Depression, Depressionen

Historical Introduction

Since its inception, biological psychiatry has embraced the use of somatic interventions for brain research and clinical treatment. Indeed, many of the founders of the 55-year-old Society of Biological Psychiatry were researchers who were interested in understanding the mechanisms of action of electroconvulsive therapy (ECT).

From the Departments of Psychiatry (MSC, ZN, JG, iCH), Radiology (MSG), and Neurology (MSG), Medical University of South Carolina, and the Ralph H. Johnson Veterans Hospital (MSG). Charleston, South Carolina; the Department of Biological Psychiatry. New York State Psychiatrie Institute (HAS. SL TB) and the Departmenls of Psychiatry (HAS, SL, TB) and Radiology WAS). College of Physicians and Surgeons, Columbia University, New York, New York; and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (AJR. MMH) and the Department of Psychiatry, Baylor College of Medicine, Houston (LBM). Texas,

Address reprint requests to Dr. Mark S. George. Radiology Department, Medicat University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425.

Received November 12, 1999; revised December 10, 1999; accepted December 13, 1999.

Although the revolution in neuropsychopharmacology over the last 40 years has captured much interest, recent advances in somatic interventions (e.g., physical, nonpharmacological) are causing a resurgence of interest in other methods that directly and, in some cases (transcranial magnetic stimulation [TMS]) noninvasively affect brain function. The field of ECT continues to advance, with recent demonstrations of the need for dosage titration (Sackeim et al 1987b) and regional specificity of ECT effects (Sackeim et al 1987a, 1993) and even the recent production of ECT-like seizures using magnetic instead of electrical currents (Lisanby et al 1999). There has also been considerable interest in TMS (without seizure production), which holds promise as a research tool with potential clinical applications (George and Belmaker 1999; George et al 1999).

The most anatomically discrete and most invasive currently employed method of stimulating deep brain structures is deep brain stimulation (DBS), in which a thin electrode is inserted directly into the brain and different currents are applied at varying depths until the desired effects are found. Recently, high-frequency (>80 Hz) electrical stimulation of the middle thalamus or subthalamic nucleus has been found to be effective in Parkinson‘s disease (Damier 1998; Limousin et al 1998). Whereas DBS has the advantage over brain surgery (pallidotomy) of being reversible, it has significant morbidity and mortality associated with the implant procedure. Although this technique has not been used to treat major depression, mood effects of the stimulation have been reported. In one Parkinson‘s disease patient who had never suffered from depression in her life, the testing of the stimulation caused the acute onset of tearfulness, sadness, and despair. These symptoms remitted immediately when the surgeon moved the stimulator away from the substantia nigra, directly below the subthalamic nucleus (Bejjani et al 1999). Parkinson‘s disease researchers lead the neuropsychiatric field in terms of understanding a disease‘s involved pathologic circuitry. Thus it is natural for DBS to be used first in Parkinson‘s disease. However, as the neuroanatomy of other neuropsychiatric disorders (mood, anxiety, and psychosis) becomes better understood, it is conceivable that DBS may be helpful to otherwise treatment-resistant patients, although to date DBS has only been shown to cause depression symptoms rather than relieve them.