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Item Alcohol Preferring P Rats Exhibit Elevated Motor Impulsivity Concomitant with Operant Responding and Self-Administration of Alcohol(Wiley, 2016-05) Wesley Beckwith, Steven; Czachowski, Cristine Lynn; Psychology, School of ScienceBACKGROUND: Increased levels of impulsivity are associated with increased illicit drug use and alcoholism. Previous research in our laboratory has shown that increased levels of delay discounting (a decision-making form of impulsivity) are related to appetitive processes governing alcohol self-administration as opposed to purely consummatory processes. Specifically, the high-seeking/high-drinking alcohol-preferring P rats showed increased delay discounting compared to nonselected Long Evans rats (LE) whereas the high-drinking/moderate-seeking HAD2 rats did not. The P rats also displayed a perseverative pattern of behavior such that during operant alcohol self-administration they exhibited greater resistance to extinction. METHODS: One explanation for the previous findings is that P rats have a deficit in response inhibition. This study followed up on this possibility by utilizing a countermanding paradigm (stop signal reaction time [SSRT] task) followed by operant self-administration of alcohol across increasing fixed ratio requirements (FR; 1, 2, 5, 10, and 15 responses). In separate animals, 24-hour access 2-bottle choice (10% EtOH vs. water) drinking was assessed. RESULTS: In the SSRT task, P rats exhibited an increased SSRT compared to both LE and HAD2 rats indicating a decrease in behavioral inhibition in the P rats. Also, P rats showed increased operant self-administration across all FRs and the greatest increase in responding with increasing FR requirements. Conversely, the HAD2 and LE had shorter SSRTs and lower levels of operant alcohol self-administration. However, for 2-bottle choice drinking HAD2s and P rats consumed more EtOH and had a greater preference for EtOH compared to LE. CONCLUSIONS: These data extend previous findings showing the P rats to have increased delay discounting (decision-making impulsivity) and suggest that P rats also have a lack of behavioral inhibition (motor impulsivity). This supports the notion that P rats are a highly impulsive as well as "high-seeking" model of alcoholism, and that the HAD2s' elevated levels of alcohol consumption are not mediated via appetitive processes or impulsivity.Item Alcohol Use Disorder Interventions Targeting Brain Sites for Both Conditioned Reward and Delayed Gratification(SpringerLink, 2020-01) Oberlin, Brandon G.; Shen, Yitong I.; Kareken, David A.; Psychiatry, School of MedicineAlcohol use disorder is a destructive compulsion characterized by chronic relapse and poor recovery outcomes. Heightened reactivity to alcohol-associated stimuli and compromised executive function are hallmarks of alcohol use disorder. Interventions targeting these two interacting domains are thought to ameliorate these altered states, but the mutual brain sites of action are yet unknown. Although interventions on alcohol cue reactivity affect reward area responses, how treatments alter brain responses when subjects exert executive effort to delay gratification is not as well-characterized. Focusing on interventions that could be developed into effective clinical treatments, we review and identify brain sites of action for these two categories of potential therapies. Using activation likelihood estimation (ALE) meta-analysis, we find that interventions on alcohol cue reactivity localize to ventral prefrontal cortex, dorsal anterior cingulate, and temporal, striatal, and thalamic regions. Interventions for increasing delayed reward preference elicit changes mostly in midline default mode network regions, including posterior cingulate, precuneus, and ventromedial prefrontal cortex-in addition to temporal and parietal regions. Anatomical co-localization of effects appears in the ventromedial prefrontal cortex, whereas effects specific to delay-of-gratification appear in the posterior cingulate and precuneus. Thus, the current available literature suggests that interventions in the domains of cue reactivity and delay discounting alter brain activity along midline default mode regions, specifically in the ventromedial prefrontal cortex for both domains, and the posterior cingulate/precuneus for delay-of-gratification. We believe that these findings could facilitate targeting and development of new interventions, and ultimately treatments of this challenging disorder.Item Application of the Acquired Preparedness Model for Alcohol and Cigarette Use Among Reserve-Dwelling First Nation Adolescents(American Psychological Association, 2022) Schick, Melissa R.; Williams, Jessica N.; Kirk-Provencher, Katelyn T.; Cyders, Melissa A.; Spillane, Nichea S.; Psychology, School of ScienceObjective: North American Indigenous youth experience disproportionate harm associated with alcohol and cigarette use compared to other racial/ethnic groups. The Acquired Preparedness Model (APM), developed and tested in primarily White samples, hypothesizes that urgency contributes to risk for substance use by influencing the degree to which adolescents attend to positive aspects of substance use, leading to the development of more positive expectations about the consequences of substance use, and increasing subsequent substance use. The purpose of the present study was to provide an initial test of whether the APM generalizes to understanding alcohol and cigarette use among high-risk First Nation adolescents. Method: First Nation adolescents (n = 106, Mage = 14.6, 50.0% female) recruited from reserve communities in Eastern Canada completed self-report measures as part of a larger community-based participatory research project. Procedures were approved by tribal chief, council, and university IRB. Results: The hypothesized model demonstrated excellent fit for alcohol use, χ²(1) = 1.07, p = .30, CFI = 0.99, RMSEA = .03, SRMR = .02, and adequate fit for cigarette use, χ²(1) = 2.58, p = .11, CFI = 0.98, RMSEA = 0.12, SRMR = 0.03. The indirect effects of urgency on alcohol consumption and cigarette smoking through alcohol and cigarette expectancies were each significant. Conclusions: Findings of the present study provide initial support for the generalizability of the APM in understanding risk for alcohol and cigarette use among reserve-dwelling First Nation youth. The next important step is to replicate this finding in a prospective sample.Item Assessment of the dopamine system in addiction using positron emission tomography(2014) Albrecht, Daniel Strakis; Hutchins, Gary D.; Saykin, Andrew J.; Kareken, David A.; Yoder, Karmen K.; Grahame, Nicholas J.Drug addiction is a behavioral disorder characterized by impulsive behavior and continued intake of drug in the face of adverse consequences. Millions of people suffer the financial and social consequences of addiction, and yet many of the current therapies for addiction treatment have limited efficacy. Therefore, there is a critical need to characterize the neurobiological substrates of addiction in order to formulate better treatment options. In the first chapter, the striatal dopamine system is interrogated with [11C]raclopride PET to assess differences between chronic cannabis users and healthy controls. The results of this chapter indicate that chronic cannabis use is not associated with a reduction in striatal D2/D3 receptor availability, unlike many other drugs of abuse. Additionally, recent cannabis consumption in chronic users was negatively correlated with D2/D3 receptor availability. Chapter 2 describes a retrospective analysis in which striatal D2/D3 receptor availability is compared between three groups of alcohol-drinking and tobacco-smoking subjects: nontreatment-seeking alcoholic smokers, social-drinking smokers, and social-drinking non-smokers. Results showed that smokers had reduced D2/D3 receptor availability throughout the striatum, independent of drinking status. The results of the first two chapters suggest that some combustion product of marijuana and tobacco smoke may have an effect on striatal dopamine concentration. Furthermore, they serve to highlight the effectiveness of using baseline PET imaging to characterize dopamine dysfunction in addictions. The final chapter explores the use of [18F]fallypride PET in a proof-of-concept study to determine whether changes in cortical dopamine can be detected during a response inhibition task. We were able to detect several cortical regions of significant dopamine changes in response to the task, and the amount of change in three regions was significantly associated with task performance. Overall, the results of Chapter 3 validate the use of [18F]fallypride PET to detect cortical dopamine changes during a impulse control task. In summary, the results reported in the current document demonstrate the effectiveness of PET imaging as a tool for probing resting and activated dopamine systems in addiction. Future studies will expand on these results, and incorporate additional methods to further elucidate the neurobiology of addiction.Item Association between concussion and mental health in former collegiate athletes(Springer, 2014-12) Kerr, Zachary Y.; Evenson, Kelly R.; Rosamond, Wayne D.; Mihalik, Jason P.; Guskiewicz, Kevin M.; Marshall, Stephen W.; Department of Social and Behavioral Sciences, Richard M. Fairbanks School of Public HealthBACKGROUND: The existing research on the association between concussion and mental health outcomes is largely limited to former professional athletes. This cross-sectional study estimated the association between recurrent concussion and depression, impulsivity, and aggression in former collegiate athletes. METHODS: Former collegiate athletes who played between 1987-2012 at a Division I university completed an online questionnaire. The main exposure, total number of self-recalled concussions (sport-related and non-sport-related), were categorized as: zero (referent), one, two, or three or more concussions. The main outcomes were the depression module of The Patient Health Questionnaire (PHQ-9), the Short Form of the Barratt Impulsiveness scale (BIS15); and the 12-item Short Form of the Buss-Perry Aggression Questionnaire (BPAQ-SF). Depression was categorized into a binomial severity classification that differentiated between no or mild depression (PHQ-9 scores <10) and moderate to severe depression (PHQ-9 scores ≥10). Impulsivity and aggression were kept as continuous outcomes. Binomial regression estimated adjusted prevalence ratios (PR). Linear regression estimated adjusted mean differences (MD). RESULTS: Of the 797 respondents with complete data (21.9% completion rate), 38.8% reported at least one concussion. Controlling for alcohol dependence and family history of depression, the prevalence of moderate to severe depression among former collegiate athletes reporting three or more concussions in total was 2.4 times that of those reporting zero concussions [95% Confidence Interval (CI): 1.0, 5.7]. Controlling for alcohol dependence, family history of anxiety, relationship status, obtaining a post-graduate degree, and playing primary college sport professionally, former collegiate athletes reporting two or more concussions in total had higher mean scores for impulsivity, compared to those reporting no concussions (2 concussions MD = 2.7; 95% CI: 1.2, 4.1; 3+ concussions MD = 1.9; 95% CI: 0.6, 3.2). Controlling for alcohol dependence, sex, and relationship status, former collegiate athletes reporting three or more concussions in total had a higher mean score for aggression, compared to those reporting no concussions (MD = 3.0; 95% CI: 1.4, 4.7). CONCLUSIONS: Our study found an association between former concussion and greater risk of severe depression and higher levels of impulsivity and aggression among former collegiate athletes. Additional prospective studies better addressing causality and ascertaining valid lifetime concussion histories and medical histories are needed.Item Associations among Impulsivity, Trauma History, and Alcohol Misuse within a Young Adult Sample(Elsevier, 2017) Bountress, Kaitlin E.; Adams, Zachary W.; Gilmore, Amanda K.; Amstadter, Ananda B.; Thomas, Suzanne; Danielson, Carla Kmett; Psychiatry, School of MedicineObjective: Young adult alcohol misuse is associated with numerous long-term adverse outcomes. Given the link between impulsivity and alcohol use, we examined whether three impulsivity-related traits differentially predicted number of drinks per drinking day (DDD). We also examined whether these effects varied for those with different trauma histories. Method: The current study (n=254) examined motor, non-planning, and attentional impulsivity as predictors of DDD. It also examined whether impulsivity was differentially predictive of DDD across individuals in: a control group (non-trauma exposed), a trauma exposed but non-PTSD group, and a PTSD group. Results: Regardless of group, more motor impulsivity was associated with more DDD. The effect of non-planning impulsivity varied according to trauma history. Specifically, more non-planning impulsivity predicted more DDD for those without PTSD. Finally, attentional impulsivity was not predictive of DDD. Conclusions: Young adults with high levels of motor impulsivity, regardless of trauma history, may be a particularly high-risk group in terms of propensity for alcohol use/misuse. Additionally, high levels of non-planning impulsivity may signify those at greater risk for alcohol misuse, among those without PTSD. Motor impulsivity and non-planning impulsivity may serve as useful intervention targets in alcohol misuse prevention efforts. Implications for future research in this area are discussed.Item Associations between Suicidal Thoughts and Behaviors and Genetic Liability for Cognitive Performance, Depression, and Risk-Taking in a High-Risk Sample(Karger, 2021) Johnson, Emma C.; Aliev, Fazil; Meyers, Jacquelyn L.; Salvatore, Jessica E.; Tillman, Rebecca; Chang, Yoonhoo; Docherty, Anna R.; Bogdan, Ryan; Acion, Laura; Chan, Grace; Chorlian, David B.; Kamarajan, Chella; Kuperman, Samuel; Pandey, Ashwini; Plawecki, Martin H.; Schuckit, Marc; Tischfield, Jay; Edenberg, Howard J.; Bucholz, Kathleen K.; Nurnberger, John I.; Porjesz, Bernice; Hesselbrock, Victor; Dick, Danielle M.; Kramer, John R.; Agrawal, Arpana; Psychiatry, School of MedicineBackground: Suicidal thoughts and behaviors (STBs) and nonsuicidal self-injury (NSSI) behaviors are moderately heritable and may reflect an underlying predisposition to depression, impulsivity, and cognitive vulnerabilities to varying degrees. Objectives: We aimed to estimate the degrees of association between genetic liability to depression, impulsivity, and cognitive performance and STBs and NSSI in a high-risk sample. Methods: We used data on 7,482 individuals of European ancestry and 3,359 individuals of African ancestry from the Collaborative Study on the Genetics of Alcoholism to examine the links between polygenic scores (PGSs) for depression, impulsivity/risk-taking, and cognitive performance with 3 self-reported indices of STBs (suicidal ideation, persistent suicidal ideation defined as ideation occurring on at least 7 consecutive days, and suicide attempt) and with NSSI. Results: The PGS for depression was significantly associated with all 4 primary self-harm measures, explaining 0.6-2.5% of the variance. The PGS for risk-taking behaviors was also associated with all 4 self-harm behaviors in baseline models, but was no longer associated after controlling for a lifetime measure of DSM-IV alcohol dependence and abuse symptom counts. Polygenic predisposition for cognitive performance was negatively associated with suicide attempts (q = 3.8e-4) but was not significantly associated with suicidal ideation nor NSSI. We did not find any significant associations in the African ancestry subset, likely due to smaller sample sizes. Conclusions: Our results encourage the study of STB as transdiagnostic outcomes that show genetic overlap with a range of risk factors.Item Discrimination and Substance Use: Examining the Moderating Role of Impulsivity Among Racial-Ethnic Minority Adolescents(Taylor & Francis, 2021) Riley, Tennisha N.; Clifton, Richelle L.; Khazvand, Shirin; Zapolski, Tamika C. B.; Psychology, School of ScienceBackground: Research on substance use among racial-ethnic minority populations notes that discrimination experiences predict substance use outcomes. Individual-level factors, such as impulsivity, are also known risk factors for substance use. However, little is known about the direct and interaction effects between discrimination experiences and impulsivity among racial-ethnic minority youth. The current study examines the effects of perceived experiences of discrimination on alcohol and marijuana use among racial-ethnic minority youth, and whether individual differences in impulsivity traits help to further understand potential risk for substance use. Methods: Participants were 112 racial-ethnic minority adolescents (Mage = 15.27; African American, Hispanic, Multiracial, Native American/Alaskan Native, or Other). Adolescents completed self-report measures of perceived experiences of discrimination, alcohol and marijuana use (past year occurrence and problematic use), and five impulsivity traits (i.e., sensation seeking, lack of planning, lack of perseverance, negative urgency, and positive urgency). Results: A significant main effect of perceived discrimination on problem marijuana use was found, as well as a significant main effect of lack of premeditation on current marijuana use. Several marginally significant main effects emerged for alcohol use and problem alcohol use (i.e., positive urgency and sensation seeking, respectively). Conclusion: While no significant moderation effects emerged, marginal findings suggest a potential interactive effect of discrimination and impulsivity traits on problem alcohol and marijuana use among racial-ethnic minority youth. Further research is needed in this area to replicate findings, which is critical to informing effective intervention and prevention efforts for this population of youth.Item Drinking Motives as Mediators of the Impulsivity-Substance Use Relation: Pathways for Negative Urgency, Lack of Premeditation, and Sensation Seeking(Elsevier, 2012) Adams, Zachary W.; Kaiser, Alison J.; Lynam, Donald R.; Charnigo, Richard J.; Milich, Richard; Psychiatry, School of MedicineTrait impulsivity is a reliable, robust predictor of risky, problematic alcohol use. Mounting evidence supports a multidimensional model of impulsivity, whereby several distinct traits serve as personality pathways to rash action. Different impulsivity-related traits may predispose individuals to drink for different reasons (e.g., to enhance pleasure, to cope with distress) and these different motives may, in turn, influence drinking behavior. Previous findings support such a mediational model for two well-studied traits: sensation seeking and lack of premeditation. This study addresses other impulsivity-related traits, including negative urgency. College students (N = 432) completed questionnaires assessing personality, drinking motives, and multiple indicators of problematic drinking. Negative urgency, sensation seeking, and lack of premeditation were all significantly related to problematic drinking. When drinking motives were included in the model, direct effects for sensation seeking and lack of premeditation remained significant, and indirect effects of sensation seeking and lack of premeditation on problematic drinking were observed through enhancement motives. A distinct pathway was observed for negative urgency. Negative urgency bore a significant total effect on problematic drinking through both coping and enhancement motives. This study highlights unique motivational pathways through which different impulsive traits may operate, suggesting that interventions aimed at preventing or reducing problematic drinking should be tailored to individuals' personalities. For instance, individuals high in negative urgency may benefit from learning healthier strategies for coping with distress.Item Emotional response inhibition in bipolar disorder: a functional magnetic resonance imaging study of trait- and state-related abnormalities(Elsevier, 2013-01-15) Hummer, Tom A.; Hulvershorn, Leslie A.; Karne, Harish S.; Gunn, Abigail D.; Wang, Yang; Anand, Amit; Psychiatry, School of MedicineBACKGROUND: Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects. METHODS: One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters. RESULTS: The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition. CONCLUSIONS: These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment.