Etiology
Obsessive-compulsive disorder (OCD) most likely results from a confluence of etiologies. Genetic factors are important, as monozygotic twins are much more likely to exhibit OCD symptoms than dizygotic twins.[11] First-degree relatives of patients with OCD have a higher risk of developing the disorder than the general population.[12] Evidence exists that the disorder is transmitted in an autosomal dominant fashion.[13][14][15][16] Candidate genes are related to the serotonin, dopamine, and glutamate neurotransmitter systems.[17] The OCD Collaborative Genetics Study aims to clarify the role that genetic factors have in the development of OCD.[18] A recent animal study has shown that deletion of genes for a glutamatergic postsynaptic scaffolding protein results in excessive grooming behavior in mice.[19]
Learning theories explain that, by temporarily reducing anxiety, compulsions are self-reinforcing.[17] Cognitive theory suggests that obsessions represent catastrophic misinterpretations of a person's thoughts, images, and impulses.[20][21][22] Several faulty cognitions in OCD have been described that are related to the overestimation of threat, intolerance of uncertainty, importance of thoughts, control of thoughts, and perfectionism.[23] In addition, there is an association between pregnancy and the development of obsessive-compulsive symptoms. In one study of 59 female patients with OCD, 39% of participants described an onset of OCD symptoms during pregnancy.[24] Rarely, striatal lesions or head trauma result in the development of OCD.[10][25]
Pathophysiology
The efficacy of selective serotonin-reuptake inhibitors (SSRIs) in the treatment of OCD suggests that serotonergic dysfunction has a role in the pathophysiology of OCD.[26] A low prolactin response to meta-chlorophenylpiperazine (m-CPP) serotonin stimulation has been implicated as a predictor of a poor response to treatment with SSRIs.[27] The dopamine and glutamate neurotransmitter systems have also been implicated.[17] Functional neuroimaging studies have shown a hypermetabolic brain circuit involving the orbital-frontal cortex, anterior cingulate, thalamus, and striatum.[17] Preliminary evidence suggests that activity of these areas is altered in both adults and children with OCD.[28] SSRIs and cognitive behavioral therapy (CBT) have been shown to result in a normalization of metabolic rate in this circuit.[29][30] Transcranial magnetic stimulation (TMS), a form of noninvasive brain stimulation (NIBS), uses magnetic fields to stimulate neurons in the brain, and enhance neuroplasticity, mostly targeting the presupplementary motor area, the dorsolateral prefrontal cortex, and the anterior cingulate.[31][32][33][34] Because TMS is an intervention that includes different patterns and locations of stimulation, treatment can be tailored to each individual’s underlying pathophysiology.
OCD is associated with low-grade inflammation, neural antibodies, and neuroinflammatory and autoimmune disorders.[25][35] In a subset of patients, OCD symptoms can be caused or exacerbated by an autoimmune reaction in which antibodies to beta-hemolytic streptococci cross-react with proteins in the basal ganglia; this phenomenon has been termed PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection).[36] More recently, another subset of patients was identified with a symptom complex similar to PANDAS but with evidence of infectious agents other than streptococcus, such as mycoplasma, mononucleosis, Lyme disease, and the H1N1 flu virus, and the term pediatric acute-onset neuropsychiatric syndrome (PANS) was introduced.[37]
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