Deep Brain Stimulation of the Bilateral Habenula for Treatment-Refractory Obsessive-Compulsive Disorder

Deep Brain Stimulation of the Bilateral Habenula for Treatment-Refractory Obsessive-Compulsive Disorder

Deep Brain Stimulation of the Bilateral Habenula for Treatment-Refractory Obsessive-Compulsive Disorder

Deep brain stimulation (DBS) offers an effective and safe treatment for patients with debilitating, otherwise treatment-refractory obsessive-compulsive disorder(OCD). Although several target areas for DBS have been used for OCD, such as the ventral capsule/ventral striatum and the subthalamic nucleus, not all patients show a clinical response, varying from 10% to 61.5%. Exploring new DBS targets may be a key approach to improve this situation. The habenula is an evolutionarily conserved structure playing an important role in depression, punishment avoiding, reward, addiction, pain and circadian rhythms. The habenula can be considered a promising target for OCD treatment based on the following hypotheses and clinical observations. The lateral habenula DBS has significant clinical antidepressant effects. The habenula plays an important role in the regulation of dopamine and serotonin systems. Selective serotonin reuptake inhibitors, the first line treatment for OCD, are commonly used to treat clinical depression. The habenula serves as a 'negative reward center' that mediates or moderates stress, negative emotions and thoughts, aversive learning, and goal-directed behavior, which are core clinical symptoms and signs of OCD. In our hospital, DBS of the habenula produced a significant improvement in OCD symptoms in one patient who failed to respond to other treatments, including capsulotomy either alone or in combination combined with cingulumotomy. These theoretical and clinical considerations indicate that the habenula can be seen as a promising DBS target for OCD treatment. This study is focused on the effectiveness of bilateral DBS of the habenula for patients with treatment-refractory OCD. Furthermore, the study is aimed at exploring the influence of DBS of the habenula on brain activity and cognition.

All subjects will undergo bilateral surgical implantation of DBS system to habenula. The DBS system will be active at one week after surgery.

The DBS device utilized in the present study may include the Medtronic, PINS and SceneRay DBS device depending on patients' choice.

The FMRI signal is to estimate Blood Oxygenation Level Dependent (BOLD) and connectivity of brain areas

Neuropsychological measures contains six tasks which are detection task, identification task, one card learning task, one back task, Groton maze learning task, set-shifting task

Inclusion Criteria: Diagnosed as having primary OCD according to DSM-IV criteria using the Structured Clinical Interview for DSM-IV Axis I disorders; YBOCSII score ≥31； Duration ≥2 years； Refractoriness to therapy was defined as no response or insufficient response following at least 2 treatments with adequate trials or intolerance to two or three selective serotonin transporter inhibitors (SSRIs) and clomipramine, augmentation strategies (antipsychotics) and cognitive behavioral therapy. Capacity to provide informed consent (understanding of the study purpose and methods. Exclusion Criteria: Except for those with major depressive disorder and mild anxiety disorders, patients with clinically significant comorbid DSM-IV diagnoses (such as schizophrenia, bipolar II disorder, alcohol or substance abuse in the last 6 months, current tic disorder, or body dysmorphic disorder) Patients with severe personality disorders, assessed using the Structured Clinical Interview for DSM-IV Axis II disorders. Serious and unstable organic diseases (e.g. unstable coronal heart disease); Pregnancy and/or lactation.

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