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1.
Artigo em Inglês | MEDLINE | ID: mdl-25637377

RESUMO

BACKGROUND: This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder (DSM-IV). METHODS: Twenty individuals were enrolled in a 17-week, open-label trial of duloxetine at Massachusetts General Hospital. Data were collected between March 2007 and September 2012. Study measures assessing obsessive-compulsive disorder symptoms, quality of life, depression, and anxiety were administered at baseline and weeks 1, 5, 9, 13, and 17. The primary outcome measures were the Yale-Brown Obsessive Compulsive Scale and Clinical Global Improvement scale. RESULTS: For the 12 study completers, pre- and posttreatment analyses revealed significant improvements (P<.05) on clinician- and self-rated measures of obsessive-compulsive disorder symptoms and quality of life. Among the 12 completers, more than one-half (n=7) satisfied full medication response criteria. Intention-to-treat analyses (n=20) showed similar improvements (P<.05) on primary and secondary study outcome measures. CONCLUSION: The results of this study suggest that duloxetine may provide a significant reduction in symptoms for patients with obsessive-compulsive disorder. ClinicalTrials.gov NCT00464698; http://clinicaltrials.gov/ct2/show/NCT00464698?term=NCT00464698&rank=1.


Assuntos
Inibidores da Captação de Neurotransmissores/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Psicotrópicos/uso terapêutico , Tiofenos/uso terapêutico , Adolescente , Adulto , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Cloridrato de Duloxetina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Captação de Neurotransmissores/efeitos adversos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/psicologia , Escalas de Graduação Psiquiátrica , Psicotrópicos/efeitos adversos , Qualidade de Vida , Tiofenos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
2.
Depress Anxiety ; 28(4): 310-3, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21456040

RESUMO

BACKGROUND: Maintenance of gains with cognitive-behavioral treatment for trichotillomania (TTM) has historically been problematic. METHODS: We conducted follow-up assessments 3 and 6 months after completion of a 3-month maintenance phase on 10 individuals with DSM-IV-TR TTM who participated in an open trial of a dialectical behavior therapy (DBT)-enhanced habit reversal treatment (HRT). RESULTS: Significant improvement from baseline was reported at 3-and 6-month follow-up on all measures of hair pulling severity and emotion regulation, although some worsening was reported on some measures from earlier study time points. At 6-month follow-up, five and four participants were full and partial responders, respectively. Significant correlations were reported at both follow-up time points between changes in hair pulling severity and emotion regulation capacity. CONCLUSIONS: DBT-enhanced HRT offers promise for improved long-term treatment results in TTM. Changes in TTM severity from baseline to 3-and 6-month follow-up is correlated with changes in emotion regulation capacity.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Hábitos , Meditação , Tricotilomania/terapia , Adaptação Psicológica , Adulto , Terapia Combinada , Comorbidade , Emoções , Feminino , Seguimentos , Humanos , Projetos Piloto , Tricotilomania/psicologia
3.
Compr Psychiatry ; 52(3): 334-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21145539

RESUMO

OBJECTIVE: Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous, and findings of underlying structure classification based on symptom grouping have been ambiguous to date. Variable-centered approaches, primarily factor analysis, have been used to identify homogeneous groups of symptoms; but person-centered latent methods have seen little use. This study was designed to uncover sets of homogeneous groupings within 1611 individuals with OCD based on symptoms. METHOD: Latent class analysis models using 61 obsessive-compulsive symptoms collected from the Yale-Brown Obsessive-Compulsive Scale were fit. Relationships between latent class membership and treatment response, sex, symptom severity, and comorbid tic disorders were tested for relationship to class membership. RESULTS: Latent class analysis models of best fit yielded 3 classes. Classes differed only in frequency of symptom endorsement. Classes with higher symptom endorsement were associated with earlier age of onset, being male, higher Yale-Brown Obsessive-Compulsive Scale symptom severity scores, and comorbid tic disorders. There were no differences in treatment response between classes. CONCLUSIONS: These results provide support for the validity of a single underlying latent OCD construct, in addition to the distinct symptom factors identified previously via factor analyses.


Assuntos
Transtorno Obsessivo-Compulsivo/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/psicologia , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Transtornos de Tique/complicações , Transtornos de Tique/diagnóstico , Transtornos de Tique/psicologia
4.
J Clin Psychol ; 67(6): 624-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21404272

RESUMO

Previous findings suggested a unique role that depression symptoms might play in the comorbid relationship between obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). However, the nature of this role remains unclear. Thus, the current study examined ways in which OCD and PTSD symptoms vary as a function of depression, as well as the mediating role of depression in the OCD-PTSD relationship, in 104 individuals seeking treatment for refractory OCD. Findings revealed that depressed individuals in the treatment-refractory OCD sample report higher levels of overall obsessing and greater severity of PTSD. In addition, depression appeared to mediate the relation between OCD and PTSD. Implications of findings are discussed.


Assuntos
Depressão/complicações , Transtorno Obsessivo-Compulsivo/complicações , Transtornos de Estresse Pós-Traumáticos/complicações , Depressão/fisiopatologia , Humanos , Entrevistas como Assunto , Massachusetts , Auditoria Médica , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/terapia , Estudos Retrospectivos , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
5.
J Clin Psychopharmacol ; 30(1): 34-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20075645

RESUMO

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common debilitating psychiatric illness that typically improves but does not remit with first-line medication and behavioral treatments. Serotonergic agents including selective serotonin reuptake inhibitors and clomipramine have provided the mainstay of OCD medication management for decades. Combined dopamine/serotonergic agents such as atypical antipsychotics are presently the only OCD-augmenting strategies proven effective via randomized controlled trials. Despite increasing evidence for a pathogenic role of glutamate in OCD, no controlled trials of glutamatergic augmenting agents have been reported. METHODS: An intent-to-treat sample included 44 subjects receiving standard treatment at the McLean/Massachusetts General Hospital Intensive Residential Treatment (IRT) program, 22 of whom also received memantine augmentation. Admission, monthly and discharge measures of OCD, depression, and psychosocial functioning were collected by raters blinded to augmentation status. Matched controls were selected based on sex, initial OCD severity, psychosocial functioning, and timing of admission. The Clinical Global Improvement Scale captured global clinical change. RESULTS: Mean (SD) Yale-Brown Obsessive Compulsive Scale score decreases were 7.2 (6.4) among the cases and 4.6 (5.9) among the matched controls, reflecting mean clinical improvement among the cases (27.0% decrease) but not the controls (16.5% decrease). Mean (SD) depression severity score decreases were 5.8 (9.5) among the cases and 4.7 (9.9) among the controls. Initial intrusive obsessions were significantly more severe among marked responders compared with limited response or nonresponse cases (4.4 vs 2.9; t = 2.15; P = 0.048). CONCLUSIONS: This study provides preliminary supportive evidence for the effectiveness of memantine as a glutamatergic augmenting agent in severe OCD. Future randomized double-blind placebo-controlled trials are warranted.


Assuntos
Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Memantina/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adulto , Antipsicóticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Estudos de Casos e Controles , Esquema de Medicação , Quimioterapia Combinada , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Humanos , Pacientes Internados , Masculino , Memantina/administração & dosagem , Transtorno Obsessivo-Compulsivo/diagnóstico , Instituições Residenciais , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Método Simples-Cego , Resultado do Tratamento
6.
Behav Genet ; 40(4): 505-17, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20361247

RESUMO

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.


Assuntos
Análise Fatorial , Família , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/genética , Algoritmos , Estudos de Coortes , Interpretação Estatística de Dados , Família/psicologia , Feminino , Genótipo , Humanos , Masculino , Modelos Psicológicos , Transtorno Obsessivo-Compulsivo/psicologia , Fenótipo , Análise de Componente Principal , Psicometria
7.
Depress Anxiety ; 27(10): 953-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20721929

RESUMO

BACKGROUND: Not all hair pullers improve acutely with cognitive-behavioral treatment (CBT) and few maintain their gains over time. METHODS: We conducted an open clinical trial of a new treatment that addresses affectively triggered pulling and emphasizes relapse prevention in addition to standard CBT approaches. Ten female participants satisfying DSM-IV criteria for trichotillomania (TTM) at two study sites received Dialectical Behavior Therapy (DBT)-enhanced CBT consisting of 11 weekly sessions and 4 maintenance sessions over the following 3 months. Independent assessors rated hair pulling impairment and global improvement at several study time points. Participants completed self-report measures of hair pulling severity and emotion regulation. RESULTS: Significant improvement in hair pulling severity and emotion regulation, as well as hair pulling impairment and anxiety and depressive symptoms, occurred during acute treatment and were maintained during the subsequent 3 months. Significant correlations were reported between changes in emotion regulation and hair pulling severity during both the acute treatment and maintenance phases. CONCLUSIONS: This study offers preliminary evidence for the efficacy of DBT-enhanced CBT for TTM and suggests the importance of addressing emotion regulation during TTM treatment.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Emoções , Hábitos , Tricotilomania/terapia , Adulto , Feminino , Humanos , Projetos Piloto , Escalas de Graduação Psiquiátrica , Psicotrópicos/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento , Tricotilomania/diagnóstico , Tricotilomania/psicologia
8.
Depress Anxiety ; 27(7): 643-51, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20602430

RESUMO

BACKGROUND: Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison (HC) subjects. However, the profile of amygdala activation in response to facial expressions in obsessive-compulsive disorder (OCD) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation [Cannistraro et al. (2004). Biological Psychiatry 56:916-920]. METHODS: In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N=12) and a HC sample (N=17) performed a gender discrimination task while viewing emotional faces (happy, fearful, disgusted) and neutral faces. RESULTS: Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. CONCLUSIONS: Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder specific.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Expressão Facial , Transtorno Obsessivo-Compulsivo/fisiopatologia , Criança , Feminino , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Fatores Sexuais
9.
Am J Psychiatry ; 165(3): 335-41; quiz 409, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18245177

RESUMO

OBJECTIVE: This study examined whether d-cycloserine, a partial agonist at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, enhances the efficacy of behavior therapy for obsessive-compulsive disorder (OCD). METHOD: A randomized, double-blind, placebo-controlled trial investigating D-cycloserine versus placebo augmentation of behavior therapy was conducted in 23 OCD patients. Patients first underwent a diagnostic interview and pretreatment evaluation, followed by a psychoeducational/treatment planning session. Then they received 10 behavior therapy sessions. Treatment sessions were conducted twice per week. One hour before each of the behavior therapy sessions, the participants received either D-cycloserine, 100 mg, or a placebo. RESULTS: Relative to the placebo group, the D-cycloserine group's OCD symptoms were significantly more improved at mid-treatment, and the D-cycloserine group's depressive symptoms were significantly more improved at posttreatment. CONCLUSIONS: These data provide support for the use of D-cycloserine as an augmentation of behavior therapy for OCD and extend findings in animals and other human disorders suggesting that behavior therapy acts by way of long-term potentiation of glutamatergic pathways and that the effects of behavior therapy are potentiated by an NMDA agonist.


Assuntos
Terapia Comportamental/métodos , Ciclosserina/uso terapêutico , Transtorno Obsessivo-Compulsivo/terapia , Adulto , Animais , Terapia Combinada , Ciclosserina/farmacologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Terapia Implosiva/métodos , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Placebos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Ratos , Receptores de N-Metil-D-Aspartato/agonistas , Prevenção Secundária , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Arch Gen Psychiatry ; 64(2): 209-14, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17283288

RESUMO

CONTEXT: Obsessive-compulsive disorder (OCD) is a debilitating familial psychiatric illness with associated brain abnormalities in the white matter. The gene for oligodendrocyte lineage transcription factor 2 (OLIG2) is an essential regulator in the development of cells that produce white matter (myelin). The OLIG2 gene is also highly expressed in brain regions implicated in OCD. OBJECTIVES: To examine OLIG2 as a candidate gene for OCD susceptibility and to explore whether comorbidity subtypes of OCD have distinct associations with OLIG2 and the functionally related OLIG1 gene. It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone. DESIGN: Family-based association candidate gene study. SETTING: Participants and their family members were recruited from tertiary care OCD and TD specialty clinics. PARTICIPANTS: Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD. MAIN OUTCOME MEASURES: Genotypes of single nucleotide polymorphism markers and related haplotypes. RESULTS: The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; P<.001), rs1059004 (minor allele frequency, 44%; P = .005), and rs9653711 (minor allele frequency, 44%; P = .004). A 5-marker haplotype (A/C/T/T/G) constituting these single nucleotide polymorphisms and exonic single nucleotide polymorphisms rs6517137 and rs13046814 was undertransmitted (frequency, 32%; permuted P=.004), whereas the G/A/T/T/C haplotype (frequency, 22%; permuted P=.02) was overtransmitted to probands with OCD alone, with a significant global P value (permuted P=.008). CONCLUSIONS: This is the first study reporting an association between OLIG2 and OCD, specifically when TD comorbidity is absent. The findings support a role for white matter abnormalities in the etiology of the disorder.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Família , Proteínas do Tecido Nervoso/genética , Transtorno Obsessivo-Compulsivo/genética , Mapeamento Cromossômico , Comorbidade , Frequência do Gene , Marcadores Genéticos , Predisposição Genética para Doença , Haplótipos/genética , Humanos , Desequilíbrio de Ligação , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Fator de Transcrição 2 de Oligodendrócitos , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Síndrome de Tourette/epidemiologia , Síndrome de Tourette/genética
11.
Biol Psychiatry ; 84(5): 355-364, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29361268

RESUMO

BACKGROUND: Despite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD. METHODS: Fifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging. RESULTS: Thirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state. CONCLUSIONS: Gamma Knife ventral capsulotomy is an effective radiosurgical procedure for many treatment-refractory OCD patients. A minority of patients developed cysts at long-term follow-up, 1 of whom had permanent neurological sequelae.


Assuntos
Cápsula Interna/patologia , Transtorno Obsessivo-Compulsivo/terapia , Radiocirurgia/métodos , Adulto , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/cirurgia , Escalas de Graduação Psiquiátrica , Psicocirurgia/métodos , Lesões por Radiação , Radiocirurgia/efeitos adversos , Resultado do Tratamento
12.
Am J Med Genet B Neuropsychiatr Genet ; 144B(8): 1027-33, 2007 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-17894418

RESUMO

CONTEXT: Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required. OBJECTIVES: This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females. DESIGN: Family-based association candidate gene study. SETTING: Participants were recruited from tertiary care OCD specialty clinics. PARTICIPANTS: OCD probands and their first degree relatives. MAIN OUTCOMES MEASURES: Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes. RESULTS: Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045). CONCLUSIONS: This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported.


Assuntos
Transportador 3 de Aminoácido Excitatório/genética , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Distribuição por Idade , Idade de Início , Criança , Mapeamento Cromossômico , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Distribuição por Sexo
13.
Nat Commun ; 8(1): 774, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-29042551

RESUMO

Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 × 10-11) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with symptoms including intrusive thoughts and time-consuming repetitive behaviors. Here Noh and colleagues identify genes enriched for functional variants associated with increased risk of OCD.


Assuntos
Transtorno Obsessivo-Compulsivo/genética , Proteínas/genética , Proteínas de Ligação ao Cálcio , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Estudos de Coortes , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Moléculas de Adesão de Célula Nervosa , Transtorno Obsessivo-Compulsivo/metabolismo , Polimorfismo de Nucleotídeo Único , Proteínas/metabolismo , Transdução de Sinais , Sinapses/genética , Sinapses/metabolismo
14.
J Clin Psychiatry ; 67(7): 1086-92, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16889452

RESUMO

BACKGROUND: Trichotillomania is a psychiatric condition characterized by chronic hair pulling. Both cognitive behavioral therapy (CBT) and the selective serotonin reuptake inhibitors (SSRIs) have shown promise in the treatment of trichotillomania, with comparison studies favoring CBT over pharmacotherapy. However, no randomized, controlled studies to date have compared the efficacy of individual SSRI or CBT treatment to the combination of both treatment modalities. METHOD: In this study, which ran from February 2000 through April 2003, subjects who met DSM-IV criteria for trichotillomania were randomly assigned to treatment with sertraline or placebo in a double-blind study design. Following 12 weeks of active pharmacotherapy, subjects not demonstrating significant trichotillomania symptom improvement had habit reversal training (HRT) added to their treatment regimen. Primary outcome measures were the Hair Pulling Scale and the Clinical Global Impressions scale. RESULTS: Thirteen subjects completing the 22-week study received single modality treatment of either sertraline or HRT, and 11 received both modalities of treatment. Trichotillomania symptoms in both groups improved, although the dual modality treatment group demonstrated larger gains and were much more likely to reach responder status at final evaluation. CONCLUSION: These results suggest that the combination of sertraline and HRT may be more efficacious in the treatment of trichotillomania than either approach alone.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Tricotilomania/terapia , Adulto , Terapia Combinada , Manual Diagnóstico e Estatístico de Transtornos Mentais , Método Duplo-Cego , Feminino , Humanos , Estudos Longitudinais , Masculino , Placebos , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Tricotilomania/diagnóstico , Tricotilomania/tratamento farmacológico
15.
J Psychiatr Res ; 40(6): 511-9, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16229857

RESUMO

Intensive residential treatment (IRT) is an effective management approach for those with severe obsessive-compulsive disorder (OCD). This study aimed to identify IRT response predictors for clinical and research use. Consecutive subjects admitted to the Massachusetts General Hospital/McLean OCD Institute (OCDI) between February 1997 and June 2003 were included (N=476). IRT responder and non-responder group characteristics were compared using t-tests and chi(2) analyses. Multiple regression analysis modeled relationships between final OCD severity (Yale-Brown Obsessive-Compulsive scale scores) and predictor variables, while accounting for multicollinearity and potential outliers. Treatment responders comprised 59.3% of the treatment sample. Responders had significantly fewer males (p=0.02), lower depression severity (p=0.03), poorer psychosocial functioning (p=0.03) and fewer tic disorders (0.04), but were not different with respect to admission length, age, marital or employment status, OCD onset, family OCD history, treatment or admission history. In the final regression model, decreased initial OCD severity (p<0.001), female gender (p=0.003) and better initial psychosocial functioning (Work and Social Adjustment scale scores) (p=0.003) were predictors of less severe OCD at discharge (adjusted R-square=0.28). Depression severity (Beck Depression Inventory scores) and insight were not predictive of treatment outcome. Future research is necessary to elucidate putative relationships between gender and OCD psychopathology, and to understand the interplay of psychosocial factors, OCD severity and treatment outcome.


Assuntos
Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/terapia , Tratamento Domiciliar/métodos , Resultado do Tratamento , Adolescente , Adulto , Idoso , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Psicometria , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais
16.
Biol Psychiatry Cogn Neurosci Neuroimaging ; 1(2): 116-124, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26949749

RESUMO

BACKGROUND: Several lines of evidence support the hypothesis that lower cerebral levels of glutathione (GSH), associated with increased oxidative stress, may contribute to obsessive-compulsive disorder (OCD). However, no studies to date have investigated brain GSH levels in individuals with OCD. METHODS: Twenty-nine individuals with OCD and 25 age-, sex-, and race-matched comparison individuals without OCD underwent single voxel 2D J-resolved proton magnetic resonance spectroscopy (MRS) to examine GSH levels in the posterior cingulate cortex (PCC). MRS data were analyzed using LCModel and a simulated basis set. Group metabolite differences referenced to total creatine (Cr), as well as relationships between metabolite ratios and symptom severity as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), were analyzed using linear regression with adjustment for age, sex, and race. RESULTS: One OCD participant failed to produce usable PCC MRS data. We found significantly lower PCC GSH/Cr in OCD participants compared with non-OCD participants (ß = -0.027 [95% CI: -0.049 to -5.9 × 10-3]; P = 0.014). PCC GSH/Cr was not significantly associated with total Y-BOCS score in the OCD group (ß = 5.7 × 10-4 [95% CI: -4.8 × 10-3 to 5.9 × 10-3]; P = 0.83). CONCLUSIONS: Lower PCC GSH/Cr may be indicative of increased oxidative stress secondary to hypermetabolism in this brain region in OCD. Future MRS studies are warranted to investigate GSH levels in other brain regions that comprise the cortico-striato-thalamo-cortical circuit thought to be abnormal in OCD.

17.
J Clin Psychiatry ; 66(7): 864-9, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16013902

RESUMO

OBJECTIVE: Chronic hair pulling and trichotillomania are putative obsessive-compulsive spectrum disorders. This study determined the prevalence of hair pulling in an inpatient obsessive-compulsive disorder (OCD) population and compared clinical characteristics and treatment response between subgroups with and without comorbid hair pulling. METHOD: Patients with severe DSM-IV-diagnosed OCD (N = 154) who were consecutively admitted to an OCD residential treatment facility between August 2000 and July 2003 were included. Clinician-rated (Yale-Brown Obsessive Compulsive Scale) and patient-rated (Massachusetts General Hospital Hairpulling Scale, Beck Depression Inventory, and Posttraumatic Diagnostic Scale) measures were administered at index evaluation. OCD patients with and without moderate to severe hair pulling were statistically compared on clinical and treatment characteristics and treatment response. RESULTS: Of the OCD subjects, 18.8% (N = 29) endorsed any hair pulling, 15.6% (N = 24) had moderate to severe hair pulling, and 7.8% (N = 12) had severe hair pulling comparable to that of a specialty trichotillomania clinic population. OCD patients with moderate to severe hair pulling were more likely to be women (p < .001), endorse > 1 comorbid tic (p < .05), and have earlier-onset OCD (p = .001). This cohort also had fewer contamination obsessions (p = .04) and checking compulsions (p = .04) and was more likely to be receiving stimulant (p = .006) or venlafaxine (p = .02) medication than those patients without hair pulling. Posttraumatic Diagnostic Scale scores were nearly significantly higher in the OCD + hair pulling group (p = .08). OCD treatment response was unaffected by the presence of comorbid hair pulling. CONCLUSION: Hair pulling is a highly common comorbidity in severe OCD. Women and early-onset OCD patients appear to be more vulnerable to comorbid hair pulling. OCD sufferers with comorbid hair pulling also exhibit an increased risk for tics and may present with different OCD symptomatology.


Assuntos
Transtorno Obsessivo-Compulsivo/epidemiologia , Tricotilomania/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Estudos de Coortes , Comorbidade , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inventário de Personalidade , Prevalência , Escalas de Graduação Psiquiátrica , Psicotrópicos/uso terapêutico , Tratamento Domiciliar , Índice de Gravidade de Doença , Fatores Sexuais , Transtornos de Tique/diagnóstico , Transtornos de Tique/epidemiologia , Resultado do Tratamento , Tricotilomania/diagnóstico , Tricotilomania/tratamento farmacológico
18.
J Psychiatr Res ; 39(6): 603-9, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16157162

RESUMO

OBJECTIVE: The aim of this study was to determine the effectiveness of an innovative Intensive Residential Treatment (IRT) program for severe refractory Obsessive-Compulsive Disorder (OCD). No formalized OCD IRT outcome studies have been completed to date in North America. METHOD: Subjects admitted to the Massachusetts General Hospital/McLean OCD Institute (OCDI) between February 1997 and June 2003 comprised the intent-to-treat sample. Measures of OCD severity, depression severity and psychosocial well-being were determined at admission, interim and discharge points, and were subsequently compared via t-tests using a last-observation-carried-forward approach. Initial OCD severity subgroups and treatment length subgroups were created and analyzed. Correlations and stepwise linear regressions were conducted to determine treatment length predictors. RESULTS: The sample of 403 individuals (58.7% male) had an average 66 day treatment length. Mean YBOCS scores decreased by 30.1%, from 26.6 (SD 6.1) at admission to 18.6 (SD 7.2) at discharge, reflecting a clinically meaningful improvement (p<0.001). Psychosocial functioning, depression severity scores and self-report global functioning ratings also indicated significant improvement. Subgroups with longer treatment lengths tended to have earlier ages of OCD onset and increased OCD severity scores at admission. CONCLUSION: IRT deserves recognition as a therapeutic approach for severe, refractory OCD. In the largest study to date for IRT significant improvements of OCD severity, depression severity and quality of life were determined. IRT should be considered prior to more invasive approaches for severe refractory OCD.


Assuntos
Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/terapia , Psicoterapia , Adulto , Feminino , Humanos , Pacientes Internados , Masculino , Recidiva , Instituições Residenciais , Índice de Gravidade de Doença , Resultado do Tratamento
19.
J Obsessive Compuls Relat Disord ; 4: 20-24, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25485229

RESUMO

OBJECTIVES: Disgust is a well-established phenomenon with known neurobiological correlates. However, it remains unclear how or whether disgust changes with clinical treatment, because few longitudinal studies have tracked the association of disgust vulnerability and clinical symptoms in patient populations. METHODS: We assessed disgust propensity and symptoms of obsessive-compulsive disorder (OCD) in 134 patients receiving intensive residential treatment for OCD. Using linear regression with adjustment for age, sex, and depression severity, we tested the association between change in disgust propensity and change in OCD symptoms from admission to discharge. RESULTS: Change in disgust propensity was significantly associated with improvement in contamination/washing symptoms (ß = 0.25 [95% confidence interval: 0.11-0.39]; P = .001). No significant association was found between change in disgust propensity and change in other OCD symptom dimensions. CONCLUSIONS: In patients with OCD undergoing intensive residential treatment, disgust propensity appears to improve in parallel with contamination/washing symptoms.

20.
Neuropsychopharmacology ; 40(8): 1866-76, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25662837

RESUMO

The anterior cingulate cortex is implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, few studies have examined functional and neurochemical abnormalities specifically in the rostral subdivision of the ACC (rACC) in OCD patients. We used functional magnetic resonance imaging (fMRI) during an emotional counting Stroop task and single-voxel J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) in the rACC to examine the function and neurochemistry of the rACC in individuals with OCD and comparison individuals without OCD. Between-group differences in rACC activation and glutamine/glutamate ratio (Gln/Glu), Glu, and Gln levels, as well as associations between rACC activation, Gln/Glu, Glu, Gln, behavioral, and clinical measures were examined using linear regression. In a sample of 30 participants with OCD and 29 age- and sex-matched participants without OCD, participants with OCD displayed significantly reduced rACC deactivation compared with those without OCD in response to OCD-specific words versus neutral words on the emotional counting Stroop task. However, Gln/Glu, Glu, and Gln in the rACC did not differ between groups nor was there an association between reduced rACC deactivation and Gln/Glu, Glu, or Gln in the OCD group. Taken together, these findings strengthen the evidence for rACC dysfunction in OCD, but weigh against an underlying association with abnormal rACC glutamatergic neurotransmission.


Assuntos
Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Transtorno Obsessivo-Compulsivo/patologia , Adolescente , Adulto , Feminino , Giro do Cíngulo/irrigação sanguínea , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Prótons , Escalas de Graduação Psiquiátrica , Adulto Jovem
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