Aetiology
Obsessive-compulsive disorder (OCD) most probably results from a confluence of aetiologies. 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 behaviour 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 behavioural therapy (CBT) have been shown to result in a normalisation of metabolic rate in this circuit.[29][30] Transcranial magnetic stimulation (TMS), a form of non-invasive brain stimulation (NIBS), uses magnetic fields to stimulate neurons in the brain, and enhance neuroplasticity, mostly targeting the pre-supplementary 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 neuro-inflammatory 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-haemolytic streptococci cross-react with proteins in the basal ganglia; this phenomenon has been termed PANDAS (paediatric 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 paediatric acute-onset neuropsychiatric syndrome (PANS) was introduced.[37]
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