Background and Objectives: To characterize the impact of pregabalin on sleep in patients with generalized anxiety disorder (GAD) and to determine whether the impact is a direct or an indirect effect, mediated through the reduction of anxiety symptoms. Methods: A post-hoc analysis of data from a randomized, double-blind, placebo- and active-controlled study in patients with GAD was conducted. Patients received pregabalin 300 mg/day, venlafaxine XR 75 mg/day or placebo for a week, followed by pregabalin 300-600 mg/day, venlafaxine XR 75-225 mg/day, or placebo for 7 weeks. Treatment effect on sleep was evaluated using the Medical Outcomes Study Sleep Scale. Anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale. A mediation model was used to estimate separately for both treatment arms the direct and indirect treatment effects on sleep disturbance. Results: Compared with placebo (n = 128), treatment with pregabalin (n = 121) significantly reduced scores on the sleep disturbance subscale and Sleep Problems Index II at both week 4 and week 8, and the sleep adequacy subscale at week 8. Venlafaxine XR (n = 125) had no significant effect on these measures. The mediation model indicated that 53% of the total pregabalin effect on sleep disturbance was direct (p < 0.01) and 47% indirect, mediated through anxiety symptoms (p < 0.05). Conclusions: Pregabalin decreased sleep disturbance in patients with GAD both directly, and indirectly by reducing anxiety symptoms. Given the drug specificity of the results, this study provides evidence of an additional important pathway of action for pregabalin and its efficacy in GAD.

Indiana University-Purdue University Indianapolis (IUPUI) / Study 1: Background: Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. Methods: 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 (CI). Results: 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%CI=1.02-1.29, p=.03). This association was nonsignificant in the fully-adjusted model (exp[b]=1.07, 95%CI=0.95-1.19, p=.25). Conclusion: 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. Study 2: Background: 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. Methods: 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 (n = 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. Results: 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 (SD) 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-SD 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. Conclusion: 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.

No description available.

Studies suggest that sleep disturbance may be an important etiological factor in the development of comorbid anxiety and depressive disorders, whereby anxiety leads to sleep difficulties, which in turn increase the vulnerability for depression. The primary aim of this study was to determine whether the sequential comorbidity patterns observed at the disorder level (i.e., where anxiety disorders most often precede insomnia, and insomnia most often precedes depression) were also present in daily fluctuations of symptoms. The secondary aim was to explore possible moderators of any observed temporal associations. Participants were 15 patients with generalized anxiety disorder (GAD; mean age = 28.9 years, SD = 9.8) and 15 good sleeper controls (mean age = 27.1 years, SD = 8.3) who were comparable in female:male ratio (73% female vs. 67% female). For 14 days, participants wore an actigraph to objectively assess sleep quality (sleep onset latency, total sleep time, wake after sleep onset, sleep efficiency) and completed daily symptom ratings multiple times each day using their smartphones to assess symptoms of anxiety, depressed mood, and subjective sleep quality. Study aims were assessed using multilevel modeling, with daily symptoms nested within individuals. Many of the analyses were lagged such that the time-varying predictor variable preceded the time-varying outcome variable temporally. Consistent with hypotheses, results demonstrated that anxious mood was predictive of later subjective and objective sleep disturbance in individuals with GAD, and this effect was strongest among individuals with higher levels of neuroticism, negative affect, and dysfunctional beliefs about sleep. Anxious mood was not associated with later subsequent sleep disturbance in healthy controls. In the GAD group, subjective and objective sleep disturbance predicted later depressed mood; this effect was moderated by temperament and dysfunctional beliefs about sleep. For the control group, the effect of subjective sleep disturbance on later depressed mood was moderated by neuroticism and the effect of objective sleep disturbance was moderated by dysfunctional beliefs about sleep, suggesting that sleep disturbance may increase vulnerability for depressed mood even in healthy individuals. These results suggest that explicitly targeting sleep disturbance during the treatment of GAD may attenuate the experience of depressive symptoms.

Sleep disturbances are prevalent among primary care patients, and psychological dysfunction, including stress, anxiety, and depression, are robust contributors to poor sleep health. Yet, the presence of potential protective characteristics, such as health self-efficacy and engaging in adaptive health behaviors, may mitigate such outcomes. Gratitude (i.e., recognition and appreciation of experiences, relationships, and surroundings), a positive psychological cognitive-emotional characteristic, may serve as a catalyst of these beneficial downstream effects, given its association with improved health functioning and sleep. In a sample of primary care patients (N = 869) from 50 urban and 30 rural practices in Germany, health self-efficacy (i.e., belief in ability to perform necessary actions to manage health) and constructive health behaviors (i.e., actions taken to modify health positively), separately and together as parallel first-order mediators, and stress, anxiety, and depression, as parallel second-order mediators, were investigated as potential serial mediators of the association between gratitude and sleep disturbances. Participants completed self-report measures in person and online. Significant serial mediation was observed across models, although effects varied. In the first model, gratitude was associated with greater health self-efficacy and, in turn, to less stress, anxiety, and depression, and fewer consequent sleep disturbances. In the second model, health behaviors, and anxiety and depression, were serial mediators, but health behaviors and stress were not. In a final combined model, serial mediation occurred on two pathways, health self-efficacy and anxiety, and health self-efficacy and depression, and a specific indirect effect was found for health behaviors, but not self-efficacy. Gratitude was associated with reduced sleep disturbances through positive health behavior engagement, and via the serial mediation effects of greater health self-efficacy and lower psychological distress. Clinical interventions that enhance gratitude (e.g., gratitude listing or diaries), self-efficacy (e.g., disease self-management programs), or health behavior engagement (e.g., weight management programs) may promote favorable downstream effects on psychological distress and sleep disturbances among primary care patients.

Impulsivity and sleep and circadian rhythm disturbance are two core features of bipolar disorder that are elevated antecedents to bipolar disorder onset and persist even between mood episodes; their pervasive presence in bipolar disorder suggests that they may be particularly relevant to better understanding bipolar disorder etiology, onset, and course. Given considerable research demonstrating bidirectional associations between sleep and circadian rhythm disturbance and impulsivity in healthy individuals, it is surprising that little research has examined how these core features interact to impact bipolar disorder symptomatology, onset, and course. In a sample of late adolescents and young adults (N = 150) at low or high risk for developing bipolar disorder, we employed a naturalistic experiment in the context of an ecological momentary assessment (EMA) design to examine relationships between impulsivity, sleep and circadian rhythm alterations, and mood symptoms in everyday life. Furthermore, we sought to understand how the relationships between sleep and circadian rhythm alterations and mood fluctuation, collected during the EMA study, prospectively predicted mood symptom severity and mood episode onset at a 6-month follow-up. Linear regression, logistic regression, and multi-level modeling (MLM) revealed that higher impulsivity predicted increased mood symptoms during the EMA study, and less total sleep time (measured by actigraphy) predicted increased next-day EMA-assessed mood symptoms. Interaction analyses suggested that dim light melatonin onset time, total sleep time, and sleep onset latency moderated the relationship between impulsivity and mood symptoms (both next-day and at 6-month follow-up). Results are discussed in terms of their contribution to the existing literature. Findings highlight the necessity of multi-method, nuanced examination of the dynamic relationships between impulsivity and sleep and circadian disturbance within bipolar disorder. / Psychology

Introdução: As preocupações referentes aos níveis de ruído no mundo moderno têm se agravado em função dos processos de urbanização e industrialização, que têm comprometido a qualidade acústica urbana devido às múltiplas fontes de ruído existentes. O impacto da exposição ao ruído na saúde da população ainda não está claramente estabelecido. Estratégias para a padronização de medidas de avaliação do ruído urbano, assim como a relação causal entre exposição ambiental e desfechos em saúde tem sido objeto de pesquisa. Objetivo: avaliar a situação acústica do distrito de Pinheiros, São Paulo e o impacto da exposição ao ruído na saúde da população residente no distrito. Metodologia: O estudo foi conduzido em duas etapas: (1) avaliação do ruído no distrito em estudo e elaboração de mapas de ruído, usando o software Predictor 8.11, em áreas selecionadas como expostas e não expostas ao ruído do tráfego rodoviário; (2) avaliação dos efeitos na saúde da população residente no distrito, por meio de um inquérito domiciliar com a população residente no distrito. Foram realizadas análises estatísticas usando o Teste Qui-quadrado e a Regressão Logística Múltipla. Resultados: Foram avaliados 75 pontos, contabilizando 20h de medição. Em todos os pontos, os níveis de ruído ultrapassaram os limites estabelecidos pela legislação. Nas áreas expostas, a situação acústica caracteriza a existência de poluição sonora. Foram conduzidas 225 entrevistas. Observou-se associação entre morar em área exposta e: perceber o ruído do tráfego e considerar o local da residência um ambiente ruidoso; relatar incômodo em função deste ruído e quando da realização de atividades como assistir televisão, descansar, conversar e se concentrar na realização de tarefas. Foi identificada relação dose-resposta entre aumento do grau de incômodo com o ruído do tráfego rodoviário e aumento dos níveis de ruído. Os fatores associados a morar nas áreas não expostas ao ruído do tráfego foram: incômodo com o ruído de vizinhança e qualidade do sono regular/ruim. Conclusão: Este estudo representa um avanço metodológico na mensuração do ruído urbano, que buscou produzir dados confiáveis e comparáveis em nível local e global. Os resultados referentes aos efeitos na saúde da população mostram a importância de se reformular as políticas públicas brasileiras visando a realização de ações direcionadas à prevenção, gestão e monitoramento do ruído no espaço urbano. / Introduction: Concerns regarding noise levels in the modern world have worsened due to the urbanization and industrialization processes, that have committed to urban acoustic quality because of the multiple noise sources. The impact of noise exposure on population health is still not clearly established. Strategies for standardizing measures for assessing urban noise, as well as the causal relationship between environmental exposure and health endpoints have been subjects of research. Objective: to evaluate the acoustical situation in the district of Pinheiros, São Paulo, and the impact of noise exposure on health in the resident population in the district. Methods: The study was conducted in two steps: (1) noise assessment in the district under study and noise mapping, using the software Predictor 8.11, in areas selected as exposed and non-exposed to road traffic noise; (2) assessment of the health effects of the resident population in the district, through a household survey. Statistical analyses using Chi Square Test and Multiple Logistic Regression were performed. Results: 75 points were evaluated, accounting for 20h of measurement. At all points, the noise levels exceeded the limits established by law. In exposed areas, the noise situation characterizes the existence of noise pollution. 225 interviews were conducted. We observed an association between living in exposed area and: perceiving the traffic noise and consider the place of residence a noisy environment; report annoyance due to this noise and when performing activities such as watching television, resting, talking and concentrate on performing tasks. A dose-response relationship between increasing degree of annoyance with road traffic noise and increased noise levels was observed. The factors associated with living in areas not exposed to traffic noise were annoyance with neighborhood noise and fair / poor sleep quality. Conclusion: This study represents a methodological advance in the measurement of urban noise, as it sought to produce reliable and comparable data on local and global level. The results regarding the effects on health of the population show the importance of reformulating the Brazilian public policies aiming to carry out actions towards the prevention, management and monitoring of noise in the urban space.

Introdução: Estudos relatam uma maior prevalência de fatores de risco cardiovascular desfavoráveis em indivíduos com migrânea, mas os resultados são conflitantes. Objetivos: Investigar a presença de fatores de risco cardiovascular em mulheres adultas portadoras de migrânea e comparar com controles sadios. Métodos: Cinquenta e nove mulheres participaram deste estudo caso-controle. Sujeitos do estudo foram divididos em grupos de pacientes eutróficas e obesas e comparadas a grupos controle pareados por idade e índice de massa corporal. Níveis séricos de lipídios, glicemia de jejum, insulinemia, resistência à insulina, pressão arterial, tabagismo, atividade física, escore de Framingham, proteína creativa, história familiar de doenças cardiovasculares (DCV), distúrbios do sono, depressão e ângulo de fase por bioimpedância elétrica foram investigados. Resultados: As pacientes obesas com migrânea apresentaram menores valores de HDL-c do que pacientes e controles eutróficas; a resistência à insulina e a insulinemia foram relacionadas à obesidade; todas as pacientes com migrânea eram sedentárias, independentemente de seu estado nutricional; o escore de Framingham foi mais elevado em pacientes obesas com migrânea; pacientes com migrânea tiveram maiores escores de depressão; assim como curta duração do sono, especialmente as obesas. Conclusão: Resultados preliminares apontam nitidamente para sedentarismo e depressão e possíveis distúrbios do sono em pacientes com migrânea, além de plausível sobreposição de efeito da obesidade e da migrânea sobre os níveis séricos de HDL-c e escore de risco de Framingham. / Background: Studies have reported a higher prevalence of unfavorable cardiovascular risk factors amongst migraineurs, but results have been conflicting. Objective: To investigate cardiovascular risk factors in adult women with migraine and compare with health controls. Design and Methods: Fifty nine adult female probands participated in this case-control study. The study group was divided into normal weight and obese migraineurs and control groups matched by age and body mass index. Serum levels of lipids, fasting glucose, insulinemia, insulin resistance, blood pressure, smoking, physical inactivity, Framingham risk, C-reactive protein, family history of cardiovascular disease, sleep disturbances, depression and bioelectrical impedance phase angle were investigated. Results: Obese migraineurs had lower HDL-c than eutrophic controls and migraineurs, insulin resistance and insulinemia were obese-related, all migraineurs were sedentary irrespective of nutritional status, Framingham risk score was higher in obese migraineurs, migraineurs had higher depression scores and shorter sleep duration, obese migraineurs and also migraineurs taken together had worst sleep quality scores. Conclusion: Preliminary results points to marked inactivity, depression and some sleep disturbance in migraine patients, and also probably overlapped effects of obesity and migraine in HDL-c levels and 10-year Framingham general cardiovascular disease risk.

Background: Insomnia is a robust correlate of suicidal ideation and behavior. Preliminary research has identified thwarted belongingness (c.f. social disconnection) as an explanatory link between insomnia and suicidal ideation. Objectives: This study replicates and extends previous findings using both cross-sectional and longitudinal designs in four demographically diverse samples. Additionally, the specificity of thwarted belongingness was evaluated by testing anxiety as a rival mediator. Method: Self-report measures of insomnia symptoms, thwarted belongingness, suicidal ideation and behavior, and anxiety were administered in four adult samples: 469 undergraduate students, 352 psychiatric outpatients, 858 firefighters, and 217 primary care patients. Results: More severe insomnia was associated with more severe thwarted belongingness and suicidality. Thwarted belongingness significantly accounted for the association between insomnia and suicidality, cross-sectionally and longitudinally, beyond anxiety. Notably, findings supported the specificity of thwarted belongingness: anxiety did not significantly mediate the association between insomnia and suicidality, and insomnia did not mediate the relation between thwarted belongingness and suicidality. Limitations: This study relied solely on self-report measures. Future studies incorporating objective sleep measurements are needed. Conclusion: Findings underscore the utility of assessing and addressing sleep disturbances and social disconnection to reduce suicide risk.

Sleep disturbance is common in patients with heart failure (HF) and the family caregivers. Sleep disturbance is known as a predictor of poor quality of life (QoL) in individual level. The manner in which patients’ and caregivers’ sleep disturbances influence each other’s QoL has not been determined. The purpose of this dissertation was to investigate the associations of sleep disturbance and outcomes in patients with HF and their primary family caregivers. The specific aims were to: 1) examine whether sleep disturbance of patients and their family caregivers predict their own and their partners’ QoL; 2) examine the mediator effects of depressive symptoms on the association between sleep disturbance and QoL in patients and family caregivers; and 3) provide evidence of the psychometric priorities of the Zarit Burden Interview (ZBI) as a measure of caregiving burden in caregivers of patients with HF. The three specific aims were addressed using secondary analyses of cross-sectional data available from 143 patients with HF and their primary family caregivers. To accomplish Specific Aim One, multilevel dyadic analysis, actor-partner interdependence model was used for 78 patient- caregiver dyads. Individuals’ sleep disturbance predicted their own poor QoL. Caregivers’ sleep disturbance predicted patients’ mental aspect of QoL. For Specific Aim Two, a series of multiple regressions was used to examine the mediation effect in patients and caregivers separately. Depressive symptoms significantly mediated the relationship between sleep disturbance and mental aspect of QoL in patients. The mediation effect was similar in caregivers. For Specific Aim Three, the internal consistency and convergent and construct validity of the ZBI in 124 family caregivers of patients with HF were examined. The results showed that the ZBI is a reliable and valid measure of caregiving burden in this population. This dissertation has fulfilled important gaps in the evidence base for the QoL outcome in patients with HF and caregivers. The findings from this dissertation provided evidence of the importance of monitoring sleep disturbance for better QoL in both patients and caregivers and the importance of assessing caregivers’ sleep disturbance for improving patients’ QoL. It also provided evidence of the importance of managing depressive symptoms when targeting sleep disturbance to improve QoL in both patients and caregivers.