[SK4-1] Positron Emission Tomography of Human Brain can Monitor Neuroinflammation and cAMP Signaling: Applications to Alzheimer's Disease and Depression
CAREER:
1980-84 Resident in Psychiatry, Yale University (1980-1984)
1984-90 Assistant Professor, Dept. Psychiatry, Yale University
1988-01 Director of Psychiatric Research, West Haven VA Medical Center
1989-01 Director of Neurochemical Brain Imaging Program (Dept. Psychiatry)
1990-94 Associate Professor, Yale Dept. Psychiatry
1994-01 Appointment with tenure, Yale University
1995-96 Associate Professor (secondary), Yale Dept. Pharmacology
1996-01 Professor of Psychiatry (primary) and Pharmacology (secondary), Yale University
1999-01 Scientific Director, Yale/VA PET Center
2001- Chief, Molecular Imaging Branch, NIMH
Professional Biosketch
Dr. Innis's distinguished career has been marked by the groundbreaking development of important new PET ligands—most notably to image dopamine transporters and neuroinflammation—and the subsequent use of these ligands to quantify targets relevant to the pathophysiology of neuropsychiatric disorders. At Yale (1984-2001), Dr. Innis used radioligands to measure excessive dopamine release in schizophrenia and to monitor the degeneration of dopaminergic terminals in Parkinson's disease. At the NIH, Dr. Innis developed and helped disseminate the use of radioligands for a number of key targets, including: the cannabinoid CB 1 receptor; the mGluR1 and mGluR5 glutamatergic receptors; the nociceptin/orphanin receptor; translocator protein (TSPO, a marker of inflammation); and P-gp, an efflux transporter at the blood-brain barrier. Two important recent accomplishments are: 1) showing that the PET radioligand for TSPO, which is highly expressed in activated microglia, can identify areas with both local (eg, stroke and epilepsy) and generalized (eg, Alzheimer's disease) inflammatory changes; and 2) showing that radioligand binding to phosphodiesterase-4 (PDE4) is decreased in unmedicated patients with depression and normalized after two months of SSRI treatment; both of these latter findings are consistent with the "cAMP theory" of depression. Dr. Innis is also developing radioligands selective for PDE4 subtypes that may have therapeutic efficacy in depression without the side effects (nausea) of non-selective agents.
Major Research Accomplishments
Dr. Innis's most seminal discoveries include: 1) developing a radioligand approved for clinical use to image dopamine transporters in suspected Parkinson's disease; 2) demonstrating that exacerbations of schizophrenic psychosis are directly linked to dopamine release; and 3) developing a radioligand used in many imaging centers worldwide to monitor neuroinflammation.
1980-84 Resident in Psychiatry, Yale University (1980-1984)
1984-90 Assistant Professor, Dept. Psychiatry, Yale University
1988-01 Director of Psychiatric Research, West Haven VA Medical Center
1989-01 Director of Neurochemical Brain Imaging Program (Dept. Psychiatry)
1990-94 Associate Professor, Yale Dept. Psychiatry
1994-01 Appointment with tenure, Yale University
1995-96 Associate Professor (secondary), Yale Dept. Pharmacology
1996-01 Professor of Psychiatry (primary) and Pharmacology (secondary), Yale University
1999-01 Scientific Director, Yale/VA PET Center
2001- Chief, Molecular Imaging Branch, NIMH
Professional Biosketch
Dr. Innis's distinguished career has been marked by the groundbreaking development of important new PET ligands—most notably to image dopamine transporters and neuroinflammation—and the subsequent use of these ligands to quantify targets relevant to the pathophysiology of neuropsychiatric disorders. At Yale (1984-2001), Dr. Innis used radioligands to measure excessive dopamine release in schizophrenia and to monitor the degeneration of dopaminergic terminals in Parkinson's disease. At the NIH, Dr. Innis developed and helped disseminate the use of radioligands for a number of key targets, including: the cannabinoid CB 1 receptor; the mGluR1 and mGluR5 glutamatergic receptors; the nociceptin/orphanin receptor; translocator protein (TSPO, a marker of inflammation); and P-gp, an efflux transporter at the blood-brain barrier. Two important recent accomplishments are: 1) showing that the PET radioligand for TSPO, which is highly expressed in activated microglia, can identify areas with both local (eg, stroke and epilepsy) and generalized (eg, Alzheimer's disease) inflammatory changes; and 2) showing that radioligand binding to phosphodiesterase-4 (PDE4) is decreased in unmedicated patients with depression and normalized after two months of SSRI treatment; both of these latter findings are consistent with the "cAMP theory" of depression. Dr. Innis is also developing radioligands selective for PDE4 subtypes that may have therapeutic efficacy in depression without the side effects (nausea) of non-selective agents.
Major Research Accomplishments
Dr. Innis's most seminal discoveries include: 1) developing a radioligand approved for clinical use to image dopamine transporters in suspected Parkinson's disease; 2) demonstrating that exacerbations of schizophrenic psychosis are directly linked to dopamine release; and 3) developing a radioligand used in many imaging centers worldwide to monitor neuroinflammation.
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