Delayed-maturation theory of obsessive–compulsive disorder

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The delayed-maturation theory of obsessive–compulsive disorder suggests that obsessive–compulsive disorder (OCD) can be caused by delayed maturation of the frontal striatal circuitry or parts of the brain that make up the frontal cortex, striatum, or integrating circuits. [1] Some researchers suspect that variations in the volume of specific brain structures can be observed in children that have OCD (Lambert, K.G; Kinsley, C.H., 2011). [1] It has not been determined if delayed-maturation of this frontal circuitry contributes to the development of OCD or if OCD is the ailment that inhibits normal growth of structures in the frontal striatal, frontal cortex, or striatum. However, the use of neuroimaging has equipped researchers with evidence of some brain structures that are consistently less adequate and less matured in patients diagnosed with OCD in comparison to brains without OCD. More specifically, structures such as the caudate nucleus, volumes of gray matter, white matter, and the cingulate have been identified as being less developed in people with OCD in comparison to individuals that do not have OCD (Lambert, K.G.; Kinsley, C.H.). [1] However, the cortex volume of the operculum (brain) is larger and OCD patients are also reported to have larger temporal lobe volumes; which has been identified in some women patients with OCD (Jenike, M.; Breiter, H.; at el, 1996). [2] Further research is needed to determine the effect of these structural size differences on the onset and degree of OCD and the maturation of specific brain structures.

Contents

History

Origins of obsessive-compulsive disorder

The first record of obsessive-compulsive disorder dates back to the 14th century in Europe. It was believed that people who had OCD were possessed by the devil, and treatment included a series of performed exorcisms. In the 1910s, Sigmund Freud, a neurologist from Austria described Obsessive Compulsive Disorder to a case of touching phobia. [3] This phobia is said to start in early childhood and happens when a person has a strong desire to touch. [2] However, the opposite can also develop where the person develops what is called external prohibition. This happens when someone has the fear of a form of touching sensation. There are some circumstances where this disorder can be delayed. The earliest signs of OCD can start showing up in as little as six months. The brain becomes even more hyperactive around 54 months, and it is easier to notice obsessive-compulsive behavior at this time. Although there is no exact date as to when OCD begins to develop in later stages of life; different environments or events in a person's life can quickly become the catalyst to the development of this disorder.

Origins of obsessive-compulsive disorder and neuroimaging

Research for psychiatric neuroimaging began in 1994 at Massachusetts General Hospital, in Boston, by Dr. Scott Rauch. The group was developed into an entire program in 2003. [4] They discovered close collaborations between several other different disorders and the brain stem. Since the research first began, there has been a significant amount of development in regards to OCD. Studies done, via neuroimaging, show that the pathophysiology of obsessive-compulsive disorder involve abnormal functioning along specific frontal-sub-cortical brain circuits. [5]

The use of fMRI imaging to predict and follow individual's responses is a new approach. The goal is to be able to increase the understanding of the neurology of OCD. [6] This specific study focuses on OCD patients with different refractory time. The timeline for the type of scan is a total of about three and a half months. These individuals undergo fMRI scanning one day prior to starting treatment, plus an additional four days following the treatment. [7]

The results of this test show the baseline brain pattern compared to the first scan they took. The first scan provides data about the activation in the frontal-striatal neural circuit, which is the area involving OCD. The difference in the brain patterns depict information regarding biological mechanisms, which underlie heterogeneity in OCD. [8]

Over time, this fMRI testing is indicated to lead to a more accurate diagnosis of the illness as well as a better understanding of the symptoms. With the knowledge of the red-flag indicators for OCD, children with the disease may be able to detect it more efficiently early on in life. The fMRI, neuroimaging technique, is the most preferable way to scan today due to accuracy. A fMRI does not expose an individual to radiation and is a safe option in most cases. [9] The combination of innovative psychopharmacology with neuroimaging technology has the potential to result in a dominant and comprehensive approach for individuals with OCD.

Supporting experiments

Van de Heuval et al, 2009

The primary suggestion for the delayed-maturation theory of OCD was conducted in the Netherlands and inspired by the research of Van de Heuvel. [10] In this study, researchers used 55 non-medicated patients with OCD and 50 age matched controls to study the relationship between symptom dimensions and specific neuroanatomical structures. It was concluded that the "specific neuroanatomical structures are associated with specific symptom dimensions". [1] The symptoms of obsessive-compulsive behavior are associated with specific regions within the brain, and patients with similar symptoms are likely to have similar regions of the brain that are comprised due to OCD. [11] [12]

Rosenberg and Keshavan, 1998

Another experiment, supporting delayed-maturation theory of obsessive compulsive disorder, was conducted by Rosenberg and Keshavan in 1998. [13] This research used voxel-based morphometry to investigate the development of the cingulate structure in a group children's brains, ranging 2–7 in age, observed to be OCD. [14] This technique enabled researchers to identify a correlation between age and cingulate volume by comparing a group of control patients to a group of children that have been diagnosed with OCD. Children that do not have OCD were found to demonstrate a correlation between age and cingulate volume growth, whereas, children exhibiting traits of OCD did not display a significant correlation between age and cingulate volume. The Rosenberg and Keshavan experiment concluded that OCD patients do not exhibit a correlation of age and cingulate volume comparable to the control group of patients that did not have OCD. [15] [16]

Lisa A. Snider, M.D. and Susan E. Swedo, M.D., 2003

Childhood-Onset Obsessive-Compulsive Disorder and Tic Disorders was another experiment that supported the delayed-maturation theory regarding OCD. It was conducted by Snider and Swedo in 2003. [17] Research included the diagnosis of pediatric autoimmune neuropsychiatric disorder, associated with streptococcal infection, also known as PANDAS. [18] Thus, requiring a prospectively determined association between group A beta-hemolytic streptococcal infection, GABHS, and obsessive-compulsive disorder or tic disorder. Screening for a GABHS infection imposes a significant burden on both patient and clinician. To heighten the index of suspicion for PANDAS, it would be useful to know if parent-reported upper respiratory infection, URI, is associated with PANDAS symptoms or associated characteristics. Eighty-three consecutive, clinically referred patients aged 6 to 17 years with a primary diagnosis of OCD and their primary caregivers were asked about. URI signs and symptoms at the time of OCD onset, PANDAS symptoms, OCD and tic symptoms, comorbidity, and putative PANDAS risk factors. Specific inquiry regarding URI symptoms proved more informative than general inquiry. In the URI present versus URI absent group, more patients experienced a sudden rather than insidious onset of symptoms. Additionally, more patients with a URI plus sudden onset exhibited a comorbid tic disorder. [19] [20]

Neuroimaging indications

The use of neuroimaging has made it possible for researchers to monitor and compare structural and functional differences of brains exhibiting OCD symptoms in comparison to brains that do not have OCD and to measure specific structure's neural activity. The MRI scanning techniques have identified smaller levels of white matter volume in women with OCD in comparison to control patients that do not have OCD.[ citation needed ] The use of positron emission tomographic scan, better known as the PET scan, has enabled researchers to observe structures of the OFC, anterior cingular cortex, and the striatum for evidence of abnormal neural activity.[ citation needed ] In relationship to delayed-maturation theory of obsessive compulsive disorder, PET scans have consistently observed the caudate nucleus, cingulate volume, and volumes of both gray matter and white matter to be less consistent in patients with OCD in comparison to patients that do not have OCD.[ citation needed ] In brief, the use of neuroimaging supports delayed-maturation theory of obsessive compulsive disorder by providing researchers with concrete proof of decreased neural activity in patients with OCD in comparison to age-related patients, specifically children, without OCD.[ citation needed ]

Treatment For OCD

Cognitive behavioral therapy

Cognitive behavioral therapy, which involves exposure and response prevention (ERP), is the psychosocial treatment of choice for obsessive‐compulsive disorder.[ citation needed ] Despite this, ERP is not widely used by mental health practitioners. ERP means a person would repeatedly approach or is "exposed to" the very thing/object that makes that individual anxious or uncomfortable. Afterwards, the individual would attempt to stop oneself from engaging in behaviors that are designed to lower that anxiety. Cognitive behavioral therapy, CBT, in contrast to traditional psychotherapy or "talk" therapy, is shorter in duration and focuses not so much on early life experiences or unconscious processes, but rather on "here and now" problems, and on the education and coaching of clients as they learn new ways of thinking and behaving in order to solve those problems. OCD or anxiety-producing intrusive thoughts or images, are normally followed by compulsions, or by behaviors that the individual does on purpose to lower anxiety. This is displayed by the forming thoughts such as "that thing is dirty or contaminated". Thereafter, the compulsion would be to avoid touching that certain object or thing, and it can also lead to excessive washing if the individual has touched it. The role ERP has in this matter would be to purposely have the individual touch "contaminated" things on purpose and have exposure to it. During ERP, with repeated "exposure trials", the person then "learns" to let go of the fear through a process called desensitization. In hopes of exposing the individual repeatedly to feared thoughts, things or situations over and over, it would become less of a bother or fear and essentially the individual would get accustomed to it. As this process is initially a scary process to OCD patients, they are either exposed gradually or quickly, in order to be able to handle their obsessive-compulsive behaviors allowing them to feel control of it.[ citation needed ]

Serotonin reuptake inhibitors

Drug treatment of OCD may be assumed to affect a proposed functional imbalance between the frontal lobes and other parts of the brain. Serotonin reuptake inhibitors, SRI, especially potent ones given at high doses over long periods of time, are often effective in the treatment of obsessive-compulsive disorder. However, a large percentage of patients do not respond to treatment with the SRI, and those who do respond often do not fully remit, which should be the standard goal of treatment in OCD. If a patient has been treated for several months and has not yet responded to treatment with several types of SRI medication, the physician should perform a careful assessment of resistant and/or residual clinical symptoms. Any comorbid conditions to determine which next-step treatment would be the most appropriate. One strategy for patients who have not responded to treatment with a SRI is to switch them to aserotonin-norepinephrine reuptake inhibitors.[ citation needed ]

Gamma ray surgery

The Gamma Ray surgery was developed from the knife experiment. It is a form of brain surgery that uses radiation to destroy spots of tissue in the brain, while giving significant relief to some people with disabling obsessive-compulsive disorder. The gamma knife directs more than 200 thin beams of gamma radiation at different angles toward a single point in a person's brain. While each beam delivers a trivial amount of radiation, the spot where they converge receives enough energy to destroy that tissue, making the gamma knife a precision tool for attacking small tumors, malformed blood vessels, and other brain disorders without opening the skull. Unfortunately, the surgical team with the most experience performing this technique has called a temporary halt to it until long-term side effects that have appeared recently can be studied.[ citation needed ]

Related Research Articles

Bilateral cingulotomy is a form of psychosurgery, introduced in 1948 as an alternative to lobotomy. Today, it is mainly used in the treatment of depression and obsessive-compulsive disorder. In the early years of the twenty-first century, it was used in Russia to treat addiction. It is also used in the treatment of chronic pain. The objective of this procedure is the severing of the supracallosal fibres of the cingulum bundle, which pass through the anterior cingulate gyrus.

<span class="mw-page-title-main">Tourette syndrome</span> Neurodevelopmental disorder involving motor and vocal tics

Tourette syndrome or Tourette's syndrome is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) tic. Common tics are blinking, coughing, throat clearing, sniffing, and facial movements. These are typically preceded by an unwanted urge or sensation in the affected muscles known as a premonitory urge, can sometimes be suppressed temporarily, and characteristically change in location, strength, and frequency. Tourette's is at the more severe end of a spectrum of tic disorders. The tics often go unnoticed by casual observers.

<span class="mw-page-title-main">Trichotillomania</span> Medical condition

Trichotillomania (TTM), also known as hair-pulling disorder or compulsive hair pulling, is a mental disorder characterized by a long-term urge that results in the pulling out of one's own hair. A brief positive feeling may occur as hair is removed. Efforts to stop pulling hair typically fail. Hair removal may occur anywhere; however, the head and around the eyes are most common. The hair pulling is to such a degree that it results in distress and hair loss can be seen.

<span class="mw-page-title-main">Obsessive–compulsive personality disorder</span> Personality disorder involving orderliness

Obsessive–compulsive personality disorder (OCPD) is a cluster C personality disorder marked by a spectrum of obsessions with rules, lists, schedules, and order, among other things. Symptoms are usually present by the time a person reaches adulthood, and are visible in a variety of situations. The cause of OCPD is thought to involve a combination of genetic and environmental factors, namely problems with attachment.

<span class="mw-page-title-main">Anterior cingulate cortex</span> Brain region

In the human brain, the anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex that resembles a "collar" surrounding the frontal part of the corpus callosum. It consists of Brodmann areas 24, 32, and 33.

<span class="mw-page-title-main">Caudate nucleus</span> Structure of the striatum in the basal ganglia of the brain

The caudate nucleus is one of the structures that make up the corpus striatum, which is a component of the basal ganglia in the human brain. While the caudate nucleus has long been associated with motor processes due to its role in Parkinson's disease, it plays important roles in various other nonmotor functions as well, including procedural learning, associative learning and inhibitory control of action, among other functions. The caudate is also one of the brain structures which compose the reward system and functions as part of the cortico–basal ganglia–thalamic loop.

<span class="mw-page-title-main">PANDAS</span> Hypothesis in pediatric medicine

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a controversial hypothetical diagnosis for a subset of children with rapid onset of obsessive-compulsive disorder (OCD) or tic disorders. Symptoms are proposed to be caused by group A streptococcal (GAS), and more specifically, group A beta-hemolytic streptococcal (GABHS) infections. OCD and tic disorders are hypothesized to arise in a subset of children as a result of a post-streptococcal autoimmune process. The proposed link between infection and these disorders is that an autoimmune reaction to infection produces antibodies that interfere with basal ganglia function, causing symptom exacerbations, and this autoimmune response results in a broad range of neuropsychiatric symptoms.

<span class="mw-page-title-main">Orbitofrontal cortex</span> Region of the prefrontal cortex of the brain

The orbitofrontal cortex (OFC) is a prefrontal cortex region in the frontal lobes of the brain which is involved in the cognitive process of decision-making. In non-human primates it consists of the association cortex areas Brodmann area 11, 12 and 13; in humans it consists of Brodmann area 10, 11 and 47.

<span class="mw-page-title-main">Intrusive thought</span> Unwelcome involuntary thought, image or idea

An intrusive thought is an unwelcome, involuntary thought, image, or unpleasant idea that may become an obsession, is upsetting or distressing, and can feel difficult to manage or eliminate. When such thoughts are associated with obsessive-compulsive disorder (OCD), Tourette's syndrome (TS), depression, body dysmorphic disorder (BDD), and sometimes attention-deficit hyperactivity disorder (ADHD), the thoughts may become paralyzing, anxiety-provoking, or persistent. Intrusive thoughts may also be associated with episodic memory, unwanted worries or memories from OCD, post-traumatic stress disorder, other anxiety disorders, eating disorders, or psychosis. Intrusive thoughts, urges, and images are of inappropriate things at inappropriate times, and generally have aggressive, sexual, or blasphemous themes.

The obsessive–compulsive spectrum is a model of medical classification where various psychiatric, neurological and/or medical conditions are described as existing on a spectrum of conditions related to obsessive–compulsive disorder (OCD). "The disorders are thought to lie on a spectrum from impulsive to compulsive where impulsivity is said to persist due to deficits in the ability to inhibit repetitive behavior with known negative consequences, while compulsivity persists as a consequence of deficits in recognizing completion of tasks." OCD is a mental disorder characterized by obsessions and/or compulsions. An obsession is defined as "a recurring thought, image, or urge that the individual cannot control". Compulsion can be described as a "ritualistic behavior that the person feels compelled to perform". The model suggests that many conditions overlap with OCD in symptomatic profile, demographics, family history, neurobiology, comorbidity, clinical course and response to various pharmacotherapies. Conditions described as being on the spectrum are sometimes referred to as obsessive–compulsive spectrum disorders.

Exposure therapy is a technique in behavior therapy to treat anxiety disorders.

Primarily obsessional obsessive–compulsive disorder, also known as purely obsessional obsessive–compulsive disorder, is a lesser-known form or manifestation of OCD. It is not a diagnosis in the DSM-5. For people with primarily obsessional OCD, there are fewer observable compulsions, compared to those commonly seen with the typical form of OCD. While ritualizing and neutralizing behaviors do take place, they are mostly cognitive in nature, involving mental avoidance and excessive rumination. Primarily obsessional OCD takes the form of intrusive thoughts often of a distressing, sexual, or violent nature.

<span class="mw-page-title-main">Obsessive–compulsive disorder</span> Mental and behavioral disorder

Obsessive–compulsive disorder (OCD) is a mental and behavioral disorder in which an individual has intrusive thoughts and feels the need to perform certain routines (compulsions) repeatedly to relieve the distress caused by the obsession, to the extent where it impairs general function.

Susan Swedo is a researcher in the field of pediatrics and neuropsychiatry. Beginning in 1998, she was Chief of the Pediatrics & Developmental Neuroscience Branch at the US National Institute of Mental Health. In 1994, Swedo was lead author on a paper describing pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a controversial hypothesis proposing a link between Group A streptococcal infection in children and some rapid-onset cases of obsessive-compulsive disorder (OCD) or tic disorders such as Tourette syndrome. Swedo retired from the NIH in 2019, and serves on the PANDAS Physician Network.

The biology of obsessive–compulsive disorder (OCD) refers biologically based theories about the mechanism of OCD. Cognitive models generally fall into the category of executive dysfunction or modulatory control. Neuroanatomically, functional and structural neuroimaging studies implicate the prefrontal cortex (PFC), basal ganglia (BG), insula, and posterior cingulate cortex (PCC). Genetic and neurochemical studies implicate glutamate and monoamine neurotransmitters, especially serotonin and dopamine.

The cause of obsessive–compulsive disorder is understood mainly through identifying biological risk factors that lead to obsessive–compulsive disorder (OCD) symptomology. The leading hypotheses propose the involvement of the orbitofrontal cortex, basal ganglia, and/or the limbic system, with discoveries being made in the fields of neuroanatomy, neurochemistry, neuroimmunology, neurogenetics, and neuroethology.

In psychology, relationship obsessive–compulsive disorder (ROCD) is a form of obsessive–compulsive disorder focusing on close or intimate relationships. Such obsessions can become extremely distressing and debilitating, having negative impacts on relationships functioning.

<span class="mw-page-title-main">Wayne Goodman</span> American psychiatrist and researcher

Wayne Goodman is an American psychiatrist and researcher who specializes in Obsessive-Compulsive Disorder (OCD). He is the principal developer, along with his colleagues, of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

<span class="mw-page-title-main">Jonathan Abramowitz</span> American clinical psychologist

Jonathan Stuart Abramowitz is an American clinical psychologist and Professor in the Department of Psychology and Neuroscience at the University of North Carolina at Chapel Hill (UNC-CH). He is an expert on obsessive-compulsive disorder (OCD) and anxiety disorders whose work is highly cited. He maintains a research lab and currently serves as the Director of the UNC-CH Clinical Psychology PhD Program. Abramowitz approaches the understanding and treatment of psychological problems from a cognitive-behavioral perspective.

<span class="mw-page-title-main">Carolyn I. Rodriguez</span> Puerto Rican psychiatrist

Carolyn I. Rodriguez is a Puerto Rican psychiatrist, neuroscientist, and clinical researcher developing treatments for obsessive compulsive disorder as well as mapping circuit dysfunction in the human brain. Rodriguez holds appointments in both clinical and academic departments at Stanford University. Rodriguez is a Clinical Lab Director at the Stanford Center for Cognitive and Neurobiological Imaging, an associate professor and Associate Chair of Psychiatry and Behavioral Sciences, and a Director of several specialized translational research programs.

References

  1. 1 2 3 4 Lambert, K.G.; Kinsley, C.H. (2011); Clinical Neuroscience: Psychopathoogy and the Brain, Oxford University Press, New York,2 ed., PG 229.
  2. 1 2 Jenike, M.A.; Breiter, H.C.; Baer, L.; Kennedy, D.N.; Savage, C.R.; Olivares, M.J.; et al. (1996). "Cerebral structural abnormalities in obsessive-compulsive disorder". Archives of General Psychiatry. 53 (7): 625–632. doi:10.1001/archpsyc.1996.01830070073011. PMID   8660129.
  3. ↑ [5]
  4. ↑ Ashburner, J.; Friston, K.J. (2000). "Voxel-based morphometry-the methods". NeuroImage. 11 (6): 805–8211. CiteSeerX   10.1.1.114.9512 . doi:10.1006/nimg.2000.0582. PMID   10860804. S2CID   16777465.
  5. ↑ Luxenberg, J.S.; Swedo, S.E.; Flamant, M.F.; Friedland, R.P.; Rapport, S.I. (1988). "Neuroanatomical abnormalities in obsessive-compulsive disorder detected with quantitative x-ray computed tomography". American Journal of Psychiatry. 145 (9): 1089–1093. doi:10.1176/ajp.145.9.1089. PMID   3414851.
  6. ↑ Jenike, M.A.; Rauch, S.L.; Cummings, J.L.; Savage, C.R.; Goodman, W.K. (1996). "Recent developments in neurobiology of obsessive-compulsive disorder". Journal of Clinical Psychiatry. 57 (10): 492–503. doi:10.4088/jcp.v57n1009. PMID   8909341.
  7. ↑ Mindus, P; Rasmussen, SA; Lindquist, C (1994). "Neurosurgical treatment for refractory obsessive-compulsive disorder: implications for understanding frontal lobe function". Journal of Neuropsychiatry and Clinical Neurosciences. 6 (4): 467–77. doi:10.1176/jnp.6.4.467. PMID   7841817.
  8. ↑ "Sigmund Freud".
  9. ↑ "Home". ocdhistory.net.
  10. ↑ McLaughlin, KA; Fox, NA; Zeanah, CH; Sheridan, MA; Marshall, P; Nelson, CA (2010). "Delayed maturation in brain electrical activity partially explains the association between early environmental deprivation and symptoms of attention-deficit/hyperactivity disorder". Biol. Psychiatry. 68 (4): 329–36. doi:10.1016/j.biopsych.2010.04.005. PMC   3010237 . PMID   20497899.
  11. ↑ "Cortical Surface Area Maturation Delayed in ADHD - (ADHD) Attention Deficit Hyperactivity Disorder Cause, Diagnosis, History". Archived from the original on 2013-04-11. Retrieved 2013-04-06.
  12. ↑ Pallanti, S; Hollander, E; Goodman, WK (2004). "A qualitative analysis of nonresponse: management of treatment-refractory obsessive-compulsive disorder". J Clin Psychiatry. 65 Suppl 14: 6–10. PMID   15554782.
  13. ↑ Valeo, T., (April 18, 2011), Experimental Radiation Treatment for OCD Hits a Snag, The DANA Foundation. http://www.dana.org/news/features/detail.aspx?id=31716. retrieved April 2, 2013.
  14. ↑ "Treat Obsessive Compulsive Disorder With Cognitive Behavioral Therapy". ABC News. Retrieved 2023-06-22.
  15. ↑ Snider, L.A, Swedo, S.E., (2003), Childhood-Onset Obsessive-Compulsive Disorder and Tic Disorders: Case Report and Literature Review, Journal of Child and Adolescent Psychopharmacology,13,1, pp. S81-S88. http://intramural.nimh.nih.gov/pdn/pubs/pub-1.pdf
  16. ↑ Swedo, S.E.; Pietrini, P.; Leonard, H.L.; Schapiro, M.B.; Rettew, D.C.; Goldberger, E.L.; et al. (1992). "Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmoacotheraphy". Archives of General Psychiatry. 49 (9): 690–694. doi:10.1001/archpsyc.1992.01820090018003. PMID   1514873.
  17. ↑ Saxena, S; Brody, AL; Schwartz, JM; Baxter, LR (1998). "Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder". Br J Psychiatry Suppl. 173 (35): 26–37. doi:10.1192/S0007125000297870. PMID   9829024. S2CID   24708540.
  18. ↑ Snider, L.A; Swedo, S.E. (2003). "Childhood-Onset Obsessive-Compulsive Disorder and Tic Disorders: Case Report and Literature Review" (PDF). Journal of Child and Adolescent Psychopharmacology. 13 (1): S81–S88. doi:10.1089/104454603322126377. PMID   12880503.
  19. ↑ Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. http://www.massgeneral.org/psychiatry/research/neuroimaging_history.aspx
  20. ↑ Obsessive-Compulsive Disorder Research http://www.lpch.org/clinicalSpecialtiesServices/COE/BrainBehavior/Psychiatry/ocdResearch.html
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