Neuroimaging Some parts of the brain showing abnormal activity in OCD Functional neuroimaging during symptom provocation has observed abnormal activity in the orbitofrontal cortex, left dorsolateral prefrontal cortex, right premotor cortex, left superior temporal gyrus, globus pallidus externus, hippocampus and right uncus. Weaker foci of abnormal activity were found in the left caudate, posterior cingulate cortex and superior parietal lobule. However, an older meta-analysis of functional neuroimaging in OCD reported that the only consistent functional neuroimaging finding was increased activity in the orbital gyrus and head of the caudate nucleus, while ACC activation abnormalities were too inconsistent. A meta-analysis comparing affective and nonaffective tasks observed differences with controls in regions implicated in salience, habit, goal-directed behavior, self-referential thinking and cognitive control. For nonaffective tasks, hyperactivity was observed in the insula, ACC, and head of the caudate/putamen, while hypoactivity was observed in the medial prefrontal cortex (mPFC) and posterior caudate. Affective tasks were observed to relate to increased activation in the precuneus and posterior cingulate cortex (PCC), while decreased activation was found in the pallidum, ventral anterior thalamus and posterior caudate. The involvement of the cortico-striato-thalamo-cortical loop in OCD as well as the high rates of comorbidity between OCD and ADHD have led some to draw a link in their mechanism. Observed similarities include dysfunction of the anterior cingulate cortex and prefrontal cortex, as well as shared deficits in executive functions. The involvement of the orbitofrontal cortex and dorsolateral prefrontal cortex in OCD is shared with bipolar disorder and may explain the high degree of comorbidity. Decreased volumes of the dorsolateral prefrontal cortex related to executive function has also been observed in OCD. People with OCD evince increased grey matter volumes in bilateral lenticular nuclei, extending to the caudate nuclei, with decreased grey matter volumes in bilateral dorsal medial frontal/anterior cingulate gyri. These findings contrast with those in people with other anxiety disorders, who evince decreased (rather than increased) grey matter volumes in bilateral lenticular/caudate nuclei, as well as decreased grey matter volumes in bilateral dorsal medial frontal/anterior cingulate gyri. Increased white matter volume and decreased fractional anisotropy in anterior midline tracts has been observed in OCD, possibly indicating increased fiber crossings. Cognitive models Generally two categories of models for OCD have been postulated, the first involving deficits in executive function, and the second involving deficits in modulatory control. The first category of executive dysfunction is based on the observed structural and functional abnormalities in the dlPFC, striatum and thalamus. The second category involving dysfunctional modulatory control primarily relies on observed functional and structural differences in the ACC, mPFC and OFC. One proposed model suggests that dysfunction in the OFC leads to improper valuation of behaviors and decreased behavioral control, while the observed alterations in amygdala activations leads to exaggerated fears and representations of negative stimuli. Because of the heterogeneity of OCD symptoms, studies differentiating various symptoms have been performed. Symptom-specific neuroimaging abnormalities include the hyperactivity of caudate and ACC in checking rituals, while finding increased activity of cortical and cerebellar regions in contamination-related symptoms. Neuroimaging differentiating content of intrusive thoughts has found differences between aggressive as opposed to taboo thoughts, finding increased connectivity of the amygdala, ventral striatum and ventromedial prefrontal cortex in aggressive symptoms while observing increased connectivity between the ventral striatum and insula in sexual/religious intrusive thoughts. Another model proposes that affective dysregulation links excessive reliance on habit-based action selection with compulsions. This is supported by the observation that those with OCD demonstrate decreased activation of the ventral striatum when anticipating monetary reward, as well as increased functional connectivity between the VS and the OFC. Furthermore, those with OCD demonstrate reduced performance in Pavlovian fear-extinction tasks, hyperresponsiveness in the amygdala to fearful stimuli, and hyporesponsiveness in the amygdala when exposed to positively valanced stimuli. Stimulation of the nucleus accumbens has also been observed to effectively alleviate both obsessions and compulsions, supporting the role of affective dysregulation in generating both. Neurobiological From the observation of the efficacy of antidepressants in OCD, a serotonin hypothesis of OCD has been formulated. Studies of peripheral markers of serotonin, as well as challenges with proserotonergic compounds have yielded inconsistent results, including evidence pointing towards basal hyperactivity of serotonergic systems. Serotonin receptor and transporter binding studies have yielded conflicting results, including higher and lower serotonin receptor 5-HT2A and serotonin transporter binding potentials that were normalized by treatment with SSRIs. Despite inconsistencies in the types of abnormalities found, evidence points towards dysfunction of serotonergic systems in OCD. Orbitofrontal cortex overactivity is attenuated in people who have successfully responded to SSRI medication, a result believed to be caused by increased stimulation of serotonin receptors 5-HT2A and 5-HT2C. A complex relationship between dopamine and OCD has been observed. Although antipsychotics, which act by antagonizing dopamine receptors may improve some cases of OCD, they frequently exacerbate others. Antipsychotics, in the low doses used to treat OCD, may actually increase the release of dopamine in the prefrontal cortex, through inhibiting autoreceptors. Further complicating things is the efficacy of amphetamines, decreased dopamine transporter activity observed in OCD, and low levels of D2 binding in the striatum. Furthermore, increased dopamine release in the nucleus accumbens after deep brain stimulation correlates with improvement in symptoms, pointing to reduced dopamine release in the striatum playing a role in generating symptoms. Abnormalities in glutamatergic neurotransmission have implicated in OCD. Findings such as increased cerebrospinal glutamate, less consistent abnormalities observed in neuroimaging studies and the efficacy of some glutamatergic drugs such as the glutamate-inhibiting riluzole have implicated glutamate in OCD. OCD has been associated with reduced N-Acetylaspartic acid in the mPFC, which is thought to reflect neuron density or functionality, although the exact interpretation has not been established.
Obsessive–compulsive disorder
Obsessive–compulsive personality disorder
Conduct disorder
Major depressive disorder
Psychopathy
Anxiety disorder
Tourette syndrome
Eating disorder