Dr. Pardo leads a research program which seeks to 1) elucidate the functional architecture of the human brain with particular emphasis on how dysfunction within neural networks relates to psychiatric disorders; 2) to identify neural systems mediating cognitive operations (e.g., attention, memory); 3) to define the pathophysiology of mental illness.
His team identified the anterior cingulate cortex as a locus of attentional operations (PNAS 1990; 87:256) and the major site of cognitive aging in otherwise healthy individuals (Neuroimage 2007; 35(3):1231. They have also applied brain imaging for early diagnosis of the dementias (Alzheimers Dement 2010; 6(4): 326).
These studies point to a high degree of genetic heterogeneity especially in psychiatric nosology. To address this issue, a major effort underway is the discovery of Mendelian genes (rare, high penetrance, simple inheritance). An international collaboration was established 1) to recruit multiplex, first-cousin marriages with a defined phenotype (e.g., psychosis); 2) whole genome sequencing of pedigree members; and 3) filtering for variants of interest, VOI (e.g., homozygosity mapping, evolutionary conservation, predicted damaged protein; absence in normative databases). Currently, the prime VOI is USP53 p.C228R. Preliminary molecular studies show this protein localizes to the hippocampus and dentate granular regions and interacts with GRIA2 and GRIP2—components of the AMPA synapse. These findings support the glutamate hypothesis of schizophrenia and motivate additional molecular studies of the variant.
Dr. Pardo leads a research program which seeks to elucidate the functional architecture of the human brain with particular emphasis on how dysfunction within neural networks relates to psychiatric disorders. The multidisciplinary approach (in close collaboration with the Brain Sciences Center, Department of Psychology, Department of Psychiatry, and GRECC) involves methods from cognitive neuroscience, including several imaging modalities, particularly PET and fMRI.His team identified the anterior cingulate cortex as a pivotal locus of cognitive aging in otherwise healthy individuals (Neuroimage. 2007 April 15; 35(3): 1231–1237). They now seek to understand the significance and pathophysiological basis of this finding in the context of systems neuroscience, biochemistry, and animal models. They are also using brain imaging for early diagnosis of the dementias (Alzheimers Dement. 2010 July; 6(4): 326–333). Given the current heterogeneity of psychiatric diagnosis, a developing interest is imaging genetics to identify genotypes with defined psychiatric phenotypes that may lead to improved models of mental disease. For additional information, see the Pardo laboratory website at http://james.psych.umn.edu/.
Mood disorders; treatment-resistant; neuroimaging
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