Richard R.J. Lewine

Automatic detection of brain contours in MRI data sets

A software procedure is presented for fully automated detection of brain contours from single-echo 3-D MRI data, developed initially for scans with coronal orientation. The procedure detects structures in a head data volume in a hierarchical fashion. Automatic detection starts with a histogram-based thresholding step, whenever necessary preceded by an image intensity correction procedure. This step is followed by a morphological procedure which refines the binary threshold mask images. Anatomical knowledge, essential for the discrimination between desired and undesired structures, is implemented in this step through a sequence of conventional and novel morphological operations, using 2-D and 3-D operations. A final step of the procedure performs overlap tests on candidate brain regions of interest in neighboring slice images to propagate coherent 2-D brain masks through the third dimension. Results are presented for test runs of the procedure on 23 coronal whole-brain data sets, and one sagittal whole-brain data set. Finally, the potential of the technique for generalization to other problems is discussed, as well as limitations of the technique.

Cognitive functioning, cortisol release, and symptom severity in patients with schizophrenia

BACKGROUND There is substantial evidence of dysregulation of cortisol secretion, hippocampal abnormalities, and memory deficits in schizophrenia and other psychotic disorders. Research also suggests that cortisol secretion augments dopaminergic activity, which may result in increased symptom expression in this clinical population. METHODS We examined the relations among cortisol release, cognitive performance, and psychotic symptomatology. Subjects were 18 adults with schizophrenia or schizoaffective disorder, seven with a nonpsychotic psychiatric disorder, and 15 normal control subjects. Tests of memory and executive function were administered. Cortisol was assayed from multiple saliva samples. RESULTS Findings indicated the following: 1) patients with psychotic disorders scored below the comparison groups on the cognitive measures; 2) for the entire sample, cortisol levels were inversely correlated with performance on memory and frontal tasks; and 3) among patients, cortisol levels were positively correlated with ratings of positive, disorganized, and overall symptom severity, but not with negative symptoms. CONCLUSIONS The present results suggest that abnormalities in the hypothalamic-pituitary-adrenal axis and hippocampal systems play a role in observed cognitive deficits across populations. Among psychotic patients, elevated cortisol secretion is linked with greater symptom severity.

The positive/negative symptom distinction in schizophrenia validity and etiological relevance

This paper presents an overview of the literature on the positive/negative symptom distinction in schizophrenia, and explores the implications of the findings for etiological models. Despite the diversity in methodology and focus, certain consistencies emerge from the research. Most important are findings that negative symptoms show a stronger relation with premorbid dysfunction than positive symptoms, and are more predictive of concordance for schizophrenia in monozygotic twins. Thus it appears that negative symptom ratings partially tap some long-standing characteristics of the individual. Moreover, these characteristics appear to be influenced by genetic factors. The implications of the findings for models of the etiology of positive and negative symptoms are discussed.

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.

Negative symptoms and platelet monoamine oxidase activity in male schizophrenic patients

A significant positive correlation was found between negative symptoms and platelet monoamine oxidase (MAO) activity in unmedicated male, but not female, schizophrenic patients. This correlation was significant in split halves of the male patients. There was no indication that the correlation was due to either outliers or medication effects. Male schizophrenic patients with high negative symptom scores had significantly higher mean platelet MAO activity than either male normal control subjects or male schizophrenic patients with low negative symptom scores. This finding suggests that the extent of negative symptoms in a population of males could affect whether the schizophrenic subjects will be found to have platelet MAO activity which differs from that of normal control subjects. The implications of the correlation between platelet MAO activity and negative symptoms for the role of brain MAO activity and two of its substrates, dopamine and serotonin, in the etiology of negative symptoms in male schizophrenic patients are discussed.

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.

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 CVAs. 5. This finding is consistent with an etiology of WMH signals in schizophrenia being related to vascular disease.

An Association between Increased Concentrations of Cerebrospinal Fluid Dopamine Sulfate and Higher Negative Symptom Scores in Patients with Schizophrenia and Schizoaffective Disorder

There has been much speculation as to the role of dopamine in the etiology and/or manifestation of positive and negative symptoms. Traditionally, cerebrospinal fluid (CSP) concentrations of homovanillic acid (HVA) has been used as an index of central dopaminergic activity. Relea~l dopamine is metabolized to HVA, by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) (Cooper et al 1991). A review of the CSF HVA literature, however, reveals no consistent correlations between HVA and schizophrenic symptomatoiogy (reviewed by Pickax et al ! 9907. Yet there is sufficient data to suggest that dopamine activity is abnormal in schizophrenia (Davis et al 19917. Therefore the evaluation of other putative measures of dopamine release or metabolism seems warranted. Released dopamine is also converted to dopamine sulfate (DASO47 by the enzyme phenolsulphotransferase (PST7 (Jenner and Rose, 1973). in the brain, it appears that the sulfoconjugation of dopamine occurs primarily outside of dopaminergic neurons (Tyce et al 1988). Therefore CSF DASO~ concentrations may reflect an important alternate route of dopamine metabolism. Assessment of PST-dependent DASO4 independently, or in re-

Cebrospinal fluid study of cannabinoid users and normal control subjects

CSF from cannbinoid users was examined and then compared to CSF parameters in age- and sex-matched normal control subjects