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1.
J Child Adolesc Psychopharmacol ; 30(1): 32-37, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31800306

RESUMO

Background: Many children and adults with Obsessive-Compulsive Disorder (OCD) fail to respond to first-line pharmacological and behavioral treatments. Glutamate dysfunction may contribute to the development of OCD. N-acetylcysteine (NAC), a glutamate modulating drug, has shown to be a promising agent in adults with OCD. Methods: We conducted a double-blind, placebo-controlled clinical trial from July 2012 to January 2017. Children ages 8 to 17 years with OCD were assigned to receive NAC (up to 2700 mg/day) or the matching placebo for a period of 12 weeks. Children were required to be on stable psychiatric treatment (both medication and therapy) but were not required to be treatment-refractory. The primary outcome was OCD symptom severity as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We used linear mixed models to analyze the effect of NAC compared to placebo. Results: Due to poor recruitment and eventual expiration of the study medication, enrollment was stopped at 11 children out of a planned sample size of 40. Nonetheless, NAC was associated with significant reduction in CY-BOCS total score compared to placebo (Satterthwaite's test: t (37) = 2.36, p = 0.024) with effects separating from placebo beginning at week 8. Mean CY-BOCS total score decreased in the NAC group from 21.4 ± 4.65 at baseline to 14.4 ± 5.55 at week 12. In the placebo group, mean CY-BOCS total score remained unchanged (21.3 ± 4.65). In the NAC group, 1 out of 5 participants achieved >35% improvement in CY-BOCS total score, while none of the six patients in placebo group reached this improvement level. NAC and placebo were well tolerated. One mild adverse event was reported in each group. Conclusions: Our trial suggests that there may be some initial improvement in OCD symptom severity with NAC treatment. NAC was well tolerated in the study population. Future trials should employ multiple sites and have a larger study population to further confirm any benefits of NAC.

2.
Neuropsychopharmacology ; 43(2): 325-333, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28849779

RESUMO

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.


Assuntos
Ansiolíticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Adulto , Ansiolíticos/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Humanos , Ketamina/administração & dosagem , Masculino , Fobia Social , Escalas de Graduação Psiquiátrica , Adulto Jovem
3.
Am J Psychiatry ; 174(7): 667-675, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28135845

RESUMO

OBJECTIVE: Bipolar disorder is associated with high risk for suicidal behavior that often develops in adolescence and young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents and young adults with bipolar disorder with and without a history of suicide attempts combines structural, diffusion tensor, and functional MR imaging methods to investigate implicated abnormalities in the morphology and structural and functional connectivity within frontolimbic systems. METHOD: The study had 26 participants with bipolar disorder who had a prior suicide attempt (the attempter group) and 42 participants with bipolar disorder without a suicide attempt (the nonattempter group). Regional gray matter volume, white matter integrity, and functional connectivity during processing of emotional stimuli were compared between groups, and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. RESULTS: Compared with the nonattempter group, the attempter group showed significant reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum; white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala functional connectivity to the left ventral and right rostral prefrontal cortex. In exploratory analyses, among attempters, there was a significant negative correlation between right rostral prefrontal connectivity and suicidal ideation and between left ventral prefrontal connectivity and attempt lethality. CONCLUSIONS: Adolescent and young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral frontolimbic neural system subserving emotion regulation. Among attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicidal ideation and attempt lethality.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/fisiopatologia , Imagem por Ressonância Magnética , Tentativa de Suicídio/psicologia , Adolescente , Tonsila do Cerebelo/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Dominância Cerebral/fisiologia , Substância Cinzenta/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Rede Nervosa/diagnóstico por imagem , Medição de Risco , Estatística como Assunto , Ideação Suicida , Tentativa de Suicídio/prevenção & controle , Substância Branca/diagnóstico por imagem , Adulto Jovem
4.
J Child Adolesc Psychopharmacol ; 26(4): 327-34, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27027204

RESUMO

BACKGROUND: Current pharmacological treatments for Tourette Syndrome (TS), such as antipsychotic agents and α-2 agonists, are moderately effective in the treatment of tics, but have substantial side effects that limit their use. N-acetylcysteine (NAC) modulates glutamatergic systems, and has been used safely as an antioxidant agent with minimal side effects for decades. NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders. We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind, placebo-controlled, add-on study. METHODS: Thirty-one children and adolescents 8-17 years of age with TS were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale (YGTSS), Total tic score. Secondary measures assessed comorbid obsessive-compulsive disorder (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD). Linear mixed models in SAS were used to examine differences between NAC and placebo. RESULTS: Of 31 randomized subjects, 14 were assigned to placebo (two females; 11.5 + 2.8 years) and 17 to active NAC (five females; 12.4 + 1.4 years) treatment. No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes. CONCLUSIONS: We found no evidence for efficacy of NAC in treating tic symptoms. Our findings stand in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults, including OCD and trichotillomania, but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC.


Assuntos
Acetilcisteína/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Tiques/tratamento farmacológico , Síndrome de Tourette/tratamento farmacológico , Adolescente , Ansiedade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Criança , Depressão/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Modelos Lineares , Masculino , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Índice de Gravidade de Doença , Tiques/etiologia , Síndrome de Tourette/fisiopatologia , Resultado do Tratamento
5.
Brain Stimul ; 8(3): 574-81, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25912296

RESUMO

BACKGROUND: A small proportion of individuals with Tourette syndrome (TS) have a lifelong course of illness that fails to respond to conventional treatments. Open label studies have suggested that low frequency (1-Hz) repetitive transcranial magnetic stimulation (rTMS) targeting the supplementary motor area (SMA) may be effective in reducing tic severity. OBJECTIVE/HYPOTHESIS: To examine the efficacy of rTMS over the SMA for TS in a randomized double-blind sham-controlled trial (RCT). METHODS: We conducted a two-site RCT-rTMS with 20 adults with severe TS for 3 weeks. Treatment consisted of 15 sessions (1-Hz; 30 min; 1800 pulses per day) of active or sham rTMS at 110% of the motor threshold over the SMA. A subsequent 3 week course of active rTMS treatment was offered. RESULTS: Of the 20 patients (16 males; mean age of 33.7 ± 12.2 years), 9 received active and 11 received sham rTMS. After 3 weeks, patients receiving active rTMS showed on average a 17.3% reduction in the YGTSS total tic score compared to a 13.2% reduction in those receiving sham rTMS, resulting in no statistically significant reduction in tic severity (P = 0.27). An additional 3 week open label active treatment for those patients (n = 7) initially randomized to active rTMS resulted in a significant overall 29.7% reduction in tic severity compared to baseline (P = 0.04). CONCLUSION: This RCT did not demonstrate efficacy of 3-week SMA-targeted low frequency rTMS in the treatment of severe adult TS. Further studies using longer or alternative stimulation protocols are warranted.


Assuntos
Córtex Motor/fisiopatologia , Síndrome de Tourette/terapia , Estimulação Magnética Transcraniana/métodos , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Tourette/fisiopatologia , Resultado do Tratamento , Adulto Jovem
6.
Artigo em Inglês | MEDLINE | ID: mdl-24255802

RESUMO

BACKGROUND: Deep brain stimulation (DBS) remains an experimental but promising treatment for patients with severe refractory Gilles de la Tourette syndrome (TS). Controversial issues include the selection of patients (age and clinical presentation), the choice of brain targets to obtain optimal patient-specific outcomes, and the risk of surgery- and stimulation-related serious adverse events. METHODS: This report describes our open-label experience with eight patients with severe refractory malignant TS treated with DBS. The electrodes were placed in the midline thalamic nuclei or globus pallidus, pars internus, or both. Tics were clinically assessed in all patients pre- and postoperatively using the Modified Rush Video Protocol and the Yale Global Tic Severity Scale (YGTSS). RESULTS: Although three patients had marked postoperative improvement in their tics (>50% improvement on the YGTSS), the majority did not reach this level of clinical improvement. Two patients had to have their DBS leads removed (one because of postoperative infection and another because of lack of benefit). DISCUSSION: Our clinical experience supports the urgent need for more data and refinements in interventions and outcome measurements for severe, malignant, and medication-refractory TS. Because TS is not an etiologically homogenous clinical entity, the inclusion criteria for DBS patients and the choice of brain targets will require more refinement.

7.
Depress Anxiety ; 30(8): 716-22, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23532944

RESUMO

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.


Assuntos
Progressão da Doença , Transtorno Obsessivo-Compulsivo/psicologia , Adulto , Antipsicóticos/uso terapêutico , Terapia Cognitivo-Comportamental , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/terapia , Inibidores de Captação de Serotonina/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Pediatrics ; 131(1): e262-72, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23248232

RESUMO

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.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Insaturados/administração & dosagem , Fórmulas Infantis/administração & dosagem , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologia , Acil Coenzima A/administração & dosagem , Acil Coenzima A/química , Ácidos Graxos Insaturados/química , Humanos , Recém-Nascido , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
9.
Biol Psychiatry ; 72(11): 964-70, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22784486

RESUMO

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.


Assuntos
Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Adolescente , Adulto , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
10.
Pediatrics ; 129(6): 1141-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22641753

RESUMO

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Cognição/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Graxos Insaturados/administração & dosagem , Fórmulas Infantis/administração & dosagem , Cognição/fisiologia , Humanos , Lactente , Comportamento do Lactente/efeitos dos fármacos , Comportamento do Lactente/fisiologia , Comportamento do Lactente/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
11.
Front Psychiatry ; 3: 20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22419912

RESUMO

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.

12.
J Child Psychol Psychiatry ; 52(9): 974-83, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21244423

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Transtorno Obsessivo-Compulsivo/psicologia , Desempenho Psicomotor , Adolescente , Fatores Etários , Criança , Feminino , Humanos , Entrevista Psicológica , Masculino , Testes Neuropsicológicos , Transtorno Obsessivo-Compulsivo/diagnóstico , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Escalas de Graduação Psiquiátrica , Escalas de Wechsler
13.
J Atten Disord ; 15(7): 593-603, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20616372

RESUMO

OBJECTIVE: Exposure to heavy maternal cigarette smoking in pregnancy and severe maternal psychosocial stress during pregnancy appear to be important risk factors for the development of ADHD. This study aimed to determine whether these perinatal risk factors were associated with neuropsychological deficits commonly seen in ADHD. METHOD: We examined the effect of these two risk factors on measures of attentional control, motor inhibition, visual-motor integration, and fine motor coordination in a group of 81 children with ADHD, aged from 8 to 18 years. The neuropsychological battery included the Connors' Continuous Performance Test (CPT), the Stroop Color-Word Interference Test, the Beery Visual-Motor Integration Test, and the Purdue Pegboard Test. RESULTS: Heavy maternal smoking during pregnancy was associated with slower reaction times (p < .002), and reaction time variability (p < .007) on the CPT. CONCLUSIONS: This study suggests a persistent negative effect of heavy prenatal maternal smoking on attentional control in children with ADHD. Future studies should examine the neurobiological basis and determine the degree to which inherited genetic susceptibility factors contribute to this finding.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Atenção , Efeitos Tardios da Exposição Pré-Natal/psicologia , Fumar/efeitos adversos , Adolescente , Criança , Feminino , Humanos , Masculino , Mães , Testes Neuropsicológicos , Gravidez , Tempo de Reação , Fatores de Risco
14.
Soc Psychiatry Psychiatr Epidemiol ; 46(4): 291-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20191262

RESUMO

OBJECTIVES: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Transtorno Obsessivo-Compulsivo/psicologia , Adolescente , Adulto , Criança , Feminino , Previsões , Humanos , Estudos Longitudinais , Masculino , Qualidade de Vida , Índice de Gravidade de Doença , Perfil de Impacto da Doença , Tempo , Adulto Jovem
15.
J Am Acad Child Adolesc Psychiatry ; 49(11): 1155-64, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20970703

RESUMO

OBJECTIVE: Neuropsychological functioning in children with Tourette syndrome (TS) has been characterized by subtle deficits in response inhibition, visual-motor integration, and fine-motor coordination. The association of these deficits with the tics of the TS versus co-occurring attention-deficit/hyperactivity disorder (ADHD) has not been well understood because of small sample sizes and lack of adequate control conditions. We examined neuropsychological functioning in relatively large and well-characterized samples of children categorized as TS, TS-plus-ADHD, ADHD, and unaffected controls. METHOD: A total of 56 children with TS-only, 45 with TS-plus-ADHD, 64 with ADHD, and 71 healthy community control subjects were assessed on a battery of neuropsychological measures including the Connors' Continuous Performance Test (CPT), the Stroop Color-Word Interference Test (Stroop), the Beery Visual-Motor Integration Test (VMI), and the Purdue Pegboard Test. RESULTS: There were no differences between children with TS-only and unaffected controls on the measures of response inhibition and visual-motor integration. Boys with TS-only but not girls with TS-only were impaired in the dominant hand Purdue performance. Children with ADHD were impaired on all study measures. Children with TS-plus-ADHD revealed no deficits on the Stroop, VMI, and Purdue tests but were impaired on the sustained attention portion of the CPT. CONCLUSIONS: These results indicate that co-occurring ADHD may be responsible for the neuropsychological deficits, or at least those assessed in the present study, in children with TS. Explanations in terms of neurobiological mechanisms of co-occurring TS and ADHD, as well as possible compensatory mechanisms in children with TS, are discussed.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Testes Neuropsicológicos , Síndrome de Tourette , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Feminino , Humanos , Masculino , Agitação Psicomotora , Desempenho Psicomotor , Inibição Reativa , Índice de Gravidade de Doença , Síndrome de Tourette/complicações , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/fisiopatologia , Síndrome de Tourette/psicologia
16.
J Affect Disord ; 121(1-2): 175-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19577308

RESUMO

BACKGROUND: Obsessive-compulsive disorder (OCD) is clinically heterogeneous. Previous studies have reported different patterns of treatment response to serotonin reuptake inhibitors (SRI) based on symptom dimension. Our objective was to replicate these results in OCD patients who participated in one of four randomized, placebo-controlled, clinical trials (RCT). METHODS: A total of 165 adult OCD subjects participated in one or more eight-week RCT with clomipramine, fluvoxamine, or fluoxetine. All subjects were classified as having major or minor symptoms in four specific OC symptom dimensions that were derived in a previous factor analytic study involving many of these same patients. Ordinal logistic regression was used to test the association between OC symptom dimensions and SRI response. RESULTS: We found a significant association between the symptom dimension involving sexual, religious and harm-related obsessions as well as checking compulsions (AGG/SR) and improved SRI response. This increased rate of SRI response was experienced primarily by individuals with harm-related obsessions. Over 60% of patients with AGG/SR OCD symptoms were rated as very much improved after SRI treatment. LIMITATIONS: As some of the RCTs included were conducted prior to the development of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), improvement in OCD severity was assessed using the Clinical Global Improvement (CGI) Scale. Data from the double-blind and open-label continuation phases of these trials was collapsed together to increase statistical power. CONCLUSIONS: Patients with OCD vary in their response to SRIs. The presence of AGG/SR symptoms is associated with an initial positive response to SRIs. These data add to the growing body of work linking central serotonin systems with aggressive behavior.


Assuntos
Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Clomipramina/efeitos adversos , Clomipramina/uso terapêutico , Connecticut , Feminino , Fluoxetina/efeitos adversos , Fluoxetina/uso terapêutico , Fluvoxamina/efeitos adversos , Fluvoxamina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Inventário de Personalidade/estatística & dados numéricos , Prognóstico , Psicometria , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Inibidores de Captação de Serotonina/efeitos adversos , Resultado do Tratamento
17.
Biol Psychiatry ; 67(7): 684-91, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19833320

RESUMO

BACKGROUND: One goal of this prospective longitudinal study was to identify new group A beta-hemolytic streptococcal infections (GABHS) in children and adolescents with Tourette syndrome (TS) and/or obsessive-compulsive disorder (OCD) compared with healthy control subjects. We then examined the power of GABHS infections and measures of psychosocial stress to predict future tic, obsessive-compulsive (OC), and depressive symptom severity. METHODS: Consecutive ratings of tic, OC, and depressive symptom severity were obtained for 45 cases and 41 matched control subjects over a 2-year period. Clinical raters were blinded to the results of laboratory tests. Laboratory personnel were blinded to case or control status and clinical ratings. Structural equation modeling for unbalanced repeated measures was used to assess the sequence of new GABHS infections and psychosocial stress and their impact on future symptom severity. RESULTS: Increases in tic and OC symptom severity did not occur after every new GABHS infection. However, the structural equation model found that these newly diagnosed infections were predictive of modest increases in future tic and OC symptom severity but did not predict future depressive symptom severity. In addition, the inclusion of new infections in the model greatly enhanced, by a factor of three, the power of psychosocial stress in predicting future tic and OC symptom severity. CONCLUSIONS: Our data suggest that a minority of children with TS and early-onset OCD were sensitive to antecedent GABHS infections. These infections also enhanced the predictive power of current psychosocial stress on future tic and OC symptom severity.


Assuntos
Acontecimentos que Mudam a Vida , Transtorno Obsessivo-Compulsivo/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/epidemiologia , Tiques/epidemiologia , Adolescente , Antibacterianos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Feminino , Previsões , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Valor Preditivo dos Testes , Estudos Prospectivos , Psicologia , Infecções Respiratórias/tratamento farmacológico , Índice de Gravidade de Doença , Infecções Estreptocócicas/tratamento farmacológico , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/epidemiologia
18.
Autism Res ; 2(6): 293-311, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20029829

RESUMO

Autism spectrum disorders (ASDs) are a phenotypically and etiologically heterogeneous set of disorders that include obsessive-compulsive behaviors (OCB) that partially overlap with symptoms associated with obsessive-compulsive disorder (OCD). The OCB seen in ASD vary depending on the individual's mental and chronological age as well as the etiology of their ASD. Although progress has been made in the measurement of the OCB associated with ASD, more work is needed including the potential identification of heritable endophenotypes. Likewise, important progress toward the understanding of genetic influences in ASD has been made by greater refinement of relevant phenotypes using a broad range of study designs, including twin and family-genetic studies, parametric and nonparametric linkage analyses, as well as candidate gene studies and the study of rare genetic variants. These genetic analyses could lead to the refinement of the OCB phenotypes as larger samples are studied and specific associations are replicated. Like ASD, OCB are likely to prove to be multidimensional and polygenic. Some of the vulnerability genes may prove to be generalist genes influencing the phenotypic expression of both ASD and OCD while others will be specific to subcomponents of the ASD phenotype. In order to discover molecular and genetic mechanisms, collaborative approaches need to generate shared samples, resources, novel genomic technologies, as well as more refined phenotypes and innovative statistical approaches. There is a growing need to identify the range of molecular pathways involved in OCB related to ASD in order to develop novel treatment interventions.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Doenças em Gêmeos/genética , Genótipo , Transtorno Obsessivo-Compulsivo/genética , Fenótipo , Animais , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/psicologia , Pré-Escolar , Comorbidade , Diagnóstico Diferencial , Modelos Animais de Doenças , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/psicologia , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Deficiência Intelectual/psicologia , Entrevista Psicológica , Testes Neuropsicológicos , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Característica Quantitativa Herdável , Comportamento Estereotipado
19.
Pediatrics ; 124(4): 1085-93, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19786445

RESUMO

OBJECTIVE: The aim of this study was to determine the childhood clinical predictors of early adult outcomes in pediatric-onset obsessive-compulsive disorder (OCD) and to assess whether dimensional subtypes of OCD and the presence of comorbid tic symptoms influence long-term outcomes. METHODS: We conducted a longitudinal cohort study in which 45 of 62 eligible children with OCD were reassessed an average of 9 years later, in early adulthood. Main outcome measures included expert-rated, obsessive-compulsive (OC) symptom severity and time to remission of OC symptoms. Baseline clinical characteristics were evaluated in terms of their influence on OCD severity in adulthood and time to remission of OC symptoms. RESULTS: Forty-four percent of subjects were determined to have subclinical OC symptoms at the follow-up evaluation. The absence of a comorbid tic disorder and the presence of prominent hoarding symptoms were associated with the persistence of OCD symptoms. Female gender, earlier age at childhood assessment, later age of OCD onset, more-severe childhood OCD symptoms, and comorbid oppositional defiant disorder also were associated with persistence of OCD symptoms into adulthood. CONCLUSIONS: These results confirm that a significant proportion of treated children with OCD experience remission by adulthood. The presence of comorbid tics heralds a positive outcome, whereas primary hoarding symptoms are associated with persistent OCD.


Assuntos
Progressão da Doença , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtornos de Tique/diagnóstico , Transtornos de Tique/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Masculino , Monitorização Fisiológica , Análise Multivariada , Transtorno Obsessivo-Compulsivo/terapia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Transtornos de Tique/terapia , Fatores de Tempo , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/epidemiologia , Síndrome de Tourette/terapia , Adulto Jovem
20.
J Am Acad Child Adolesc Psychiatry ; 48(9): 884-893, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19625978

RESUMO

OBJECTIVE: The Food and Drug Administration currently requires the package inserts of most psychostimulant medications to list the presence of a tic disorder as a contraindication to their use. Approximately half of children with Tourette's syndrome experience comorbid attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of different medications in treating ADHD and tic symptoms in children with both Tourette's syndrome and ADHD. METHOD: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of medications in the treatment of ADHD in the children with comorbid tics. We used a random effects meta-analysis with standardized mean difference as our primary outcome to estimate the effect size of pharmaceutical agents in the treatment of ADHD symptoms and tics. RESULTS: Our meta-analysis included nine studies involving 477 subjects. We assessed the efficacy of six medications-dextroamphetamine, methylphenidate, alpha-2 agonists (clonidine and guanfacine), desipramine, atomoxetine, and deprenyl. Methylphenidate, alpha-2 agonists, desipramine, and atomoxetine demonstrated efficacy in improving ADHD symptoms in children with comorbid tics. Alpha-2 agonists and atomoxetine significantly improved comorbid tic symptoms. Although there was evidence that supratherapeutic doses of dextroamphetamine worsens tics, there was no evidence that methylphenidate worsened tic severity in the short term. CONCLUSIONS: Methylphenidate seems to offer the greatest and most immediate improvement of ADHD symptoms and does not seem to worsen tic symptoms. Alpha-2 agonists offer the best combined improvement in both tic and ADHD symptoms. Atomoxetine and desipramine offer additional evidence-based treatments of ADHD in children with comorbid tics. Supratherapeutic doses of dextroamphetamine should be avoided.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Psicotrópicos/uso terapêutico , Transtornos de Tique/epidemiologia , Síndrome de Tourette/epidemiologia , Agonistas alfa-Adrenérgicos/efeitos adversos , Agonistas alfa-Adrenérgicos/uso terapêutico , Cloridrato de Atomoxetina , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Comorbidade , Contraindicações , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Metilfenidato/efeitos adversos , Metilfenidato/uso terapêutico , Propilaminas/efeitos adversos , Propilaminas/uso terapêutico , Psicotrópicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos de Tique/diagnóstico , Transtornos de Tique/psicologia , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/psicologia
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