ABSTRACT
BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms. METHODS: Fifty-five individuals with AS (aged < 5 years: n = 16, 5-12 years: n = 27, ≥ 18 years: n = 12; deletion genotype: n = 40, nondeletion genotype: n = 15) and 20 typically developing children (aged 1-12 years) were enrolled across six USA sites. Several clinical outcome assessments and digital health technologies were tested, together with overnight 19-lead electroencephalography (EEG) and additional polysomnography (PSG) sensors. Participants were assessed at baseline (Clinic Visit 1), 12 months later (Clinic Visit 2), and during intermittent home visits. RESULTS: The participants achieved high completion rates for the clinical outcome assessments (adherence: 89-100% [Clinic Visit 1]; 76-91% [Clinic Visit 2]) and varied feasibility of and adherence to digital health technologies. The coronavirus disease 2019 (COVID-19) pandemic impacted participants' uptake of and/or adherence to some measures. It also potentially impacted the at-home PSG/EEG recordings, which were otherwise feasible. Participants achieved Bayley-III results comparable to the available natural history data, showing similar scores between individuals aged ≥ 18 and 5-12 years. Also, participants without a deletion generally scored higher on most clinical outcome assessments than participants with a deletion. Furthermore, the observed AS EEG phenotype of excess delta-band power was consistent with prior reports. CONCLUSIONS: Although feasible clinical outcome assessments and digital health technologies are reported herein, further improved assessments of meaningful AS change are needed. Despite the COVID-19 pandemic, remote assessments facilitated high adherence levels and the results suggested that at-home PSG/EEG might be a feasible alternative to the in-clinic EEG assessments. Taken altogether, the combination of in-clinic/at-home clinical outcome assessments, digital health technologies, and PSG/EEG may improve protocol adherence, reduce patient burden, and optimize study outcomes in AS and other rare disease populations.
Subject(s)
Angelman Syndrome , COVID-19 , Humans , Angelman Syndrome/complications , Prospective Studies , Pandemics , ElectroencephalographyABSTRACT
BACKGROUND: Angelman syndrome (AS) is a rare, heterogenous neurogenetic condition, which significantly impacts the lives of people with AS and their families. Valid and reliable measures reporting key symptoms and functional impairments of AS are required to support development of patient-centered therapies. We describe the development of clinician- and caregiver-reported, AS-specific Global Impression scales for incorporation into clinical trials. Best practice US Food and Drug Administration guidance for measure development was followed with input from expert clinicians, patient advocates, and caregivers during content generation and refinement. RESULTS: Initial measurement domains for the Symptoms of AS-Clinician Global Impression (SAS-CGI) and the Caregiver-reported AS Scale (CASS) were identified from a conceptual disease model of AS symptoms and impacts, derived from interviews with caregivers and clinicians. Two rounds of cognitive debriefing (CD) interviews were performed; clinicians debriefed the SAS-CGI, with patient advocates and caregivers debriefing the CASS to ensure relevance and comprehension. Feedback was used to refine items and ensure wording was age-appropriate and captured AS-specific symptoms, as well as associated impacts and functional impairments. The SAS-CGI and CASS capture global assessments of seizures, sleep, maladaptive behaviors, expressive communication, fine and gross motor skills, cognition, and self-care, which were determined by clinicians, patient advocates, and caregivers to be the most challenging aspects of AS. Additionally, the measures include items for assessing overall AS symptoms and the meaningfulness of any change. In addition to ratings for severity, impact, and change, a notes field was included in the SAS-CGI to provide the rationale for the chosen rating. CD interviews confirmed the measures covered key concepts of AS from the perspective of clinicians and caregivers, and demonstrated that the measures' instructions, items, and response options were clear and appropriate. Interview feedback informed adjustments to the wording of the instructions and the items. CONCLUSIONS: The SAS-CGI and CASS were designed to capture multiple AS symptoms, reflecting the heterogeneity and complexity of AS in children 1 to 12 years old. These clinical outcome assessments have been incorporated into AS clinical studies, which will allow for the evaluation of their psychometric properties and inform further refinements if needed.
Subject(s)
Angelman Syndrome , Caregivers , Child , Humans , Infant , Child, Preschool , Caregivers/psychology , Surveys and Questionnaires , Patient-Centered CareABSTRACT
Whilst the association between Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity is supported by meta-analytic evidence, the mechanisms underpinning this link need to be further elucidated. Inflammatory processes may increase the risk of ADHD symptoms in individuals with obesity. This pilot study set out to start testing this hypothesis by assessing the correlation between serum levels of inflammatory cytokines and ADHD symptoms severity in a sample of children and adolescents with obesity. We measured ADHD symptoms severity in 52 children/adolescents with obesity (BMI > 95th centile) with the Conners questionnaire, revised, short version, parent (CPRS-R:S) and teacher (CTRS-R:S) versions. Additionally, a categorical diagnosis of ADHD was established using the Kiddie-SADS-PL. Serum levels of IL-6, Il-10, and TNF-alpha were also obtained. The prevalence of ADHD was 9.6%. We found a significant correlation between IL-6, as well as TNF-alpha, and hyperactivity/impulsivity subscores of the CPRS-R:S and CTRS-R:S, that held even after controlling for BMI and oppositional symptoms. This study provides a rationale for larger, longitudinal studies to gain insight into inflammatory processes underpinning the link between obesity and ADHD. This line of research has the potential to lead to novel, pathophysiologically-based management strategies for individuals with obesity and ADHD.
Subject(s)
Attention Deficit Disorder with Hyperactivity/blood , Attention Deficit Disorder with Hyperactivity/diagnosis , Cytokines/blood , Pediatric Obesity/blood , Pediatric Obesity/diagnosis , Adolescent , Attention Deficit Disorder with Hyperactivity/epidemiology , Biomarkers/blood , Child , Cross-Sectional Studies , Female , Humans , Inflammation Mediators/blood , Male , Pediatric Obesity/epidemiology , Pilot Projects , Prevalence , Surveys and QuestionnairesABSTRACT
The goal of this 21-year naturalistic study of clozapine-treated patients was to examine the cardiovascular risk factors following clozapine initiation and resultant mortality estimates from cardiovascular disease. Data were collected from January 1992 to February 2012 medical records from clozapine-treated patients with schizophrenia or schizoaffective disorder. Demographics, clozapine dosage and laboratory results were extracted at 12-month intervals. At clozapine initiation, the mean age of the 96 patients was 36.4 years±7.6 years; n=27 (28%) were women. The mean duration of clozapine use was 13 years. The Kaplan-Meier estimate for 21-year cardiovascular events was 29%, while the Kaplan-Meier estimate for 21-year mortality from cardiovascular disease was 10%. The mean cardiovascular risk increased during the first ten years (p<.01), while a slight decrease occurred beyond ten years (p<.01). Patients involved in cardiometabolic research showed a greater decrease in cardiovascular risk factors over 21 years (p=.05). The Kaplan-Meier estimate for 21-year all-cause mortality was 22%. Forty-one patients were diagnosed with diabetes (42.7%), compared to a nationwide prevalence of 13.7% in a similar age group. These results support the hypothesis that clozapine-treated patients are at risk for cardiovascular events and death secondary to an increased risk of medical disorders. Interventions that target weight loss, smoking cessation, and lipid profile improvement may alleviate the increased risk of cardiovascular mortality.
Subject(s)
Antipsychotic Agents , Cardiovascular Diseases , Clozapine , Diabetes Mellitus , Schizophrenia , Adult , Antipsychotic Agents/adverse effects , Cardiovascular Diseases/chemically induced , Clozapine/adverse effects , Diabetes Mellitus/chemically induced , Female , Humans , Male , Psychotic Disorders/drug therapy , Risk Factors , Schizophrenia/drug therapyABSTRACT
OBJECTIVE: People with schizophrenia are at greater risk for cardiovascular disease and their overall mortality rate is elevated compared to the general population. The metabolic side effects of antipsychotic medications have been widely studied; however, the effect of adding conventional mood stabilizers, such as lithium and valproate, to antipsychotic medication has not been assessed in terms of metabolic risk. The primary purpose of this secondary analysis was to examine whether treatment with lithium or valproate in addition to a second-generation antipsychotic is associated with poorer metabolic outcomes than treatment with a second-generation antipsychotic without lithium or depakote. METHODS: Baseline data from 3 studies, which included measurement of body mass index, waist circumference, fasting glucose, insulin, homeostatic model assessment of insulin resistance, insulin sensitivity index, glucose utilization, and acute insulin response to glucose, were included in the analysis. RESULTS: No differences were found between those taking lithium or valproate and those who were not in terms of fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance. Insulin sensitivity was lower among participants taking lithium or valproate. Participants taking lithium or valproate had a higher body mass index than those not taking conventional mood stabilizers, although the difference did not reach statistical significance. CONCLUSIONS: These cross-sectional findings suggest it may be beneficial to monitor insulin sensitivity and body mass index in patients taking lithium or valproate in combination with a second-generation antipsychotic.
Subject(s)
Antimanic Agents/adverse effects , Antipsychotic Agents/adverse effects , Blood Glucose/drug effects , Body Mass Index , Insulin/blood , Lithium Compounds/adverse effects , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Valproic Acid/adverse effects , Adult , Cross-Sectional Studies , Drug Therapy, Combination , Female , Humans , Male , Middle AgedABSTRACT
Patients with schizophrenia have increased mortality and morbidity compared with the general population. These patients have a 20-year shorter lifespan than peers without schizophrenia, mainly due to premature cardiovascular disease, suicide, and cancer. Patients with severe mental illness are at increased risk for cardiovascular disease related to increased incidence of diabetes, hypertension, smoking, poor diet, obesity, dyslipidaemia, metabolic syndrome, low physical activity, and side-effects of antipsychotic drugs. Some second-generation antipsychotics (eg, clozapine, olanzapine, quetiapine, and risperidone) are associated with an increased risk of weight gain and obesity, impaired glucose tolerance and new-onset diabetes, hyperlipidaemia, and cardiovascular disease. The mechanisms by which schizophrenia and patients with severe mental illness are susceptible to cardiometabolic disorders are complex and include lifestyle risks and direct and indirect effects of antipsychotic drugs. An understanding of these risks might lead to effective interventions for prevention and treatment of cardiometabolic disorders in schizophrenia and severe mental illness.
Subject(s)
Cardiovascular Diseases/epidemiology , Mental Disorders/physiopathology , Schizophrenia/physiopathology , Severity of Illness Index , Humans , Risk FactorsABSTRACT
OBJECTIVE: To determine whether physician's attitudes toward patients with comorbid mental illness affect management of a chronic disease. DATA SOURCE: A total of 256 primary care physicians interviewed in 2010. STUDY DESIGN: This randomized factorial experiment entailed physicians observing video vignettes of patient-actors with poorly controlled diabetes. Patients were balanced across age, gender, race, and comorbidity (schizophrenia with bizarre or normal affect, depression, eczema). DATA COLLECTION: Physicians completed structured and semistructured interviews plus chart notes about clinical management and attitudes. PRINCIPAL FINDINGS: Physicians reported more negative attitudes for patients with schizophrenia with bizarre affect (SBA). There were few differences in clinical decisions measured quantitatively or in charting, but qualitative data revealed less trust of patients with SBA as reporters, with more reliance on sources other than engaging the patient in care. Physicians often alerted colleagues about SBA, thereby shaping expectations before interactions occurred. CONCLUSIONS: Results are consistent with common stereotypes about people with serious mental illness. Vignettes did not include intentional indication of unreliable reporting or danger. Reducing health care disparities requires attention to subtle aspects of managing patients--particularly those with atypical affect--as seemingly slight differences could engender disparate patient experiences over time.
Subject(s)
Attitude of Health Personnel , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Mental Disorders/epidemiology , Physicians, Primary Care/psychology , Adult , Aged , Comorbidity , Decision Making , Female , Humans , Interviews as Topic , Male , Middle Aged , Patient SimulationABSTRACT
OBJECTIVE: The aim of this study was to investigate the role of pravastatin, as an adjunctive therapy, on inflammatory markers, lipid and glucose metabolism, psychopathology, and cognition in subjects with schizophrenia and schizoaffective disorder. METHODS: Schizophrenia or schizoaffective subjects (N=60) were randomized to receive either a 12-week supply of pravastatin 40 mg/day or placebo treatment. Anthropometric measures, lipids and glucose metabolism, inflammatory markers, psychopathology and cognitive performance were assessed at baseline, 6 weeks and 12 weeks. RESULTS: Pravastatin use was associated with a significant decrease in total cholesterol, low density lipoprotein (LDL) cholesterol and LDL particle number levels, but was not associated with any significant changes in cognition or psychopathology in the participants, except a significant decrease in the Positive and Negative Syndrome Scale (PANSS) positive symptom score from baseline to week 6. However, this decrease failed to remain significant at 12 weeks. Interestingly, triglycerides, LDL-cholesterol, total cholesterol, LDL particle number, small LDL particle number, large very low density lipoprotein (VLDL) particle number and C-reactive protein (CRP) followed a similar pattern at 6 and 12 weeks as psychopathology. CONCLUSIONS: These results suggest that a randomized trial with a larger sample size and a higher dosage of pravastatin would be helpful in further evaluating the anti-inflammatory properties of pravastatin, its association with improvements in cognitive symptoms, and its potential to reduce positive and negative symptoms associated with schizophrenia or schizoaffective disorders.
Subject(s)
Anticholesteremic Agents/pharmacology , Pravastatin/pharmacology , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adult , Anticholesteremic Agents/administration & dosage , Cognition Disorders/drug therapy , Drug Synergism , Female , Humans , Inflammation/drug therapy , Lipid Metabolism/drug effects , Male , Middle Aged , Pilot Projects , Pravastatin/administration & dosage , Psychotic Disorders/immunology , Psychotic Disorders/metabolism , Psychotic Disorders/physiopathology , Schizophrenia/immunology , Schizophrenia/metabolism , Schizophrenia/physiopathology , Treatment OutcomeABSTRACT
BACKGROUND: An increasing body of research points to a significant association of obesity to Attention-Deficit/Hyperactivity Disorder (ADHD) and deficits in executive functions. There is also preliminary evidence suggesting that children with ADHD may be at risk of obesity in adulthood. DISCUSSION: In this article, we discuss the evidence showing that ADHD and/or deficits in executive functions are a barrier to a successful weight control in individuals enrolled in weight loss programs. Impairing symptoms of ADHD or deficits in executive functions may foster dysregulated eating behaviors, such as binge eating, emotionally-induced eating or eating in the absence of hunger, which, in turn, may contribute to unsuccessful weight loss. ADHD-related behaviors or neurocognitive impairment may also hamper a regular and structured physical activity. There is initial research showing that treatment of comorbid ADHD and executive functions training significantly improve the outcome of obesity in individuals with comorbid ADHD or impairment in executive functions. SUMMARY: Preliminary evidence suggests that comorbid ADHD and deficits in executive functions are a barrier to a successful weight loss in individuals involved in obesity treatment programs. If further methodologically sound evidence confirms this relationship, screening and effectively managing comorbid ADHD and/or executive functions deficits in individuals with obesity might have the potential to reduce not only the burden of ADHD but also the obesity epidemics.
Subject(s)
Attention Deficit Disorder with Hyperactivity/psychology , Executive Function/physiology , Feeding Behavior/psychology , Obesity/psychology , Weight Loss/physiology , Attention/physiology , Attention Deficit Disorder with Hyperactivity/complications , Humans , Neuropsychological Tests , Obesity/complications , Weight Reduction ProgramsABSTRACT
Previous studies have linked vitamin D deficiency to hypertension, dyslipidemia, diabetes mellitus, and cardiovascular disease. The aim of this study was to investigate the short-term effects of vitamin D3 supplementation on weight and glucose and lipid metabolism in antipsychotic-treated patients. A total of 19 schizophrenic or schizoaffective patients (BMI>27 kg/m²) taking atypical antipsychotics were recruited and dispensed a 2000 IU daily dose of vitamin D3. On comparing baseline with week 8 (study end) results, we found a statistically significant increase in vitamin D3 and total vitamin D levels but no statistically significant changes in weight, glucose, or lipids measurements. Patients whose vitamin D3 level at week 8 was 30 ng/ml or more achieved a significantly greater decrease in total cholesterol levels compared with those whose week 8 vitamin D3 measurement was less than 30 ng/ml. These results suggest that a randomized trial with a longer follow-up period would be helpful in further evaluating the effects of vitamin D3 on weight, lipid metabolism, and on components of metabolic syndrome in antipsychotic-treated patients.
Subject(s)
Antipsychotic Agents/adverse effects , Cholecalciferol/therapeutic use , Dietary Supplements , Hypercholesterolemia/prevention & control , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Vitamin D Deficiency/diet therapy , Adult , Aged , Antipsychotic Agents/therapeutic use , Body Mass Index , Cholecalciferol/blood , Female , Humans , Hypercholesterolemia/epidemiology , Hypercholesterolemia/etiology , Male , Massachusetts/epidemiology , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Metabolic Syndrome/prevention & control , Middle Aged , Overweight/complications , Overweight/epidemiology , Pilot Projects , Psychiatric Status Rating Scales , Psychotic Disorders/blood , Psychotic Disorders/complications , Psychotic Disorders/metabolism , Risk Factors , Schizophrenia/blood , Schizophrenia/complications , Schizophrenia/metabolism , Vitamin D Deficiency/complications , Vitamin D Deficiency/physiopathologyABSTRACT
BACKGROUND: We present a retrospective study examining response to treatment with fibrates or statins in schizophrenia patients. METHODS: We identified the patient population using the Research Patient Data Registry. Demographic data, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL cholesterol (non-HDL-C) levels were obtained before initiation of treatment with lipid-lowering medication (LLM) and after LLM treatment was initiated (N = 183). RESULTS: Treatment with LLMs resulted in a statistically significant decrease in total cholesterol, triglycerides, LDL-C, and non-HDL-C. An independent-samples t test comparing the statin treatment-alone group with the fibrate treatment-alone group showed a significant reduction in triglyceride levels from baseline to 1-year follow-up in the fibrate treatment-alone group. CONCLUSIONS: The results of this study indicate that schizophrenia patients respond to LLMs in a manner consistent with the general population. Future studies would benefit from a larger sample, as well as comparisons between more specific treatment groups, such as those defined by type of statin or fibrate, to observe differential effects on specific markers of dyslipidemia in this population.
Subject(s)
Antipsychotic Agents/adverse effects , Fibric Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/drug therapy , Hypolipidemic Agents/therapeutic use , Schizophrenia/drug therapy , Aged , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Humans , Hyperlipidemias/chemically induced , Hyperlipidemias/complications , Male , Middle Aged , Retrospective Studies , Schizophrenia/complications , Treatment Outcome , Triglycerides/bloodABSTRACT
INTRODUCTION: Even though cognitive impairment is manifested in almost all patients with schizophrenia, the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) study showed no significant difference between first- and second-generation psychotropic drugs in improving cognitive abilities. Discovering new drugs that can improve impaired cognition, thus, is an attractive treatment target for patients with schizophrenia. AREAS COVERED: This article briefly reviews about donepezil, a highly selective (IC(50) = 6.7 nM) centrally acting reversible acetylcholinesterase inhibitor that has been approved by FDA for treating cognitive deficit states such as in Alzheimer's disease and its uses in clinical trials for the treatment of schizophrenia. The literature search included PubMed and Cochrane library with the following words: donepezil, schizophrenia and cognitive impairments. EXPERT OPINION: The results of several clinical trials utilizing donepezil as an adjunct to second-generation antipsychotic drugs targeting cognitive deficits in schizophrenia subjects have been disappointing and would not lead clinicians to consider this as a potential treatment option. While longer randomized controlled trials, increase dosage and selected groups of patients at different stage of cognitive impairment may provide a better understanding of the potential for this drug in addressing cognitive deficits, results to date have not been encouraging.
Subject(s)
Cholinesterase Inhibitors/therapeutic use , Cognition Disorders/drug therapy , Indans/therapeutic use , Piperidines/therapeutic use , Schizophrenia/drug therapy , Binding Sites , Cholinesterase Inhibitors/administration & dosage , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Clinical Trials as Topic , Cognition Disorders/psychology , Donepezil , Humans , Indans/administration & dosage , Indans/chemistry , Indans/pharmacology , Models, Molecular , Molecular Structure , Piperidines/administration & dosage , Piperidines/chemistry , Piperidines/pharmacology , Schizophrenia/complications , Schizophrenic Psychology , Treatment OutcomeABSTRACT
Although quite overlooked, increasing evidence points to a significant association between attention-deficit/hyperactivity disorder (ADHD) and obesity. Here, we present an updated systematic review and a critical discussion of studies on the relationship between ADHD and obesity, with a particular emphasis on the possible behavioral, neurobiological, and genetics underlying mechanisms. Available empirically based studies indicate that the prevalence of ADHD in clinical samples of patients seeking treatment for their obesity is higher than that in the general population. Moreover, although still limited, current evidence shows that individuals with ADHD have higher-than-average body mass index z-scores and/or significantly higher obesity rates compared with subjects without ADHD. Three mechanisms underlying the association between ADHD and obesity have been proposed: (1) obesity and/or factors associated with it (such as sleep-disordered breathing and deficits in arousal/alertness) manifest as ADHD-like symptoms; (2) ADHD and obesity share common genetics and neurobiological dysfunctions, involving the dopaminergic and, possibly, other systems (e.g., brain-derived neurotropic factor, melanocortin-4-receptor); and (3) impulsivity and inattention of ADHD contribute to weight gain via dysregulated eating patterns. With regards to the possible clinical implications, we suggest that it is noteworthy to screen for ADHD in patients with obesity and to look for abnormal eating behaviors as possible contributing factors of obesity in patients with ADHD. If further studies confirm a causal relationship between ADHD and obesity, appropriate treatment of ADHD may improve eating patterns and, as a consequence, weight status of individuals with both obesity and ADHD.
Subject(s)
Attention Deficit Disorder with Hyperactivity/complications , Attention Deficit Disorder with Hyperactivity/epidemiology , Obesity/epidemiology , Obesity/etiology , HumansABSTRACT
This study assessed how body size dissatisfaction (BSD) varies in relationship to specific body mass index (BMI) values in a sample of preadolescents. A novel statistical approach based on spline function, suitable to assess in detail how two variables are related, was used. The study was conducted between December 2004 and March 2005. Students (aged 11 to 14 years) from seven selected secondary schools in Verona, Italy, were invited to participate. The final study group included 678 subjects. BSD was assessed using the Body Image Assessment Procedure. BMI values were expressed as z scores. It was found that, in the total sample, slightly underweight subjects (BMI z scores=-0.5) had no BSD. BSD progressively increased (current body size > ideal body size) for BMI z scores >-0.5 and became negative (ideal body size > current body size) for BMI z scores <-0.5. In boys, average weight subjects had no BSD. BSD progressively increased for BMI z scores >0 and became negative for BMI z scores <0. In girls, moderately underweight subjects (BMI z scores=-1) had no BSD. BSD progressively increased for BMI z scores >-1 and became negative for BMI z scores <-1. Although sex significantly moderated the relationship between BMI and BSD (P<0.001), socioeconomic status did not (P=0.459). Because average weight and slightly underweight young girls desired a thinner body, our study suggests that these subgroups should receive particular attention in public health programs as well as in dietetics clinical practice.
Subject(s)
Body Composition/physiology , Body Image , Body Mass Index , Personal Satisfaction , Students/psychology , Adolescent , Body Size , Child , Female , Humans , Italy , Male , Obesity/psychology , Psychology, Adolescent , Sex Factors , Students/statistics & numerical data , Thinness/psychologyABSTRACT
OBJECTIVE: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) should be considered in sudden onset, prepubertal Anorexia Nervosa (AN), arising shortly after an apparent streptococcal infection. However, the absence of a specific biological marker of PANDAS renders the diagnosis difficult. This paper critically reviews available tests for PANDAS and recommends a standardized approach to its investigation. METHOD: Medline database review between 1990 and 2008. RESULTS: Existing tests may be categorized as: (i) Non-specific markers of inflammation or immune response (Erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; Neopterin), (ii) specific markers of streptococcal infection (throat swab and anti-streptococcal antibodies, Anti-streptolysin, ASO; Antideoxyribonuclease B, antiDNaseB), (iii) non-specific markers of auto-immune reaction (Antineuronal antibodies, AnAb; D8/17). No one test reliably identifies PANDAS. The lack of specificity and methodological problems may lead to errors of diagnosis. DISCUSSION: When PANDAS-Anorexia Nervosa (PANDAS-AN) is suspected clinically we recommend conducting all the above investigations. The more positive results there are the more likely is the diagnosis, but particular weighting should be given to AnAb and D8/17.
Subject(s)
Anorexia Nervosa/complications , Autoimmune Diseases/complications , Autoimmune Diseases/diagnosis , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Anorexia Nervosa/blood , Anorexia Nervosa/diagnosis , Anorexia Nervosa/immunology , Autoantibodies/blood , Autoimmune Diseases/blood , Autoimmune Diseases/immunology , Biomarkers/blood , C-Reactive Protein/metabolism , Diagnosis, Differential , Humans , Streptococcal Infections/blood , Streptococcal Infections/immunologyABSTRACT
Recent studies suggest a possible comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity. To gain insight into this potential association, we performed a systematic review of the literature excluding case reports, non-empirical studies, and studies not using ADHD diagnostic criteria. Empirically based evidence suggests that obese patients referred to obesity clinics may present with higher than expected prevalence of ADHD. Moreover, all reviewed studies indicate that subjects with ADHD are heavier than expected. However, data on the prevalence of obesity in subjects with ADHD are still limited. As for the mechanisms underlying the potential association between ADHD and obesity, ADHD might lead to obesity via abnormal eating behaviors, impulsivity associated with binge eating might contribute to ADHD in obese patients, or, alternatively, both obesity and ADHD might be the expression of common underlying neurobiological dysfunctions, at least in a subset of subjects. In patients with obesity and ADHD, both conditions might benefit from common therapeutic strategies. Further empirically based studies are needed to understand the potential comorbidity between obesity and ADHD, as well as the possible mechanisms underlying this association. This might allow a more appropriate clinical management and, ultimately, a better quality of life for patients with both obesity and ADHD.
Subject(s)
Attention Deficit Disorder with Hyperactivity/complications , Obesity/complications , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/epidemiology , Central Nervous System Stimulants/adverse effects , Central Nervous System Stimulants/therapeutic use , Humans , Obesity/drug therapy , Obesity/epidemiology , Weight Loss/drug effectsABSTRACT
OBJECTIVE: Recent evidence suggests an association between obesity and Attention Deficit/Hyperactivity Disorder (ADHD) or ADHD traits. The characteristics of obese subjects with a higher probability of ADHD symptoms are still unclear. We explore the hypothesis that obese adolescents with sleep/alertness problems represent a subgroup at high risk for ADHD traits, independently from associated symptoms of anxiety/depression. The aim of this study was to assess the relationship between parent reports of sleep/alertness problems and ADHD traits in a clinical sample of obese adolescents, controlling for symptoms of anxiety/depression. METHODS: Seventy obese subjects (age range, 10-16 years) were included. The parents filled out the Sleep Disturbance Scale for Children (SDSC), the Conners Parents Rating Scale-Revised (Short Version) (CPRS-R:S), and the Child Behavior Checklist (CBCL). The ADHD Rating Scale (ADHD-RS) was completed by a child psychiatrist. RESULTS: Using multiple regression models controlling for symptoms of anxiety/depression, scores of excessive daytime sleepiness on the SDSC were significantly associated with ADHD traits on the CPRS-R:S as well as on the ADHD-RS. CONCLUSIONS: Obese adolescents described as excessively sleepy by their parents may be at higher risk of ADHD symptoms, independently from symptoms of anxiety/depression. Although the clinician may overlook a potential diagnosis of ADHD in obese adolescents described as sleepy, the results of this study suggest to systematically look for symptoms of ADHD in this subgroup of obese patients. Further studies using objective methods to assess sleep/alertness disturbances are needed to gain insight into the relationship between sleep/alertness disturbances and ADHD in obese individuals.