC3179837  PMID: 21855223
alcohol; neurocognition; attention; nicotine; smoking
The recent proposal to dissolve the National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse and create a new institute for substance use, abuse, and addiction will require significant effort by the staff of both institutes, the Advisory Councils, and outside experts to overcome complex challenges that could threaten its success. Although integration of the grants portfolios can be achieved, harmonization of goals and policies related to legal use of alcohol versus illegal consumption of drugs will present serious challenges. Consolidating the infrastructure of the two existing institutes would entail avoiding encroachment on grant funding. A new institute for substance use, abuse, and addiction would require an enormous amount of cooperation from other institutes since the portfolios of research on alcohol, tobacco, and other drug abuse should logically be transferred to the new institute. In the near term, a structural reorganization would be less efficient and more costly than the individual institutes are currently. Increasing efficiency and reducing costs over time will necessitate careful strategic planning. Success in this difficult task would be made easier and less costly by first implementing carefully placed building blocks of increasing functional reorganization. The newly created institute should increase opportunities for specialization within disorders of addiction, attract new leadership, and build a novel strategic plan that will energize scientists and staff and incorporate ideas of stakeholders to advance the public good in preventing and treating alcohol, tobacco, and all addictions. Attention must be paid to the devil in the details.
PMCID: PMC3068603  PMID: 21443646
12.  Nicotine as a Factor in Stress Responsiveness Among Detoxified Alcoholics 
Aims: The effect of transdermal nicotine on stress reactivity was investigated in currently smoking, detoxified, substance-dependent individuals (65% alcohol dependent, n = 51; 31 male) following a psychosocial stressor. Methods: Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either active transdermal nicotine (low or high dose) or placebo. Six hours following nicotine administration, subjects performed a laboratory psychosocial stressor consisting of two 4-min public-speaking sessions. Results: Consistent with prior reports, substance-dependent individuals displayed a blunted stress response. However, a review of the cortisol distribution data encouraged additional analyses. Notably, a significant minority of the substance-dependent individuals (33%) demonstrated elevated poststress cortisol levels. This group of responders was more likely to be alcohol dependent and to have received the high dose of nicotine [χ2(2) = 32, P < 0.0001], [χ2(2) = 18.66, P < 0.0001]. Differences in salivary cortisol responses between responders and nonresponders could not be accounted for by the length of sobriety, nicotine withdrawal levels, anxiety or depressive symptomatology at the time of the psychosocial stressor. Conclusion: These results suggest that nicotine administration may support a normalization of the salivary cortisol response following psychosocial stress in subgroups of substance-dependent individuals, particularly those who are alcohol dependent. Given the association between blunted cortisol levels and relapse, and the complex actions of nicotine at central and peripheral sites, these findings support the systematic study of factors including nicotine, which may influence stress reactivity and the recovery process in alcohol-dependent individuals.
PMCID: PMC3002844  PMID: 21045074
14.  Chronic Cigarette Smoking: Implications for Neurocognition and Brain Neurobiology 
Compared to the substantial volume of research on the general health consequences associated with chronic smoking, little research has been specifically devoted to the investigation of its effects on human neurobiology and neurocognition. This review summarizes the peer-reviewed literature on the neurocognitive and neurobiological implications of chronic cigarette smoking in cohorts that were not seeking treatment for substance use or psychiatric disorders. Studies that specifically assessed the neurocognitive or neurobiological (with emphasis on computed tomography and magnetic resonance-based neuroimaging studies) consequences of chronic smoking are highlighted. Chronic cigarette smoking appears to be associated with deficiencies in executive functions, cognitive flexibility, general intellectual abilities, learning and/or memory processing speed, and working memory. Chronic smoking is related to global brain atrophy and to structural and biochemical abnormalities in anterior frontal regions, subcortical nuclei and commissural white matter. Chronic smoking may also be associated with an increased risk for various forms of neurodegenerative diseases. The existing literature is limited by inconsistent accounting for potentially confounding biomedical and psychiatric conditions, focus on cross-sectional studies with middle aged and older adults and the absence of studies concurrently assessing neurocognitive, neurobiological and genetic factors in the same cohort. Consequently, the mechanisms promoting the neurocognitive and neurobiological abnormalities reported in chronic smokers are unclear. Longitudinal studies are needed to determine if the smoking-related neurobiological and neurocognitive abnormalities increase over time and/or show recovery with sustained smoking cessation.
PMCID: PMC2996190  PMID: 21139859
chronic cigarette smoking; neurocognition; neurobiology; neuroimaging; genetics
15.  Transdermal Nicotine Administration and the Electroencephalographic Activity of Substance Abusers in Treatment 
Journal of addiction medicine  2008;2(4):202-214.
It is widely recognized that individuals with alcohol or illicit substance abuse disorders often smoke cigarettes. However, few studies have examined the direct effects of nicotine among substance abuse subgroups. The current study examined patterns of electroencephalographic (EEG) activity in alcohol-dependent (AD), stimulant-dependent (StimD), alcohol- and stimulant-dependent (ASD) participants, as well as community controls (CC). All participants were regular smokers.
After overnight nicotine abstinence, subjects were administered either a high (14 or 21 mg) or low (7mg) dose transdermal nicotine patch. EEG data were collected during a 2 minute eyes open and 5 minute eyes closed baseline recording session, which occurred as part of a larger study of brain electrophysiology.
The most interesting finding was a differential pattern of nicotine dose effects by group. EEGs of Controls and ASD participants did not distinguish between high and low nicotine doses; whereas, nicotine administration in the AD and StimD groups resulted in opposite findings across a range of spectral bands.
Although further research is warranted, these results may have implications for the study of smoking cessation and attentional functioning among substance abusers in treatment. These data suggest that nicotine–related changes in neurophysiology may be associated with specific brain areas and/or specific drug histories and reinforce the need for caution in generalizing among such groups.
PMCID: PMC2665044  PMID: 19347067
Nicotine; Alcohol; Cocaine; Methamphetamine; Electroencephalogram
16.  The Role of Selected Factors in the Development and Consequences of Alcohol Dependence 
Alcohol Research & Health  2008;31(4):389-399.
Gender, family history, comorbid psychiatric and substance use disorders, and age all influence a person’s risk for alcoholism. In addition, these factors interact with alcoholism to influence neurocognitive functioning following detoxification. This article examines these factors and considers how they interact with each other. This complexity reinforces the need for both animal and human studies and suggests multiple factors that may be sensitive to differential prevention, intervention, and treatment efforts. Thus, it is imperative that hypothesis-driven research designs be directed to identifying the relative potency of these factors and their interactions.
PMCID: PMC3860467  PMID: 23584012
Alcoholism; alcohol and other drug (AOD) dependence; risk factors; genetic factors; family factors; environmental factors; gender differences; family AOD use (AODU) history; comorbidity; multiple drug use; age of AODU onset; AOD effects; brain
17.  Exposure and peritraumatic response as predictors of posttraumatic stress in children following the 1995 Oklahoma City bombing 
Studies have demonstrated a positive relationship between exposure and posttraumatic stress, but one's subjective appraisal of danger and threat at the time of exposure may be a better predictor of posttraumatic stress than more objective measures of exposure. We examined the role of peritraumatic response in posttraumatic stress reactions in over 2,000 middle school children 7 weeks after the 1995 Oklahoma City, Oklahoma, bombing. While many children reported hearing and feeling the blast and knowing direct victims, most were in school at the time of the explosion and therefore were not in direct physical proximity to the incident. Physical, interpersonal, and television exposure accounted for 12% of the total variance in our measure of posttraumatic stress when peritraumatic response was ignored. Peritraumatic response and television exposure accounted for 25% of the total variance, and physical and interpersonal exposure were not significant in this context. These findings suggest the importance of peritraumatic response in children's reactions to terrorism. These carly responses can be used to help determine which children may experience difficulty over time.
PMCID: PMC3456793  PMID: 12200504
Children; Disaster; Posttraumatic Stress; Terrorism; Trauma

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