Do QEEG topographic map data have a multivariate normal distribution? Implications for tests of individual maps.

The study was designed to test whether topographic map data expressed in log power units have a multivariate normal (MVN) distribution in a healthy population, and to determine if any deviation from normality poses serious difficulties for the use of standard multivariate statistical tests in assessing the significance of deformations of the map in individual cases. Data on 361 healthy adults using 20 electrodes in the classic 10/20 configuration were recorded in six frequency bands. The log-transformed power data were shown to deviate markedly from MVN. The actual distributions of multivariate tests were computed for the sample using the 'jackknife' method, and shown to deviate markedly from the F-distributions that would be expected for MVN data. These 'jackknife' sampling distributions were then used to demonstrate significant deformations in the topographic maps of a patient who had sustained traumatic head injury.

Clozapine: current status and role in the pharmacotherapy of schizophrenia.

OBJECTIVE: This study evaluates clozapine and its present role in the pharmacotherapy of schizophrenia. METHOD: Clozapine's current clinical status is reviewed, as is its position with respect to other treatment options. RESULTS: Clozapine represents the prototype of "atypical" neuroleptics, with evidence of clinical efficacy in both positive and negative symptoms, as well as a diminished risk of extrapyramidal side effects. It is the only neuroleptic to date that has established itself as having little, if any, risk of tardive dyskinesia. More recent research has focused on its potential for overall savings in health care costs, as well as possible benefits in the area of neuropsychological functioning. CONCLUSION: Evidence suggesting that the course of schizophrenia can be altered by effective treatment favours a systematic approach that optimizes treatment options. While clozapine does not represent a 1st-line agent because of its risk of agranulocytosis, it has an integral role to play in treatment-resistant schizophrenia or in individuals experiencing intolerable side effects with conventional neuroleptics.

The effect of laterality of stimulus presentation on auditory P300 topography in schizophrenia.

Reduced P300 amplitude in schizophrenia has been a consistent finding. Recent studies have raised the question of characteristic topographic distribution. This study reports the effects of binaural and unilateral stimuli on the P300 topography in schizophrenia. An auditory "oddball" paradigm was repeated 3 times with left, right and binaural stimulation. Data were recorded using a 19-electrode montage with linked ear reference. Subjects were 18 untreated, hallucinating, paranoid patients with schizophrenia and 24 healthy matched volunteers. For the control subjects, stimulus conditions had no effect on P300 topography. For the sample with schizophrenia, topography under unilateral left stimulation resembled that of control subjects. Binaural and right-sided stimulation shifted peak amplitudes to the right and frontally. In addition to the usually observed parietal peak, a second P300 maximum having a different time course appeared over right frontal areas. The data provide further support for lateralized dysfunction in schizophrenia.

Computerized pattern recognition of EEG artifact.

Automated artifact classification of quantified EEG (QEEG) epochs from 9 males using linear discriminant analysis showed greater than 85% agreement with judges' opinions. These results were replicated (n = 600 epochs for each sample). Testing the entire sample (n = 5800) illustrated reliable eye artifact (94%) but reduced muscle artifact classification (70%) accuracy. Agreement was lowest in the case of more subtle forms of muscle artifact (i.e., low amplitude muscle), however, less than 4% of these were wrongly classified as non-artifact. Improved data collection techniques retaining high frequency energies are anticipated to improve muscle artifact recognition. Results indicate that low levels of artifact contamination would result when only those epochs classified as non-artifact were accepted for inclusion in further analysis.

Clozapine in the treatment of refractory schizophrenia: Canadian policies and clinical guidelines.

Clozapine is an atypical neuroleptic agent that has recently become available in Canada with potential clinical efficacy in the treatment of refractory schizophrenia, and in patients with schizophrenia neurologically intolerant to conventional neuroleptics. Although it causes few extra-pyramidal symptoms, the drug has a number of other adverse effects including a risk of agranulocytosis in one to two percent of all patients. Because of this, the use of the drug is permitted only if the white blood count is monitored weekly. The monitoring system, outlined in this article, requires a coordinated effort between clinical staff, pharmacy, laboratory and the Clozaril Support and Assistance Network. Clinical guidelines are proposed, detailing the indications and contraindications for treatment and the pharmacokinetics, dosing, adverse effects, and drug interactions with clozapine. In addition, the economics, government policies and implications for future research are considered. Although there are administrative and clinical difficulties associated with its use, clozapine represents an advance in therapeutic research. Patients and family members will be inquiring about the drug and may deserve a trial. This article aims to inform Canadian mental health professionals about the safe and beneficial use of clozapine.

Serotonergic interhemispheric asymmetry: gender difference in the orbital cortex.

The asymmetry of tritiated imipramine (IMI) binding sites (which are associated with serotonergic mechanisms) were investigated in the orbital frontal cortex in 6 women and men who died of natural causes, and who did not have a history of mental disorders. There was significant interhemispheric asymmetry in both sexes, higher Bmax on the right side compared with the left. The Bmax values of IMI binding in the right orbital cortex in women were significantly higher than in men. Our preliminary findings--gender difference of serotonergic mechanisms in some area of the human brain--are in accordance with the observed gender differences in a variety of serotonin-regulated behaviors (sexual behavior, aggression and impulse control), and serotonergic mental disorders (eating disorders, suicidal behavior, anxiety disorders and depression).

Serotonergic interhemispheric asymmetry: neurochemical and pharmaco-EEG evidence.

1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side. 2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men. 3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.

Limbic system dysfunction as a factor in some schizophreniform psychoses: case report and overview.

A case is presented of a young woman whose schizophreniform psychosis was unresponsive to neuroleptic treatment, but who subsequently responded well to Carbamazepine. Several converging lines of investigation, suggesting an underlying Limbic System dysfunction, are discussed. Background to the Limbic System concept is provided.

Prepreparatory interval effects on redundancy deficit reaction time patterns in schizophrenic and normal subjects using the embedded-set procedure.

The relative influence of genuine "redundancy deficit" and the artifactual effects of prepreparatory interval on measures of the redundancy deficit reaction time pattern (faster reaction time on trials with long preparatory intervals when the interval is of predictable vs. unpredictable length) was investigated in a study using the "embedded-set" procedure. Twenty normal and 20 schizophrenic subjects received two series of reaction time trials containing embedded sets (blocks) of four isotemporal 1-, 3-, and 7-second trials. The 7-second blocks (the blocks of interest for the calculation of redundancy deficit) were preceded by long prepreparatory intervals in one condition and by short intervals for the second. Each subject received both conditions, with the orders counterbalanced. The results indicated redundancy deficit for both schizophrenics and normals with short prepreparatory intervals, but in neither group with long prepreparatory intervals. This suggests that redundancy deficit in the embedded-set procedure (which is normally heavily biased with short prepreparatory intervals) may be more related to the enhancing effect of short prepreparatory intervals on the first (unpredictable) trial of the set than to impaired performance on the fourth (predictable) trial. The finding of similar effects in both schizophrenic and normal subjects raises questions about the specificity of redundancy deficit to schizophrenic reaction time performance. The results were discussed with reference to the original "long run" reaction time procedure for studying the same phenomenon, and theoretical issues related to the interpretation of results from the two procedures were considered.

Growth hormone responses to apomorphine HCl in schizophrenic patients on drug holidays and at relapse.

In nine schizophrenic patients on drug holiday, growth hormone (GH) response to apomorphine HCl 0.75 mg (APO) was compared with normal control data. Patients were tested at two month intervals for up to 14 months. Seven patients relapsed, and of these, five had exaggerated GH responses to APO at that time. Of these five, three had exaggerated GH responses to APO prior to clinical deterioration. Further work is required to determine whether this test can be a useful predictor of relapse.

Attention/information processing, neuropsychological functioning, and thought disorder during the acute and partial recovery phases of schizophrenia: a longitudinal study.

Schizophrenic subjects were administered the span of apprehension task, which is a measure of visual information processing; two neuropsychological tests; and measures of specific aspects of thought disorder and general clinical state. The measures were administered both when patients were acutely disturbed and when they were partially recovered. Normal control subjects were tested over a comparable 12-week interval. Improvements in both overall clinical condition and specific aspects of thought disorder occurred in the schizophrenic patients during this time. The patients, however, continued to show impaired information processing, indicating that the span of apprehension task is sensitive to schizophrenic dysfunction across wide variations in clinical state and, therefore, may be a marker of vulnerability to schizophrenia. The span of apprehension task was found to be significantly correlated with a measure of thought disorder that assesses resistance to associative distractors and two neuropsychological tests--the Trail-Making Test from the Halstead-Reitan battery and the Digit Symbol Substitution Test--during the testing session conducted while the subjects were partially recovered.

Span of apprehension deficits during the postpsychotic stages of schizophrenia. A replication and extension.

Thirty-five schizophrenic and 20 manic-depressive outpatients and 20 normal controls were administered a measure of visual information processing, the span of apprehension. The schizophrenic outpatients made significantly fewer correct detections of the target stimuli than did the manic-depressives and normal controls, particularly for conditions in which the target stimuli were embedded in four and nine irrelevant stimuli. A subgroup of schizophrenics produced the overall group differences. In a comparison of a subgroup of schizophrenics who showed impaired performance on the ten-letter array with the remaining schizophrenics, the ten-letter array appeared to be tapping processes that are independent of overall adjustment, the presence of particular symptoms, premorbid social adjustment, general demographic characteristics, and the presence of generalized performance deficits. The span of apprehension may be a marker for some subgroups of schizophrenia.

Long-term lithium treatment and the kidney. Interim report on fifty patients.

This is a report on the first part of our study of the effects of long-term lithium treatment on the kidney. Creatinine clearance, maximum urinary osmolality and 24 hour urine volume have been tested in 50 affectively ill patients who have been on long-term lithium for more than one year. These findings have been compared with norms and with values of the same tests from screening prior to lithium, available for most of our patients. No evidence was found for any reduction of glomerular filtration during lithium treatment. Low clearance values found in several patients could be accounted for by their age and their pre-lithium values. Urinary concentration defect appeared frequent but the extent of the impairment is difficult to assess because of the uncertainty about the norms applicable to this group of patients. The concentration defect appeared reversible, at least in part. Polyuria above 3 litres/24 hours was found in 10% of patients. An attempt is made to draw practical conclusions from the preliminary findings.

Children at risk for schizophrenia. Clinical and attentional characteristics.

Adolescent high-risk subjects, offspring of schizophrenic mothers, who were placed in foster homes at an early age, are compared with foster children whose biological parents have no record of psychiatric hospitalization and with non-foster children. The high-risk group showed increased social isolation, difficulties in the student role, elevated total symptom scores on the Psychiatric Status Schedule, and elevated schizophrenic scale scores on the Minnesota Multiphasic Personality Inventory. Half of the high-risk subjects showed significant impairment on a battery of eight attention-demanding tasks.

Emotional disturbance and cognitive deficits in hyperthyroidism.

Assessment of cognitive and emotional variables in 19 females with hyperthyroidism was made pretreatment, at 3 weeks, and after euthyroidism was established. A matched group of normal controls was similarly tested. Group differences on cognitive measures did not reach statistical significance, but cognitive deficits and symptoms of emotional disorder were significantly associated with the severity of thyroid toxicity previous to treatment. Measures of cognitive function and personality features moved towards control group values as euthyroidism was established. The implication of these findings is discussed in the context of a review of previous literature. The observed cognitive disturbance and emotional distress appear to be reflections of thyroid toxicity.

Fluphenazine decanoate and fluphenazine enanthate in the out-patient management of chronic schizophrenia.

39 chronic schizophrenic out-patients were given either fluphenazine decanoate or enanthate for a 1-year double-blind trial. Doses of 25 mg were given for the first 6 months and 37.5 mg for the last 6 months. For both agents the intervals between treatments lengthened significantly over the course of the trial. Fluphenazine decanoate showed a non-significant trend for a longer duration of action coupled with a significantly lower incidence of extrapyramidal side effects.