Psychiatry 2008 - September 2008 - (Page 28)

FIGURE 2. Neural circuitry of MDD and DBS targets. Circuitry is divided into cortical and limbic compartments with links between amygdala, ACG, and HPA axis forming a modulatory circuit between the cortical and limbic compartments. DBS interventions for MDD target nodes within the limbic compartment. KEY: DBS: deep brain stimulation; MDD: major depressive disorder; HPA: hypothalamic-pituitary axis have been implicated in symptoms of OCD involving feedback loops between the cortex, striatum, and thalamus. A multicircuit hypothesis of OCD states that the primary pathogenic mechanism is a dysregulation of the basal ganglia and limbic striatal circuitry working in concert with portions of the orbitofrontal and anterior cingulate cortex. Simplified, one can postulate the following three components to this model (Figure 1):2 1. A positive feedback loop from the orbital and prefrontal cortex to the thalamus via the anterior limb of the internal capsule. This cortico-thalamic pathway is 28 Psychiatry 2008 [SEPTEMBER] excitatory and bidirectional. 2. A circuit linking the orbitofrontal cortex, caudate nucleus, globus pallidus, and the thalamus, known as the CSTC loop (cortexstriatum-thalamus-cortex). The overall output of this pathway is inhibitory and is thought to serve as a counterweight to the excitatory positive feedback loop as described in this article. This inhibitory pathway also receives serotonergic projections from the midbrain into the striatum. 3. A component linking portions of the limbic system, including the hippocampus, mammillary bodies and fornix, to the thalamus to the anterior cingulate cortex (ACC). These connections are hypothesized to contribute to the affective anxiety component of OCD symptoms. Bringing together these three components of the circuit, OCD symptoms occur when there is an abnormal positive feedback in the orbito-fronto-thalamic circuit (# 1) that is, in turn, inadequately inhibited or modulated by the CSTC loop (# 2). One would then expect OCD symptoms to appear when the CSTC loop is abnormally decreased (too little inhibition), or when orbitofronto-thalamic activity is abnormally increased (too much excitation).

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Psychiatry 2008 - September 2008 Editor’s Message Editorial Advisory Board Contents Psych Rx Letters to the Editor Use of Benzodiazepines in the Treatment of Anxiety Functional Neurosurgery in the Treatment of Severe Obsessive Compulsive Disorder and Major Depression: Overview of Disease Circuits and Therapeutic Targeting for the Clinician Treatment of Comorbid Adolescent Cannabis Use and Major Depressive Disorder Risperidone Long-acting Injections: Successful Alternative Deltoid Muscle Injections for Refractory Schizophrenia Alcohol/Substance Misuse and Treatment Nonadherence: Fatal Attraction Transforming the Psychiatric Inpatient Unit from Short-term Pseudo-asylum Care to State-of-the-art Treatment Setting Journal Watch Classified Advertising Information for Authors

Psychiatry 2008 - September 2008

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