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Monoamine metabolite measurements are being increasingly used for making nosological, symptomatological and pharmacological profiles of the affective disorders. A number of unresolved methodological issues question the validity of using baseline metabolite levels for predicting treatment response. Some studies show correlations between baseline metabolite levels and response to treatment with specific antidepressant agents. Effects of antidepressant treatment on metabolite levels may be useful in predicting drug response.

There is evidence to indicate that 15% of patients diagnosed as schizophrenic will become chronically hospitalized, and that worldwide one-third to one-half of all psychiatric beds are occupied by schizophrenic patients. In spite of these figures and the public health problem they represent, little attention is paid to chronic hospitalized schizophrenic patients. Even the most recent classification schemas fail to recognize the heterogeneity, exemplified by differential responsiveness to psychotropic drugs, within the chronic schizophrenic population. One systematic approach to classification which does address this problem has been proposed by Leonhard. In this paper, findings and procedures that demonstrate the clinical relevance of Leonhard's system along with some preliminary results and observations from psychopharmacological studies that indicate Leonhard's different subtypes of chronic schizophrenia may represent biologically distinct populations are presented.

In the 1950s antipsychotic antidopaminergic drugs were introduced as the pharmacological treatment of schizophrenia. In the last 35 years a large fund of knowledge has been acquired about these drugs. Still, a number of issues regarding them require further addressing. We have reviewed the literature on some of these issues, focusing on those factors that the previous studies have resolved inadequately. The issue of optimal dosages of antipsychotics in schizophrenia has been analyzed from the perspective of the dose requirements during "rapid tranquilization", "in acute psychotic phases of schizophrenia", "in chronically hospitalized psychotic schizophrenic patients" and during "maintenance phases of schizophrenia". We have briefly discussed the different methodologies available for measuring neuroleptic levels in plasma, their methodological weaknesses and strengths and some of the larger studies done with chlorpromazine, haloperidol and fluphenazine to establish correlations between levels, treatment response, oral dosages and side-effects. The theoretically fascinating concept of supersensitivity psychosis has been reviewed and the theoretical and practical weaknesses that exist in most of the papers that have claimed validity for this concept are presented. The article also reviews the preclinical, postmortem and clinical research that demonstrates the presence of site selectivity for dopamine receptors in the newer atypical neuroleptics. Finally, the article briefly reviews the current status of some unorthodox clinical strategies, that may be potentially applicable in managing schizophrenic disorders.

We compared central cholinergic responsiveness (using the latency to induction of rapid eye movement sleep after arecoline challenge as a response marker) in 90 subjects: patients with major depressive disorder (MDD) (n = 53), nonaffective psychiatric controls (n = 17), and normal controls (n = 20). MDD patients as a whole showed a supersensitive cholinergic response compared to nonaffective patients and normal subjects. Further analysis indicated a strong association between cholinergic supersensitivity and endogenous subtype of MDD, including a significant correlation with specific endogenous features such as distinct quality of mood, anhedonia, lack of reactivity, and agitation. Unlike rapid eye movement (REM) latency (a more conventional physiological marker), cholinergic sensitivity did not correlate with age or severity of illness but only with the presence of endogenous features. Previously described sleep physiological correlates such as REM latency and REM density of the first REM period also distinguished between endogenous and nonendogenous MDD. There was a statistically significant correlation between REM latency and arecoline REM induction response.

Basic physiological and neurochemical control mechanisms of human iris musculature are reviewed. The advantages and limitations of using pupillary responses to cholinergic and adrenergic drug challenges as peripheral indices of neuronal receptor sensitivity, are examined. A group of 15 depressed patients were tested with ocular instillation of pilocarpine and phenylephrine before and during treatment with Tranylcypromine. No change of pilocarpine sensitivity was found. A significant enhancement of phenylephrine sensitivity during weeks 3-5, but not during the first or second week of treatment was noted. The above potentiation of alpha-adrenergic responsiveness was correlated with clinical recovery.

In a double-blind comparative clinical study, both thiothixene and haloperidol were found to be effective agents for rapid tranquilization of manic and schizophrenic patients. While no statistically significant difference in any of the psychopathological areas which may create a psychiatric emergency was found, results of this study provide further substantiation of the notion that thiothixene has favorable effects on anergia .

Lithium treatment in 9 elderly individuals with Alzheimer's disease led to a marked accentuation of extra-pyramidal symptoms (EPS) in 5 of 6 patients with preexisting EPS. EPS scores significantly correlated with plasma and RBC lithium levels. Lithium treatment had no such effects in the 3 patients without preexisting extrapyramidal symptoms.

Nine narcoleptic and nine control subjects underwent 4 nights of sleep recordings. On nights 3 and 4, they received continuous intravenous infusions of saline. Additionally, on both nights they received 0.2 mg glycopyrrolate at the end of the first REM period (REM1) and 0.5 mg arecoline or placebo in random order 20 min after the end of REM1. Heart rates were counted for a 40-min period following the end of REM1. There was a significant and similar cardioacceleratory effect after arecoline in both narcoleptic and normal subjects, beginning at 5 min from the start of the infusion and peaking at 9 min. Placebo had no effect. Narcoleptic subjects had consistently higher baseline heart rates than controls on infusion and noninfusion nights, most likely owing to age differences between the two groups. The results suggest that narcoleptic persons do not have increased cholinergic sensitivity, or that the canine model of narcolepsy differs from the human model, or that the muscarinic receptors that play a role in the pathophysiology of narcolepsy differ in sensitivity from those that regulate heart rate.

The antipsychotic efficacy of tiaspirone, a new atypical antipsychotic agent, was compared to standard neuroleptics, in a single-blind cross-over study. Nine actively psychotic schizophrenic patients entered the study and 6 completed it. Significant overall improvement, on BPRS and CGI ratings, occurred by week 4, on both--tiaspirone and standard neuroleptics. There were no significant differences between tiaspirone and standard neuroleptics, in their antipsychotic efficacy. In keeping with the preclinical profile of tiaspirone, no extrapyramidal symptoms (EPS) were observed with tiaspirone. Two patients showed EPS on standard neuroleptics. Five of the 6 patients showed mild transient elevation of liver enzymes while on tiaspirone. Liver enzymes returned to normal within 3 weeks of discontinuation of tiaspirone. Tiaspirone appears to be a promising new antipsychotic agent that may be clinically effective without causing extrapyramidal syndromes.