<b>Study 1:</b><div><b>Background:</b> Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. <b>Methods:</b> We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people living with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, “Difficulty falling or staying asleep?,” with the following response options: “I do not have this symptom” or “I have this symptom and…” “it doesn’t bother me,” “it bothers me a little,” “it bothers me,” “it bothers me a lot.” Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (<i>CI</i>). <b>Results:</b> For sCD14 and D-dimer, we observed no significant associations. For IL-6, veterans in the “bothers a lot” group had 15% higher IL-6 than veterans in the “I do not have this symptom” group in the demographic-adjusted model (exp[b]=1.15, 95%<i>CI</i>=1.02-1.29, <i>p</i>=.03). This association was nonsignificant in the fully-adjusted model (exp[b]=1.07, 95%<i>CI</i>=0.95-1.19, <i>p</i>=.25). <b>Conclusion:</b> We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.</div><div><p><b>Study 2:</b></p><p><b>Background:</b> While insomnia has been identified as a potential risk factor for cardiovascular disease in HIV (HIV-CVD), research on the underlying pathophysiological mechanisms is scarce. <b>Methods:</b> We examined associations between 0-to-12-week changes in sleep disturbance and the concurrent 0-to-12-week changes and the subsequent 12-to-24-week changes in markers of systemic inflammation, coagulation, and endothelial dysfunction among people living with HIV (<i>n</i> = 33-38) enrolled in a depression clinical trial. Sleep disturbance was measured using the Pittsburgh Sleep Quality Index. Inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) and coagulation marker D-dimer were determined from blood specimens; endothelial dysfunction marker brachial flow-mediated dilation (FMD) was determined by ultrasound. 0-to-12-week variables were calculated as 12-week visit minus baseline, and 12-to-24-week variables were calculated as 24-week minus 12-week. We constructed multivariate linear regression models for each outcome adjusting for age, sex, race/ethnicity, Framingham risk score, and baseline depressive symptoms. <b>Results:</b> We did not observe statistically significant associations between 0-to-12-week changes in sleep disturbance and 0-to-12-week or 12-to-24-week changes in IL-6, CRP, D-dimer, or FMD. However, we did observe potentially meaningful associations, likely undetected due to low power. For 0-to-12-weeks, every 1-standard deviation (<i>SD</i>) increase, or worsening, in the sleep disturbance change score was associated with a 0.41 pg/mL and 80 ng/mL decease in IL-6 and D-dimer, respectively. For 12-to-24-weeks, every 1-<i>SD</i> increase in sleep disturbance change score was associated with a 0.63 mg/L, 111 ng/mL, and 0.82% increase in CRP, D-dimer, and FMD, respectively. <b>Conclusion:</b> We observed potentially meaningful, though not statistically significant, associations between changes in sleep disturbance and changes in biological mechanisms underlying HIV-CVD over time. Some associations were in the expected direction, but others were not. Additional studies are needed that utilize larger samples and validated, comprehensive assessments of insomnia.</p></div>

Tidigare forskning pekar på att det kan finnas samband mellan vissa psykologiska faktorer och utveckling av depression och ångest. Därför var syftet med denna studie att undersöka huruvida olika psykologiska faktorer påverkar risken att utveckla depression samt ångest vid en uppföljning efter tre år. Studien baserades på data som insamlats vid det första (T1) och det andra (T2) mättillfället i den longitudinella populationsbaserade Miljöhälsostudien i Västerbotten. Samplen i denna undersökning bestod av deltagare som inte hade ångest (n=1930), och deltagare som inte hade depression (n=2120) vid T1. I studien undersöktes i vilken utsträckning upplevelse av utmattning, insomni, känsla av hjälp- och hopplöshet, stress, självskattad ohälsa, ångest och depression vid T1 ökade risken för depression respektive ångest vid T2. Logistiska regressionsanalyser visade på en signifikant ökad risk för att utveckla depression vid T2 (Oddskvot; OK=1.99-3.64) för samtliga riskfaktorer. Riskfaktorerna depression, utmattning, hjälp- och hopplöshet och självskattad ohälsa ökade risken för att utveckla ångest vid T2 signifikant (OK=2.37-3.78). Sammanfattningsvis visar resultaten att riskfaktorerna indikerar en i varierande grad ökad risk för att utveckla depression och ångest. Kännedom om riskfaktorer kan vara ett betydelsefullt stöd för att i ett tidigt skede sätta in interventioner och därmed förhindra senare insjuknande i depression och ångest. / Previous research suggests that there may be a link between certain psychological factors and development of depression and anxiety. The purpose of this study was therefore to investigate how different psychological factors affect the risk of developing depression and anxiety in a follow-up three years later. The study was based on data from baseline (T1) and follow-up (T2) in the Västerbotten Environmental Health Study, a longitudinal population- based study. The sample consisted of participants who did not have anxiety (n = 1930), and participants who did not have depression (n = 2120) at T1. The study examined the extent to which experience of exhaustion, insomnia, feelings of helplessness and hopelessness, stress, low self-rated health, anxiety and depression at T1 increased the risk of depression and anxiety at T2, respectively. Logistic regression analyses showed a significantly increased risk of developing depression at T2 (Odds ratio; OR = 1.99-3.64) for all risk factors. The risk factors depression, exhaustion, feelings of helplessness and hopelessness and low self-rated health significantly increased the risk of developing anxiety at T2 (OR = 2.37-3.78). In conclusion, the results show that the risk factors indicate a varying degree of increased risk of developing depression and anxiety. Knowledge of risk factors is important as support for initiating interventions at an early stage and thus preventing later onset of depression and anxiety.

Insomnia is one of the most common health issues, with occasional symptoms affecting up to 50% of the general population. Lack of sleep is associated with many negative health effects. A new evolutionary hypothesis has been proposed to explain the mechanism behind insomnia symptoms. The evolutionary-emotional hypothesis proposes that while acute insomnia might be advantageous from an evolutionary perspective, chronic insomnia is maladaptive and may follow from a failure or delay of fear extinction. The aim of the current thesis was to investigate which neural mechanisms might be at work if one is to consider the evolutionaryemotional hypothesis about the causes of insomnia plausible and to review studies from cognitive neuroscience to discover what support there might be for the hypothesis. Studies have found heightened activation in fear-related brain areas in insomnia patients. Delayed fear extinction and altered emotion regulation circuitry, among other things, were also observed for insomnia patients. However, few experimental studies on the effect of fear extinction on sleep in insomnia patients have been conducted. At this time, some emerging evidence lends support for the evolutionary-emotional hypothesis of insomnia, but more studies that directly assess fear conditioning and fear extinction processes in insomnia patients are needed to assess the explanatory power of the theory.

L’anxiété et l’insomnie représentent des affections parmi les plus répandues, avec plusieurs conséquences négatives pour les personnes qui en souffrent, leur famille et la société en général. Parmi les solutions les plus communément utilisées pour la prise en charge de l’anxiété et de l’insomnie, nous avons l’option pharmacologique qui, malgré une certaine efficacité initiale présente plusieurs conséquences à long terme comme la présence d’effets indésirables et l’installation progressive du phénomène de tolérance. Une autre possibilité thérapeutique est la psychothérapie et dans cette catégorie, le traitement de choix recommandé pour la solution à long terme de ces troubles est représenté par la thérapie cognitivo- comportementale. Mais, malheureusement, les ressources pour l’administrer sont limitées et couteuses et les temps d’attente sont souvent longs. Il a été alors question de trouver des alternatives pour permettre à plus de personnes souffrant d’anxiété et d’insomnie d’avoir accès rapidement à des solutions pour leur problème. C’est ainsi que notre réflexion s’est tournée vers les nouvelles technologies qui se sont répandues à grande échelle dans la population et qui montrent progressivement leur utilité pour remédier à la difficulté d’accès à certaines ressources traditionnelles dans la prise en charge de problématiques reliées à la santé mentale. Notre équipe, déjà impliquée dans le développement de plusieurs approches thérapeutiques par internet, a pris l’initiative de tester l’efficacité de l’application Muzzz, conçue pour réduire l’anxiété et améliorer le sommeil et qui consiste en l’écoute de suggestions positives inspirées du training autogène de Schultz. Ces suggestions ont la particularité d’être progressivement masquées par une musique relaxante et deviennent donc préconscientes. Muzzz est une dérivée du programme APAP (Augmentation de la Psychothérapie Par Amorçage Préconscient) dont le concept, basé sur l’écoute de suggestions positives personnalisées masquées par de la musique relaxante, a été évalué positivement en termes de validité et de faisabilité dans l’étude de Borgeat et collaborateurs réalisée en 2013 [augmentation des cognitions positives (d = 0,53) et diminution des cognitions négatives (d = 0,73) au Test d’Auto-Évaluation des Pensées en Interaction Sociale (TAPIS)]. Pour évaluer l’efficacité de l’application, 20 personnes (parmi lesquelles 10 hommes et 10 femmes, qui avaient un âge moyen de 41,25 ans, variant de 20 à 67 ans avec écart-type de 15,82) ont été recrutées dans les CLSC (centre local de services communautaires) Saint-Michel et Rosemont de la région de Montréal et ont été invitées à utiliser l’application pendant 4 semaines, dans un contexte de psychoéducation. Les effets ont été mesurés en les soumettant à l’index d’anxiété de Beck (mesure principale) ainsi qu’à l’index de sévérité de l’Insomnie et au questionnaire pour les inquiétudes du Penn State (mesures secondaires), respectivement au début de l’étude, puis après 2 et 4 semaines. L’anxiété, l’insomnie et les inquiétudes ont aussi été mesurées quotidiennement avec l’application Emax qui sert à recueillir les données en temps réel. Nous avons aussi évalué les processus cognitifs avec la mesure idiosyncratique de la conviction dans les pensées au début et à la fin de l’étude. Les résultats ont montré une réduction statistiquement significative de l’anxiété (d=0,78) au terme de la période d’intervention. Le même résultat a été observé avec les autres variables avec une amélioration de la qualité du sommeil (d=0,78) et une réduction des inquiétudes (d=0,77) toutes deux significatives. Une amélioration des cognitions, reflétée par la diminution significative des valeurs de la mesure idiosyncratique de la conviction dans les pensées (d=1,59), a aussi été observée. L’utilisation de l’application Muzzz dans un contexte de psychoéducation a montré son utilité pour soulager temporairement les symptômes de personnes souffrant d’anxiété et d’insomnie, dans l’attente de consulter un professionnel de la santé. Notre étude ne disposait que d’une faible taille d’échantillon. Ces résultats devraient donc être confirmés par d’autres études futures de plus grande ampleur. / Anxiety and insomnia are among the most common mental health disorders with negative consequences for patients, their families and society as a whole. Pharmacological treatment options with initial efficacy are available but are associated with unwanted side effects and tolerance in the longer term. Cognitive-behavioral therapy is a treatment of choice that provides an effective and longer-term solution, but availability is limited with long waiting-lists. Alternative effective options are needed to address the needs of all those suffering from anxiety and insomnia in a cost effective and timely manner. In particular, the development of new applications of technologies that are already widely used in the general population hold the potential to address the lack of access to traditional resources for those with mental health problems. Our team took the initiative to evaluate the efficacy of the Muzzz app, which consists of listening to positive suggestions inspired by Schultz's autogenic training., and is designed to reduce anxiety and to improve sleep These suggestions are masked by relaxing music and delivered in a subliminal format as a derivative of the APAP (Augmentation of Psychotherapy through Alternative Preconscious Priming) program. The APAP program developed by Borgeat et al. (2013) consists of listening of positive personalized suggestions masked by relaxing music, which has previously shown effectiveness in increasing positive cognitions (d = 0.53) and decreasing negative cognitions (d = 0.73). To assess the effectiveness of the Muzzz app and its application among those with anxiety and insomnia a total of 20 participants (10 men and 10 women were recruited at the Saint-Michel and Rosemont CLSCs (local community service centers) and invited to use the app for 4 weeks in a psychoeducational context. To measure the effects of the app they were administered the Beck Anxiety Inventory, the Insomnia Severity Index and the Penn State Worry Questionnaire at the beginning of the study and then at 2 and 4 weeks respectively. Anxiety, insomnia and worry was also assessed with the Emax app which is used to collect data in real time. In addition, change in cognitions were assessed with the Idiosyncratic Measure of Convictions in Thoughts at the beginning and at the end of the study. The results showed a statistically significant reduction in anxiety (d=0.78) at the end of the intervention period. In addition, there was a significant improvement in the quality of sleep (d=0.78) and reduction in worries (d=0.77). Finally, a significant improvement in cognitions was observed with the decrease in negative cognitions as assessed by the Idiosyncratic Measure of Convictions in Thoughts (d=1.59). We can therefore conclude that the use of the Muzzz app in a psychoeducational context is effective for temporarily relieving symptoms of people with anxiety and insomnia, while they are on waiting-list to see a healthcare professional. Results are limited by a relatively small size and await confirmation in future larger-scale studies.

博士(心理学) / Doctor of Philosophy in Psychology / 同志社大学 / Doshisha University

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Approximately 2-11% of adolescents report chronic insomnia. The study used an archival data set from ADDHealth that assessed adolescent health and health-related behaviors. Adolescents (N = 4102) provided data at baseline (Time 1) and at 1-year follow-up (Time 2). Participants were excluded if no ethnicity, gender, or insomnia data were given at Time 1 or 2. Females were more likely to report insomnia than males at Times 1 and 2. In addition, adolescents with remitted insomnia were significantly younger than adolescents without insomnia at Times 1 and 2. Analyses found a prevalence of 9.6%, a remittance of 6.2%, an incidence of 4.4%, and a chronicity of 2.9%. At Time 1 and 2, AWI were significantly more likely to have depression, suicidal behaviors, and behavioral problems in school than AWOI. At Time 2, incidence and chronic insomnia increased the risk of depression, suicidal behaviors and behavioral problems in school. Risk and protective factors analyses indicated psychological counseling was associated with both remitted and chronic insomnia and depression was associated with incidence insomnia.

Insomni är ett vanligt problem och det finns behov av ökad tillgänglighet till kostnadseffektiva behandlingar. Syftet var att undersöka om en enkomponentsbehandling (EK), bestående av sömnrestriktion/sömnkomprimering, var non-inferior till en multikomponent (MK) KBT- behandling vid insomni och om det fanns en skillnad i symtomreduktion. Gränsvärden för non- inferiority var d = 0.8, utifrån tidigare forskning, respektive en strängare gräns d = 0.4. Data från en forskningsstudie där deltagarna erhöll EK (n = 193) jämfördes mot en riktlinje i form av en KBT-behandling i reguljärvården, MK (n = 289). Båda grupper erhöll behandling via samma internetplattform, och Insomnia Severity Index (ISI) användes som utfallsmått. Resultaten visade att EK inte kunde bekräftas som non-inferior till MK direkt efter behandling eller vid 1-årsuppföljning när en sträng gräns användes. När en liberal gräns användes kunde EK bekräftas som non-inferior direkt efter behandling men inte ett år senare. Direkt efter behandling och vid 1-årsuppföljningen visade båda grupperna en signifikant minskning av insomnisymtom, men vid 1-årsuppföljningen visade MK en större minskning. Ett stort bortfall vid 1-årsuppföljning och mer terapeutstöd för MK kan ha påverkat resultaten. Fler RCT-studier med långtidsuppföljningar behövs inom området, och även studier på andra populationer. MK är att föredra, men vid begränsade resurser kan EK erbjudas med god effekt på både kort och lång sikt. / Insomnia is a common problem and there is a need for increased accessibility to cost-effective treatments. The purpose was to examine if an one-component treatment (EK), consisting of sleep-restriction/sleep-compression, were non-inferior to a multi-component (MK) CBT treatment for insomnia and if there was a difference in symptom reduction. The prestated margins for non-inferiority were d = 0.8, based on previous research, and a stricter margin of d = 0.4. Data from a research study where participants received EK (n = 193) was compared to a benchmark consisting of a CBT treatment in regular health care (MK) (n = 289). Both groups received treatment at the same Internet platform, and Insomnia Severity Index (ISI) was used as outcome measurement. The results showed that EK could not be confirmed as non-inferior to MK directly after treatment or at the one-year follow up when using a strict limit. When a liberal limit was used, EK could be confirmed as non-inferior directly after treatment but not one year later. Directly after treatment and at the one-year follow up both groups showed a significant symptom reduction, but at the one-year follow up MK showed a greater reduction. A large number of missing data at the one-year follow up and more therapeutic support in MK may have affected the results. More RCT-studies with longterm follow ups are needed in the area, and also studies of other populations. MK is preferable, but with limited resources EK can be offered with good effect both short term and long term.