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Several lines of evidence support a neurobiological model of OCD (Saxena and Rauch, 2000; Nakao et al., 2014; Burguière et al., 2015) that includes abnormalities in a neural loop connecting the basal ganglia (caudate and globus pallidus), frontal lobe (particularly orbitofrontal cortex), thalamus, and anterior cingulate cortex (Figure 1). First, computerized tomography (CT) scans of the brains of patients with OCD show significant differences in the caudate, an area that normally helps to sequence and elaborate behaviors. Abnormal function of the caudate might produce OCD symptoms such as stereotyped behavior and perseveration (the inability to turn one’s attention to new situations). Further, the repetitive, aimless, and stereotypical behaviors observed in animals following amphetamine and cocaine administration provide empirical support for the importance of dopamine in the caudate–putamen (see Chapter 12).
Figure 1 The neural network involved in OCD. The network includes the caudate (part of the basal ganglia), which lies under the cerebral cortex but has rich connections to the frontal lobe and the cingulate cortex as well as to the subcortical thalamus.
Second, PET, single-photon emission computerized tomography (SPECT), and fMRI studies show distinct patterns of glucose metabolism in the basal ganglia, dorsomedial thalamus, and frontal lobes (prefrontal, orbitofrontal, and anterior cingulate) of patients with OCD during symptom provocation (i.e., presenting patients with their feared stimuli). Successful treatment with behavior therapy and pharmacological treatment reduces the hyperactivity of these regions. Since frontal lobes modulate functions such as planning, regulating, controlling, and evaluating behaviors, it seems plausible that dysfunction might be responsible for reduced response inhibition and inflexible behavior. Increased neural activity of the anterior cingulate cortex also has been linked to compulsive behavior.
Third, pharmacotherapy with an SSRI or cognitive behavior therapy that significantly decreases symptoms also decreases regional cerebral metabolism or blood flow. Those areas with the greatest change once again include the caudate, anterior cingulate, orbitofrontal cortex, and thalamus (Figure 2). A total of 8 to 12 weeks of treatment with the SSRI paroxetine decreased striatal metabolism in patients with OCD who showed symptom reduction of more than 25% compared with those who showed no improvement. In contrast, patients effectively treated for both OCD and major depression showed an increase in striatal activity compared with nonresponders. These results suggest that SSRIs produce brain metabolic responses that are specific to both the disorder and the therapeutic response (Saxena et al., 2002). The SSRIs may be effective for OCD because they enhance the activity of the serotonergic neurons of the raphe nuclei, and this interrupts the neural loop by inhibiting cell firing in the caudate.
Figure 2 PET scans of the brains of patients with OCD. The scans show hyperactivity in the head of the caudate. Both SSRI treatment (bottom left) and cognitive therapy (bottom right) reduce the hyperactivity in the caudate compared with pretreatment levels (top left and right). Arrows indicate the “head of the caudate”. (From Baxter et al., 1992.)
The most compelling evidence for the overactive circuit model comes from neurosurgical procedures. Neurosurgery that destroys the anterior cingulate (Figure 3) or severs the connection between the frontal cortex and subcortical areas, including the basal ganglia and the thalamus, is successful in relieving symptoms in 50% to 70% of cases (Mindus et al., 1994). It appears that interrupting the circuitry at any one of several points may relieve symptoms of OCD. These results demonstrate the importance of considering the functional interaction of multiple brain areas when looking for the biological basis of any psychiatric disorder. Understanding the neural network associated with behavior also means that psychopharmacology can be used to target the symptoms at multiple sites by modulating the synaptic connections.
Figure 3 Magnetic resonance image (MRI) of the brain of a patient with OCD. The patient had neurosurgery to disrupt the neural connections of the cingulate cortex (see arrows) from the frontal cortex, basal ganglia, and thalamus. (From Martuza et al., 1990; courtesy of Robert L. Martuza.)
References
Baxter, L. R., Jr., Schwartz, J. M., Bergman, K. S., Szuba, M. P., Guze, B. H., Mazziotta, J. C., et al. (1992). Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch. Gen. Psychiatry, 49(9), 681–689.
Burguière, E., Monteiro, P., Mallet, L., Feng, G., and Graybiel, A. M. (2015). Striatal circuits, habits, and implications for obsessive-compulsive disorder. Curr. Opin. Neurobiol., 30, 59–65.
Martuza, R. L., Chiocca, E. A., Jenike, M. A., Giriunas, I. E., and Ballantine, H. T. (1990). Stereotactic radiofrequency thermal cingulotomy for obsessive compulsive disorder. J. Neuropsychiatry Clin. Neurosci., 2, 331–336.
Mindus, P., Rasmussen, S. A., and Lindquist, C. (1994). Neurosurgical treatment for refractory obsessive-compulsive disorder: Implications for understanding frontal lobe function. J. Neuropsychiatry, 6, 467–477.
Nakao, T., Okada, K., and Kanba, S. (2014). Neurobiological model of obsessive-compulsive disorder: Evidence from recent neuropsychological and neuroimaging findings. Psychiatr. Clin. Neurosci., 68, 587–605.
Saxena, S., Brody, A. L., Ho, M. L., Alborzian, S., Maidment, K. M., Zohrabi, N., et al. (2002). Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs. major depression. Arch. Gen. Psychiatry, 59, 250–261.
Saxena, S., and Rauch, S. L. (2000). Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr. Clin. North Am., 23, 563–586.