Biobehavioral and Cognitive Studies of Major Psychoses
Psychology Research Laboratory, McLean Hospital
Philip S. Holzman, Ph.D., Deborah L. Levy, Ph.D., Steven Matthysse, Ph.D., Yue Chen, Ph.D., Debra Titone, Ph.D., Michael Coleman, M.A., Anne Gibbs, MSN, Curtis Deutsch, Ph.D., Donald Rubin, Ph.D., Ken Nakayama, Ph.D.
The Psychology Research Laboratory (PRL) studies the basic behavioral neurobiology and cognition of schizophrenia through in-depth probes in several domains that are relevant to fundamental discoveries we have made about schizophrenia. These studies examine eye movement dysfunctions, spatial working memory impairments, the specific qualities of formal thought disorder associated with each of the major psychoses, cranio-facial dysmorphology, and psycholinguistics. In addition to testing patients with psychotic disorders, we also study their first-degree relatives so that both familial and genetic linkage studies can be undertaken. The PRL is the only laboratory in the Mailman Research Center that addresses the neurobiological, cognitive, perceptual, and executive functions implicated in the major psychoses, particularly schizophrenia, in living human populations.
We collaborate closely with the Harvard Vision Sciences Lab on basic work in visual processing that probes the abnormality of smooth pursuit eye movements in schizophrenic patients and in a proportion of their relatives. Using the methods of psychophysics, we have established that a crucial component of this abnormality is a disorder of motion discrimination, regulated in the middle temporal area of the extra-striate cortex. We are investigating the generality and specificity of working memory dysfunctions to see whether spatial working memory is selectively impaired or whether other kinds of working memory (e.g., verbal, object, shape) are compromised as well. We have also been studying formal thought disorder, and have recently incorporated psycholinguistic approaches in this work. With the close involvement of the Harvard Department of Statistics, we have devised new statistical methods that take into account the special features of some of our data. We make use of the Brain Imaging Center at McLean Hospital for fMRI (with both 1.5T and 4T magnets) studies. A major focus is the familial distribution of our behavioral data and their capacity to inform about genetic transmission of behavioral phenotypes associated with schizophrenia, which may be useful for increasing the power of linkage analysis.
Key words: schizophrenia, genetics, working memory, dysmorphology, thought disorder, motion processing, psycholinguistics, statistics, linkage analysis, eye movements.
Grant Support: NIMH: R01 MH31340, Psychomotility and Cognitive Style in the Schizophrenias; RO1 MH49487,
Characterization of Schizophrenia-related Traits; RO1 MH59513, Bayesian Analysis for Genes with Pleiotropic Effects;
RO1 GM57453, Convergence Rates of Markov Chains in Genetic Analysis; RO3 MH 60272, Parsing Contextual Insensitivity in Schizophrenia; RO1 MH 61824, Motion Processing System in Schizophrenia; PO1 MH31154, Biological Research in Schizophrenia; KO5 MH01021, Psychobiological Studies of Schizophrenia. The Hunt Foundation. Eli Lilly.
Program Site: Mailman Research Center, McLean Hospital; Vision Sciences Laboratory, Harvard University; Department of Statistics, Harvard University.
Program Directors: Philip S. Holzman, Ph.D., Steven Matthysse, Ph.D., Deborah L. Levy, Ph.D. Psychology Research Laboratory, McLean Hospital, 115 Mill St., Belmont, MA 02478. e-mail addresses: psh@wjh.harvard.edu; levy@wjh.harvard.edu; swm@wjh.harvard.edu .
Contact Person: Nancy Maxwell, Administrative Assistant, (617) 855-3505; FAX (617) 855-2778.
Training Opportunities: Both pre- and post-doctoral training positions are available.
Representative Publications:
Chen Y, Nakayama K, Levy DL, Matthysse S, Holzman PS. Psychophysical isolation of motion processing deficits in schizophrenics and their relatives and its relation to eye tracking deficits. Proc Nat'l Acad Sci 1999; 6:4724-9.
Holzman PS, Kringlen E, Levy DL, Haberman S. Deviant eye tracking in twins discordant for psychosis. Arch Gen Psychiatry 1980;37:627-631.
Holzman PS, Proctor LR, Hughes DW. Eye tracking patterns in schizophrenia. Science 1973;181:179-181.
Levy DL, Holzman PS, Matthysse S, Mendell NR. Eye tracking and schizophrenia: A critical perspective. Schiz Bull 1993;19:461-536.
Matthysse S, Holzman PS, Lange K. The genetic transmission of schizophrenia: Application of Mendelian latent structure analysis to eye tracking dysfunctions in schizophrenia and affective disorder. J Psychiatr Res 1986; 20:57-65.
Matthysse S, Levy DL, Wu Y, Rubin D, Holzman PS. Modeling intermittent degradation in schizophrenic performance. Schiz Res 1999;40:131-146.
Park S, Holzman PS. Schizophrenics show spatial working memory deficits. Arch Gen Psychiatry 1992;49:975-982.
Titone D, Levy DL, Holzman PS. Contextual insensitivity in schizophrenic language processing: Evidence from lexical
ambiguity. J Abnormal Psychol 2000;109:761-767.