This is an application for a K24 Midcareer Investigator in Patient Oriented Research award. I am a psychiatrist with clinical expertise in psychotic disorders and background in neurobiology. I have been conducting noninvasive neuroimaging studies probing cellular abnormalities in schizophrenia and bipolar disorder. I have built a group of junior investigators engaged in patient oriented research and I am the Chief of the Psychotic Disorders Division at McLean Hospital. However, I have a need for protected time to enhance my mentoring activities and to develop new areas of expertise to meet my long-term career goals of identifying therapeutic targets in psychotic disorders and to train the next generation of investigators in this field. In this proposal, I outline a mentoring lan for recruiting and retaining high caliber junior investigators into my research group. In addition,I will obtain additional training in mitochondrial function, brain bioenergetics, and peripheral glucose metabolism/diabetes. My research to date has examined abnormalities in glutamatergic and GABAergic neurotransmission. I will use this training to expand my studies into 31P magnetic resonance spectroscopy which provides detailed information about ATP synthesis and metabolism - processes which are intricately linked with neurotransmission. There are multiple indications that brain metabolism is also related to peripheral metabolism. Since patients with psychotic disorders are also prone to the metabolic syndrome, I will also initiate a new series of studies on muscle metabolism and peripheral markers of insulin resistance. I predict that these measures will correlate with brain measures, and they will suggest potential new opportunities for treating schizophrenia - an area of great unmet need.

Public Health Relevance

Schizophrenia is a common and severe psychiatric disorder with poorly understood pathophysiology. This K24 Patient Oriented Research Mentoring Award will allow the PI to enhance and expand his mentoring of junior investigators and to develop new expertise in brain bioenergetics in the pathophysiology of schizophrenia. In addition, the PI will begin a series of studies examining the relationships between metabolic abnormalities in the brain and body, and their implications for the metabolic syndrome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24MH104449-05
Application #
9763643
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Wijtenburg, Andrea
Project Start
2015-08-01
Project End
2020-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Kim, Sang-Young; Kaufman, Marc J; Cohen, Bruce M et al. (2018) In Vivo Brain Glycine and Glutamate Concentrations in Patients With First-Episode Psychosis Measured by Echo Time-Averaged Proton Magnetic Resonance Spectroscopy at 4T. Biol Psychiatry 83:484-491
Atagün, Murat ?lhan; ??ko?lu, Elif Muazzez; Can, Serdar Süleyman et al. (2018) Neurochemical differences between bipolar disorder type I and II in superior temporal cortices: A proton magnetic resonance spectroscopy study. J Affect Disord 235:15-19
Chouinard, Virginie-Anne; Henderson, David C; Dalla Man, Chiara et al. (2018) Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis. Mol Psychiatry :
Du, Fei; Yuksel, Cagri; Chouinard, Virginie-Anne et al. (2018) Abnormalities in High-Energy Phosphate Metabolism in First-Episode Bipolar Disorder Measured Using 31P-Magnetic Resonance Spectroscopy. Biol Psychiatry 84:797-802
Kim, Sang-Young; Chen, Wei; Ongur, Dost et al. (2018) Rapid and simultaneous measurement of phosphorus metabolite pool size ratio and reaction kinetics of enzymes in vivo. J Magn Reson Imaging 47:210-221
Lewandowski, Kathryn E; Ongur, Dost; Keshavan, Matcheri S (2018) Development of novel behavioral interventions in an experimental therapeutics world: Challenges, and directions for the future. Schizophr Res 192:6-8
Dogan, Asli Ercan; Yuksel, Cagri; Du, Fei et al. (2018) Brain lactate and pH in schizophrenia and bipolar disorder: a systematic review of findings from magnetic resonance studies. Neuropsychopharmacology 43:1681-1690
Shinn, Ann K; Roh, Youkyung S; Ravichandran, Caitlin T et al. (2017) Aberrant cerebellar connectivity in bipolar disorder with psychosis. Biol Psychiatry Cogn Neurosci Neuroimaging 2:438-448
Shinn, Ann K; Bolton, Kirsten W; Karmacharya, Rakesh et al. (2017) McLean OnTrack: a transdiagnostic program for early intervention in first-episode psychosis. Early Interv Psychiatry 11:83-90
Atagün, Murat ?lhan; ??ko?lu, Elif Muazzez; Soykan, Ça?lar et al. (2017) Perisylvian GABA levels in schizophrenia and bipolar disorder. Neurosci Lett 637:70-74

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