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Dr. Fisher is a professor of medicine and of community and family medicine, Dr. Bynum an assistant professor of medicine and of community and family medicine, and Dr. Skinner a professor of economics and of community and family medicine at Dartmouth Medical School, Lebanon, NH, where Dr. Fisher also directs the Center for Health Policy Research, Dartmouth Institute for Health Policy and Clinical Practice.

New findings in rodents and human brain shed light on the mechanisms of major depressive disorder (MDD), uncovering over-expression of MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1)...and identifying a new therapeutic target. MKP-1, also known as dual-specificity phosphatase-1 (DUSP1), is a member of a family of proteins that dephosphorylate both threonine and tyrosine residues and thereby serves as a key negative regulator of the MAPK cascade4, a major signaling pathway involved in neuronal plasticity, function and survival This study identifies MKP-1 as a key factor in MDD pathophysiology, and as a new target for therapeutic interventions.f Here we use whole-genome expression profiling of postmortem tissue and show significantly increased expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1, encoded by DUSP1, but hereafter called MKP-1) in the hippocampal subfields of subjects with MDD compared to matched controls. MKP-1, also known as dual-specificity phosphatase-1 (DUSP1), is a member of a family of proteins that dephosphorylate both threonine and tyrosine residues and thereby serves as a key negative regulator of the MAPK cascade4, a major signaling pathway involved in neuronal plasticity, function and survival. We tested the role of altered MKP-1 expression in rat and mouse models of depression and found that increased hippocampal MKP-1 expression, as a result of stress or viral-mediated gene transfer, causes depressive behaviors. Conversely, chronic antidepressant treatment normalizes stress-induced MKP-1 expression and behavior, and mice lacking MKP-1 are resilient to stress. These postmortem and preclinical studies identify MKP-1 as a key factor in MDD pathophysiology and as a new target for therapeutic interventions.

"Hop up on the table, Honey." mThat's how an x-ray technician addressed my 89-year-old mother-in-law in 2001, when we took her for knee x-rays. Mom, who had advanced osteoporosis and arthritis as well as confusion and heart problems, had long since given up hopping. When it became obvious that she needed assistance, the technician grabbed her arm -- as if pulling on another sore appendage would magically raise the rest of her onto the table. It didn't. This incident has become our personal mantra for expressing what is wrong with America's health care system. Having helped our four parents during their final years and having both had cancer ourselves as well as other medical problems, we have had experiences with five nursing homes, two personal care facilities and a half dozen hospitals. We've lost count of the doctors, drugstores and health insurance plans. All of us have had health insurance, though some policies were better than others. Nonetheless, we have experienced incident after incident demonstrating the waste, ignorance and apathy which is rampant in the system. Unable to list them all, I have been heretofore reluctant to write about a handful of them lest the reader be persuaded that the problem is with only that hospital, only that nursing home or only that doctor. There is, however, an increasing crisis of confusion, mismanagement and ill-preparedness which is at the core of our healthcare system. We are all familiar at least with the trend line if not the specifics for healthcare costs. According to WhiteHouse.gov, "The United States spends over $2.2 trillion on health care each year-almost $8,000 per person." That's sixteen percent of the economy. Healthcare costs are projected to increase to almost twenty percent ($4 trillion a year) by 2017. Meanwhile forty-six million Americans are without health insurance (14,000 more each day), premiums and co-pays are rising and more reasons are used to refuse coverage both to those willing to pay and thos

"Hop up on the table, Honey." mThat's how an x-ray technician addressed my 89-year-old mother-in-law in 2001, when we took her for knee x-rays. Mom, who had advanced osteoporosis and arthritis as well as confusion and heart problems, had long since given up hopping. When it became obvious that she needed assistance, the technician grabbed her arm -- as if pulling on another sore appendage would magically raise the rest of her onto the table. It didn't. This incident has become our personal mantra for expressing what is wrong with America's health care system. Having helped our four parents during their final years and having both had cancer ourselves as well as other medical problems, we have had experiences with five nursing homes, two personal care facilities and a half dozen hospitals. We've lost count of the doctors, drugstores and health insurance plans. All of us have had health insurance, though some policies were better than others. Nonetheless, we have experienced incident after incident demonstrating the waste, ignorance and apathy which is rampant in the system. Unable to list them all, I have been heretofore reluctant to write about a handful of them lest the reader be persuaded that the problem is with only that hospital, only that nursing home or only that doctor. There is, however, an increasing crisis of confusion, mismanagement and ill-preparedness which is at the core of our healthcare system. We are all familiar at least with the trend line if not the specifics for healthcare costs. According to WhiteHouse.gov, "The United States spends over $2.2 trillion on health care each year-almost $8,000 per person." That's sixteen percent of the economy. Healthcare costs are projected to increase to almost twenty percent ($4 trillion a year) by 2017. Meanwhile forty-six million Americans are without health insurance (14,000 more each day), premiums and co-pays are rising and more reasons are used to refuse coverage both to those willing to pay and thos