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Eye tracking dysfunction in offspring from the New York high-risk project
624
B1OL PSYCHIATRY 1995;37:593 683
112. EFFECTS OF RACE ON EEG SLEEP IN MAJOR DEPRESSION D.E. Giles & D.J. Kupfer University o f Pittsburgh Medical School, Pittsburgh, P A 15213 The constellation of EEG sleep changes observed in unipolar depression includes reduced REM latency, increased REM time, increased phasic REM activity, and slow-wave sleep deficits. Effects of depressive severity, medication, family history, episode history, sleep schedules, season, reproductive phase, age, and sex on these measures have been characterized with varying precision. One influence that is virtually uneharacterized is race. Data from an epidemiologically representative sample indicate that races differ with regard to prevalence of affective disorders, with African-Americans at reduced risk relative to Euro-Americans. Studies implicating EEG sleep abnormalities in vulnerability for onset and recurrence of depression indicate that effects of race must be understood. To evaluate the effects of race on sleep, we have conducted a retrospective study of unipolar depressed patients who had participated in research protocols at Western Psychiatric Institute and Clinic from 1981-1994. Groups were based on self-described race (black/white) and were matched blind to EEG sleep data within research protocol to control for diagnostic practices, age, and sex. Patients with histories of substance abuse, alcohol abuse, psychotic disorders, and bipolar disorders were excluded. Only patients with at least two consecutive nights of EEG sleep were included. To date, 46 African-American unipolar depressed patients have been matched to 90 age-, sex-, and protocol-matched Euro-Americans. A double-matched control group was generated to reduce error variance and increase power to detect differences. Results will be discussed with regard to an array of vulnerability factors for unipolar depression.
113. TIMECOURSE OF ANTIDEPRESSANT EFFECT OF ELECTROCONVULSIVE THERAPY D. Maixner, R. Tandon, J.R. DeQuardo, L. Grunhaus, H. Kales, & L. Becks Electroconvulsive T h e r a p y P r o g r a m , University o f M i c h i g a n , A n n Arbor, MI 48109-01 16 Although electroconvulsive therapy (ECT) is an extremely effective modality for treating depression, the specific timecourse and pattern of its antidepressant effect are not clearly delineated. A better understanding of the temporal profile of ECT's antidepressant effect would be clinically useful and can potentially elucidate underlying neurobiological mechanisms. In an effort to address this question, we studied the course of depressive symptomatology during 150 courses of electroconvulsive therapy. Ninety patients with recurrent major depressive disorder (MDD), who received these 150 courses of ECT, constituted the sample for this study. ECT dosage parameters were not strictly contrnlled but were determined by the ECT consultant administering the treatments. The severity of depression was assessed by the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Depression Rating (GDR) which were administered on a weekly basis. Mean HRSD scores improved by 18 points over the course of ECT. Approximately 40% of this improvement occurred over the first week, as reflected by reduction in total HRSD scores from week 0 to week 1. The extent of clinical improvement progressively decreased with increasing number of weeks; while this effect was most pronounced when the entire sample was considered, it was also noted in the subgroup of patients receiving >9 ECT lreatments. Vegetative symptoms (sleep, appetite) improved first, closely followed by psychomotor activity (retardation/agitation), followed by mood and depressive cognition. Although the greatest degree of improvement occurred during the initial phases of the ECT course, there was a distinct group of patients
FRIDAE, MAY 19
who responded late in the course; this suggests that minimal/no response early in the course of ECT treatment does not necessarily predict nonresponse over the entire course. Although the antidepressant effect of ECT is more rapid than that observed with antidepressant medications, the overall profile of response of various components of depression is similar; this suggests a commonality in the neurobiologieal mechanisms underlying the antidepressant effects of ECT and antidepressant medications.
114. EFFECTS OF PRIOR ELECTROCONVULSIVE THERAPY ON SEIZURE INDUCTION & DURATION S. Mahapatra, R. Tandon, J.R. DeQuardo, L. Grunhaus, H. Kales, & L. Becks E l e c t r o c o n v u l s i v e T h e r a p y P r o g r a m , University o f M i c h i g a n , A n n Arbor, MI 4 8 1 0 9 - 0 1 1 6 During a course ofelectroconvulsive therapy (ECT), resistance to seizure induction (seizure threshold) increases and seizure duration decreases; in fact, this "'anticonvulsant" effect of ECT has been related by some experts to the antidepressant effects of ECT. How long these effects persist is unclear and a topic of controversy. In general, ECT has not been associated with many long-term effects. To further study this question, we compared seizure characteristics and ECT stimulus parameters across different courses of ECT in patients with recurrent major depressive disorder (MDD) who received two or more courses of electroconvulsive therapy over a 10-year period. Forty patients with l 17 courses of ECT over this period were studied. Patients were not receiving any benzodiazepines, anticonvulsants, or any psychotropic medications during any of these courses of ECT. Controlling for the stimulus parameters, seizure duration was significantly affected by course (p <0.02); seizure duration decreased with increasing course number. When analyzed separately, this effect was observed for treatments 1, 2, 3, and 4 of each course. Sequential significant decreases in seizure duration were observed until course 4, when reduced sample size and a possible floor effect may have limited our ability to detect such a relationship. Higher energy levels were utilized in later courses of ECT, suggesting the possibility of higher seizure threshold in later courses of ECT; however, seizure threshold was not directly assessed in this study. These data suggest that ECT may have relatively long-lasting effects on seizure induction and maintenance. The precise duration of this effect is, however, unclear. Teasing out this relationship from effects of long-term depressive illness and other factors on seizure induction and maintenance is also difficult. The precise mechanisms underlying this hmg-term anticonvulsant effect of ECT is unclear; the relevance of this effect to antidepressant efficacy of ECT and process of relapse in depression merits further study.
115. EYE TRACKING DYSFUNCTION IN OFFSPRING FROM THE NEW YORK HIGHRISK PROJECT D. Rosenberg ~, J. Sweeney 1, B. Cornblatt2, E. Squires-Wheeler 3, K. O'Hearn l, & L. ErlenmeyerKimling 3 ~University o f Pittsburgh Medical Center, Pittsburgh, P A 15213; 2 M o u n t Sinai School o f Medicine, N e w York, N Y 10029; 3 C o l u m b i a University, N e w York, N Y The identification of neurobehavioral indicators of susceptibility to schizophrenia is a major aim of research into this illness. The New York High-
FRIDAE, MAY 19
Risk Project characterized and studied a large sample of children at high risk for schizophrenia, unipolar depression, and bipolar disorder, and followed their developmental trajectory into young adulthood with cognitive, neurophysiologic, and psychosocial assessments. This study was conducted to evaluate the diagnostic specificity of eye tracking deficits as a biological marker for schizophrenia. To our knowledge, this study is the first comparison of offspring of unipolar depressed and bipolar subjects with offspring of schizophrenic probands. Measures of eye movement activity included the global spectral purity index of pursuit performance and the frequency of anticipatory saccades. Offspring of schizophrenic and depressed probands both had significant global performance deficits, but only the offspring of schizophrenic probands had an increased rate of intrusive anticipatory saccades. Interestingly, attention facilitation procedures effectively normalized eye tracking deficits in the offspring of schizophrenic patients. This is the first demonstration that a specific oculomotor abnormality (increased anticipatory saccade rate) may provide a more specific biological marker of risk for schizophrenia than the more widely used global indices of eye tracking performance. Since anticipatory saccades are not visually guided and result from a failure to attend sufficiently to an external stimulus, they may be triggered by an internal representation of future target movement.
~tOL PSYCHIATRY 625 1995:37:593-683
schizophrenic children, 19 ADHD children, and 22 normal children were studied while there were engaged in a smooth-pursuit eye tracking task using infrared oculography. Eye-tracking variables were compared across the three groups, covarying for age and IQ, and, within the schizophrenic group, were correlated with clinical measures, neurologic signs, and ventricular/brain ratio. Schizophrenic children exhibited significantly greater smooth pursuit impairments than either normal or ADHD subjects, as reflected by greater root mean square error (RMSE), lower percentage of total task time engaged in tracking the target, and greater frequency and frequency-mean saccadic amplitude product of anticipatory and back-up saccades. ADHD subjects were significantly worse than normals only on RMSE. Within the schizophrenic group, there were no significant relationships between eye-tracking variables, clinical variables, or ventricular/brain ratio. Neurologic signs were positively correlated with frequency-mean saccadic amplitude product of anticipatory saccades. Frequency-mean saccadic amplitude product of anticipatory saccades in childhood-onset schizophrenics was greater than that observed in two comparable studies of adult-onset schizophrenics. Childhood-onset schizophrenia is associated with a similar pattern of smooth-pursuit abnormalities to that seen in adult-onset schizophrenia. Saccadic disinhibition, as measured by frequency and amplitude of anticipatory saccades, may be more severe in childhood-onset schizophrenia.
116. CHILDHOOD-ONSET SCHIZOPHRENIA: THE SEVERITY OF PREMORBID COURSE J. Alaghband-Rad, K. McKenna, & C.T. Gordon Child Psychiatry Branch, National Institute o f Mental Health, Bethesda, M D 20892-1600 The premorbid histories (up to 1 year before onset of first psychotic symptoms) of 23 children meeting DSM-III-R criteria for schizophrenia with onset before age 12 were reviewed and compared with childhood data of later-onset schizophrenics. The premorbid features were rated from hospital and clinical records, clinical interviews, rating scales, and tests. In keeping with previous studies, specific developmental disabilities and transient early symptoms of autism, particularly motor stereotypies were common. Comparison with the childhood of later-onset schizophrenia showed greater delay in language development, more premorbid speech and language disorders, learning disorders, and disruptive behavior disorders. (Sixty percent had received or was estimated to meet criteria for one or more clinical diagnoses.) In conclusion, childhood-onset schizophrenia represents a more malignant form of the disorder. The presence of prepsychotic language difficulties focuses attention toward early importance of left temporal and frontal lobe brain development; early transient motor stereotypies suggest developmental basal ganglia abnormalities.
117. SMOOTH-PURSUIT EYE MOVEMENTS IN CHILDHOOD-ONSET SCHIZOPHRENIA L.K. Jacobsen l, W. Hong 2, D.W. Hommer 3, F.X. Castellanos l, J.A. Frazier l, J.N. Giedd 1, C.T. Gordon l, B.I. Karp4, K. McKenna l, & J.L. Rapoport I nChild Psychiatry Branch, NIMH, Bethesda, M D 20894; ZExperimental Therapeutics Branch, NIMH; 3Laboratory o f Clinical Studies, N I A A A ; 4Office o f the Clinical Director, NINDS Smooth-pursuit eye movements were examined in schizophrenic children and contrasted with those of normal and ADHD subjects. Seventeen
118. BRAIN VOLUME CORRELATED WITH NEUROPSYCHOLOGICAL ABILITY IN FIRST EPISODE SCHIZOPHRENIA R.M. Bilder l, H. Wu l, B. Bogerts 2, D. Willson 1,3, & J.A. Lieberman I lHillside Hospital Division o f Long Island Jewish Medical Center, Glen Oaks, N Y 11004; 2University o f Magdeburg, Magdeburg, Germany; 3St. J o h n ' s University, Jamaica, NY 11439 It remains controversial whether schizophrenia is associated with reduced overall or regional cerebral volumes, and whether variations in cerebral w~lume may be associated with functional abnormalities. We examined relations of regional cerebral w~lumes with neuropsychological (NP) functions among 60 patients participating in a study of first episode schizophrenia. Regional cerebral volumes were measured on magnetic resonance images acquired using a "FLASH" sequence at 1.0T, with contiguous 3.1ram slices and in-plane resolution of 1 mm × 1 mm. Regional volumes included cortical gray and white matter; subcortical and ventricular volumes were excluded. Regions included right and left prefrontal. premotor, sensorimotor, occipitoparietal, and temporal regions, along with total left and right hemispheres, and total cortical volume (all adjusted for effects of height, age, and socioeconomic status). NP measures were drawn from an extensive battery administered after patients were stabilized on antipsychotic medications. Composite scales were constructed to measure language, memory, attentional, executive, motor, and visuospatial functions; a "global" NP scale was the mean of these functional scales. Larger total cortical volume was correlated with better global performance r~ 0.31, p < 0.05, two-tailed). This effect was due to a relatively robust relation among men (R 2 ~ 0.22) but not women (R 2 = 0.0015). Total cortical volume tended to correlate slightly but not significantly more robustly with motor and visuospatial compared to other NP scales. Global NP function correlated moderately with all regions except the premotor region. More specific structure-function correlates were not apparent. The results suggest that total cerebral volume is associated with better global NP function in schizophrenia, at least among men.
B1OL PSYCHIATRY 1995;37:593 683
112. EFFECTS OF RACE ON EEG SLEEP IN MAJOR DEPRESSION D.E. Giles & D.J. Kupfer University o f Pittsburgh Medical School, Pittsburgh, P A 15213 The constellation of EEG sleep changes observed in unipolar depression includes reduced REM latency, increased REM time, increased phasic REM activity, and slow-wave sleep deficits. Effects of depressive severity, medication, family history, episode history, sleep schedules, season, reproductive phase, age, and sex on these measures have been characterized with varying precision. One influence that is virtually uneharacterized is race. Data from an epidemiologically representative sample indicate that races differ with regard to prevalence of affective disorders, with African-Americans at reduced risk relative to Euro-Americans. Studies implicating EEG sleep abnormalities in vulnerability for onset and recurrence of depression indicate that effects of race must be understood. To evaluate the effects of race on sleep, we have conducted a retrospective study of unipolar depressed patients who had participated in research protocols at Western Psychiatric Institute and Clinic from 1981-1994. Groups were based on self-described race (black/white) and were matched blind to EEG sleep data within research protocol to control for diagnostic practices, age, and sex. Patients with histories of substance abuse, alcohol abuse, psychotic disorders, and bipolar disorders were excluded. Only patients with at least two consecutive nights of EEG sleep were included. To date, 46 African-American unipolar depressed patients have been matched to 90 age-, sex-, and protocol-matched Euro-Americans. A double-matched control group was generated to reduce error variance and increase power to detect differences. Results will be discussed with regard to an array of vulnerability factors for unipolar depression.
113. TIMECOURSE OF ANTIDEPRESSANT EFFECT OF ELECTROCONVULSIVE THERAPY D. Maixner, R. Tandon, J.R. DeQuardo, L. Grunhaus, H. Kales, & L. Becks Electroconvulsive T h e r a p y P r o g r a m , University o f M i c h i g a n , A n n Arbor, MI 48109-01 16 Although electroconvulsive therapy (ECT) is an extremely effective modality for treating depression, the specific timecourse and pattern of its antidepressant effect are not clearly delineated. A better understanding of the temporal profile of ECT's antidepressant effect would be clinically useful and can potentially elucidate underlying neurobiological mechanisms. In an effort to address this question, we studied the course of depressive symptomatology during 150 courses of electroconvulsive therapy. Ninety patients with recurrent major depressive disorder (MDD), who received these 150 courses of ECT, constituted the sample for this study. ECT dosage parameters were not strictly contrnlled but were determined by the ECT consultant administering the treatments. The severity of depression was assessed by the 17-item Hamilton Rating Scale for Depression (HRSD) and the Global Depression Rating (GDR) which were administered on a weekly basis. Mean HRSD scores improved by 18 points over the course of ECT. Approximately 40% of this improvement occurred over the first week, as reflected by reduction in total HRSD scores from week 0 to week 1. The extent of clinical improvement progressively decreased with increasing number of weeks; while this effect was most pronounced when the entire sample was considered, it was also noted in the subgroup of patients receiving >9 ECT lreatments. Vegetative symptoms (sleep, appetite) improved first, closely followed by psychomotor activity (retardation/agitation), followed by mood and depressive cognition. Although the greatest degree of improvement occurred during the initial phases of the ECT course, there was a distinct group of patients
FRIDAE, MAY 19
who responded late in the course; this suggests that minimal/no response early in the course of ECT treatment does not necessarily predict nonresponse over the entire course. Although the antidepressant effect of ECT is more rapid than that observed with antidepressant medications, the overall profile of response of various components of depression is similar; this suggests a commonality in the neurobiologieal mechanisms underlying the antidepressant effects of ECT and antidepressant medications.
114. EFFECTS OF PRIOR ELECTROCONVULSIVE THERAPY ON SEIZURE INDUCTION & DURATION S. Mahapatra, R. Tandon, J.R. DeQuardo, L. Grunhaus, H. Kales, & L. Becks E l e c t r o c o n v u l s i v e T h e r a p y P r o g r a m , University o f M i c h i g a n , A n n Arbor, MI 4 8 1 0 9 - 0 1 1 6 During a course ofelectroconvulsive therapy (ECT), resistance to seizure induction (seizure threshold) increases and seizure duration decreases; in fact, this "'anticonvulsant" effect of ECT has been related by some experts to the antidepressant effects of ECT. How long these effects persist is unclear and a topic of controversy. In general, ECT has not been associated with many long-term effects. To further study this question, we compared seizure characteristics and ECT stimulus parameters across different courses of ECT in patients with recurrent major depressive disorder (MDD) who received two or more courses of electroconvulsive therapy over a 10-year period. Forty patients with l 17 courses of ECT over this period were studied. Patients were not receiving any benzodiazepines, anticonvulsants, or any psychotropic medications during any of these courses of ECT. Controlling for the stimulus parameters, seizure duration was significantly affected by course (p <0.02); seizure duration decreased with increasing course number. When analyzed separately, this effect was observed for treatments 1, 2, 3, and 4 of each course. Sequential significant decreases in seizure duration were observed until course 4, when reduced sample size and a possible floor effect may have limited our ability to detect such a relationship. Higher energy levels were utilized in later courses of ECT, suggesting the possibility of higher seizure threshold in later courses of ECT; however, seizure threshold was not directly assessed in this study. These data suggest that ECT may have relatively long-lasting effects on seizure induction and maintenance. The precise duration of this effect is, however, unclear. Teasing out this relationship from effects of long-term depressive illness and other factors on seizure induction and maintenance is also difficult. The precise mechanisms underlying this hmg-term anticonvulsant effect of ECT is unclear; the relevance of this effect to antidepressant efficacy of ECT and process of relapse in depression merits further study.
115. EYE TRACKING DYSFUNCTION IN OFFSPRING FROM THE NEW YORK HIGHRISK PROJECT D. Rosenberg ~, J. Sweeney 1, B. Cornblatt2, E. Squires-Wheeler 3, K. O'Hearn l, & L. ErlenmeyerKimling 3 ~University o f Pittsburgh Medical Center, Pittsburgh, P A 15213; 2 M o u n t Sinai School o f Medicine, N e w York, N Y 10029; 3 C o l u m b i a University, N e w York, N Y The identification of neurobehavioral indicators of susceptibility to schizophrenia is a major aim of research into this illness. The New York High-
FRIDAE, MAY 19
Risk Project characterized and studied a large sample of children at high risk for schizophrenia, unipolar depression, and bipolar disorder, and followed their developmental trajectory into young adulthood with cognitive, neurophysiologic, and psychosocial assessments. This study was conducted to evaluate the diagnostic specificity of eye tracking deficits as a biological marker for schizophrenia. To our knowledge, this study is the first comparison of offspring of unipolar depressed and bipolar subjects with offspring of schizophrenic probands. Measures of eye movement activity included the global spectral purity index of pursuit performance and the frequency of anticipatory saccades. Offspring of schizophrenic and depressed probands both had significant global performance deficits, but only the offspring of schizophrenic probands had an increased rate of intrusive anticipatory saccades. Interestingly, attention facilitation procedures effectively normalized eye tracking deficits in the offspring of schizophrenic patients. This is the first demonstration that a specific oculomotor abnormality (increased anticipatory saccade rate) may provide a more specific biological marker of risk for schizophrenia than the more widely used global indices of eye tracking performance. Since anticipatory saccades are not visually guided and result from a failure to attend sufficiently to an external stimulus, they may be triggered by an internal representation of future target movement.
~tOL PSYCHIATRY 625 1995:37:593-683
schizophrenic children, 19 ADHD children, and 22 normal children were studied while there were engaged in a smooth-pursuit eye tracking task using infrared oculography. Eye-tracking variables were compared across the three groups, covarying for age and IQ, and, within the schizophrenic group, were correlated with clinical measures, neurologic signs, and ventricular/brain ratio. Schizophrenic children exhibited significantly greater smooth pursuit impairments than either normal or ADHD subjects, as reflected by greater root mean square error (RMSE), lower percentage of total task time engaged in tracking the target, and greater frequency and frequency-mean saccadic amplitude product of anticipatory and back-up saccades. ADHD subjects were significantly worse than normals only on RMSE. Within the schizophrenic group, there were no significant relationships between eye-tracking variables, clinical variables, or ventricular/brain ratio. Neurologic signs were positively correlated with frequency-mean saccadic amplitude product of anticipatory saccades. Frequency-mean saccadic amplitude product of anticipatory saccades in childhood-onset schizophrenics was greater than that observed in two comparable studies of adult-onset schizophrenics. Childhood-onset schizophrenia is associated with a similar pattern of smooth-pursuit abnormalities to that seen in adult-onset schizophrenia. Saccadic disinhibition, as measured by frequency and amplitude of anticipatory saccades, may be more severe in childhood-onset schizophrenia.
116. CHILDHOOD-ONSET SCHIZOPHRENIA: THE SEVERITY OF PREMORBID COURSE J. Alaghband-Rad, K. McKenna, & C.T. Gordon Child Psychiatry Branch, National Institute o f Mental Health, Bethesda, M D 20892-1600 The premorbid histories (up to 1 year before onset of first psychotic symptoms) of 23 children meeting DSM-III-R criteria for schizophrenia with onset before age 12 were reviewed and compared with childhood data of later-onset schizophrenics. The premorbid features were rated from hospital and clinical records, clinical interviews, rating scales, and tests. In keeping with previous studies, specific developmental disabilities and transient early symptoms of autism, particularly motor stereotypies were common. Comparison with the childhood of later-onset schizophrenia showed greater delay in language development, more premorbid speech and language disorders, learning disorders, and disruptive behavior disorders. (Sixty percent had received or was estimated to meet criteria for one or more clinical diagnoses.) In conclusion, childhood-onset schizophrenia represents a more malignant form of the disorder. The presence of prepsychotic language difficulties focuses attention toward early importance of left temporal and frontal lobe brain development; early transient motor stereotypies suggest developmental basal ganglia abnormalities.
117. SMOOTH-PURSUIT EYE MOVEMENTS IN CHILDHOOD-ONSET SCHIZOPHRENIA L.K. Jacobsen l, W. Hong 2, D.W. Hommer 3, F.X. Castellanos l, J.A. Frazier l, J.N. Giedd 1, C.T. Gordon l, B.I. Karp4, K. McKenna l, & J.L. Rapoport I nChild Psychiatry Branch, NIMH, Bethesda, M D 20894; ZExperimental Therapeutics Branch, NIMH; 3Laboratory o f Clinical Studies, N I A A A ; 4Office o f the Clinical Director, NINDS Smooth-pursuit eye movements were examined in schizophrenic children and contrasted with those of normal and ADHD subjects. Seventeen
118. BRAIN VOLUME CORRELATED WITH NEUROPSYCHOLOGICAL ABILITY IN FIRST EPISODE SCHIZOPHRENIA R.M. Bilder l, H. Wu l, B. Bogerts 2, D. Willson 1,3, & J.A. Lieberman I lHillside Hospital Division o f Long Island Jewish Medical Center, Glen Oaks, N Y 11004; 2University o f Magdeburg, Magdeburg, Germany; 3St. J o h n ' s University, Jamaica, NY 11439 It remains controversial whether schizophrenia is associated with reduced overall or regional cerebral volumes, and whether variations in cerebral w~lume may be associated with functional abnormalities. We examined relations of regional cerebral w~lumes with neuropsychological (NP) functions among 60 patients participating in a study of first episode schizophrenia. Regional cerebral volumes were measured on magnetic resonance images acquired using a "FLASH" sequence at 1.0T, with contiguous 3.1ram slices and in-plane resolution of 1 mm × 1 mm. Regional volumes included cortical gray and white matter; subcortical and ventricular volumes were excluded. Regions included right and left prefrontal. premotor, sensorimotor, occipitoparietal, and temporal regions, along with total left and right hemispheres, and total cortical volume (all adjusted for effects of height, age, and socioeconomic status). NP measures were drawn from an extensive battery administered after patients were stabilized on antipsychotic medications. Composite scales were constructed to measure language, memory, attentional, executive, motor, and visuospatial functions; a "global" NP scale was the mean of these functional scales. Larger total cortical volume was correlated with better global performance r~ 0.31, p < 0.05, two-tailed). This effect was due to a relatively robust relation among men (R 2 ~ 0.22) but not women (R 2 = 0.0015). Total cortical volume tended to correlate slightly but not significantly more robustly with motor and visuospatial compared to other NP scales. Global NP function correlated moderately with all regions except the premotor region. More specific structure-function correlates were not apparent. The results suggest that total cerebral volume is associated with better global NP function in schizophrenia, at least among men.