Bipolar disorders (BD) are characterized by symptoms of grandiosity, decreased need for sleep, pressure to keep talking, flight of ideas, distractibility, increased goal-directed activities, psychomotor agitation, and excessive involvement in pleasurable activities. Those with a bipolar disorder have a high degree of psychiatric comorbidity including substance use disorders, and they also experience increased mortality. Despite the widespread recognition of BD as an important psychiatric condition, available population-based estimates for BD prevalence differs across data sources. Cannabis is one of the most widely-used illicit substances. Evidence supports it as a risk factor for psychotic symptoms and disorders. Because populations with psychotic disorders and populations with bipolar disorder share genetic characteristics, cannabis may increase risk for bipolar disorders through the same pathways as it does with psychotic disorders. Limited and conflicting evidence regarding the association of cannabis use and bipolar disorder is currently available. This dissertation investigates cannabis use as a risk factor for incident manic symptoms and bipolar disorders in a large nationally representative longitudinal cohort. The first aim of this dissertation is to evaluate the implications for manic, hypomanic and major depressive episode prevalence estimates arising from the different approaches to assessing DSM-IV criterion between two national surveys. Differences in the assessment of impairment strongly influence manic or hypomanic classification within the NESARC. Compared to multiple imputation estimates (19.7% [95% CI: 19.3-20.1]) which treat depressed mood and anhedonia as separate symptoms, symptom assessment in the NESARC substantially underestimates major depressive episode prevalence (16.9% [95% CI: 16.1-17.6]). The second research objective examined self-reported cannabis use as a risk factor for incident manic symptoms, bipolar spectrum disorders (including manic and hypomanic episodes) and SCID-based recalibrated BD I and II. Cannabis use risk was assessed in the population as a whole and in sub-populations defined by age, substance abuse/dependence status, and family history. Among those reporting no lifetime major depressive or manic symptoms at baseline, self-reported past-year cannabis use was associated with increased odds of an incident week of extremely elevated or irritable mood accompanied by at least two manic episode criterion B symptoms (adj. OR 1.69, 95% CI: 1.08-2.65, p=.02) over the three year follow-up period. Among adults (ages 26 to 45) >=1 reported use(s) of cannabis per week was associated with incident manic or hypomanic episodes (adjusted OR 2.52, 95% CI: 1.32-4.80, p=.006). Among those endorsing no major depressive symptoms, substance abuse/dependence, or anti-social traits in their first degree relatives, past year cannabis use is associated with increased risk for incident bipolar spectrum disorders (adjusted OR 2.27, 95% CI: 1.01-5.10, p=.05) and CIDI recalibrated BD I and II (adjusted OR 5.49, 95% CI: 1.38-21.9, p=.02). Past year cannabis use risk for DSM-IV manic or hypomanic episodes among those aged 26 to 45 is concentrated in those with a baseline history of a substance use disorder (adj. OR 2.00, 95% CI: 1.10-3.66, p=.02) as compared to those with no such history (adj. OR 1.87, 95% CI: 0.49-7.21, p=.36). The third research objective of this dissertation was a sensitivity analysis using externally-predicted categorized exposures and continuous cannabis use propensities. The sensitivity analysis found evidence of exposure misclassification. Exposures defined by external propensity scores had improved cross-sectional association with bipolar spectrum disorders compared to reported use when both were compared to an external standard. No significant risk estimates were found for categorized predicted cannabis use among groups that were previously found to have significant risk from reported exposure. However, among adults 18 to 45 years of age with no manic or major depressive symptoms at baseline, past year cannabis use propensity (as a log transformed continuous measure) was associated with incident manic or hypomanic episodes (adj. OR 1.49, 95% CI: 1.10-2.03, p=.01). Elevated risk for high cannabis use propensity (>=1 use/week in the past year) was also found in this same group (adj. OR 1.33, 95% CI: 1.03-1.72, p=.03). Among those with no reported history of depression, substance abuse/dependence, or anti-social traits among their first-degree relatives, propensity for past year cannabis use (adj. OR 1.61, 95% CI: 1.11-2.32, p=.01) and propensity for >=1 use/week of cannabis in the past year (adj. OR 1.38, 95% CI: 1.03-1.85, p=.03) were associated with incident manic or hypomanic episodes. Among those without a substance use history at baseline, propensity for past year cannabis use (adj. OR 1.63, 95% CI: 1.33-1.55, p=1 use/week of cannabis in the past year (adj. OR 1.54, 95% CI: 1.26-1.88, p The findings of the first aim support the conclusion that the AUDADIS substantially under-estimated lifetime major depressive episode prevalence compared to an imputed estimate that treated anhedonia and depressed mood as separate and concurrent MDE symptoms. The operationalization of impairment for manic disorders in both the AUDADIS and CIDI strongly influences case identification, with the CIDI having suppressed manic and hypomanic prevalence estimates. Evidence was found supporting the conclusion that self-reported cannabis use is a significant risk factor for incident bipolar spectrum outcomes within subpopulations in a nationally representative cohort. A sensitivity analysis finds evidence that supports the conclusion that increasing cannabis use propensity is associated with increased risk of bipolar spectrum outcomes within population subgroups, with the greatest increased risk among those with the lowest innate risk. Under-reporting of illicit substance use is a major limitation in this dissertation; further study is needed with improved exposure measures.

Chronic intake of alcohol can result in a range of pathology in the liver. Whilst the earliest changes observed with chronic ethanol, including the accumulation of lipid, or steatosis, are readily reversible upon cessation of alcohol consumption, longer exposure to ethanol may achieve more complex disease states including steatohepatitis, fibrosis, and cirrhosis that can cause irreversible damage and progress to fulminant hepatic failure. A key concept in the pathogenesis of alcoholic liver disease is that chronic ethanol primes the liver to increased injury through an interplay between hepatocytes and non-parenchymal cells, chiefly immune cells, of the liver. These relationships between hepatocytes and non-parenchymal cell types in alcoholic liver disease are reviewed in Chapter 1A. The Hypoxia Inducible Factors are a set of transcription factors that classically have been described as affecting a homeostatic response to conditions of low oxygen tension. Alcoholic liver disease is marked by increased hepatic metabolic demands, and some evidence exists for increased hepatic tissue hypoxia and upregulation of hypoxia-inducible factor mRNA with chronic alcohol. However, the biological significance of these findings is unknown. In Chapter 1B, we review the literature on recent investigations on the role of hypoxia inducible factors in a broad array of liver diseases, seeking to find common themes of biological function. In subsequent chapters, we investigate the hypothesis that a member of the hypoxia inducible- factor family, HIF1α, has a role in the pathogenesis of alcoholic liver disease. In Chapter 2, we establish a mouse model of alcoholic liver disease and report data confirming HIF1α activation with chronic ethanol. We demonstrate that HIF1α protein, mRNA, and DNA binding activity is upregulated in ethanol-fed mice versus pair-fed mice, and that some upregulation of HIF2α protein is observable as well. In Chapter 3, we utilize a mouse model of hepatocyte-specific HIF1α activation and demonstrate that such mice have exacerbated liver injury, including greater triglyceride accumulation than control mice. Using cre-lox technology, we introduce a degradation resistant mutant of HIF1α in hepatocytes, and after four weeks of ethanol feeding, we demonstrate that mice with the HIF1α transgene have increased liver-weight to body weight ratio and higher hepatic triglyceride levels. Additionally, several HIF1α target genes are upregulated. In Chapter 4, we examine the relationship between HIF1α activation and hepatic lipid accumulation using a recently published in vitro system, in which lipid accumulation was observed after treating Huh7 cells with the chemokine Monocyte Chemoattractant Protein-1 (MCP-1). We report that MCP-1 treatment induces HIF1α nuclear protein accumulation, that HIF1α overexpression in Huh7 cells induces lipid accumulation, and finally, that HIF1α siRNA prevents MCP-1 induced lipid accumulation. In Chapter 5, we use mouse models to investigate the hypothesis that suppression of HIF1α in hepatocytes or cells of the myeloid lineage may have differing effects on the pathogenesis of alcoholic liver disease. We find that ethanol-fed mice expressing a hepatocyte-specific HIF1α deletion mutant exhibit less elevation in liver-weight body ratio and diminished hepatic triglycerides versus wild-type mice; furthermore, we find that challenging these mice with lipopolysaccharide (LPS) results in less liver enzyme elevation and inflammatory cytokine secretion than in wild-type mice. In Chapter 6, we offer a final summary of our findings and some directions for future work.

Background Herbal marijuana alternatives (HMA), legal plant products adulterated with synthetic cannabinoid receptor agonists, represent a growing public health concern. Only a few case reports describe HMA and synthetic cannabinoid’s clinical toxicity. We describe an outbreak of HMA abuse primarily in the Midwest, the clinical presentation of HMA toxicity, and clinical and forensic testing. Methods During the course of ongoing surveillance for emerging drugs of abuse between November 2009 and August 2010, we retrospectively and prospectively identified a convenience sample comprising 81 cases of abuse of HMA products. Subject demographics, vital signs, lab results and urine were obtained (when available) and tested via gas chromatography mass spectrometry (GCMS) analysis. Samples of HMAs and synthetic cannabinoids were also analyzed via GCMS. Results HMA users were predominantly young males who inhaled HMAs. Analysis of their urine detected synthetic cannabinoid parent compound in one subject. GCMS analysis of synthetic cannabinoids established a reference library that confirmed the presence of synthetic cannabinoids in sampled HMA products. Conclusion HMA products were available in head shops, gas stations, and via the Internet. We have confirmed the presence of synthetic cannabinoids in these HMA products. The tachycardia, hypertension, agitation, anxiety, vomiting and hallucinations observed in this convenience sample are not readily explained by the presence of synthetic cannabinoids acting on CB1 and CB2 receptors. Further research must be done on HMA products and their abusers.

First responders, especially law enforcement, frequently encounter individuals experiencing substance use concerns. Previous research has documented that a greater understanding of substance use disorders promotes a decrease in stigmatizing perspectives. We present a novel approach to training law enforcement officers to improve their interactions with community members exhibiting substance use disorders, while also promoting their professional well-being. The present study sought to evaluate the feasibility and acceptability of the Stigma Reduction and Resiliency Training for First Responders (SRRT-FR) in a sample of law enforcement officers, as well as its efficacy in decreasing stigmatizing perspectives towards substance use disorders and increasing professional resiliency. One hundred and ten law enforcement officers participated in SRRT-FR and completed pre-, post- (n = 77), and four-month follow-up (n = 42) surveys that assessed their perceptions towards individuals with substance use disorders, as well as their well-being within their profession. Preliminary results suggest that SRRT-FR is feasible and acceptable amongst officers and may decrease some stigmatizing perspectives and increase resiliency. The findings warrant replication with larger sample sizes and randomized controlled trials involving law enforcement officers, as well as other first responders.

Bakgrund: Psykisk ohälsa förekommer i alla åldrar och är ett växande problem. Animal Assisted Therapy (AAT) är en målinriktad, planlagd och strukturerad terapeutisk insats som leds eller utförs av personal inom hälso- och sjukvård, skola eller omsorg. Inom hälso- och sjukvården syftar AAT till att förbättra individens psykiska, fysiska, emotionella och kognitiva förmågor. Syfte: Att kartlägga effekter avseende ångest hos vuxna personer med psykisk ohälsa som genomgår Animal Assisted Therapy. Metod: Litteraturstudien baseras på åtta empiriska interventionsstudier med kvantitativ design. Databassökningar genomfördes i Cinahl, PubMed och PsycInfo. Analysprocessen genomfördes enligt Popenoes analysmodell. Resultat: Samtliga studier resulterade i en minskning avseende ångest. Sex av studierna visade en signifikant minskning inom gruppen som fått AAT och två studier visade en positiv effekt men utan signifikant skillnad. Två studier visade en signifikant skillnad mellan interventions- och kontrollgruppen.  Konklusion: Litteraturstudiens resultat visade att AAT kan reducera ångest hos individer med psykisk ohälsa och kan därför vara ett bra komplement i omvårdnaden hos denna patientgrupp. Ytterligare forskning behövs för att kartlägga hur effektivt AAT är jämfört med befintliga behandlingar. / Background: Mental illness occurs at all ages and is a growing problem. Animal Assisted Therapy (AAT) is a targeted, planned and structured therapeutic intervention led or performed by staff in health care, school or care. Animal Assisted Therapy aims in healthcare to improve the individual's mental, physical, emotional and cognitive abilities. Aim: To map the effects regarding anxiety in adults with mental illness who undergo Animal Assisted Therapy.  Methods: The literature review is based on eight empirical intervention studies with quantitative design. Database search was conducted in Cinahl, PubMed and PsycInfo. The analysis process was carried out according to Popenoe´s analysis model. Results: All studies resulted in decreased anxiety-levels. Six of the studies showed a significant difference within the group that received AAT and two studies showed a positive effect but without a significant difference. Two studies showed a significant difference between the intervention and control groups. Conclusion: The results of the literature study showed that AAT can reduce anxiety in individuals with mental illness and could therefore be a good complement to the care of this patient group. Further research is needed to map how effective AAT is compared to existing treatments.

Problemformulering: En av de vanligaste orsakerna till sjukskrivning i Sverige är psykiatriska diagnoser såsom depressioner och stressreaktioner. Sjukfrånvaro innebär stora kostnader både för arbetsgivare och för samhället, och är på olika sätt drabbande även för den som är sjukskriven. Det finns därmed goda skäl att undersöka olika sätt på vilka rehabiliteringsprocessen kan förbättras och göra återgången i arbete enklare. Tidigare forskning har visat att det finns ett flertal faktorer som går att förändra för att förbättra möjligheterna till återgång i arbete, såsom bättre kommunikation och bättre samordning av rehabiliteringsinsatserna. Få studier har dock undersökt hur tidigare sjukskrivna upplevt rehabiliteringsprocessen i sin helhet, från första sjukskrivningsdag till och med återgång i arbete. Syfte: Syftet med denna studie var att undersöka upplevelsen av rehabiliteringsprocessen, bland offentligt anställda i Sverige som tidigare varit sjukskrivna i psykiatriska diagnoser. Metod: Studien hade en kvalitativ design, och för att samla in data användes semistrukturerade intervjuer, vilka analyserades med hjälp av kvalitativ innehållsanalys. Deltagarna bestod av tio kvinnor som arbetade inom offentlig sektor i Sverige, hade varit sjukskrivna på 100 procent i en psykiatrisk diagnos i minst en månad samt återgått fullt i arbete. Resultat: Resultatet visade att upplevelsen av rehabiliteringsprocessen var att den förändrar en som person, att den innebär sårbarhet och att därför är viktigt med bra bemötande, tillräckliga anpassningar och en fungerande struktur kring rehabiliteringsprocessen där den sjukskrivne själv involveras utan att behöva vara ansvarig. Slutsats: Utifrån studiedeltagarnas upplevelser verkar det finnas behov av ett tydligare ramverk kring rehabiliteringsprocessen, tydligare ansvarsfördelning och vägledning till individen. Med kunskap om hur rehabiliteringsprocessen upplevs och vilka delar av processen som exempelvis anses bristfälliga, kan också förbättringar göras vilket i sin tur kan göra återgången i arbete mer hälsosam och hållbar. / Aim: The aim of this study was to examine the experience of the rehabilitation process, among Swedish public employees, who had returned to work after sick leave due to common mental disorders. Method: To examine this, qualitative method was used. To collect data, semi-structured interviews was carried out and then analyzed with qualitative content analysis. Ten women participated in the study. They were employed in the public sector in Sweden and had returned to work after being on full time sick leave. Result: The analysis resulted in six categories. Summarized, the experience of the rehabilitation process was being changed as a person, feeling vulnerable, and consequently, the importance of good treatment, appropriate work adaptations, and a functioning structure around the rehabilitation process, where the person going through rehabilitation is involved without having to be responsible. Conclusion: Based on the experiences of the study participants, there seems to be a need for a clearer framework for the rehabilitation process, clearer division of responsibilities and guidance for the individual. With knowledge of how the rehabilitation process is experienced, and of facilitating and hindering factors, improvements can be made.

Syftet med denna uppsats är att ta reda på hur fem olika personer med OCD upplever framställningen av OCD i komediserien Scrubs samt dramafilmen The Aviator. Vidare togs det reda på varför intervjupersonerna upplever dessa framställningar som de gör och på vilka sätt de kan identifiera sig med dem. Studiens teoretiska ramverk är representationsteori, kodning och avkodning samt självkategoriseringsteori. Uppsatsens material består av kvalitativa intervjuer med fem olika intervjupersoner som alla har diagnosen OCD. Inför besvarandet av intervjufrågorna har intervjupersonerna tittat på avsnitt från Scrubs samt på filmen The Aviator där karaktärer med OCD finns med. Resultatet visar att fyra av fem intervjupersoner kan identifiera sig med fysiska tvångshandlingar som karaktären med OCD i Scrubs utför. Framställningen av OCD i The Aviator kan samtliga fem intervjupersoner identifiera sig med där majoriteten av dem identifierar sig i känslostämningen i form av stress, frustration och ångest som huvudkaraktären med OCD bitvis uppvisar. Den första slutsatsen är att intervjupersonerna upplever en mer adekvat framställning av OCD i The Aviator än i Scrubs, då framställningen i The Aviator innefattar en betydligt större del av det psykiska och känslomässiga lidande som OCD innebär. Den andra slutsatsen är att intervjupersonernas inställning till hur OCD framställs i Scrubs och The Aviator är beroende av den utsträckning i vilken de kan identifiera sig med detta.

Objective:The present study examined mothers’ emotion socialization of 3-year–old children with behavior problems, to determine whether emotion socialization practices, as well as the relation between these practices and child functioning, varied across ethnicities. Method: Participants were 156 preschoolers with behavior problems. Mothers were European American (n = 98), Latina American (n = 40; predominately Puerto Rican), and African American (n = 18). Audio taped mother-child interactions were coded for emotion socialization behaviors. Results: Overall, this study provided evidence for both differences and similarities across ethnicities on parental emotion socialization practices. Ethnic differences in use of emotion socialization practices were only found for mothers’ emotion focused reactions, minimizing reactions, and non-responses to negative affect. However, ethnic differences emerged in the relations between emotion socialization practices and child functioning. Several emotion socialization parental behaviors were differentially related to current child internalizing and externalizing problems across ethnic groups. Conclusions: Results provide some support for the existence of cultural differences in emotion socialization practices and their associated child outcomes.

Training delivered to medical students and residents in behavioral health is widely acknowledged to be inadequate. While the use of standardized patients is common in medical training and education for physical health conditions via the adherence to clinical protocols for evaluation and treatment, this approach is infrequently used for behavioral health conditions. Used under specific circumstances, standardized patient encounters have long been considered a reliable method of training and assessing trainee performance on addressing physical health conditions, and are even comparable to ratings of directly observed encounters with real patients. This paper discusses common issues and challenges that arise in using standardized patients in behavioral health. Although current evidence of its value is modest and challenges in implementation exist, the use of standardized patients holds promise for medical training and education and as an evaluation tool in behavioral health.

Despite a mandated 1-month rotation in developmental-behavioral pediatrics (DBP), pediatric residents report inadequate training in behavioral health care. As a first step in much needed curriculum development in this area, this study sought to assess learner experiences regarding the management of behavioral health problems during residency. Four focus groups were conducted for residents in years 1-3 of training in 2 residency programs in a northeastern state. Transcripts were analyzed and coded by researchers through qualitative classical content analysis. The exploratory analysis revealed 9 key themes: time requirements, rapport building, resources and referrals for behavioral health, psychiatric medications, diagnosis vs. treatment, working with families, the importance of behavioral health, fears of working with a pediatric population, and training issues. These qualitative data further identify gaps in the behavioral health training of pediatric residents and may inform future innovations in training curricula.