Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients.

Gamma ventral capsulotomy (GVC) radiosurgery is intended to minimize side effects while maintaining the efficacy of traditional thermocoagulation techniques for the treatment of refractory obsessive-compulsive disorder (OCD). Neuropsychological outcomes are not clear based on previous studies and, therefore, we investigated the effects of GVC on cognitive and motor performance. A double-blind, randomized controlled trial (RCT) was conducted with 16 refractory OCD patients allocated to active treatment (n=8) and sham (n=8) groups. A comprehensive neuropsychological evaluation including intellectual functioning, attention, verbal and visuospatial learning and memory, visuospatial perception, inhibitory control, cognitive flexibility, and motor functioning was applied at baseline and one year after the procedure. Secondary analysis included all operated patients: eight from the active group, four from the sham group who were submitted to surgery after blind was broken, and five patients from a previous open pilot study (n=5), totaling 17 patients. In the RCT, visuospatial memory (VSM) performance significantly improved in the active group after GVC (p=0.008), and remained stable in the sham group. Considering all patients operated, there was no decline in cognitive or motor functioning after one year of follow-up. Our initial results after 1 year of follow-up suggests that GVC not only is a safe procedure in terms of neuropsychological functioning but in fact may actually improve certain neuropsychological domains, particularly VSM performance, in treatment refractory OCD patients.

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.

Treatment of resistant obsessive-compulsive disorder with ventral capsular/ventral striatal gamma capsulotomy: a pilot prospective study.

A subgroup of obsessive-compulsive disorder (OCD) patients remains refractory to conventional treatments. For them, a new stereotactic radiosurgery has been recently developed: the ventral capsular/ventral striatal (VC/VS) gamma capsulotomy. The authors aim to report efficacy and adverse events of VC/VS gamma capsulotomy. Five refractory OCD patients were selected. The authors assessed OCD, anxiety and depressive symptoms, and side effects pre- and postoperatively. Three patients (60%) met response criteria 48 months after surgery. Adverse effects were episodic and transient. Ventral capsular/ventral striatal gamma capsulotomy holds therapeutic promise, with few adverse effects.

Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study.

Five refractory obsessive-compulsive patients were assessed using a neuropsychological battery after a modified gamma knife capsulotomy. The surgical technique was not associated with profound cognitive deficits. The authors found improvements in attention, vocabulary, learning, abstract reasoning, and memory.

The drug-naïve OCD patients imaging genetics, cognitive and treatment response study: methods and sample description / Estudo de genética, imagem, cognição e resposta a tratamento em pacientes com TOC virgens de tratamento: métodos e descrição da amostra

OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.

OBJETIVO: Descrever um protocolo integrativo de investigação neurobiológica para melhor compreender as bases patofisiológicas do transtorno obsessivo-compulsivo e apresentar as características clínicas e demográficas da amostra. MÉTODO: Protocolo padronizado que combina diferentes modalidades de investigação (genética, neuropsicologia, ressonância magnética cerebral e imagem molecular do transportador de dopamina) obtidas antes e depois do tratamento em pacientes com transtorno obsessivo-compulsivo nunca expostos à medicação submetidos a um ensaio clínico comparando um inibidor seletivo da recaptação de serotonina (fluoxetina) e terapia cognitivo-comportamental em grupo. RESULTADOS: Cinquenta e dois pacientes com transtorno obsessivo-compulsivo entraram no ensaio clínico (27 no grupo fluoxetina e 25 no grupo de terapia). No início, foram realizadas 47 coletas de sangue para genética, 50 avaliações neuropsicológicas, 50 ressonâncias magnéticas cerebrais e 48 exames de tomografia computadorizada por emissão de fóton único (SPECT) com TRODAT-1. Depois de 12 semanas, 38 pacientes terminaram o protocolo (20 no grupo de fluoxetina e 18 no grupo de terapia). Trinta e oito reavaliações neuropsicológicas, 31 ressonâncias magnéticas de crânio e 34 exames de SPECT foram obtidos após o tratamento. Quarenta e um controles pareados foram submetidos ao mesmo protocolo inicial. CONCLUSÃO: Os dados genéticos, neuropsicológicos, volumétricos e moleculares do transportador de dopamina aliados à resposta a tratamento podem tanto gerar informações importantes a respeito da neurobiologia do transtorno obsessivo-compulsivo quanto ter uma aplicação clínica.

Performance of patients with refractory obsessive-compulsive disorder in the Frontal Systems Behavior Scale.

OBJECTIVE: To compare the performance of patients with obsessive-compulsive disorder (OCD) refractory to conventional treatments to healthy controls according to the Frontal Systems Behaviour Scale (FrSBe), comparing the scale scores within each group (Self or Family) and correlating FrSBe with Y-BOCS, DY-BOCS, tic disorder and age of first symptoms. METHOD: Twenty OCD patients and 20 healthy controls were assessed using the FrSBe, a scale designed to evaluate frontal syndromes. RESULTS: The patients had higher scores when compared with the control group (p value < .001) in terms of total score on the scale for both profile forms (Self and Family). In addition, there was a significant difference between the scores reported by the patients and their respective relatives. However, no correlation was observed between the scale and the other variables. CONCLUSIONS: The scale was able to clearly differentiate patients with OCD from healthy controls. This finding suggests that the FrSBe can be used not only in neurologic patients but also in psychiatric cases such as refractory OCD.

The drug-naïve OCD patients imaging genetics, cognitive and treatment response study: methods and sample description.

OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.