Loren James Chapman - US grants

The goal of this research is to identify and to describe systematically those psychotic patients who demonstrate abnormal hemispheric asymmetries of function. Hemispheric functioning will be measured by three left-hemisphere and three right-hemisphere clinical neuropsychological tests. The left-hemisphere tasks will be 1) analogies, 2) a test for naming, 3) identification of unseen forms felt by the right hand. The right hemisphere tasks will be 1) line orientation, 2) dot localization, and 3) identification of unseen forms felt by the left hand. The measures of left- and right-hemispheric functioning will be psychometrically matched so that specific differential deficits in hemispheric functioning can be measured independently of generalized performance deficit. A broadly heterogenous sample of nonorganic psychotics will be included who will be diagnosed by three alternative diagnostic systems: RDC, Feighner, and DSM-III. In addition, the patients will be rated on the Cannon-Spoor et al. Premorbid Adjustment Scale, the Andreasen positive-negative symptom dimension, chronicity, the Tsuang & Winokur paranoid-hebephrenic distinction, and a behavioral measure of handedness. Handedness of first-degree relatives will also be obtained. A replication study will be done to validate initial findings.

Hypothetically psychosis-prone subjects (N = 343) and control subjects (N = 158), who were identified and interviewed approximately ten years earlier, will be followed up and re- interviewed to determine their incidence of clinical attention for psychosis. Other dependent variables will be diagnostic category of psychosis, incidence of mood disorders, incidence of schizotypal personality disorder, and level of social adjustment. The hypothetically psychosis-prone subjects were originally identified by their deviant scores on three scales produced by this project: the Perceptual Aberration-Magical Ideation Scale (N = 195), the Physical Anhedonia Scale (N = 74), and the Impulsive Nonconformity Scale (N = 74). (Subjects with high scores on these scales have been found in previous studies to show many traits and symptoms expected in psychosis-prone individuals. Three subjects identified by the Perceptual Aberration-Magical Ideation Scale were found at a 25-month follow-up to have already received clinical attention for psychosis). Independent variables, other than group membership, will be scores on each of the three scales mentioned above, as well as handedness and ratings of several symptoms from the initial interviews 10 years earlier. Three interview schedules will be used in the follow-up: a modified Schedule for Affective Disorders and Schizophrenia- Lifetime version a revised version of the Social Adjustment Scale, and the Schedule for Schizotypal Personalities.

The goal of the proposed research is to develop diverse psychometrically sound cognitive markers of the predisposition to schizophrenia. The research plan focuses on solutions to psychometric problems because such problems appear to be a major obstacle in this area. The tasks chosen are ones that appear especially promising for measuring important but separate aspects of schizophrenic cognitive defect and that seem suitable for measuring the mild degree of cognitive defect that is expected in the nonpsychotic relatives of psychotic patients. The measures are: 1) associatively based semantic priming, a phenomenon that reflects persistence of associative arousal; 2) a version of the span-of-apprehension task, which measures attentional breadth and possibly controlled allocation of attentional resources; 3) defective comprehension in binaural listening which is thought to reflect defective interhemispheric transfer; 4) the Navon task which measures the failure to inhibit responses to material that should be screened out to facilitate cognitive processing; and 5) a version of the Place and Gilmore task which measures an aberrant perceptual response to groupings of stimuli. The psychometric problems of special concern are: 1) the artifactual curvilinear relationship in measures of differential deficit, for Tasks A and B, between the (A - B) difference score and the (A + B) score of overall accuracy, and 2) the effects of differential discriminating power of the two tasks coupled with differences among subjects in overall accuracy in yielding artifactual difference scores. The design solutions will be either the use of psychometrically matched tasks or the use of titration in which (A + B) overall accuracy is maintained at a constant level by manipulation of an appropriate stimulus variable. Schizophrenic, schizophreniform, and bipolar patients will be tested as well as relatives of schizophrenic and schizophreniform patients and control subjects. Schizophrenics will be tested at different stages of their illness and both on-drug and drug-free patients will be included.

This application for a Research Scientist Award is for the support of two lines of research. The first is an attempt to develop diverse psychometrically sound cognitive markers of the predisposition to schizophrenia. The research plan focuses on psychometric problems that appear to be a major obstacle in this area. The tasks are ones that appear especially promising for measuring important but separate aspects of schizophrenic cognitive defect and that seem suitable for measuring the mild degree of cognitive defect that is expected in the nonpsychotic relatives of patients. The measures are: 1) associatively based semantic priming, which reflects persistence of associative arousal; 2) a version of the span-of-apprehension task, which measures attentional breadth; 3) defective comprehension in binaural listening, which is thought to reflect defective interhemispheric transfer; 4) the Navon task, which measures the failure to inhibit responses to stimuli that should be screened out to facilitate cognitive processing; and 5) a version of the Place and Gilmore task, which measures an aberrant perceptual response to groupings of stimuli. The psychometric problems of special concern are: 1) the artifactual curvilinear relationship in measures of differential deficit, for Tasks A and B, between the (A - B) difference score and the (A + B) score of overall accuracy, and 2) the effects of differential discriminating power of the two tasks coupled with differences among subjects in overall accuracy in yielding artifactual difference scores. The design solutions will be either the use of psychometrically matched tasks on the use of titration in which (A + B) overall accuracy is maintained at a constant level by manipulation of an appropriate stimulus variable. Schizophrenic, schizophreniform, and bipolar patients will be tested as well as relatives of patients and control subjects. The second line of research is a ten-year follow-up of 343 college students identified as psychosis prone by their scores on scales of psychosis proneness, and 158 control subjects. Laboratory findings, as well as the results of a two-year follow-up, indicate that this group is at elevated risk for psychosis.

Hypothetically psychosis-prone subjects (N = 343) and control subjects (N = 158), who were identified and interviewed approximately ten years earlier, will be followed up and re- interviewed to determine their incidence of clinical attention for psychosis. Other dependent variables will be diagnostic category of psychosis, incidence of mood disorders, incidence of schizotypal personality disorder, and level of social adjustment. The hypothetically psychosis-prone subjects were originally identified by their deviant scores on three scales produced by this project: the Perceptual Aberration-Magical Ideation Scale (N = 195), the Physical Anhedonia Scale (N = 74), and the Impulsive Nonconformity Scale (N = 74). (Subjects with high scores on these scales have been found in previous studies to show many traits and symptoms expected in psychosis-prone individuals. Three subjects identified by the Perceptual Aberration-Magical Ideation Scale were found at a 25-month follow-up to have already received clinical attention for psychosis). Independent variables, other than group membership, will be scores on each of the three scales mentioned above, as well as handedness and ratings of several symptoms from the initial interviews 10 years earlier. Three interview schedules will be used in the follow-up: a modified Schedule for Affective Disorders and Schizophrenia- Lifetime version a revised version of the Social Adjustment Scale, and the Schedule for Schizotypal Personalities.