CLINICAL UNIT BASED RESEARCH
Schizophrenia and Bipolar Disorder Program
As director of McLean's Schizophrenia and Bipolar Disorder Program, Dr. Dost Öngür also heads a research aspect of the program with offices located directly above the inpatient unit on the third floor of the Admissions Building. We are interested in chemical, functional, and structural brain abnormalities in patients with schizophrenia and bipolar disorder. Our main focus is using neuroimaging techniques to probe the role of the medial prefrontal cortex in these conditions. In collaboration with Dr. Perry Renshaw, we use magnetic resonance spectroscopy (MRS) to measure the levels of two major neurotransmitters in the brain, glutamate and GABA (Figure 1).
We also carry out resting state functional MRI studies to examine abnormalities in neural networks subserving ongoing brain function. Figure 2 shows a set of brain areas that are active at rest and share a similar timecourse of activity. The top row represents the average "resting state network" from a group of 15 healthy controls, the middle row 14 schizophrenia patients, and the bottom row 17 bipolar disorder patients. It is clear that there are broad similarities in the brain areas in this network across conditions, but there are also subtle differences, which we are currently investigating.
Figure 3 shows significant differences in default mode network spatial extent between normal control and bipolar disorder subjects in whole brain analysis mapped onto parasagittal, coronal, and axial slices from a single subjects' structural image in Talairach space; A) Normal control > Bipolar disorder; B) Bipolar disorder > Normal control. In each panel, average z-scores from a highlighted cluster are shown for normal control (gray) and bipolar disorder (black) groups. p=0.001, uncorrected; spatial extent > 25 voxels.
Figure 4 shows metabolite signal decay due to T2 relaxation. The panel on the right shows the first fast Fourier transformed echo of a control subject dataset from the ACC. To the left are sets of 48 spectral fragments around the metabolite peak of interest (tNAA, tCr, or tCho) as indicated by the horizontal lines. There are 3 sets each from one control and one BD subject, and they span the 30 - 500 ms range (left to right) in 10 ms increments. Each series is presented with spectral amplitude normalized to the first spectrum for presentation purposes. The difference in signal decay due to T2 relaxation is evident: fastest in tCr, followed by tCho, and finally by tNAA.
- Öngür, Dost , MD, PhD Clinical Director, Schizophrenia and Bipolar Disorder Program
- Lewandowski, Kathryn, PhD Assistant Research Psychologist
- Shinn, Ann Kyungah, M.D., MPH Assistant Psychiatrist
- Du, Fei, PhD, MR Physicist
- Sonal Mallya, Research Assistant
- Lauren O'Connor, Research Assistant
- Samira Pingali, Research Assistant
- Selma Sehovic, Research Assistant
- Sarah Sperry, Research Assistant
- Brennan BP, Hudson JI, Jensen JE, McCarthy JM, Roberts JL, Prescot AP, Cohen BM, Pope HG, Renshaw PF, Öngür D (2010). Rapid enhancement of glutamatergic neurotransmission in bipolar depression following treatment with riluzole. Neuropsychopharmacology 35: 834-46.
- Öngür D, Lundy M, Greenhouse I, Shinn AK, Menon V, Cohen BM, Renshaw PF (2010) Default mode network abnormalities in bipolar disorder and schizophrenia. Psychiatry Res Neuroimaging, 183(1), 59-68.
- Öngür D, Prescot AP, McCarthy JM, Cohen BM, Renshaw PF (2010) Elevated gamma-aminobutyric acid levels in chronic schizophrenia. Biol Psychiatry, 68(7), 667-670.
- Lewandowski KE, Cohen BM, Öngür D (2010) Evolution of neuropsychological dysfunction during the course of schizophrenia and bipolar disorder. Psychol Med., 41(2), 225-41.
- Bechtholt-Gompf AJ, Walther HV, Adams MA, Carlezon WA, Öngür D, Cohen BM (2010) Blockade of astrocytic glutamate uptake in rats induces signs of anhedonia without dysphoria and impaired spatial memory. Neuropsychopharmacology 35(10):2049-59.
- England ML, Öngür D, Konopaske GT, Karmacharya R (2011) Catatonia in Psychotic Patients: Clinical Features and Treatment Response. J Neuropsych Clin Neurosci 23(2):223-226.
- Yuksel AC, Öngür D (2010) Magnetic resonance spectroscopy studies of glutamate-related abnormalities in mood disorders. Biol Psychiatry 68(9):785-94.
- Bechtholt-Gompf A, Smith K, John C, Kang H, Carlezon WA, Cohen BM, Öngür D (2011) CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy. Psychopharmacology 215(4):689-95.
- MRI studies of Brain Chemistry and Function in Bipolar Disorder and Schizophrenia
- Genetic Association Studies in Bipolar Disorder and Schizophrenia
- Cognitive Functioning in Bipolar Disorder and Schizophrenia
- MRI studies of auditory hallucinations