Psychiatry 2008 - September 2008 - (Page 29)

From a therapeutic standpoint, increasing activity of the CSTC loop or decreasing activity of the orbitofronto-thalamic loop would be expected decreased symptoms of OCD. Lastly, decreasing activity in the limbic component of the circuit (# 3) would decrease the distressing negative affects associated with obsessions. MDD. MDD is a complex and heterogeneous disorder that is highly prevalent, recurrent, and disabling. It is a major cause of disability and functional impairment worldwide. A large proportion of sufferers, in the range of 20 to 40 percent, fail to benefit adequately from currently available treatments (e.g., antidepressants, psychotherapies, and electroconvulsive therapy), due to either a lack of efficacy or lack of tolerability of our current treatment options.13 The etiology of depression is complex and still only partially understood. Genetics, early environmental factors, and neurohormonal factors have all been implicated in the pathophysiology of depression. A neurological basis for depression has been posited based on certain disorders having a higher association with depression, as seen with left hemisphere strokes, certain types of epilepsy, Huntington’s disease, and numerous other neurodegenerative disorders and injuries to discrete brain regions. Recent evidence suggests that specific neuronal pathways are implicated in depression. It is hypothesized that depressive symptoms occur when these neural systems do not exhibit appropriate, adaptive plasticity in response to external stimuli such as stressors. The dysfunction of specific pathways that help promote neuronal plasticity might also contribute to the depressive symptomatology.14 Systems model of depression. Depression is not the result of dysfunction in a single brain region or of a single neurotransmitter system. It can instead be conceptualized as a systems-level disorder affecting discrete but functionally integrated pathways. The symptoms of depression are not simply the result of one or more of these pathways not functioning appropriately, but also a failure of the other components of the system to maintain homeostasis in times of increased stress to the organism.15 Circuitry. Neurobiological correlates of depressive illness can be grouped into the following three main components: cortical, subcortical, and limbic (Figure 2): 1. Cortical component. This component appears to give rise to the psychomotor and FIGURE 3. Sites of lesioning neurosurgical cognitive aspects of procedures for OCD and MDD. Limbic leucotomy depressive symptoms and combines the cingulotomy and subcaudate consists of the prefrontal tractotomy procedures. [Adapted from Lipsman N, cortex, the dorsal portion of Neimat JS, Lozano AM. Deep brain stimulation for the anterior cingulate gyrus, treatment-refractory obsessive-compulsive disorder: and areas of the premotor the search for a valid target. Neurosurgery cortex. This cortical 2007;61(1):1-11] component has access to the striatum and then creates a feedback loop via the thalamus. neuroendocrine aspects of 2. Subcortical component. This depressive symptoms. This component involves the affective “modulating pathway” involves the experiencing of depressive amygdala, pregenual anterior symptoms, including anhedonia cingulate cortex, and the and sadness. This aspect of the hypothalamic-pituitary-adrenal neural circuit includes, among axis. It is hypothesized that it others, the subgenual anterior mediates the cortical and limbic cingulate (Brodman’s area 25), circuits via inhibitory projections the orbitofrontal cortex, and limbic to these circuits.2 structures in the brain involved with negative emotions, including NEUROSURGICAL INTERVENTIONS the nucleus accumbens and IN OCD AND MDD amygdala. This component also Frontal leucotomy, the first interacts with the striatum and applied neurosurgical procedure for psychiatric symptoms, was a gross subsequently the thalamus to method of interrupting the white create a loop. Brain imaging research and functional blood flow matter tracts associated with the frontal cortex. Unfortunately, such studies (positron emission procedures were performed tomography [PET] and functional indiscriminately without careful magnetic resonance imaging patient selection and were associated [fMRI]) support depressive illness with serious neuropsychiatric involving decreases in cortical morbidity. Recent approaches to regions with relative increases in treating treatment-refractory limbic areas.11 3. Modulatory component. It is patients with neurosurgery differ postulated that a modulatory substantially from these early component regulates the corticol interventions. Surgery is reserved for and subcortical circuits and only the most severe of cases, when includes the critical psychopharmacological and [SEPTEMBER] Psychiatry 2008 29

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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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