Nightshift Work and Nighttime Eating Are Associated With Higher Insulin and Leptin Levels in Hospital Nurses.

Background: Circadian misalignment between behaviors such as feeding and endogenous circadian rhythms, particularly in the context of shiftwork, is associated with poorer cardiometabolic health. We examined whether insulin and leptin levels differ between dayshift versus nightshift nurses, as well as explored whether the timing of food intake modulates these effects in nightshift workers. Methods: Female nurses (N=18; 8 dayshift and 10 nightshift) completed daily diet records for 8 consecutive days. The nurses then completed a 24-h inpatient stay, during which blood specimens were collected every 3 h (beginning at 09:00) and meals were consumed at regular 3-h intervals (09:00, 12:00, 15:00, and 18:00). Specimens were analyzed for insulin and leptin levels, and generalized additive models were used to examine differences in mean insulin and leptin levels. Results: Mean insulin and leptin levels were higher in nightshift nurses by 11.6 ± 3.8 mU/L (p=0.003) and 7.4 ± 3.4 ng/ml (p=0.03), respectively, compared to dayshift nurses. In an exploratory subgroup analysis of nightshift nurses, predominately eating at night (21:00 - 06:00) was associated with significantly higher insulin and leptin levels than consuming most calories during the daytime (06:00 - 21:00). Conclusions: In our study of hospital nurses, working the nightshift was associated with higher insulin and leptin levels, and these effects were driven by eating predominately at night. We conclude that although nightshift work may raise insulin and leptin levels, eating during the daytime may attenuate some of the negative effects of nightshift work on metabolic health.

Medication Optimization Using Pharmacogenomic Testing in a Complex Mental Health Population Prescribed Psychiatric Polypharmacy.

The use of polypharmacy has become significantly more common over the past two decades, increasing the risk of drug-drug interactions and adverse drug reactions. Pharmacogenomic (PGx) assays have the purported benefit of being able to predict an individual's response to a specific medication based on genetic markers, which may facilitate the development of optimized medication regimens for patients prescribed polypharmacy. This 12-week pilot study examined the impact of the PGx results on the clinical management of Veterans who were prescribed psychiatric polypharmacy. Psychiatric medication providers were given access to the PGx assay results, including notification of drug-drug-gene interactions computed from an algorithm decision tool, to assist with medication management decisions. Veteran outpatients (N = 53) prescribed polypharmacy (mean = 13.15 medications) were enrolled into the study. In 92.4% of cases, providers changed medications at baseline, with 83% of providers indicating that they changed their original medication plan based on the PGx results. Clinical improvement over the 12-week treatment phase was seen in depression (F(1.63, 45) = 5.45, P = .01, η2  = .11) and mental health quality of life (F(2.00, 45) = 4.16, P < .05, η2  = .16). Adverse drug effects were unchanged or improved over time. Rates of polypharmacy remained unchanged. The results suggest that medication changes based on the PGx assay may be beneficial in a complex patient population prescribed polypharmacy.

Appraisals of insomnia identity in a clinical sample.

BACKGROUND: Insomnia identity, the conviction that one has insomnia, occurs independently of sleep quality or quantity, and is associated with numerous negative health outcomes. Little is known about factors influencing insomnia identity. This study planned to evaluate insomnia identity, perceived sleep experience, and sleep parameters. METHOD: Individuals seeking treatment for an insomnia complaint reported demographics, insomnia identity ratings, and daily sleep diaries. Insomnia complaint and insomnia identity were independently crossed with sleep diary data yielding: complaining good (n = 10) and poor sleepers (n = 51), and good (n = 7) and poor sleepers (n = 40) with insomnia identity. Participants were additionally classified as with (n = 50) and without (n = 14) insomnia identity. Group differences and predictors of insomnia identity were assessed. RESULTS: Complaining poor sleepers and poor sleepers with insomnia identity reported significantly poorer sleep ratings compared to their counterparts. Insomnia identity severity was predicted by worse sleep quality comparisons and increased helplessness. Analyses revealed poorer sleep parameters among those with an insomnia identity versus without. DISCUSSION: Group differences may reflect variation in perceived sleep assessment and insomnia identity rating. Results further indicated that not all who complain of insomnia (and seek treatment) endorse insomnia identity. Implications of results and future study directions on insomnia identity are discussed.

Validating Invalidation: Examining the Construct Validity of the Illness Invalidation Inventory Among Individuals With Chronic Low Back Pain.

OBJECTIVES: The Illness Invalidation Inventory (3*I) was designed to assess individuals' perceived invalidation regarding chronic pain experiences. However, no study has yet investigated the psychometric properties of the 3*I among individuals with chronic low back pain (CLBP). Given the personal and societal impact of CLBP and the potential for invalidation associated with this condition, the current study sought to examine the psychometric properties of the 3*I among individuals with CLBP. MATERIALS AND METHODS: Community-dwelling adults with CLBP living in the Southwestern United States (N=134) completed the 3*I. In line with previous literature, current analyses focused on the 3*I "family members" subscale. Exploratory and confirmatory factor analysis was performed on participant responses. Hierarchical linear regression analyses examined the relationship between the identified factors and participant self-reported pain severity, disability, and depression. RESULTS: Exploratory factor analysis conducted on the 3*I "family members" subscale found 2 factors with high internal consistency (α>0.70) that cumulatively accounted for 49.04% of the variance in scores. Consistent with previous findings, factor loadings suggested that these factors correspond to "discounting" and "lack of understanding." Subsequent confirmatory factor analysis found that this 2-factor model demonstrated a good fit with the data. Greater perceived discounting by family members was associated with greater pain severity, disability, and depression. DISCUSSION: The 2-factor model of the 3*I "family members" subscale identified in the current study reflects previous findings and extends the psychometric validity of the 3*I to a US multiethnic sample of individuals with CLBP.

Health and demographic discriminators of an insomnia identity and self-reported poor quantitative sleep.

OBJECTIVES: To identify factors that most saliently characterize the profile of individuals who complain of chronic insomnia, with or without quantitative sleep impairment. DESIGN: Community-dwelling adults reported on their demographics and functioning via questionnaires and completed 2 weeks of sleep diaries. SETTING: Shelby County in the Memphis, TN, area. PARTICIPANTS: Population-based sample, stratified by sex and age to maximally represent sleep and health across the life span. MEASUREMENTS: Participants were classified into 4 groups according to whether or not they endorsed a chronic insomnia complaint and whether they demonstrated good or poor quantitative sleep on diaries. Discriminant analysis determined which of the following variables significantly maximized spread among the sleep groups: age, sex, race, body mass index, household education, number of medications, frequency of substance use, number of medical conditions, depression, anxiety, fatigue, daytime sleepiness, and daytime insomnia impact. RESULTS: On the most powerful discriminant function, participants with more medical conditions, greater depression and anxiety, and older age were more likely to complain of chronic insomnia than to not complain and, within these levels, to have poor rather than good quantitative sleep. A second function found African Americans particularly likely to be noncomplaining poor sleepers compared to Whites. CONCLUSIONS: Findings make progress in clarifying the profile of individuals who self-identify as having chronically poor sleep. Notably, general depression and anxiety surpassed sleep-related daytime impairment measures in discriminating complaining sleepers. Negativistic self-appraisals driving diffuse psychological symptoms may thus be viable intervention targets for reducing persistent insomnia complaints independently of sleep-specific concerns.

Misaligned core body temperature rhythms impact cognitive performance of hospital shift work nurses.

Circadian rhythms greatly influence 24-h variation in cognition in nearly all organisms, including humans. Circadian clock impairment and sleep disruption are detrimental to hippocampus-dependent memory and negatively influence the acquisition and recall of learned behaviors. The circadian clock can become out of sync with the environment during circadian misalignment. Shift work represents a real-world model of circadian misalignment that can be studied for its physiological implications. The present study aimed to test the hypothesis that circadian misalignment disrupts vigilance and cognitive performance on occupationally relevant tasks using shift work as a model. As such, we sought to (1) explore the general effects of night- and day-shift worker schedules on sleep-wake parameters and core body temperature (CBT) phase, and (2) determine whether shift-type and CBT phase impact cognitive performance and vigilance at the end of a 12-h shift. We observed a sample of day-shift and night-shift hospital nurses over a 10-day period. At the end of three, consecutive, 12-h shifts (7 pm-7am or 7am-7 pm), participants completed a cognitive battery assessing vigilance, cognitive throughput, and medication calculation fluency (via an investigator developed and tested metric). Night-shift nurses exhibited significantly greater sleep fragmentation as well as a greater disparity between their wake-time and time of CBT minimum compared to day-shift nurses. Night-shift nurses exhibited significantly slower cognitive proficiency at the end of their shifts, even after adjustment for CBT phase. These results suggest that circadian disruption and reduced sleep quality both contribute to cognitive functioning and performance.

Intraindividual sleep variability and its association with insomnia identity and poor sleep.

OBJECTIVE: Insomnia identity refers to the conviction that one has insomnia, which can occur independently of poor sleep. Night-to-night variability in sleep (termed intraindividual variability [IIV]) may contribute to insomnia identity yet remain undetected via conventional mean analyses. This study compared sleep IIV across four subgroups: noncomplaining good sleepers (NG), complaining poor sleepers (CP), complaining good sleepers (CG), and noncomplaining poor sleepers (NP). METHODS: This study analyzed 14 days of sleep diary data from 723 adults. Participants were classified according to presence/absence of a sleep complaint and presence/absence of poor sleep. A 2 × 2 multivariate analysis of covariance (MANCOVA) was performed to explore differences on five measures of sleep IIV: intraindividual standard deviation in total sleep time (iSD TST), sleep onset latency (iSD SOL), wake after sleep onset (iSD WASO), number of nightly awakenings (iSD NWAK), and sleep efficiency (iSD SE). RESULTS: MANCOVA revealed significant main effects of poor sleep, sleep complaint, and their interaction on sleep IIV. Poor sleepers exhibited greater IIV across all sleep parameters compared to good sleepers. Similarly, individuals with a sleep complaint exhibited greater IIV compared to individuals with no complaint. The interaction revealed that iSD SOL was significantly greater among CP than NP, and iSD NWAK was significantly greater among CG than NG. CONCLUSIONS: Greater night-to-night variability in specific sleep parameters was present among complaining versus noncomplaining sleepers in good and poor sleep subgroups. These findings suggest certain aspects of sleep consistency may be salient for treatment-seeking individuals based on their quantitative sleep status.

Multilevel modeling of chronotype and weekdays versus weekends to predict nonrestorative sleep.

Nonrestorative sleep, a form of subjective sleep disturbance that has been largely neglected in the literature, is newly accessible to researchers via the validated restorative sleep questionnaire (RSQ). The daily version of the RSQ allows for analysis of within-subjects variation in restorative sleep across repeated samplings, and such day-to-day regularity in sleep variables has been highlighted as an important new direction for research. The present study used a sophisticated statistical approach, multilevel modeling, to examine the contributions of circadian chronotype, calendar day of questionnaire completion (weekends versus weekdays), and their interaction in explaining both interindividual and intraindividual variance in restorative sleep. Analyses were conducted using an archival dataset of college undergraduates who continuously completed daily RSQs over a 14-day sampling period. In the final multilevel model, possessing an evening type predicted lower restorative sleep between subjects, while sampling on weekdays predicted lower restorative sleep within subjects. Furthermore, a cross-level interaction was observed, such that the difference in restorative sleep on weekends versus weekdays was more pronounced among those with greater evening circadian preference. All of the effects were maintained after accounting for the significant influence of gender (women had less restorative sleep than men). These results are theoretically consistent with findings that evening types display stronger disparities in sleep schedules across free and workdays (i.e., social jet lag), and attest to the usefulness of multilevel models for statistically investigating how stable traits interact with factors that vary day to day (e.g., work or school schedules) in influencing sleep outcomes.

The impact of meal timing on cardiometabolic syndrome indicators in shift workers.

The aims of this study were to 1) compare the inflammatory potential of night- and day-shift nurses' diets with regard to time of day and work status and 2) explore how the timing of food intake during work and off-work is associated with cardiometabolic syndrome (CMS) risk factors between these two groups. Female nurses (N = 17; 8 day-shift and 9 night-shift) reported food intake over 9 days. On a middle day off of work, metabolic parameters were measured after an overnight fast. Energy/macronutrient intake and inflammatory potential of dietary intake (as assessed via the Dietary Inflammatory IndexTM) were calculated for nurses' workdays, work nights, off-work days, and off-work nights. Work-night total food intake (grams) accounted for a significant amount of variance in CMS risk factors for night-shift nurses only. Increased total gram consumption during night-shift nurses' work nights was associated with increased lipid levels - independent of the macronutrient composition of the food consumed. Alternatively, for night-shift nurses, work-day intake of several food parameters accounted for a significant proportion of variance in HDL cholesterol levels, with higher intake associated with higher HDL levels. For both day- and night-shift nurses, food intake during the day was more pro-inflammatory regardless of shift type or work status. Our novel approach of combining time-of-day-specific and work-day-specific analyses of dietary inflammatory factors and macronutrient composition with measurement of CMS risk factors suggests a link between meal timing and cardiometabolic health for shift-working nurses.

GIRK Channels Mediate the Nonphotic Effects of Exogenous Melatonin.

Melatonin supplementation has been used as a therapeutic agent for several diseases, yet little is known about the underlying mechanisms by which melatonin synchronizes circadian rhythms. G-protein signaling plays a large role in melatonin-induced phase shifts of locomotor behavior and melatonin receptors activate G-protein-coupled inwardly rectifying potassium (GIRK) channels in Xenopus oocytes. The present study tested the hypothesis that melatonin influences circadian phase and electrical activity within the central clock in the suprachiasmatic nucleus (SCN) through GIRK channel activation. Unlike wild-type littermates, GIRK2 knock-out (KO) mice failed to phase advance wheel-running behavior in response to 3 d subcutaneous injections of melatonin in the late day. Moreover, in vitro phase resetting of the SCN circadian clock by melatonin was blocked by coadministration of a GIRK channel antagonist tertiapin-q (TPQ). Loose-patch electrophysiological recordings of SCN neurons revealed a significant reduction in the average action potential rate in response to melatonin. This effect was lost in SCN slices treated with TPQ and SCN slices from GIRK2 KO mice. The melatonin-induced suppression of firing rate corresponded with an increased inward current that was blocked by TPQ. Finally, application of ramelteon, a potent melatonin receptor agonist, significantly decreased firing rate and increased inward current within SCN neurons in a GIRK-dependent manner. These results are the first to show that GIRK channels are necessary for the effects of melatonin and ramelteon within the SCN. This study suggests that GIRK channels may be an alternative therapeutic target for diseases with evidence of circadian disruption, including aberrant melatonin signaling. SIGNIFICANCE STATEMENT: Despite the widespread use of melatonin supplementation for the treatment of sleep disruption and other neurological diseases such as epilepsy and depression, no studies have elucidated the molecular mechanisms linking melatonin-induced changes in neuronal activity to its therapeutic effects. Here, we used behavioral and electrophysiological techniques to address this scientific gap. Our results show that melatonin and ramelteon, a potent and clinically relevant melatonin receptor agonist, significantly affect the neurophysiological function of suprachiasmatic nucleus neurons through activation of G-protein-coupled inwardly rectifying potassium (GIRK) channels. Given the importance of GIRK channels for neuronal excitability (with >600 publications on these channels to date), our study should generate broad interest from neuroscientists in fields such as epilepsy, addiction, and cognition.

Sleep Strategies of Night-Shift Nurses on Days Off: Which Ones are Most Adaptive?

OBJECTIVES: To determine the off-shift sleep strategies of bi-ethnic night-shift nurses, the relationship between these sleep strategies and adaptation to shift work, and identify the participant-level characteristics associated with a given sleep strategy. METHODS: African-American and non-Hispanic White female, night-shift nurses from an academic hospital were recruited to complete a survey on sleep-wake patterns (n = 213). Participants completed the standard shiftwork index and the biological clocks questionnaire to determine sleep strategies and adaptation to night-shift work. In addition, chronotype was determined quantitatively with a modified version of the Munich ChronoType Questionnaire. Most participants worked ~3 consecutive 12-h night-shifts followed by several days off. RESULTS: Five sleep strategies used on days off were identified: (a) night stay, (b) nap proxy, (c) switch sleeper, (d) no sleep, and (e) incomplete switcher. Nap proxy and no sleep types were associated with poorer adaptation to night-shift work. The switch sleeper and incomplete switcher types were identified as more adaptive strategies that were associated with less sleep disturbance, a later chronotype, and less cardiovascular problems. CONCLUSION: Behavioral sleep strategies are related to adaptation to a typical night-shift schedule among hospital nurses. Nurses are crucial to the safety and well-being of their patients. Therefore, adoption of more adaptive sleep strategies may reduce sleep/wake dysregulation in this population, and improve cardiovascular outcomes.