Childhood obesity, weight loss and developmental trajectories predict the persistence and remission of childhood sleep-disordered breathing.

BACKGROUND: Obesity has been recognized as a risk factor for childhood sleep-disordered breathing (SDB), yet it remains unclear how obesity and weight change predict the course of childhood SDB. OBJECTIVE: The objective of the study is to investigate the role of body weight, upper airway abnormalities and developmental trajectories on the persistence and remission of childhood SDB in the transition to adolescence. METHODS: The Penn State Child Cohort is a representative population sample of 700 children (5-12 years), of whom 421 were followed up as adolescents (12-23 years). Participants underwent a clinical history, physical examination and polysomnography at both time points. RESULTS: Obesity and enlarged tonsils were cross-sectionally associated with childhood SDB. Longitudinally, baseline obesity predicted the persistence of childhood SDB (OR = 3.75, 95% CI = 2.00-7.05), while weight loss predicted its remission (OR = 1.67, 95% CI = 1.11-2.50). Children with enlarged tonsils who remitted from SDB had not experienced significant weight loss and only 4.4% had undergone adeno/tonsillectomy. Body fat distribution/composition at follow-up was similar in those who had remitted from childhood SDB as compared with those who had never experienced SDB, while those who persisted with childhood SDB showed significant android distribution and visceral adiposity at follow-up. CONCLUSIONS: Our data support a causal role for obesity and weight loss in the chronicity and remission, respectively, of childhood SDB in the transition to adolescence and suggest that remission of SDB is related to developmental trajectories of the upper airway in a significant proportion of children. Thus, targeting childhood obesity and weight gain should be a priority in the prevention and treatment of SDB during this critical developmental period.

Characterization of a Multiple-Scan-Rate Voltammetric Waveform for Real-Time Detection of Met-Enkephalin.

Opioid peptides are critically involved in a variety of physiological functions necessary for adaptation and survival, and as such, understanding the precise actions of endogenous opioid peptides will aid in identification of potential therapeutic strategies to treat a variety of disorders. However, few analytical tools are currently available that offer both the sensitivity and spatial resolution required to monitor peptidergic concentration fluctuations in situ on a time scale commensurate with that of neuronal communication. Our group has developed a multiple-scan-rate waveform to enable real-time voltammetric detection of tyrosine containing neuropeptides. Herein, we have evaluated the waveform parameters to increase sensitivity to methionine-enkephalin (M-ENK), an endogenous opioid neuropeptide implicated in pain, stress, and reward circuits. M-ENK dynamics were monitored in adrenal gland tissue, as well as in the dorsal striatum of anesthetized and freely behaving animals. The data reveal cofluctuations of catecholamine and M-ENK in both locations and provide measurements of M-ENK dynamics in the brain with subsecond temporal resolution. Importantly, this work also demonstrates how voltammetric waveforms can be customized to enhance detection of specific target analytes, broadly speaking.

Neurocognitive and behavioral functioning in adolescents with sleep-disordered breathing: a population-based, dual-energy X-ray absorptiometry study.

BACKGROUND/OBJECTIVES: Sleep-disordered breathing (SDB) has been associated with neurocognitive and behavioral problems in young children; however, this association is less studied in adolescents. Evidence suggests that obesity plays a key role in the development of SDB, although its relative association with neurobehavioral functioning remains unclear. We examined whether SDB and obesity are associated with neurocognitive and behavioral problems in adolescents. SUBJECTS/METHODS: A total of 421 adolescents (17.0±2.2y, 53.9% male) from the Penn State Child Cohort, a general population sample, underwent a 9-h polysomnography, clinical history, physical examination, neurocognitive evaluation and Dual-energy X-ray Absorptiometry (DXA) scan, and completed the Child or Adult Behavior Checklist. Obstructive sleep apnea (OSA) was defined as an apnea-hypopnea index (AHI)⩾2, primary snoring (PS) as AHI<2+snoring and no-SDB as AHI<2 without snoring. Body weight measures included body mass index (BMI) percentile, waist circumference (WC) and DXA-measured total adipose tissue (TAT). RESULTS: WC and TAT were significantly associated with impaired vigilance, processing speed, working memory, and control interference and greater internalizing and externalizing behaviors, while BMI percentile was marginally associated. SDB per se (PS, AHI or OSA) was not significantly associated with impaired neurocognitive outcomes or greater behavioral problems. However, TAT was significantly associated with impaired vigilance and greater internalizing and externalizing behaviors and, to a lesser extent, slower processing speed and greater control interference, only in adolescents with OSA. CONCLUSIONS: Central obesity, an etiopathogenic mechanism of OSA, is more strongly associated with neurocognitive and behavioral problems in adolescents than SDB alone. Deficits in low-order (vigilance) and high-order (executive) functions and behavioral problems observed in adolescents with OSA are primarily associated with increased central adiposity, a finding not entirely captured with less precise measures of obesity. These data support that OSA and its associated neurocognitive and behavioral morbidity are related to underlying metabolic dysfunction as early as adolescence.

The relative association of obstructive sleep apnea, obesity and excessive daytime sleepiness with incident depression: a longitudinal, population-based study.

BACKGROUND: It is postulated that obstructive sleep apnea (OSA) is a risk factor for the development of depression. However, obesity and excessive daytime sleepiness (EDS) are associated with both OSA and depression. The goal of this study was to examine the relative contribution of OSA, obesity and EDS to incident depression. METHODS: A representative random sample of 1137 adults without depression from the Penn State Adult Cohort was followed up after 7.5 years. All subjects underwent a full medical examination and polysomnography at baseline. OSA was defined as an apnea/hypopnea index (AHI) ⩾5, overweight as a body mass index (BMI) of 25-29.9 kg m(-)(2), obesity as a BMI⩾30 kg m(-)(2) and EDS as moderate-to-severe drowsiness/sleepiness and/or irresistible sleep attacks. RESULTS: Overweight, obesity and EDS were associated with incident depression, whereas OSA alone was not. Overweight was associated with incident depression in women, while obesity and EDS were associated with incident depression in both genders. The association of overweight and obesity with incident depression was independent of premorbid emotional distress, while that of EDS was not. The association between BMI and EDS with incident depression was stronger in women 20-40 years old. The severity of EDS predicted incident depression in those with OSA, while AHI or oxygen desaturation did not. CONCLUSIONS: Overweight, obesity and EDS are the main predictors of incident depression. Obesity may be linked to depression through psychobiological mechanisms, while EDS may be an early sign of depression. Obesity should be a target of our preventative strategies for depression.

Stability of Disruptive Mood Dysregulation Disorder Symptoms (Irritable-Angry Mood and Temper Outbursts) Throughout Childhood and Adolescence in a General Population Sample.

DSM-5 Disruptive Mood Dysregulation Disorder (DMDD) is a controversial new diagnosis. The DSM-5 conceptualizes DMDD as persistent and chronic, but the stability of the two DMDD symptoms (irritable-angry mood and temper outbursts) over time is not known. Mothers rated DMDD symptoms in a population-based sample of 376 children (54 % male) evaluated at 6-12 years (M 9) and again an average of 8 years later (M 16). Mean scores on irritable-angry mood plus temper outbursts at baseline and follow-up were below sometimes a problem, but were higher at baseline than follow-up. Irritable-angry mood and temper outbursts were both often or very often a problem for 9 % of children at baseline, 6 % at follow-up, and 3 % at baseline and follow-up. Only 29 % of children whose baseline symptoms were often or very often continued to have follow-up symptoms at this level (remission rate 71 %). Less than half (45 %) of the children whose symptoms were often or very often at follow-up had these symptoms 8 years earlier (55 % new cases). Our finding of 71 % remission and 55 % new cases indicates instability of DMDD symptoms over an 8-year period. However, the finding that 29 % still had symptoms often or very often 8 years later is clinically significant. DMDD symptoms were found in only one child who did not have symptoms of oppositional defiant disorder (ODD), conduct disorder, ADHD, anxiety, or depression. This suggests that DMDD symptoms are a feature of multiple disorders, particularly ODD, and do not occur in isolation, questioning the validity of DMDD as a unique and independent diagnosis.

Sleep problems in children.

Sleep complaints and sleep disorders are common during childhood and adolescence. The impact of not getting enough sleep may affect children's' physical health as well emotional, cognitive and social development. Insomnia, sleep-disordered breathing, parasomnias and sleep disturbances associated with medical and psychiatric disorders are some of the commonly encountered sleep disorders in this age group. Changes in sleep architecture and the amount of sleep requirement associated with each stage of development should be considered during an evaluation of sleep disorders in children. Behavioral treatments should be used initially wherever possible especially considering that most pharmacologic agents used to treat pediatric sleep disorders are off-label. In this review we address the most common sleep problems in children/adolescents as they relate to prevalence, presentation and symptoms, evaluation and management.

Short sleep duration and obesity: the role of emotional stress and sleep disturbances.

OBJECTIVE: Many epidemiologic studies have reported that obesity is associated with short sleep duration. How the degree of obesity or other clinical characteristics of the obese individuals, such as sleep disturbances or emotional stress, define this relation is not known. DESIGN: We studied a random sample of 1300 middle-aged men and women from the Penn State Cohort in the sleep laboratory for one night. Sleep disturbances were recorded as insomnia, excessive daytime sleepiness (EDS) or sleep difficulty. Chronic emotional stress was determined by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). RESULTS: Obese individuals (body mass index, BMI>30) reported shorter duration of sleep, had a higher incidence of subjective sleep disturbances (47.4 vs 25.5%; P<0.01) and scored higher for chronic emotional stress than nonobese subjects. However, there was no difference in self-reported sleep duration between obese and nonobese individuals without subjective sleep disturbances, while both obese men and women with sleep complaints scored higher in the MMPI-2 compared to obese individuals without sleep complaints. The shortest sleep duration was reported by the obese insomniac patients (5.9 h), followed by obese with EDS (6.3 h) or sleep difficulty (6.6 h). The effect of chronic emotional stress was stronger than that of the BMI on the reported sleep duration, with a synergistic joint effect. The presence of a sleep disturbance was associated with a reduction of reported sleep by 18 min for men and 42 min in women, whereas a 10 kg m(-2) increase of BMI was associated with a 16 and 6 min decrease of sleep in men and women, respectively. Interestingly, there was no association between objective sleep duration and BMI. CONCLUSION: Self-reported short sleep duration in obese individuals may be a surrogate marker of emotional stress and subjective sleep disturbances, whose detection and management should be the focus of our preventive and therapeutic strategies for obesity.

Functional analysis of brome mosaic virus coat protein RNA-interacting domains.

The coat proteins (CP) of cowpea chlorotic mottle (CCMV) and brome mosaic virus (BMV), two members of the genus Bromovirus, share 70% identity at the amino acid (aa) level and contain four highly conserved regions, identified as putative RNA-interacting domains (RIDs). To assess the contribution of the conserved aa sequence within each RID and the structural features contained therein toward virion assembly and RNA packaging, we engineered a set of fourteen independent mutations (deletions and substitutions) encompassing all four RIDs. The effect of each mutation on viral biology, pathogenesis, and RNA packaging was analyzed in whole-plant infection assays. Among the four RIDs, two mutations engineered into the N-proximal domain (RID I) and two of the four mutations engineered into the C-proximal domain (RID IV) proved to be more debilitating (compared to wild-type) while only selected regions in the central domains (RID II or III) showed a detectable effect. Neutral effects were observed when aa residues that are predicted to affect calcium binding were mutated. To further analyze the importance of N and C terminal interactions leading to virus assembly and RNA packaging, four CP hybrids were constructed by precisely exchanging either the N-terminal 77 or the C-terminal 113/112aa between BMV and CCMV. Despite the fact that the CP composition of the hybrid viruses is distinct from either of the parents, the symptom phenotype in Chenopodium quinoa, migration pattern of CP in Western blots and virion mobility in agarose gels was indistinguishable from the respective parent providing the genetic background. Collectively, the data provide insight for assessing the relative importance of each RID during genome packaging and in molecular processes regulating the overall architecture of the assembled virions.

Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression.

CONTEXT: Excessive daytime sleepiness (EDS) is commonly considered a cardinal sign of sleep apnea; however, the mechanism underlying the association is unclear. OBJECTIVE: The purpose of this study was to assess the association between the complaint of EDS and sleep apnea, considering a wide range of possible risk factors in a population sample. DESIGN AND SETTING: We examined this question in the Penn State cohort (a random sample of 16,583 men and women from central Pennsylvania, ranging in age from 20 to 100 yr). A random subset of this cohort (n = 1,741) was further evaluated for one night in the sleep laboratory. MAIN OUTCOME MEASURE: The main measure was a complaint of EDS. RESULTS: The final logistic regression model indicated depression was the most significant risk factor for EDS followed by body mass index, age, typical sleep duration, diabetes, smoking, and finally sleep apnea. The strength of the association with EDS decreased with increasing age, whereas the association of depression with EDS was stronger in the young. EDS is more prevalent in the young (<30 yr), suggesting the presence of unmet sleep needs and depression, and in the very old (>75 yr), suggesting increasing medical illness and health problems. EDS was associated with a reduced report of typical sleep duration without any association with objective polysomnographic measures. CONCLUSIONS: It appears that the presence of EDS is more strongly associated with depression and metabolic factors than with sleep-disordered breathing or sleep disruption per se. Our findings suggest that patients with a complaint of EDS should be thoroughly assessed for depression and obesity/diabetes independent of whether sleep-disordered breathing is present.

Persistent post-laparoscopy pneumoperitoneum.

BACKGROUND: Persistent pneumoperitoneum after a laparoscopic operation can represent either residual postoperative pneumoperitoneum or free intraperitoneal gas released from the gastrointestinal tract. This animal study was conducted to better characterize the extent and duration of postoperative pneumoperitoneum as detected by computed tomography (CT). METHODS: Five pigs underwent cholecystectomy, four laparoscopically and one open. All pigs were followed serially with upright chest radiographs and abdominal CT scans beginning immediately postoperatively and continuing daily until resolution of pneumoperitoneum as detected by both imaging modalities. All radiographs and CT scans were reviewed by dedicated radiologists who reported the extent and duration of pneumoperitoneum in a blinded fashion. RESULTS: Pneumoperitoneum resolved on upright chest radiographs in all five pigs by or on postoperative day 1. Serial CT scans demonstrated that the laparoscopic group had either resolution of pneumoperitoneum or minimal persistence of free intraperitoneal gas by postoperative day 2. In contrast, the single pig in the open group had CT evidence of persistent pneumoperitoneum through postoperative day 6. CONCLUSIONS: In the pig model, small pockets of free intraperitoneal gas detected by CT scanning are expected to resolve by postoperative day 2 following laparoscopic surgery. Persistence of pneumoperitoneum beyond this interval is abnormal and may represent a perforated viscus. Whereas a prospective CT imaging study in humans is not ethically feasible, we believe that parallel conclusions between the pig and human may be drawn.

Extramedullary hematopoiesis in a child with hereditary spherocytosis: an uncommon cause of an adrenal mass.

We report a case of extramedullary hematopoiesis presenting as an adrenal mass in a young male with hereditary spherocytosis. The unilateral adrenal mass was discovered during an abdominal ultrasound performed for jaundice. CT and MR imaging were subsequently performed, followed by an excisional biopsy at the time of splenectomy and cholecystectomy. Although extramedullary hematopoiesis is a rare cause of an adrenal mass, the diagnosis must be considered in any patient with a history of a congenital hemolytic disorder such as hereditary spherocytosis. In this regard, the morbidity of an unnecessary procedure may be avoided.

Non-significance of early speech delay in children with autism and normal intelligence and implications for DSM-IV Asperger's disorder.

According to the DSM-IV, children with Asperger's disorder do not have significant cognitive or speech delays, whereas children with autistic disorder may or may not. In our study, children with normal intelligence who had clinical diagnoses of autism or Asperger syndrome were divided into two groups: those with and without a significant speech delay. The purpose was to determine if clinically meaningful differences existed between the two groups that would support absence of speech delay as a DSM-IV criterion for Asperger's disorder. No significant differences were found between the 23 children with a speech delay and the 24 children without a speech delay on any of the 71 variables analyzed, including autistic symptoms and expressive language. Results suggest that early speech delay may be irrelevant to later functioning in children who have normal intelligence and clinical diagnoses of autism or Asperger syndrome and that speech delay as a DSM-IV distinction between Asperger's disorder and autism may not be justified.

Variables related to outcome following child psychiatric hospitalization.

Children (N = 110) hospitalized on a child psychiatric unit improved significantly in psychological functioning at discharge and 1- and 6-months follow-up relative to their functioning at admission. Children who were more impaired at admission made more progress during admission but were more impaired at follow-up than children who had milder symptoms at admission. Children without a behavior disorder had a better outcome than children with a behavior disorder. None of the other variables, alone or in combination, was significantly related to admission progress or follow-up outcome, including specific diagnoses, gender, race, age, IQ, family functioning, negative life events, parent education and employment, biological family history, length of hospitalization, parent involvement during admission and follow-up services.

Does DSM-IV Asperger's disorder exist?

DSM-IV criteria for autistic and Asperger's disorders were applied to 157 children with clinical diagnoses of autism or Asperger's disorder. All children met the DSM-IV criteria for autistic disorder and none met criteria for Asperger's disorder, including those with normal intelligence and absence of early speech delay. The reason for this was that all children had social impairment and restricted and repetitive behavior and interests (required DSM-IV symptoms for both autistic and Asperger's disorders) and all had a DSM-IV communication impairment (which then qualified them for a diagnosis of autistic disorder and not Asperger's disorder). Communication problems exhibited by all children were impaired conversational speech or repetitive, stereotyped, or idiosyncratic speech (or both), which are DSM-IV criteria for autism. These findings are consistent with those of 5 other studies and indicate that a DSM-IV diagnosis of Asperger's disorder is unlikely or impossible.

Outcome following child psychiatric hospitalization.

Admission, discharge, and follow-up evaluations of 110 children admitted to a child psychiatric unit (mean 14 days) showed that the children's psychological functioning improved significantly during hospitalization. Gains were not fully maintained at follow-up (1 and 6 months), but the children were still significantly less impaired after discharge than at admission. A nonsignificant difference existed between follow-up scores, indicating no loss of progress or decline in functioning from 1- to 6-month follow-up. The results are consistent with an ABA (A = no inpatient intervention, B = inpatient intervention, A = no inpatient intervention) treatment effect. They are not explained by removal from and return to an unsatisfactory home environment. Psychological functioning after admission was significantly better than after 1 to 6 months of post-discharge psychiatric services. This study offers a clinically feasible approach to evidence-based practice by documenting patient improvement during and after inpatient treatment using a simple, empirically supported assessment instrument.

Clinical validity and interpretation of the Gordon Diagnostic System in ADHD assessments.

Gordon Diagnostic System (GDS) data were analyzed for 165 referred children with ADHD combined type and 46 referred children without ADHD, 6-16 years of age. Results showed significant differences between children with and without ADHD on the GDS standard scores and the IQ-GDS differences scores. Using a GDS composite standard score of 13 points or more below IQ to classify children as having ADHD resulted in the highest diagnostic accuracy (86%), with positive predictive power equal to 91%, and negative predictive power 67%. Results for the GDS compared favorably with those reported for other continuous performance tests. The findings lend support to the GDS as a clinically useful component of an ADHD evaluation.

Learning disabilities and ADHD: overlapping spectrumn disorders.

Clinical and psychoeducational data were analyzed for 119 children ages 8 to 16 years who were evaluated in a child diagnostic clinic. A learning disability (LD) was present in 70% of the children with attention-deficit/hyperactivity disorder (ADHD), with a learning disability in written expression two times more common (65%) than a learning disability in reading, math, or spelling. Children with LD and ADHD had more severe learning problems than children who had LD but no ADHD, and the former also had more severe attention problems than children who had ADHD but no LD. Further, children with ADHD but no LD had some degree of learning problem, and children with LD but no ADHD had some degree of attention problem. Results suggest that learning and attention problems are on a continuum, are interrelated, and usually coexist.

Abuse potential of dronabinol (Marinol).

Dronabinol is an oral form of delta-9-tetrahydrocannabinol indicated for treatment of anorexia associated with weight loss in individuals with AIDS, and nausea and vomiting associated with cancer chemotherapy. The authors reviewed the literature and conducted surveys and interviews among addiction medicine specialists, oncologists, researchers in cancer and HIV treatment, and law enforcement personnel to determine the abuse liability of dronabinol. There is no evidence of abuse or diversion of dronabinol. Available prescription tracking data indicates that use remains within the therapeutic dosage range over time. Healthcare professionals have detected no indication of "scrip-chasing" or "doctor-shopping" among the patients for whom they have prescribed dronabinol. Cannabis-dependent populations, such as those treated in our Clinic and seen by the addiction medicine specialists we interviewed, have demonstrated no interest in abuse of dronabinol. There is no street market for dronabinol, and no evidence of any diversion of dronabinol for sale as a street drug. Furthermore, dronabinol does not provide effects that are considered desirable in a drug of abuse. The onset of action is slow and gradual, it is at most only weakly reinforcing, and the overwhelming majority of reports of users indicate that its effects are dysphoric and unappealing. This profile of effects gives dronabinol a very low abuse potential.

Comparison of scores on two recent editions of the Developmental Test of Visual-Motor Integration.

Standard scores on the third and fourth editions of the Developmental Test of Visual-motor Integration (VMI-3 and VMI-4) were compared for a sample of 120 children (4-17 years of age) referred to an outpatient diagnostic clinic for developmental learning, attention, mood, and behavior problems. The two editions of the test have the same items, so the test was administered only once to each child, but the editions differ in their scoring systems and norms. The correlation between the pairs of standard scores on the two editions was .99, and the absolute mean difference between scores was only 1.5 points.