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OBJECTIVE: We aim to investigate whether: 1) social skills (SS) are impaired in obsessive-compulsive disorder (OCD); 2) SS would change over the course of treatment; and 3) severity of OCD, age of onset of OCD symptoms and illness duration would be associated with SS impairments. METHODS: 41 treatment-naive patients with OCD and 34 control participants (CP) were assessed using a SS inventory. Patients were reevaluated 12-weeks after standardized treatment. Group differences, as well as the treatment effect on OCD symptomatology over time, were analyzed with independent and paired tests, respectively. OCD severity, age at illness onset and illness duration were tested as predictors of SS. RESULTS: Patients had lower total SS scores compared to controls (p-value < 0.001). After treatment, although OCD symptomatology (p-value < 0.001) improved, there was no statistical difference in SS performance (p-value = 0.673). Earlier age of onset of OCD symptoms predicted worse SS total score (p-value = 0.016). CONCLUSION: This study suggests that, despite the amelioration of OCD symptomatology, there was no alteration in Social Skills (SS) performance. Subsequent treatment investigations incorporating larger sample sizes and extended follow-up periods could elucidate whether enhancements in social skills are likely to manifest over time.
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Background: Recent studies using magnetic resonance spectroscopy (1H-MRS) indicate that patients with obsessive-compulsive disorder (OCD) present abnormal levels of glutamate (Glu) and gamma aminobutyric acid (GABA) in the frontal and striatal regions of the brain. These abnormalities could be related to the hyperactivation observed in cortico-striatal circuits of patients with OCD. However, most of the previous 1H-MRS studies were not capable of differentiating the signal from metabolites that overlap in the spectrum, such as Glu and glutamine (Gln), and referred to the detected signal as the composite measure-Glx (sum of Glu and Gln). In this study, we used a two-dimensional JPRESS 1H-MRS sequence that allows the discrimination of overlapping metabolites by observing the differences in J-coupling, leading to higher accuracy in the quantification of all metabolites. Our objective was to identify possible alterations in the neurometabolism of OCD, focusing on Glu and GABA, which are key neurotransmitters in the brain that could provide insights into the underlying neurochemistry of a putative excitatory/inhibitory imbalance. Secondary analysis was performed including metabolites such as Gln, creatine (Cr), N-acetylaspartate, glutathione, choline, lactate, and myo-inositol. Methods: Fifty-nine patients with OCD and 42 healthy controls (HCs) underwent 3T 1H-MRS in the ventromedial prefrontal cortex (vmPFC, 30 × 25 × 25 mm3). Metabolites were quantified using ProFit (version 2.0) and Cr as a reference. Furthermore, Glu/GABA and Glu/Gln ratios were calculated. Generalized linear models (GLMs) were conducted using each metabolite as a dependent variable and age, sex, and gray matter fraction (fGM) as confounding factors. GLM analysis was also used to test for associations between clinical symptoms and neurometabolites. Results: The GLM analysis indicated lower levels of Glu/Cr in patients with OCD (z = 2.540; p = 0.011). No other comparisons reached significant differences between groups for all the metabolites studied. No associations between metabolites and clinical symptoms were detected. Conclusions: The decreased Glu/Cr concentrations in the vmPFC of patients with OCD indicate a neurochemical imbalance in the excitatory neurotransmission that could be associated with the neurobiology of the disease and may be relevant for the pathophysiology of OCD.
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OBJECTIVE: To evaluate the efficacy of serotonin reuptake inhibitor (SRI) augmentation with N-acetylcysteine (NAC), a glutamate modulator and antioxidant medication, for treatment-resistant obsessive-compulsive disorder (OCD). METHODS: We conducted a randomized, double-blind, placebo-controlled, 16-week trial of NAC (3,000 mg daily) in adults (aged 18-65 years) with treatment-resistant OCD, established according to DSM-IV criteria. Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital (May 2012-October 2014). The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To evaluate the variables group, time, and interaction effects for Y-BOCS scores at all time points, we used nonparametric analysis of variance with repeated measures. Secondary outcomes were the severity scores for anxiety, depression, specific OCD symptom dimensions, and insight. RESULTS: Both groups showed a significant reduction of baseline Y-BOCS scores at week 16: the NAC group had a reduction of 4.3 points (25.6 to 21.3), compared with 3.0 points (24.8 to 21.8) for the placebo group. However, there were no significant differences between groups (P = .92). Adding NAC was superior to placebo in reducing anxiety symptoms (P = .02), but not depression severity or specific OCD symptom dimensions. In general, NAC was well tolerated, despite abdominal pain being more frequently reported in the NAC group (n [%]: NAC = 9 [60.0], placebo = 2 [13.3]; P < .01). CONCLUSIONS: Our trial did not demonstrate a significant benefit of NAC in reducing OCD severity in treatment-resistant OCD adults. Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01555970.
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Acetilcisteína/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Acetilcisteína/efeitos adversos , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Comorbidade , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/psicologia , Método Duplo-Cego , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Adulto JovemRESUMO
We aimed to investigate which items of the Yale-Brown Obsessive-Compulsive Severity Scale best discriminate the reduction in total scores in obsessive-compulsive disorder patients after 4 and 12 weeks of pharmacological treatment. Data from 112 obsessive-compulsive disorder patients who received fluoxetine (⩽80 mg/day) for 12 weeks were included. Improvement indices were built for each Yale-Brown Obsessive-Compulsive Severity Scale item at two timeframes: from baseline to week 4 and from baseline to week 12. Indices for each item were correlated with the total scores for obsessions and compulsions and then ranked by correlation coefficient. A correlation coefficient ⩾0.7 was used to identify items that contributed significantly to reducing obsessive-compulsive disorder severity. At week 4, the distress items reached the threshold of 0.7 for improvement on the obsession and compulsion subscales although, contrary to our expectations, there was greater improvement in the control items than in the distress items. At week 12, there was greater improvement in the time, interference, and control items than in the distress items. The use of fluoxetine led first to reductions in distress and increases in control over symptoms before affecting the time spent on, and interference from, obsessions and compulsions. Resistance did not correlate with overall improvement. Understanding the pathway of improvement with pharmacological treatment in obsessive-compulsive disorder may provide clues about how to optimize the effects of medication.
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Comportamento Obsessivo/psicologia , Transtorno Obsessivo-Compulsivo/psicologia , Adulto , Feminino , Fluoxetina/uso terapêutico , Humanos , Masculino , Comportamento Obsessivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Escalas de Graduação Psiquiátrica , Psicometria/métodos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Early prediction of treatment response could reduce exposure to ineffective treatments and optimize the use of medical resources. Neuroimaging techniques have been used to identify biomarkers that are predictive of outcomes. The aims of this study were to investigate orbitofrontal cortex (OFC) thickness as a potential morphometric biomarker to discriminate outcomes in obsessive-compulsive disorder (OCD) and then to reexamine this biomarker in an independent cohort METHODS: Using a logistic regression model based on the mean baseline thickness of subregions of the OFC, we estimated the probability of treatment response in 29 treatment-naïve OCD patients who participated in a clinical trial. That algorithm was then tested in an independent cohort of 12 patients with a confirmed diagnosis of refractory OCD RESULTS: Among the treatment-naïve OCD patients, measures of OFC thickness statistically significantly differentiated responders (n = 13) and nonresponders (n = 16), with an overall classification accuracy of ≈80%, a sensitivity of 77% (10/13), and a specificity of 81% (13/16). Of the refractory OCD patients in the second independent cohort, 67% were correctly classified as nonresponders. The most discriminative measures in the initial cohort of treatment-naïve patients were the thicknesses of the left and right medial OFC (P = .009 and P = .028, respectively) CONCLUSIONS: We found OFC thickness to be a strong predictor of treatment response in treatment-naïve OCD patients. Although there are not yet any brain imaging biomarkers with clinical utility, our results highlight the potential of these measures as tools for predicting treatment outcomes in OCD.
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Mapeamento Encefálico , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/terapia , Córtex Pré-Frontal/patologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Tamanho do Órgão , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
BACKGROUND: Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, "just-right" perceptions, feelings of incompleteness, or "urge-only" phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive-compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. METHODS: We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. RESULTS: We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. LIMITATIONS: Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. CONCLUSION: We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.
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Encéfalo/patologia , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Percepção , Adulto , Brasil , Feminino , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/psicologia , Tamanho do Órgão , Escalas de Graduação Psiquiátrica , EspanhaRESUMO
IMPORTANCE: Select cases of intractable obsessive-compulsive disorder (OCD) have undergone neurosurgical ablation for more than half a century. However, to our knowledge, there have been no randomized clinical trials of such procedures for the treatment of any psychiatric disorder. OBJECTIVE: To determine the efficacy and safety of a radiosurgery (gamma ventral capsulotomy [GVC]) for intractable OCD. DESIGN, SETTING, AND PARTICIPANTS: In a double-blind, placebo-controlled, randomized clinical trial, 16 patients with intractable OCD were randomized to active (n = 8) or sham (n = 8) GVC. Blinding was maintained for 12 months. After unblinding, sham-group patients were offered active GVC. INTERVENTIONS: Patients randomized to active GVC had 2 distinct isocenters on each side irradiated at the ventral border of the anterior limb of the internal capsule. The patients randomized to sham GVC received simulated radiosurgery using the same equipment. MAIN OUTCOMES AND MEASURES: Scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression-Improvement (CGI-I) Scale. Response was defined as a 35% or greater reduction in Y-BOCS severity and "improved" or "much improved" CGI-I ratings. RESULTS: Three of 8 patients randomized to active treatment responded at 12 months, while none of the 8 sham-GVC patients responded (absolute risk reduction, 0.375; 95% CI, 0.04-0.71). At 12 months, OCD symptom improvement was significantly higher in the active-GVC group than in the sham group (Y-BOCS, P = .046; Dimensional Y-BOCS, P = .01). At 54 months, 2 additional patients in the active group had become responders. Of the 4 sham-GVC patients who later received active GVC, 2 responded by post-GVC month 12. The most serious adverse event was an asymptomatic radiation-induced cyst in 1 patient. CONCLUSIONS AND RELEVANCE: Gamma ventral capsulotomy benefitted patients with otherwise intractable OCD and thus appears to be an alternative to deep-brain stimulation in selected cases. Given the risks inherent in any psychiatric neurosurgery, such procedures should be conducted at specialized centers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01004302.
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Cápsula Interna/cirurgia , Transtorno Obsessivo-Compulsivo/cirurgia , Radiocirurgia/métodos , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto JovemRESUMO
This study aimed to investigate the phenomenology of obsessive-compulsive disorder (OCD), addressing specific questions about the nature of obsessions and compulsions, and to contribute to the World Health Organization's (WHO) revision of OCD diagnostic guidelines. Data from 1001 patients from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders were used. Patients were evaluated by trained clinicians using validated instruments, including the Dimensional Yale-Brown Obsessive-Compulsive Scale, the University of Sao Paulo Sensory Phenomena Scale, and the Brown Assessment of Beliefs Scale. The aims were to compare the types of sensory phenomena (SP, subjective experiences that precede or accompany compulsions) in OCD patients with and without tic disorders and to determine the frequency of mental compulsions, the co-occurrence of obsessions and compulsions, and the range of insight. SP were common in the whole sample, but patients with tic disorders were more likely to have physical sensations and urges only. Mental compulsions occurred in the majority of OCD patients. It was extremely rare for OCD patients to have obsessions without compulsions. A wide range of insight into OCD beliefs was observed, with a small subset presenting no insight. The data generated from this large sample will help practicing clinicians appreciate the full range of OCD symptoms and confirm prior studies in smaller samples the degree to which insight varies. These findings also support specific revisions to the WHO's diagnostic guidelines for OCD, such as describing sensory phenomena, mental compulsions and level of insight, so that the world-wide recognition of this disabling disorder is increased.
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Comportamento Compulsivo/diagnóstico , Comportamento Obsessivo/diagnóstico , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Determinação da Personalidade/normas , Escalas de Graduação Psiquiátrica/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Comportamento Compulsivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento Obsessivo/psicologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Panic Disorder (PD) and agoraphobia (AG) are frequently comorbid with obsessive-compulsive disorder (OCD), but the correlates of these comorbidities in OCD are fairly unknown. The study aims were to: 1) estimate the prevalence of PD with or without AG (PD), AG without panic (AG) and PD and/or AG (PD/AG) in a large clinical sample of OCD patients and 2) compare the characteristics of individuals with and without these comorbid conditions. METHOD: A cross-sectional study with 1001 patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders using several assessment instruments, including the Dimensional Yale-Brown Obsessive-Compulsive Scale and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Bivariate analyses were followed by logistic regression models. RESULTS: The lifetime prevalence of PD was 15.3% (N=153), of AG 4.9% (N=49), and of PD/AG 20.2% (N=202). After logistic regression, hypochondriasis and specific phobia were common correlates of the three study groups. PD comorbidity was also associated with higher levels of anxiety, having children, major depression, bipolar I, generalized anxiety and posttraumatic stress disorders. Other independent correlates of AG were: dysthymia, bipolar II disorder, social phobia, impulsive-compulsive internet use, bulimia nervosa and binge eating disorder. Patients with PD/AG were also more likely to be married and to present high anxiety, separation anxiety disorder, major depression, impulsive-compulsive internet use, generalized anxiety, posttraumatic stress and binge eating disorders. CONCLUSIONS: Some distinct correlates were obtained for PD and AG in OCD patients, indicating the need for more specific and tailored treatment strategies for individuals with each of these clinical profiles.
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Agorafobia/epidemiologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno de Pânico/epidemiologia , Adulto , Agorafobia/terapia , Brasil/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Transtorno de Pânico/terapia , Prevalência , Adulto JovemRESUMO
Our aim was to investigate the impact of comorbid body dysmorphic disorder (BDD) on the response to sequential pharmacological trials in adult obsessive-compulsive disorder (OCD) patients. The sequential trial initially involved fluoxetine monotherapy followed by one of three randomized, add-on strategies: placebo, clomipramine or quetiapine. We included 138 patients in the initial phase of fluoxetine, up to 80 mg or the maximum tolerated dosage, for 12 weeks. We invited 70 non-responders to participate in the add-on trial; as 54 accepted, we allocated 18 to each treatment group and followed them for an additional 12 weeks. To evaluate the combined effects of sex, age, age at onset, initial severity, type of augmentation and BDD on the response to sequential treatments, we constructed a model using generalized estimating equations (GEE). Of the 39 patients who completed the study (OCD-BDD, n = 13; OCD-non-BDD, n = 26), the OCD-BDD patients were less likely to be classified as responders than the OCD-non-BDD patients (Pearson Chi-Square = 4.4; p = 0.036). In the GEE model, BDD was not significantly associated with a worse response to sequential treatments (z-robust = 1.77; p = 0.07). The predictive potential of BDD regarding sequential treatment strategies for OCD did not survive when the analyses were controlled for other clinical characteristics.