<p>Substance use disorders are one of the most common psychiatric diagnoses among adolescents; marijuana is the illicit drug used most frequently by youth. Treatment dropout and relapse following treatment are common; innovative strategies are needed to improve treatment outcomes for youth substance abusers. The aim of this study was to develop and evaluate the feasibility of a virtual reality (VR) cue reactivity paradigm for adolescent cannabis abusers and to compare it to a video cue reactivity paradigm. Forty-two treatment-seeking youth with a cannabis use disorder completed the study, which incorporated three parts. During Part 1, drug and neutral video clips were shown to 11 youth and five substance-abuse experts who provided craving/usefulness ratings for each video clip. During Part 2, five youth met in a focus group and then individually to provide input on the development of the VR paradigm. During Part 3, 26 youth completed a laboratory procedure involving neutral and drug-related video clips and VR presentations. Heart rate, skin conductance, and skin temperature were measured as well as craving. Higher levels of craving and skin conductance were observed during drug-related presentations. The presentations did not significantly differ in their ability to elicit craving and arousal. Results suggest that youth can experience subjective and physiological reactivity to VR drug cues warranting further study with a larger, more diverse sample. Implications are discussed.</p> / Dissertation

Natural recovery is inhibition or moderation of problematic substance use without employing the use of formal addiction services. A neuroanthropological approach to natural recovery highlights the importance of both social and biological aspects of achieving this "self" led process of change. Throughout this project I take a critical anthropological approach to natural recovery, which explores a more holistic conception and historically situated view of current natural recovery theory. This research project employs a neuroanthropological perspective to assess how college students perform natural recovery. Using ethnographic methods, which highlight the social and physical experience of moderation, I discuss how students negotiate pathways for cessation/moderation within the university structure. The university is increasingly a neoliberal space, which influences the way key stakeholders (faculty, staff, and students) perceive and pursue pathways for cessation/moderation. Thus, I found students pursue natural recovery by pulling on recovery capital, facilitated by the university, but outside of traditional cessation pathways, to stop problematic use. Additionally, I employed Bourdieu’s notions of practice and habitus to highlight how students negotiate their lives within this structure and pull on their recovery capital to mitigate cues, proposing a biocultural perspective of natural recovery. The goal of this research is to show how students leverage social relationships and cues in ways that are meaningful to sustaining abstinence/moderation without formal guidance or structure. This work contributes to the small body of literature already established around natural recovery and cue reactivity, and shows how ethnographic methods can and should be applied to both of these fields of research.

The study examined the overlap between cognitive and affective measures of alcohol expectancies as they related to risk for developing alcohol use disorders. It was hypothesized that cognitive-based, paper-and-pencil measures and appetitive psychophysiological reactivity to alcohol cues would correlate and independently correlate to drinking behavior in a sample of college drinkers. It was also hypothesized that genetic risk would impact the relationship between upstream and downstream expectancy measures, given that children of alcoholics displayed blunted reactivity to appetitive cues. A sample of 137 college drinkers (67 males; mean age = 20.23 ± 1.61) reporting a range of drinking behavior (mean quantity/occasion = 4.03 ± 2.34; mean frequency/month = 6.24 ± 4.31) and genetic risk for alcohol use disorders (47 children of alcoholics) participated in this study. The cue reactivity paradigm included the measurement of skin conductance, cardiac response, and acoustic startle eyeblink response to a randomized sequence of alcohol and neutral pictures. Questionnaires and interviews assessed alcohol expectancies, family history, drinking behavior, and risk. Findings revealed that cognitive and affective measures shared modest overlap in the overall sample, such that sedating and negative alcohol expectancies were positively correlated with less appetitive early acoustic startle response. However, alcohol expectancies were not significantly correlated with any of the remaining psychophysiological measures. Further, affective measures were not related to drinking behavior, indicating failure to detect drinking variance in a sample of college drinkers. Findings also indicated that genetic risk impacted the relationship between cognitive and affective measures of expectancy. Specifically, children of alcoholics (COAs) displayed stronger relationships between both positive and negative expectancies and early startle response than their peers. Further, COA Status moderated the relationship between early startle response and Social/Physical Pleasure and Positive/Arousing alcohol expectancies. This dissertation provided evidence that cognitive and affective measures of alcohol expectancies shared modest overlap, indicating that expectancy subscales and early acoustic startle response tapped into the same expectancy construct. Further, genetic risk moderated the strength of relationships between upstream and downstream expectancy measures, which were stronger in children of alcoholics. Overall, affective measures of expectancy were more sensitive to expectancy variation in high-risk college drinkers.

<p>  </p> <p>Posttraumatic stress disorder involves a constellation of neural and behavioral alterations in response to trauma exposure. Aside from symptoms involved in posttraumatic stress disorder diagnosis, patients frequently present with working memory impairments. Working memory training has been established as an effective intervention to reduce posttraumatic stress symptoms. Working memory is associated with posttraumatic stress disorder in that it is commonly impaired in patients and that training can reduce the severity of posttraumatic stress symptoms. Taken together, these points suggest the possibility of a shared mechanism between working memory and posttraumatic stress disorder but working memory has not been studied thoroughly in rodent models of posttraumatic stress disorder. The present study utilizes footshock trauma to induce a posttraumatic stress state in rats and evaluates the effect of trauma and trauma-paired cues on working memory performance. Results demonstrate the emergence of chronic deficits in working memory among traumatized animals three weeks post-trauma. Presentation of trauma-paired cues caused further decrement in working memory performance. Regression analysis indicates that the degree of working memory impairment in response to a trauma-paired cue can be significantly predicted by behavioral phenotypes typic of diagnostic symptoms for posttraumatic stress disorder. This study enhances existing animal models by replicating the clinical observations of working memory deficits associated with posttraumatic stress disorder. This will pave the way for future work to probe underlying mechanistic dysregulation of working memory following trauma exposure and for future development of novel treatment strategies. </p>

Theoretical background: Considerable progress has been made in illuminating the neural basis of the compulsive use patterns characterizing substance use disorders. It has been suggested to utilize these findings to alleviate the health burden associated with substance use. Objective: We address how neuroimaging research can provide these benefits. Methods: Based on neurobiological models of addiction, we highlight neuroimaging research elucidating neural predictors of relapse and how treatments modify these markers. Results: With the focus on cue reactivity, brain activity related to the motivational salience of drugs and automatized use behaviors can predict relapse. Cue reactivity changes with abstinence, and it remains to be determined whether such changes confer periods of critical relapse susceptibility. Conclusions: Several established and emerging interventions modulate brain activity associated with drug value. However, executive deficits in addiction may compromise interventions targeting control-related prefrontal brain areas. Lastly, it remains more difficult to change the brain responses mediating habitual behaviors. / Theoretischer Hintergrund: Es wurden beträchtliche Fortschritte im Verständnis der neuronalen Grundlagen der für Substanzkonsumstörungen charakteristischen kompulsiven Konsummuster erzielt. Diese Erkenntnisse könnten genutzt werden, um die mit dem Substanzkonsum verbundene gesundheitliche Belastung zu mindern. Fragestellung: Wir untersuchen, wie neurobiologische Forschung zu diesem Ziel beitragen kann. Methoden: Basierend auf neurobiologischen Modellen der Sucht beleuchten wir Arbeiten, die neuronale Prädiktoren von Rückfallen identifizieren und zeigen, wie Interventionen diese Marker verändern. Ergebnisse: Es zeigt sich, dass Cue Reactivität im Zusammenhang mit der motivationalen Bedeutung von Drogen und automatisiertem Konsumverhalten Rückfalle vorhersagen kann. Cue Reactivität verändert sich mit Abstinenz, und es bleibt zu klären, ob solche Veränderungen die Rückfallanfälligkeit beeinflussen. Schlussfolgerungen: Mehrere etablierte und neuere Interventionen modulieren Gehirnaktivität, die mit dem Anreizwert von Drogen assoziiert ist. Exekutivdefizite könnten die Wirkung von Interventionen beeinträchtigen, welche die Nutzung kontrollrelevanter präfrontaler Hirnareale erfordern. Schließlich ist es nach wie vor schwieriger Gehirnaktivität zu verändern, die habituelle Verhaltensweisen mediiert.

Le craving est considéré comme une composante centrale de l’addiction, potentiellement impliquée dans les processus de rechute, et influencée par de nombreux facteurs. Les études ayant examiné le lien entre craving et rechute montrent cependant des résultats contradictoires. Ces divergences pourraient s’expliquer par les limites méthodologiques rencontrées pour évaluer le craving de façon rétrospective ou pour l’induire expérimentalement en laboratoire. La méthode EMA (Ecological Momentary Assessment) utilise des technologies mobiles afin d’évaluer les sujets dans leur environnement naturel et de récolter des données en temps réel. Cette approche est particulièrement intéressante pour étudier les fluctuations rapides du craving, capturer l’influence des variables environnementales, ainsi que pour examiner le lien prospectif entre plusieurs variables. L’objectif général de cette thèse était d’utiliser la méthode EMA afin d’examiner en vie quotidienne le craving, ses modérateurs, et son lien avec l’usage de substances chez des sujets dépendants débutant une prise en charge pour une addiction à une substance. L’analyse de la littérature révèle que la majorité des études EMA examinant le craving concerne le tabac et l’alcool, et que peu d’études ont examiné ce phénomène pour des substances illégales. La partie expérimentale de cette thèse a permis de 1) démontrer la faisabilité et la validité de la méthode EMA chez des sujets dépendants, quelle que soit la substance de dépendance (tabac, alcool, cannabis ou opiacés), 2) montrer un lien prospectif unidirectionnel entre l’intensité du craving et l’usage de substances pour les 4 groupes de substances, et 3) mettre en évidence une augmentation du craving face à des stimuli conditionnés (cues) rencontrés en vie quotidienne, augmentation d’autant plus importante qu’il s’agissait de cues individuels (personnels à chaque sujet). Cette étude démontre l’intérêt de la méthode EMA dans l’étude des addictions, souligne le rôle du craving dans les processus de rechute, et encourage le développement de protocoles d’extinction de la réactivité aux cues centrés sur des cues individuels propres à chaque sujet. / Craving is a central component of addiction, involved in relapse process and under the influence of many factors. However, studies examining the link between craving and relapse have revealed some contradictory results. These inconsistencies could be due to limits encountered to assess craving in laboratory or clinical settings. Ecological Momentary Assessment (EMA) methods use mobile technologies to assess subjects in their daily life, and collect data in real time. EMA is particularly well suited to assess fluctuations of craving, capture influence of environmental moderators, and examine prospective link between variables. The objective of this thesis was to use EMA to examine craving, its moderators, and its link with substance use in daily life among substance-dependent outpatients evaluated at treatment intake. Review of the literature revealed that majority of EMA studies examining craving concerned tobacco and alcohol, but only few examined illegal substances. The experimental part of this thesis 1) demonstrated that EMA methods are feasible and provide valid data in individuals with dependence for different types of substances (tobacco, alcohol, cannabis, opiates), 2) showed a prospective unidirectional association between craving and subsequent substance use in the 4 groups of substances, and 3) confirmed that conditioned stimuli (cues) encountered in daily life are associated with an increase of craving intensity, and showed that individual personalized cues elicit a more robust effect on craving compared to standard cues. These results highlight the relevance of using EMA methods to study addiction, suggest that craving has a key place in the relapse process, and encourage to develop tailorised extinction protocols centered on individual cues rather than standard non-specific cues.