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Obsessive-compulsive disorder (OCD) is a common psychiatric condition classically characterized by obsessions (recurrent, intrusive and unwanted thoughts) and compulsions (excessive, repetitive and ritualistic behaviors or mental acts). OCD is heterogeneous in its clinical presentation and not all patients respond to first-line treatments. Several neurocircuit models of OCD have been proposed with the aim of providing a better understanding of the neural and cognitive mechanisms involved in the disorder. These models use advances in neuroscience and findings from neuropsychological and neuroimaging studies to suggest links between clinical profiles that reflect the symptoms and experiences of patients and dysfunctions in specific neurocircuits. Several models propose that treatments for OCD could be improved if directed to specific neurocircuit dysfunctions, thereby restoring efficient neurocognitive function and ameliorating the symptomatology of each associated clinical profile. Yet, there are several important limitations to neurocircuit models of OCD. The purpose of the current review is to highlight some of these limitations, including issues related to the complexity of brain and cognitive function, the clinical presentation and course of OCD, etiological factors, and treatment methods proposed by the models. We also provide suggestions for future research to advance neurocircuit models of OCD and facilitate translation to clinical application.

INTRODUÇÃO: O transtorno obsessivo-compulsivo (TOC) é uma doença neuropsiquiátrica frequente e potencialmente debilitante, com altas taxas de falha aos tratamentos de primeira linha. A estimulação elétrica por corrente contínua (ETCC) é uma modalidade de tratamento baseada em neuromodulação não-invasiva, segura e tolerável. No entanto, não há estudos e evidências suficientes que elucidem suas aplicações no tratamento do TOC. OBJETIVO: Avaliar a eficácia e a tolerabilidade da ETCC no tratamento do TOC. METODOLOGIA: Foi realizado um ensaio clínico, duplo cego e controlado por placebo, em um ambulatório terciário de um hospital especializado. Quarenta e três pacientes com TOC, com falha a pelo menos um tratamento farmacológico de primeira linha, foram randomizados em dois grupos: ativo e placebo. O grupo ativo recebeu 20 sessões de ETCC e o grupo placebo recebeu 20 sessões simuladas. As sessões ocorreram em dias da semana consecutivos (exceto finais de semana) e tinham a duração de 30 minutos, totalizando 4 semanas de intervenção. A estimulação foi aplicada com corrente de 2mA/25cm2 , com o cátodo posicionado sobre o crânio, na projeção da área suplementar motora e o ânodo sobre o músculo deltoide direito. Após as 4 semanas de intervenção, os pacientes foram acompanhados por mais 8 semanas, totalizando 12 semanas de seguimento. O desfecho primário foi a avaliação da gravidade dos sintomas de TOC por meio da escala Yale-Brown de Sintomas Obsessivos Compulsivos (YBOCS) da linha de base até a semana 12. Os desfechos secundários foram as alterações na gravidade dos sintomas depressivos e ansiosos, avaliados respectivamente pelo Inventário de Depressão de Beck e Inventário de Ansiedade de Beck, da linha de base até a semana 12. O critério de resposta utilizado foi baseado em um consenso internacional que considera o paciente como respondedor quando ocorre uma redução maior ou igual a 35% no escore inicial da escala Y-BOCS, e escore 1 (muito melhor) ou 2 (melhor) na escala de Impressão Clínica Global - Melhora (Clinical Global Impression - Improvement). O estudo foi registrado na plataforma ClinicalTrials.gov (NCT02743715). RESULTADOS: Foram realizadas 91 consultas de triagem e 44 pacientes foram randomizados e iniciaram o estudo. Destes, 2 desistiram do estudo e 1 foi excluído por desvio do protocolo. Assim, 43 pacientes foram incluídos na análise por intenção de tratamento. Os pacientes que receberam o tratamento ativo obtiveram maior redução dos sintomas do TOC, avaliados pela escala YBOCS, do que os que receberam tratamento placebo, com redução média de 6,68 e 2,84 pontos, nos grupos ativo e placebo, respectivamente (Cohens d: 0,62 (0,06 a 1.18), p=0,03). No entanto, não houve diferença entre a quantidade de pacientes considerados respondedores ao tratamento comparando o grupo ativo e placebo (4 pacientes no grupo ativo e um paciente no grupo placebo). Apesar do grupo ativo também ter apresentado maior redução dos sintomas depressivos e ansiosos do que o grupo placebo, esta diferença não foi estatisticamente significativa. O tratamento foi bem tolerado e não houve eventos adversos graves. CONCLUSÃO: Neste estudo a ETCC foi eficaz, segura e tolerável numa amostra de pacientes com TOC resistentes aos tratamentos de primeira linha. No entanto, outros estudos serão necessários, com amostras maiores e com perfil de gravidade menor, até que possamos determinar mais claramente o lugar da ETCC no tratamento do TOC INTRODUCTION: Obsessive-Compulsive Disorder (OCD) is a frequent and potentially disabling neuropsychiatry condition, with high rates of resistance to first-line treatments. Transcranial direct current stimulation (tDCS) is a safe, tolerable non-invasive neuromodulation treatment, with scarce evidence for its use in patients with OCD. OBJECTIVE: To evaluate the efficacy and safety of tDCS as a treatment for OCD. METHODS: A randomized, double-blind and sham-controlled trial was conducted in an OCD outpatient clinic at a tertiary hospital. Forty-three OCD patients who failed at least one previous pharmacological treatment were randomized to the active or placebo group. Patients in the active group received 20 sessions of tDCS, whereas patients in the placebo group received 20 simulated sessions. tDCS intervention was conducted in daily sessions of 30 min, in the weekdays, during 4 weeks. Stimulations was delivered with a 2mA/25cm2 current, with the cathode placed over the projection of the supplementary motor area and the anode placed over the right deltoid muscle. After 4 weeks of intervention, patients were followed along 8 weeks, until completing 12 weeks of follow-up. The primary outcome was the change in the baseline Y-BOCS score at week 12. Secondary outcomes were changes in the severity of mood and anxiety symptoms, as evaluated by the Beck Depression and Beck Anxiety inventories from baseline to week 12. Response criteria were based on an international consensus that determined response as a 35% decrease in baseline Y-BOCS scores plus a Clinical Global Impression Improvement rating of 1 (much improved) or 2 (improved). The study was registered at ClinicalsTrial.gov (NCT02743715). RESULTS: We assessed 91 patients, and 44 were randomized and initiated the interventions. Of those 44 patients, 2 dropped out of the study and 1 was excluded due to protocol deviation. Thus, 43 patients were included in the intention-to-treat analysis. Patients that received active tDCS achieved a significantly greater reduction of OCD symptoms than the sham group, with mean (SD) baseline Y-BOCS score changes of 6.68 and 2.84 points, respectively (Cohens d: 0.62 (0.06 to 1.18), p=0.03). We found no significant differences between groups in the number of responders (four patients in the active tDCS and one in the sham group). Active tDCS was not superior to sham in reducing the severity of depression or anxiety. The treatment was well tolerated and there were no severe adverse events. CONCLUSION: In this trial, tDCS was effective, safe and tolerable in a sample of patients with treatment-resistant OCD. However, further studies are needed in larger samples and less severe OCD symptoms, so that we can determine more clearly the role of tDCS in the treatment of OCD

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has been increasingly examined as an alternative treatment modality for Obsessive-Compulsive Disorder (OCD), due to its low costs, ease of use, and portability. Previous studies have suggested that tDCS may achieve a reasonably good response and present a safe tolerability profile. However, at this point there is not strong evidence for the use of this modality of treatment. Considering that OCD is very heterogeneous with regard to clinical presentation, clinical severity and comorbidities, we have conducted a systematic review of studies on tDCS for OCD aiming to evaluate the clinical characteristics of the selected patients and to discuss perspectives for future studies. A literature search was conducted from inception until March 2019 at PubMed/MedLine and Scielo using the following keywords: "tdcs" or "transcranial direct current stimulation" and "obsessive compulsive disorder". Out of 45 manuscripts, twelve were included. Most of the included studies are uncontrolled. A few controlled studies reported improvement of OCD, but some limitations need to be considered. Our main findings were that the selected patients were adults with severe OCD and psychiatric comorbidities, medicated at the time of assessment and resistant to at least one previous conventional treatment. We could not find any studies including specific populations such as adolescents, elderly, pregnant and breastfeeding participants. Similarly, the potential use of tDCS has not been tested in patients with less severe OCD, as a first treatment option, or for those who do not tolerate pharmacological treatments. These opportunities should be explored in future controlled trials.

Introduction: Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation intervention that has been investigated for several psychiatric disorders, including Obsessive-Compulsive Disorder (OCD). As there are several candidate brain regions for targeting OCD relevant networks, clinical studies using tDCS have considerably varied in terms of the electrode montages used. Computer modeling of electric field currents induced by tDCS can help guiding the research of relevant targets for OCD. In this review, the authors used this tool to investigate targeted brain areas from previous studies of tDCS in OCD. Areas covered: A literature search for articles with the keywords 'tDCS', 'Transcranial Direct Current Stimulation' and 'Obsessive Compulsive Disorder' was conducted to identify relevant publications. For comparing different electrode montages, electric field (EF) models were performed using high-resolution brain scan templates. Authors found 13 studies mostly showing an improvement in OCD symptoms. The electrode montages varied considerably between studies. Nonetheless, two main patterns of EFs could be identified: 'focal montages', with EFs concentrated in the prefrontal cortex, and 'diffuse montages', with widespread EFs over cortical areas. Expert opinion: Electric field simulation can guide future clinical trials in psychiatry, using personalized tDCS montages with distinct electrode positioning according to clusters of symptoms.

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.

Background While previous studies have implicated white matter (WM) as a core pathology of obsessive-compulsive disorder (OCD), the underlying neurobiological processes remain elusive. This study used free-water (FW) imaging derived from diffusion magnetic resonance imaging to identify cellular and extracellular WM abnormalities in patients with OCD compared with control subjects. Next, we investigated the association between diffusion measures and clinical variables in patients. Methods We collected diffusion-weighted magnetic resonance imaging and clinical data from 83 patients with OCD (56 women/27 men, age 37.7 ± 10.6 years) and 52 control subjects (27 women/25 men, age 32.8 ± 11.5 years). Fractional anisotropy (FA), FA of cellular tissue, and extracellular FW maps were extracted and compared between patients and control subjects using tract-based spatial statistics and voxelwise comparison in FSL Randomise. Next, we correlated these WM measures with clinical variables (age of onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication. Results Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), lower FA of cellular tissue (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared with control subjects. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures. Conclusions Our findings of widespread FA, FA of cellular tissue, and FW abnormalities suggest that OCD is associated with microstructural cellular and extracellular abnormalities beyond the corticostriatothalamocortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory.

Obsessive-compulsive disorder (OCD) is a frequent, disabling disorder with high rates of treatment resistance. Transcranial direct current stimulation (tDCS) is a safe, tolerable noninvasive neuromodulation therapy with scarce evidence for OCD. This double-blind, randomized, and sham-controlled study investigates the efficacy of tDCS as add-on treatment for treatment-resistant OCD (failure to respond to at least one previous pharmacological treatment). On 20 consecutive weekdays (4 weeks), 43 patients with treatment-resistant OCD underwent 30 min active or sham tDCS sessions, followed by a 8 week follow-up. The cathode was positioned over the supplementary motor area (SMA) and the anode over the left deltoid. The primary outcome was the change in baseline Y-BOCS score at week 12. Secondary outcomes were changes in mood and anxiety and the occurrence of adverse events. Response was evaluated considering percent decrease of baseline Y-BOCS scores and the Improvement subscale of the Clinical Global Impression (CGI-I) between baseline and week 12. Patients that received active tDCS achieved a significant reduction of OCD symptoms than sham, with mean (SD) Y-BOCS score changes of 6.68 (5.83) and 2.84 (6.3) points, respectively (Cohen's d: 0.62 (0.06-1.18), p = 0.03). We found no between-group differences in responders (four patients in the active tDCS and one in the sham group). Active tDCS of the SMA was not superior to sham in reducing symptoms of depression or anxiety. Patients in both groups reported mild adverse events. Our results suggest that cathodal tDCS over the SMA is an effective add-on strategy in treatment-resistant OCD.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has been increasingly examined as an alternative treatment modality for Obsessive-Compulsive Disorder (OCD), due to its low costs, ease of use, and portability. Previous studies have suggested that tDCS may achieve a reasonably good response and present a safe tolerability profile. However, at this point there is not strong evidence for the use of this modality of treatment. Considering that OCD is very heterogeneous with regard to clinical presentation, clinical severity and comorbidities, we have conducted a systematic review of studies on tDCS for OCD aiming to evaluate the clinical characteristics of the selected patients and to discuss perspectives for future studies. A literature search was conducted from inception until March 2019 at PubMed/MedLine and Scielo using the following keywords: “tdcs” or “transcranial direct current stimulation” and “obsessive compulsive disorder”. Out of 45 manuscripts, twelve were included. Most of the included studies are uncontrolled. A few controlled studies reported improvement of OCD, but some limitations need to be considered. Our main findings were that the selected patients were adults with severe OCD and psychiatric comorbidities, medicated at the time of assessment and resistant to at least one previous conventional treatment. We could not find any studies including specific populations such as adolescents, elderly, pregnant and breastfeeding participants. Similarly, the potential use of tDCS has not been tested in patients with less severe OCD, as a first treatment option, or for those who do not tolerate pharmacological treatments. These opportunities should be explored in future controlled trials., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/7N1ARRWQ1f0

The obsessive-compulsive disorder (OCD) is a chronic disease that can cause serious functional and family impairment. According to Cloninger 's personality model some temperament and character factors have been associated with specific psychopathology and disease severity of OCD. However, some trait characters like self-transcendence (ST) still wasn’t properly explored in this context. Descriptions of religious content of OCD symptoms are found in sacred books from the 2nd century and are called scrupulosity. There are few studies evaluating the role of spirituality in the OCD concept, which differs from religion, since spirituality could be defined as the focus on spiritual things and the spirit world rather than on earthly and physical things, while religion is a set of beliefs and rituals that claim to put his followers in a right relationship with God. This article aims to assess whether the construct of SF in Temperament and Character Inventory (TCI) may be related to the concept of spirituality and if it could have a protective property in OCD psychopathology. This is an exploratory case-control study involving 49 patients with OCD divided into two groups: high and low ST. Variables with a P

CONTEXT AND OBJECTIVE: Neuromodulation techniques for treating obsessive-compulsive disorder (OCD) have expanded through greater understanding of the brain circuits involved in this disorder. Transcranial direct current stimulation (tDCS), a non-invasive technique, has been studied as an alternative for treatment-resistant OCD. We describe the design of a clinical trial using tDCS for OCD and report on the outcomes from two patients with primary OCD who were resistant to cognitive-behavioral therapy and to selective serotonin reuptake inhibitors, and who received tDCS in an open manner during the training phase for the study procedures. DESIGN AND SETTING: Methodological description of a clinical trial using tDCS for treatment-resistant OCD at a university hospital; and a report on two cases. METHODS: The proposed study is randomized, sham-controlled and double-blind. Forty-four patients will be randomized to either active or sham intervention. The active intervention consists of applying an electric current of 2 mA, with the cathode positioned in the region corresponding to the supplementary motor cortex (bilaterally) and the anode positioned in the deltoid. The primary outcome will be the reduction in baseline YBOCS (Yale-Brown Obsessive Compulsive Scale) score at the end of week 4. The secondary outcomes will be depression and anxiety symptoms. Genetic markers, cortical excitability and neurocognitive performance will be investigated. RESULTS: The first patient showed significant improvement, whereas the second remained symptomatic after four weeks and after six months. tDCS was well tolerated. CONCLUSION: tDCS for treatment-resistant OCD merits randomized controlled trials that test its effectiveness. RESUMO CONTEXTO E OBJETIVO: Técnicas de neuromodulação para o tratamento do transtorno obsessivo compulsivo (TOC) vêm se expandindo com o melhor entendimento dos circuitos cerebrais envolvidos no transtorno. A estimulação transcraniana por corrente contínua (ETCC), uma técnica não invasiva, vem sendo estudada como alternativa para o TOC resistente aos tratamentos convencionais. Descrevemos o desenho de um ensaio clínico utilizando a ETCC para o TOC e relatamos os desfechos de dois pacientes com TOC primário resistentes à terapia cognitivo-comportamental e aos inibidores seletivos de recaptura da serotonina, que receberam ETCC de modo aberto durante a fase de treino dos procedimentos do estudo. TIPO DE ESTUDO E LOCAL: Descrição metodológica de um ensaio clínico utilizando ETCC para o TOC resistente num hospital universitário e relato de dois casos. MÉTODOS: O estudo proposto é randomizado, controlado por sham e duplo-cego. 44 pacientes serão randomizados para intervenção ativa ou simulada (sham ). A intervenção ativa consiste em aplicar uma corrente elétrica de 2 mA, com cátodo posicionado na região correspondente à área cortical motora suplementar (bilateralmente) e ânodo posicionado no deltoide. Desfecho primário: redução do escore inicial da escala YBOCS (Yale-Brown Obsessive Compulsive Scale) ao final da quarta semana. Desfechos secundários: sintomas depressivos e ansiosos. Marcadores genéticos, excitabilidade cortical e performance em testes neurocognitivos serão investigados. RESULTADOS: O primeiro paciente apresentou melhora significativa, enquanto o segundo permaneceu sintomático ao término das quatro semanas e após seis meses. A ETCC foi bem tolerada. CONCLUSÃO: A ETCC para o tratamento do TOC resistente merece ensaios clínicos randomizados que testem sua efetividade.