Misophonia is related to stress but not directly with traumatic stress.

The relationship between misophonia, stress, and traumatic stress has not been well characterized scientifically. This study aimed to explore the relationships among misophonia, stress, lifetime traumatic events, and traumatic stress. A community sample of adults with self-reported misophonia (N = 143) completed structured diagnostic interviews and psychometrically validated self-report measures. Significant positive correlations were observed among perceived stress, traumatic stress, and misophonia severity. However, multivariate analyses revealed that perceived stress significantly predicted misophonia severity, over and above traumatic stress symptoms. The number of adverse life events was not associated with misophonia severity. Among symptom clusters of post-traumatic stress disorder, only hyperarousal was associated with misophonia severity. These findings suggest that transdiagnostic processes related to stress, such as perceived stress and hyperarousal, may be important phenotypic features and possible treatment targets for adults with misophonia.

Acceptability and feasibility of plasma phosphorylated-tau181 in two memory services.

BACKGROUND: Plasma phosphorylated-tau181 (p-tau181) represents a novel blood-based biomarker of Alzheimer's disease pathology. We explored clinicians' experience of the utility of plasma p-tau181 in Camden and Islington Memory Services. METHODS: Patients were identified by their clinician as appropriate for p-tau181. Their p-tau181 result was plotted on a reference range graph provided to clinicians. This was discussed with the patient at diagnostic feedback appointment. RESULTS: Twenty-nine participants' plasma p-tau181 samples were included (mean age 74 SD 8.5, 65% female). Nine clinicians participated in the study. Eighty-six percent of clinicians found the p-tau181 result to be helpful and in 93% of cases it was clearly understandable. The p-tau181 result was useful in making the diagnosis in 44% of cases. CONCLUSIONS: Plasma p-tau181 is a feasible test for use in memory services and acceptable to clinicians. Clinician feedback on utility in dementia diagnoses was mixed. Further work is required to provide education and training in understanding and interpreting ambiguity in biomarker results.

The unified protocol for transdiagnostic treatment of emotional disorders for misophonia: a pilot trial exploring acceptability and efficacy.

Introduction: Misophonia is a recently defined disorder characterized by distressing responses to everyday sounds, such as chewing or sniffling. Individuals with misophonia experience significant functional impairment but have limited options for evidenced-based behavioral treatment. To address this gap in the literature, the current pilot trial explored the acceptability and efficacy of a transdiagnostic cognitive-behavioral approach to treating symptoms of misophonia. Methods: This trial was conducted in two studies: In Study 1, the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) was delivered to eight patients in order to receive feedback to guide revisions to the treatment to suit this population. In Study 2, ten patients received the revised UP treatment to explore its acceptability and preliminary efficacy. This study used a single-case experimental design with multiple baselines, randomizing patients to either a 2-week baseline or 4-week baseline prior to the 16 weeks of treatment, followed by four weeks of follow-up. Results: The findings from these studies suggested that patients found both the original and adapted versions of the UP to be acceptable and taught them skills for how to manage their misophonia symptoms. Importantly, the findings also suggested that the UP can help remediate symptoms of misophonia, particularly the emotional and behavioral responses. Discussion: These findings provide preliminary evidence that this transdiagnostic treatment for emotional disorders can improve symptoms of misophonia in adults.

Sleep in Children with Autism Spectrum Disorder: A Narrative Review and Systematic Update.

Purpose of Review: Sleep problems are a common comorbidity for children with autism spectrum disorder (ASD), and research in this area has a relatively long history. Within this review, we first outline historic patterns in the field of sleep and ASD. Second, we conducted a systematic update and coded these studies based on their alignment with historic patterns. Research on ASD and sleep over the past two decades has primarily focused on four principal areas: (1) documenting the prevalence and types of sleep problems; (2) sleep problem treatment options and efficacy; (3) how sleep problems are associated with other behavioral, contextual, or biological elements; and (4) the impact of child sleep problems on families and care providers. The systematic update in this paper includes empirical studies published between 2018 and 2021 with terms for sleep and ASD within the title, keywords, or abstract. Recent Findings: In sum, 60 studies fit the inclusion/exclusion criteria and most fit within the historic patterns noted above. Notable differences included more global representation in study samples, studies on the impacts of COVID-19, and a growing body of work on sleep problems as an early marker of ASD. The majority of studies focus on correlates of sleep problems noting less optimal behavioral, contextual, and biological elements are associated with sleep problems across development for children with ASD. Summary: Recommendations for future directions include continued expansion of global and age representation across samples, a shift toward more treatment and implementation science, and studies that inform our mechanistic understanding of how sleep and ASD are connected. Supplementary Information: The online version contains supplementary material available at 10.1007/s40675-022-00234-5.

Phenotyping misophonia: Psychiatric disorders and medical health correlates.

Misophonia is characterized by decreased tolerance to specific sounds and associated stimuli that causes significant psychological distress and impairment in daily functioning (Swedo et al., 2022). Aversive stimuli (often called "triggers") are commonly repetitive facial (e.g., nose whistling, sniffling, and throat clearing) or oral (e.g., eating, drinking, and mouth breathing) sounds produced by other humans. Few empirical studies examining the nature and features of misophonia have used clinician-rated structured diagnostic interviews, and none have examined the relationship between misophonia and psychiatric disorders in the Diagnostic and Statistical Manual-5th version (DSM-5; American Psychiatric Association, 2013). In addition, little is known about whether there are any medical health problems associated with misophonia. Accordingly, the purpose of the present study was to improve the phenotypic characterization of misophonia by investigating the psychiatric and medical health correlates of this newly defined disorder. Structured diagnostic interviews were used to assess rates of lifetime and current DSM-5 psychiatric disorders in a community sample of 207 adults. The three most commonly diagnosed current psychiatric disorders were: (1) social anxiety disorder, (2) generalized anxiety disorder, and (3) specific phobia. The three most common lifetime psychiatric disorders were major depressive disorder, social anxiety disorder, and generalized anxiety disorder. A series of multiple regression analyses indicated that, among psychiatric disorders that were correlated with misophonia, those that remained significant predictors of misophonia severity after controlling for age and sex were borderline personality disorder, obsessive compulsive disorder, and panic disorder. No medical health problems were significantly positively correlated with misophonia severity.

Brief Report: A Specialized Fitness Program for Individuals with Autism Spectrum Disorder Benefits Physical, Behavioral, and Emotional Outcomes.

Individuals with autism spectrum disorder (ASD) engage in less physical activity than typically-developing peers. This can result in serious negative consequences for individual well-being and may contribute to the physical, behavioral, and emotional challenges associated with ASD. This study explored the potential benefits of trainer-led, individualized, physical fitness sessions specialized for ASD. Eleven individuals (ages 7-24 years) with ASD were assessed at baseline and following 15 fitness sessions. Participants demonstrated improvements in core and lower-body strength and reductions in restricted and repetitive patterns of behavior, along with non-significant but marked reductions in issues with daytime sleepiness. Results suggest the merit of specialized fitness programs and emphasize the need for larger and more rigorous research studies on this topic.

Associations between sleep problems and domains relevant to daytime functioning and clinical symptomatology in autism: A meta-analysis.

Autistic individuals experience significantly higher rates of sleep problems compared to the general population, which negatively impacts various aspects of daytime functioning. The strength of associations across domains of functioning has not yet been summarized across studies. The present meta-analysis examined the strength of associations between sleep problems and various domains of daytime functioning in autistic individuals. Searches were conducted in EMBASE, PubMed, Web of Science, and Google Scholar through May 2020. Inclusion criteria were: an index of sleep disturbance in individuals diagnosed with autism spectrum disorder (ASD); data collected prior to any sleep-related intervention; statistical data indicating relations between sleep problems and outcomes relevant to behavior, cognition, and physical or mental health. Exclusion criteria were: statistics characterizing the relationship between sleep disturbance and outcome variables that partialled out covariates; studies examining correlations between different measures of sleep disturbance. Participants totaled 15,074 from 49 published articles and 51 samples, yielding 209 effect sizes. Sleep problems were significantly associated with more clinical symptomatology and worse daytime functioning. Subgroup analyses demonstrated that sleep problems were most strongly associated with internalizing and externalizing symptoms and executive functioning, followed by core autism symptoms, family factors, and adaptive functioning. Findings highlight the far-reaching consequences of sleep problems on daytime functioning for autistic individuals and support the continued prioritization of sleep as a target for intervention through integrated care models to improve wellbeing. LAY SUMMARY: Autistic individuals experience higher rates of sleep problems, such as difficulty falling asleep and staying asleep, compared to the general population. We quantitatively summarized the literature about how sleep problems are related to different aspects of daytime functioning to identify areas that may be most affected by sleep. Sleep problems were related to all areas assessed, with the strongest associations for mood and anxiety symptoms. We recommend prioritizing sleep health in autistic individuals to improve wellbeing and quality of life.

Knockdown of Amyloid Precursor Protein: Biological Consequences and Clinical Opportunities.

Amyloid precursor protein (APP) and its cleavage fragment Amyloid-ß (Aß) have fundamental roles in Alzheimer's disease (AD). Genetic alterations that either increase the overall dosage of APP or alter its processing to favour the generation of longer, more aggregation prone Aß species, are directly causative of the disease. People living with one copy of APP are asymptomatic and reducing APP has been shown to lower the relative production of aggregation-prone Aß species in vitro. For these reasons, reducing APP expression is an attractive approach for AD treatment and prevention. In this review, we will describe the structure and the known functions of APP and go on to discuss the biological consequences of APP knockdown and knockout in model systems. We highlight progress in therapeutic strategies to reverse AD pathology via reducing APP expression. We conclude that new technologies that reduce the dosage of APP expression may allow disease modification and slow clinical progression, delaying or even preventing onset.

A systematic review of the association between sleep health and stress biomarkers in children.

Sleep is intimately linked with the stress response system. While the evidence for this connection has been systematically reviewed in the adult literature, to our knowledge no studies have examined this relationship in young children. Recent scientific interest in understanding the effects of adverse environments in early childhood, including an emphasis on understanding the role of sleep, highlights the importance of synthesizing the current evidence on the relationship between sleep and the stress response system in early childhood. The aim of this systematic review is to examine the relationship between sleep health and biomarkers of physiologic stress (neuroendocrine, immune, metabolic, cardiovascular) in healthy children ages 0-12 y. Following PRISMA guidelines, we identified 68 empirical articles and critically reviewed and synthesized the results across studies. The majority of studies included school-age children and reported sleep dimensions of duration or efficiency. Overall, evidence of associations between sleep health and stress biomarkers was strongest for neuroendocrine variables, and limited or inconsistent for studies of immune, cardiovascular, and metabolic outcomes. Gaps in the literature include prospective, longitudinal studies, inclusion of children under the age of 5 y, and studies using objective measures of sleep.

Plasma amyloid-ß ratios in autosomal dominant Alzheimer's disease: the influence of genotype.

In vitro studies of autosomal dominant Alzheimer's disease implicate longer amyloid-ß peptides in disease pathogenesis; however, less is known about the behaviour of these mutations in vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from individuals who were at risk of inheriting a mutation or were symptomatic. We tested for differences in amyloid-ß (Aß)42:38, Aß42:40 and Aß38:40 ratios between presenilin 1 (PSEN1) and amyloid precursor protein (APP) carriers. We examined the relationship between plasma and in vitro models of amyloid-ß processing and tested for associations with parental age at onset. Thirty-nine participants were mutation carriers (28 PSEN1 and 11 APP). Age- and sex-adjusted models showed marked differences in plasma amyloid-ß between genotypes: higher Aß42:38 in PSEN1 versus APP (P < 0.001) and non-carriers (P < 0.001); higher Aß38:40 in APP versus PSEN1 (P < 0.001) and non-carriers (P < 0.001); while Aß42:40 was higher in both mutation groups compared to non-carriers (both P < 0.001). Amyloid-ß profiles were reasonably consistent in plasma and cell lines. Within the PSEN1 group, models demonstrated associations between Aß42:38, Aß42:40 and Aß38:40 ratios and parental age at onset. In vivo differences in amyloid-ß processing between PSEN1 and APP carriers provide insights into disease pathophysiology, which can inform therapy development.

Sleep Dysregulation and Daytime Electrodermal Patterns in Children With Autism: A Descriptive Study.

Sleep deficiency influences emotion and behavior regulation but the mechanisms of influence are poorly understood. Emotion, behavioral, and sleep theories highlight differences in autonomic function as a potential pathway of influence and research in typical populations draw links between sleep deficiency and autonomic dysregulation (e.g., elevated reactivity within the sympathetic nervous system). In populations at elevated risk for sleep deficiency/problems (i.e., individuals with autism), greater variability in sleep and autonomic/arousal profiles may be particularly informative. Using electrodermal activity (EDA) as an indicator of sympathetic nervous system activation, this descriptive pilot study aimed to document daytime EDA patterns in children with autism and to explore their relations with sleep dysregulation/deficiency. EDA and sleep were measured using ankle and wrist worn sensors in 13 children (Meanage 6.11 years). EDA indices included nonspecific skin conductance responses (NSSCR) and tonic skin conductance levels (SCL). Descriptively, children in the dysregulated sleep group had fewer NSSCRs and lower SCL in the afternoon. This blunted physiological arousal profile/pattern is consistent with previous research, but this is the first study to explore how sleep may be linked. Notably, this pattern may not reflect sleep but an overall dysregulation profile which in this sample included: dysregulated sleep, a blunted afternoon arousal profile, and elevated ASD symptom severity. Replication with larger, more diverse samples is needed to disentangle the complex relations among sleep, arousal, and ASD behavioral features. However, this study represents an important first step in documenting extended daytime arousal patterns.

A novel presenilin 1 duplication mutation (Ile168dup) causing Alzheimer's disease associated with myoclonus, seizures and pyramidal features.

Mutations in the Presenilin 1 (PSEN1) gene are the most common cause of autosomal dominant familial Alzheimer's disease. We report the clinical, imaging and postmortem findings of kindred carrying a novel duplication mutation (Ile168dup) in the PSEN1 gene. We interpret the pathogenicity of this novel variant and discuss the additional neurological features (pyramidal dysfunction, myoclonus and seizures) that accompanied cognitive decline. This report broadens the clinical phenotype of PSEN1 insertion mutations while also highlighting the importance of considering duplication, insertion and deletion mutations in cases of young onset dementia.

Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study.

Blood biomarkers have great potential to advance clinical care and accelerate trials in Alzheimer's disease (AD). Plasma phospho-tau181 (p-tau181) is a promising blood biomarker however, it is unknown if levels increase in presymptomatic AD. Therefore, we investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD). Plasma p-tau181 was measured, using an in-house single molecule array assay. We compared p-tau181 between symptomatic carriers, presymptomatic carriers, and non-carriers, adjusting for age and sex. We examined the relationship between p-tau181 and neurofilament light and estimated years to/from symptom onset (EYO), as well as years to/from actual onset in a symptomatic subgroup. In addition, we studied associations between p-tau181 and clinical severity, as well testing for differences between genetic subgroups. Twenty-four were presymptomatic carriers (mean baseline EYO -9.6 years) while 27 were non-carriers. Compared with non-carriers, plasma p-tau181 concentration was higher in both symptomatic (p < 0.001) and presymptomatic mutation carriers (p < 0.001). Plasma p-tau181 showed considerable intra-individual variability but individual values discriminated symptomatic (AUC 0.93 [95% CI 0.85-0.98]) and presymptomatic (EYO ≥ -7 years) (AUC 0.86 [95% CI 0.72-0.94]) carriers from non-carriers of the same age and sex. From a fitted model there was evidence (p = 0.050) that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Our finding that plasma p-tau181 concentration is increased in symptomatic and presymptomatic FAD suggests potential utility as an easily accessible biomarker of AD pathology.

Brief Report: A Gene Enrichment Approach Applied to Sleep and Autism.

Sleep disorders (SD) are common in autism spectrum disorder (ASD), yet relatively little is known about the potential genetic mechanisms involved in SD and ASD comorbidity. The current study begins to fill this gap with a gene enrichment study that (1) identifies risk genes that contribute to both SD and ASD which implicate circadian entrainment, melatonin synthesis, and several genetic syndromes. An over-representation analysis identified several enriched pathways that suggest dopamine and serotonin synapses as potential shared SD and ASD mechanisms. This overlapping gene set and the highlighted biological pathways may serve as a preliminary stepping-stone for new genetic investigations of SD and ASD comorbidity.

Diversity in pediatric behavioral sleep intervention studies.

Studies designed to assess the efficacy of behavioral sleep interventions for infants and young children often report sleep improvements, but the generalization to children and families of diverse backgrounds is rarely assessed. The present study describes a systematic review of the racial, ethnic, and socioeconomic diversity of behavioral sleep intervention studies for young children. Thirty-two behavioral sleep intervention studies (5474 children) were identified using PRISMA guidelines. Each study was coded for racial and ethnic composition, parental educational attainment (an index of socioeconomic resources), and country of origin. Racial or ethnic information was obtained for 19 studies (60%). Study participants were primarily White and from predominantly White countries. Overall, 21 (66%) of the included studies provided information on parental education. Most of these studies had samples with moderate to high educational attainment. Behavioral sleep intervention studies to date include samples with insufficient diversity. Overall, this study highlights a critical gap in pediatric sleep intervention research and supports a call to further include families from diverse backgrounds when assessing behavioral sleep interventions.

Longitudinal Associations of Sleep Duration, Morning and Evening Cortisol, and BMI During Childhood.

OBJECTIVE: This study aimed to examine associations between sleep duration, BMI, and cortisol levels across childhood. METHODS: Participants included 361 children adopted domestically in the United States. Random-intercept cross-lagged panel models tested for between-person and bidirectional within-person associations of sleep duration, BMI, and morning and evening cortisol at age 4.5 to 9 years. RESULTS: Sleep duration and BMI were stable during childhood, inversely associated at the between-person level, and unrelated to morning or evening cortisol. BMI at age 6 years predicted longer sleep duration and lower evening cortisol at age 7 years, and lower morning cortisol at age 7 years predicted higher BMI at age 9 years within individuals. CONCLUSIONS: The association between sleep and BMI is more likely a stable between-person phenomenon rather than a unidirectional association that develops within individuals over time.

Pediatric Videosomnography: Can Signal/Video Processing Distinguish Sleep and Wake States?

The term videosomnography captures a range of video-based methods used to record and subsequently score sleep behaviors (most commonly sleep vs. wake states). Until recently, the time consuming nature of behavioral videosomnography coding has limited its clinical and research applications. However, with recent technological advancements, the use of auto-videosomnography techniques may be a practical and valuable extension of behavioral videosomnography coding. To test an auto-videosomnography system within a pediatric sample, we processed 30 videos of infant/toddler sleep using a series of signal/video-processing techniques. The resulting auto-videosomnography system provided minute-by-minute sleep vs. wake estimates, which were then compared to behaviorally coded videosomnography and actigraphy. Minute-by-minute estimates demonstrated moderate agreement across compared methods (auto-videosomnography with behavioral videosomnography, Cohen's kappa = 0.46; with actigraphy = 0.41). Additionally, auto-videosomnography agreements exhibited high sensitivity for sleep but only about half of the wake minutes were correctly identified. For sleep timing (sleep onset and morning rise time), behavioral videosomnography and auto-videosomnography demonstrated strong agreement. However, nighttime waking agreements were poor across both behavioral videosomnography and actigraphy comparisons. Overall, this study provides preliminary support for the use of an auto-videosomnography system to index sleep onset and morning rise time only, which may have potential telemedicine implications. With replication, auto-videosomnography may be useful for researchers and clinicians as a minimally invasive sleep timing assessment method.

Sleep and Challenging Behaviors in the Context of Intensive Behavioral Intervention for Children with Autism.

This study examined the associations between sleep and challenging behaviors for average and night-to-night fluctuations in sleep, in 39 children with autism spectrum disorder (ASD) receiving intensive behavioral intervention (IBI). Child sleep was recorded (via actigraphy) for five nights in conjunction with clinician-reported observations of challenging behaviors. Results indicated that on average, poor sleep was associated with higher rates of repetitive behavior, negative affect, and a composite of overall challenging behaviors. These findings suggest that average sleep patterns are important within the context of IBI (rather than night-to-night fluctuations). Interventions aimed at improving overall patterns of sleep may have important cascading effects on challenging behaviors and developmental outcomes for children with ASD and their families.