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1.  Biased Behaviors: Towards Understanding Vulnerability and Resilience Factors in Addictions 
Biological psychiatry  2014;75(2):94-95.
PMCID: PMC4088321  PMID: 24331645
stimulants; cocaine; attention; control; Stroop; fMRI
2.  Gender differences in the relationship between gambling problems and the incidence of substance-use disorders in a nationally representative population sample 
Drug and alcohol dependence  2013;133(1):204-211.
Cross-sectional studies have demonstrated gender-related differences in the associations between problem-gambling severity and substance-use disorders; however, these associations have not been examined longitudinally. We aimed to examine the prospective associations between problem-gambling severity and incident substance-use disorders in women versus men.
Analyses were conducted using Wave-1 and Wave-2 NESARC data focusing on psychiatric diagnoses from 34,006 non-institutionalized US adults. Inclusionary criteria for pathological gambling were used to categorize Wave-1 participants as at-risk/problem gambling (ARPG) and non-ARPG (i.e. non-gambling/low-frequency gambling/low-risk gambling). Dependent variables included the three-year incidence of any substance-use disorder, alcohol-use disorders, nicotine dependence, drug-use disorders, prescription drug-use disorders, and illicit drug-use disorders.
Significant gender-by-ARPG status interactions were observed with respect to the three-year incidence of nicotine dependence and prescription drug-use disorders, and approached significance with respect to incident alcohol-use disorders. ARPG (relative to non-ARPG) was positively associated with nicotine dependence among women (OR=2.00; 95% CI=1.24-3.00). ARPG was negatively associated with incident prescription drug-use disorders among men (OR=0.30; 95% CI=0.10-0.88)). Finally, ARPG was positively associated with incident alcohol-use disorders among men (OR=2.20; 95% CI=1.39-3.48).
Gambling problems were associated with an increased 3-year incidence of nicotine dependence in women and alcohol dependence in men. These findings highlight the importance of considering gender in prevention and treatment initiatives for adults who are experiencing gambling problems. Moreover, the specific factors underlying the differential progressions of specific substance-use disorders in women and men with ARPG warrant identification.
PMCID: PMC3786018  PMID: 23755930
Problem/pathological gambling; gender differences; substance use disorders; incidence
3.  Increased incidence of cardiovascular conditions among older adults with pathological gambling features in a prospective study 
Journal of addiction medicine  2013;7(6):10.1097/ADM.0b013e31829e9b36.
To evaluate the prospective associations between at-risk/problem/pathological gambling (ARPG) and incident medical conditions among older adults.
Secondary data analysis of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), Waves 1 and 2, collected from 2001–2002 and 2004–2005, respectively. Participants are adults aged 55 years and older (n=10,231) who were selected from a nationally representative community sample of adults residing in the United States. Past-year DSM-IV diagnostic criteria for pathological gambling at Wave 1 were evaluated with the Alcohol Use Disorder and Associated Disabilities Interview Schedule—Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition. Physical-health conditions were assessed at Wave 1 and Wave 2. Logistic regression modeling was conducted on groups categorized as ARPG (participants endorsing one or more inclusionary criteria for pathological gambling) and non-ARPG (non-gambling/low-frequency gambling or gambling without endorsement of pathological gambling criteria).
Relative to non-ARPG, ARPG is prospectively associated with elevated incidences of arteriosclerosis and any heart condition, independently of Wave-1 socio-demographic characteristics, psychiatric comorbidity, substance use, and body mass index.
Older adults who demonstrate risky or problematic levels of gambling may be at particular risk for the onset of some physical-health conditions. ARPG individuals should be monitored more closely for the development of these conditions and encouraged to adopt activities that confer health benefits. Efforts should be made to educate older adults and their caretakers on the adverse incident physical-health conditions associated with ARPG.
PMCID: PMC3818298  PMID: 24104190
At-risk/problem/pathological gambling; physical illness; older adults; addiction; aging
4.  Stress and Eating Behaviors 
Minerva endocrinologica  2013;38(3):255-267.
Obesity is a heterogeneous construct that, despite multiple and diverse attempts, has been difficult to treat. One conceptualization gaining media and research attention in recent years is that foods, particularly hyperpalatable (e.g., high-fat, high sugar) ones, may possess addictive qualities. Stress is an important factor in the development of addiction and in addiction relapse, and may contribute to an increased risk for obesity and other metabolic diseases. Uncontrollable stress changes eating patterns and the salience and consumption of hyperpalatable foods; over time, this could lead to changes in allostatic load and trigger neurobiological adaptations that promote increasingly compulsively behavior. This association may be mediated by alterations in the hypothalamic-pituitary-adrenal (HPA) axis, glucose metabolism, insulin sensitivity, and other appetite-related hormones and hypothalamic neuropeptides. At a neurocircuitry level, chronic stress may affect the mesolimbic dopaminergic system and other brain regions involved in stress/motivation circuits. Together, these may synergistically potentiate reward sensitivity, food preference, and the wanting and seeking of hyperpalatable foods, as well as induce metabolic changes that promote weight and body fat mass. Individual differences in susceptibility to obesity and types of stressors may further moderate this process. Understanding the associations and interactions between stress, neurobiological adaptations, and obesity is important in the development of effective prevention and treatment strategies for obesity and related metabolic diseases.
PMCID: PMC4214609  PMID: 24126546
Obesity; Food Addiction; Stress; HPA axis; Mesolimbic Dopaminergic System
5.  Neural Correlates of Stress and Favorite-Food Cue Exposure in Adolescents: A Functional Magnetic Resonance Imaging Study 
Human brain mapping  2012;34(10):2561-2573.
Adolescence is a critical period of neurodevelopment for stress and appetitive processing, as well as a time of increased vulnerability to stress and engagement in risky behaviors. The current study was conducted to examine brain activation patterns during stress and favorite-food-cue experiences relative to a neutral-relaxing condition in adolescents. Functional magnetic resonance imaging was employed using individualized script-driven guided imagery to compare brain responses to such experiences in 43 adolescents. Main effects of condition and gender were found, without a significant gender-by-condition interaction. Stress imagery, relative to neutral, was associated with activation in the caudate, thalamus, left hippocampus/parahippocampal gyrus, midbrain, left superior/middle temporal gyrus, and right posterior cerebellum. Appetitive imagery of favorite food was associated with caudate, thalamus, and midbrain activation compared to the neutral-relaxing condition. To understand neural correlates of anxiety and craving, subjective (self-reported) measures of stress-induced anxiety and favorite-food-cue-induced craving were correlated with brain activity during stress and appetitive food-cue conditions, respectively. High self-reported stress-induced anxiety was associated with hypoactivity in the striatum, thalamus, hippocampus and midbrain. Self-reported favorite-food-cue-induced craving was associated with blunted activity in cortical-striatal regions, including the right dorsal and ventral striatum, medial prefrontal cortex, motor cortex, and left anterior cingulate cortex. The current findings in adolescents indicate the activation of predominantly subcortical-striatal regions in the processing of stressful and appetitive experiences and link hypoactive striatal circuits to self-reported stress-induced anxiety and cue-induced favorite-food craving.
PMCID: PMC3479342  PMID: 22504779
Stress; Psychological; Adolescence; Motivation; Appetite; fMRI
6.  Serious Physical Fighting and Gambling-Related Attitudes and Behaviors in Adolescents 
Background and Aims
Physical fighting and gambling are common risk behaviors among adolescents. Prior studies have found associations among these behaviors in adolescents but have not examined systematically the health and gambling correlates of problem-gambling severity amongst youth stratified by fight involvement.
Survey data were used from 2,276 Connecticut high-school adolescents regarding their physical fight involvement, gambling behaviors and perceptions, and health and functioning. Gambling perceptions and correlates of problem-gambling severity were examined in fighting and non-fighting adolescents.
Gambling perceptions were more permissive and at-risk/problem gambling was more frequent amongst adolescents reporting serious fights versus those denying serious fights. A stronger relationship between problem-gambling severity and regular smoking was observed for adolescents involved in fights.
Discussion and Conclusions
The more permissive gambling attitudes and heavier gambling associated with serious fights in high-school students suggest that youth who engage in physical fights warrant enhanced prevention efforts related to gambling. The stronger relationship between tobacco smoking and problem-gambling severity amongst youth engaging in serious fights suggest that fighting youth who smoke might warrant particular screening for gambling problems and subsequent interventions.
PMCID: PMC3840436  PMID: 24294502
Fighting; gambling; physical violence; adolescents; risk behaviors; high school
7.  A Human Alcohol Self-Administration Paradigm to Model Individual Differences in Impaired Control over Alcohol Use 
We developed an alcohol self-administration paradigm to model individual differences in impaired control. The paradigm includes moderate drinking guidelines meant to model limits on alcohol consumption, which are typically exceeded by people with impaired control. Possible payment reductions provided a disincentive for excessive drinking. Alcohol use above the guideline, despite possible pay reductions, was considered to be indicative of impaired control. Heavy-drinking 21–25 year-olds (N = 39) were randomized to an experimental condition including the elements of the impaired control paradigm or to a free-drinking condition without these elements. Alcohol self-administration was compared between these two conditions to establish the internal validity of the experimental paradigm. In both conditions, participants self-administered beer and non-alcoholic beverages for 3 hours in a bar setting with 1–3 other participants. Experimental condition participants self-administered significantly fewer beers and drank to lower blood-alcohol concentrations (BACs) on average than those in the free-drinking condition. Experimental condition participants were more likely than free-drinking condition participants to intersperse non-alcoholic beverages with beer and to drink at a slower pace. Although experimental condition participants drank more moderately than those in the free-drinking condition overall, their range of drinking was considerable (BAC range = .024–.097) with several participants drinking excessively. A lower initial subjective response to alcohol and earlier age of alcohol use onset were associated with greater alcohol self-administration in the experimental condition. Given the variability in response, the impaired control laboratory paradigm may have utility for preliminary tests of novel interventions in future studies and for identifying individual differences in problem-drinking risk.
PMCID: PMC4131292  PMID: 23937598
laboratory methods; young adult; negative consequences; protective strategies; subjective response
8.  Neurobiology of Gambling Behaviors 
Current opinion in neurobiology  2013;23(4):660-667.
For many, gambling is a recreational activity that is performed periodically without ill effects, but for some, gambling may interfere with life functioning. A diagnostic entity, pathological gambling, is currently used to define a condition marked by excessive and problematic gambling. In this review, the current status of understanding of the neurobiologies of gambling and pathological gambling is described. Multiple neurotransmitter systems (norepinephrine, serotonin, dopamine, opioid and glutamate) and brain regions (ventral striatum, ventromedial prefrontal cortex, insula, among others) have been implicated in gambling and pathological gambling. Considerations for future directions in gambling research, with a view towards translating neurobiological advances into more effective prevention and treatment strategies, are discussed.
PMCID: PMC3803105  PMID: 23541597
Gambling; neuroimaging; neurobiology; treatment development
9.  Neurobiological considerations in understanding behavioral treatments for pathological gambling 
Pathological gambling (PG), a disorder currently categorized as an impulse-control disorder but being considered as a non-substance addiction in DSM-5 discussions, represents a significant public health concern. Over the past decade, considerable advances have been made with respect to understanding the biological underpinnings of PG. Research has also demonstrated the efficacies of multiple treatments, particularly behavioral therapies, for treating PG. Despite these advances, relatively little is known regarding how biological measures, particularly those assessing brain function, relate to treatments for PG. In this article, we present a conceptual review focusing on the neurobiology of behavioral therapies for PG. To illustrate issues related to study design, we present proof-of-concept preliminary data that link Stroop-related brain activations prior to treatment onset to treatment outcome in individuals with PG receiving a cognitive behavioral treatment incorporating aspects of imaginal desensitization and motivational interviewing. We conclude with recommendations about current and future directions regarding how to incorporate and translate biological findings into improved therapies for individuals with non-substance and substance addictions.
PMCID: PMC3700568  PMID: 23586456
Gambling; neuroimaging; treatment development; behavioral therapy; cognitive control; nutraceuticals
10.  Functional Brain Networks Associated with Cognitive Control, Cocaine Dependence and Treatment Outcome 
Individuals with cocaine dependence often evidence poor cognitive control. The purpose of this exploratory study was to investigate networks of functional connectivity underlying cognitive control in cocaine dependence and examine the relationship of the networks to the disorder and its treatment. Independent component analysis (ICA) was applied to fMRI data to investigate if regional activations underlying cognitive control processes operate in functional networks, and whether these networks relate to performance and treatment outcome measures in cocaine dependence. Twenty patients completed a Stroop task during fMRI prior to entering outpatient treatment and were compared to 20 control participants. ICA identified five distinct functional networks related to cognitive control interference events. Cocaine-dependent patients displayed differences in performance-related recruitment of three networks. Reduced involvement of a “top-down” fronto-cingular network contributing to conflict monitoring correlated with better treatment retention. Greater engagement of two “bottom-up” subcortical and ventral prefrontal networks related to cue-elicited motivational processing correlated with abstinence during treatment. The identification of subcortical networks linked to cocaine abstinence and cortical networks to treatment retention suggests that specific circuits may represent important, complementary targets in treatment development for cocaine dependence.
PMCID: PMC3743442  PMID: 22775772
fMRI; substance use disorders; cocaine dependence; cognitive control; cognitive behavioral therapy
11.  An exploratory examination of marijuana use, problem-gambling severity, and health correlates among adolescents 
Background and aims: Gambling is common in adolescents and at-risk and problem/pathological gambling (ARPG) is associated with adverse measures of health and functioning in this population. Although ARPG commonly co-occurs with marijuana use, little is known how marijuana use influences the relationship between problem-gambling severity and health- and gambling-related measures. Methods: Survey data from 2,252 Connecticut high school students were analyzed using chi-square and logistic regression analyses. Results: ARPG was found more frequently in adolescents with lifetime marijuana use than in adolescents denying marijuana use. Marijuana use was associated with more severe and a higher frequency of gambling-related behaviors and different motivations for gambling. Multiple health/functioning impairments were differentially associated with problem-gambling severity amongst adolescents with and without marijuana use. Significant marijuana-use-by-problem-gambling-severity-group interactions were observed for low-average grades (OR = 0.39, 95% CI = [0.20, 0.77]), cigarette smoking (OR = 0.38, 95% CI = [0.17, 0.83]), current alcohol use (OR = 0.36, 95% CI = [0.14, 0.91]), and gambling with friends (OR = 0.47, 95% CI = [0.28, 0.77]). In all cases, weaker associations between problem-gambling severity and health/functioning correlates were observed in the marijuana-use group as compared to the marijuana-non-use group. Conclusions: Some academic, substance use, and social factors related to problem-gambling severity may be partially accounted for by a relationship with marijuana use. Identifying specific factors that underlie the relationships between specific attitudes and behaviors with gambling problems and marijuana use may help improve intervention strategies.
PMCID: PMC4117289  PMID: 25215219
marijuana; gambling; at-risk/problem gambling; adolescence; risk behaviors
12.  Monetary Reward Processing in Obese Individuals With and Without Binge Eating Disorder 
Biological psychiatry  2013;73(9):877-886.
An important step in obesity research involves identifying neurobiological underpinnings of nonfood reward processing unique to specific subgroups of obese individuals.
Nineteen obese individuals seeking treatment for binge eating disorder (BED) were compared with 19 non-BED obese individuals (OB) and 19 lean control subjects (LC) while performing a monetary reward/loss task that parses anticipatory and outcome components during functional magnetic resonance imaging. Differences in regional activation were investigated in BED, OB, and LC groups during reward/loss prospect, anticipation, and notification.
Relative to the LC group, the OB group demonstrated increased ventral striatal and ventromedial prefrontal cortex activity during anticipatory phases. In contrast, the BED group relative to the OB group demonstrated diminished bilateral ventral striatal activity during anticipatory reward/loss processing. No differences were observed between the BED and LC groups in the ventral striatum.
Heterogeneity exists among obese individuals with respect to the neural correlates of reward/loss processing. Neural differences in separable groups with obesity suggest that multiple, varying interventions might be important in optimizing prevention and treatment strategies for obesity.
PMCID: PMC3686098  PMID: 23462319
Binge eating disorder; fMRI; inferior frontal gyrus; insula; obesity; reward; ventral striatum
13.  Gambling-Related Attitudes and Behaviors in Adolescents Having Received Instant (Scratch) Lottery Tickets as Gifts 
Instant (scratch) lottery ticket gambling is popular among adolescents. Prior research has not determined whether adolescents’ gambling behavior and attitudes toward gambling are influenced by the receipt of scratch lottery tickets as gifts.
Cross-sectional survey data from 2,002 Connecticut high school students with past-year gambling were analyzed using bivariate approaches and logistic regression analyses. Interactions between gambling-problem severity and lottery-gift status were examined in relation to multiple outcomes.
Adolescents who received a scratch lottery ticket as a gift compared with those who did not were more likely to report features of problem gambling, buy scratch lottery tickets for themselves, and buy and receive other types of lottery tickets; they were also less likely to report parental disapproval of gambling and to see gambling prevention efforts as important. Later (≥15 years) age-at-gambling-onset was inversely linked to gambling-problem severity in the lottery gift group (odds ratio [OR] = .38) but not in the nongift group (OR = .91), yielding a significant severity by gift status interaction. Other academic, health, and gambling-related correlates of gambling-problem severity were similar in the gift and nongift groups.
For adolescents, the receipt of scratch lottery tickets as gifts during childhood or adolescence was associated with risky/problematic gambling and with gambling-related attitudes, behaviors, and views suggesting greater gambling acceptability. The extent to which the receipt of scratch lottery tickets may promote gambling behaviors and the development of gambling problems warrants consideration. Education, prevention, and treatment strategies should incorporate findings relating to receipt of gambling products by underage individuals.
PMCID: PMC3667499  PMID: 23299004
Gambling; Adolescence; Lottery; Risk behaviors; Gifts
14.  Problem gambling severity and the incidence of Axis I psychopathology among older adults in the general population 
Journal of psychiatric research  2013;47(4):534-541.
To examine the longitudinal relationship between past-year problem-gambling severity and incident Axis I psychopathology among older adults (aged 55 to 90), analyses were conducted on data from the National Epidemiologic Study of Alcohol and Related Conditions (NESARC). This nationally-representative population-based survey was conducted in two waves (Wave 1, 2000-2001; and Wave 2, 2004-2005). Past-year problem-gambling severity at Wave 1 and incident Axis I psychopathology at Wave 2 were evaluated with the Alcohol Use Disorder and Associated Disabilities Interview Schedule—Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition. Multivariate logistic regression modeling was conducted on groups categorized into low-frequency gambling/non-gambling (LFG/NG), low-risk gambling (LRG), and at-risk/problem/pathological gambling (ARPG) based on DSM-IV criteria for pathological gambling. Relative to LFG/NG, ARPG at Wave 1 was positively associated with the incidence of generalized anxiety disorder (OR=2.51; p=.011) and any substance use disorder (OR=2.61; p=.0036); LRG was negatively associated with the incidence of hypomania (OR=0.33; p=.017). Models were adjusted for demographic characteristics, psychiatric comorbidity, health behaviors, physical health, and stressful life events assessed at baseline. While gambling may represent a positive activity for some older adults, data suggest that risky/problematic gambling behavior may be associated with the development of psychiatric problems in this population. Older-adult gamblers, as well as their clinicians, friends, and family, should be aware of potential risks associated with gambling, adopt strategies to prevent the onset of secondary disorders, and monitor themselves and others for signs of problems.
PMCID: PMC3668329  PMID: 23333039
pathological gambling; older adults; mental health; incidence; epidemiology; substance abuse
15.  Risk-taking and decision-making in youth: relationships to addiction vulnerability 
Journal of behavioral addictions  2013;2(1):10.1556/JBA.2.2013.1.1.
Decision-making and risk-taking behavior undergo developmental changes during adolescence. Disadvantageous decision-making and increased risk-taking may lead to problematic behaviors such as substance use and abuse, pathological gambling and excessive internet use.
Based on MEDLINE searches, this article reviews the literature on decision-making and risk-taking and their relationship to addiction vulnerability in youth.
Decision-making and risk-taking behaviors involve brain areas that undergoing developmental changes during puberty and young adulthood. Individual differences and peer pressure also relate importantly to decision-making and risk-taking.
Brain-based changes in emotional, motivational and cognitive processing may underlie risk-taking and decision-making propensities in adolescence, making this period a time of heightened vulnerability for engagement in additive behaviors.
PMCID: PMC3840427  PMID: 24294500
adolescence; risk-taking; decision-making; behavioral addictions; addiction vulnerability
16.  Biological Contributions to Addictions in Adolescents and Adults: Prevention, Treatment and Policy Implications 
Despite significant advances in our understanding of the biological bases of addictions, these disorders continue to represent a huge public health burden that is associated with substantial personal suffering. Efforts to target addictions require consideration of how the improved biological understanding of addictions may lead to improved prevention, treatment and policy initiatives.
In this article, we provide a narrative review of current biological models for addictions with a goal of placing existing data and theories within a translational and developmental framework targeting the advancement of prevention, treatment and policy strategies.
Data regarding individual differences, intermediary phenotypes, and main and interactive influences of genetic and environmental contributions in the setting of developmental trajectories that may be influenced by addictive drugs or behavior indicate complex underpinnings of addictions.
Consideration and further elucidation of the biological etiologies of addictions hold significant potential for making important gains and reducing the public health impact of addictions.
PMCID: PMC3935152  PMID: 23332567
Addiction; Neurobiology; Adolescence; Public Health; Development
17.  Neural Correlates of Stress- and Food Cue–Induced Food Craving in Obesity 
Diabetes Care  2013;36(2):394-402.
Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR.
Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI.
Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus.
These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity.
PMCID: PMC3554293  PMID: 23069840
18.  Are Internet use and video-game-playing addictive behaviors? Biological, clinical and public health implications for youths and adults 
Minerva psichiatrica  2012;53(3):153-170.
Internet use and video-game playing are experiencing rapid growth among both youth and adult populations. Research suggests that a minority of users experience symptoms traditionally associated with substance-related addictions. Mental health professionals, policy makers and the general public continue to debate the issue of Internet addiction (IA) and problematic video-game playing (PVG). This review identifies existing studies into the clinical and biological characteristics of these disorders that may help guide decisions as to whether or not IA and PVG should be grouped together with substance use disorders (SUDs).
PMCID: PMC3840433  PMID: 24288435
Internet addiction; Video-games; Substance use disorder; Classification; Prevalence; Neurobiology; Growth and development
19.  A preliminary investigation of Stroop-related intrinsic connectivity in cocaine dependence: Associations with treatment outcomes 
The American journal of drug and alcohol abuse  2013;39(6):10.3109/00952990.2013.841711.
Cocaine-dependent individuals demonstrate neural and behavioral differences compared to healthy comparison subjects when performing the Stroop color-word inference test. Stroop measures also relate to treatment outcome for cocaine dependence. Intrinsic connectivity analyses assess the extent to which task-related regional brain activations are related to each other in the absence of defining a priori regions-of-interest.
This study examined: 1) the extent to which cocaine-dependent and non-addicted individuals differed on measures of intrinsic connectivity during fMRI Stroop performance; and, 2) the relationships between fMRI Stroop intrinsic connectivity and treatment outcome in cocaine dependence.
Sixteen treatment-seeking cocaine-dependent patients and matched non-addicted comparison subjects completed an fMRI Stroop task. Between-group differences in intrinsic connectivity were assessed and related to self-reported and urine-toxicology-based cocaine-abstinence measures.
Cocaine-dependent patients vs. comparison subjects showed less intrinsic connectivity in cortical and sub-cortical regions. When adjusting for individual degree of intrinsic connectivity, cocaine-dependent vs. comparison subjects showed relatively greater intrinsic connectivity in the ventral striatum, putamen, inferior frontal gyrus, anterior insula, thalamus, and substantia nigra. Non-mean-adjusted intrinsic-connectivity measures in the midbrain, thalamus, ventral striatum, substantia nigra, insula, and hippocampus negatively correlated with measures of cocaine abstinence.
The diminished intrinsic connectivity in cocaine-dependent vs. comparison subjects suggests poorer communication across brain regions during cognitive-control processes. In mean-adjusted analyses, the cocaine-dependent group displayed relatively greater Stroop-related connectivity in regions implicated in motivational processes in addictions. The relationships between treatment outcomes and connectivity in the midbrain and basal ganglia suggest that connectivity represents a potential treatment target.
PMCID: PMC3827911  PMID: 24200209
intrinsic connectivity; cocaine dependence; functional magnetic resonance imaging; Stroop color-word interference test; treatment outcome; addiction; cognitive control
20.  Control Yourself: Alcohol and Impulsivity 
Alcoholism, clinical and experimental research  2010;34(8):10.1111/j.1530-0277.2010.01214.x.
PMCID: PMC3822522  PMID: 20491735
21.  Sex differences moderate the relationship between adolescent language and mentalization 
Personality disorders  2012;3(4):393-405.
Mentalization refers to the ability to infer mental states of self and others, and this capacity facilitates social interactions. Advances in mentalization theory have proposed that there are both explicit and implicit mentalizing capacities and language may be identified as being an important factor in differentiating these two components of mentalization. Moreover, given apparent sex differences in language and mentalization, we hypothesized that sex may moderate the relationship between language and mentalization. In this study, measures assessing implicit and explicit mentalization as well as language were examined in 49 adolescents (25 girls and 24 boys) aged 14 to 18 years. Participants were administered the Mentalizing Stories for Adolescents to assess explicit mentalization, and the Reading Mind in the Eyes Task to assess implicit mentalization. Language was assessed using the Clinical Evaluation of Language Fundamentals. Sex was found to moderate the relationship between language and explicit mentalization; while language and explicit mentalization were related in boys, these domains were unrelated in girls. There was no moderation of language and implicit mentalization by sex, and these two domains were also uncorrelated. These findings suggest an important role for language development in the capacity for explicit mentalization in boys, and we interpret this as a benefit in girls who may be more socially motivated and less limited by language in their efforts to mentalize.
PMCID: PMC3691855  PMID: 22800178
Mentalization; language; adolescence; sex differences
22.  Serious physical fighting and gambling-related attitudes and behaviors in adolescents 
Journal of Behavioral Addictions  2013;2(3):167-178.
Background and aims: Physical fighting and gambling are common risk behaviors among adolescents. Prior studies have found associations among these behaviors in adolescents but have not examined systematically the health and gambling correlates of problem-gambling severity amongst youth stratified by fight involvement. Methods: Survey data were used from 2,276 Connecticut high school adolescents regarding their physical fight involvement, gambling behaviors and perceptions, and health and functioning. Gambling perceptions and correlates of problem-gambling severity were examined in fighting and non-fighting adolescents. Results: Gambling perceptions were more permissive and at-risk/problem gambling was more frequent amongst adolescents reporting serious fights versus those denying serious fights. A stronger relationship between problem-gambling severity and regular smoking was observed for adolescents involved in fights. Discussion and conclusions: The more permissive gambling attitudes and heavier gambling associated with serious fights in high school students suggest that youth who engage in physical fights warrant enhanced prevention efforts related to gambling. The stronger relationship between tobacco smoking and problem-gambling severity amongst youth engaging in serious fights suggest that fighting youth who smoke might warrant particular screening for gambling problems and subsequent interventions.
PMCID: PMC3840436  PMID: 24294502
fighting; gambling; physical violence; adolescents; risk behaviors; high school
23.  Divergent neural substrates of inhibitory control in binge eating disorder relative to other manifestations of obesity 
Obesity (Silver Spring, Md.)  2013;21(2):367-377.
An important endeavor involves increasing our understanding of biobehavioral processes underlying different types of obesity. The current study investigated the neural correlates of cognitive control (involving conflict monitoring and response inhibition) in obese individuals with binge eating disorder (BED) as compared to BMI-matched non-BED obese (OB) individuals and lean comparison (LC) participants. Alterations in cognitive control may contribute to differences in behavioral control over eating behaviors in BED and obesity. Participants underwent functional magnetic resonance imaging (fMRI) while completing the Stroop color-word interference task. Relative to the OB and LC groups, activity in the BED group was differentiated by relative hypoactivity in brain areas involved in self-regulation and impulse control. Specifically, the BED group showed diminished activity in the ventromedial prefrontal cortex (vmPFC), inferior frontal gyrus (IFG) and insula during Stroop performance. In addition, dietary restraint scores were negatively correlated with right IFG and vmPFC activation in the BED group, but not in the OB or HC groups. Thus, BED individuals’ diminished ability to recruit impulse-control-related brain regions appears associated with impaired dietary restraint. The observed differences in neural correlates of inhibitory processing in BED relative to OB and LC groups suggest distinct neurobiological contributions to binge eating as a subgroup of obese individuals.
PMCID: PMC3610836  PMID: 23404820
binge eating disorder; obesity; inhibition; ventromedial prefrontal cortex; inferior frontal gyrus; restraint; fMRI
24.  The Neurobiology of Impulse Control Disorders 
To review the neurobiological substrates of impulse control disorders (ICDs). Pathological gambling (PG) is a main focus of the review in that most biological studies of the formal ICDs have examined this disorder.
The medical database MedLine from 1966 to present was searched to identify relevant articles that were subsequently reviewed to generate this manuscript.
Preclinical studies suggest that differential brain monoamine neuromodulation is associated with impulsive decision-making and risk-taking behaviors. Clinical studies implicate multiple neurotransmitter systems (serotonergic, dopaminergic, adrenergic, and opioidergic) in the pathophysiology of PG and other ICDs. Initial neuroimaging studies have implicated the ventromedial prefrontal cortex and ventral striatum in the pathophysiology of PG and other ICDs. Genetic contributions to PG seem substantial and initial studies have implicated specific allelic polymorphisms, although genome-wide analyses have yet to be published.
Although significant advances have been made in our understanding of the neurobiology of ICDs, more research is needed to extend existing knowledge and translate these findings into clinical advances.
PMCID: PMC3676928  PMID: 18278382
Pathological Gambling; Serotonin; Norepinephrine; Dopamine; Opioids; Impulsivity; Stress; Genetics; Brain Imaging; Biochemistry
25.  Past-year recreational gambling in a nationally representative sample: Correlates of casino, non-casino, and both casino/non-casino gambling 
Psychiatry research  2011;188(2):269-275.
Data from the Gambling Impact and Behavior Study (GIBS), a national survey of 2,417 U.S. adults, were examined by multivariate analysis to investigate characteristics of past-year recreational gamblers who participated in casino-only, non-casino-only, and both casino and non-casino gambling. Compared to non-casino-only gamblers, individuals who gambled in both locations had higher rates of alcohol use and abuse/dependence, lower rates of drug use, more frequent gambling, and larger wins and losses. Compared to casino-only gamblers, individuals who gambled in both locations reported less drug use, poorer subjective health, earlier age of gambling onset, greater frequency of gambling, and larger wins and losses. Compared to casino-only or non-casino-only gambling, gambling in both locations was associated with more frequent and heavier gambling. Findings suggest aspects of recreational gambling, such as gambling venue, may have important public health implications and should be considered in guidelines for responsible gambling.
PMCID: PMC3673308  PMID: 21550124
gambling; alcohol; drug use; casino; public health

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