Alice M. Gregory

Sleep Problems in Childhood: A Longitudinal Study of Developmental Change and Association With Behavioral Problems

OBJECTIVE The objective of the study was to examine specificity, order of appearance, and developmental changes in the relationships between sleep problems and behavioral problems in children. METHOD Four hundred ninety children were selected from a large-scale longitudinal study of children growing up in adoptive and nonadoptive (biological) families in Colorado. Parental ratings of childrens sleep and behavioral problems on the Child Behavior Checklist were obtained from ages 4 to 15 years. RESULTS Sleep problems decreased from age 4 years to mid-adolescence, but there was modest stability of individual differences across this age range (r = 0.29). Regression analyses indicated that sleep problems at age 4 predicted behavioral/emotional problems in mid-adolescence after accounting for child sex, adoptive status, and stability of behavioral/emotional problems. Finally, the correlation between sleep problems and depression/anxiety increased significantly during this age period from r = 0.39 at age 4 years to r = 0.52 at mid-adolescence. CONCLUSIONS Early sleep problems may forecast behavioral/emotional problems, and there may be important developmental change in the overlap between sleep problems and behavioral/emotional problems.

Sleep, emotional and behavioral difficulties in children and adolescents.

Links between sleep and psychopathology are complex and likely bidirectional. Sleep problems and alteration of normal sleep patterns have been identified in major forms of child psychopathology including anxiety, depression and attention disorders as well as symptoms of difficulties in the full range. This review summarizes some key findings with regard to the links between sleep and associated difficulties in childhood and adolescence. It then proposes a selection of possible mechanisms underlying some of these associations. Suggestions for future research include the need to 1) use multi-methods to assess sleep; 2) measure sleep in large-scale studies; 3) conduct controlled experiments to further establish the effects of sleep variations on emotional and behavioral difficulties; 4) take an interdisciplinary approach to further understand the links between sleep and associated difficulties.

Objective Sleep in Pediatric Anxiety Disorders and Major Depressive Disorder.

OBJECTIVE To examine objective and subjective sleep problems in early-onset anxiety and depression. METHOD Children and adolescents (46% female, ages 7 to 17 years) with anxiety disorders (n = 24), major depressive disorder (MDD) without comorbid anxiety disorders (n = 128), or no history of psychiatric disorder (n = 101) spent two consecutive nights in a sleep laboratory and completed self-reports of sleep quality. RESULTS On objective measures, the anxiety group exhibited more awakenings than the MDD group, less slow-wave sleep than the control or MDD group, and greater night 2 sleep latency than the MDD or control group. The anxiety group exhibited no decrease in rapid eye movement latency from the first night to the second. The MDD group exhibited less time awake than the control group and less stage 1 sleep than the anxiety or control group. On subjective measures, young people with anxiety reported greater sleep latency on the second night and no decrease in sleep latency. Age was covaried in analyses. CONCLUSIONS Findings provide objective and subjective evidence of sleep disturbance in children and adolescents with anxiety disorders and replicate findings of limited objective sleep disturbance in those with MDD. Sleep problems are an important consideration when treating young people with anxiety.

Parent-reported sleep problems during development and self-reported anxiety/depression, attention problems, and aggressive behavior later in life

OBJECTIVE To examine associations between sleep problems during development and subsequent emotional and behavioral difficulties. DESIGN Prospective longitudinal study. SETTING The Dutch province of Zuid-Holland. PARTICIPANTS At time 1 of data collection, a representative sample of 2076 children aged 4 to 16 years participated in the study. OUTCOME MEASURES Parents rated their childrens (4-19 years old) sleep at 5 assessments by completing the Child Behavior Checklist. Participants reported on their own emotional and behavioral symptoms at a later assessment (when aged 18-32 years) by completing the Young Adult Self-Report. RESULTS After adjusting for sex, age, socioeconomic status, and parent-rated scores through development for the difficulty being predicted, having any parental reports of sleeping less than others was a risk indicator of high scores on the Anxious/Depressed scale (odds ratio, 1.43; 95% confidence interval, 1.07-1.90; P = .01) and the Aggressive Behavior scale (odds ratio, 1.51; 95% confidence interval, 1.13-2.02; P = .005). There was some (albeit less robust) support for links between other reported sleep difficulties and later problems. Parental reports of sleeping more than others and nightmares were not associated with later difficulties. CONCLUSIONS Physicians should inquire about sleep problems during child development and should be aware that some, but perhaps not others, may constitute risk indicators of later difficulties.

DIURNAL PREFERENCE AND SLEEP QUALITY: SAME GENES? A STUDY OF YOUNG ADULT TWINS

The aims of this study were to examine the genetic and environmental influences on diurnal preference and sleep quality, the association between these phenotypes, the genetic and environmental influences on this association, and the magnitude of overlap between these influences. Using a twin design, data on diurnal preference (measured by the Morningness-Eveningness Questionnaire) and sleep quality (measured by the Pittsburgh Sleep Quality Index) were collected from 420 monozygotic twins, 773 dizygotic twins, and 329 siblings (mode age = 20 yrs, range = 18–27 yrs) from a population-based twin registry across the UK. Univariate analyses indicated that dominance genetic influence accounted for 52% and non-shared environment 48% of variance in diurnal preference. For sleep quality, additive genetic influence explained 43% and non-shared environment 57% of the variance. The bivariate analysis indicated a significant association between greater eveningness preference and poorer sleep quality (r = .27). There was substantial overlap in the additive genetic influences on both phenotypes (rA = .57), and overlap in the dominance genetic influences common to both phenotypes was almost absolute (rD = .99). Overlap in non-shared environment was much smaller (rE = .02). Additive genetic influence accounted for 2% of the association, dominance genetic influence accounted for 94%, and non-shared environmental influences accounted for the remaining 4%. The substantial overlap in genetic influence between these phenotypes indicates that similar genes are important for diurnal preference and sleep quality. Therefore, those genes already known to influence one phenotype may be possible candidates to explore with regards to the other phenotype. (Author correspondence: ps701nh@gold.ac.uk)

Associations Between Sleep Problems, Anxiety, and Depression in Twins at 8 Years of Age

OBJECTIVES. Associations between sleep and internalizing problems are complex and poorly understood. To better understand these covarying difficulties, genetic and environmental influences were estimated by using a twin design. METHODS. Three hundred 8-year-old twin pairs reported on their anxiety and depression by completing the Screen for Childhood Anxiety Related Emotional Disorders and the Childrens Depression Inventory. Parents reported on their childrens sleep problems by completing the Child Sleep Habits Questionnaire. RESULTS. Children reported by their parents to have different types of sleep problems self-reported more depression symptoms than those without. The correlation between total sleep-problem score and depression was moderate. That between sleep problems and anxiety was smaller and was not examined further. The association between sleep problems and depression was mainly explained by genes, and there was substantial overlap between the genes influencing sleep problems and those influencing depression. There was smaller influence from environmental factors making family members alike, and environmental factors making family members different decreased the association between sleep problems and depression. CONCLUSIONS. A range of sleep difficulties are associated with depression in school-aged children, and the overall association between the 2 difficulties may be largely influenced by genes.

Heart-beat perception, panic/somatic symptoms and anxiety sensitivity in children

There is considerable evidence implicating heart-beat perception (HBP) accuracy and anxiety sensitivity (AS) in the development of panic in adults. However, to date there have been no studies exploring the association between HBP, AS and childhood panic/somatic symptoms. Seventy-nine children aged 8 to 11 years completed a mental tracking paradigm (Psychophysiology 18 (1981) 483) to assess HBP, the Childrens Anxiety Sensitivity Index (J Clin Chil Psychol 20 (1991) 162) and the Screen for Childhood Anxiety Related Emotional Disorders (J Am Acad Child Adoles Psych 38 (1999) 1230). Those with good HBP (n = 7, 9%) had significantly higher panic/somatic symptoms (t = -1.71, P < 0.05), and AS (t = -2.16, P < 0.02) than those with poor HBP. There were no effects of age, sex or BMI on HBP. Those with high levels of panic/somatic symptoms were seven times more likely to have good HBP and had AS scores 1 S.D. higher than the remainder of the sample. Multivariate analyses revealed that these two phenotypes had independent associations with high panic/somatic symptoms. These results extend the literature on HBP and panic and suggest that in children, as in adults, increased panic/somatic symptoms are associated with enhanced ability to perceive internal physiological cues, and fear of such sensations.

Social jetlag, obesity and metabolic disorder: investigation in a cohort study

Background:Obesity is one of the leading causes of preventable death worldwide. Circadian rhythms are known to control both sleep timing and energy homeostasis, and disruptions in circadian rhythms have been linked with metabolic dysfunction and obesity-associated disease. In previous research, social jetlag, a measure of chronic circadian disruption caused by the discrepancy between our internal versus social clocks, was associated with elevated self-reported body mass index, possibly indicative of a more generalized association with obesity and metabolic dysfunction.Methods:We studied participants from the population-representative Dunedin Longitudinal Study (N=1037) to determine whether social jetlag was associated with clinically assessed measurements of metabolic phenotypes and disease indicators for obesity-related disease, specifically, indicators of inflammation and diabetes.Results:Our analysis was restricted to N=815 non-shift workers in our cohort. Among these participants, we found that social jetlag was associated with numerous clinically assessed measures of metabolic dysfunction and obesity. We distinguished between obese individuals who were metabolically healthy versus unhealthy, and found higher social jetlag levels in metabolically unhealthy obese individuals. Among metabolically unhealthy obese individuals, social jetlag was additionally associated with elevated glycated hemoglobin and an indicator of inflammation.Conclusions:The findings are consistent with the possibility that ‘living against our internal clock’ may contribute to metabolic dysfunction and its consequences. Further research aimed at understanding that the physiology and social features of social jetlag may inform obesity prevention and have ramifications for policies and practices that contribute to increased social jetlag, such as work schedules and daylight savings time.

Sleep quality and diurnal preference in a sample of young adults: Associations with 5HTTLPR, PER3, and CLOCK 3111†

Research investigating associations between specific genes and individual differences with regards to the quality and timing of sleep has primarily focussed on serotonin‐related and clock genes. However, there are only a few studies of this type and most of those to date have not considered the possibility of gene–environment interaction. Here, we describe associations between sleep quality and diurnal preference and three functional polymorphisms: 5HTTLPR, PERIOD3, and CLOCK 3111. Furthermore, we assessed whether associations between genotypes and sleep phenotypes were moderated by negative life events—a test of gene–environment interaction. DNA from buccal swabs was collected from 947 individuals [mean age = 20.3 years (SD = 1.77), age range = 18–27 years; 61.8% female] and genotyped for the three polymorphisms. Participants completed the Pittsburgh Sleep Quality Index and the Morningness‐Eveningness Questionnaire. There was a significant main effect of 5HTTLPR on sleep quality, indicating that “long–long” homozygotes experienced significantly poorer sleep quality (mean = 6.35, SD = 3.36) than carriers of at least one “short” allele (mean = 5.67, SD = 2.96; β = −0.34, P = 0.005). There were no main effects of 5HTTLPR on diurnal preference; no main effects of PERIOD3 or CLOCK on sleep quality or diurnal preference; and no significant interactions with negative life events. The main effect of the “long” 5HTTLPR allele contradicts previous research, suggesting that perhaps the effects of this gene are heterogeneous in different populations. Failure to replicate previous research in relation to PERIOD3 and CLOCK concurs with previous research suggesting that the effects of these genes are small and may be related to population composition.

Genome-wide Methylomic Analysis of Monozygotic Twins Discordant for Adolescent Depression

Background Adolescent depression is a common neuropsychiatric disorder that often continues into adulthood and is associated with a wide range of poor outcomes including suicide. Although numerous studies have looked at genetic markers associated with depression, the role of epigenetic variation remains relatively unexplored. Methods Monozygotic (MZ) twins were selected from an adolescent twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. There were 18 pairs of MZ twins identified in which one member scored consistently higher (group mean within the clinically significant range) on self-rated depression than the other. We assessed genome-wide patterns of DNA methylation in twin buccal cell DNA using the Infinium HumanMethylation450 BeadChip from Illumina. Quality control and data preprocessing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. The top differentially methylated DMP was successfully validated by bisulfite-pyrosequencing, and identified DMPs were tested in postmortem brain samples obtained from patients with major depressive disorder (n = 14) and matched control subjects (n = 15). Results Two reproducible depression-associated DMPs were identified, including the top-ranked DMP that was located within STK32C, which encodes a serine/threonine kinase, of unknown function. Conclusions Our data indicate that DNA methylation differences are apparent in MZ twins discordant for adolescent depression and that some of the disease-associated variation observed in buccal cell DNA is mirrored in adult brain tissue obtained from individuals with clinical depression.