Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviours that are experienced as unwanted. Family and twin studies have demonstrated that OCD is a multifactorial ...familial condition that involves both polygenic and environmental risk factors. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuit in the pathophysiology of the disorder, which is supported by the observation of specific neuropsychological impairments in patients with OCD, mainly in executive functions. Genetic studies indicate that genes affecting the serotonergic, dopaminergic and glutamatergic systems, and the interaction between them, play a crucial part in the functioning of this circuit. Environmental factors such as adverse perinatal events, psychological trauma and neurological trauma may modify the expression of risk genes and, hence, trigger the manifestation of obsessive-compulsive behaviours.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Assessing the scope of acute medication harms to patients should include both therapeutic and nontherapeutic medication use. OBJECTIVE: To describe the characteristics of emergency ...department (ED) visits for acute harms from both therapeutic and nontherapeutic medication use in the US. DESIGN, SETTING, AND PARTICIPANTS: Active, nationally representative, public health surveillance based on patient visits to 60 EDs in the US participating in the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance Project from 2017 through 2019. EXPOSURES: Medications implicated in ED visits, with visits attributed to medication harms (adverse events) based on the clinicians’ diagnoses and supporting data documented in the medical record. MAIN OUTCOMES AND MEASURES: Nationally weighted estimates of ED visits and subsequent hospitalizations for medication harms. RESULTS: Based on 96 925 cases (mean patient age, 49 years; 55% female), there were an estimated 6.1 (95% CI, 4.8-7.5) ED visits for medication harms per 1000 population annually and 38.6% (95% CI, 35.2%-41.9%) resulted in hospitalization. Population rates of ED visits for medication harms were higher for patients aged 65 years or older than for those younger than 65 years (12.1 vs 5.0 95% CI, 7.4-16.8 vs 4.1-5.8 per 1000 population). Overall, an estimated 69.1% (95% CI, 63.6%-74.7%) of ED visits for medication harms involved therapeutic medication use, but among patients younger than 45 years, an estimated 52.5% (95% CI, 48.1%-56.8%) of visits for medication harms involved nontherapeutic use. The proportions of ED visits for medication harms involving therapeutic use were lowest for barbiturates (6.3%), benzodiazepines (11.1%), nonopioid analgesics (15.7%), and antihistamines (21.8%). By age group, the most frequent medication types and intents of use associated with ED visits for medication harms were therapeutic use of anticoagulants (4.5 95% CI, 2.3-6.7 per 1000 population) and diabetes agents (1.8 95% CI, 1.3-2.3 per 1000 population) for patients aged 65 years and older; therapeutic use of diabetes agents (0.8 95% CI, 0.5-1.0 per 1000 population) for patients aged 45 to 64 years; nontherapeutic use of benzodiazepines (1.0 95% CI, 0.7-1.3 per 1000 population) for patients aged 25 to 44 years; and unsupervised medication exposures (2.2 95% CI, 1.8-2.7 per 1000 population) and therapeutic use of antibiotics (1.4 95% CI, 1.0-1.8 per 1000 population) for children younger than 5 years. CONCLUSIONS AND RELEVANCE: According to data from 60 nationally representative US emergency departments, visits attributed to medication harms in 2017-2019 were frequent, with variation in products and intent of use by age.
Research in etiology, neurobiology, genetics, clinical correlates, and evidence-based treatments in children and adolescents with obsessive-compulsive disorder indicate a need for the revision of the ...Practice Parameters for the Assessment and Treatment of Children and Adolescents with Obsessive-Compulsive Disorder first published a decade ago. The present article highlights the clinical assessment and reviews and summarizes the evidence base for treatment. Based on this evidence, specific recommendations are provided for assessment, cognitive behavioral therapy, pharmacotherapy, combined treatment, and other interventions.
The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that ...perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05). Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-β (TGF-β) signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There appear to be two peaks of incidence of Obsessive Compulsive Disorder (OCD), one with a pre-adolescent onset and another in early adulthood. As new cases are added, the cumulative prevalence of ...OCD increases, but the great majority of cases have an onset in youth. The notion that early onset OCD represents a unique developmental subtype of the disorder has been considered by many researchers based on several specific age-related factors. Ascertainment and early intervention in affected youth is critical to abbreviate the functional impairments associated with untreated illness. In this paper we review the clinical, familial and translational biomarker correlates seen in early onset OCD that support the notion of a developmental subtype and discuss implications for research and treatment aimed at this cohort. The importance of cognitive, academic and social development tasks of childhood and adolescence, illness-specific and familial factors, and immune-mediated inflammatory factors are discussed, with their implications for management.
Obsessive-compulsive disorder (OCD) frequently affects children and adolescents, with most cases beginning during this time. Symptoms of OCD in youth may present as exaggerated developmental concerns ...and excessive ritualistic behavior beyond what is part of normal development, yet low levels of insight may prevent recognition. Affected youth commonly have comorbid neurodevelopmental diagnoses, especially males. Early detection and intervention are critical to recovery and remission, as well as family involvement in treatment. Cognitive behavioral therapy and serotonin reuptake inhibitors are first-line treatments.
Objective:
To use a family genetic study to evaluate familial risk of obsessive compulsive disorder (OCD) and common comorbid illnesses in first-degree relatives of pediatric-onset probands with ...primary OCD.
Method:
One hundred and thirty youth with OCD and their 133 siblings and 241 parents and 49 pediatric controls were directly evaluated along multiple domains including psychopathology using structured diagnostic interviews and clinical corroboration.
Results:
Rates of anxiety, mood, disruptive behavior, and tic disorders were markedly elevated in the probands while rates in siblings were elevated at rates between the probands and controls. Twenty six percent of first-degree relatives had clinical OCD, 9% had chronic tics or Tourette’s disorder, and 21% met criteria for ADHD.
Conclusion:
Rates of familial transmission of OCD and common comorbid illnesses were significantly higher in our pediatric-onset probands than rates reported in the literature in relatives of those with adult-onset OCD.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
In this issue of the Journal, we publish two letters pertaining to the article "Systematic Review and Meta-analysis: Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder in Children and ...Adolescents" by Uhre et al.
Their protocol employed the Cochrane Handbook for Systematic Reviews of Interventions to evaluate risk of bias (selection, performance, detection, attrition, and reporting biases) in the included 25 trials, contacting trial authors to obtain missing data where possible. They controlled for random errors owing to sparse data or multiple testing using Trial Sequential Analysis and evaluated the certainty of the evidence using the Grading of Recommendations Assessment Development and Evaluation approach. They concluded that cognitive-behavioral therapy (CBT) (versus no intervention) is effective for pediatric obsessive-compulsive disorder (OCD), but that the certainty of evidence was low or very low for all outcomes and that moderator analyses could often not be completed for lack of data. The authors made the point that blinding is always possible, even in CBT trials.
Limited extant research on neurocognitive endophenotypes in obsessive-compulsive disorder (OCD) show inconsistent results. Limitations of this body of literature include small sample sizes, strict ...exclusion criteria, lack of objective standard normalized test scores, and significant lack of studies utilizing pediatric probands. This study aimed to address these limitations.
A large carefully screened cohort of pediatric OCD (n = 102), their unaffected siblings (n = 78), and parents (n = 164), completed a neuropsychological battery. To compare participants at different ages and developmental stages, standard scores were computed using test norms. Cluster-robust regression with sample size-adjusted sandwich estimates of variance, and interclass correlations were computed. False Discovery Rate procedures were employed to correct for multiplicity.
Probands, siblings and parents demonstrated deficient task performance (Z < −0.5) on the ‘number of trials to complete first category’ on the Wisconsin Card Sorting Test, and on the Stroop color naming trials. Compared to test norms, the three groups exhibited medium to large effect sizes on these outcome measures. No other meaningful familial trends were found.
OCD probands, their unaffected siblings and parents exhibited deficiencies in specific subdomains of cognitive flexibility and inhibitory control, namely, initial concept formation and proactive control, which may be valid candidate neurocognitive endophenotypes of OCD. No other meaningful familial effect has been found on other functions, including other executive function indices such as perseverations and interference control. These results highlight the need to carefully examine individual outcomes from executive function tests instead of the tendency to focus largely on major outcome measures.
•A large cohort of pediatric OCD probands, their unaffected siblings and parents completed a neuropsychological battery.•Deficient performance found among OCD probands and unaffected relatives on initial concept formation and proactive control.•These subdomains of cognitive flexibility and inhibitory control may be candidate endophenotypes of OCD.•These results echo the need for a high-resolution examination of secondary neurocognitive outcome measures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Greenberg and Geller discuss the study by Grant et al which describes strikingly positive results for a randomized, double-blind, placebo-controlled study of memantine for body-focused repetitive ...behavior (BFRB) disorders. BFRBs are common and include a variety of "grooming behaviors," such as repetitive hair pulling, skin picking, cheek biting, and nail biting. They are predominantly subclinical, with upwards of 60% of individuals engaging in one or more BFRBs. As Grant et al point out, BFRB disorders are frequently debilitating. Individuals with pathological BFRBs can spend hours a day picking or pulling and engaging in efforts to conceal the physical impact of their symptoms.
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