Decreased platelet monoamine oxidase activity in chronic schizophrenia, shown with novel substrates.

Platelet monoamine oxidase (MAO) was kinetically evaluated in chronic schizophrenics and matched controls, using substrates of major physiologic importance and substrates of particular interest in the study of schizophrenia, such as serotonin (5-ht), N,N-dimethyltryptamine (DMT), 5-methoxytryptamine (5-MT), and dopamine (DA). Substrates were measured at six concentrations; values for maximal velocity (Vmax) and Michaelis constant (Km) were obtained by using Lineweaver-Burk plots. The Vmax was decreased for all substrates in chronic schizophrenia and the Km was decreased for DA, 5-HT, and DMT, but remained unchanged for 5-MT. The value of Km/Vmax was similar for schizophrencis and normal persons when DA, 5-HT, and DMT were used as substrates, which may indicate that "uncompetitive" inhibition is responsible for the observed decrease in activity among chronic schizophrenics. The finding of a decreased Vmax but unchanged Km with 5-MT would be consistent with noncompetitive inhibition.     

Electrophoresis of platelet monoamine oxidase in schizophrenia and manic-depressive illness

Monoamine oxidase is an important enzyme in the catabolism of biogenic amines and can be measured in human platelets. Platelet MAO has been reported to be reduced in schizophrenic and manicdepressive patients, though other reports are contradictory. The present study evaluated the possibility that qualitative genetic enzyme abnormalities of MAO could be responsible for the different enzyme activities of platelet MAO in different populations. However, polyacrylamide gel electrophoresis of platelet MAO from 10 manic-depressive, 12 schizophrenic, and 11 normal individuals did not reveal any genetic mutant forms.     

Neuroleptic drug effect on platelet monoamine oxidase and plasma amine oxidase in schizophrenia

Activity levels of platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) were determined in eight chronic schizophrenic patients who had been treated with neuroleptic drugs for 3 months. The mean reduction in platelet MAO activity was 18.6%. The extent of decrease was statistically significant. The reduction in enzyme activity was unrelated to serum iron levels. PAO activity was unaltered. The implications for schizophrenia research are discussed.     

Platelet monoamine oxidase in alcoholism

We studied platelet monamine oxidase (MAO) activity using 14C-tyramine as substrate in hospitalized alcoholic patients in the early phases of abstinence and in nonhospitalized normal control volunteers. Platelet MAO was determined in 75 patients (67 men, 8 women) with alcoholism and 123 normal control volunteers (52 men, 71 women). The platelet MAO activity in alcoholic patients was significantly lower than in normal control volunteers. We also observed that the mean platelet MAO activity in male alcoholics was significantly lower than in normal males. The analysis of platelet MAO in alcoholics revealed a mixture of two normal distributions. Alcoholic patients falling into the low MAO component were younger in age, with a lower age of onset of alcoholism, and had higher frequencies of family history of alcoholism. They thus resembled type II alcoholics described by other investigators. Platelet MAO may thus serve as a useful biological marker for subtyping alcoholism and identifying high-risk groups at an early stage. The findings of this study are consistent with previous reports of low platelet MAO activity in alcoholic patients.     

Urinary trace amine excretion and platelet monoamine oxidase activity in schizophrenia

The relationship between subtypes of schizophrenia classified by ICD-9 and 24-hour urinary beta-phenylethylamine (PEA) and phenylacetic acid (PAA) excretion has been studied. Schizophrenia was divided into two types: paranoid and nonparanoid. Increased urinary PEA excretion was found in paranoid schizophrenics, but urinary PAA excretion did not show any significant difference between schizophrenics and normal subjects. A relationship between platelet monoamine oxidase (MAO) activity and urinary PEA excretion was found. These findings offer some indication that PEA may play a role in the pathogenesis of schizophrenia.     

Substrate-typic changes of platelet monoamine oxidase activity in sub-types of schizophrenia

Summary Monoamine oxidase (MAO) activity has been measured in the platelets of controls (n=42) and schizophrenic patients (n=49) of three subtypes, using -phenylethylamine, p-tyramine, and tryptamine as substrates. Characteristic differences of MAO activity were observed between platelets of patients and controls; the differences were substrate-typic: decreased enzyme activity was found with all three substrates in platelets of the parnaoid subtype. With tryptamine, MAO activity was decreased in the platelets of all three sub-types of schizophrenia. With p-tyramine, MAO was low in patients with affective psychoses and paranoid schizophrenia.The value of MAO activity measurements as a means for distinguishing sub-types of schizophrenic disorders is improved by using two substrates; tryptamine and p-tyramine. Possible mechanisms of the substrate-typic changes of platelet MAO activity in schizophrenia are discussed.     

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.     

Platelet and fibroblast monoamine oxidase in alcoholism

Monoamine oxidase (MAO) activity has been reported to be low in platelets (MAO B) and brain (MAO A and B) of some patients with alcoholism compared to control subjects. Whether the decreased platelet MAO activity found in alcoholism is secondary to the effect of alcohol or exists before alcohol abuse is not clear. The hypothesis that altered MAO A activity is determined by an abnormality in the genetic regulation of the enzyme can be tested by measuring MAO A activity in human fibroblasts cultured under controlled conditions. We first studied the kinetic parameters of platelet MAO B activity in patients hospitalized for treatment of alcoholism. Vmax was 38% lower in the patients (n = 14) than in normal controls (n = 22), but the enzyme affinity (Km) for the substrate tyramine was unchanged. Patients with the five lowest levels of platelet MAO activity had MAO activity measured from fibroblasts cultured from skin punch biopsies. Their fibroblast MAO activity was within the normal range, showing a dissociation between platelet MAO B and fibroblast MAO A activities and suggesting that MAO A activity is not low for genetic reasons in alcoholic subjects who do have low platelet MAO B activity.     

Psychiatric morbidity and platelet monoamine oxidase activity in cancer patients

Psychometric ratings for both anxiety and depression in 30 cancer patients were significantly elevated compared with values in 16 controls. The scores were especially high in the 14 patients who did not have breast cancer. This group also had significantly greater platelet monoamine oxidase activity than either the breast cancer patients or controls. Platelet monoamine oxidase activity values correlated significantly with both depression and anxiety scores in the whole cancer group.     

Classification of patients with affective disorders using platelet monoamine oxidase activity,serum melatonin and post-dexamethasone Cortisol

Platelet monoamine oxidase activity (MAO), melatonin and Cortisol post-dexamethasone suppression test (DST) were examined in 28 patients with major affective disorder and in 20 controls. MAO activity was lower and Cortisol post-dexamethasone was higher in depressed patients. Platelet MAO activity and Cortisol in depressed and controls yielded high sensitivity (90%) and specificity (89%). The patients were re-examined after 10 years and categorized into affective psychosis or neurotic depression (ICD-9). Multidimensional analysis identified one subgroup coinciding in 92% with affective psychosis and another subgroup coinciding in 87% with neurotic depression. Combination of MAO, melatonin and post-DST Cortisol may be useful in the diagnosis of subgroups of depressed patients and in choice of therapy.     

Low platelet monoamine oxidase activity: A possible biochemical correlate of borderline schizophrenia

Platelet monoamine oxidase (MAO) activity, psychiatric disorders, and family history of psychopathology were studied in 115 nonhospitalized, previously undiagnosed college student volunteers. Subjects were classified into two extreme groups: those with platelet MAO activity two standard deviations below the mean (“low-MAO” probands) and those with platelet MAO activity two standard deviations above the mean (“high”-MAO probands). Low-MAO probands were found to have a significant increase in the incidence of borderline schizophrenia and other psychiatric disorders compared to high-MAO probands. First-degree relatives of low-MAO probands were more often affected with psychiatric disorders and borderline schizophrenia than relatives of high-MAO probands. The data suggest that reduced platelet MAO activity is associated with psychiatric vulnerability and that the spectrum of schizophrenia may be more closely related to this vulnerability than other psychiatric disorders.     

Effect of neuroleptic drugs on platelet monoamine oxidase in psychiatric patients

The authors determined the platelet MAO activity of 57 psychotic patients after a placebo period and after 3-65 days of neuroleptic treatment. Platelet MAO activity significantly decreased in both men and women after neuroleptic treatment. The platelet MAO activity of neuroleptic-treated schizophrenic women was significantly less than that of drug-free schizophrenic women, who did not differ from normal women. There were trends in the same direction for the schizophrenic men. Previous studies that reported lower platelet MAO activity in neuroleptic-treated schizophrenic patients than in normal controls may have been influenced by this neuroleptic effect.     

Lymphocyte monoamine oxidase activity and chronic schizophrenia

Lymphocyte monoamine oxidase (MAO) activity was assayed in 62 chronic schizophrenic patients, 113 normal volunteers, and 23 first-degree relatives of schizophrenic patients. Mean lymphocyte MAO activity was significantly lower (p < 0.001) in the chronic schizophrenic group than in controls; first-degree relatives had a mean lymphocyte MAO activity midway between the schizophrenics and normals. No relationship was found between lymphocyte MAO activity and sex or age of subjects. When subjects were subgrouped by race, blacks had significantly lower MAO activity than whites (p < 0.001).     

Genetic analysis of platelet monoamine oxidase activity in families of schizophrenic patients

Platelet monoamine oxidase (MAO) has been implicated in the biology of several psychiatric disorders, including schizophrenia. Genetic factors contribute to the variance of MAO activity; however, its mode of inheritance is unknown. To assess the distribution and familial patterns of platelet MAO activity, we studied 73 chronic schizophrenic patients and 219 of their first-degree relatives. The activity distribution was skewed and admixture of two distributions gave a better fit to the data than a single distribution. Single-major-locus hypotheses were tested by pedigree analysis methods for quantitative traits. Using the transmission probability model, the familial transmission of MAO activity was consistent with either recessive or additive inheritance but not with dominant inheritance; the environmental hypothesis was strongly rejected. No effect of genotype on probability of illness was observed suggesting no relationship between the particular major locus tested and schizophrenia. The implications for genetic research in schizophrenia were discussed.     

Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients.

Platelet monoamine oxidase (MAO) activity was significantly lower than control values in a subgroup of 16 schizophrenic patients (most of whom were paranoid) characterized by the presence of auditory hallucinations and delusions. Platelet MAO activity was not reduced in 16 other schizophrenic patients without auditory hallucinations. This finding suggests that reduced platelet MAO activity is not found in all schizophrenic patients but tends to occur in a clinically identifiable subgroup.     

Pentametric distribution of platelet monoamine oxidase activity

The distribution of catalytic activity of platelet monoamine oxidase (MAO) with both tryptamine and phenylethylamine as substrates was examined in 1,129 Swedish men at age 18 years. A mixture of five components was needed to describe the distribution, even when the original scale was transformed to remove skewness. The proportions of admixture were 2% for the extremely low component with a mean of -2.3 sigma, 29% for moderately low MAO (mean -0.8 sigma), 51% for intermediate MAO (mean 0.0 sigma), 15% for moderately high MAO (mean + 1.3 sigma), and 3% for extremely high MAO (mean + 3.0 sigma). Thus, the upper and lower deciles each contain contributions from two extreme components that differ from a much larger intermediate component with activity near the mean of the general population. This is compatible with a minimum of three alleles at a single major locus or with at least two polymorphic loci. The hypothesis that MAO activity is controlled by two alleles at a single locus was tested and rejected. The demonstration of at least five distinct components to the distribution of MAO warrants further research to characterize the biochemical structure and function of MAO enzyme variants as well as study of the behavioral correlates of the components.     

Platelet monoamine oxidase and clinical phenomenology of schizophrenia

Platelet monoamine oxidase activity (MAO) was determined in 39 unmedicated chronic schizophrenic patients and 88 normal control subjects. Platelet MAO activity did not distinguish paranoid from nonparanoid patients or patients who met Taylor and Abrams criteria for narrowly defined schizophrenia from other schizophrenics. Enzyme activity was not related to either prognostic scores or age at onset of illness. MAO activity was decreased in patients compared to controls, and was lower in males than in females. Our findings indicate that clinical phenomenology, as defined in the present study, is of limited use in identifying biological subtypes of schizophrenia with deviant platelet MAO activity.     

Low platelet monoamine oxidase activity in pathological gambling

Decreased platelet monoamine oxidase (MAO) activity has been reported in association with sensation-seeking personality type and in some mental disorders associated with a lack of impulse control. Pathological gambling itself has been related with both sensation-seeking and reduced impulse control. Platelet MAO activity was investigated in 15 DSM-III-R pathological gamblers from our outpatient clinic. Gamblers had a significantly lower platelet MAO activity than a group of 25 healthy controls. The range of MAO levels in gamblers was also significantly shorter than in controls. In controls, platelet MAO levels showed the previously described negative correlations with sensation-seeking scores but not in gamblers. The findings are consistent with previous studies showing an association of low platelet MAO activity with impulse control disorders and raise some interesting therapeutic alternatives for pathological gambling.     

Schizophrenia and platelet monoamine oxidase: research strategies

The most widely replicated neurochemical finding in schizophrenia is that of lower levels of monoamine oxidase (MAO) in the platelets of chronic schizophrenics than in normal controls. Yet, the etiological role of MAO in schizophrenia remains to be demonstrated. The incidence of low MAO in other psychiatric disorders, effects of diet, hormones and drugs, and relationships of platelet MAO to brain levels and genetic mechanisms remain unclear. This article examines factors which make any biological indicator suitable for use as a diagnostic test for schizophrenia and inquires into the methodological pitfalls and unexamined assumptions of various research strategies which use this measure.