Weill Cornell Medical College has been awarded more than $1.9 million by the National Institute of Mental Health of the National Institutes of Health to lead an innovative research study using advanced neuroimaging and clinical evaluations of patients with chronic fatigue syndrome (CFS). The new four-year clinical study, to be conducted in collaboration with Icahn School of Medicine at Mount Sinai and Beth Israel Medical Center, will aim to expand the scientific understanding of CFS, improve diagnostics for the condition and discover novel biomarkers, all of which may lead to the identification of new and more effective treatment targets.
"Research funding for chronic fatigue syndrome has been historically limited," says principal investigator Dr. Dikoma Shungu, professor of physics in radiology and chief of the Laboratory for Advanced Magnetic Resonance Spectroscopy Research at Weill Cornell Medical College. "This large, generous NIH grant award will allow us to accelerate in-depth, novel clinical research for CFS to make the significant strides we vitally need for research discovery and clinical care."
The new multidisciplinary clinical research study will be headquartered at Weill Cornell in Dr. Shungu's laboratory at Weill Cornell's Citigroup Biomedical Imaging Center using advanced magnetic resonance spectroscopy neuroimaging technology, including its 3.0 T MRI scanner. Clinical research and assessments will also be conducted at Mount Sinai's Mood and Anxiety Disorders Program and through the Pain & Fatigue Study Center at Beth Israel Medical Center.
CFS is a difficult to diagnose and complex, multi-system disorder. It is considered a medically mysterious illness and is often misdiagnosed. Differentiation of CFS and neuropsychiatric illnesses, such as major depressive disorder (MDD), can be daunting and is a continuing challenge.
Symptoms of CFS include severe, debilitating and lasting fatigue that is not alleviated by rest and may be accompanied by a constellation of symptoms, including musculoskeletal pain, sore throat, headaches, impaired concentration, short-term memory and sleep disturbances. A characteristic feature of CFS is post-exertional relapse, a recurrence or worsening of symptoms after even minor physical or mental activity. Its clinical presentation, combined with the lack of current validated diagnostic tests and its overlap of symptoms with disorders like MDD, can make CFS difficult to diagnose.
This NIH supported clinical research study will build upon the last seven years of research conducted by the partnering institutions Weill Cornell, Mount Sinai and Beth Israel. In recent small pilot clinical studies, generously supported by The CFIDS Association of America, these three academic medical research centers have investigated CFS using sophisticated neuroimaging and battery of clinical tests. Their preliminary, small pilot study findings show the key culprit in CFS may be increased and sustained oxidative stress evidenced in the neuroimaging scans, blood and bodily fluid tests of CFS patients. Specifically, their research shows levels of cortical glutathione (GSH) -- the most abundant and one of the most important antioxidants in living tissue -- are decreased by 36 percent in CFS patients. This novel cortical GSH deficit finding was also correlated with those patients with increased levels of blood markers of oxidative stress and symptoms of CFS. Study results also show CFS patients also have significantly elevated ventricular cerebrospinal fluid (CSF) lactate and decreased regional cerebral blood flow (rCBF).
"Our initial studies implicate oxidative stress as a key factor in the pathophysiology of CFS," says Dr. Shungu. "We look forward to investigating further our highly promising and consistent findings in an expanded study thanks to NIH support. This new study will help give validity and the specificity of our oxidative stress hypothesis, and we aim to find promising therapeutic targets and novel treatments for patients."
However, researchers found in their pilot studies that the abnormalities identified in CFS patients are similar to the abnormalities witnessed in MDD patients. In the new study, researchers hope to decode CFS and distinguish it from neuropsychiatric conditions such as MDD. This current uncertainty makes it critical for research studies to investigate the nature of comorbidity in CFS.
"The discovery of specific biomarkers that can differentiate CFS from similarly presenting psychiatric disorders will have a profound impact for how the disorder is perceived, managed, diagnosed and for the development of objective diagnostic tests, therapeutic targets and advanced scientific understanding of this mysterious debilitating illness," says Dr. Shungu.
Researchers believe this study is highly innovative, representing a departure from nearly all previous studies for CFS to date. They trust it may be the first comprehensive attempt to identify brain biomarkers for the condition.
"This new CFS research will help show distinct medical patterns in CFS patients helping to drive discovery of more efficient diagnostics and treatments, ultimately improving the health and quality of life of patients," says K. Kim McCleary, president & CEO of The CFIDS Association of America. "This tremendous $2 million in NIH support validates the need for more research and new treatments for this chronic illness that typically suddenly hits patients like a tornado. We hope this study closes the scientific gap for the disorder so we can halt this debilitating condition in its tracks, finally restoring hope for patients and their families battling CFS."
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