HMGP - Robert Freedman, Ph.D

Dr. Freedman's laboratory is concerned with understanding the development of schizophrenia. Using psychophysiological tools such as auditory evoked potentials with schizophrenics and their families, his laboratory identifies individuals who may carry genes which convey risk for schizophrenia. Molecular biological tools such as gene sequencing and in situ hybridization are used to search for the genetic abnormalities in schizophrenia. Facilities range from a laboratory nursery school, where one can observe the development of children of schizophrenic mothers, to basic science laboratories, where psychophysiological abnormalities can be modeled in animals and studied at the single neuron level. The fellowship is an opportunity for clinically trained fellows to learn the application of neurobiological and molecular biological techniques to psychopathological problems and for those with basic science background to learn to work with human materials.

Ross RG, Olincy A, Harris JG, Radant A, Hawkins M, Adler LE, Freedman R. Evidence for bilineal inheritance of physiological indicators of risk in childhood-onset schizophrenia. American Journal of Medical Genetics: Neuropsychiatric Genetics, 88, 188-199, 1999.

Freedman R, Adams C, Leonard S. The alpha7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia. J. Chem. Neuroanatomy 20:295-306, 2000.

Olincy, A, Ross, RG., Harris, JG., Young, DA., McAndrews, MA, Cawthra, E., McRae, KA., Sullivan, B., Adler, LE, Freedman RF. The P50 Auditory Event-Evoked Potential in Adult Attention-Deficit Disorder: Comparison with Schizophrenia. Biol. Psych. 47:969-977, 2000.

Adams, C.E., Stevens, K.E., Kem. W.R., Freedman, R. Inhibition of nitric oxide synthase prevents a7 nicotinic receptor-mediated restoration of inhibitory auditory gating in rat hippocampus. Brain Research, 877:235-244, 2000.

Simosky, J.K., Stevens, K.E., Kem, W.R., Freedman, R. Intragastric DMXB-A, an ?7 nicotinic agonist, improves deficient sensory inhibition in DB/2 mice. Biol. Psychiatry 50(7): 493-500, 2001.

Kisley, M.A., Olincy, A., Freedman, R. The effect of state on sensory gating: comparison of waking, REM and non-REM sleep. Clinical Neurophysiology 112:1154-1165, 2001.
Freedman R and Leonard S. Genetic linkage to schizophrenia at chromosome 15q14. Am. J. Med. Gen., Neuropsych. Gen., 105:655-657,2001.

Adams CE, Stitzel JA, Collins AC, Freedman R. alpha7-Nicotinic receptor expression and the anatomical organization of hippocampal interneurons. Brain Res 20;922(2):180-190, 2001.

Freedman R, Leonard S, Olincy A, Kaufmann, CA, Malaspina D, Cloninger CR, Svrakic D, Faraone SV, and Tsuang M. Evidence for the multigenic inheritance of schizophrenia. American J of Medical Genetics 105:794-800, 2001.

Freedman, R. Electrophysiological Phenotypes. Psychiatric Genetics, Humana Press. 9:211-221, 2002.

Tanabe,J., Miller,D., Tregellas,J., Freedman,R., and Meyer,F.G.. Comparison of Detrending Methods for Optimal fMRI Preprocessing. Neuroimage. 15, 902-907,2002.

Simosky JK, Stevens KE, Freedman R. Nicotinic Agonists in Psychosis. Current Drug Targets: CNS and Neurological Disorders, 1 (2): 149-162, 2002.

Freedman, R. Long-term effects of early genetic influences on behavior. New England Journal of Medicine. 347(3):213-215-2002.

Harris, JG, Young, DA, Rojas, DC, Cajade-Law A., Scherzinger. A., Nawroz, S., Adler, LE, Cullum, CM, Simon J. and Freedman, R. Increased hippocampal volume in schizophrenics’ parents with ancestral history of schizophrenia. Schizophrenia Research. 55(1-2):11-17,2002.

Freedman, R., Adler, LE, Olincy, A., Waldo, MC, Ross, RG, Stevens, KE., Leonard, S. Input dysfunction, schizotypy, and genetic models of schizophrenia. Schizophrenia Research. 54(1-2)25-32, 2002.

Tanabe J, Tregellas J, Miller D, Ross R. Freedman R. Brain activation during smooth pursuit eye movements. Neuroimage 17:1315-1234, 2002.

Simosky,J.K., Stevens,K.E., Adler,L.E., and Freedman,R. Clozapine improves deficient inhibitory auditory processing in DBA/2 mice via a nicotinic cholinergic mechanism. Psychopharmacology 165:386-396, 2003.

Ross,R.G., Olincy,A., Mikulich,S.K., Radant,A.D., Harris,J.G., Waldo,M., Compagnon,N., Heinlein,S., Leonard,S., Zerbe,G.O., Adler,L., and Freedman,R. Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes. Psychophysiology, 39:809-819, 2002.

Leonard,S., Gault,J., Hopkins,J., Logel,J., Drebing,C., Vianzon,R., Short,M., Berger,R., Robinson,M., and Freedman,R. Promoter variants in the a7 nicotinic acetylcholine receptor subunit gene are assoicated with an inhibitory deficit found in schizophrenia. Arch Gen Psychiatry 59:1085-1096, 2002.

Adams CE, Broide RS, Chen Y, Winzer-Serhan UH, Henderson TA, Leslie FM, Freedman R. Development of the ?7 nicotinic receptor in rat hippocampal formation. Developmental Brain Res 139:175-187, 2002.

Leonard S and Freedman R. Recombination in an NIMH Schizophrenia Genetics Initiative Family Fails to Exclude the 15q14 CHRNA7 Locus. Molecular Psychiatry 8:145-146, 2003.

Kisley,M.A., Olincy,A., Robbins,E., Polk,S.D., Adler,L.E., Waldo,M.C., and Freedman,R. (2002). Sensory gating impairment associated with schizophrenia persists into REM sleep. Psychophysiology, 4); 29-38., 2003.

Kisley MA. Polk SD. Ross RG. Levisohn PM. Freedman R. Early postnatal development of sensory gating. Neuroreport. 14:693-7, 2003.

Tregellas JR, Jody L. Tanabe, David E. Miller, Randal G. Ross, Ann Olincy, Robert Freedman. Neurobiology of Smooth Pursuit Eye Movement Deficits in Schizophrenia: An fMRI Study. American J of Psychiatry, in press.

Gault,J., Hopkins,J., Berger,R., Drebing,C., Logel,J., Walton,K., Short,M., Vianzon,R., Olincy,A., Ross,R.G., Adler,L.E., Freedman,R. and Leonard,S. (2003). Comparison of polymorphisms in the a7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects. Neuropsychiatric Genetics, in press.

Freedman, R. Current Drug Therapy: Schizophrenia. New England Journal of Medicine, in press.