Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives.

It is well known that head-twitch response (HTR) in mice represents hallucinations, since administration of lysergic acid diethylamide (LSD) produces hallucinations in humans, and the HTR in mice is induced by administration of LSD as a hallucinogen. The HTR is produced by excitation of 5-hydroxytryptamine (5-HT)2A receptors. In this paper, we review the mechanisms of HTR induced by various drugs such as 5-HT precursor, 5-HT receptor agonist, 5-HT releaser, hallucinogenic compounds, benzodiazepins and cannabinoid. The response induced by HTR-inducers is significantly enhanced by combined treatment with a non-selective form of monoamine oxidase (MAO) inhibitor. Thus, the relationship between MAO activity and HTR caused by these drugs (especially, alpha-methylated analogous compounds which 5-fluoro-alpha-methyltryptamine, 6-fluoro-alpha-methyltryptamine and p-hydroxyamphetamine) is presented in detail.

Association analyses between polymorphisms of the phase II detoxification enzymes (GSTM1, NQO1, NQO2) and alcohol withdrawal symptoms.

BACKGROUND: NRH-quinone oxidoreductase 2 (NQO2) along with glutathione S-transferase M1 (GSTM1) and NAD(P)H-quinone oxidoreductase 1 (NQO1), which is involved in phase II detoxification reactions, is thought to be important for detoxification of catechol o-quinones in the central nervous system. Our previous study revealed that the human NQO2 gene is highly polymorphic. In this study, we investigated a possible association between polymorphisms of the GSTM1, NQO1, and NQO2 genes and alcohol withdrawal symptoms such as delirium tremens, hallucination, and seizure. METHODS: A total of 247 Japanese male alcoholic patients with alcohol withdrawal symptoms or without the symptoms, and 134 age-matched Japanese male controls (nonhabitual drinkers), were examined by using polymerase chain reaction (PCR), PCR restriction fragment length polymorphism, PCR-based single-strand conformational change polymorphism, and PCR direct sequencing analyses. RESULTS A significant difference was found between alcoholic patients and controls in genotype frequency at an insertion/deletion site in the promoter region of the NQO2 gene (p = 0.0014). The frequency of the homozygous genotype for the D allele at this locus was significantly higher in delirium tremens-positive patients (p = 0.0004) and in hallucination-positive patients (p = 0.0001), and in patients displaying both delirium tremens and hallucination (p = 0.0002), than in controls. The values were still significant after Bonferroni correction. On the other hand, no significant difference was detected for allele frequencies or genotype frequencies for the other polymorphic loci of the NQO2 gene. Moreover, GSTM1 gene deletion and missense mutation (Pro187Ser) of the NQO1 gene showed no significant association with alcohol withdrawal symptoms. CONCLUSION: Present data suggest that an insertion/deletion polymorphism in the promoter region of the NQO2 gene plays an important role in the pathogenesis of alcoholism and alcohol withdrawal symptoms.

The neural basis of Charles Bonnet hallucinations: a hypothesis.

OBJECTIVES: To describe the hallucinations occurring as a result of a macular hole in each eye and to investigate the neural basis. METHODS: Psychophysical observations including sketches of the hallucinations calibrated for size. RESULTS: All the hallucinations were of the geometric (patterned) type and lasted for only a few days. CONCLUSIONS: The observations can be explained on the basis of a "deafferentation" model, which is described in some detail. It is proposed that the hallucinations result from activation of the "blobs" of area V1 and the "stripes" of area V2 in the visual cortex. A theory is proposed to account for the disappearance of the hallucinations by a "filling in" mechanism.

Arylsulfatase A levels in patients with chronic alcoholism.

BACKGROUND: The goal of this study was to find the association between low arylsulfatase A (ASA) activity and psychiatric disorders in chronic alcoholic patients. METHODS: The study was carried out in 30 chronic alcoholic patients (27 male, 3 female); age range was 25-65 years. There were 20 normal controls (18 males, 2 females), and age range was 24-67 years. ASA and routine aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity laboratory tests were measured in blood serum from all patients and control subjects. RESULTS: Alcoholic patients with psychiatric disorders have ASA average values of 68.25 nmol/mL/4 h. This is less than averages found in the alcoholics without psychiatric disorders group (82.48 nmol/mL/4 h) and the control group (90.8 nmol/mL/4 h). There were no statistically significant differences among the three groups studied. Alcoholic subjects with elevated activity of AST and ALT (n = 10) have ASA activity average values of 134.82 nmol/mL/4 h), which is 48.8% higher than the control group (90.6 nmol/mL/4 h). These means show statistically significant differences (p <0.05). CONCLUSIONS: Results indicate an association between low serum ASA activity and alcoholism. The appearance of psychiatric manifestations could be related to the low activity of this enzyme in chronic alcoholic patients. Alcoholic patients with elevated enzyme activity of AST and ALT in sera also have elevated sera arylsulfatase A (ASA) activity. We consider that these findings may be useful for evaluating the psychiatric state as a prognosis in chronic alcoholic patients, and should be a routine laboratory test in alcoholic patients.

Platelet MAO activity in hallucinating and paranoid schizophrenics: a review and meta-analysis.

Published studies of platelet monoamine oxidase (MAO) activity of paranoid (P) and nonparanoid (NP) schizophrenics and normal controls, and of hallucinating (H) and nonhallucinating (NH) schizophrenics and normal controls were critically reviewed, and summary analyses were conducted on the original published data. Methods of comparing results across studies are discussed. Meta-analysis of the results of 11 analyses from 9 studies, examining a total of 165 P and 152 NP schizophrenics and 985 normal controls, indicated that the typical P schizophrenic studied had platelet MAO activity lower than that of 61% of NP schizophrenics and 79% of normal controls. Meta-analysis of the results of 8 separate analyses from 6 studies comprising 130 H, 81 NH schizophrenics, and 186 normal controls indicated that the average H schizophrenic studied had platelet MAO activity lower than that of 84% of NH schizophrenics and 80% of normal controls. In comparison with normal control values, P schizophrenics had the greatest mean percentage decrease in platelet MAO activity (30%), followed by NP schizophrenics (24%), and H schizophrenics (24%). These findings could not readily be attributed to diagnostic, demographic, or methodological factors, nor to the effects of alcohol or neuroleptics.

Relationship of auditory hallucinations and paranoia to platelet MAO activity in schizophrenics: sex and race interactions.

Platelet monoamine oxidase (MAO) activity was determined in 37 female and 64 male patients with Research Diagnostic Criteria diagnoses of paranoid or undifferentiated schizophrenia, or schizoaffective disorder, mainly schizophrenic, and for 71 female and 65 male normal controls (NCs). Female NCs had significantly higher adjusted mean platelet MAO activity than male NCs and female, paranoid, nonhallucinating schizophrenics. Male NCs had significantly higher adjusted mean platelet MAO activity than male, paranoid, hallucinating schizophrenics. Examination of main and interactive effects of diagnostic subtype, presence/absence of auditory hallucinations, gender, and race within the group of schizophrenic patients revealed no statistically significant main effect but, rather, significant interactive effects of auditory hallucinations with gender, with diagnostic group and gender, and with diagnostic group and race in the prediction of platelet MAO activity. The interaction of diagnostic subtype with race and gender in the prediction of platelet MAO activity was also statistically significant. In general, significantly decreased platelet MAO activity was associated with both paranoid subtype and presence of auditory hallucinations in male and in black schizophrenics; and with paranoid subtype alone in white male schizophrenics. These interactive relationships with platelet MAO activity in schizophrenics may account for discrepancies in previous reports of the activity of this enzyme in schizophrenics, and are consistent with reduced platelet MAO activity in subgroups of schizophrenics.

Platelet monoamine oxidase and plasma amine oxidase in psychiatric patients.

Platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) activities were determined in 70 normal controls and 76 psychiatric patients. Platelet MAO activity did not differ between the normal controls and patients diagnosed as schizophrenic or primary affective illness, although there was a strong trend for chronic schizophrenics to have lower MAO activity. Schizophrenic patients with Schneiderian-type hallucinatiions had significantly lower MAO activity than normal controls or schizophrenic patients who did not hallucinate. There was no relationship between hallucinations and platelet MAO activity in patients with affective psychoses. Paranoid schizophrenics did not have significantly different MAO activity from nonparanoid schizophrenics. PAO activity was generally lower in all diagnostic groups than in normal controls, but the results were statistically significant only for acute schizophrenics.

Platelet monoamine oxidase activity in subgroups of schizophrenic disorders.

This article summarizes findings from a series of studies that examined platelet monoamine oxidase (MAO) activity in patients with nonaffective schizophrenic disorders and schizophrenia-related depressions. The findings indicate that mean platelet MAO activity was not different from control values in the subgroup of nonaffective schizophrenic disorders without auditory hallucinations (that is, the S-1 subgroup). However, mean platelet MAO activity was reduced in the subgroup of nonaffective schizophrenic disorders characterized by the presence of auditory hallucinations often occurring in conjunction with paranoid features (that is, the S-2 subgroup). Moreover, we found that mean platelet MAO activity was increased in schizophrenia-related depressions characterized by histories of chronic asocial, eccentric, or bizarre behavior.

Platelet MAO activity: relationships to clinical and psychometric variables.

Platelet monoamine oxidase (MAO) activity was measured in a group of hospitalized male psychiatric patients. The findings of this study confirm previous reports of: (1) reduced platelet MAO activity in patients with auditory hallucinations, (2) reduced platelet MAO activity in patients with alcoholism, and (3) a positive correlation between platelet MAO activity and a psychometric index of social introversion.

Platelet monoamine oxidase activity in schizophrenia. Relationship to disease, treatment, institutionalization and outcome.

A study was made of platelet monoamine oxidase (MAO) activity in non-medicated, newly-admitted schizophrenics and institutionalized chronic schizophrenics both on and off medication. These patients were compared to two control groups: normal subjects and brain-damaged institutionalized patients. No relationship was found between platelet MAO activity and the severity or duration of illness, duration of psychotropic medication, presence of auditory hallucinations or institutionalization. Mean platelet MAO activity did not differ significantly between the schizophrenic subgroups and control groups. Thirty-one patients studied before and after treatment with phenothiazines showed no significant change in platelet MAO activity. The findings did not indicate a relationship between schizophrenia, its treatment or outcome and platelet MAO activity.

Monoamine oxidase (MAO) of platelets, plasma, lymphocytes and granulocytes in schizophrenia.

Monoamine oxidase (MAO) levels in plasma, platelets, lymphocytes and granulocytes have been compared in schizophrenics and controls using three substrates. No significant difference was found between MAO levels in controls and the schizophrenic group as a whole, but platelets and lymphocytes of the latter (tyramine or benzylamine substrate) showed greater variation and in some cases higher values than controls, irrespective of treatment. Schizophrenics who experienced auditory hallucinations had significantly lower MAO levels in lymphocytes and platelets than those who did not.

Differences in platelet monoamine oxidase activity in subgroups of schizophrenic and depressive disorders.

Platelet monoamine oxidase (MAO) activity was measured in patients with nonaffective schizophrenic disorders (i.e., without prominent symptoms of depressions or manias), and in patients with schizophrenia-related depressions. MAO activity was significantly lower than control values in a subgroup of 16 patients with nonaffective schizophrenic disorders (most of whom were paranoid) characterized by the presence of auditory hallucinations and delusions. Platelet MAO activity was not reduced in 16 other nonaffective schizophrenic patients without auditory hallucinations. Platelet MAO activity was significantly higher than control values in a group of 8 depressed patients with schizophrenia-related depressions characterized by the presence of chronic asocial, eccentric, or bizarre behavior. These findings of differences in platelet MAO activity in clinically defined subgroups of nonaffective schizophrenic disorders and the schizophrenia-related depressive disorders may help to account for some of the discrepancies in findings among the various studies of platelet MAO activity in schizophrenic and affective disorders.

Platelet monoamine oxidase activity during the course of a schizophreniform psychosis.

A case is reported in which platelet monoamine oxidase (MAO) activity fluctuated in the course of a schizophreniform psychosis in a way which suggests a direct relationship between low levels of MAO activity and the psychosis.

Indolethylamine-N-methyltransferase activity in psychiatric patients and controls.

The level of INMT activity was determined in the sera of 29 psychiatric patients and 11 healthy controls from St. Louis; and in 13 psychiatric patients and 15 healthy controls from Chicago. The level of enzyme activity in the serum of paranoid schizophrenics in the St. Louis group was significantly higher than in other types of schizophrenics. The mean level of enzyme activity in the serum in nonschizophrenic psychiatric patients in the Chicago group was significantly higher than that in the same group of patients from St. Louis. The serum level of INMT activity in all psychiatric patients and schizophrenic patients from St. Louis was positively correlated with severity of delusions. The only significant difference in the Chicago patients was that the occurrence of depressive features was greater in the group of patients with a low serum INMT level than in the group with a high enzyme level.