Racial effects on neuropsychological functioning in schizophrenia.

OBJECTIVE: This study assessed the effects of race on neuropsychological functioning in patients with schizophrenia. METHOD: A total of 160 patients with schizophrenia completed an extensive neuropsychological test battery. Scores were standardized to a group of 99 psychiatrically and physically healthy subjects and categorized into seven functional domains: concentration, executive function, language, motor function, spatial memory, verbal memory, and visual processing. RESULTS: African Americans (N=25) had significantly lower mean scores on executive function, language, spatial memory, and visual processing than did Caucasians (N=135). Statistical control for patient and family education eliminated all significant effects. CONCLUSIONS: Educational differences in patients and families may account for some of the performance heterogeneity reported in patients with schizophrenia and should be routinely analyzed with other sociodemographic factors such as race and sex.

Race in the "decade of the brain".

Despite NIMH efforts to facilitate the study of women and minorities in federally funded schizophrenia research, there is a significant lack of information about race differences in brain morphology and neuropsychological function in schizophrenia. A review of three major psychiatric journals between 1994 and 1996 revealed that only 14 (2.8%) of 502 schizophrenia articles reported the results of race analyses. Only 84 (16.7%) even reported the racial composition of the study sample. The study of race differences in schizophrenia, although fraught with methodological complexity and social/political tension, is necessary to prevent inappropriate generalization of research results across racial groups.

Schizophrenia, substance use, and brain morphology.

The high rate of comorbid substance abuse in schizophrenia and the consistently poor outcome of this comorbidity are well established findings in the research literature. However, the reasons for the high rate of comorbidity are not adequately understood, and the question of why some patients with schizophrenia abuse substances and others do not remains unanswered. There is widespread agreement about the clinical heterogeneity of schizophrenia, and there is some evidence suggesting that the heterogeneous clinical presentation may reflect a parallel underlying heterogeneity of brain morphology. We were interested in examining the possibility that the high rate of substance abuse and the characteristically poor outcome may be associated with the underlying brain morphology. Our hypothesis was that study subjects with schizophrenia and substance abuse would have higher rates of gross brain abnormalities than subjects with only schizophrenia. In an attempt to explore this possibility, we looked at qualitative differences in magnetic resonance imaging scans for a large sample (n = 176) of schizophrenia patients. In the group of patients who abused both alcohol and drugs, we found the rate of gross brain abnormalities to be slightly less than half the rate found among the patients with no history of alcohol or substance abuse (8 vs. 19). Although these results are not statistically significant, they reflect a trend that is compatible with previous findings, suggesting that substance abuse history may be accompanied by less impairment in certain areas, which in turn may be reflected in a better premorbid adjustment. However, our findings are not compatible with previous findings that show substance abuse to be associated with more severe symptoms and a poorer outcome in schizophrenia.

Age at onset and sex differences in corpus callosum area in schizophrenia.

Previous research on neuropsychological function among schizophrenia patients suggests that typical onset males (first psychiatric hospital admission before age 25) and typical onset females (first admission after age 25) may exhibit less lateralization of behavioral function ('hypolateralization') than atypical onset males and atypical onset females. To explore whether these differences were reflected in corpus callosum area, brain morphometric data from a large sample of subjects diagnosed with schizophrenia were analyzed. Typical onset females and typical onset males were compared to atypical onset females and atypical onset males on corpus callosum area. While neither sex nor onset effect on total corpus callosum area was statistically significant, analysis of standard subregions of the corpus callosum revealed a significant interaction effect on the posterior 20% area of the corpus callosum, with typical onset women having particularly large corpora callosa. The anterior 50% area did not differ among the groups. The results are discussed in terms of the role of anomalies in the integration and hemispheric transfer of information as underlying mechanisms of schizophrenia.

Brain torque and sex differences in schizophrenia.

The opposing asymmetry of the frontoparietal brain regions has been referred to as 'torque' and may be used as an index of speed of neurodevelopment. It has been recently suggested that torque is minimized in male schizophrenia, reflecting anomalous neurodevelopment. This study examined volumetric and linear torque in a group of 20 schizophrenia patients and 20 healthy individuals; all were right-handed and under the age of 46 years. None of the main or interaction effects on torque were statistically significant, although the sex difference in torque among schizophrenia patients (male larger than female) was more than seven times that in healthy subjects. Torque was significantly associated with years of education and age of illness onset (schizophrenia). These findings support the hypothesis that slowed neurodevelopment may be associated with male schizophrenia and may contribute to earlier age of onset and fewer years of education.

Sex differences in verbal IQ-performance IQ discrepancies among patients with schizophrenia and normal volunteers.

Substantial verbal IQ (VIQ)-performance IQ (PIQ) discrepancies may reflect brain dysfunction. The authors examined 159 patients with schizophrenia (115 men and 44 women) or schizoaffective disorder (25 men and 19 women) and 79 normal participants (33 men and 46 women), calculated mean VIQ-PIQ discrepancy scores by sex and diagnosis, and identified persons with large VIQ-PIQ discrepancies (15-point difference in either direction). Schizophrenic/schizoaffective men had a larger mean VIQ-PIQ discrepancy than did other groups. The proportion of all patients with either VIQ > PIQ or PIQ > VIQ (17.8%) was not significantly different from that of normal participants (22.8%). However, significantly more men than women with schizophrenia exhibited a VIQ > PIQ pattern (20% vs. 3.2%). No unusual discrepancy patterns were noted among normal participants. Results were interpreted in light of theories of hemisphere dysfunction in schizophrenia.

Childhood behavioral characteristics and adult brain morphology in schizophrenia.

It is well established that many schizophrenia patients manifest behavioral dysfunction long before the onset of clinical symptoms of illness. Some show signs of motor and socioemotional deficit as early as infancy. The present study examines the relations among childhood neuromotor, affective and behavior characteristics, and the association of these factors with adult brain morphology (MRI) in schizophrenia patients. Data on neuromotor functions and negative affect were obtained from coding of childhood films. Parents of patients provided information about six dimensions of childhood behavior problems. Analyses of data from patients and healthy siblings revealed that childhood neuromotor abnormalities and negative affect were associated with some of the behavioral dimensions. Among the patients, early childhood neuromotor deficits and negative affect were linked with greater ventricular enlargement in adulthood. The ratings of the behavior problem dimensions showed a complex relation with adult brain morphology, suggesting that externalized problems are linked with more abnormalities (smaller brain volume and larger ventricles), whereas internalized problems are associated with less abnormality. The findings are discussed in light of their implications for the developmental origins of brain abnormalities in schizophrenia.

Sex differences in neuropsychological functioning among schizophrenic patients.

OBJECTIVE: The view of schizophrenic men as having poorer premorbid development, earlier age at onset, and worse outcome than schizophrenic women predicts greater neuropsychological impairment in the former than the latter. The authors examined in detail neuropsychological functioning in a large group of schizophrenic patients and a healthy comparison group. METHOD: Neuropsychological functioning in 132 male and 63 female patients with schizophrenia or schizoaffective disorder was extensively studied and compared with that of 99 (40 male, 59 female) healthy individuals. RESULTS: As expected, the schizophrenic patients as a group were pervasively and significantly more impaired than the comparison group. Within schizophrenia, in contrast to the prediction, women performed significantly more poorly than men in verbal memory, spatial memory, and visual processing. Female schizophrenic patients also had significantly poorer right than left hemisphere performance, whereas male schizophrenic patients had identical scores for right and left hemisphere impairment. CONCLUSIONS: The findings are consistent with the hypothesis that schizophrenia among women may be partially understood as a right hemisphere dysfunction. Sampling, diagnostic, and epidemiologic factors may have affected the results.

Differences in qualitative brain morphology findings in schizophrenia, major depression, bipolar disorder, and normal volunteers.

This study examined the frequency and type of qualitative brain morphologic anomaly as a function of sex and diagnosis. Magnetic resonance imaging brain scans were evaluated by an experienced neuroradiologist blind to diagnosis. The scans of 325 individuals (108 schizophrenic, 20 schizoaffective, 27 major depressive, 20 bipolar and 150 healthy volunteers) were categorized into one of five groups: normal, hyperintensity signals, volume loss, ventricular anomaly or "other" abnormality. Schizophrenic men had significantly more morphologic anomalies, especially of the lateral ventricles than healthy male volunteers. Schizophrenic women did not differ from healthy women. Schizoaffective patients of both sexes, male depressive and female bipolar patients were also characterized by higher rates of brain anomalies. Independent of diagnosis, women were more likely than men to have hyperintensity signals among individuals with positive scan findings. The overall rate of brain morphologic anomalies is significantly higher among male schizophrenic patients than healthy volunteers; this is not specific to male schizophrenics, however, suggesting a global sex effect. Type of anomaly may differ by sex and give us clues about sex differences in the pathophysiology of psychopathology.

White matter hyperintensity signals associated with vascular risk factors in schizophrenia.

1. A sample of 165 schizophrenic subjects was compared to a normal control group in order to evaluate associations between white matter hyperintensity signals and vascular risk factors. 2. A comprehensive medical chart review was completed on all subjects evaluating potential vascular risk factors. Brain MRI acquisition was performed with 0.5 and 1.5 Telsa Philips scanners. 3. Prevalence rates of WMH signals in schizophrenic subjects and normal controls were 4.8% and 4.9%, respectively. 4. A significant association was found for schizophrenics with WHM signals to schizophrenics without signals for hypertension and history of CVA's. 5. This finding is consistent with an etiology of WMH signals in schizophrenia being related to vascular disease.

A double-blind dose-reduction trial of fluphenazine decanoate for chronic, unstable schizophrenic patients.

OBJECTIVE: This study evaluated the feasibility and impact of gradually reducing relatively high doses of fluphenazine decanoate by one-half for chronically impaired, poor inner-city patients with schizophrenia. METHOD: Forty-three patients currently receiving an average of 23 mg (0.3 mg/kg) of fluphenazine decanoate every 2 weeks were divided alternately into a group to remain at current doses (control group) and a group to undergo stepwise 50% dose reduction over 5 months under double-blind conditions. Clinical status and side effects were assessed quarterly for a year. Relapse was determined clinically and by changes in psychopathology ratings. RESULTS: Eighty-six percent (N = 37) of the patients (control group, N = 17; reduced-dose group, N = 20) completed the study. The groups did not differ at baseline in demographic or clinical variables or neuroleptic dose. In the reduced-dose group, doses were lowered to an average of 11.5 mg every 2 weeks. The two groups did not differ throughout the year in number of relapses, and hospitalization rates fell similarly in both (overall, by about 67%). Clinical measures changed little. Extrapyramidal symptoms worsened in the control group but improved slightly in the reduced-dose group. Tardive dyskinesia worsened in both groups, but less in the reduced-dose group. CONCLUSIONS: Maintenance neuroleptic doses much lower than the conventional ones can be achieved safely in schizophrenic patients by gradual reduction, without clinical worsening and perhaps with fewer extrapyramidal symptoms and less tardive dyskinesia. The two-thirds lower hospitalization rate, with substantial financial savings, apparently was due to nonspecific effects of research intervention.

Sex: an imperfect marker of gender.

As the study of sex differences in schizophrenia gains popularity, inconsistent use of terms such as "sex," "gender," "sex-related," and "sex-linked" can lead to conceptual ambiguity. I review briefly why precise terminology is important and draw the reader's attention to a well-developed literature, a knowledge of which should benefit our studies. Adoption of the term "sex" in reference to comparisons based on the demographic categories of female and male and the term "gender" in reference to comparisons of femaleness and maleness, as suggested by Kay Deaux (1993), is urged in the study of schizophrenia.

Sampling biases in studies of gender and schizophrenia.

Gender differences in schizophrenia are of great interest to researchers, and some have recently concluded that female patients suffer from a more benign form of the illness. However, the research findings do not support this conclusion consistently, and some reports suggest greater impairment in female patients. In this article, we discuss the potential effects of sampling biases on the findings from studies that compare male and female patients. More specifically, we assume that females do manifest a less severe schizophrenic illness than males, and we propose that sex differences in severity thresholds for voluntary and involuntary treatment are contributing to inconsistencies in the research findings. Some other sources of sampling bias that may influence findings on gender differences are also discussed.

Lateral ventricle-brain ratio and balance between CSF HVA and 5-HIAA in schizophrenia.

OBJECTIVE: Lateral ventricle enlargement in schizophrenia has been positively correlated with poor premorbid competence, negative symptoms, and poor treatment response and negatively correlated with concentrations of homovanillic acid (HVA), a dopaminergic metabolite. The authors provide further evidence of a reciprocal relationship between lateral ventricle size and dopaminergic activity in schizophrenia. METHOD: They assessed the relationship between lateral ventricle enlargement (ventricle-brain ratio, VBR) and CSF neurotransmitter metabolite concentrations (HVA and 5-hydroxyindoleacetic acid [5-HIAA]) in 45 patients with schizophrenia, 28 with affective disorders (19 patients with major depression and nine with bipolar disorder), and 91 normal comparison subjects. RESULTS: No group mean differences were significant. Although individual correlations of VBR with HVA and 5-HIAA were not statistically significant, the ratio of HVA to 5-HIAA was significantly correlated with VBR in the patients with schizophrenia, a finding consistent with dopaminergic-serotonergic balance hypotheses. CONCLUSIONS: These data suggest that it is the balance between HVA and 5-HIAA rather than their absolute levels which is associated with brain morphology and that this relationship between brain chemistry and morphology may be characteristic of the normal range of functioning for these systems. In other words, independent of whether brain morphology and chemistry differentiate psychopathological from nonpsychopathological states, there may be an orderly relationship between lateral ventricle size and the balance between HVA and 5-HIAA balance that is especially prominent in schizophrenia.

A discriminant validity study of negative symptoms with a special focus on depression and antipsychotic medication.

If the construct validity of the negative symptom syndrome is to be established, the conceptual and operational overlap between negative symptoms and other syndromes such as depression and the effects of medication must be explained. The author assessed 26 patients with schizophrenia and 21 patients without schizophrenia, most of whom had depression, at the end of an average 2-week drug washout period and after approximately 2 months of psychotropic medication administration. Negative symptoms were remarkably consistent in patients with schizophrenia despite pharmacological intervention. In contrast, the patients without schizophrenia manifested significant decreases in negative symptoms.

Reflections on Saugstad's "social class, marriage, and fertility in schizophrenia".

Saugstad (1989) recently proposed a neurodevelopmental model of schizophrenia and manic depressive illness that emphasizes the importance of biological maturation. Early maturation is proposed to be critical to manic-depressive illness and late maturation to schizophrenia. There are three goals of the comments that follow: (1) to place the neurodevelopmental theory in a broader context of ongoing research in sex differences in psychopathology; (2) to address some conceptual ambiguities in the model, especially with respect to within-schizophrenia comparisons; and (3) to offer a suggestion for a critical test of a maturation hypothesis of schizophrenia.