Central catecholamines, cognitive impairment, and affective state in elderly schizophrenics and controls.

Central catecholamine concentrations were determined in autopsy samples from older schizophrenic and control subjects for both the hypothalamus and the nucleus accumbens. The results of these analyses and demographic variables were regressed on antemortem measures of cognitive function and mood state. In the hypothalamus, there are significant direct relationships of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) with depressed mood, as measured by an adaptation of the Hamilton Rating Scale for depression. In the nucleus accumbens, dopamine (DA) and MHPG had significant inverse relationships with antemortem cognitive function, as measured by an adaptation of the Mini Mental State Exam. Results in this sample indicate that after controlling for age, the catecholamine concentrations accounted for approximately 50% of the variance in the antemortem measures of mood or cognition, depending on the loci measured.

Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria.

To test the effect of selegiline, a specific monoamine oxidase B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h later by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus was evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ("high") produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1.21, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1.20, p = .012). The concomitant changes in both the subjective experience of the "high" and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence.

Lymphocyte monoamine oxidase and plasma prolactin and growth hormone in tardive dyskinesia.

Twelve elderly women with tardive dyskinesia were matched with 12 patients without dyskinesia. Lymphocyte monoamine oxidase (MAO) activity and plasma prolactin and growth hormone concentrations were determined "blind" in these 12 pairs of patients. Chronic schizophrenic patients with tardive dyskinesia had significantly lower lymphocyte MAO activity as compared to controls. Organic brain syndrome patients with dyskinesia did not differ from controls in the lymphocyte MAO activity. These results with lymphocyte MAO parallel our earlier findings on platelet MAO. No significant differences were found between dyskinesia group and controls in the plasma prolactin and growth hormone concentrations. Possible implications of our findings are discussed.

Paraphrenia: paranoid states of late life. I. European research.

American psychiatry has traditionally viewed late-life paranoid states either as rare or not part of the schizophrenic syndrome. European psychiatry has not subscribed to this view. The literature (chiefly European) is reviewed from the standpoints of history of the disorder, diagnostic reliability, pre-onset sensory loss, the multiple determinants of paranoia, and the response of paraphrenic patients to treatment with phenothiazines. The evidence leads to the conclusion that late-life paranoid states are not rare, and that the diagnosis "paraphrenia" has real clinical utility. Moreover, there seems to be a substantial relationship between schizophrenia and paraphrenia.

Paraphrenia: paranoid states of late life. II. American research.

In Part I of this study, a review of the European literature on paraphrenia demonstrated that the disorder affects a significant number of older persons and is probably part of the schizophrenic spectrum. Part II presents the current research evidence and issues concerning paraphrenia, a disorder commonly misdiagnosed or overlooked in the United States. Recommendations are made for a rigorous investigation of this group of patients that American psychiatry has not studied adequately. Comparisons of paraphrenic and schizophrenic patients undoubtedly will provide new insights into both the process of schizophrenia and the process of aging.

Peripheral catecholamine enzyme function and cognitive impairment of elderly schizophrenics and controls.

Alterations of peripheral and central catecholamine systems are found in both schizophrenic and demented subjects. Reported here are the results of bivariate and multivariate analyses of cognitive function and peripheral catecholamine enzyme activities in a group of elderly schizophrenic patients and controls. The entire sample shows an inverse relationship of platelet monoamine oxidase (MAO) activity with cognitive impairment after controlling for the effects of age, race, and gender. Schizophrenic subjects also demonstrated an inverse relationship of plasma dopamine beta hydroxylase (DBH) activity with cognitive impairment. Demented subjects were characterized in both groups as having increments in platelet MAO activity. Demented schizophrenic subjects also were characterized by increments in plasma DBH activity. Results from this sample are discussed with respect to findings from other studies and future research.

Monoamine oxidase in schizophrenia: an overview.

A brief history and summary of studies designed to elucidate the role of monoamine oxidase (MAO) in schizophrenia are presented. The majority of these studies have reported a decrease in the platelet enzyme activity of chronic schizophrenic patients when compared to controls. Difficulties encountered when comparing MAO activity measured in different patient populations are also considered. Finally, the significance of decreased platelet MAO activity is discussed with respect to its possible etiological role in some forms of schizophrenia.

Pharmacokinetics of peptide T in patients with acquired immunodeficiency syndrome (AIDS).

1. The pharmacokinetics of Dala1-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiency disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intravenous (i.v.) or intranasal (i.n.), via metered sprayer, administration. 2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearance rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA. 3. Bioavailability, determined for a 2 mg test dose in six individuals was 9.3 +/- 6.9 nmol/L. Peak plasma levels of 41 +/- 30 nmol/L after 10 mg i.n., 2.8 +/- 5.9 nmol/L after 2 mg i.n., and 0.13 +/- 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.

Platelet monoamine oxidase: studies on the rate of heat inactivation in normal and in paranoid and nonparanoid chronic schizophrenic groups.

The heat inactivation curves for platelet monoamine oxidase (MAO) in chronic schizophrenic and normal subjects were virtually identical. There were also no differences found when schizophrenic patients were subgrouped into paranoid and nonparanoid types. However, the MAO from one of the normal subjects showed a substantially greater thermolability than that of any other control or schizophrenic subject.

Schizophrenic outcome in late life: symptom state and platelet monoamine oxidase activity.

Reported here are the results of a study of symptom state, platelet monoamine oxidase (MAO) activity, and demographic variables in a group of elderly neuroleptic-free schizophrenics. Analyzed by both bivariate and multivariate techniques, the data from this sample indicate that after the effects of demographic variables upon the variance of enzyme activity have been controlled for, the patients most likely to continue to manifest schizophrenic symptomatology in the senium are those with low platelet MAO activity. The results are discussed with respect to other studies of platelet MAO and prognosis in schizophrenia and with respect to future studies.

Some kinetic parameters of platelet monoamine oxidase in chronic schizophrenia.

The michaelis constants (Vmax and Km) for platelet monoamine oxidase (MAO) with tyramine as substrate are found to be significantly lower in chronic schizophrenic patients than in normal controls. Furthermore, these kinetic parameters for the MAO of paranoid chronic schizophrenics are significantly lower than those for nonparanoid chronic schizophrenics. Paranoid chronic schizophrenia may be a separate biochemical disorder from other chronic schizophrenias.

A probable neuroleptic effect on platelet monoamine oxidase in chronic schizophrenic patients.

Platelet monoamine oxidase activity (MAO) was studied serially over time in 16 chronic schizophrenic patients when medication free and then when medicated. Thirteen of the 16 patients had significant decreases in platelet MAO activity following neuroleptic drug treatment. The change in MAO activity was found to be correlated with response to treatment and to dose of medication.

A biochemical study of tardive dyskinesia in young male patients.

Based on specific criteria, tardive dyskinesia was diagnosed in 6 out of 29 young schizophrenic male inpatients. We compared several biochemical parameters in these six dyskinesia patients with those in six matched controls. The patients with dyskinesia had significantly lower platelet monoamine oxidase activity and significantly higher plasma dopamine-beta-hydroxylase activity as compared with the controls, thus confirming our previous findings in a population of elderly female inpatients. The dyskinetic and nondyskinetic groups did not differ from each other in mean whole blood serotonin concentration and mean serum neuroleptic concentration as measured with a radioreceptor binding assay. Possible significance of our results is discussed.

Design and application of an expert system for mobile phase optimisation in reversed-phase liquid chromatography.

The selection of the optimum composition for the mobile phase in reversed-phase high-performance liquid chromatography (HPLC) is a complex task; conventional approaches require the expenditure of significant amounts of time by the analyst, particularly for complex mixtures of solutes of biological origin. Some of the existing strategies for the automated optimisation of mobile phase composition (e.g. Simplex), may fail if the elution order of the components changes; or they may require that standards be chromatographed in order to establish the retention behaviour of each component in a mixture (e.g. resolution mapping). These problems may be overcome if the retention behaviour of each individual solute can be established from the chromatogram of the mixture. In this regard, components can be tracked by exploiting the spectral information generated by a rapid scanning photodiode array detector. Unfortunately this information is often insufficiently detailed to allow an unambiguous model of retention behaviour to be constructed. The system developed by the Authors uses these spectral data as a basis for constructing one or more hypothetical retention models, each of which is refined or rejected as further information is obtained during the progress of the experiment. To improve the reliability of the retention models proposed by the system, the spectral data are utilised in a number of tests designed to assess the purity of each chromatographic peak. The information so generated may be used in conjunction with any previously acquired spectral data both to select an appropriate method for extracting spectra for each component from the matrix of (A, lambda, t) data and to establish reliability parameters for the resultant spectra. The development and philosophy of the expert system developed for eluent optimisation in reversed-phase HPLC is discussed.