Polyamines are small positively charged alkylamines that are essential in a number of crucial eukaryotic processes, like normal cell growth and development. In normal physiological conditions, intracellular polyamine content is tightly regulated through a fine regulated network of biosynthetic and catabolic enzymes and a transport system. The dysregulation of this network is frequently associated to different tumors, where high levels of polyamines has been detected. Polyamines also modulate ion channels and ionotropic glutamate receptors and altered levels of polyamines have been observed in different brain diseases, including mental disorders and epilepsy. The goal of this article is to review the role of polyamines in mental disorders and epilepsy within a frame of the possible link between these two brain pathologies. The high comorbidity between these two neurological illnesses is strongly suggestive that they share a common background in the central nervous system. This review proposes an additional association between the noradrenalin/serotonin and glutamatergic neuronal circuits with polyamines. Polyamines can be considered supplementary defensive shielding molecules, important to protect the brain from the development of epilepsy and mental illnesses that are caused by different types of neurons. In this contest, the modulation of polyamine metabolism may be a novel important target for the prevention and therapeutic treatment of these diseases that have a high impact on the costs of public health and considerably affect quality of life.

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.

We did a meta-analysis on all publications (English and other languages) concerned with platelet monoamine oxidase (MAO) in schizophrenia. Essentially, when patients were medicated with a neuroleptic, most studies found that schizophrenics had lower platelet MAO levels than controls. Administration of neuroleptic lowers MAO levels. MAO levels in drug-free schizophrenics were similar to controls. Only a minority of studies found drug-free schizophrenics had decreased platelet MAO levels.

Platelet monoamine oxidase (MAO) activity was significantly lower in nonpsychotic, nonorganic, unmedicated male inpatients with DSM-III-R borderline personality disorder (BPD) than in nonpsychiatric controls. Patients with BPD who also met DSM-III-R criteria for antisocial personality disorder had significantly lower MAO activity than those with BPD alone. Low MAO activity in this sample did not appear to be related to the comorbid presence of major depressive disorder or a history of substance abuse.

Plasma benzylamine oxidase (BzAO) activity was analysed in a group of 40 schizophrenic patients and compared with that of healthy controls. Although plasma BzAO was significantly decreased in schizophrenics as a whole, when patients were divided into type I (favourable course) and type II (poor course) it was found that the reduced BzAO activity was only observed in type I. Several clinical features were associated with a low BzAO level. The clinical and biological significance of the identification of a biochemical alteration in a subgroup of schizophrenic patients is discussed, and we suggest that the possibility of BzAO being a marker for prognosis in schizophrenia should be further investigated.

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.

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 MAO activity was measured in 75 hospitalized depressed patients and in 31 healthy subjects. Plasmas post dexamethasone cortisol levels were examined in 73 patients. Results indicate that higher platelet MAO activity does not occur in all, but only in male major depressed patients. No relationship between changes of MAO activity and specific clinical subtypes was found. Platelet MAO activity is not different between DST suppressors and DST non suppressors. The authors suggest that platelet MAO activity may be related to non specific factors such as sex, age, but not to diagnosis of depression.

Although the clinical presentation and course of schizophrenia is highly variable, it is unclear whether this reflects heterogeneity at an aetiological level. The genetic evidence is reviewed concerning 'traditional' clinical subtypes as more novel categories derived from multivariate statistical methods and Crow's type I-type II classification. Recent data based on a twin series and re-analysis of older published family material suggest that attempts to divide up schizophrenia have resulted in splits between two or more categories of disorder which occupy different positions on the same continuum of liability. Thus, apparent heterogeneity is more likely to be due to quantitative difference in familial-genetic loading rather than qualitative differences. Similarly, the hypothesis that schizophrenia can be broadly divided into two groups, one genetic and the other non-genetic has little to support it. It seems improbable that any further useful and genetically relevant subdivision of schizophrenia can be effected on purely clinical grounds. Further progress awaits developments in the discovery of endophenotypes and the application of molecular genetic marker strategies.

Preliminary data are presented on levels of plasma cortisol, dopamine (DA), epinephrine (EPI), and norepinephrine (NE) before and after dexamethasone in 22 depressed patients (of whom 4 were psychotic). Platelet monoamine oxidase (MAO) activity, determined in 19 of the depressed patients, was significantly higher in the 4 psychotic patients than it was in the 15 nonpsychotic patients. Positive correlations were observed before and after dexamethasone among cortisol, DA, EPI, and platelet MAO. After dexamethasone, plasma NE correlated negatively with DA, EPI, and cortisol. The various correlations were due largely to the inclusion of the psychotic depressive subgroup. Data are also presented on the relationships between these biological measures and specific signs and symptoms.

Plasma amine oxidase (PAO) activity has been implicated in the biology of schizophrenia. PAO activity is, in part, under genetic control, but its mode of inheritance has not been determined. To assess the genetic pattern of PAO activity and its relation to the transmission of schizophrenia, we studied 73 chronic schizophrenic probands and 217 first-degree relatives (siblings and parents). Single-major-locus hypotheses were tested by pedigree analysis methods for quantitative traits. The distribution of PAO activity indicated significant admixture. When the transmission probability model was used, the familial pattern of PAO activity was consistent with mendelian transmission; the environmental hypothesis was rejected. PAO activity was lower in schizophrenic patients than in unaffected relatives, but the mean reduction in enzyme activity was small (10.7%) and the two groups of subjects overlapped greatly in their PAO values. The difference between ill and well relatives was not statistically significant. However, schizophrenia spectrum disorders segregated with low PAO activity in families of low-activity probands, and a greater proportion of ill than well subjects clustered in the low PAO activity mode. The results are interpreted as follows: (1) The transmission of PAO activity may be determined in part by a single major autosomal gene. (2) Low PAO activity does not qualify as a major risk factor in the schizophrenic population at large; however, a relationship may exist between low PAO activity and the transmission of schizophrenia in families of patients with extremely low enzyme activity.

A significant positive correlation was found between negative symptoms and platelet monoamine oxidase (MAO) activity in unmedicated male, but not female, schizophrenic patients. This correlation was significant in split halves of the male patients. There was no indication that the correlation was due to either outliers or medication effects. Male schizophrenic patients with high negative symptom scores had significantly higher mean platelet MAO activity than either male normal control subjects or male schizophrenic patients with low negative symptom scores. This finding suggests that the extent of negative symptoms in a population of males could affect whether the schizophrenic subjects will be found to have platelet MAO activity which differs from that of normal control subjects. The implications of the correlation between platelet MAO activity and negative symptoms for the role of brain MAO activity and two of its substrates, dopamine and serotonin, in the etiology of negative symptoms in male schizophrenic patients are discussed.

Inhibitory activity against the enzyme monoamine oxidase is present in low molecular weight fractions (less than 100,000) of human cerebrospinal fluid. These endogenous substances of different molecular weights (3000 to more than 35,000) act like monoamine oxidase inhibitor drugs to inhibit both type A and type B monoamine oxidase.

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.

We studied 24-hour urinary excretion of phenylethylamine (PEA) and creatinine in 50 schizophrenic (39 paranoid and 11 nonparanoid) and 19 nonpsychiatric patients from Bombay, India. Methods for diagnosis, clinical assessment, and 24-hour urine collection were identical to those used in an earlier study done in a Washington, D.C. hospital. Clinical evaluations were done in Bombay, while urinary PEA and creatinine estimations were performed at NIMH, Washington, without knowledge of the subjects' identify. Paranoid schizophrenic patients had significantly greater 24-hour urinary excretion of PEA than both nonparanoid schizophrenic patients and nonpsychiatric controls. The mean amount of PEA per g creatinine in urine was also highest of paranoid schizophrenic patients. Our findings provide cross-cultural support to the possibility of abnormal PEA metabolism in at least some patients with paranoid schizophrenia.

The authors compared platelet monoamine oxidase activity in schizophrenic patients and normal controls. A significant reduction in the enzyme activity was found in the male schizophrenic patients but not in the females. No differences were detected among the subgroups of schizophrenia. Sources of bias and the possible mechanism for the findings are discussed.

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.

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.