This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to examine the mechanism of electroconvulsive therapy (ECT) as an antidepressant treatment to better understand how bioelectrical stimulation modulates brain activity related to the negative symptoms of severe depressive and schizophrenic disorders. ECT as an antidepressant treatment has the highest efficacy of any antidepressant treatment modality and is most beneficial in patients diagnosed with medication resistant major depression with psychotic features. However, the mechanism by which ECT mediates its effect on the brain remains unclear. Understanding this mechanism could potentially provide information about brain activity during the administration of antidepressant treatments in general, as well as how and where bioelectric stimulation interacts with brain biochemistry to improve negative-mood symptoms and cognitive function. There is some evidence that the anterior cingulate cortex (ACC) is the site of ECT action since ECT significantly decreases the blood flow to that brain area 45 minutes after a course of ECT. Patients with depression have decreased metabolic activity in the ACC that reverts back to normal control levels with an improved clinical response to antidepressant treatments. The ACC is a part of the limbic system shown to play an executive role in processing emotion and cognition. Compared to patients without psychiatric disorders, the ACC in patients with severe depression and schizophrenia is signficantly decreased in volume, metabolic function and brain activity. These abnormalities are most prominent at the rostral and subgenual regions of the ACC. Both 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and electro-encephalography (EEG) have shown a metabolic increase an an amplitude increase for four frequency bands (delta: 1.5-3.5 Hz, theta: 3.5-7.5 Hz, alpha: 7.5-12.5 Hz, and beta: 12.5-25 Hz) at the rostral region of the ACC with low-resolution electromagnetic tomography analysis (LORETA) and quantitative EEG (qEEG). However, no studies have used FDG-PET and EEG to determine the response rate to ECT in patients with severe depression who are partially or totally resistant to antidepressant medication. The hypotheses to be explored in this study are: (1) Patients requiring ECT will have decreased metabolic and altered bioelectrical activity in all areas of the ACC; (2) A good clinical response to ECT will be correlated with metabolism and bioelectrical activity in the dorsal and rostral regions of the ACC reverting to that of normal control states; (3) Metabolic activity in the subgenual ACC will remain lower than normal as a trait marker of severe depression with a tendancy for psychotic symptoms; (4) The degress of decreased metabolism and current theta frequency band density at the ACC can predict the degree of clinical improvement with ECT; (5) A genetic polymorphism for one of the major neurotransmitter receptors or transporters may predict a genetic predisposition to psychoses and a good response to bioelectrical treatments.
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