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Despite the fact that more men are diagnosed with substance use disorder, women escalate their drug consumption faster, exhibit higher craving during withdrawal, and have poorer treatment outcomes. Furthermore, as our cultural expectations of men and women have changed, there has been an increase in drug use in women and this increase is likely to persist. Preclinically, female rodents show stronger behavioral responses to drugs of abuse during initiation, escalation, and reinstatement of drug seeking. These behavioral differences are accompanied by alterations in structural plasticity within the mesocorticolimbic reward system. However, little is known about what functional sex differences exist in glutamate transmission in these circuits. The goal of these experiments was to determine functional sex differences in reward circuitry that may underlie behavioral sex differences in substance use disorder. We found heightened glutamate transmission in both the medial prefrontal cortex and nucleus accumbens in females compared to males. These findings corresponded with the nucleus accumbens being less plastic in females. We then investigated the role of PKMζ, a glutamatergic AMPA receptor trafficking protein, in plasticity and opioid-taking. We found PKMζ plays a role in synaptic plasticity within the nucleus accumbens and it works to blunt oxycodone-taking and motivation in a dose-dependent manner. Taken together these findings suggest there are functional sex differences at many levels within the reward system and gaining a better understanding of these differences could provide insight into improved treatments for substance use disorder. / Psychology

Bakgrund: Beroendeproblematik är kostsamt för individ, familj och samhälle. I Sverige erbjuds psykologisk och psykosocial behandling vid beroendeproblematik vilket ofta kombineras med motiverande samtal och/eller läkemedelsbehandling. Flera systematiska litteraturöversikter visar studier med positiva effekter och rekommenderar fysisk aktivitet som del i behandling vid beroendeproblematik. Studier saknas dock där fysisk aktivitet och beroendeproblematik undersöks i svensk kontext. Förhoppningen var att studien kunde bidra med information till nytta vid framtida utformning av genomförbar, godtagbar och hållbar intervention med fysisk aktivitet inom svensk öppenvård. Syfte: Beskriva upplevelser, tankar och känslor kopplade till fysisk aktivitet hos personer deltagande i Luleå kommuns öppenvård för beroendeproblematik. Metod: Studien utfördes med kvalitativ ansats och sju deltagare med pågående öppenvårdsinsats rekryterades genom ändamålsenligt urval. Data samlades genom semistrukturerade intervjuer och analyserades med kvalitativ innehållsanalys. Resultat: Två kategorier framkom med tre subkategorier vardera. Första kategorin ”Från fysisk aktivitet till inaktivitet” innehöll subkategorierna ”Att röra sig, sporta och idrotta främjar social delaktighet och hälsa”, ”Fysisk aktivitet har biopsykosociala effekter” samt ”Beroende kan leda till en negativ spiral av inaktivitet”. Den andra kategorin ”Mod att skifta perspektiv” innehöll subkategorierna ”Tankar och känslor påverkar deltagande i fysisk aktivitet”, ”Att se motgångar eller möjligheter i relation till fysisk aktivitet” och ”Att vidmakthålla deltagande i fysisk aktivitet”. Slutsats: Den första kategorin beskriver hur deltagarna tidigt i livet varit delaktiga i fysisk aktivitet. Senare i deras liv minskade delaktigheten i fysisk aktivitet samtidigt som beroendet ökade och tog över deras intresse vilket ledde till inaktivitet. Den andra kategorin beskriver olika hinder samt hur inställningen till hinder, fysiska aktiviteter och sig själv är avgörande för tolkningen och delaktigheten i fysisk aktivitet. Förutom inställningen beskrevs att gå emot känslor, ett personligt ansvarstagande och önskan att utvecklas som viktiga för att bibehålla delaktighet i fysisk aktivitet. Mer studier behövs som undersöker godtagbarhet och genomförbarhet av fysisk aktivitet samt dess effekter för personer med beroendeproblematik i Sverige. / Background: Addiction is a costly condition for the individual, their family, and the society. In Sweden, psychological and psychosocial treatment is offered to people suffering from addiction which is often also combined with motivational interviewing and/or medical treatment. Several systematic literature reviews show studies with positive effects and recommend physical activity as part of treatment for addiction. There are no studies that examine the effects of physical activity on people with addiction in a Swedish context. The study was anticipated to contribute useful information when designing a feasible, acceptable, and sustainable intervention with physical activity in Swedish outpatient care. Purpose: Describe experiences, thoughts and feelings linked to physical activity in people participating in Luleå municipality's outpatient care for addiction. Method: The study was carried out with a qualitative approach and seven participants with ongoing outpatient care were recruited through purposeful sampling. Data were collected through semi-structured interviews and analyzed using qualitative content analysis. Results: Two categories emerged with three subcategories each. The first category "From physical activity to inactivity" contained the subcategories "To move, take part in athletics and play sports promote social participation and health", "Physical activity has biopsychosocial effects" and "Addiction can lead to a negative spiral of inactivity". The second category "Courage to shift perspectives" contained the subcategories "Thoughts and feelings affect participation in physical activity", "Seeing setbacks or opportunities in relation to physical activity" and "Sustaining participation in physical activity". Conclusion: The first category describes how the participants early in life were involved in physical activity. Later in life, participation in physical activity decreased while drug dependence increased and became their main interest, leading to inactivity. The second category describes various obstacles and how the attitude towards those obstacles, physical activities and oneself is decisive for the interpretation and participation in physical activity. In addition to the attitude, to go against emotions, taking personal responsibility and the desire to develop were described as important for maintaining participation in physical activity. More studies are needed that examine the acceptability and feasibility of physical activity and its effects on people with addiction in Sweden.

Bipolar spectrum disorders (BSDs) and substance use disorders (SUDs) are highly co-occurring and both are associated with dysfunction in neural networks that mediate reward processing and motivated behavior. Furthermore, despite their high comorbidity rate, limited research into their shared neural mechanisms or potential prospective risk factors exists. This study attempted to elucidate common neural pathways for these disorders, and adds to the small but growing literature on possible prospective predictors of these disorders. We employed a task-based functional magnetic resonance imaging (fMRI) study to examine regions-of-interest (ventral striatum [VS], orbitofrontal cortex [OFC], ventromedial prefrontal cortex [vmPFC], dorsolateral prefrontal cortex [dlPFC]) and connectivity (VS-OFC, VS-vmPFC, vmPFC-dlPFC) analyses to examine neural reward processing as potential predictors of future substance and mood symptoms, and to explore differences among groups of participants with and without BSDs and SUDs. Results from this study provided evidence that blunted activation in the VS and dlPFC and greater negative connectivity between the vmPFC and dlPFC, key reward and control circuits, is implicated in prospective substance use. However, we did not find evidence to support our hypothesis that reward-related neural responses predict BSD symptoms or could differentiate individuals with co-occurring BSDs and SUDs from healthy volunteers. The study highlights the importance of larger, longitudinal studies to more fully probe neurodevelopmental trajectories in mood, substance, and related disorders. We also conducted an extensive review of the neural reward literature in BSDs and SUDs to understand possible pre-existent mechanisms. Results of the review provided support for an equifinality/multifinality perspective in that similar neural reward processing dysfunctions can lead to both BSDs and SUDs and different neural reward processing abnormalities can lead to a single outcome (e.g., SUDs). Taken together, results from the dissertation address an important gap in the literature on BSD-SUD comorbidity, suggest possible shared mechanisms that predispose to both disorders, and provide a backdrop for future work in this area to inform more theoretically-targeted interventions and prevention. / Psychology

Nearly 50% of Americans will meet the diagnostic criteria of some form of mental illness in their lifetime (Mehta & Edwards, 2018). However, only 40% of these individuals will seek treatment for them. Patients with mental illness have a lifespan that is, on average, 25 years shorter than individuals without mental illness and are at 2-3 times the risk of diabetes, heart, and lung disease than the average population but do not receive adequate treatment at a proportionate rate. As a country, there are very negative stereotypes held towards individuals struggling with mental illness and substance use disorders even though they are among the most common conditions in the population. This stigma against mental illness often prevents individuals from seeking care for their symptoms and causes medical providers to treat patients with mental illness differently than those without them. Stigma can be seen in the way providers speak about patients with mental illness, the way the medical record labels patients with mental illness, and even how health care providers themselves fail to seek treatment when suffering from mental illness themselves. This thesis examines the types of stigmas that exist, describes how it interferes with clinical care and causes adverse clinical outcomes for patients with mental illness and substance use disorders and provides recommendations for improving the treatment of individuals with mental illness and the importance of normalizing talking about mental illness. / Urban Bioethics