ArticleLiterature Review

Circadian rhythms and attention deficit hyperactivity disorder: The what, the when and the why

January 2016
Progress in Neuro-Psychopharmacology and Biological Psychiatry 67(3)

DOI:10.1016/j.pnpbp.2016.01.006

Authors:

Andrew N Coogan

National University of Ireland, Maynooth

Aurel Popa-Wagner

Universität Greifswald

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition charactetised by impulsivity, inattention and hyperactivity. Aside from these core psychopathologies, sleep disturbances are found to be highly comorbid with ADHD, and indeed dysregulated sleep may contribute to some of the symptoms of the disorder. It is not clear how sleep disturbances come to be so common in ADHD, but one putative mechanism is through the circadian timekeeping system. This system underpins the genertaion of near twenty four hour rhythms in a host of physiological, behavioural and psychological parameters, and is a key determinant of the sleep/wake cycle. In this paper we review the evidence for sleep and circadian rhythm disturbance in ADHD, examine the possible mechanistic links between these factors and the disorder and discuss future directions through which the circadian clock can be targetted for ADHD symptom relief.

Chronobiology in Paediatric Neurological and Neuropsychiatric Disorders: Harmonizing Care with Biological Clocks

Article

Full-text available

Dec 2024

Background: Chronobiology has gained attention in the context of paediatric neurological and neuropsychiatric disorders, including migraine, epilepsy, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD). Disruptions in circadian rhythms are associated with key symptoms such as sleep disturbances, mood dysregulation, and cognitive impairments, suggesting a potential for chronobiology-based therapeutic approaches. Methods: This narrative review employs a systematic approach to identify relevant studies through searches of three major scientific databases, NCBI/PubMed, ScienceDirect, and Scopus, up to July 2024. We used a combination of broad and condition-specific keywords, such as “chronobiology”, “biorhythm”, “pediatric”, “epilepsy”, “ADHD”, and “ASD”, among others. Articles in English that focused on clinical features, treatments, or outcomes related to circadian rhythms in paediatric populations were included, while non-peer-reviewed articles and studies lacking original data were excluded. Rayyan software was used for article screening, removing duplicates, and facilitating consensus among independent reviewers. Results: A total of 87 studies were included in the analysis. Findings reveal a consistent pattern of circadian rhythm disruptions across the disorders examined. Specifically, dysregulation of melatonin and cortisol secretion is observed in children with ASD, ADHD, and PTSD, with altered circadian timing contributing to sleep disturbances and mood swings. Alterations in core clock genes (CLOCK, BMAL1, PER, and CRY) were also noted in children with epilepsy, which was linked to seizure frequency and timing. Chronotherapy approaches showed promise in managing these disruptions: melatonin supplementation improved sleep quality and reduced ADHD symptoms in some children, while light therapy proved effective in stabilizing sleep–wake cycles in ASD and ADHD patients. Additionally, behaviour-based interventions, such as the Early Start Denver Model, showed success in improving circadian alignment in children with ASD. Conclusions: This review highlights the significant role of circadian rhythm disruptions in paediatric neurological and neuropsychiatric disorders, with direct implications for treatment. Chronobiology-based interventions, such as melatonin therapy, light exposure, and individualized behavioural therapies, offer potential for improving symptomatology and overall functioning. The integration of chronotherapy into clinical practice could provide a paradigm shift from symptom management to more targeted, rhythm-based treatments. Future research should focus on understanding the molecular mechanisms behind circadian disruptions in these disorders and exploring personalized chronotherapeutic approaches tailored to individual circadian patterns.

The impact of psychological theory on the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults: A scoping review

Article

Full-text available

Dec 2021
PLOS ONE

Psychological theory and interpretation of research are key elements influencing clinical treatment development and design in Attention Deficit Hyperactivity Disorder (ADHD). Research-based treatment recommendations primarily support Cognitive Behavioural Therapy (CBT), an extension of the cognitive behavioural theory, which promotes a deficit-focused characterisation of ADHD and prioritises symptom reduction and cognitive control of self-regulation as treatment outcomes. A wide variety of approaches have developed to improve ADHD outcomes in adults, and this review aimed to map the theoretical foundations of treatment design to understand their impact. A scoping review and analysis were performed on 221 documents to compare the theoretical influences in research, treatment approach, and theoretical citations. Results showed that despite variation in the application, current treatments characterise ADHD from a single paradigm of cognitive behavioural theory. A single theoretical perspective is limiting research for effective treatments for ADHD to address ongoing issues such as accommodating context variability and heterogeneity. Research into alternative theoretical characterisations of ADHD is recommended to provide treatment design opportunities to better understand and address symptoms.

The Impact of Psychological Theory on the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Adults: A Scoping Review

Preprint

Jun 2021

Evaluating the Effect of Cranial Electrotherapy Stimulation on Attention and Sleep in ADHD: A Pilot Study

Thesis

Full-text available

Nov 2020

Erika Rachel Skerrett

Abstract This quantitative double-blind, pretest–posttest experimental pilot study examined two research questions in a sample of adults diagnosed with ADHD in the Niagara Region of Ontario, Canada. The questions asked, if and to what extent cranial electrotherapy stimulation (CES) increases attention (measured using the IVA-FSAQ) and sleep quality measured using the PSQI. The biopsychosocial model provided the framework for this study. Fifteen participants were randomly assigned to sham or active treatment conditions and used CES for 60 min each day for 5 weeks. A mixed between-within-subjects MANOVA demonstrated a significant multivariate main effect of time F(2, 12) = 7.09, p =.009; Wilks’ Λ = .458; and partial η2 = .542. Both groups showed improvement in attention and sleep quality at posttest. Follow-up univariate analysis revealed that the time effect was statistically significant for both attention F(1, 13) = 5.30, p = .038; partial η2 = .29 and sleep quality F(1, 13) = 15.33, p = .002; partial η2 = .541. There was no statistically significant multivariate effect of the treatment (sham vs. active CES) or for the interaction between time and treatment group. Effect sizes were large, and it is likely that a larger sample size would have revealed conclusive results regarding the interaction between time and treatment group. Qualitative data showed that sham participants had engaged in extraneous activities that could improve sleep during participation. Results support the use of CES as an adjunctive sleep aid in adults suffering from ADHD. Keywords: ADHD, sleep quality, auditory attention, visual attention, cranial electrotherapy stimulation, CES, PSQI, CPT, IVA

Timing is everything: Circadian rhythms and their role in the control of sleep

Article

Jan 2022

Sleep and the circadian clock are intertwined and have persisted throughout history. The suprachiasmatic nucleus (SCN) orchestrates sleep by controlling circadian (Process C) and homeostatic (Process S) activities. As a "hand" on the endogenous circadian clock, melatonin is critical for sleep regulation. Light serves as a cue for sleep/wake control by activating retino-recipient cells in the SCN and subsequently suppressing melatonin. Clock genes are the molecular timekeepers that keep the 24 h cycle in place. Two main sleep and behavioural disorder diagnostic manuals have now officially recognised the importance of these processes for human health and well-being. The body's ability to respond to daily demands with the least amount of effort is maximised by carefully timing and integrating all components of sleep and waking. In the brain, the organization of timing is essential for optimal brain physiology.

Actigraphy-Derived Sleep Profiles of Children with and without Attention-Deficit/Hyperactivity Disorder (ADHD) over Two Weeks-Comparison, Precursor Symptoms, and the Chronotype

Article

Full-text available

Nov 2021
BSRCCS

Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning (n = 44). A total of 57 children (6-12 years) with (n = 24) and without ADHD (n = 33) were recruited in one center of the large ESCAlife study to wear actigraphs for two weeks. Actigraphy-derived dependent variables, including IIV, were analyzed using linear mixed models in order to find differences between the groups. A stepwise regression model was used to investigate neuropsychological function. Overall, children with ADHD showed longer sleep onset latency (SOL), higher IIV in SOL, more movements during sleep, lower sleep efficiency, and a slightly larger sleep deficit on school days compared with free days. No group differences were observed for chronotype or sleep onset time. Sleep problems in infancy predicted later SOL and the total number of movements during sleep in children with and without ADHD. No additional effect of sleep problems, beyond ADHD symptom severity, on neuropsychological functioning was found. This study highlights the importance of screening children with ADHD for current and early childhood sleep disturbances in order to prevent long-term sleep problems and offer individualized treatments. Future studies with larger sample sizes should examine possible biological markers to improve our understanding of the underlying mechanisms. Brain Sci. 2021, 11, 1564. https://doi.org/10.3390/brainsci11121564 https://www.mdpi.com/journal/brainsci Brain Sci. 2021, 11, 1564

Autistic Traits and Attention-Deficit Hyperactivity Disorder Symptoms Associated With Greater Pain Interference and Depression, and Reduced Health-Related Quality of Life in Children With Chronic Pain

Article

Full-text available

Nov 2021

Previous research indicates elevated levels of clinically significant traits and symptoms of autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD) in children with chronic pain, but associations with functioning and depression are yet unclear. The current study examined the relationships of autistic traits and ADHD symptoms with pain interference, depression, and health-related quality of life, as well as the mediating roles of insomnia and psychological inflexibility, in children with chronic pain (n = 146, 8–17 years, 102 girls) presenting at a tertiary pain clinic. Children completed measures of pain intensity, depression, pain interference, health-related quality of life, insomnia, and psychological inflexibility. Parents (n = 146, 111 mothers) completed measures to assess autistic traits and ADHD symptoms in their children. Children with clinically significant autistic traits and ADHD symptoms presented with significantly higher levels of depressive symptoms and pain interference, and significantly lower health-related quality of life, than did the other children. Autistic traits and ADHD symptoms contributed significantly to the prediction of pain interference and depressive symptoms, as well as health-related quality of life. Psychological inflexibility mediated the relationships between ADHD symptoms and autistic traits on the one hand and depression, pain interference, and health-related quality of life on the other, while insomnia mediated the relationships between ADHD symptoms and depression, pain interference, and health-related quality of life. All analyses were adjusted for demographics and pain intensity. Results suggest the utility of screening for neurodevelopmental disorders in children with chronic pain. Furthermore, the findings may indicate insomnia and skills related to psychological flexibility as potential treatment targets in interventions aiming at improving functioning and health-related quality of life in children with chronic pain and co-occurring symptoms of neurodevelopmental disorders.

Evening circadian preference is associated with sleep problems and daytime sleepiness in adolescents with ADHD

Article

Oct 2019

Adolescence is a developmental period characterized by disruptions in sleep and changes in circadian preferences. Although adolescents with attention‐deficit/hyperactivity disorder (ADHD) are at even higher risk of sleep disruption than their peers, no study has examined whether circadian preference is associated with sleep problems and daytime sleepiness in adolescents with ADHD. This study provides an initial test of the hypothesis that greater evening preference would be associated with more sleep problems and daytime sleepiness in adolescents diagnosed with ADHD. Participants were 80 adolescents (69% male), aged 13–17 years, with ADHD. Adolescents completed measures assessing circadian preference, pubertal development, anxiety/depressive symptoms and weeknight sleep duration. Both adolescents and parents completed measures of sleep problems and daytime sleepiness. In regression analyses controlling for a number of other variables (i.e., age, sex, pubertal development, ADHD medication use, and ADHD, oppositional defiant disorder and internalizing symptom severity), greater evening preference was associated with both adolescent‐ and parent‐reported sleep problems and daytime sleepiness. Greater evening preference remained significantly associated with each of these sleep problems and daytime sleepiness when also controlling for weeknight sleep duration. This is the first study to demonstrate that evening circadian preference is associated with both sleep problems and daytime sleepiness in adolescents with ADHD. The results indicate that it is important to consider circadian function as research examining sleep in adolescents with ADHD continues to advance.

Targeting inflammation: a potential approach for the treatment of depression

Article

Full-text available

Oct 2022
METAB BRAIN DIS

Major depressive disorder (MDD) or Depression is one of the serious neuropsychiatric disorders affecting over 280 million people worldwide. It is 4th important cause of disability, poor quality of life, and economic burden. Women are more affected with the depression as compared to men and severe depression can lead to suicide. Most of the antidepressants predominantly work through the modulation on the availability of monoaminergic neurotransmitter (NTs) levels in the synapse. Current antidepressants have limited efficacy and tolerability. Moreover, treatment resistant depression (TRD) is one of the main causes for failure of standard marketed antidepressants. Recently, inflammation has also emerged as a crucial factor in pathological progression of depression. Proinflammatory cytokine levels are increased in depressive patients. Antidepressant treatment may attenuate depression via modulation of pathways of inflammation, transformation in structure of brain, and synaptic plasticity. Hence, targeting inflammation may be emerged as an effective approach for the treatment of depression. The present review article will focus on the preclinical and clinical studies that targets inflammation. In addition, it also concentrates on the therapeutic approaches’ that targets depression via influence on the inflammatory signaling pathways. Graphical abstract Graphical abstract demonstrate the role of various factors in the progression and neuroinflammation, oxidative stress. It also exhibits the association of neuroinflammation, oxidative stress with depression.

Role of Melatonin in the Management of Sleep and Circadian Disorders in the Context of Psychiatric Illness

Article

Full-text available

Oct 2022
Curr Psychiatr Rep

Purpose of Review We present a review of research on the role of melatonin in the management of sleep and circadian disorders, stressing current overall view of the knowledge across psychiatric disorders. Recent Findings Dysregulation of sleep and circadian rhythms has been established in several psychiatric and neurocognitive disorders for long. Recent research confirms this finding consistently across disorders. The secretion of melatonin in schizophrenia and neurocognitive disorders is reduced due to a smaller volume and enlarged calcification of the pineal gland. On the other hand, melatonin dysregulation in bipolar disorder may be more dynamic and caused by light-sensitive melatonin suppression and delayed melatonin secretion. In both cases, exogenous melatonin seems indicated to correct the dysfunction. However, a very limited number of well-designed trials with melatonin to correct sleep and circadian rhythms exist in psychiatric disorders, and the evidence for efficacy is robust only in autism, attention deficit hyperactivity disorder (ADHD), and neurocognitive disorders. This topic has mainly not been of interest for recent work and well-designed trials with objective circadian parameters are few. Overall, recent studies in psychiatric disorders reported that melatonin can be effective in improving sleep parameters such as sleep onset latency, sleep efficiency, and sleep quality. Recent meta-analysis suggests that optimal dosage and dosing time might be important to maximize the efficacy of melatonin. The knowledge base is sufficient to propose well-designed, larger trials with circadian parameters as inclusion and outcome criteria. Based on the partly fragmentary information, we propose testing efficacy in disorders with neurocognitive etiopathology with later and higher dosing, and affective and anxiety disorders with lower and earlier dosing of melatonin. Summary Melatonin is promising for the correction of sleep and circadian abnormalities in psychiatric disorders. However, research results on its effect are still few and need to be accumulated. For effective use of melatonin, it is necessary to consider the appropriate dosage and administration time, depending on the individual abnormality of sleep and circadian rhythms.

Intrinsically photosensitive retinal ganglion cells in glaucoma

Article

Full-text available

Sep 2022

Glaucoma is a group of eye diseases afflicting more than 70 million people worldwide. It is characterized by damage to retinal ganglion cells (RGCs) that ultimately leads to the death of the cells and vision loss. The diversity of RGC types has been appreciated for decades, and studies, including ours, have shown that RGCs degenerate and die in a type-specific manner in rodent models of glaucoma. The type-specific loss of RGCs results in differential damage to visual and non-visual functions. One type of RGC, the intrinsically photosensitive retinal ganglion cell (ipRGC), expressing the photopigment melanopsin, serves a broad array of non-visual responses to light. Since its discovery, six subtypes of ipRGC have been described, each contributing to various image-forming and non-image-forming functions such as circadian photoentrainment, the pupillary light reflex, the photic control of mood and sleep, and visual contrast sensitivity. We recently demonstrated a link between type-specific ipRGC survival and behavioral deficits in a mouse model of chronic ocular hypertension. This review focuses on the type-specific ipRGC degeneration and associated behavioral changes in animal models and glaucoma patients. A better understanding of how glaucomatous insult impacts the ipRGC-based circuits will have broad impacts on improving the treatment of glaucoma-associated non-visual disorders.

Musicokinetic and exercise therapies decrease the depression level of elderly patients undergoing post-stroke rehabilitation: The moderating effect of health regulatory focus

Article

Full-text available

Aug 2022

This study aims to investigate the impact of musicokinetic and exercise therapies on the depression level of elderly patients undergoing post-stroke rehabilitation and its possible moderators, the promotion focus (i.e., achieve gains) and prevention focus (i.e., avoid losses or non-gains), which are the two motivational orientations of health regulatory focus. An eight-week randomized controlled trial was employed. Sixty-five elderly patients undergoing post-stroke rehabilitation in a hospital in Shanghai, China. Patients were randomly assigned to the musicokinetic (n = 32) therapy group or the exercise (n = 33) therapy group. The Mini-mental State Examination Scale measuring the patients’ cognitive functions was used to screen participants. The Hamilton Depression Rating Scale and the Health Regulatory Focus Scale were applied to assess their levels of depression and health regulatory focus on weeks 0, 4, and 8, respectively. The musicokinetic therapy had a significantly better effect than the exercise therapy for individuals who had a lower level of prevention focus, whereas the exercise therapy had a significantly better effect than the musicokinetic therapy for individuals who had a higher level of prevention focus. Musicokinetic therapy and exercise therapy were both effective in decreasing post-stroke depression for elderly patients. But it is important to choose an appropriate type of therapy per the health regulatory focus of elderly patients with post-stroke rehabilitation.

Tumor markers and depression scores are predictive of non-suicidal self-injury behaviors among adolescents with depressive disorder: A retrospective study

Article

Full-text available

Aug 2022

Background Non-suicidal self-injury (NSSI) is an important risk factor for suicide in adolescents with depressive disorders; therefore, it is important to predict NSSI occurrence as early as possible. Disturbances in biological rhythms are characteristic manifestations of depressive disorders and can lead to immune dysfunction, leading to changes in tumor markers. This study aimed to produce an index that utilizes tumor markers to predict NSSI behaviors among adolescents with depressive disorders. Methods A total of 120 hospitalized adolescent patients with depressive disorders aged 14–24 years were included in this study. Participants were divided into NSSI and non-NSSI groups based on self-reports using the Ottawa Self-Injury Inventory. Demographics, tumor marker concentrations, other peripheral blood indices, Hamilton Depression Rating Scale (HDRS) scores, and Hamilton Anxiety Rating Scale (HAMA) scores were compared between the two groups. Logistic regression analysis was conducted to develop a joint index, and a receiver operating characteristic (ROC) curve was created to predict NSSI behaviors among adolescents with depressive disorders. Results Compared with the non-NSSI group, the NSSI group had significantly higher insight, retardation, insomnia, hopelessness, psychiatric anxiety, total HDRS and HAMA scores, and significantly higher levels of cancer antigen 125 (CA-125), cancer antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). In addition, a joint index was developed by combining CA-125, CA19-9, CEA, HDRS total score, HAMA total score and age using multiple logistic regression to predict NSSI behaviors. The area under the curve was 0.831, with a sensitivity and specificity of 0.734 and 0.891, respectively. Conclusion A combination of depression score, tumor marker levels, and age can identify NSSI behaviors among adolescents with depressive disorders.

Phosphatidylethanolamine Deficiency and Triglyceride Overload in Perilesional Cortex Contribute to Non-Goal-Directed Hyperactivity after Traumatic Brain Injury in Mice

Article

Full-text available

Apr 2022

Traumatic brain injury (TBI) is often complicated by long-lasting disabilities, including headache, fatigue, insomnia, hyperactivity, and cognitive deficits. In a previous study in mice, we showed that persistent non-goal-directed hyperactivity is a characteristic post-TBI behavior that was associated with low levels of endocannabinoids in the perilesional cortex. We now analyzed lipidome patterns in the brain and plasma in TBI versus sham mice in association with key behavioral parameters and endocannabinoids. Lipidome profiles in the plasma and subcortical ipsilateral and contralateral brain were astonishingly equal in sham and TBI mice, but the ipsilateral perilesional cortex revealed a strong increase in neutral lipids represented by 30 species of triacylglycerols (TGs) of different chain lengths and saturation. The accumulation of TG was localized predominantly to perilesional border cells as revealed by Oil Red O staining. In addition, hexosylceramides (HexCer) and phosphatidylethanolamines (PE and ether-linked PE-O) were reduced. They are precursors of gangliosides and endocannabinoids, respectively. High TG, low HexCer, and low PE/PE-O showed a linear association with non-goal-directed nighttime hyperactivity but not with the loss of avoidance memory. The analyses suggest that TG overload and HexCer and PE deficiencies contributed to behavioral dimensions of post-TBI psychopathology.

Melatonergic agents influence the sleep-wake and circadian rhythms in healthy and psychiatric participants: a systematic review and meta-analysis of randomized controlled trials

Article

Full-text available

Feb 2022

Exogenous melatonergic agents are widely used to treat insomnia and sleep disturbance. Several studies have shown that they might also modulate circadian rhythms. The purpose of this systematic review and meta-analysis was to summarize current knowledge about the effects of melatonin supplements and melatonin agonists on the sleep-wake cycle as well as on the circadian rhythm of melatonin in healthy participants and in patients with psychiatric disorders. The following electronic databases were searched: EMBASE, PubMed, Web of Science, CINAHL, and Cochrane Library. Of the 12,719 articles, we finally selected 30 studies including 1294 healthy participants and 8 studies including 687 patients with psychiatric disorders. Cochrane risk of bias tool was used to assess the risk of bias. Using meta-ANOVA, studies on healthy participants showed advancing effects of melatonergic supplements and agonists on sleep-wake cycle according to dosing time and dosage, despite the fact that the original individual melatonin rhythm was within a normal range (fixed effect model standardized mean difference [95% Confidence Interval] = −0.639[−0.968 to −0.310]). In a limited number of randomized controlled trials with psychiatric patients, the findings seemed similar to those with healthy participants, despite the psychiatric disorders and treatment related factors affecting circadian rhythms. Given the unmet clinical need for evidence-based treatments to correct circadian rhythms in psychiatric disorders, efficacy of melatonergic agents seen in healthy participants, and similarity of findings among psychiatric patients, large scale, well-designed randomized controlled trials are needed to test efficacy on circadian parameters in psychiatric disorders.

The Use of Drosophila to Understand Psychostimulant Responses

Article

Full-text available

Jan 2022

The addictive properties of psychostimulants such as cocaine, amphetamine, methamphetamine, and methylphenidate are based on their ability to increase dopaminergic neurotransmission in the reward system. While cocaine and methamphetamine are predominately used recreationally, amphetamine and methylphenidate also work as effective therapeutics to treat symptoms of disorders including attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Although both the addictive properties of psychostimulant drugs and their therapeutic efficacy are influenced by genetic variation, very few genes that regulate these processes in humans have been identified. This is largely due to population heterogeneity which entails a requirement for large samples. Drosophila melanogaster exhibits similar psychostimulant responses to humans, a high degree of gene conservation, and allow performance of behavioral assays in a large population. Additionally, amphetamine and methylphenidate reduce impairments in fly models of ADHD-like behavior. Therefore, Drosophila represents an ideal translational model organism to tackle the genetic components underlying the effects of psychostimulants. Here, we break down the many assays that reliably quantify the effects of cocaine, amphetamine, methamphetamine, and methylphenidate in Drosophila. We also discuss how Drosophila is an efficient and cost-effective model organism for identifying novel candidate genes and molecular mechanisms involved in the behavioral responses to psychostimulant drugs.

Norepinephrine influences the circadian clock in human dermal fibroblasts from study participants with a diagnosis of attention-deficit hyperactivity disorder

Article

Full-text available

Jul 2021
J NEURAL TRANSM

Attention-deficit hyperactivity disorder (ADHD) is characterized by changes to the circadian process. Many medications used to treat the condition, influence norepinephrine levels. Several studies have, in addition, reported that norepinephrine itself has an effect on circadian function. The aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after norepinephrine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with an ADHD diagnosis. Circadian preference was evaluated with German Morningness–Eveningness Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different norepinephrine concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. The exposure of 1 µM norepinephrine to confluent cultures of human dermal fibroblasts from participants with a diagnosis of ADHD, was shown to dampen Per1 rhythmicity. The expression of Bmal1 , Per1 and Per3 in control subjects was also influenced by incubation with 1 µM norepinephrine. Cultures from the ADHD group revealed no statistically significant overall differences in circadian gene expression, between cultures with and without norepinephrine incubation. Per3 expression showed a significant ZT × group interaction via mixed ANOVA. Per3 expression at ZT4 was significant higher in the group of control samples incubated with 1 µM norepinephrine, compared to the control group without norepinephrine. This effect was also shown in the control samples incubated with 1 µM norepinephrine and cultures from subjects with ADHD without norepinephrine incubation. Per3 expression differed between the healthy control group and the ADHD group without norepinephrine incubation at ZT28. The results of the present study illustrate that norepinephrine impacts on circadian function. In both groups, control group and cultures taken from subjects with ADHD, the expression of the periodic genes ( Per1–3 ) was significantly influenced by incubation with norepinephrine.

Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

Article

Full-text available

Jul 2021
J NEURAL TRANSM

A link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression ( Clock, Bmal1, Per1-3, Cry1 ) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2 . Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3 .

The Effect of Cognitive Rehabilitation, Physical and Concurrent Training on Sustained, Selective and Shifting Attention in Children with ADHD

Article

Full-text available

Jun 2021

Amir Shams

Objectives: Attention Deficit/ Hyperactivity Disorder (ADHD) is one of the most common nervous disorders in childhood. The purpose of this study was to investigate effect of cognitive rehabilitation, physical and concurrent training on sustained, selective and shifting attention in ADHD children. Materials and Methods: The study participants included 40 children aged 9-12 years old who were randomly divided into four groups of cognitive rehabilitation training, physical training, combined (physical-cognitive) training and control group. The attendees trained for 16 minutes and each session for 60 minutes. Post test was performed 24 and 72 hours later. Results: The results of Covariance analysis showed that, the sustained, selective and transitional attention of the combined practice group (physical rehabilitation) have significantly lower error than another group. In the deletion response variable, the mean score of the withdrawal response in the children of the combined exercise group was significantly lower than that of the control group (p <0.05). Conclusion: Overall, the results of this study showed that cognitive rehabilitation and physical training can improve attention in children with overactive disorders. But the combination of physical training with rehabilitation training can improve the types of attention in children with ADHD.

Exposure to Short Photoperiod Regime Restores Spatial Cognition in Ventral Subicular Lesioned Rats: Potential Role of Hippocampal Plasticity, Glucocorticoid Receptors, and Neurogenesis

Article

Full-text available

Sep 2021
MOL NEUROBIOL

Ambient light influences our mood, behavior, and cognition. Phototherapy has been considered as an effective non-pharmacological intervention strategy in the restoration of cognitive functions following central nervous system insults. However, the cellular and molecular underpinnings of phototherapy-mediated functional recovery are yet to be studied. The present study examines the effectiveness of short photoperiod regime (SPR; 6:18-h light:dark cycle) in restoring the cognitive functions in ventral subicular lesioned rats. Bilateral ventral subicular lesion (VSL) resulted in significant impairment of spatial navigational abilities when tested in the Morris water maze (MWM) task. Further, VSL resulted in reduced expression of glucocorticoid receptors (GRs) and activity-regulated cytoskeletal (Arc) protein and suppression of neurogenesis in the hippocampus. VSL also suppressed the magnitude of long-term potentiation (LTP) in the hippocampal Schaffer collateral-CA1 synapses. However, exposure to SPR for 21 days showed significant restoration of spatial performance in the MWM task as the ventral subicular lesioned rats could deploy higher cognitive allocentric navigational strategies to reach the hidden platform. Further, SPR resulted in enhanced expression of hippocampal GR and Arc protein and neurogenesis but not hippocampal LTP suggestive of appropriate need-based SPR intervention. In conclusion, the study demonstrates the effectiveness of SPR in establishing functional recovery as well as the possible molecular and cellular basis of cognitive recovery in a rat model of neurodegeneration. Such studies provide a framework in understanding the efficacy of non-pharmacological strategies in establishing functional recovery in neurodegenerative conditions.

The Effect of Cognitive Rehabilitation, Physical and Concurrent Training on Sustained, Selective and Shifting Attention in Children with ADHD

Article

Full-text available

Mar 2021

Objectives: Attention Deficit/ Hyperactivity Disorder (ADHD) is one of the most common nervous disorders in childhood. The purpose of this study was to investigate effect of cognitive rehabilitation, physical and concurrent training on sustained, selective and shifting attention in ADHD children. Materials and Methods: The study participants included 40 children aged 9-12 years old who were randomly divided into four groups of cognitive rehabilitation training, physical training, combined (physical-cognitive) training and control group. The attendees trained for 16 minutes and each session for 60 minutes. Posttest was performed 24 and 72 hours later. Results: The results of Covariance analysis showed that, the sustained, selective and transitional attention of the combined practice group (physical rehabilitation) have significantly lower error than another group. In the deletion response variable, the mean score of the withdrawal response in the children of the combined exercise group was significantly lower than that of the control group (p <0.05). Conclusion: Overall, the results of this study showed that cognitive rehabilitation and physical trainings can improve attention in children with overactive disorders. But the combination of physical trainings with rehabilitation trainings can improve the types of attention in children with ADHD.

Pharmacological challenges examining the underlying mechanism of altered response inhibition and attention due to circadian disruption in adult Long-Evans rats

Article

Mar 2020
PHARMACOL BIOCHEM BE

Endogenous circadian rhythms govern behavior and physiology, while circadian disruption is an environmental factor that impacts cognition by altering the circadian clock at a molecular level. We modeled the effects of 2 sources of circadian disruption –activity occurring during typical rest periods and untimely light exposure – to evaluate the effects of circadian disruption on behavior and underlying neurochemistry. Firstly, adult Long-Evans rats of both sexes were maintained on a 12 h:12 h light:dark cycle and tested using a 5-choice serial reaction time task (5-CSRTT) under 3 conditions: 4 h into the dark phase with no exposure to ambient light during testing (control), 4 h into the dark phase with exposure to ambient light during testing, and 4 h into the light phase. Both models resulted in impulsive behavior and reduced attention compared to control. We established that changes in the diurnal expression pattern occur in the clock gene Period 2 (Per2) in the light phase-tested model. Choline acetyltransferase (Chat) and Dopamine receptor1 (Drd1) showed rhythmic expression with peak expression during the dark phase regardless of light-testing condition. Next, we performed drug challenges in a new rat cohort to examine the interaction between the cholinergic and dopaminergic neurotransmitter systems in regulating the behavioral changes caused by circadian disruption. We administered the cholinergic agonist nicotine and either the dopamine receptor 1 (DR1) antagonist SCH23390 or the DR2 antagonist eticlopride under the 3 circadian conditions to identify differential drug responses between treatment groups. Rats in both models demonstrated increased sensitivity to nicotine as compared to control, while SCH23390 and eticlopride ameliorated the effect of nicotine on 5-CSRTT performance in both models. Our study is the first to identify detrimental effects of both models of circadian disruption on impulsive behavior, and that the effects of circadian disruption are mediated by an interaction between cholinergic and dopaminergic systems.

An exploration of the neuropsychology and neuroelectrophysiology of university students experiencing symptoms of ADHD

Thesis

Jan 2019

Sophia Boyson Amy

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders affecting approximately 5% of school-aged children and 2-5% of adults. Evidence suggests that childhood symptoms of the disorder continue into adulthood for the majority of those affected. University students with ADHD continue to struggle compared to students without the disorder, but never the less they achieve higher academic outcomes than those with ADHD who do not continue on to university and therefore they may represent a ‘better-adjusted’ subset of the ADHD population. However, little is known about the difficulties faced by this group in UK universities. Several theoretical models of ADHD pathophysiology/psychopathology have been proposed over the years, initially focused on inhibitory control and executive functions, then reward processing and motivation, and now multiple pathways encompassing a wide range of difficulties. However, current models have not been able to account for all of the variability in the samples tested, suggesting that additional pathways may be needed. One possibility could be the entrainment of ongoing neural oscillations which is implicated in the perception and processing of stimuli, as well as neural communication within and between regions of the brain. The aims of this research were first to investigate the neuropsychological difficulties faced by university students experiencing symptoms of ADHD, and second to explore the possibility that any such difficulties might be explained by an entrainment deficit. Across two studies, it was found that students who reported a higher level of ADHD symptoms exhibited deficits in working memory and temporal processing, but no difficulties in sustained attention, selective attention, or inhibitory control. There were also no differences between high and low symptom participants in neuro-electrophysiological measures, suggesting no underlying compensatory neural mechanisms which might explain the equivalent performance in the selective attention and inhibitory control tasks. Understanding the neuropsychological domains in which these students do and do not have difficulties allows the focusing of resources toward support strategies to aid students with ADHD symptoms through their studies. Two paradigms for eliciting an entrainment response were tested, but neither were successful in eliciting the effect, meaning the question of whether an entrainment deficit might underlie the working memory and temporal processing difficulties remains unanswered. Being unable to elicit the entrainment of ongoing neural oscillations calls into question the ubiquity of this effect, meaning more research and the publication of null results are needed to further our understanding of this phenomenon. In conclusion, university students with ADHD symptoms show deficits in working memory and temporal processing, but no difficulties with sustained attention, selective attention, or inhibitory control. These findings need to be replicated in larger samples to address the lack of statistical power in these studies and more research is needed to investigate the possibility that the neuropsychological deficits found here could be subserved by an entrainment deficit.

Shedding light on the etiology of ADHD: The influence of disturbed sleep on symptomatology

Preprint

Jun 2019

Objective: A circadian pathway has been proposed where artificial blue light exposure in the evening delays sleep onset, thereby reducing sleep duration, which, in turn, results in increased symptoms of inattention. Hyperactivity, on the other hand, may be part of a different pathway, where symptoms of disordered breathing in sleep (DBS) result in increased hyperactivity/impulsivity symptoms (DBS pathway). The current study aimed to investigate the separate components described within the proposed pathways. Method: Data from 143 children with ADHD from a multicenter study were available for DBS pathway analyses and a subset (N=114) for circadian pathway analyses. Results: Each hypothesized step of both pathways was in accordance with the data when analyzing teacher- but not parent-rated symptoms.Conclusion: Relationships within the circadian and DBS pathways that were previously established in separate studies using separate samples were now reproduced in one sample, albeit only for teacher-rated symptoms of primary school-aged children.

CLOCK Polymorphisms in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence Linking Sleep and Circadian Disturbances and ADHD

Article

Full-text available

Jan 2019

Circadian and sleep disorders, short sleep duration, and evening chronotype are often present in attention-deficit/hyperactivity disorder (ADHD). CLOCK, considered the master gene in the circadian rhythm, has been explored by few studies. Understanding the relationship between ADHD and CLOCK may provide additional information to understand the correlation between ADHD and sleep problems. In this study, we aimed to explore the association between ADHD and CLOCK, using several genetic markers to comprehensively cover the gene extension. A total of 259 ADHD children and their parents from a Brazilian clinical sample were genotyped for eight single nucleotide polymorphisms (SNPs) in the CLOCK locus. We tested the individual markers and the haplotype effects using binary logistic regression. Binary logistic and linear regressions considering ADHD symptoms among ADHD cases were conducted as secondary analysis. As main result, the analysis showed a risk effect of the G-A-T-G-G-C-G-A (rs534654, rs1801260, rs6855837, rs34897046, rs11931061, rs3817444, rs4864548, rs726967) haplotype on ADHD. A suggestive association between ADHD and rs534654 was observed. The results suggest that the genetic susceptibility to circadian rhythm attributed to the CLOCK gene may play an important role on ADHD.

ADHD symptoms in adults with delayed sleep phase disorder

Article

Full-text available

Oct 2018

The aims of the study are to investigate the prevalence of ADHD in delayed sleep phase disorder (DSPD) patients and to explore the relationship between circadian phase and ADHD symptoms, using the dim light melatonin onset (DLMO), and to compare this relationship with patients with sleep problems other than DSPD. 353 adult patients with sleep problems were assessed for self-reported ADHD symptoms using ADHD rating scale, self-reported sleep disorders using Holland Sleep Disorders Questionnaire (HSDQ), and circadian rhythmicity using salivary DLMO. From the 353 patients with sleep problems, 63 were designated as DSPD and 107 (30.3%) reported probable ADHD. Probable ADHD was reported by 47.6% of the DSPD patients and by 26.9% of the non-DSPD patients (p = 0.059). The DSPD group showed significant higher total ADHD-RS scores (p = 0.011). In the probable ADHD group more patients were designated as DSPD (28%) compared to the non-ADHD group (13.6% [χ² = 10.402, p = 0.001]). Also 20 min later, DLMO (22:46 h) was found (p = 0.017) and more positive HSDQ scores on insomnia, parasomnia, hypersomnia, and sleep-related breathing disorders were reported in the probable ADHD group than in the non-probable ADHD group (χ² resp. 16.07; p < 0.001, 9.245; p = 0.002, 19.391; p < 0.00 and 5.865; p = 0.059). The data suggest a high prevalence of probable ADHD in DSPD patients and increased prevalence of DSPD and other sleep disorders in patients with probable ADHD. Consequence is that awareness of these findings might help with treatment of both DSPD and ADHD.

Modern approach to pharmacotherapy of chronic insomnia in childhood

Article

Jun 2024

Aim. Insomnia is a widespread problem in the pediatric population. The prevalence of insomnia in childhood varies from 5 to 50%. The lack of adequate therapy can lead to chronicity of the disease, impairment of the child’s cognitive and motor functions, and in the long term – the development of cardiovascular and metabolic diseases, diabetes, gastrointestinal and mental disorders. Thus, timely identification and treatment of childhood insomnia is important. The goal is to summarize and systematize current information about the modern approach to pharmacotherapy of chronic insomnia in childhood. Materials and methods: an analysis of modern and foreign publications, randomized controlled trials over the past 10 years was carried out. Results. Treatment of chronic insomnia includes non-pharmacological and pharmacological approaches. Behavioral strategies are recommended as first-line treatment for childhood insomnia. The presence of different pharmacological groups of drugs allows for a personalized approach to treatment. The use of “off-label” drugs requires justified prescription. Conclusion. The lack of large-scale clinical studies on the effectiveness, tolerability, dosing and safety profile of drugs dictates the need for further research to better understand the risks (negative side effects) and benefits of using medications for sleep disorders in children.

Armodafinil as a Potential Pharmacological Treatment for Attention Deficit Hyperactivity Disorder in Adults: A Review

Article

Mar 2024
CURR NEUROPHARMACOL

Introduction Armodafinil is a psychostimulant that promotes alertness, and it has been shown to improve attention, memory, and fatigue in healthy adults and adults with neurodevelopmental conditions that share symptoms with Attention Deficit Hyperactivity Disorder (ADHD). It is generally well tolerated and safe, and most of the adverse events reported are considered not serious. However, the available evidence on the efficacy of armodafinil for the treatment of ADHD in adults is scarce. Objective The present review aims to perform a systematized search of the available evidence on the possible therapeutic benefit of armodafinil treatment in adult patients with ADHD. Methods A literature review using PubMed was conducted to compile and summarize the available clinical and scientific evidence on the possible use of armodafinil as a pharmacological treatment in adult patients with ADHD. Results From the 86 articles reviewed, the available evidence showed that both acute and chronic treatment with armodafinil can improve wakefulness, memory, impulse control, and executive functions in adults with sleep disorders and other conditions. In addition, evidence of improvement in cognitive functions and mood alterations in other neuropsychiatric conditions was shown. Conclusion Armodafinil could be useful for the treatment of ADHD in adults, according to the review of the literature from both pre-clinical and clinical studies.

Psychostimulanzien und andere Arzneistoffe, die zur Behandlung der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) angewendet werden

Chapter

Dec 2023

Human Derived Dermal Fibroblasts as in Vitro Research Tool to Study Circadian Rhythmicity in Psychiatric Disorders

Article

May 2023

A number of psychiatric disorders are defined by persistent or recurrent sleep-wake disturbances alongside disruptions in circadian rhythm and altered clock gene expression. Circadian rhythms are present not only in the hypothalamic suprachiasmatic nucleus but also in peripheral tissues. In this respect, cultures of human derived dermal fibroblasts may serve as a promising new tool to investigate cellular and molecular mechanisms underlying the pathophysiology of mental illness. In this article, we discuss the advantages of fibroblast cultures to study psychiatric disease. More specifically, we provide an update on recent advances in modeling circadian rhythm disorders using human fibroblasts.

Machine Learning-Based Prediction of Attention-Deficit/Hyperactivity Disorder and Sleep Problems With Wearable Data in Children

Article

Full-text available

Mar 2023

Importance: Early detection of attention-deficit/hyperactivity disorder (ADHD) and sleep problems is paramount for children's mental health. Interview-based diagnostic approaches have drawbacks, necessitating the development of an evaluation method that uses digital phenotypes in daily life. Objective: To evaluate the predictive performance of machine learning (ML) models by setting the data obtained from personal digital devices comprising training features (ie, wearable data) and diagnostic results of ADHD and sleep problems by the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version for Diagnostic and Statistical Manual of Mental Disorders, 5th edition (K-SADS) as a prediction class from the Adolescent Brain Cognitive Development (ABCD) study. Design, setting, and participants: In this diagnostic study, wearable data and K-SADS data were collected at 21 sites in the US in the ABCD study (release 3.0, November 2, 2020, analyzed October 11, 2021). Screening data from 6571 patients and 21 days of wearable data from 5725 patients collected at the 2-year follow-up were used, and circadian rhythm-based features were generated for each participant. A total of 12 348 wearable data for ADHD and 39 160 for sleep problems were merged for developing ML models. Main outcomes and measures: The average performance of the ML models was measured using an area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, the Shapley Additive Explanations value was used to calculate the importance of features. Results: The final population consisted of 79 children with ADHD problems (mean [SD] age, 144.5 [8.1] months; 55 [69.6%] males) vs 1011 controls and 68 with sleep problems (mean [SD] age, 143.5 [7.5] months; 38 [55.9%] males) vs 3346 controls. The ML models showed reasonable predictive performance for ADHD (AUC, 0.798; sensitivity, 0.756; specificity, 0.716; PPV, 0.159; and NPV, 0.976) and sleep problems (AUC, 0.737; sensitivity, 0.743; specificity, 0.632; PPV, 0.036; and NPV, 0.992). Conclusions and relevance: In this diagnostic study, an ML method for early detection or screening using digital phenotypes in children's daily lives was developed. The results support facilitating early detection in children; however, additional follow-up studies can improve its performance.

Sleep Disorders

Chapter

Feb 2023

Sleep problems are a common comorbidity in children with neurodevelopmental disorders (NDD), which can result in a number of deleterious effects for both the child and their family. Understanding what sleep is, how it is regulated, and how sleep physiology can differ for children with NDD is important to inform assessment and treatment. Both genetic and environmental factors are known to contribute to sleep problems; therefore, this chapter will consider a biopsychosocial framework when describing the etiology of sleep disorders in children with NDD. A number of sleep assessment measures are used to identify and diagnose sleep disorders as well as to monitor the efficacy of interventions. These include subjective measures such as a sleep diary and questionnaires, and objective measures such as actigraphy and polysomnography. Treatment of sleep disorders can vary depending on the specific diagnosis, as well as any other comorbid disorders the child may have. Insomnia is the most common sleep disorder in pediatric populations, and therefore, this chapter describes the recommended stepped care approach to the treatment of insomnia in children with NDD. This stepwise approach includes psychoeducation, the implementation of healthy sleep practices, behavioral and cognitive sleep interventions, and lastly pharmacotherapy. Moving forward, a transdiagnostic approach to treatment of sleep problems should be considered, whereby the same basic treatment principles are applied across disorders without tailoring specifically to each individual NDD diagnosis.

Exosomes rich in Wnt5 improved circadian rhythm dysfunction via enhanced PPARγ activity in the 6-hydroxydopamine model of Parkinson's disease

Article

Feb 2023
NEUROSCI LETT

Sleep disorder is one of the most common non-motor symptoms in Parkinson's disease (PD) and even appear as early symptoms. Here we investigated the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-EXOs) on sleep disorder in PD rats. 6-hydroxydopa (6-OHDA) was used to establish the PD rat model. BMSCquiescent-EXO and BMSCinduced-EXO groups were given intravenous injection 100 µg/g per day for 4 weeks, while control groups were given intravenous injection of the same volume of normal saline. The total sleep time, slow-wave sleep time and fast-wave sleep time in the BMSCquiescent-EXO and BMSCinduced-EXO groups were significantly prolonged (P<0.05) compared with PD group, while the awakening time was significantly shortened (P<0.05). In addition, increased levels of dopamine (P<0.05) and 5-hydroxytryptamine (P<0.05) levels were observed in the striatum of BMSCquiescent-EXO and BMSCinduced-EXO groups. Further, qPCR and western blot revealed that the mRNA levels of CLOCK, BMAL1 and PER2 in suprachiasmatic nucleus (SCN) were notably increased in BMSCquiescent-EXO and BMSCinduced-EXO groups compared to those from PD rats. More importantly, peroxisome proliferation-activated receptor γ (PPARγ) activities were significantly enhanced after treatment with BMSCquiescent-EXO and BMSCinduced-EXO. JC-1 fluorescence staining showed that mitochondrial membrane potential imbalance was repaired after inoculation of BMSCinduced-EXO. In summary, MSC-EXOs showed the improvement of sleep disorder in PD rats through recovering circadian rhythm associated gene expression. The potential mechanisms may be related with increased PPARγ activities and rescued mitochondrial membrane potential imbalance in Parkinson striatum.

The Effect of self-Compassion Training on the Quality of life Components of Mothers of Children with Attention deficit / hyperactivity Disorder

Article

Full-text available

Oct 2022

The aim of this study was to evaluate the effectiveness of self-compassion training on the quality of life of mothers of children with attention-deficit / hyperactivity disorder. In this study, a quasi-experimental method with a pre-test-post-test design with a control group was used and its statistical population also included mothers of children aged 5 to 11 years, boys and girls with attention-deficit/hyperactivity disorder in Rasht in 2020-2021. The study sample consisted of 28 mothers from the statistical population selected by convenience sampling method and randomly placed in experimental and control groups. The experimental group participated in the compassion training group as a group for 8 weekly sessions. Both groups were evaluated in two stages of pre-test and post-test with the Short Form Quality of Life Questionnaire (1996). The results showed that the self-compassion training intervention had a significant effect on the scores of quality of life components (physical health, psychological health, social relations, and environmental health), in the post-test stage the scores of quality of life of the experimental group increased significantly (p <0.001). Self-compassion training in comparison with other kinds of training can have very useful results for mothers, especially in order to increase their quality of life, and can be introduced and implemented as one of the axes of parental training in comparison with other methods and training.

Circadian Effects on Attention and Working Memory in College Students With Attention Deficit and Hyperactivity Symptoms

Article

Full-text available

May 2022

Objective Individuals with an evening chronotype prefer to sleep later at night, wake up later in the day and perform best later in the day as compared to individuals with morning chronotype. Thus, college students without ADHD symptoms with evening chronotypes show reduced cognitive performance in the morning relative to nighttime (i.e., desynchrony effect). In combination with symptoms presented in attention deficit hyperactivity disorder (ADHD), we predicted that having evening chronotype renders impairment in attention during the morning, when students require optimal performance, amplifying desynchrony. Method Four hundred college students were surveyed for evening chronotype and symptoms of ADHD. Of those surveyed, 43 students with evening chronotype (19 with ADHD symptoms) performed laboratory attention tasks and were queried about fatigue during morning and evening sessions. Results Students with ADHD symptoms demonstrated a greater decrement in sustained attentional vigilance when abstaining from stimulants and asked to perform cognitive tests at times misaligned with natural circadian rhythms in arousal compared to their non-ADHD counterparts with the same chronotype. While individuals with ADHD symptoms had slower reaction-times during sustained attention tasks in the morning session compared to those without symptoms, there was no significant group difference in working memory performance, even though both groups made more errors in the morning session compared to the evening session. Conclusion These findings suggest that evening chronotype students with ADHD symptoms are at a greater disadvantage when having to perform sustained attention tasks at times that are not aligned to their circadian rhythm compared to their neuro-typical peers. The implications of this finding may be useful for the provision of disability accommodations to college age students with ADHD when they are expected to perform tasks requiring sustained attention at times misaligned with their circadian rhythms.

Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

Article

Full-text available

Dec 2021
INT J MOL SCI

Aiming at exploring vascular components in multiple sclerosis (MS) with brain outflow disturbance, we combined transcriptome analysis in MS internal jugular vein (IJV) wall with WES in MS families with vertical transmission of disease. Main results were the differential expression in IJV wall of 16 MS-GWAS genes and of seven genes (GRIN2A, GRIN2B, IL20RB, IL26, PER3, PITX2, and PPARGC1A) not previously indicated by GWAS but encoding for proteins functionally interacting with MS candidate gene products. Strikingly, 22/23 genes have been previously associated with vascular or neuronal traits/diseases, nine encoded for transcriptional factors/regulators and six (CAMK2G, GRIN2A, GRIN2B, N1RD1, PER3, PPARGC1A) for circadian entrainment/rhythm components. Among the WES low-frequency (MAF ≤ 0.04) SNPs (n = 7) filtered in the 16 genes, the NR1D1 rs17616365 showed significantly different MAF in the Network for Italian Genomes affected cohort than in the 1000 Genome Project Tuscany samples. This pattern was also detected in five nonintronic variants (GRIN2B rs1805482, PER3 rs2640909, PPARGC1A rs2970847, rs8192678, and rs3755863) in genes coding for functional partners. Overall, the study proposes specific markers and low-frequency variants that might help (i) to understand perturbed biological processes in vascular tissues contributing to MS disease, and (ii) to characterize MS susceptibility genes for functional association with disease-pathways.

The Role of the Circadian System in Attention Deficit Hyperactivity Disorder

Chapter

Nov 2021
ADV EXP MED BIOL

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterised by the core symptoms of inattention, impulsivity and hyperactivity. Similar to many other neuropsychiatric conditions, ADHD is associated with very high levels of sleep disturbance. However, it is not clear whether such sleep disturbances are precursors to, or symptoms of, ADHD. Neither is it clear through which mechanisms sleep and ADHD are linked. One possible link is via modulation of circadian rhythms. In this chapter we overview the evidence that ADHD is associated with alterations in circadian processes, manifesting as later chronotype and delayed sleep phase in ADHD, and examine some mechanisms that may lead to such changes. We also interrogate how the circadian clock may be a substrate for therapeutic intervention in ADHD (chronotherapy) and highlight important new questions to be addressed to move the field forward.

Sleep disorders and associated factors in children with cerebral palsy

Article

Full-text available

Aug 2021

Background Sleep disorders are a condition affecting quality and quantity of sleep. Children with cerebral palsy (CP) have higher risk of sleep disorders than those with no chronic disease. Objective To determine the prevalence and factors associated with sleep disorders in children with CP. Methods We conducted an analytic, observational study with cross-sectional design in children aged 4-10 years with CP. Subjects were recruited consecutively; children with chronic diseases (cardiovascular, malignancy, chronic obstructive pulmonary disease, and diabetes mellitus) were excluded from the study. Primary data including sociodemographics, intensity of physiotherapy outside Sardjito General Hospital (SGH), sleep hygiene, and sleep disorders were collected from the Children’s Sleep Habit Questionnaire (CSHQ). Secondary data were acquired from medical records, such as type of CP, severity of motor function impairment, presence of epilepsy, intensity of physiotherapy performed at SGH, as well as anti-epileptic, anti-spastic, and sleep-affecting medicines. Results We found sleep disorders in 64 of 75 (85%) subjects, mostly bedtime resistance (66%). Spastic quadriplegia (OR=3.63; 95%CI 1.82 to15.94) and presence of epilepsy (OR=7.82; 95%CI 1.53 to 39.84) were significantly associated with sleep disorders in children with CP aged 4-10 years. Conclusion Sleep disorders are common in children with CP, with the majority experiencing bedtime resistance. Sleep disorders are more prevalent in subjects with spastic quadriplegia and epilepsy.

Autism Spectrum Disorder

Chapter

Jan 2021

Autism spectrum disorder (ASD) is a common neurobehavioral disorder with considerable complexity and without clearly defined etiologic underpinnings. A variety of factors are intertwined in this condition including genetic, biochemical, and cellular characteristics. A major aspect of ASD management is behavioral therapy, though pharmacologic agents produce major benefits as well. This work considers current pharmacologic principles in treatment of ASD in children, adolescents, and adults. Pharmacologic intervention is particularly helpful for treatment of the conditions that are frequently co-morbid with ASD—including anxiety, depression, aggressive/violent behaviors, repetitive behaviors, inattention with hyperactivity, and sleep disorders.

Environmental Light Exposure, Rest-Activity Rhythms, and Symptoms of Inattention and Hyperactivity: An Observational Study of Australian Preschoolers

Article

Full-text available

Jan 2021

Environmental light increases acute alertness and is the main regulator of the circadian clock in humans. In turn, circadian processes are strongly associated with inattention and hyperactivity symptoms in both children and adults. Evidence from animal studies suggest that light exposure may affect inattention and hyperactivity related behaviors during critical windows in early development. However, very little is known about the associations between light exposure, rest-activity rhythms and symptoms of inattention and hyperactivity in young children. Our aim was to examine whether the stability in rest-activity rhythms and the dosage, intensity and duration of environmental light were associated with symptoms of inattention and hyperactivity in children between 3 and 6 years of age. The present study used a subsample of the E4Kids Study. Objective measures of light exposure and stability of rest-activity rhythms were collected from 48 preschool children continuously over a period of two weeks. Parental reports of inattention and hyperactivity symptoms were collected concurrently and again 12 months later. Longer durations of light exposure were strongly associated with lower levels of hyperactivity symptoms at baseline (b = -0.64, CI = -.97; -0.25), but not at follow up. The stability of rest-activity rhythms was associated with hyperactivity symptoms at follow up (b = -0.44, -0.81; -0.08), but not at baseline. Neither the stability of rest-activity rhythms or light exposure were associated with inattention symptoms. We provide the first evidence that the duration and intensity of environmental light exposure is inversely and strongly associated with symptoms of hyperactivity in young children in a naturalistic setting. Potential mechanistic pathways are discussed.

Circadian zinc feeding regime in laying hens related to laying performance, oxidation status, interaction of zinc and calcium

Article

Full-text available

Aug 2020

This study investigated that circadian zinc (Zn) feeding regime affected laying performance, Zn and calcium (Ca) status, antioxidant capacity and gene expression of circadian clock, Ca and Zn transporter in laying hens. In total, 162 of 21-week Hyline Sophie laying hens were assigned randomly into three groups including CON group (Control Zn, basal diets supplemented 60 mg/kg Zn), HL group (High-low Zn, basal diets supplemented 120 mg/kg Zn - basal diets) and LH group (Low-high Zn, basal diets - basal diets supplemented 120 mg/kg Zn), which were fed at 0530 h and 1530 h respectively. Blood, tibia, duodenum and eggshell gland samples were collected at 8 h intervals with starting at 0000 h in one day after 10 weeks of experiment. Compared with CON group: 1) Feed conversion ratio (FCR) of LH and HL group decreased significantly (P < 0.05). 2) In serum, total antioxidant capacity (T-AOC) and CuZn-superoxide dismutase (CuZn-SOD) at 0000 h increased significantly, as well as Ca and Zn concentration of tibia at 0800 h in LH group (P < 0.05). 3) In duodenum, mRNA expression of CaBP and NCX1 at 1600 h in HL group up regulated significantly, as well as Per2 and Per3 at 0000 h, CLOCK, Cry2, Per2 and Per3 at 1600 h (P < 0.05). But, Zn5 at 0800 h in HL group down regulated significantly (P < 0.05). 4) In eggshell gland, the mRNA expression of CaBP at 0000 h and Zn5 at 1600 h in HL group down regulated significantly (P < 0.05). However, SOD at 1600 h in HL group up regulated significantly, as well as Cry1 and Per3 at 0800 h in HL group up regulated significantly (P < 0.05). In conclusion, circadian Zn feeding diet regime was beneficial to improvement of FCR. The regulation of laying hens’ circadian rhythms affected Zn and Ca transporter and interrelationship between Ca and Zn metabolism, also altered antioxidant capacity in present study. Therefore, circadian Zn feeding regime can be considered as a new method to improve laying performance in laying hens.

Adult Attention-Deficit Hyperactivity Disorder and clinical correlates of Delayed Sleep Phase Disorder

Article

Jun 2020
PSYCHIAT RES

The purpose of the study was to assess the prevalence and clinical correlates of Delayed Sleep Phase Disorder (DSPD) in adults with Attention-Deficit/Hyperactivity Disorder. Participants were 102 adults (Female= 27), aged 18-65 (mean age= 28.2 years), with ADHD diagnosed in adulthood. ADHD and DSPD diagnosis were made according to DSM-5 criteria. Assessing instruments included the Morningness-Eveningness Questionnaire, the brief Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire, the Barratt Impulsiveness Scale, the Reactivity Intensity Polarity Stability Questionnaire-40 and the World Health Organization Disability Assessment Schedule 2.0. Epidemiological and Clinical features were compared in patients with and without DSPD. 34 out of 102 patients were classified as having a Delayed Sleep Phase Disorder. As expected, DSPD patients reported a more frequent evening chronotype. In the multivariate logistic regression analysis, Delayed Sleep Phase Disorder was significantly associated with young age, cannabis use, cyclothymic temperamental traits and severe global impairment. An early diagnosis with a proper treatment targeted to both disorders may be fundamental in order to improve the overall functioning and the outcome of adult ADHD patients.

ADHD Circuitries in the R-Do-C Perspective

Chapter

Apr 2020

Even though the DSM and ICD have been of value in facilitating communication between clinicians and researchers, they failed in implementing the neuroscientific data, missing to establishing “external validator” of the clinical syndrome, and therefore were unsuccessful in establishing the validity of their diagnostic categories beyond the clinical level.

Pathology of Sibling Sub System: Phenomenal World of Sibling in Families with Children with ADHD Disorder; a Qualitative Study

Article

Oct 2019

The Association between Attention-Deficit/Hyperactivity Disorder and Atopic Dermatitis: A Study among Iranian Children

Article

Nov 2019
Indian J Dermatol

Background: The co-occurrence of attention-deficit/hyperactivity disorder (ADHD) with atopic dermatitis (AD) has been well described in some recent association studies; however, we did not have any perspective on this relationship in our country. Aim and objective: Hence, the present study aimed to assess the prevalence of ADHD in children with AD. Materials and methods: This cross-sectional study was performed on 95 consecutive children and adolescents (aged 4-18 years) who were referred to dermatology clinics at the two hospitals in Tehran during 2017 with atopic dermatitis. The evidence of atopy was assessed using the 2003 National Survey of Children's Health. The diagnosis of ADHD was based on the Conner Rating Scale. The sleep disorder was also assessed by the Pittsburg sleep quality questionnaire. Results: The prevalence of hyperactivity and attention deficit in our AD patients was 20.0% and 29.47%, respectively. Furthermore, patients with sleep problem were significantly more likely to have hyperactivity disorder (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.04-8.16, P = 0.04). According to the results of multiple logistic regression analyses, flexor involvement was the only predictor of hyperactivity disorder in the final model. The univariate and multivariate analyses showed that having attention deficit was associated with having cheek involvement (OR = 3.63, 95% CI: 1.44-9.14, P = 0.01) and sleep problem (OR = 3.68, 95% CI: 1.45-9.33, P = 0.01). Conclusion: It seems that neurocognitive disturbances due to sleep restriction in AD children may be one of the main trigger, especially for attention deficit.

Therapeutic Effects

Chapter

Aug 2019

Wout van Bommel

Chronotherapy is timing the treatment of a disease (like surgery or medicine administration) relative to the circadian phase of a patient. The reason that chronotherapy often works is that the actual composition of various bodily properties varies with the circadian phase. Light can sometimes be a therapy for a disrupted circadian system. Light therapy, specifically timed exposure to light, is a particular form of chronotherapy. The reason for the circadian disruption may either be the way of living or be connected with a disease. In some cases, light therapy does not cure the disease itself but helps to reduce negative symptoms of the disease. Although a detailed treatment of the subject of clinical light therapy is outside the scope of this book, a short survey is given to give insight into the possibilities of light in this respect. In some cases, specific interior lighting can be applied as light therapy, next to its task of providing proper visual conditions. Light therapy for depressions (seasonal and non-seasonal), sleep disorders, Alzheimer’s disease, Parkinson’s disease, attention-deficit hyperactivity disorders (ADHD) and eating disorders are dealt with. Irregular light-dark rhythms quite often occur in the patient rooms of hospitals. Specifically designed artificial lighting that supplements daylight entering the patient room can improve the sleep quality and mood of the patient and reduce the length of stay in the hospital. Ongoing research investigates whether lighting as part of a multicomponent approach can help to fight the critical intensive care delirium in hospitals.

Treatment Resistance in Psychiatry Risk Factors, Biology, and Management: Risk Factors, Biology, and Management

Book

Jan 2019

Yong-Ku Kim

This book reviews all the important aspects of treatment-resistant psychiatric disorders, covering issues such as definitions, clinical aspects, neurobiological correlates, treatment options, and predictors of treatment response. The book is divided into three sections, the first of which examines the most recent thinking on treatment resistance in psychiatry, including definition and epidemiology, paradigm shift in the study of the subjects, individual susceptibility and resilience, abnormal structural or functional connectivity, and insights from animal models. The second section then discusses treatment resistance in each of the major psychiatric disorders, with particular focus on the responsible clinical and biological factors and the available management strategies. Finally, more detailed information is presented on diverse pharmacological and non-pharmacological therapeutic interventions. The book, written by leading experts from across the world, will be of value to all who seek a better understanding of the clinical-neurobiological underpinnings and the development of management for treatment resistance in psychiatric disorders.

Treatment Resistance in Attention-Deficit/Hyperactivity Disorder: Risk Factors, Biology, and Management

Chapter

Jan 2019

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common and widely researched disorders of childhood. US prevalence estimates of attention-deficit/hyperactivity disorder in youth ages 4–17 range from 5% to 11%, with the childhood male to female ratio estimated to be 3–4:1 in epidemiological samples. The economic and psychosocial costs of ADHD are significant for patients, their families, and the society, and ADHD is associated with a higher risk for substance use disorders and other comorbid psychiatric disorders, increased mortality due to accidents, unwanted pregnancies, lower academic achievement and occupational performance, adult antisocial behavior, and poor social functioning, including higher divorce rates. ADHD is a heterogeneous disorder with a variety of core symptom presentations, degree of severity, and psychiatric comorbidities. Therefore, treatment involves a stepwise, systematic approach targeting the predominant clinical symptoms with the goal of minimizing the negative impact on social and academic functioning. Pharmacological treatment for ADHD, although highly effective, is associated with marked variabilities in clinical response, optimal dosage needed, and tolerability. In this chapter, the authors discuss both established and novel pharmacological treatment and neuromodulation in treatment-resistant ADHD.

Media Use, Sleep Quality, and ADHD Symptoms in a Community Sample and a Sample of ADHD Patients Aged 8 to 18 Years

Article

Oct 2018

Objective: Relationships between sleep, screen-based media, and ADHD symptomatology were investigated using a case- and community-based approach. Method: N = 357 healthy and N = 61 children with ADHD (12.72 ± 2.83 years) completed a sleep and media questionnaire. To measure ADHD symptomatology, parents filled out the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale. Two samples were formed: a matched ( N = 61 patients and N = 61 controls) and a community sample ( N = 357 healthy participants and N = 20 patients). Results: Compared with controls, participants with ADHD reported delayed sleep onset and more screen time on school days. Adolescent patients showed more behavior promoting delayed sleep phase. In the community sample, media time, sleep deviation, and circadian rhythm were correlated with ADHD symptomatology. Furthermore, media time, sleep-wake behavior, and sleep deviation were predictive of ADHD symptomatology (variance explained = 4%-15%). Conclusion: Longer media time and inadequate sleep-wake behavior increase the risk of ADHD-like symptoms. However, research using objective assessments is needed to disentangle this distinct association and to provide possible directions for intervention.

ADHD 24/7: Circadian Clock Genes, Chronotherapy and Sleep/Wake Cycle Insufficiencies in ADHD

Article

Full-text available

Sep 2018

Objectives: The current paper addresses the evidence for circadian clock characteristics associated with Attention-Deficit Hyperactivity Disorder (ADHD), and possible therapeutic approaches based on chronomodulation through bright light therapy. Methods: We review the data reported in ADHD on genetic risk factors for phase-delayed circadian rhythms and on the role of photic input in circadian re-alignment. Results: Single nucleotide polymorphisms (SNPs) in circadian genes were recently associated with core ADHD symptoms, increased evening-orientation and frequent sleep problems. Additionally, alterations in exposure and response to photic input may underlie circadian problems in ADHD. Bright light (BL) therapy was shown to be effective for re-alignment of circadian physiology toward morningness, reducing sleep disturbances and bringing overall improvement in ADHD symptoms. The susceptibility of the circadian system to phase shift by timed BL exposure may have broad cost-effective potential implications for the treatment of ADHD. Conclusions: We conclude that further research of circadian function in ADHD should focus on detection of genetic markers (e.g., using human skin fibroblasts) and development of BL-based therapeutic interventions.

Practice Parameters for the Role of Actigraphy in the Study of Sleep and Circadian Rhythms: An Update for 2002

Article

Full-text available

May 2003

Actigraphy is a method used to study sleep-wake patterns and circadian rhythms by assessing movement, most commonly of the wrist. These evidence-based practice parameters are an update to the Practice Parameters for the Use of Actigraphy in the Clinical Assessment of Sleep Disorders, published in 1995. These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Recommendations are based on the accompanying comprehensive review of the medical literature regarding the role of actigraphy, which was developed by a task force commissioned by the American Academy of Sleep Medicine. The following recommendations serve as a guide to the appropriate use of actigraphy. Actigraphy is reliable and valid for detecting sleep in normal, healthy populations, but less reliable for detecting disturbed sleep. Although actigraphy is not indicated for the routine diagnosis, assessment, or management of any of the sleep disorders, it may serve as a useful adjunct to routine clinical evaluation of insomnia, circadian-rhythm disorders, and excessive sleepiness, and may be helpful in the assessment of specific aspects of some disorders, such as insomnia and restless legs syndrome/periodic limb movement disorder. The assessment of daytime sleepiness, the demonstration of multiday human-rest activity patterns, and the estimation of sleep-wake patterns are potential uses of actigraphy in clinical situations where other techniques cannot provide similar information (e.g., psychiatric ward patients). Superiority of actigraphy placement on different parts of the body is not currently established. Actigraphy may be useful in characterizing and monitoring circadian rhythm patterns or disturbances in certain special populations (e.g., children, demented individuals), and appears useful as an outcome measure in certain applications and populations. Although actigraphy may be a useful adjunct to portable sleep apnea testing, the use of actigraphy alone in the detection of sleep apnea is not currently established. Specific technical recommendations are discussed, such as using concomitant completion of a sleep log for artifact rejection and timing of lights out and on; conducting actigraphy studies for a minimum of three consecutive 24-hour periods; requiring raw data inspection; permitting some preprocessing of movement counts; stating that epoch lengths up to 1 minute are usually sufficient, except for circadian rhythm assessment; requiring interpretation to be performed manually by visual inspection; and allowing automatic scoring in addition to manual scoring methods.

Treatment of attention deficit hyperactivity disorder insomnia with blue wavelength light-blocking glasses

Article

Full-text available

Jan 2013

Rachel E Fargason, Taylor Preston, Emily Hammond, Roberta May, Karen L GambleDepartment of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USABackground: The aim of this study was to examine a nonmedical treatment alternative to medication in attention deficit hyperactivity disorder (ADHD) insomnia, in which blue wavelength light-blocking glasses are worn during the evening hours to counteract the phase-delaying effect of light. Outcome measures included sleep quality and midsleep time. The capacity of ADHD subjects to comply with treatment using the glasses was assessed.Methods: Daily bedtime, wake-up time, and compliance diaries were used to assess sleep quality and timing during a baseline observation week and a 2-week intervention period. The Pittsburgh Sleep Quality Index (PSQI) was administered following baseline and intervention. The intervention protocol consisted of use of blue wavelength-blocking glasses and a moderate lighting environment during evening hours.Results: Partial and variable compliance were noted, with only 14 of 22 subjects completing the study due to nonadherence with wearing the glasses and diary completion. Despite the minimum 3-hour recommendation, glasses were worn, on average, for 2.4 hours daily. Lighting was reduced for only 58.7% of the evening. Compared with baseline, the intervention resulted in significant improvement in global PSQI scores, PSQI subcomponent scores, and sleep diary measures of morning refreshment after sleep (P = 0.037) and night-time awakenings (P = 0.015). Global PSQI scores fell from 11.15 to 4.54, dropping below the cut-off score of 5 for clinical insomnia. The more phase-delayed subjects, ie, those with an initial midsleep time after 4:15 am, trended towards an earlier midsleep time by 43.2 minutes following the intervention (P = 0.073). Participants reported less anxiety following the intervention (P = 0.048).Conclusions: Despite only partial compliance with intervention instructions, subjects completing the study showed subjectively reduced anxiety and improved sleep quality on multiple measures. The more sleep-delayed subjects trended toward an earlier sleep period following use of the glasses. Blue-blocking glasses are a potential insomnia treatment for more compliant subjects with ADHD insomnia, especially those with prominent sleep delay. Larger studies of blue light-blocking glasses in more phase-delayed groups could reveal significant advances in chronotherapeutics.Keywords: insomnia, attention deficit hyperactivity disorder, circadian rhythm disorders, chronobiological treatment

EphA4 is Involved in Sleep Regulation But Not in the Electrophysiological Response to Sleep Deprivation

Article

Full-text available

Nov 2015
SLEEP

Study objectives: Optimal sleep is ensured by the interaction of circadian and homeostatic processes. Although synaptic plasticity seems to contribute to both processes, the specific players involved are not well understood. The EphA4 tyrosine kinase receptor is a cell adhesion protein regulating synaptic plasticity. We investigated the role of EphA4 in sleep regulation using electrocorticography in mice lacking EphA4 and gene expression measurements. Methods: EphA4 knockout (KO) mice, Clock(Δ19/Δ19) mutant mice and littermates, C57BL/6J and CD-1 mice, and Sprague-Dawley rats were studied under a 12 h light: 12 h dark cycle, under undisturbed conditions or 6 h sleep deprivation (SD), and submitted to a 48 h electrophysiological recording and/or brain sampling at different time of day. Results: EphA4 KO mice showed less rapid eye movement sleep (REMS), enhanced duration of individual bouts of wakefulness and nonrapid eye movement sleep (NREMS) during the light period, and a blunted daily rhythm of NREMS sigma activity. The NREMS delta activity response to SD was unchanged in EphA4 KO mice. However, SD increased EphA4 expression in the thalamic/hypothalamic region in C57BL/6J mice. We further show the presence of E-boxes in the promoter region of EphA4, a lower expression of EphA4 in Clock mutant mice, a rhythmic expression of EphA4 ligands in several brain areas, expression of EphA4 in the suprachiasmatic nuclei of the hypothalamus (SCN), and finally an unchanged number of cells expressing Vip, Grp and Avp in the SCN of EphA4 KO mice. Conclusions: Our results suggest that EphA4 is involved in circadian sleep regulation.

Association Between Sleep Problems and Symptoms of Attention Deficit Hyperactivity Disorder in Adolescence: Results From a Large Population-Based Study

Article

Full-text available

Oct 2015
Behav Sleep Med

Sleep problems and symptoms of ADHD are common in adolescence, but detailed epidemiological assessment of their association is lacking. Using data from a recent population-based study, 9,846 adolescents aged 16 to 19 provided detailed information on sleep and symptoms of ADHD. Results confirmed a large overlap between self-reported symptoms of ADHD and all sleep variables studied. Symptoms of ADHD were linked to shorter sleep duration, longer sleep latency, and nocturnal wake time, as well as larger sleep deficiency. ADHD symptoms also increased the odds of insomnia and delayed sleep phase syndrome. The associations were only partially explained by confounders (mainly depression). The findings suggest that sleep problems should be included as a treatment target in efforts to reduce symptoms of ADHD in adolescence.

ADHD Prevalence: Altitude or Sunlight? Better Understanding the Interrelations of Dopamine and the Circadian System

Article

Full-text available

Sep 2015
J Attention Disord

Association Between Altitude and Regional Variation of ADHD in Youth

Article

Full-text available

Mar 2015
J Attention Disord

The purpose of this study was to evaluate the effect of altitude on rates of ADHD. As decreased dopamine (DA) activity has been reported with ADHD and hypoxia has shown to be associated with increased DA, we hypothesized that states at higher altitudes would have lower rates of ADHD. State estimates from the 2007 National Survey of Children's Health (NSCH) report and 2010 National Survey of Children with Special Health Care Needs (NS-CSHCN) report were used to extract the percentages of youth ages 4 to 17 diagnosed with ADHD. Both the datasets independently revealed that the prevalence of ADHD decreases with increasing altitude (R (2) = .38, p < .001; R (2) = .31, p < .001), respectively. This study controlled for potential confounds (e.g., low birth weight, ethnicity, and household size). These findings suggest a need for further investigation into the extent by which altitude may serve as a protective factor for ADHD. © 2015 SAGE Publications.

Clocking in: Chronobiology in rheumatoid arthritis

Article

Full-text available

Mar 2015
NAT REV RHEUMATOL

Circadian rhythms are of crucial importance for cellular and physiological functions of the brain and body. Chronobiology has a prominent role in rheumatoid arthritis (RA), with major symptoms such as joint pain and stiffness being most pronounced in the morning, possibly mediated by circadian rhythms of cytokine and hormone levels. Chronobiological principles imply that tailoring the timing of treatments to the circadian rhythm of individual patients (chronotherapy) could optimize results. Trials of NSAID or methotrexate chronotherapy for patients with RA suggest such an approach can improve outcomes and reduce adverse effects. The most compelling evidence for RA chronotherapy, however, is that coordinating the timing of glucocorticoid therapy to coincide with the nocturnal increase in blood IL-6 levels results in reduced morning stiffness and pain compared with the same glucocorticoid dose taken in the morning. Aside from optimizing relief of the core symptoms of RA, chronotherapy might also relieve important comorbid conditions such as depression and sleep disturbances. Surprisingly, chronobiology is not mentioned in official guidelines for conducting RA drug registration trials. Given the imperative to achieve the best value with approved drugs and health budgets, the time is ripe to translate the 'circadian concept' in rheumatology from bench to bedside.

Thomas R, Sanders S, Doust J, BellerE, Glasziou P, Prevalence of Attention Deficit Hyperactivity Disorder: A systematic review and meta-analysis.

Article

Full-text available

Mar 2015

Rae Thomas

Background and objective: Overdiagnosis and underdiagnosis of attention-deficit/hyperactivity disorder (ADHD) are widely debated, fueled by variations in prevalence estimates across countries, time, and broadening diagnostic criteria. We conducted a meta-analysis to: establish a benchmark pooled prevalence for ADHD; examine whether estimates have increased with publication of different editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM); and explore the effect of study features on prevalence. Methods: Medline, PsycINFO, CINAHL, Embase, and Web of Science were searched for studies with point prevalence estimates of ADHD. We included studies of children that used the diagnostic criteria from DSM-III, DSM-III-R and DSM-IV in any language. Data were extracted on sampling procedure, sample characteristics, assessors, measures, and whether full or partial criteria were met. Results: The 175 eligible studies included 179 ADHD prevalence estimates with an overall pooled estimate of 7.2% (95% confidence interval: 6.7 to 7.8), and no statistically significant difference between DSM editions. In multivariable analyses, prevalence estimates for ADHD were lower when using the revised third edition of the DSM compared with the fourth edition (P = .03) and when studies were conducted in Europe compared with North America (P = .04). Few studies used population sampling with random selection. Most were from single towns or regions, thus limiting generalizability. Conclusions: Our review provides a benchmark prevalence estimate for ADHD. If population estimates of ADHD diagnoses exceed our estimate, then overdiagnosis may have occurred for some children. If fewer, then underdiagnosis may have occurred.

Circadian Modulation of Dopamine Levels and Dopaminergic Neuron Development Contributes to Attention Deficiency and Hyperactive Behavior

Article

Full-text available

Feb 2015
J NEUROSCI

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children and adults. While ADHD patients often display circadian abnormalities, the underlying mechanisms are unclear. Here we found that the zebrafish mutant for the circadian gene period1b (per1b) displays hyperactive, impulsive-like, and attention deficit-like behaviors and low levels of dopamine, reminiscent of human ADHD patients. We found that the circadian clock directly regulates dopamine-related genes monoamine oxidase and dopamine β hydroxylase, and acts via genes important for the development or maintenance of dopaminergic neurons to regulate their number and organization in the ventral diencephalic posterior tuberculum. We then found that Per1 knock-out mice also display ADHD-like symptoms and reduced levels of dopamine, thereby showing highly conserved roles of the circadian clock in ADHD. Our studies demonstrate that disruption of a circadian clock gene elicits ADHD-like syndrome. The circadian model for attention deficiency and hyperactive behavior sheds light on ADHD pathogenesis and opens avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder. Copyright © 2015 the authors 0270-6474/15/352572-16$15.00/0.

Manipulating circadian clock neuron firing rate resets molecular circadian rhythms and behavior

Article

Full-text available

Feb 2015

To examine the interaction between molecular, electrical and behavioral circadian rhythms, we combined optogenetic manipulation of suprachiasmatic nucleus (SCN) firing rate with bioluminescence imaging and locomotor activity monitoring. Manipulating firing rate reset circadian rhythms both ex vivo and in vivo, and this resetting required spikes and network communication. This suggests that SCN firing rate is fundamental to circadian pacemaking as both an input to and output of the molecular clockworks.

The molecular genetic architecture of attention deficit hyperactivity disorder

Article

Full-text available

Jan 2015

Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition which affects 2-10% of school age children worldwide. Although the underlying molecular mechanism for the disorder is poorly understood, familial, twin and adoption studies suggest a strong genetic component. Here we provide a state-of-the-art review of the molecular genetics of ADHD incorporating evidence from candidate gene and linkage designs, as well as genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs) and rare copy number variations (CNVs). Bioinformatic methods such as functional enrichment analysis and protein-protein network analysis are used to highlight biological processes of likely relevance to the aetiology of ADHD. Candidate gene associations of minor effect size have been replicated across a number of genes including SLC6A3, DRD5, DRD4, SLC6A4, LPHN3, SNAP-25, HTR1B, NOS1 and GIT1. Although case-control SNP-GWAS have had limited success in identifying common genetic variants for ADHD that surpass critical significance thresholds, quantitative trait designs suggest promising associations with Cadherin13 and glucose-fructose oxidoreductase domain 1 genes. Further, CNVs mapped to glutamate receptor genes (GRM1, GRM5, GRM7 and GRM8) have been implicated in the aetiology of the disorder and overlap with bioinformatic predictions based on ADHD GWAS SNP data regarding enriched pathways. Although increases in sample size across multi-center cohorts will likely yield important new results, we advocate that this must occur in parallel with a shift away from categorical case-control approaches that view ADHD as a unitary construct, towards dimensional approaches that incorporate endophenotypes and statistical classification methods.Molecular Psychiatry advance online publication, 20 January 2015; doi:10.1038/mp.2014.183.

Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice

Article

Full-text available

Jan 2015
MOL PSYCHIATR

Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here, we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of euthymia at night. Mood-cycling coincides with abnormal daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine hydroxylase (TH) levels and dopamine synthesis. To determine the significance of daytime increases in VTA dopamine activity to manic behaviors, we developed a novel optogenetic stimulation paradigm that produces a sustained increase in dopamine neuronal activity and find that this induces a manic-like behavioral state. Time-dependent dampening of TH activity during the day reverses manic-related behaviors in ClockΔ19 mice. Finally, we show that CLOCK acts as a negative regulator of TH transcription, revealing a novel molecular mechanism underlying cyclic changes in mood-related behavior. Taken together, these studies have identified a mechanistic connection between circadian gene disruption and the precipitation of manic episodes in bipolar disorder. Molecular Psychiatry advance online publication, 6 January 2015; doi:10.1038/mp.2014.167 INTRODUCTION

A circadian gene expression atlas in mammals: Implications for biology and medicine

Article

Full-text available

Oct 2014

Significance We generated high-resolution multiorgan expression data showing that nearly half of all genes in the mouse genome oscillate with circadian rhythm somewhere in the body. Such widespread transcriptional oscillations have not been previously reported in mammals. Applying pathway analysis, we observed new clock-mediated spatiotemporal relationships. Moreover, we found a majority of best-selling drugs in the United States target circadian gene products. Many of these drugs have relatively short half-lives, and our data predict which may benefit from timed dosing.

The Role of the Circadian Clock in Animal Models of Mood Disorders

Article

Full-text available

Mar 2014

An association between circadian clock function and mood regulation is well established and has been proposed as a factor in the development of mood disorders. Patients with depression or mania suffer disturbed sleep-wake cycles and altered rhythms in daily activities. Environmentally disrupted circadian rhythms increase the risk of mood disorders in the general population. However, proof that a disturbance of circadian rhythms is causally involved in the development of psychiatric disorders remains elusive. Using clock gene mutants, manipulations of sleep-wake and light-dark cycles, and brain lesions affecting clock function, animal models have been developed to investigate whether circadian rhythm disruptions alter mood. In this review, selected animal models are examined to address the issue of causality between circadian rhythms and affective behavior. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Complete sleep-wake cycle reversal related to ADHD detected by actigraphy

Article

Full-text available

Aug 2013
Ann Clin Psychiatr

Geographic Variation in the Prevalence of Attention-Deficit/Hyperactivity Disorder: The Sunny Perspective

Article

Full-text available

Mar 2013

Background: Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder of childhood, with average worldwide prevalence of 5.3%, varying by region. Methods: We assessed the relationship between the prevalence of ADHD and solar intensity (SI) (kilowatt hours/square meters/day) on the basis of multinational and cross-state studies. Prevalence data for the U.S. were based on self-report of professional diagnoses; prevalence data for the other countries were based on diagnostic assessment. The SI data were obtained from national institutes. Results: In three datasets (across 49 U.S. states for 2003 and 2007, and across 9 non-U.S. countries) a relationship between SI and the prevalence of ADHD was found, explaining 34%-57% of the variance in ADHD prevalence, with high SI having an apparent preventative effect. Controlling for low birth weight, infant mortality, average income (socioeconomic status), latitude, and other relevant factors did not change these findings. Furthermore, these findings were specific to ADHD, not found for the prevalence of autism spectrum disorders or major depressive disorder. Conclusions: In this study we found a lower prevalence of ADHD in areas with high SI for both U.S. and non-U.S. data. This association has not been reported before in the literature. The preventative effect of high SI might be related to an improvement of circadian clock disturbances, which have recently been associated with ADHD. These findings likely apply to a substantial subgroup of ADHD patients and have major implications in our understanding of the etiology and possibly prevention of ADHD by medical professionals, schools, parents, and manufacturers of mobile devices.

Delayed Sleep Timing and Symptoms in Adults With Attention-Deficit/Hyperactivity Disorder: A Controlled Actigraphy Study

Article

Full-text available

Feb 2013
CHRONOBIOL INT

Patients with attention-deficit/hyperactivity disorder (ADHD) often exhibit disrupted sleep and circadian rhythms. Determination of whether sleep disturbance and/or circadian disruption are differentially associated with symptom severity is necessary to guide development of future treatment strategies. Therefore, we measured sleep and ADHD symptoms in participants aged 19-65 who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) criteria for ADHD and insomnia without psychiatric comorbidities by monitoring actigraphy and daily sleep logs for 2 wks, as well as the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), the ADHD Rating Scale (ADHD-RS), and a clinic-designed sleep behavior questionnaire. Principal components analysis identified correlated circadian- and sleep-related variables in all participants with ADHD who completed the study (n = 24). The identified components were entered into a backwards stepwise linear regression analysis, which indicated that delayed sleep timing and increased sleepiness (ESS) (but not sleep duration or sleep efficiency) significantly predicted greater severity of both hyperactive-impulsive and inattentive ADHD symptoms (p < .05 for partial regression coefficients). In addition, combined subtypes had the most impaired age-adjusted sleep quality (PSQI scores; p < .05 compared with healthy controls; n = 13), and 91.7% of them reported going to bed late due to being "not tired/too keyed up to sleep" compared with 57.2% and 50% of inattentive and symptom-controlled participants, respectively (p < .05). In conclusion, the results of this study suggest that ADHD symptom severity correlates with delayed sleep timing and daytime sleepiness, suggesting that treatment interventions aimed at advancing circadian phase may improve daytime sleepiness. In addition, ADHD adults with combined hyperactive-impulsive and inattentive symptoms have decreased sleep quality as well as the delayed sleep timing of predominately inattentive subtypes. (Author correspondence: rfargason@uab.edu ).

Adults With ADHD-Without Insomnia History Have Subclinical Sleep Disturbance but Not Circadian Delay: An ADHD Phenotype?

Article

Full-text available

Sep 2012
J Attention Disord

Objective: To explore the potential ADHD phenotype of ADHD-without reported insomnia in comparison with controls and their tolerance of stimulants in a cohort rigorously screened for comorbidities. Method: Adults meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria for ADHD-without insomnia and matched controls were administered a sleep/medication-timing questionnaire and the Pittsburgh Sleep Quality Index. Results: Among 105 participants, ADHD participants scored in the mild insomnia range and showed reduced sleep quality compared with controls, F(3, 101) = 34.9, p < .05, but no delay in bedtime/mid-sleep-time circadian measures. Sleep quality was similar between stimulant, nonstimulant, and unmedicated groups, χ(2) 2 = 0.445, p = .80. However, later timing of stimulant dosing was correlated with later sleep times, p < .01. Conclusion: We isolated a potential phenotype of ADHD-without circadian delay in adults who demonstrated insomnia/sleep quality disturbance by sleep instrument, but lacked sleep-timing delay. Nevertheless, sleep delays were associated temporally with late-dosed stimulants in this group.

Transcriptional Architecture and Chromatin Landscape of the Core Circadian Clock in Mammals

Article

Full-text available

Aug 2012
SCIENCE

The mammalian circadian clock involves a transcriptional feed back loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression, and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases: a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Only 22% of messenger RNA (mRNA) cycling genes are driven by de novo transcription, suggesting that both transcriptional and posttranscriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.

Sleep disturbance, circadian preference and symptoms of adult attention deficit hyperactivity disorder (ADHD)

Article

Full-text available

Jul 2012
J NEURAL TRANSM

Inattention is a core symptom of attention deficit hyperactivity disorder (ADHD) and one of the main impairments resulting from insomnia disorders. These disorders have also been reported to be linked with disturbances in circadian rhythms and with increased eveningness. To explore these associations, more than 550 adults were surveyed across Romania. Using self-reported questionnaires, the presence and severity of ADHD and insomnia symptoms were determined, together with sleep and circadian typology parameters. ADHD symptoms were more frequent and severe among younger individuals. Subjects with probable ADHD complained more frequently of sleep disturbance of the insomnia type (more than 50 %) and reported shorter sleep durations and longer sleep latencies and more frequent unwanted awakenings. Individuals likely to suffer from ADHD and/or insomnia disorder were significantly more evening oriented than controls. Inattention was associated with both insomnia and eveningness, while impulsivity was associated with poor sleep. Hyperactivity and sleep timing were associated with poor sleep only in probable insomnia group. These findings highlight the reciprocal links between ADHD symptoms, sleep and diurnal preference.

Circadian entrainment and its role in depression: A mechanistic review

Article

Full-text available

Jul 2012
J NEURAL TRANSM

The natural rotation of the earth generates an environmental day-night cycle that repeats every 24 h. This daily transition from dawn to dusk provides one of the most important time cues to which the majority of organisms synchronise their activity. Under these conditions, natural light, a photic stimulus, provides the principal entraining cue. In mammals, an endogenous circadian pacemaker located within the suprachiasmatic nucleus (SCN) of the hypothalamus acts as a coordinating centre to align physiological activity with the environmental light-dark cycle. However, the SCN also receives regulatory input from a number of behavioural, non-photic, cues such as physical activity, social interactions and feeding routines. The unique ability of the SCN to integrate both photic and non-photic cues allows it to generate a rhythm that is tailored to the individual and entrained to the environment. Here, we review the key neurotransmitter systems involved in both photic and non-photic transmission to the SCN and their interactions that assist in generating an entrained output rhythm. We also consider the impact on health of a desynchronised circadian system with a focus on depressive affective disorders and current therapies aimed at manipulating the relationship between photic and non-photic SCN regulators.

Methylphenidate Modifies the Motion of the Circadian Clock

Article

Full-text available

Jul 2012
NEUROPSYCHOPHARMACOL

People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.

Evaluating the links between schizophrenia and sleep and circadian rhythm disruption

Article

Full-text available

May 2012
J NEURAL TRANSM

Sleep and circadian rhythm disruption (SCRD) and schizophrenia are often co-morbid. Here, we propose that the co-morbidity of these disorders stems from the involvement of common brain mechanisms. We summarise recent clinical evidence that supports this hypothesis, including the observation that the treatment of SCRD leads to improvements in both the sleep quality and psychiatric symptoms of schizophrenia patients. Moreover, many SCRD-associated pathologies, such as impaired cognitive performance, are routinely observed in schizophrenia. We suggest that these associations can be explored at a mechanistic level by using animal models. Specifically, we predict that SCRD should be observed in schizophrenia-relevant mouse models. There is a rapidly accumulating body of evidence which supports this prediction, as summarised in this review. In light of these emerging data, we highlight other models which warrant investigation, and address the potential challenges associated with modelling schizophrenia and SCRD in rodents. Our view is that an understanding of the mechanistic overlap between SCRD and schizophrenia will ultimately lead to novel treatment approaches, which will not only ameliorate SCRD in schizophrenia patients, but also will improve their broader health problems and overall quality of life.

Treating ADHD with agomelatine

Article

Full-text available

May 2012
J Attention Disord

Helmut Niederhofer

Agomelatine is a relatively new antidepressant, with affinities to MT1 and MT2 (responsible for the circadian rhythm) as well as to 5-HT2C receptors. Since antidepressants have demonstrated some benefit in the treatment of ADH and because of the fact, that ADHD is often associated with sleep disorders, we assumed, that it might be a therapeutic alternative also for ADHD. We proved this assumption in ten ADHD patients in a placebo controlled manner. Agomelatine's effect was superior to that of placebo, but seems to be less than that of Methylphenidate or placebo. If ADHD therapy with Methylphenidate or Atomoxetine is not indicated e.g. because of adverse side effects and if an ADHD patient suffers from additional sleep disorders, Agomelatine might be a helpful therapeutic alternative.

High self-perceived stress and many stressors, but normal diurnal cortisol rhythm, in adults with ADHD (attention-deficit/hyperactivity disorder)

Article

Full-text available

Mar 2009
HORM BEHAV

Attention-deficit/hyperactivity disorder (ADHD) in adults is associated with significant impairment in many life activities and may thus increase the risk of chronic stress in everyday life. We compared adults with a DSM-IV ADHD diagnosis (n = 28) with healthy controls (n = 28) regarding subjective stress and amounts of stressors in everyday life, diurnal salivary cortisol in the everyday environment and salivary cortisol before and after cognitive stress in a laboratory setting. The association between cortisol concentrations and impulsivity was also investigated. Consistent with assumptions, individuals with ADHD reported significantly more self-perceived stress than controls, and subjective stress correlated with the amount of stressors in everyday life. The two groups were comparable with respect to overall diurnal cortisol levels and rhythm, as well as in pre- and post-stress cortisol concentrations. Post-stress cortisol (but not baseline cortisol) concentration was positively correlated with impulsivity. The group with high post-stress cortisol also reported more symptoms of depression and anxiety, as well as self-perceived stress and stressors in every-day life. The diagnosis of ADHD significantly increased the risk of belonging to the group with high post-stress cortisol levels. The results in this study warrant a focus not only on the primary diagnosis of ADHD, but also calls for a broader assessment of stressors and subjective stress in everyday life, as well as support comprising stress management and coping skills.

Association study between a polymorphism at the 3 '-untranslated region of CLOCK gene and attention deficit hyperactivity disorder

Article

Full-text available

Aug 2010
BEHAV BRAIN FUNCT

The circadian locomotor output cycles kaput (CLOCK) gene encodes protein regulation circadian rhythm and also plays some roles in neural transmitter systems including the dopamine system. Several lines of evidence implicate a relationship between attention-deficit hyperactivity disorder (ADHD), circadian rythmicity and sleeping disturbances. A recent study has reported that a polymorphism (rs1801260) at the 3'-untranslated region of the CLOCK gene is associated with adult ADHD. To investigate the association between the polymorphism (rs1801260) in ADHD, two samples of ADHD probands from the United Kingdom (n = 180) and Taiwan (n = 212) were genotyped and analysed using within-family transmission disequilibrium test (TDT). Bonferroni correction procedures were used to just for multiple comparisons. We found evidence of increased transmission of the T allele of the rs1801260 polymorphism in Taiwanese samples (P = 0.010). There was also evidence of preferential transmission of the T allele of the rs1801260 polymorphism in combined samples from the Taiwan and UK (P = 0.008). This study provides evidence for the possible involvement of CLOCK in susceptibility to ADHD.

Associations Between Sleep Characteristics, Seasonal Depressive Symptoms, Lifestyle, and ADHD Symptoms in Adults

Article

Full-text available

Dec 2011
J Attention Disord

Objective: The authors explored associations between ADHD symptoms, seasonal depressive symptoms, lifestyle, and health. Method: Adult ADHD patients (n = 202) and controls (n = 189) completed the ASESA questionnaire involving lifestyle, eating pattern, and physical and psychological health, and validated measures on ADHD and sleep. ASESA is the Dutch acronym for inattention, sleep, eating pattern, mood, and general health questionnaire. Results: Indication for delayed sleep phase syndrome (DSPS) was 26% in patients and 2% in controls (p < .001). Patients reported shorter sleep, longer sleep-onset latency, and later midsleep. Shorter (R (2) = .21) and later (R (2) = .27) sleep were associated with hyperactivity, male gender, younger age, and seasonal depressive symptoms. Seasonal depressive symptoms were related to hyperactivity, female gender, unemployment, and l

Circadian rhythms and attention deficit hyperactivity disorder: The what, the when and the why

Abstract

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