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Michael H Bloch,
Christy Green,
Stephen A Kichuk,
Philip A Dombrowski,
Suzanne Wasylink,
Eileen Billingslea,
Angeli Landeros-Weisenberger,
Benjamin Kelmendi,
Wayne K Goodman,
James F Leckman,
Vladimir Coric,
Christopher Pittenger
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ABSTRACT: BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic condition that often produces lifelong morbidity, but few studies have examined long-term outcome (greater than 5 years) in adult patients. Available studies suggest that 32-74% of adult OCD patients will experience clinical improvement over the long term. However, these studies were conducted before validated OCD rating scales were established and the development of evidence-based treatments for OCD. METHODS: We investigated the 10-20 year outcome of 83 of 165 eligible subjects previously enrolled after participation in placebo-controlled trials of serotonin reuptake inhibitor (SRI) medications for OCD. We examined the association between clinical characteristics at initial assessment and OCD symptom severity at follow-up. We hypothesized that primary OCD symptom dimension and initial response to pharmacotherapy with serotonin reuptake inhibitors would be associated with later symptom severity. RESULTS: Only 20% (17 of 83) of subjects had experienced a remission of their OCD symptoms at follow-up (Y-BOCS ≤ 8). Forty-nine percent (41 of 83) of subjects were still experiencing clinically significant OCD symptoms. Response to initial SRI pharmacotherapy was significantly associated with long-term outcome: 31% (13 of 42) of subjects who responded (CGI < 3) to initial SRI pharmacotherapy were remitted at follow-up, compared to 12% (3 of 25) of partial responders and none of the 16 subjects who had no response to initial SRI pharmacotherapy. We did not find a significant association between long-term clinical outcome and any of the OCD symptom dimensions. CONCLUSION: Despite the introduction and dissemination of several evidence-based treatments for OCD, most adult OCD patients do not achieve remission. Initial response to pharmacotherapy was strongly associated with long-term outcome. Depression and Anxiety, 2013. © 2013 Wiley Periodicals, Inc.
Depression and Anxiety 03/2013; · 4.18 Impact Factor
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ABSTRACT: Our goals were to examine clinical characteristics and age and gender correlates in pediatric trichotillomania.
A total of 62 children (8-17 years of age) were recruited for a pediatric trichotillomania treatment trial and characterized using structured rating scales of symptoms of hairpulling and common comorbid conditions. We analyzed the association between qualitative and quantitative characteristics of pulling, comorbidities, and age and gender. We also examined the type of treatments these children previously received in the community.
We found lower rates of comorbid depression and anxiety disorders than have been reported in adult trichotillomania samples. Focused hairpulling significantly increased with age, whereas automatic pulling remained constant. Older children with hairpulling experienced more frequent urges and a decreased ability to refrain from pulling. Female participants reported greater distress and impairment associated with hairpulling, even though the severity of pulling did not differ from that of male participants.
These results confirm several findings from the Children and Adolescent Trichotillomania Impact Project (CA-TIP). Our cross-sectional findings suggest there may be a developmental progress of symptoms in trichotillomania. Children appeared to develop more focused pulling, to become more aware of their urges, and to experience more frequent urges to pull, as they get older. Although these are important findings, they need to be confirmed in prospective longitudinal studies.
Journal of the American Academy of Child and Adolescent Psychiatry 03/2013; 52(3):241-9. · 4.98 Impact Factor
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ABSTRACT: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study.
A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of hairpulling as measured by the Massachusetts General Hospital-Hairpulling Scale (MGH-HPS). Secondary measures assessed hairpulling severity, automatic versus focused pulling, clinician-rated improvement, and comorbid anxiety and depression. Outcomes were examined using linear mixed models to test the treatment×time interaction in an intention-to-treat population.
No significant difference between N-acetylcysteine and placebo was found on any of the primary or secondary outcome measures. On several measures of hairpulling, subjects significantly improved with time regardless of treatment assignment. In the NAC group, 25% of subjects were judged as treatment responders, compared to 21% in the placebo group.
We observed no benefit of NAC for the treatment of children with trichotillomania. Our findings stand in contrast to a previous, similarly designed trial in adults with TTM, which demonstrated a very large, statistically significant benefit of NAC. Based on the differing results of NAC in pediatric and adult TTM populations, the assumption that pharmacological interventions demonstrated to be effective in adults with TTM will be as effective in children, may be inaccurate. This trial highlights the importance of referring children with TTM to appropriate behavioral therapy before initiating pharmacological interventions, as behavioral therapy has demonstrated efficacy in both children and adults with trichotillomania.
Journal of the American Academy of Child and Adolescent Psychiatry 03/2013; 52(3):231-40. · 4.98 Impact Factor
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ABSTRACT: BACKGROUND AND OBJECTIVE:Long-chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to affect visual acuity development in infants. Randomized controlled trials (RCTs) have been conducted to assess whether supplementation of LCPUFAs of infant formulas affects infant visual acuity. This meta-analysis was conducted to evaluate whether LCPUFA supplementation of infant formulas improves infants' visual acuity.METHODS:PubMed and PsycInfo were searched for RCTs assessing the efficacy of LCPUFA supplementation of infant formulas on infant visual acuity. RCTs assessing the effects of LCPUFA supplementation on visual acuity (by using either visual evoked potential or behavioral methods) in the first year of life were included in this meta-analysis. Our primary outcome was the mean difference in visual resolution acuity (measured in logarithm of minimum angle of resolution [logMAR]) between supplemented and unsupplemented infants. We also conducted secondary subgroup analyses and meta-regression examining the effects of LCPUFA dose and timing, preterm versus term birth status, and trial methodologic quality.RESULTS:Nineteen studies involving 1949 infants were included. We demonstrated a significant benefit of LCPUFA supplementation on infants' visual acuity at 2, 4, and 12 months of age when visual acuity was assessed by using visual evoked potential and at 2 months of age by using behavioral methods. There was significant heterogeneity between trials but no evidence of publication bias. Secondary analysis failed to show any moderating effects on the association between LCPUFA supplementation and visual acuity.CONCLUSIONS:Current evidence suggests that LCPUFA supplementation of infant formulas improves infants' visual acuity up to 12 months of age.
PEDIATRICS 12/2012; · 4.47 Impact Factor
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ABSTRACT: Tourette Syndrome (TS) is a neuropsychiatric disorder involving multiple motor and phonic tics. Tics, which usually begin between the ages of 6 and 8, are sudden, rapid, stereotyped, and apparently purposeless movements or sounds that involve discrete muscle groups. Individuals with TS experience a variety of different sensory phenomena, including premonitory urges prior to tics and somatic hypersensitivity due to impaired sensorimotor gating. In addition to other conditions, stress, anxiety, fatigue, or other heightened emotional states tend to exacerbate tics, while relaxation, playing sports, and focused concentration on a specific task tend to alleviate tic symptoms. Ninety percent of children with TS also have comorbid conditions, such as Attention deficit hyperactivity disorder (ADHD), Obsessive-compulsive disorder (OCD), or an impulse control disorder. These disorders often cause more problems for the child both at home and at school than tics do alone. Proper diagnosis and treatment of TS involves appropriate evaluation and recognition, not only of tics, but also of these associated conditions.
Neuroscience & Biobehavioral Reviews 11/2012; · 8.65 Impact Factor
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ABSTRACT: We conducted a meta-analysis of randomized, placebo-controlled trials to determine the efficacy of antipsychotic and alpha-2 agonists in the treatment of chronic tic disorders and examine moderators of treatment effect. Meta-analysis demonstrated a significant benefit of antipsychotics compared to placebo (standardized mean difference (SMD)=0.58 (95% confidence interval (CI): 0.36-0.80). Stratified subgroup analysis found no significant difference in the efficacy of the 4 antipsychotic agents tested (risperidone, pimozide, haloperidol and ziprasidone). Meta-analysis also demonstrated a benefit of alpha-2 agonists compared to placebo (SMD=0.31 (95% confidence interval CI: 0.15-0.48). Stratified subgroup analysis and meta-regression demonstrated a significant moderating effect of co-occurring ADHD. Trials which enrolled subjects with tics and ADHD demonstrated a medium-to-large effect (SMD=0.68 (95%CI: 0.36-1.01) whereas trials that excluded subjects with ADHD demonstrated a small, non-significant benefit (SMD=0.15 (95%CI: -0.06-0.36). Our findings demonstrated significant benefit of both antipsychotics and alpha-2 agonists in treating tics but suggest alpha-2 agonists may have minimal benefit in tic patients without ADHD.
Neuroscience & Biobehavioral Reviews 10/2012; · 8.65 Impact Factor
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Alan Anticevic,
Mark Gancsos,
John D Murray,
Grega Repovs,
Naomi R Driesen,
Debra J Ennis,
Mark J Niciu,
Peter T Morgan,
Toral S Surti, Michael H Bloch,
Ramachandran Ramani,
Mark A Smith,
Xiao-Jing Wang,
John H Krystal,
Philip R Corlett
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ABSTRACT: Glutamatergic neurotransmission mediated by N-methyl-d-aspartate (NMDA) receptors is vital for the cortical computations underlying cognition and might be disrupted in severe neuropsychiatric illnesses such as schizophrenia. Studies on this topic have been limited to processes in local circuits; however, cognition involves large-scale brain systems with multiple interacting regions. A prominent feature of the human brain's global architecture is the anticorrelation of default-mode vs. task-positive systems. Here, we show that administration of an NMDA glutamate receptor antagonist, ketamine, disrupted the reciprocal relationship between these systems in terms of task-dependent activation and connectivity during performance of delayed working memory. Furthermore, the degree of this disruption predicted task performance and transiently evoked symptoms characteristic of schizophrenia. We offer a parsimonious hypothesis for this disruption via biophysically realistic computational modeling, namely cortical disinhibition. Together, the present findings establish links between glutamate's role in the organization of large-scale anticorrelated neural systems, cognition, and symptoms associated with schizophrenia in humans.
Proceedings of the National Academy of Sciences 09/2012; 109(41):16720-5. · 9.68 Impact Factor
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ABSTRACT: BACKGROUND: Treatments for obsessive-compulsive disorder (OCD) usually lead to incomplete symptom relief and take a long-time to reach full effect. Convergent evidence suggests that glutamate abnormalities contribute to the pathogenesis of OCD. Ketamine is a potent noncompetitive antagonist of the N-methyl-D-aspartate glutamate receptor. Trials have reported rapid antidepressant effects after low-dose ketamine infusion. METHODS: We conducted an open-label trial of ketamine (.5 mg/kg IV over 40 min) in 10 subjects with treatment-refractory OCD. Response was defined as >35% improvement in OCD symptoms and >50% improvement in depression symptoms from baseline at any time between 1 and 3 days after infusion. RESULTS: None of 10 subjects experienced a response in OCD symptoms in the first 3 days after ketamine. Four of seven patients with comorbid depression experienced an antidepressant response to ketamine in the first 3 days after infusion. Both OCD and depression symptoms demonstrated a statistically significant improvement in the first 3 days after infusion compared with baseline, but the OCD response was <12%. The percentage reduction in depressive symptoms in the first 3 days after ketamine infusion was significantly greater than the reduction in OCD symptoms. CONCLUSIONS: Ketamine effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated.
Biological psychiatry 07/2012; · 8.93 Impact Factor
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ABSTRACT: Infant formula is supplemented with long-chain polyunsaturated fatty acids (LCPUFAs) because they are hypothesized to improve cognition. Several randomized controlled clinical trials have examined the effect of LCPUFA supplementation of infant formula on cognitive development. We conducted this meta-analysis to examine the efficacy of LCPUFA supplementation of infant formula on early cognitive development.
Two authors searched PubMed, PsychInfo, and Scopus for randomized controlled clinical trials assessing the efficacy of LCPUFA supplementation of infant formulas on cognition. Our analysis was restricted to randomized controlled clinical trials that examined the effect of LCPUFA supplementation on infant cognition using Bayley Scales of Infant Development. Our primary outcome was the weighted mean difference in Bayley Scales of Infant Development score between infants fed formula supplemented with LCPUFA compared with unsupplemented formula. We conducted secondary subgroup analyses and meta-regression to examine the effects of study sample, LCPUFA dose, and trial methodologic quality on measured efficacy of supplementation.
Twelve trials involving 1802 infants met our inclusion criteria. Our meta-analysis demonstrated no significant effect of LCPUFA supplementation of formula on infant cognition. There was no significant heterogeneity or publication bias between trials. Secondary analysis failed to show any significant effect of LCPUFA dosing or prematurity status on supplementation efficacy.
LCPUFA supplementation of infant formulas failed to show any significant effect on improving early infant cognition. Further research is needed to determine if LCPUFA supplementation of infant formula has benefits for later cognitive development or other measures of neurodevelopment.
PEDIATRICS 05/2012; 129(6):1141-9. · 4.47 Impact Factor
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ABSTRACT: To determine the efficacy of D-cycloserine augmentation of behavioral therapy for the treatment of anxiety disorders.
Using the search terms D-cycloserine AND anxiety disorders (MeSH), PubMed (1965-June 2011), PsycINFO, and Scopus were searched for randomized, double-blind, placebo-controlled trials of D-cycloserine augmentation of behavioral therapy for the treatment of anxiety disorders. Anxiety disorders were defined as any disorder categorized as such in DSM-IV-TR.
A random-effects model was used to calculate the standardized mean difference of change in anxiety rating scale scores with D-cycloserine augmentation compared to placebo, which was the primary outcome measure. Subgroup analysis and meta-regression were used to examine the effects of D-cycloserine dosage and timing (relative to exposure therapy), diagnostic indication, number of therapy sessions, and trial methodological quality on D-cycloserine efficacy.
Meta-analysis of 9 trials involving 273 subjects demonstrated a significant benefit from D-cycloserine augmentation (standardized mean difference = 0.46 [95% CI, 0.15 to 0.77], z = 2.89, P = .004). There was no evidence of publication bias, but a moderate, nonsignificant degree of heterogeneity between trials (I2 = 36%, Q = 12.6, df = 8, P = .12) was found. Secondary analyses yielded no significant findings.
D-Cycloserine appears to be an effective augmentation agent that enhances the effects of behavioral therapy in the treatment of anxiety disorders. In contrast to a previous meta-analysis that examined D-cycloserine's effects in both animals and humans, we found no evidence of an effect of dose number, dose timing, or dosage of D-cycloserine on reported efficacy in the ranges studied.
The Journal of Clinical Psychiatry 04/2012; 73(4):533-7. · 5.80 Impact Factor
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ABSTRACT: Family accommodation refers to ways in which family members take part in the performance of rituals, avoidance of anxiety-provoking situations or modification of daily routines to assist a relative with obsessive-compulsive disorder (OCD). Our goal is to review the available data on the role of family accommodation in both children and adults with OCD. A search of available peer-reviewed English language papers was conducted through PubMed and PsycINFO cross-referencing the keyword OCD with accommodation, family relations and parents. The resulting 641 papers were individually evaluated for relevance to the scope of the review. It was found that accommodation is common in OCD and is strongly and consistently correlated with OCD symptom severity. Family accommodation also appears to be increased when the proband has cleaning contamination symptoms and increased internalizing or externalizing problems. Family accommodation is associated with increased parental OCD and anxiety symptoms. Levels of accommodation are associated with treatment outcomes for both behavioral and pharmacological treatment. Significant improvement of OCD symptoms with treatment is associated with reductions in family accommodation. Family accommodation represents important clinical data that is worth measuring, monitoring and tracking in clinical care. Therapies targeting family accommodation may be successful in improving treatment outcomes in OCD.
Expert Review of Neurotherapeutics 02/2012; 12(2):229-38.
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ABSTRACT: School dropout has significant consequences for both individuals and societies. Only 21% of adults in Mexico achieve the equivalent of a high school education. We examined the relationship between school dropout and self-reported psychiatric symptoms in a middle school in a suburb of Mexico City. We used binomial logistic regression to examine the odds ratio (OR) of school dropout associated with students' self-reported psychopathology. Two-hundred thirty-seven students participated in the study. Psychosis [OR = 8.0 (95% confidence interval, CI: 1.7-37.2)], depression [OR = 4.7 (95% CI: 2.2-9.7)], tic disorders [OR = 3.7 (95% CI: 1.4-9.5)], ADHD [OR = 3.2 (95% CI: 1.5-6.4)], and social phobia [OR = 2.6 (95% CI: 1.2-5.8)] were associated with increased risk of school dropout after controlling for age and gender as covariates. Our study suggested that students' self-reported psychopathology is associated with increased school dropout in Mexico. ADHD and depression may be particularly useful childhood psychiatric disorders to target with public health interventions because they explain the greatest amount of the variance in school dropout of child psychiatric disorders.
Frontiers in psychiatry / Frontiers Research Foundation. 01/2012; 3:20.
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ABSTRACT: Several studies have demonstrated differences in omega-3 fatty acid composition in plasma and in erythrocyte membranes in patients with attention-deficit/hyperactivity disorder (ADHD) compared with unaffected controls. Omega-3 fatty acids have anti-inflammatory properties and can alter central nervous system cell membrane fluidity and phospholipid composition. Cell membrane fluidity can alter serotonin and dopamine neurotransmission. The goal of this meta-analysis was to examine the efficacy of omega-3 fatty acid supplementation in children with ADHD.
PubMed was searched for randomized placebo-controlled trials examining omega-3 fatty acid supplementation in children with ADHD symptomatology. The primary outcome measurement was standardized mean difference in rating scales of ADHD severity. Secondary analyses were conducted to determine the effects of dosing of different omega-3 fatty acids in supplements.
Ten trials involving 699 children were included in this meta-analysis. Omega-3 fatty acid supplementation demonstrated a small but significant effect in improving ADHD symptoms. Eicosapentaenoic acid dose within supplements was significantly correlated with supplement efficacy. No evidence of publication bias or heterogeneity between trials was found.
Omega-3 fatty acid supplementation, particularly with higher doses of eicosapentaenoic acid, was modestly effective in the treatment of ADHD. The relative efficacy of omega-3 fatty acid supplementation was modest compared with currently available pharmacotherapies for ADHD such as psychostimulants, atomoxetine, or α(2) agonists. However, given its relatively benign side-effect profile and evidence of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacologic interventions or for families who decline other psychopharmacologic options.
Journal of the American Academy of Child and Adolescent Psychiatry 10/2011; 50(10):991-1000. · 4.98 Impact Factor
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ABSTRACT: Obsessive compulsive disorder is prevalent, disabling, incompletely understood, and often resistant to current therapies. Established treatments consist of specialized cognitive-behavioral psychotherapy and pharmacotherapy with medications targeting serotonergic and dopaminergic neurotransmission. However, remission is rare, and more than a quarter of OCD sufferers receive little or no benefit from these approaches, even when they are optimally delivered. New insights into the disorder, and new treatment strategies, are urgently needed. Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder. Here we review the current state of this evidence, including neuroimaging studies, genetics, neurochemical investigations, and insights from animal models. Finally, we review recent findings from small clinical trials of glutamate-modulating medications in treatment-refractory OCD. The precise role of glutamate dysregulation in OCD remains unclear, and we lack blinded, well-controlled studies demonstrating therapeutic benefit from glutamate-modulating agents. Nevertheless, the evidence supporting some important perturbation of glutamate in the disorder is increasingly strong. This new perspective on the pathophysiology of OCD, which complements the older focus on monoaminergic neurotransmission, constitutes an important focus of current research and a promising area for the ongoing development of new therapeutics.
Pharmacology [?] Therapeutics 09/2011; 132(3):314-32. · 8.56 Impact Factor
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ABSTRACT: Cross-sectional studies have associated poor insight in patients with obsessive-compulsive disorder (OCD) with increased OCD symptom severity, earlier age of onset, comorbid depression, and treatment response. The goal of this current study was to examine the relationship between dimensions of OCD symptomatology and insight in a large clinical cohort of Brazilian patients with OCD. We hypothesized that poor insight would be associated with total symptom severity as well as with hoarding symptoms severity, specifically.
824 outpatients underwent a detailed clinical assessment for OCD, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS), the Brown Assessment of Beliefs Scale (BABS), a socio-demographic questionnaire, and the Structured Clinical Interview for axis I DSM-IV disorders (SCID-P). Tobit regression models were used to examine the association between level of insight and clinical variables of interest.
Increased severity of current and worst-ever hoarding symptoms and higher rate of unemployment were associated with poor insight in OCD after controlling for current OCD severity, age and gender. Poor insight was also correlated with increased severity of current OCD symptoms.
Hoarding and overall OCD severity were significantly but weakly associated with level of insight in OCD patients. Further studies should examine insight as a moderator and mediator of treatment response in OCD in both behavioral therapy and pharmacological trials. Behavioral techniques aimed at enhancing insight may be potentially beneficial in OCD, especially among patients with hoarding.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 05/2011; 35(7):1677-81. · 3.25 Impact Factor
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ABSTRACT: To determine whether there is evidence of a time-lag bias in the publication of pediatric antidepressant trials.
We conducted a meta-analysis of published and unpublished randomized placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years of age with major depressive disorder. Our main outcomes were (1) time to publication of positive versus negative trials, and (2) proportion of treatment responders in trials with standard (<3 years after study completion) versus delayed publication.
We identified 15 randomized, placebo-controlled trials of SRIs for pediatric depression. Trials with negative findings had a significantly longer time to publication (median years ± standard deviation = 4.2 ± 1.9) than trials with positive findings (2.2 ± 0.9; log-rank χ(2) = 4.35, p = .037). The estimated efficacy in trials with standard publication time (number needed to treat = 7, 95% CI = 5-11) was significantly greater than those with delayed publication (17, 95% CI = 9-∞; χ(2) = 4.98, p = .025). The inflation-adjusted impact factor of journals for published trials with positive (15.33 ± 11.01) and negative results (7.54 ± 7.90) did not statistically differ (t = 1.4, df = 10, p = .17).
Despite a small number of trials of SRIs for pediatric antidepressants, we found a significant evidence of time-lag bias in the publication of findings. This time-lag bias altered the perceived efficacy of pediatric antidepressants in the medical literature. Time-lag bias is not unique to child psychiatry and reflects a larger problem in scientific publishing.
Journal of the American Academy of Child and Adolescent Psychiatry 01/2011; 50(1):63-72. · 4.98 Impact Factor
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ABSTRACT: Half of pediatric-onset OCD cases remit by adulthood. Studies have demonstrated that initial response to pharmacotherapy, age of onset, prominent hoarding symptoms, and the presence of comorbid tic disorders are associated with long-term outcome. Our goal was to examine the association between childhood performance on neuropsychological testing and persistence of OCD into adulthood.
Twenty-four children with OCD were followed for an average of 7.5 years into early adulthood. Neuropsychological performance in childhood (<16 years) was measured. The battery included the Wechsler Intelligence Scale for Children (WISC-III), the Purdue pegboard test, the Rey-Osterreith Complex Figure Task (RCFT) and the Beery-Buktenica test of Visual Motor Integration (VMI). We hypothesized that deficits in fine-motor skills, visuospatial skills, and nonverbal memory as well as overall intelligence would be associated with adulthood outcome. We used a Cox proportional hazard model of survival analysis in which time to remission of OCD symptoms was the main outcome variable.
Poor childhood performance on the Purdue pegboard task and the block design subscale of WISC-III was associated with persistence of OCD symptoms into adulthood. IQ, VMI, and nonverbal memory performance did not predict significantly the persistence of OCD.
These results suggest that visuospatial and fine-motor skill deficits are predictive of poor long-term outcome in pediatric-onset OCD. Future longitudinal studies are needed to chart the course of these deficits relative to the course of symptoms in OCD and to determine whether the association of these neuropsychiatric deficits with long-term outcome is specific to pediatric-onset OCD or generalizes to other psychiatric disorders.
Journal of Child Psychology and Psychiatry 01/2011; 52(9):974-83. · 4.28 Impact Factor
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ABSTRACT: This article reviews the available scientific literature concerning the neurobiological substrates of Tourette's disorder (TD).
The electronic databases of PubMed, ScienceDirect, and PsycINFO were searched for relevant studies using relevant search terms.
Neuropathological as well as structural and functional neuroimaging studies of TD implicate not only the sensorimotor corticostriatal circuit, but also the limbic and associative circuits as well. Preliminary evidence also points to abnormalities in the frontoparietal network that is thought to maintain adaptive online control. Evidence supporting abnormalities in dopaminergic and noradrenergic neurotransmission remains strong, although the precise mechanisms remain the subject of speculation.
Structural and functional abnormalities in multiple parallel corticostriatal circuits may underlie the behavioral manifestations of TD and related neuropsychiatric disorders over the course of development. Further longitudinal research is needed to elucidate these neurobiological substrates.
Journal of child and adolescent psychopharmacology 08/2010; 20(4):237-47. · 2.59 Impact Factor
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ABSTRACT: OCD is a psychiatric disorder with a lifetime prevalence of 1-3% and is a significant cause of disability worldwide. Family studies indicate that OCD has a significant hereditable component, with relatives of OCD cases being 4 times more likely to develop the disorder than the general population. Linkage studies in OCD have generally been underpowered and have failed to reach the statistical threshold for genome-wide significance, but they have nevertheless been useful for revealing potential regions of interest for future candidate gene studies. Candidate gene studies in OCD have thus far focused on genes involved in the serotonergic, dopaminergic, and glutamatergic pathways. These studies have been for the most part inconclusive, and failures to replicate have been the norm until very recently. The only genetic association replicated by multiple groups is with a glutamate transporter gene (SLC1A1). Genome-wide association studies in OCD are in progress, but final results have not yet been reported. As with the study of many other psychiatric disorders, an improved understanding of OCD will only be achieved [1] with larger collaborative efforts involving more probands, [2] the use of probands and controls drawn from epidemiologically-based populations rather than clinical samples, [3] developing a more precise phenotypic description of OCD and [4] measuring important environmental influences that affect OCD pathogenesis and severity.
Current Psychiatry Reviews 04/2010; 6(2):91-103.
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ABSTRACT: The goal of this study was to determine childhood clinical predictors of quality of life (QoL) in early adulthood in children with obsessive-compulsive disorder (OCD).
A longitudinal cohort study was conducted with 36 (out of 62 eligible) children with OCD, interviewed once at childhood baseline (mean age 12.1 ± 2.1, range 8.0-15.8), and again in early adulthood after an average follow-up interval of 9 years. QoL was measured in adulthood with the longitudinal interval follow-up evaluation range of impaired functioning tool (LIFE-RIFT).
Forty-two percent of children experienced a remission of OCD symptoms by early adulthood. OCD appeared to most strongly impair the interpersonal relationships and work domains of QoL. QoL and severity of OCD and anxiety symptoms were significantly associated in early adulthood. Primary hoarding symptoms in childhood predicted poor QoL in adulthood. Increased symptoms in the forbidden thoughts dimension in both childhood and adulthood were associated with improved adulthood QoL.
Children for whom OCD symptoms remitted by adulthood showed no evidence of residual impairment in QoL, whereas children whose OCD symptoms failed to remit by adulthood showed at most mild impairment in QoL. Hoarding symptoms in childhood appear to portend not only the persistence of OCD symptoms but also poorer QoL in early adulthood.
Social Psychiatry 02/2010; 46(4):291-7. · 2.05 Impact Factor
