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.

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.

White matter hyperintensity signals in psychiatric and nonpsychiatric subjects.

OBJECTIVE: As part of an ongoing study investigating the relationship between brain morphology/function and neuropsychological performance in psychopathology, the authors conducted brain magnetic resonance imaging (MRI) studies to investigate the prevalence and psychiatric significance of white matter hyperintensity signals. METHOD: Brain MRI acquisition was done with 0.5 and 1.5 Tesla Philips scanners. Psychiatric subjects (N = 229) and normal volunteers (N = 154) were recruited by newspaper and local advertising and by physician referral. DSM-III-R criteria were used. White matter hyperintensity signals were rated on a 4-point scale of severity. Prevalence rates and risk ratios were calculated. RESULTS: Prevalence rates of hyperintensity signals in all psychiatric subjects (mean age = 34 years, SD = 9) and normal volunteers (mean age = 34, SD = 10) were 6.6% and 9.1%, respectively (a nonsignificant difference). When all psychiatric subjects, subjects under age 45, and subjects age 45 and over in a diagnostic category were considered, there were no statistically significant differences between them and normal volunteers in the same age groups in prevalence of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, and obsessive-compulsive disorder. A significant difference existed between the severity of deep white matter hyperintensity signals in subjects with major depression and normal volunteers. Older age was correlated as a risk factor for white matter hyperintensity signals for psychiatric subjects. CONCLUSIONS: These results do not support previous findings of greater prevalence of hyperintensity signals in bipolar disorder. Significantly higher prevalence rates of hyperintensity signals were seen in subjects with major depression only when severity of the deep white matter hyperintensity signals was considered. Older age is an indirect risk factor for the presence of white matter hypertensity signals, probably as a result of vascular changes associated with concurrent medical illnesses.

Limbic-hypothalamic-pituitary-adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia.

Some investigators have speculated that structural brain alterations observed in some psychiatric patients might be related to increased limbic-hypothalamic-pituitary-adrenal axis (LHPA) activity. To explore this hypothesis, we prospectively studied 166 research volunteers (19 patients with research diagnostic criteria (RDC) major depression, 9 patients with RDC bipolar depression, 45 patients with RDC schizophrenia, and 94 RDC normal controls), examining the relationship between magnetic resonance image-determined ventricular-to-brain ratio (VBR) and indices of LHPA axis function (cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), CSF adrenocorticotropic hormone (ACTH), and 24-hour urinary-free cortisol secretion). We observed no significant differences in mean VBR among the three patient groups and the normal control volunteers. Of the indices of LHPA activity, only CSF CRF concentrations distinguished the four subject groups, with CSF CRF being significantly elevated in the more severely depressed major depression patients. Indices of LHPA activity were not significantly correlated with VBR in any of the three patient groups or in the normal volunteers. These preliminary results suggest that VBR is not highly associated with alterations in LHPA activity, at least as determined cross-sectionally. Further longitudinal studies with reference to diagnostic subtypes, severity, symptom profiles, and more specific neuroanatomic regions may allow the elucidation of possible relationships between LHPA pathology and structural brain alterations.

CSF 5-HIAA as a predictor of treatment response in trichotillomania.

Trichotillomania is characterized by chronic hair-pulling resulting in noticeable hair loss. In a preliminary study, cerebrospinal fluid (CSF) measures in 8 medication-free, female, trichotillomania patients were compared to those of matched, normal controls. There was no difference between patients and controls in measures of CSF cortisol, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). CSF measures did not correlate with measures of trichotillomania symptomatology. However, degree of response to treatment with serotonin re-uptake inhibitors significantly correlated with baseline CSF 5-HIAA. This suggests that central serotonin turnover is specifically relevant to treatment response to serotonin re-uptake inhibitors in trichotillomania.

Prediction of adult-onset schizophrenia from childhood home movies of the patients.

In a preliminary study of developmental precursors of schizophrenia, home movies of adult-onset schizophrenic patients and their healthy siblings filmed during their childhood were viewed by judges who were blind to the psychiatric outcome of the subjects. The films began with the infancy of all subjects and extended through at least the first 5 years of their lives. Although none of the subjects had any psychiatric disorder in childhood, the preschizophrenic children were reliably identified by the viewers. This represents the first demonstration that preschizophrenic subjects can be distinguished from sibling control subjects within the first 8 years of life by observing their behavior.

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.

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.