Pathophysiology of Obsessive-Compulsive Disorder: Insights from Normal Function and Neurotoxic Effects of Drugs, Infection, and Brain Injury

The clinical presentation of obsessive–compulsive disorder (OCD) is summarized and a theoretical model of the disorder and its neurobiology are described. The model is used as a framework to account for the observed pattern of clinical symptoms, for the pathophysiology of OCD, and for medical reports of OCD-like symptoms from neurotoxic effects of drugs, brain injury, and infection. The essential clinical feature of OCD is preoccupation with ideas and behaviors called “obsessions” and “compulsions,” respectively. The characteristic content of obsessions and compulsions is concern about dangers that might happen in the future – as opposed to actual threats that are direct and immediate. Hence, OCD is a clinical preoccupation with potential threats. A model is considered where normal concerns regarding potential danger and security are handled by a biologically ancient hard-wired motivational system, called security motivation system (SMS), which has as its output the same repertoire of precautionary behaviors that characterize OCD compulsions. In the model, OCD symptoms emerge because security motivation is normally deactivated by a negative feedback signal generated by performance of precautionary behaviors, but in patients with OCD, this signal is inoperative, resulting in continued motivation to perform security-related behaviors. The neurobiology of SMS consists of functional loops involving a cascade of cortico-striato-pallido-thalamo-cortical connections, with inhibitory connections from the brainstem. Accordingly, OCD pathophysiology is overly persistent and uncontrolled neural activity in SMS, possibly due to a dopamine–serotonin imbalance. Evidence of OCD symptoms from drugs, brain injury, and infection is consistent with disturbed basal ganglia regulation as the pathophysiology of OCD.