Antonio Carlos Lopes

Gray matter volumes in obsessive-compulsive disorder before and after fluoxetine or cognitive-behavior therapy: a randomized clinical trial.

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n=38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n=36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n=26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n=13), whereas no significant GM volume changes were observed in CBT-treated patients (n=13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action.

Prenatal, Perinatal, and Postnatal Risk Factors in Obsessive–Compulsive Disorder

BACKGROUNDnThe etiology of obsessive-compulsive disorder (OCD) remains unknown, although it is thought to involve an interaction of genetic and environmental factors. This study aimed to identify prenatal, perinatal, and postnatal risk factors in OCD.nnnMETHODSnWe compared retrospectively 68 OCD patients to 70 control subjects based on responses given on a standardized questionnaire. The questionnaire was designed to evaluate environmental factors, with a special focus on gestation, labor, birth, and early infancy aspects.nnnRESULTSnThe group of OCD patients had risk factors with greater frequency than the control group. Notable among the significant findings (p < or = 0.001) were edema of the hands, feet, or face and excessive weight gain during gestation; hyperemesis gravidarum; prolonged labor; preterm birth; and jaundice. When socioeconomic class was used as a covariable in the logistic regression analysis, prolonged labor and edema during pregnancy remained statistically significant.nnnCONCLUSIONSnSome early risk factors may be associated with the expression of OCD later in life such as edema during pregnancy and prolonged labor. If our findings are confirmed in future studies, greater attention should be given to such factors in predisposed individuals, especially in prenatal care and delivery.

Gamma Ventral Capsulotomy for Obsessive-Compulsive Disorder: A Randomized Clinical Trial

IMPORTANCEnSelect 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.nnnOBJECTIVEnTo determine the efficacy and safety of a radiosurgery (gamma ventral capsulotomy [GVC]) for intractable OCD.nnnDESIGN, SETTING, AND PARTICIPANTSnIn a double-blind, placebo-controlled, randomized clinical trial, 16 patients with intractable OCD were randomized to active (nu2009=u20098) or sham (nu2009=u20098) GVC. Blinding was maintained for 12 months. After unblinding, sham-group patients were offered active GVC.nnnINTERVENTIONSnPatients 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.nnnMAIN OUTCOMES AND MEASURESnScores 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.nnnRESULTSnThree 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, Pu2009=u2009.046; Dimensional Y-BOCS, Pu2009=u2009.01). 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.nnnCONCLUSIONS AND RELEVANCEnGamma 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.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT01004302.

Atualização sobre o tratamento neurocirúrgico do transtorno obsessivo-compulsivo

Responses to pharmacotherapy and psychotherapy in obsessive-compulsive disorder (OCD) range from 60 to 80% of cases. However, a subset of OCD patients do not respond to adequately conducted treatment trials, leading to severe psychosocial impairment. Stereotactic surgery can be indicated then as the last resource. Five surgical techniques are available, with the following rates of global post-operative improvement: anterior capsulotomy (38-100%); anterior cingulotomy (27-57%); subcaudate tractotomy (33-67%); limbic leucotomy (61-69%), and central lateral thalamotomy/anterior medial pallidotomy (62.5%). The first technique can be conducted as a standard neurosurgery, as radiosurgery or as deep brain stimulation. In the standard neurosurgery neural circuits are interrupted by radiofrequency. In radiosurgery, an actinic lesion is provoked without opening the brain. Deep brain stimulation consists on implanting electrodes which are activated by stimulators. Literature reports a relatively low prevalence of adverse events and complications. Neuropsychological and personality changes are rarely reported. However, there is a lack of randomized controlled trials to prove efficacy and adverse events/complication issues among these surgical procedures. Concluding, there is a recent development in the neurosurgeries for severe psychiatric disorders in the direction of making them more efficacious and safer. These surgeries, when correctly indicated, can profoundly alleviate the suffering of severe OCD patients.

Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive-compulsive disorder

Nearly one-third of patients with obsessive-compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naïve OCD patients randomized between trials of fluoxetine or CBT. Treatment-naïve OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetines effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602.

Neuropsychological predictors of response to randomized treatment in obsessive-compulsive disorder

OBJECTIVEnTo identify neuropsychological predictors of treatment response to cognitive-behavioral therapy (CBT) and fluoxetine in treatment-naïve adults with obsessive-compulsive disorder (OCD).nnnMETHODnThirty-eight adult outpatients with OCD underwent neuropsychological assessment, including tasks of intellectual function, executive functioning and visual and verbal memory, before randomization to a 12-week clinical trial of either CBT or fluoxetine. Neuropsychological measures were used to identify predictors of treatment response in OCD.nnnRESULTSnNeuropsychological measures that predicted a better treatment response to either CBT or fluoxetine were higher verbal IQ (Wechsler Abbreviated Scale of Intelligence) (p=0.008); higher verbal memory on the California Verbal Learning Test (p=0.710); shorter time to complete part D (Dots) (p<0.001), longer time to complete part W (Words) (p=0.025) and less errors on part C (Colors) (p<0.001) in the Victoria Stroop Test (VST). Fewer perseverations on the California Verbal Learning Test, a measure of mental flexibility, predicted better response to CBT, but worse response to fluoxetine (p=0.002).nnnCONCLUSIONnIn general, OCD patients with better cognitive and executive abilities at baseline were more prone to respond to either CBT or fluoxetine. Our finding that neuropsychological measures of mental flexibility predicted response to treatment in opposite directions for CBT and fluoxetine suggests that OCD patients with different neuropsychological profiles may respond preferentially to one type of treatment versus the other. Further studies with larger samples of OCD patients are necessary to investigate the heuristic value of such findings in a clinical context.

Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: A structural MRI pilot prospective study

OBJECTIVEnThe purpose of this study was to investigate regional structural abnormalities in the brains of five patients with refractory obsessive-compulsive disorder (OCD) submitted to gamma ventral capsulotomy.nnnMETHODSnWe acquired morphometric magnetic resonance imaging (MRI) data before and after 1 year of radiosurgery using a 1.5-T MRI scanner. Images were spatially normalized and segmented using optimized voxel-based morphometry (VBM) methods. Voxelwise statistical comparisons between pre- and post-surgery MRI scans were performed using a general linear model. Findings in regions predicted a priori to show volumetric changes (orbitofrontal cortex, anterior cingulate gyrus, basal ganglia and thalamus) were reported as significant if surpassing a statistical threshold of p<0.001 (uncorrected for multiple comparisons).nnnRESULTSnWe detected a significant regional postoperative increase in gray matter volume in the right inferior frontal gyri (Brodmann area 47, BA47) when comparing all patients pre and postoperatively.nnnCONCLUSIONSnOur results support the current theory of frontal-striatal-thalamic-cortical (FSTC) circuitry involvement in OCD pathogenesis. Gamma ventral capsulotomy is associated with neurobiological changes in the inferior orbitofrontal cortex in refractory OCD patients.

Obsessive–compulsive symptoms in sibling pairs concordant for obsessive–compulsive disorder†‡

Obsessive–compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. Phenotypic studies of affected sib‐pairs (SPs) may help to characterize familial components of the phenotype. To determine whether SPs affected with OCD are similar in age at onset of obsessive–compulsive symptoms (OCS), symptom dimensions and presence of tic disorders (TDs). Forty OCD siblings ranging from 13 to 59 years old were evaluated by expert psychiatrists or psychologists. Families with two or more siblings affected with OCD were recruited from several OCD clinics in Brazil. The Yale Brown Obsessive–Compulsive Scale Checklist was used to assess OCS and the severity of OCD. The OCD diagnoses were made according to the DSM‐IV. The chi‐square test was used to assess concordance of TD presence within SPs based on the TD frequency reported in the literature (30%). There were significantly more siblings with early‐onset OCS than with late‐onset OCS (Pu2009=u20090.002). Age at onset of OCS correlated positively and significantly between the two members of each SP (Pu2009=u20090.005). Fourteen patients (35%) were diagnosed with TDs. There was no concordance of the TD presence within the SPs. When both were male, there was a significant sibling correlation in the contamination obsessions/cleaning compulsions dimension (ICCu2009=u20090.74; Pu2009=u20090.002). Similarly, when both siblings were female, they were comparable in the hoarding obsessions/compulsions dimension (ICCu2009=u20090.76; Pu2009=u20090.01). Familial factors seem to contribute to specific OCD phenotypic components such as age at onset of OCS and specific dimensions. The obvious influence of gender is as yet unexplained.

Personality traits and treatment outcome in obsessive-compulsive disorder

OBJECTIVEnComorbidity with personality disorders in obsessive-compulsive patients has been widely reported. About 40% of obsessive-compulsive patients do not respond to first line treatments. Nevertheless, there are no direct comparisons of personality traits between treatment-responsive and non-responsive patients. This study investigates differences in personality traits based on Cloningers Temperament and Character Inventory scores between two groups of obsessive-compulsive patients classified according to treatment outcome: responders and non-responders.nnnMETHODnForty-four responsive and forty-five non-responsive obsessive-compulsive patients were selected. Subjects were considered treatment-responsive (responder group) if, after having received treatment with any conventional therapy, they had presented at least a 40% decrease in the initial Yale-Brown Obsessive Compulsive Scale score, had rated better or much better on the Clinical Global Impressions scale; and had maintained improvement for at least one year. Non-responders were patients who did not achieve at least a 25% reduction in Yale-Brown Obsessive Compulsive Scale scores and had less than minimal improvement on the Clinical Global Impressions scale after having received treatment with at least three selective serotonin reuptake inhibitors (including clomipramine), and at least 20 hours of cognitive behavioral therapy. Personality traits were assessed using Temperament and Character Inventory.nnnRESULTSnNon-responders scored lower in self-directedness and showed a trend to score higher in persistence than responders did.nnnCONCLUSIONnThis study suggests that personality traits, especially self-directedness, are associated with poor treatment response in obsessive-compulsive patients.

Hoarding symptoms and prediction of poor response to limbic system surgery for treatment-refractory obsessive-compulsive disorder

UNLABELLEDnOBJECT.: Recent findings have suggested a correlation between obsessive-compulsive disorder (OCD) symptom dimensions and clinical outcome after limbic system surgery for treatment-refractory patients. Based on previous evidence that the hoarding dimension is associated with worse outcome in conventional treatments, and may have a neural substrate distinct from OCD, the authors examined a large sample of patients undergoing limbic surgery (40 with capsulotomy, 37 with cingulotomy) and investigated if symptom dimensions, in particular hoarding, could influence treatment outcome.nnnMETHODSnData from 77 patients from 3 different research centers at São Paulo (n = 17), Boston (n = 37), and Stockholm (n = 23) were analyzed. Dimensional Yale-Brown Obsessive Compulsive Scale (Y-BOCS; São Paulo) or Y-BOCS Symptom Checklist scores (Boston and Stockholm) were used to code the presence of 4 well-established symptom dimensions: forbidden thoughts, contamination/cleaning, symmetry/order, and hoarding. Reductions in YBOCS scores determined clinical outcome.nnnRESULTSnMean Y-BOCS scores decreased 34.2% after surgery (95% CI 27.2%-41.3%), with a mean follow-up of 68.1 months. Patients with hoarding symptoms had a worse response to treatment (mean Y-BOCS decrease of 22.7% ± 25.9% vs 41.6% ± 32.2%, respectively; p = 0.006), with no significant effect of surgical modality (capsulotomy vs cingulotomy). Patients with forbidden thoughts apparently also had a worse response to treatment, but this effect was dependent upon the co-occurrence of the hoarding dimension. Only the negative influence of the hoarding dimension remained when an ANOVA model was performed, which also controlled for preoperative symptom severity.nnnCONCLUSIONSnThe presence of hoarding symptoms prior to surgery was associated with worse clinical outcome after the interventions. Patients with OCD under consideration for ablative surgery should be carefully screened for hoarding symptoms or comorbid hoarding disorder. For these patients, the potentially reduced benefits of surgery need to be carefully considered against potential risks.