This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Literature from the first part of the 20th century suggested an association between severe mental illness and diabetes or glucose intolerance. The mechanism by which patients with a major mood disorder have increased risk is not known, but elevated glucocorticoids, activation of the sympathetic nervous system, dysregulated feeding behavior, poor self care, comorbid disorders such as tobacco or alcohol use, and sociodemographic risk factors such as low socioeconomic status, poor access to health care, and poor social support, have been thought to increase the risk of weight gain, insulin resistance, and type 2 diabetes. Greater cognitive deficits are observed in patients with both mood disorders and with diabetes or insulin resistance. The present study seeks to examine the effects of insulin resistance on neurocognitive measures in depressed patients at baseline and again after 90 days of an insulin-sensitizing medication (Metformin). We hypothesize that participants with high levels of insulin resistance, as determined by response to glucose tolerance testing, will show greater cognitive deficits. Further, we hypothesize that participants with insulin resistance will demonstrate cognitive improvement after treatment with an insulin-sensitizing medication.
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