Publications

The Circadia Study (Circadia) is a novel "direct-to-participant" research study investigating the genetics of circadian rhythm disorders of advanced and delayed sleep phase and non-24 hour rhythms. The goals of the Circadia Study are twofold: (i) to create an easy-to-use toolkit for at-home circadian phase assessment for patients with circadian rhythm disorders through the use of novel in-home based surveys, tests, and collection kits; and (ii) create a richly phenotyped patient resource for genetic studies that will lead to new genetic loci associated with circadian rhythm disorders revealing possible loci of interest to target in the development of therapeutics for circadian rhythm disorders. Through these goals, we aim to broaden our understanding and elucidate the genetics of circadian rhythm disorders across a diverse patient population while increasing accessibility to circadian rhythm disorder diagnostics reducing health disparities through self-directed at-home dim light melatonin onset (DLMO) collections.

STUDY OBJECTIVES: We examined the impact of adding a single-high-melanopic-illuminance task lamp in an otherwise low-melanopic-illuminance environment on alertness, neurobehavioral performance, learning, and mood during an 8-h simulated workday.

METHODS: Sixteen healthy young adults [mean(±SD) age = 24.2 ± 2.9, 8F] participated in a 3-day inpatient study with two 8-h simulated workdays and were randomized to either ambient fluorescent room light ( 30 melanopic EDI lux, 50 lux), or room light supplemented with a light emitting diode task lamp ( 250 melanopic EDI lux, 210 lux) in a cross-over design. Alertness, mood, and cognitive performance were assessed throughout the light exposure and compared between conditions using linear mixed models.

RESULTS: The primary outcome measure of percentage correct responses on the addition task was significantly improved relative to baseline in the supplemented condition (3.15% ± 1.18%), compared to the ambient conditions (0.93% ± 1.1%; FDR-adj q = 0.005). Additionally, reaction time and attentional failures on the psychomotor vigilance tasks were significantly improved with exposure to supplemented compared to ambient lighting (all, FDR-adj q ≤ 0.030). Furthermore, subjective measures of sleepiness, alertness, happiness, health, mood, and motivation were also significantly better in the supplemented, compared to ambient conditions (all, FDR-adj q ≤ 0.036). There was no difference in mood disturbance, affect, declarative memory, or motor learning between the conditions (all, FDR-adj q ≥ 0.308).

CONCLUSIONS: Our results show that supplementing ambient lighting with a high-melanopic-illuminance task lamp can improve daytime alertness and cognition. Therefore, high-melanopic-illuminance task lighting may be effective when incorporated into existing suboptimal lighting environments.

CLINICAL TRIALS: NCT04745312. Effect of Lighting Supplementation on Daytime Cognition. https://clinicaltrials.gov/ct2/show/NCT04745312.

CONTEXT: Perturbations to the hypothalamic-pituitary-adrenal (HPA) axis have been hypothesized to increase postmenopausal cardiometabolic risk. Although sleep disturbance, a known risk factor for cardiometabolic disease, is prevalent during the menopause transition, it is unknown whether menopause-related sleep disturbance and estradiol decline disturb the HPA axis.

OBJECTIVE: We examined the effect of experimental fragmentation of sleep and suppression of estradiol as a model of menopause on cortisol levels in healthy young women.

METHODS: Twenty-two women completed a 5-night inpatient study during the mid-to-late follicular phase (estrogenized). A subset (n = 14) repeated the protocol after gonadotropin-releasing hormone agonist-induced estradiol suppression. Each inpatient study included 2 unfragmented sleep nights followed by 3 experimental sleep fragmentation nights. This study took place with premenopausal women at an academic medical center. Interventions included sleep fragmentation and pharmacological hypoestrogenism, and main outcome measures were serum bedtime cortisol levels and cortisol awakening response (CAR).

RESULTS: Bedtime cortisol increased 27% (P = .03) and CAR decreased 57% (P = .01) following sleep fragmentation compared to unfragmented sleep. Polysomnographic-derived wake after sleep-onset (WASO) was positively associated with bedtime cortisol levels (P = .047) and negatively associated with CAR (P < .01). Bedtime cortisol levels were 22% lower in the hypoestrogenized state compared to the estrogenized state (P = .02), while CAR was similar in both estradiol conditions (P = .38).

CONCLUSION: Estradiol suppression and modifiable menopause-related sleep fragmentation both independently perturb HPA axis activity. Sleep fragmentation, commonly seen in menopausal women, may disrupt the HPA axis, which in turn may lead to adverse health effects as women age.

OBJECTIVES: Many women experience sleep problems during midlife. Associations of adverse lifetime experiences-more common among women-with sleep outcomes are understudied.

METHODS: We studied 476 women enrolled in Project Viva 1999-2002. At enrollment, participants reported any lifetime history of abuse and/or financial hardship. At midlife follow-up ∼20 years later, they reported a history of up to 10 adverse childhood experiences (ACEs); 7-day sleep quality (patient-reported outcomes measurement information system sleep disturbance and sleep-related impairment T-scores); and past month average sleep duration. We examined associations of adverse experiences with sleep outcomes, adjusted for childhood sociodemographic variables. We also explored mediation by current depression and anxiety symptoms, hot flash severity, general health, and body mass index.

RESULTS: ACEs were common: 301 women (63%) reported one or more. Each additional ACE was associated with higher midlife sleep disturbance (adjusted β = 0.65 points, 95% confidence interval [CI]: 0.27, 1.02) and sleep-related impairment (0.98, 95% CI: 0.54, 1.41) T-scores, and with sleep duration <6 hour/night (odds ratio 1.19, 95% CI: 1.00, 1.42), but not with continuous sleep duration (-2 minutes, 95% CI: -5, 1). Adverse experiences in adulthood were less consistently associated with sleep quality but were associated with sleep duration, for example, financial hardship during the index pregnancy was associated with 75 minutes (95% CI: -120, -29) shorter sleep duration 2 decades later. Associations of ACEs with sleep disturbance and sleep-related impairment were mediated by midlife depression anxiety and physical health but not by hot flash severity or body mass index.

CONCLUSIONS: Adverse lifetime experiences have deleterious associations with sleep duration and quality in midlife women.

Parenting children with conduct problems (CP) is challenging, yet very little research has examined parenting using both quantitative and qualitative methods, from the perspective of the child and their parent/caregiver, and separately for those with high vs. low levels of callous-unemotional traits (HCU vs. LCU). One hundred and forty-six boys aged 11-16 [Typically developing (TD) n = 31; CP/HCU n = 35; CP/LCU n = 35] and their parents/caregivers completed the Alabama Parenting Questionnaire and provided a written qualitative statement describing their respective experiences of parenting/being parented. Parents/caregivers of CP/HCU boys reported more difficulty with child monitoring and supervision than parents of TD boys. This was echoed in qualitative reports of parents of CP/HCU boys reporting concerns regarding their child's safety. Parents/caregivers of both groups of CP boys reported more inconsistent discipline than parents of TD boys. Parental qualitative descriptions of challenging behavior in CP/HCU boys, and difficulties with setting boundaries and motivating CP/LCU boys, provided further insight to the potential triggers for inconsistent discipline. Qualitative reports from boys with CP indicated that they understood the parenting challenges their parents/caregivers faced. These findings replicate and extend previous work on the associations between parenting and CP. Children with CP/HCU and CP/LCU show some commonalities and differences in their parenting experiences and CP children and their parents/caregivers do not necessarily share all the same perceptions or concerns. CP interventions often involve parent/family engagement and this research highlights the continued importance of examining both parent and child perspectives.

The overturning of Roe v Wade has resulted in the loss of reproductive rights for millions of women in the United States. It has also put these women at risk of severe mental and physical health consequences. When legal abortions are restricted, there is a rise in illegal abortion with the risk of hemorrhage, infection, infertility, and death. There are many more risks of carrying a pregnancy to term than health or psychological risks of a legal abortion. Women who have a miscarriage risk having to prove they did not abort. In cases of medical emergencies, doctors may be restricted from performing life-saving abortions for fear of penalties. Women or children who have been victims of rape or incest will have to either have an illegal abortion or carry an unwanted pregnancy to term. In states that allow an abortion in cases of severe risk to a mother's health, panels of internists and psychiatrist may, again, be charged with deciding whether her risks are valid. Women's physical and mental health will suffer.

The perinatal period has been well-established as a time of vulnerability to anxiety, as has the COVID-19 pandemic. Perinatal women with a prior diagnosis of Generalized Anxiety Disorder (GAD) may be anticipated to be at particular risk for elevated symptom burden when facing the overlay of these stressors. This study examined whether pre-existing anxiety exacerbates COVID-19-related health worries on anxiety symptom severity among a sample of women who entered perinatal status during the COVID-19 pandemic. We assessed COVID-19-related health worries, past diagnosis of GAD, and current generalized anxiety symptoms cross-sectionally in 1,587 perinatal U.S. women during the COVID-19 pandemic (May 21, 2020 to June 24, 2021). Among perinatal women who reported high levels of COVID-19-related health worries, those with a pre-existing GAD diagnosis were 3.56 times more likely to score at clinically significant levels of generalized anxiety, while those without a pre-existing GAD diagnosis were 6.51 times more likely. COVID-19-related health worries posed a larger risk for elevated anxiety symptoms among those without a pre-existing diagnosis of GAD. Greater access to treatment and psychoeducation for such individuals may be warranted for individuals without a pre-existing mental health diagnosis.

COVID-19 compounds the already high levels of psychological distress experienced by NICU mothers. We aimed to describe the rates of NICU-related maternal stress during the COVID-19 pandemic and to determine how COVID-19 experiences correlate with high levels of stress experienced by NICU mothers. We conducted a cross-sectional analysis based on responses to a nationwide online survey to understand the relationship between COVID-19-related experiences and the stress experienced by mothers of infants admitted to U.S. NICUs (n = 108) during the pandemic. Results indicate that 61.9% of surveyed mothers reported experiencing high levels of stress on the Parental Stressor Scale: NICU. COVID-19-related grief was significantly associated with higher levels of maternal stress, as it related to seeing the baby's appearance and behavior in the NICU and exposure to sights and sounds within the NICU environment. No significant associations were noted between parental stress and COVID-19-related health worries or worries about resources. Of note, our recruitment relied on convenience sampling, limiting the generalizability of study results. In conclusion, mothers who experience COVID-19-related grief appear to be more vulnerable to NICU-related stress. Prioritizing parent involvement and enhancing psychosocial support are essential strategies to mitigate the long-term consequences of heightened stress for NICU families.

RATIONALE: Endocannabinoids are well poised to regulate crosstalk between energy sensing of hunger and satiety and reward-driven motivation.

OBJECTIVES: Here, we aimed to unravel associations between plasma endocannabinoids and brain connectivity in homeostatic and reward circuits across hunger and satiety states.

METHODS: Fifteen participants (7 females) underwent two counter-balanced resting-state functional magnetic resonance imaging scans, one after overnight fasting and one after consumption of a standardized filling meal (satiety). Before each scan, we drew blood to measure plasma endocannabinoid concentrations (anandamide [AEA], anandamide-derived POEA, and 2-arachidonoylglycerol [2-AG]), analyzed with liquid chromatography tandem mass spectrometry.

RESULTS: We found that AEA levels were associated with increased connectivity between the lateral hypothalamus and the ventral striatum during satiety. Furthermore, fasting AEA levels correlated with connectivity between the ventral striatum and the anterior cingulate cortex and the insula.

CONCLUSIONS: Altogether, results suggest that peripheral AEA concentrations are sensitive to homeostatic changes and linked to neural communication in reward and salience networks. Findings may have significant implications for understanding normal and abnormal interactions between homeostatic input and reward valuation.