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Mood DisordersGiven that the Department of Psychiatry and Psychology treats approximately 10,000 patients a year with some form of mood disorder, developing a better understanding of depressive illness is a critical component of the development of our practice. We are conducting current research in the following areas:
Our goal is to use state-of-the-art technology to better define the biological basis of mood disorders through collaborations with the Genomics of Mood Disorder Team and the use of creative functional neuroimaging studies that are being done in the department. Additionally, the Mood Disorders Research Program is committed to developing new forms of treatment. This includes new psychopharmacological approaches and the use of somatic treatments. The link between physical symptoms and the symptoms of depression is dramatic in neurological disorders where there are physical changes in the brain that affect function. Good examples of this association are Huntington’s Disease, Parkinson’s Disease and Traumatic Brain Injury. However, depression is also commonly co-morbid with other complex illnesses such as asthma, diabetes, and cancer. Consequently, a key objective is to search for the genetic basis of depressive symptoms that are co-morbid with physical illnesses. Key Mayo personnel:
Pharmacogenomics of antidepressantsMayo Clinic has a long tradition of leadership in the area of pharmacogenomics. Pharmacogenomics is the study of how genomic variability can be used to predict medication response. At this time, psychiatric pharmacogenomics is focused primarily on the avoidance of adverse effects and the identification of medications that have a low probability of therapeutic response. A series of studies looking at a wide range of psychotropic medications is underway, with the goal of linking specific genetic profiles with responses to specific drugs. Included in these studies has been a study of the pharmacogenomics of venlafaxine led by Dr. McAlpine and Dr. Mrazek. Additionally, investigators in the Departments of Psychiatry and Psychology, Laboratory Medicine and Pathology, and Molecular Pharmacology and Experimental Therapeutics have been collaborating with Dr. John Rush at the University of Texas-Southwestern at Dallas to do the genomic analyses the NIH funded STAR*D study. The next phase of pharmacogenomic research will be focusing on target genes, including the receptor and transporter genes. An excellent example of this effort is a recently funded collaboration with Dr. Richard Weinshilboum, as part of the NIGMS Pharmacogenomic Research Network. A sophisticated team of investigators across the institution, along with a number of key national collaborators, will be studying variations in a network of genes that are associated with escitalopram response. One of the goals of the program is to discover specific associations between variations in genes and the efficacy of psychiatric treatments. Additionally, genetic testing is utilized to better understand the “causes” of psychiatric illness. Finally, with the development of our more accurate understanding of genetic susceptibility for psychiatric illness, we hope that our department will be able to intervene earlier in the course of these illnesses. Our ultimate objective is to prevent the onset of psychiatric disease. This is an ambitious goal, but because of a series of innovative technological breakthroughs, the pathways leading to this objective are now clearly visible. Key Mayo Personnel
Genomics of psychosisThe Genomics of Psychosis team has recently been developed to study illnesses characterized by genomic variability (Mrazek lab) in the development of psychotic symptoms. Psychotic symptoms include delusions and hallucinations, which are the hallmarks of some of the most debilitating psychiatric illnesses such as schizophrenia and bipolar disorder. Key Mayo personnel:
Neuroimaging studiesA complementary partner in this work is the Mood Disorder Neuroimaging Program. “Functional” neuroimaging allows us the opportunity to directly measure brain function. Magnetic Resonance Spectroscopic Imaging (MRSI) is a relatively new functional neuroimaging strategy that is being utilized at the Mayo Clinic to assess variation and abnormalities in patients with mood disorders. One MRSI project, “Brain Choline and Neurocognitive Functioning in Depressed Adolescents: In Vivo Detection of Potential Effects of Fluoxetine Therapy Using Magnetic Resonance Spectroscopic Imaging,” is designed to examine the effects of treatment with fluoxetine on patterns of cognitive performance, mood and brain chemistry in depressed adolescents. Another project is entitled “1H-MRS and 31P-MRS Correlates of Early Onset Bipolar Disorder in Dorsolateral-Prefrontal and Anterior Cingular Cortex.” The aim of this study was to determine spectroscopic findings in drug-free children and adolescents with bipolar disorder versus an age and sex matched comparison group. We recently completed another study entitled “MRSI markers of Bipolar Disorder.” This protocol was supported by the Radiological Society of North America (RSNA). This study examined the biological markers of bipolar disorder in adult patients with bipolar disorder. Key Mayo personnel:
Neuropsychiatric therapeutic proceduresElectroconvulsive Therapy for Mood Disorders The Department of Psychiatry and Psychology Psychogenomic Laboratory is starting a program to identify variations in central nervous system genes that are associated with treatment responsiveness, relapse after treatment, and treatment side effects. In one study, patients diagnosed with depression are referred for electroconvulsive therapy (ECT) are randomly assigned to one of three electrode placements: right unilateral; bitemporal; or bifrontal. Serial neuropsychological profiles as well as depression ratings are undertaken by blinded assessors to compare the clinical efficacy and cognitive side effects of these three modalities. It is hoped that one electrode placement will emerge as highly effective and sparing of cognitive impairment with ECT. In another study, patients diagnosed with depression are followed after a successful course of ECT treatments with either medication therapy or continued ECT for six months to compare the prophylactic efficacy against recurrence and tolerability of these two strategies. Key Mayo personnel:
Transcranial Magnetic Stimulation Transcranial Magnetic Stimulation (TMS) is a new somatic treatment for mood disorder and some related psychiatric conditions. Mayo Clinic has made a major investment in studying this promising technique. One large multicenter study of TMS safety and efficacy in treating depression is being performed at 16 sites in the United States. The plan is to enroll 18 to 20 subjects here at Mayo Clinic Rochester. Data will be used to apply for FDA approval of TMS for use in treating depression. Another study will use low frequency TMS with adolescents with treatment resistant depression. This will be the first prospective study using TMS in adolescents. Key personnel:
Suicide studiesSuicide is one of the leading causes of death in the young and the elderly. Although suicide is a highly complex problem with many environmental and social implications, there is emerging evidence that the behavior is also partly under genetic control. This group is studying genetic influences on suicidal behavior by examining the influence of genetic polymorphisms of genes involved in serotonin and norepinephrine neurotransmission. Key Mayo personnel:
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