Obsessive-Compulsive Disorder

Background

Clinical KeyObsessive-compulsive disorder (OCD) is a mental illness characterized by recurring, anxiety provoking thoughts (obsessions) which are alleviated only by ritualistic actions or purposeful contemplation (compulsions) of the intruding emotion or idea. For example, a fear of germs may lead to repetitive hand washing. Obsessions vary among individuals and persist despite efforts to ignore them, ultimately impairing everyday functioning. 

It is generally accepted that OCD is caused by both psychological and biological factors. OCD has been linked to imbalances in the neurotransmitters serotonin and dopamine, which are thought to play a role in regulating anxiety. Brain scans of patients with OCD revealed different brain activity patterns and functioning within the brain’s striatum, which is linked to planning and initiation of appropriate actions, than in individuals without OCD.

OCD is a chronic disorder with a waxing and waning course. The incidence in the general population is 2-3%, with most people being diagnosed by age 19. Symptoms are wide ranging and varied, and 2/3 of OCD patients develop major depression during their lifetime. 

Current Treatment

First line treatments for OCD include psychotherapy and medications. OCD typically responds well to these treatments, but in some patients with severe unremitting OCD, psychosurgery may be necessary.

Psychotherapy:

  • Behavioral Therapy: OCD may respond to techniques such as exposure and ritual prevention which involves gradual exposure to situations that the patient fears. In this way, the patient may learn to manage stressful situations and overcome their compulsions.
  • Psychological Therapy: patients may be taught to identify obsessive thoughts and gradually replace them with more rational thoughts.

Medications:

  • Selective Serotonin Reuptake Inhibitors (SSRIs): Used to treat depression and anxiety disorders by increasing the amount of serotonin available to bind its receptor
  • Tricyclic Antidepressants (Clomipramine): Clomipramine is a highly selective inhibitor of serotonin reuptake which also works to increase levels of serotonin

Psychosurgery:

  • Modified cingulotomy: This is a surgical procedure in which a portion of the brain’s anterior cingulate cortex is destroyed. This region is part of the brain’s limbic system, which integrates feelings and emotion in the cortex.
  • Radiofrequency thermal ablation: This invasive procedure involves drilling a hole in the skull and inserting an electrode through the brain cortex into the target. This surgical procedure carries risks, including damage to the brain, hemorrhage and infection.
  • Stereotactic Radiosurgery: This is a non-invasive procedure used to destroy the target tissue. It often takes months for the patient to experience relief and is occasionally associated with radiation side effects. Unable to monitor target site during treatment.
  • Deep brain stimulation (DBS): DBS does not require destruction of brain tissue and is FDA-approved for compassionate treatment of OCD. DBS also carries the same risks as radiofrequency ablation.

Focused Ultrasound

Focused Ultrasound is a non-invasive modality for the ablation of tissue. Thermal ablation allows for cell death in a precise location with minimal damage to surrounding tissue, monitored real time during the FUS procedure. FUS has been used in the treatment of functional brain disorders by creating thermal lesions deep within the brain. OCD is ideal for MRgFUS therapy as the area of the brain that is targeted is relatively small. A pilot clinical trial conducted at Yonsei University College of Medicine used MRgFUS to perform bilateral anterior limb capsulotomies in 12 OCD patients, all of which were refractory to medical therapy. The results of the first four patients with six months follow-up were recently published. These patients experienced gradual improvement in obsessive-compulsive thoughts and behaviors and showed nearly immediate and sustained improvement in depression and anxiety over six months.  Larger studies are needed to confirm these early results.

Clinical Trials

A clinical trial is enrolling in Seoul, Korea. For more information, contact Eun Jung, Kweon at +82-2-2227-4578 or

Notable Papers

Jung HH, Kim SJ, Roh D, Chang JG, Chang WS, Kweon EJ, Kim CH, Chang JW. Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mol Psychiatry. 2015 Oct;20(10):1205-11. doi: 10.1038/mp.2014.154.

Jung HH, Chang WS, Rachmilevitch I, Tlusty T, Zadicario E, Chang JW. Different magnetic resonance imaging patterns after transcranial magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus of the thalamus and anterior limb of the internal capsule in patients with essential tremor or obsessive-compulsive disorder. J Neurosurg. 2015 Jan;122(1):162-8. doi: 10.3171/2014.8.JNS132603.

Bauer R, Martin E, Haegele-Link S, Kaegi G, von Specht M, Werner B. Noninvasive functional neurosurgery using transcranial MR imaging-guided focused ultrasound. Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S197-9. doi: 10.1016/S1353-8020(13)70046-4.

Martin E, Jeanmonod D, Morel A, Zadicario E, Werner B: High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol 66:858–861, 2009

Cohen ZR, Zaubermann J, Harnof S, Mardor Y, Nass D, Zadicario E, et al.: Magnetic resonance imaging-guided focused ultrasound for thermal ablation in the brain: a feasibility study in a swine model. Neurosurgery 60:593–600, 2007

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