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The science and marketing of psychiatric treatment are rapidly changing, and the changes are reflected, in part, in the recent evolution of the use of laboratory services. Nevertheless, there are few, if any, articles in the literature addressing how a laboratory service can best assist a psychiatric hospital. This article presents a scaffolding of current issues to be considered when determining how a laboratory can assist the psychiatric facility. It cites the special laboratory needs of the psychiatric hospital and issues to be considered when evaluating laboratory service.

A controlled study investigated the relationship between steady-state plasma and RBC concentrations of the phenothiazine derivative butaperazine maleate and the therapeutic response in 24 hospitalized schizophrenic patients who received constant maintenance doses of butaperazine during the first two weeks of treatment. Butaperazine concentrations in RBCs correlated significantly with clinical improvement in an inverted U-shaped pattern, whereas plasma levels of butaperazine were not significantly related to clinical response. Both plasma and RBC levels of butaperazine showed large interpatient variations. The level of RBC-bound drug might be a better peripheral correlate of drug levels in the brain than are drug levels in plasma. Thus, monitoring drug levels in RBCs might have an advantage over measured drug levels in plasma. These findings might not allow generalization to other antipsychotic agents.

The authors measured the urinary metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in 21 hyperactive boys and 12 matched healthy boys. The hyperactive boys excreted lower amounts of MHPG than control boys. Hyperactive drug responders excreted lower amounts of HVA than control boys and hyperactive nonresponders. Drug responders with normal MHPG excreted low amounts of HVA and those with normal HVA excreted low amounts of MHPG. d-Amphetamine decreased MHPG in all drug responders and HVA in drug responders with normal HVA levels, although it tended to increase HVA in those with low HVA levels. The authors discuss their data in terms of the possible involvement of norepinephrine and dopamine in the etiology of hyperactivity in children.

The authors studied the excretion of 3-methoxy-4-hydroxyphenyl glycol (MHPG), normetanephrine (NM), metanephrine, and homovanillic acid in 7 hyperactive and 12 control children. MHPG was lower but NM was significantly higher in hyperactive children than in controls. Administration of d-amphetamine for 2 weeks depressed the levels of MHPG, NM, and metanephrine. The authors suggest a decreased central norepinephrine activity, which may be secondary to the interruption of norepinephrine fibers in the medial forebrain bundle.

Plasma and red blood cell levels of haloperidol were measured in psychotic patients after an acute dose of haloperidol and during treatment with fixed doses for several weeks. There was wide variability of haloperidol plasma and red blood cell levels at a given dose and a nonlinear relationship between haloperidol dose and blood levels. The red blood cell/plasma ratio (0.40) had a narrow range among different patients. Haloperidol blood levels were not correlated with the age of the patient. Concomitant administration of benztropine mesylate did not decrease plasma haloperidol levels. Steady state plasma or red cell haloperidol levels could not be predicted from levels 24 hours after the acute dose.

It has been found that in the brain of the non-human primate (Macaca arctoides) MHPG occurs principally if not exclusively in the free rather than the conjugated form. It has also been found that in all areas of human brain examined MHPG is present in the free form rather than the conjugated form. The quantity of free MHPG present in various structures of human brain ranged from 46.4 to 69.8 microng/gm of tissue.

The authors examined the effect of diets with low and high monoamine content on the 24-hour urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) and creatinine in eight healthy preadolescent boys. The subjects were admitted to a clinical research center and were placed on a diet low in monoamines--the vanillylmandelic acid (VMA)-exclusion diet--for 5 consecutive days. They were switched on the 6th day to a diet rich in monoamines, and urine specimens were collected for 4 more consecutive days. There were no differences in MHPG or creatinine excretion between the urine taken on the low and high monoamine diet days.

Previous reports have indicated that some depressed patients excrete less than normal quantities of 3-methoxy-4-hydroxyphenyl glycol (MHPG). The authors present data indicating that a subgroup of depressed patients who excrete less than normal quantities of MHPG may be identified by the application of explicit clinical criteria. They found no significant difference in the excretion of normetanephrine (NM), metanephrine (M), and 3-methoxy-4-hydroxymandelic acid (VMA) among any of the diagnostic subgroups or between each patient group and a healthy comparison group. However, depressed patients diagnosed as having primary affective disorder and bipolar illness excreted significantly less MHPG than did the healthy comparison group.

The 24-hour urinary catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol, normetanephrine, and metanephrine were measured in 23 hyperactive boys and 13 matched healthy controls. The hyperactive children excreted lower MHPG and higher NM (low MHPG/NM ratio) amounts than in controls. The administration of d-amphetamine in the dose of 0.5 mg/kg body weight divided over two doses daily for two weeks decreased MHPG excretion in the hyperactive children. When the hyperactive children group was divided into drug responders and nonresponders according to their pre- and post-treatment scores on the Conners Teacher Questionnaire, d-amphetamine administration decreased MHPG excretion in the responders and did not change it in the nonresponders. Percent decrease in MHPG excretion correlated significantly with percent change in the hyperactivity factor of the questionnaire on the Spearman Rank Order Correlation Coefficient. Pretreatment urinary metabolites did not differentiate the responders from nonresponders. It is suggested that a relationship between CNS norepinephrine metabolism and hyperactivity exists and that d-amphetamine may achieve its therapeutic action in hyperactive children by altering CNS NE metabolism.

A review of the clinical profile of congenital sensory neuropathy with anhydrosis is presented. It is stressed that major diagnostic criteria of this recessively inherited condition should be limited to insensitivity to pain with normal tactile perception, anhydrosis, recurrent unexplained fever, self-mutilation, mental retardation, hypotonia, histologically normal sweat glands and variable autonomic abnormality. A case conforming to this description is reported and compared with 13 published cases. Special investigations of the autonomic nervous system through measurement of urinary catecholamine metabolites and psychophysiologic variables were conducted on this patient. Based on the analysis of 5 X 24-hour urine, values of metabolites of dopamine and epinephrine were normal. Metabolites of norepinephrine, such as 3-methoxy-4-hydroxy phenylglycol and normetanephrine, however, were significantly low when compared with those of four controls, suggesting decreased peripheral and central norepinephrine activity. Polygraph recording and evaluation of some orienting response components revealed no obvious signs of autonomic perturbation and, specifically, no phasic electrodermal activity. These two findings (biochemical and electrodermal) strongly suggest an autonomic imbalance, specifically component, both central and peripheral. It is suggested that autonomic disorder is an integral part of the syndrome and may be demonstrated by special investigations.

Urinary catecholamine levels were measured in 25 anorexia nervosa patients at the time when they were acutely ill with secondary depressive symptoms and again after treatment and weight gain to see whether changes in weight, activity levels, and symptoms of depression occurring during treatment might be associated with changes in urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations. The latter was significantly lower in the acutely ill anorectics than in the control group. An increase in urinary MHPG concentration after treatment was significantly correlated with a decrease in depressive symptomatology. The increase in urinary MHPG level during treatment did not correlate significantly with change in patient's activity level. There seems to be a relationship between MHPG and the symptom of depression in a group of patients who do not carry a primary diagnosis of depression.

Catecholamine metabolites excreted by long-term methadone hydrochloride-dependent subjects were studied in a protocol involving a two-study design. After a two-week methadone maintenance period, 15 subjects underwent abrupt methadone withdrawal and 12 subjects, gradual methadone withdrawal. The first study compared levels of catecholamine metabolites excreted during the stable methadone period with those excreted during the abrupt withdrawal period, as well as with those eliminated by healthy nonaddicted controls. No changes in the excretion of 3-methoxy-4-hydroxyphenylglycol and normetanephrine were noted between the methadone maintenance period and the time of abrupt methadone withdrawal. These values did not differ from those obtained for controls. However, higher levels of metanephreine were excreted during the stable methadone period than those in controls. During withdrawal, levels of metanephrine dropped a statistically significant amount in comparison with levels observed during the stable methadone period. The gradual withdrawal study confirmed these findings.

Pharmacokinetics of the phenothiazine, butaperazine, were studied in relationship to acute dystonic reactions. Dystonias appeared on falling drug concentrations, more than one half-life after plasma and red blood cell (RBC) peak butaperazine concentrations. Red blood cell butaperazine kinetics differentiated better than did plasma butaperazine levels those subjects in whom dystonias would develop from those in whom they did not. We conclude that RBC phenothiazine levels may more clearly reflect drug concentration at critical brain sites than do simple plasma drug levels. Furthermore, dystonic reactions may be the result of differential sensitivity of two or more receptor systems to receptor blockade by antischizophrenic agents.

The authors studied neuroleptic concentration-therapeutic response curves for butaperazine (BPZ), a piperazine phenothiazine, in 10 schizophrenic patients during the first 12 days of treatment. BPZ bound to red blood cells (RBC) was more strongly correlated with therapeutic response than was plasma BPZ. RBC BPZ concentrations could be used to define a "therapeutic window", an optimun concentration for therapeutic response, above and below which favorable response diminishes. The authors emphasize the preliminary nature of the data but suggest that levels of RBC-bound neuroleptic may provide an important guide for dosage regulation in schizophrenic patients.

The authors studied the excretion of 3-methoxy-4-hydroxyphenlyglycol (MHPG) in 15 hyperactive boys and 13 controls. They further examined soft neurologic signs and clinical drug response to d-amphetamine administration for two weeks in the hyperactive boys. MHPG excretion was significantly lower in the hyperactive boys than in the controls. d-Amphetamine decreased MHPG excretion significantly in the drug responders only. Pretreatment MHPG excretion did not predict clinical drug response. The responders had more soft neurologic signs than the nonresponders. Furthermore, soft neurologic signs were not related to pretreatment MHPG levels.

The occurrence of acute dystonic reactions was studied relative to drug pharmacokinetic parameters following a single dose of the phenothiazine, butaperazine. Dystonias occurred more than one half-life from peak butaperazine levels, 23 to 56 h after drug administration. The authors postulate that the appearance of dystonias on falling plasma concentrations may be due to disruption of dopaminergic-cholinergic balance caused by differential antidopaminergic and anticholinergic potencies of the drug.

The relationship of plasma prolactin to plasma or red blood cell butaperazine levels was investigated in chronic schizophrenic patients treated with clinical doses of butaperazine, both after a single acute dose of the drug and during regular, twice daily butaperazine administration. Although there was a significant curvilinear relationship between peak plasma butaperazine levels after an acute single oral dose of butaperazine and the maximum prolactin response that we measured, steady-state levels of plasma or red cell butaperazine and plasma prolactin were not related. We conclude that plasma prolactin cannot be used as a substitute for or even as a rough indicator of butaperazine blood levels in chronic schizophrenic patients being treated with clinical doses of butaperazine.