Insomnia symptoms and biomarkers of monocyte activation, systemic inflammation, and coagulation in HIV: Veterans Aging Cohort Study.

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 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: We observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the "Bothers a Lot" group had, on average, 17% higher D-dimer than veterans in the "No Difficulty Falling or Staying Asleep" group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01-1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94-1.26, p = .27). 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.

The effect of insomnia on development of Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of dementia and a neurodegenerative disorder characterized by memory deficits especially forgetting recent information, recall ability impairment, and loss of time tracking, problem-solving, language, and recognition difficulties. AD is also a globally important health issue but despite all scientific efforts, the treatment of AD is still a challenge. Sleep has important roles in learning and memory consolidation. Studies have shown that sleep deprivation (SD) and insomnia are associated with the pathogenesis of Alzheimer's disease and may have an impact on the symptoms and development. Thus, sleep disorders have decisive effects on AD; this association deserves more attention in research, diagnostics, and treatment, and knowing this relation also can help to prevent AD through screening and proper management of sleep disorders. This study aimed to show the potential role of SD and insomnia in the pathogenesis and progression of AD.

The role of Yoga in working from home during the COVID-19 global lockdown.

BACKGROUND: The COVID-19 pandemic has become a major cause of stress and anxiety worldwide. Due to the global lockdown, work, employment, businesses and the economic climate have been severely affected. It has generated stress among people from all sections of society, especially to workers who have been assigned to cater to healthcare service or those constrained to secure daily essential items. It is widely perceived that elderly or those affected by diabetes, hypertension and other cardiovascular diseases are prone to COVID-19. As per an ongoing survey, the initial data shows that the above-mentioned anxiety and stress cause insomnia, and has the considerable potential to weaken the immune system, the sole protection against the virus. OBJECTIVE: This study focuses on the need of Yoga practice at work places and at home during the global lockdown due to the COVID-19 pandemic. METHODS: Literature was searched using PubMed and Google Scholar for COVID-19-related stress and anxiety at work and society due to the worldwide lockdown. The predisposing comorbidities, viral mechanism of action and treatment regimen were also searched. Yoga-based intervention studies and online programs were also searched. RESULTS: As the lockdown cannot last forever and workplaces will have to be functional soon, there is an increased possibility of recurrent infection. Therefore, Yoga can provide the necessary tool for risk reduction, amelioration of stress and anxiety and strengthening of the immune function. The online platforms provide a good media for Yoga training at work places and homes. CONCLUSION: Due to social distancing norms, the availability of Yoga trainers has become restricted. Yoga practice is actively sought to achieve reduced anxiety and stress so that improved sleep may positively impact immunity. As a consequence, there is a spurt in social media, catering to daily online Yoga sessions which apparently prove useful in providing accessible means to achieve mental as well as physical well-being.

Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors.

Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors. We screened for psychiatric symptoms 402 adults surviving COVID-19 (265 male, mean age 58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels. A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depression and anxiety at follow-up. PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.

Factors related to mental health of inpatients with COVID-19 in Wuhan, China.

OBJECTIVE: To evaluate the mental health status of hospitalized patients with coronavirus disease 2019 (COVID-19) and to explore the related factors. METHOD: This was a cross-sectional survey among COVID-19 inpatients in two isolation wards of a designated hospital in Wuhan, China, from March 7, 2020, to March 24, 2020. Participants' demographic data, clinical data and levels of circulating inflammatory markers were collated. Mental health symptoms were evaluated with questionnaires, which included the Insomnia Severity Index (ISI) scale, the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder (GAD-7) scale, and questions about patients' self-perceived illness severity. Multivariate linear regression analysis was performed to explore factors that associated with mental symptoms, and a structural equation model (SEM) was used to assess the possible relationships between those factors and the patients' mental health. RESULTS: Among the 85 participants, 45.9% had symptoms of depression (PHQ-9 ≥ 5), 38.8% had anxiety (GAD-7 ≥ 5), and 54.1% had insomnia (ISI ≥ 8). According to multivariate regression analysis, female sex, a higher level of interleukin (IL)-1ß and greater self-perceived illness severity were all significantly associated with a higher PHQ-9 score, higher GAD-7 score and higher ISI score. In addition, the disease duration and the neutrophil to lymphocyte ratio (NLR) were positively related to patients' self-perceived illness severity. The results of the SEM analyses suggested that sex (ß = 0.313, P < 0.001), self-perceived illness severity (ß = 0.411, P < 0.001) and levels of inflammatory markers (ß = 0.358, P = 0.002) had direct effects on patients' mental health. The disease duration (ß = 0.163, P = 0.003) and levels of inflammatory markers (ß = 0.101, P = 0.016) also indirectly affected patients' mental health, with self-perceived illness severity acting as a mediator. CONCLUSION: A majority of COVID-19 infected inpatients reported experiencing mental health disturbances. Female sex, disease duration, levels of inflammatory markers and self-perceived illness severity are factors that could be used to predict the severity of patients' mental symptoms.

Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system.

As a Traditional Chinese Medicine (TCM), Shuangxia Decoction (SXD) has been used to treat insomnia in oriental countries for more than thousands of years and it presents remarkable clinical effects. However, its active pharmacological fraction and the mechanism of sedative-hypnotic effects have not been explored. In this paper, we investigated active pharmacological fraction and revealed the detailed mechanisms underlying the sedative-hypnotic effects of SXD. It showed that SXD water extract compared to ethanol extract possessed better sedative effects on locomotion activity in normal mice and increased sleep duration in subhypnotic dose of sodium pentobarbital-treated mice. SXD alleviated p-chlorophenylalanine (PCPA) -induced insomnia by increasing the content of 5-HT in cortex [F (4, 55) = 12.67], decreasing the content of dopamine (DA) and norepinephrine (NE). Furthermore, SXD enhanced the expression of 5-HT1A and 5-HT2A receptors in hypothalamic and reduced serum levels of IL-1,TNF-α [F (5, 36) = 15.58]. In conclusion, these results indicated that SXD produced beneficial sedative and hypnotic bioactivities mediated by regulating the serotonergic and immune system.

Systematic genetic analyses of GWAS data reveal an association between the immune system and insomnia.

BACKGROUND: Previous studies have inferred a strong genetic component for insomnia. However, the etiology of insomnia is still unclear. The aim of the current study was to explore potential biological pathways, gene networks, and brain regions associated with insomnia. METHODS: Using pathways (gene sets) from Reactome, we carried out a two-stage gene set enrichment analysis strategy. From a large genome-wide association studies (GWASs) of insomnia symptoms (32,155 cases/26,973 controls), significant gene sets were tested for replication in other large GWASs of insomnia complaints (32,384 cases/80,622 controls). After the network analysis of unique genes within the replicated pathways, a gene set analysis for genes in each cluster/module of the enhancing neuroimaging genetics through meta-analysis GWAS data was performed for the volumes of the intracranial and seven subcortical regions. RESULTS: A total of 31 of 1,816 Reactome pathways were identified and showed associations with insomnia risk. In addition, seven functionally and topologically interconnected clusters (clusters 0-6) and six gene modules (named Yellow, Blue, Brown, Green, Red, and Turquoise) were associated with insomnia. Moreover, significant associations were detected between common variants of the genes in Cluster 2 with hippocampal volume (p = 0.035; family wise error [FWE] correction) and the red module with intracranial volume (p = 0.047; FWE correction). Functional enrichment for genes in the Cluster 2 and the Red module revealed the involvement of immune responses, nervous system development, NIK/NF-kappaB signaling, and I-kappaB kinase/NF-kappaB signaling. Core genes (UBC, UBB, and UBA52) in the interconnected functional network were found to be involved in regulating brain development. CONCLUSIONS: The current study demonstrates that the immune system and the hippocampus may play central roles in neurodevelopment and insomnia risk.

Psychophysiological insomnia and respiratory tract infections: results of an infection-diary-based cohort study.

STUDY OBJECTIVES: The immune theory of sleep suggests an important role of sleep for a functioning immune system. Insomnia has been associated with heightened risk for infections. The aim of the study was to test whether psychophysiological insomnia (PI) is associated with subsequent respiratory tract infections (RTIs) in the context of an infection-diary-based cohort study. METHODS: We recruited 674 adults from a cross-sectional survey on airway infections into the airway infection susceptibility (AWIS) cohort and invited them to self-report in diaries incident RTIs experienced during 7097 months (mean of 11.9 months of completed infection diaries per individual). The Regensburg Insomnia Scale (RIS) was assessed at baseline to measure PI. As outcome, we considered an infection diary score summing up prospectively reported RTIs. RESULTS: The RIS score correlated significantly with the infection diary score summarizing reported RTIs (correlation coefficient = 0.265, p < 0.001). Adjustments by putative confounders did only marginally affect this relationship. No significant differences in the relationship between RIS score and diary score were found for subgroups including those by gender, body mass index, perceived stress, and comorbidity. People affected by a combination of high PI and obesity were eight times more likely to belong to the group reporting the highest 10% of RTIs compared to the nonobese group with low RIS score (p < 0.001). A high RIS score in men was associated with a higher neutrophil-to-lymphocyte ratio, an indicator of inflammation. CONCLUSIONS: Our data support the relevance of adequate sleep for an immune system ready to fight pathogens and prevent airway infections.

Clinical Phenotype of Depression Affects Interleukin-6 Synthesis.

Major depressive disorder (MDD) is not a single disease, but a number of various ailments that form one entity. Psychomotor retardation, anhedonia, sleep disorders, an increased suicide risk, and anxiety are the main symptoms that often define the clinical diagnosis of depression. Interleukin-6 (IL-6), as one of the proinflammatory cytokines, seems to be overexpressed during certain mental disorders, including MDD. Overexpression of IL-6 in depression is thought to be a factor associated with bad prognosis and worse disease course. IL-6 may directly affect brain functioning and production of neurotransmitters; moreover, its concentration is correlated with certain clinical symptoms within the wide range of depressive symptomatology. Furthermore, there is a strong correlation between IL-6 synthesis and psychosomatic functioning of the patient. This article discusses potential sources and significance of IL-6 in the pathogenesis of depression.

Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women's Health Initiative Study.

BACKGROUND: Insomnia symptoms are associated with vulnerability to age-related morbidity and mortality. Cross-sectional data suggest that accelerated biological aging may be a mechanism through which sleep influences risk. A novel method for determining age acceleration using epigenetic methylation to DNA has demonstrated predictive utility as an epigenetic clock and prognostic of age-related morbidity and mortality. METHODS: We examined the association of epigenetic age and immune cell aging with sleep in the Women's Health Initiative study (N = 2078; mean 64.5 ± 7.1 years of age) with assessment of insomnia symptoms (restlessness, difficulty falling asleep, waking at night, trouble getting back to sleep, and early awakenings), sleep duration (short sleep 5 hours or less; long sleep greater than 8 hours), epigenetic age, naive T cell (CD8+CD45RA+CCR7+), and late differentiated T cells (CD8+CD28-CD45RA-). RESULTS: Insomnia symptoms were related to advanced epigenetic age (ß ± SE = 1.02 ± 0.37, p = .005) after adjustments for covariates. Insomnia symptoms were also associated with more late differentiated T cells (ß ± SE = 0.59 ± 0.21, p = .006), but not with naive T cells. Self-reported short and long sleep duration were unrelated to epigenetic age. Short sleep, but not long sleep, was associated with fewer naive T cells (p < .005) and neither was related to late differentiated T cells. CONCLUSIONS: Symptoms of insomnia were associated with increased epigenetic age of blood tissue and were associated with higher counts of late differentiated CD8+ T cells. Short sleep was unrelated to epigenetic age and late differentiated cell counts, but was related to a decline in naive T cells. In this large population-based study of women in the United States, insomnia symptoms are implicated in accelerated aging.

Is Insomnia a Risk Factor for Decreased Influenza Vaccine Response?

Healthy young adult college students (N = 133) with Insomnia (n = 65) or No Insomnia (n = 68) were compared on influenza serum antibody levels pre- and four weeks postvaccination. Volunteers underwent structured clinical interviews for sleep disorders to ensure insomnia diagnoses, as well as psychiatric interviews, physical examinations, and drug testing to ensure comorbid health problems were not potential confounds. There were significant time (both groups had increases in antibody levels pre- to postvaccination) and group (Insomnia group had lower HI antibody levels overall) main effects, but the time × group interaction was nonsignificant. Exploratory analyses did find significant PSQI x Time (p < .001) and Insomnia Status × Time (p = .002) interaction effects. Results indicate insomnia may be a risk factor for lowered immunity to the influenza virus.

Effect of Pet Insects on the Psychological Health of Community-Dwelling Elderly People: A Single-Blinded, Randomized, Controlled Trial.

BACKGROUND: There is evidence that animal-assisted therapy has positive effects on mental health, especially in elderly people. Caring for insects is easy, relatively inexpensive, and does not require much space. OBJECTIVE: The aim of this 8-week randomized, controlled, single-blinded study was to investigate the effect of pet insects on the psychological health of community-dwelling elderly people. METHODS: Elderly subjects (≥65 years old) attending a community center in Daegu, Korea, were enrolled in the study between April and May 2014 and randomized at a 1:1 ratio to receive insect therapy and health advice or only health advice. The insect group received 5 crickets in a cage with sufficient fodder and a detailed instruction manual. At baseline and at 8 weeks, all subjects underwent psychometric tests via a direct interview [Beck Anxiety Inventory, Geriatric Depression Scale (GDS-15), Mini-Mental State Examination (MMSE), 36-Item Short Form Health Survey, Insomnia Severity Index, Fatigue Severity Scale, and Brief Encounter Psychosocial Instrument] and laboratory analyses of inflammatory and oxidative stress markers (erythrocyte sedimentation rate, high-sensitivity C-reactive protein, biological antioxidant potential, and derivatives of reactive oxygen metabolites). RESULTS: The insect-caring (n = 46) and control (n = 48) groups did not differ in baseline characteristics. The insect-caring group had significantly lower GDS-15 scores at week 8 (3.20 vs. 4.90, p = 0.004) and, after adjustment for baseline values, a significantly greater change in GDS-15 scores relative to baseline (-1.12 vs. 0.20, p = 0.011). They also had a significantly greater change in MMSE scores relative to baseline (1.13 vs. 0.31, p = 0.045). The two groups did not differ in terms of other psychometric and laboratory tests. No serious risks or adverse events were reported. CONCLUSION: Caring for insects, which is cost-effective and safe, was associated with a small to medium positive effect on depression and cognitive function in community-dwelling elderly people.

Chapter 8 Military Personnel With Traumatic Brain Injuries and Insomnia Have Reductions in PTSD and Improved Perceived Health Following Sleep Restoration: A Relationship Moderated by Inflammation.

BACKGROUND: Up to one-third of deployed military personnel sustain a traumatic brain injury (TBI). TBIs and the stress of deployment contribute to the vulnerability for chronic sleep disturbance, resulting in high rates of insomnia diagnoses as well as symptoms of posttraumatic stress disorder (PTSD), depression, and declines in health-related quality of life (HRQOL). Inflammation is associated with insomnia; however, the impact of sleep changes on comorbid symptoms and inflammation in this population is unknown. METHODS: In this study, we examined the relationship between reported sleep changes and the provision of the standard of care, which could include one or more of the following: cognitive behavioral therapy (CBT), medications, and continuous positive airway pressure (CPAP). We compared the following: (a) the group with a decrease in the Pittsburgh Sleep Quality Index (PSQI; restorative sleep) and (b) the group with no change or increase in PSQI (no change). Independent t tests and chi-square tests were used to compare the groups on demographic and clinical characteristics, and mixed between-within subjects analysis of variance tests were used to determine the effect of group differences on changes in comorbid symptoms. Linear regression models were used to examine the role of inflammation in changes in symptoms and HRQOL. RESULTS: The sample included 70 recently deployed military personnel with TBI, seeking care for sleep disturbances. Thirty-seven participants reported restorative sleep and 33 reported no sleep changes or worse sleep. The two groups did not differ in demographic characteristics or clinical symptoms at baseline. The TBI+restored sleep group had significant reductions in PTSD and depression over the 3-month period, whereas the TBI+no change group had a slight increase in both PTSD and depression. The TBI+restored sleep group also had significant changes in HRQOL, including the following HRQOL subcomponents: physical functioning, role limitations in physical health, social functioning, emotional well-being, energy/fatigue, and general health perceptions. In a linear regression model using a forced entry method, the dependent variable of change in C-reactive protein (CRP) concentrations was significantly related to changes in PTSD symptoms and HRQOL in the TBI+restored sleep group, with R2=0.43, F33,3=8.31, p<.01. CONCLUSIONS: Military personnel with TBIs who have a reduction in insomnia symptoms following a standard-of-care treatment report less severe symptoms of depression and PTSD and improved HRQOL, which relate to decreased plasma concentrations of CRP. These findings suggest that treatment for sleep disturbances in this TBI+military population is associated with improvements in health and decreases in inflammation. The contributions of inflammation-induced changes in PTSD and depression in sleep disturbances in TBI + military personnel require further study.

Exercise improves immune function, antidepressive response, and sleep quality in patients with chronic primary insomnia.

The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 ± 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symptoms and plasma cortisol. Immunologic assays revealed a significant increase in plasma apolipoprotein A (140.9 ± 22 to 151.2 ± 22 mg/dL) and decreases in CD4 (915.6 ± 361 to 789.6 ± 310 mm(3)) and CD8 (532.4 ± 259 to 435.7 ± 204 mm(3)). Decreases in cortisol were significantly correlated with increases in total sleep time (r = -0.51) and REM sleep (r = -0.52). In summary, long-term moderate aerobic exercise training improved sleep, reduced depression and cortisol, and promoted significant changes in immunologic variables.

Attachment anxiety is related to Epstein-Barr virus latency.

Attachment theory provides a framework for understanding individual differences in chronic interpersonal stress. Attachment anxiety, a type of relationship insecurity characterized by worry about rejection and abandonment, is a chronic interpersonal stressor. Stress impacts cellular immunity, including herpesvirus reactivation. We investigated whether attachment anxiety was related to the expression of a latent herpesvirus, Epstein-Barr virus (EBV), when individuals were being tested for breast or colon cancer and approximately 1 year later. Participants (N=183) completed a standard attachment questionnaire and provided blood to assess EBV viral capsid antigen (VCA) IgG antibody titers. Individuals with more attachment anxiety had higher EBV VCA IgG antibody titers than those with less attachment anxiety. The strength of the association between attachment anxiety and antibody titers was the same at both assessments. This study is the first to show an association between latent herpesvirus reactivation and attachment anxiety. Because elevated herpesvirus antibody titers reflect poorer cellular immune system control over the latent virus, these data suggest that high attachment anxiety is associated with cellular immune dysregulation.

Physiological and medical findings in insomnia: implications for diagnosis and care.

This review will examine objective physiological abnormalities and medical comorbidities associated with insomnia and assess the need to measure parameters associated with these abnormalities for diagnosis and to monitor treatment outcomes. Findings are used to develop a decision tree for the work-up of insomnia patients. Currently available measures and those with possible future predictive value will be discussed. Costs, advantages, and the development of screening laboratory tests will be presented. It is concluded that there is a need to differentially evaluate insomnia patients based upon their comorbidities and the presence of objectively decreased total sleep time to direct optimal treatment. The development of objective diagnostic criteria and treatment outcome goals beyond subjective symptomatic relief will establish insomnia as a true medical problem and improve patient care.

Self-reported sleep disturbance is associated with lower CD4 count and 24-h urinary dopamine levels in ethnic minority women living with HIV.

BACKGROUND: Sleep disturbance is associated with dopamine dysregulation, which can negatively impact immune status. Individuals living with HIV experience more sleep difficulties, and poor sleep may compound immune decrements associated with HIV infection. Little research has examined associations between sleep, dopamine, and immune status (CD4 count) in individuals with HIV. As ethnic minority women living with HIV (WLWH) are at heightened risk for HIV disease progression, we related sleep reports to both CD4 count and dopamine levels in a cohort of ethnic minority WLWH. METHODS: Participants were 139 low-income WLWH (ages 20-62; 78.3% African-American or Caribbean) who reported both overall sleep quality and sleep disturbance on the Pittsburgh sleep quality index (PSQI). CD4 count and HIV viral load were measured via morning peripheral venous blood samples, and concentrations of dopamine were measured via 24-h urine collection. Covariates included HIV viral load, length of time since HIV diagnosis, HAART adherence, perceived stress and depression. RESULTS: After controlling for all covariates, greater sleep disturbance was associated with significantly lower CD4 count (ß=-.20, p=.03) and lower levels of dopamine (ß=-.25, p=.04). Poorer overall sleep quality was marginally associated with lower CD4 count (ß=-.16, p=.08), and was not associated with dopamine. CONCLUSION: Our analyses suggest that sleep disturbance is independently related with immune status and dopamine levels in WLWH. Lower levels of dopamine may indicate neuroendocrine dysregulation and may impact immune and health status. Results highlight sleep disturbance rather than overall sleep quality as potentially salient to neuroendocrine and immune status in ethnic minority WLWH.

Cross-translational studies in human and Drosophila identify markers of sleep loss.

Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss.