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.     

Patterns of urinary excretion among patients with self-induced water intoxication and psychosis

Parameters of water metabolism were measured serially in nine patients with the syndrome of self-induced water intoxication and psychosis (SIWIP). Clinical and laboratory findings indicated that SIWIP patients are type A of the syndrome of inappropriate antidiuresis. Estimated 24-hour urinary excretion of creatinine and early morning urinary creatinine concentration measurements were used to calculate 24-hour urine volumes. Polyuria was considered present for male patients when excretion was estimated to be greater than 2,600 ml of urine/24 hours or early morning urinary specific gravity was less than or equal to 1.003. Male patients with a specific gravity of less than or equal to 1.003 predictably excreted 28,000 ml of urine/day. Severe hyposthenuria may be a biological marker for a population at risk to develop complications of SIWIP, including seizures, coma, and death.     

Plasma phenylethylamine and phenylalanine in chronic schizophrenic patients

The hypothesis that phenylethylamine (PEA) is an endogenous psychotogen in schizophrenics, particularly those with the paranoid subtype, has been previously studied by measuring PEA levels in urine and cerebrospinal fluid (CSF) of schizophrenic patients. However, plasma PEA may more accurately reflect simultaneous alterations of PEA in many organ systems, as might occur in a genetic disorder of PEA metabolism. No study to date has examined phenylalanine (Phe), which is thought to be a precursor of PEA, in the same patients who had PEA measured. In this study, we measure both plasma PEA and Phe in 17 drug-free schizophrenic patients and 17 matched controls. Plasma PEA in normal controls was found to be lower by three orders of magnitude compared to normal controls from previous studies--a finding that has not previously been reported. PEA was significantly lower in those schizophrenic patients who had a Research Diagnostic Criteria diagnosis of paranoid schizophrenia. PEA did not differ between patients and controls, and the correlation between plasma Phe and PEA was not significant.     

Left hemispheric overactivation in schizophrenia: relationship to clockwise circling

Schizophrenic patients, nonschizophrenic patients, and nonpsychiatric controls were compared in their demonstration of clockwise circling (CC), and in lateral eye movement responses to verbal and spatial questions. Only schizophrenic subjects who did not evidence CC showed inappropriate left hemisphere arousal to spatial stimuli. A tendency was noted for CC to occur more frequently among paranoid than nonparanoid schizophrenics. The results, taken together with other recent findings, suggest that the absence of CC may correlate with a more severe form of schizophrenia, and one more likely to be characterized by overarousal of the left cerebral hemisphere.     

Differences between paranoid and nonparanoid schizophrenic patients on the somatosensory P300 event-related potential

Event-related potentials were recorded from schizophrenic patients (n = 30) and healthy controls (n = 30) using a somatosensory-reaction-time version of the oddball paradigm, by stimulating the right and the left median nerve. Latency, amplitude, duration and area of the P300 were measured. The patient group was subdivided into a paranoid (n = 16) and a nonparanoid (n = 14) subgroup and each was compared to controls. After stimulation of the right median nerve the nonparanoid group had a significantly prolonged P300 latency and a normal amplitude. The paranoid subgroup had a trend toward reduction of the P300 amplitude; its P300 latency was normal. After stimulation of the left median nerve, a prolongation of the P300 latency was observed in the paranoid subgroup. This subgroup had also a reduced P300 amplitude, while the nonparanoid patients had both values comparable to those of the controls. Duration and area were not significantly different between the two subgroups of patients and controls. Paranoid and nonparanoid patients showed a different behavior on reaction time parameters. No relationship was observed between P300 parameters and clinical ratings, neuroleptic dose and demographic data. The P300 parameters did not correlate with the reaction time measures. These results are discussed in terms of a disturbance of CNS inhibitory mechanisms in cognitive processes of paranoid schizophrenic patients and could be a further indication that different subtypes of schizophrenia may have different biological substrates.     

Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements

To test the hypothesis that 2-phenylethylamine (PEA) modulates affect, plasma levels and urinary excretion of its main metabolite, phenylacetic acid (PAA), were studied in depressed and manic subjects, and the mood-elevating effects of its precursor, L-phenylalanine, were studied in depressed subjects. Mean total plasma PAA concentrations were 491.83 +/- 232.84 ng/ml in 12 healthy volunteers and 300.33 +/- 197.44 ng/ml in 23 drug-free patients with major depression. The 24-hour urinary PAA excretion was also measured in 48 healthy volunteers (141.1 +/- 10.2 mg PAA/24 hr) and in 144 patients with major depression (78.2 +/- 41.0 mg PAA/24 hr). The results suggest that low plasma and urinary PAA may be state markers for depression and are compatible with the PEA hypothesis. In further support, phenylalanine elevated mood in 31 of 40 depressives.     

Ethological study of facial behavior in nonparanoid and paranoid schizophrenic patients

This investigation addressed the question of affective disturbance in schizophrenia by applying quantitative measurement techniques to patients' facial behavior. The subjects were medication-free male inpatients: nine nonparanoid and six paranoid schizophrenic patients and 12 drug- or alcohol-abuse rehabilitation control patients. Two judges scored the subjects' behavior, which was recorded on videotape, according to a system that included 16 different types of facial movements. Eye blinks, eye contact, and words spoken were also scored. Compared to the control patients, the nonparanoid schizophrenic patients spoke significantly fewer words and had significantly less eye contact, while the paranoid schizophrenic patients had significantly fewer eyebrow and lower facial movements.     

Subtype diagnosis in schizophrenia and its relation to neuropsychological and computerized tomography measures

We compared schizophrenic patients with a subtype diagnosis of paranoia (n = 14) to those with nonparanoid subtype diagnoses (n = 18) on the Wisconsin Card Sorting Test (WCST) and multiple computed tomography (CT) scan measures. The results showed that patients with nonparanoid diagnoses sorted fewer categories and made more perseverative errors on the WCST than did patients with the paranoid diagnosis. However, patients in the nonparanoid group could not be distinguished from those in the paranoid group on CT scan measures of brain structure. Additionally, a significant correlation was found between right frontal sulcal enlargement on CT scans and the number of perseverative errors made on the WCST.     

Phenylethylaminergic mechanisms in attention-deficit disorder

Urinary excretion (24-hr) of beta-phenylethylamine (PEA), phenylacetic acid (PAA), phenylalanine (Phe), and p-tyrosine (Tyr), and plasma levels of PAA, Phe, and Tyr were examined in 18 normal children and 26 children diagnosed as having attention-deficit hyperactivity disorder (ADHD). The results indicated that urinary excretion (expressed per g of creatinine) of free and total PEA was significantly lower in the ADHD patients, and plasma levels of Phe and Tyr were also decreased in the ADHD subjects compared with the normal controls.     

Platelet monoamine oxidase: studies on the rate of heat inactivation in normal and in paranoid and nonparanoid chronic schizophrenic groups.

The heat inactivation curves for platelet monoamine oxidase (MAO) in chronic schizophrenic and normal subjects were virtually identical. There were also no differences found when schizophrenic patients were subgrouped into paranoid and nonparanoid types. However, the MAO from one of the normal subjects showed a substantially greater thermolability than that of any other control or schizophrenic subject.     

Effects of diet on urinary excretion of MHPG in normal preadolescent boys

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.     

Subclinical polydipsia and polyuria in young patients with schizophrenia or obsessive-compulsive disorder vs normal controls

1. 1. Increased water intake and output is more common among psychiatric patients, especially those with schizophrenia, than in the general population. Animal studies suggest that polydipsia and polyuria derive, in part, from dopamine dysregulation. Stimulated by these observations this study sought to elucidate relationships among water homeostasis, monoamine metabolism, and electrolyte excretion in schizophrenic patients with and without paranoid hallucinatory symptoms (PH vs. NP), thought to reflect hyper- and hypo-dopaminergic states respectively, and to compare these with those shown by patients with obsessive compulsive disorder (OCD).

2. 2. 24hr-urine samples for electrolyte, monoamine and metabolite measures were taken from 14 schizophrenic patients with PH symptoms, 13 with predominantly nonparanoid (NP) symptoms, 11 OCD patients and 27 healthy controls (matched for age, weight and creatinine production). Water intake and serum electrolytes was sampled during psychological testing.

3. 3. PH patients drank 2–3 times more than the others in a 3–4hr test, yet 24hr-urinary volumes were 75% larger in both PH and NP patients than in the two comparison groups.

4. 4. Daily potassium excretion was a bit higher in PH patients, but concentrations of sodium, potassium and phosphate tended to be lower in PH and NP patients than in the others.

5. 5. Positive associations of electrolyte with homovanillic acid excretion were consistent across groups and not directly related to medication. But associations of electrolyte excretion with noradrenergic activity in controls were absent in psychotic patients and associations with serotonin in OCD patients were absent in the other groups.

6. 6. Increased water intake and output in PH patients along with the disturbed association with noradrenergic metabolism are consistent with altered autonomie activity in these patients.

7. 7. The independence of measures of water homeostasis from dopaminergic medication indicates that the associations in clinically responding PH patients of polydipsia with DA function (decreased DA levels) may be pertinent to this subgroup but not to schizophrenia in general.

     

Platelet serotonin in subtypes of schizophrenia and unipolar depression.

In subtypes of schizophrenia and unipolar depression, both increased and decreased levels of platelet serotonin were found. Hyperserotonemia was usually observed in patients with psychotic features (i.e., in paranoid schizophrenia and psychotic depression). Hyposerotonemia, although less common than hyperserotonemia, was present in nonparanoid schizophrenia and nonpsychotic depression (i.e., in patients without psychotic symptoms). A sex difference in platelet monoamine oxidase activity was observed among healthy subjects, but not among schizophrenic patients. The activity of platelet monoamine oxidase in paranoid and nonparanoid schizophrenic patients did not differ from that in healthy subjects. The findings in this study suggest that biological differences between subtypes of unipolar depression or schizophrenia might depend upon the presence of psychotic symptoms.     

Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man

Urinary phenylacetic acid (PAA) excretion was found to be decreased in a group of chronic schizophrenic patients, particularly in a nonparanoid subtype. No significant change in PAA excretion was observed in a group of 21 unipolar depressed patients. Urinary PAA was studied following the administration of phenylethylamine, monoamine oxidase inhibitors, a dopa decarboxylase inhibitor, a low phenylalanine diet, and phenylalanine loads in several groups of psychiatric patients and normal volunteers. While Phenylethylamine ingestion increased urine PAA, inhibition of both phenylethylamine metabolism and synthesis failed to alter urine PAA. These studies suggest that urine PAA is primarily derived from phenylalanine transamination or pathways not involving monoamine oxidase or both. The observed decrease in PAA excretion in some schizophrenic patients may reflect an alteration in this pathway. The high phenylethylamine excretion previously reported in some chronic schizophrenic patients is not directly related to the observed low PAA excretion. Therefore measurement of urine PAA is not expected to be useful in assessing any phenylethylamine abnormalities in psychiatric disorders. The possible contribution of reduced phenylalanine transamination and its subsequent increased availability for the possible synthesis of phenylethylamine in schizophrenia is discussed.     

Homovanillic acid (HVA) urinary excretion and day/night rhythm of chronic schizophrenic patients. Preliminary observations

The authors report, as compared to healthy subjects, a higher daily excretion and a higher urinary variations of homovanillic acid (HVA) for schizophrenic chronic paranoid patients (patients with positive symptomatology predominating, CROW,s type I). Inversely, a lower HVA excretion and probably an inversion of the circadian rhythm of urinary HVA were found for schizophrenic chronic undifferentiated patients (patients with negative symptomatology predominating, CROW's type II). These results have to be confirmed by the study of a greater number of patients and the measure, for comparison among themselves, of other precursors and metabolites of monoamines.     

Urine beta-thromboglobulin concentration or beta-thromboglobulin/creatinine ratio in single voided urine samples cannot be reliably used to estimate quantitative beta-thromboglobulin excretion

Different procedures are currently used in the urine beta-thromboglobulin (BTG) assay. We investigated the reliability of limited urine collections and of different expressions of urine BTG results (concentration, urine BTG/creatinine ratio) for the measurement of hourly or daily BTG excretion rates. BTG was measured by a sensitive RIA method in various urine collections of normal subjects (n.80) and patients (n.120) with miscellaneous diseases where an enhanced in-vivo platelet activation could be expected. The BTG concentration in a 6-hour urine collection appeared to change in relation to the urine flow rate (r = -0.53 in normals, r = 0.27 in patients, p less than 0.01) and urine osmolality (r = 0.46 in normals, r = 0.31 in patients, p less than 0.01). In both normals and patients not a very good correlation was observed between the urine BTG/creatinine ratio and the BTG excretion rate (r = 0.54 and r = 0.48; p less than 0.001, respectively). Variable coefficients of correlation (r = 0.83-0.34) were observed between the BTG excretion rate of single voidings of the morning, afternoon-evening and night and the daily BTG excretion both in normals and patients. Reliable measurements of the BTG in urine should be expressed as the hourly excretion rate in a given period of the day for limited urine collections or as the daily excretion for 24-hour urine collections.     

Hypertension and paranoia

No differences in blood pressure on admission were found between samples of paranoid, paranoid schizophrenic, and nonparanoid psychiatric inpatients. The findings provide evidence against the catecholamine hypotheses of these disorders.     

Plasma phenylethylamine in schizophrenic patients

Plasma samples were collected from 41 patients who met DSM-III criteria for schizophrenia and from 34 healthy controls. Phenylethylamine (PE) levels were determined using a gas chromatography-mass spectrometry negative chemical ionization method. PE was significantly higher in the schizophrenic patients compared with controls. There were no differences in PE between paranoid and nonparanoid patients. Plasma PE did not appear to be influenced by the severity of schizophrenic symptoms (rated by BPRS, SANS, and SAPS) or by the amount of dietary phenylalanine ingested within 24 hr of testing. Plasma PE did not correlate with current or past exposure to neuroleptic medication. It was not possible, however, to test individual patients during two periods when they were taking and not taking medication. Thus it is possible that neuroleptic exposure may have confounded the results. This study provides further evidence that PE excess may play a role in the etiology of schizophrenia but does not support previous studies which suggest that such an abnormality is limited to the paranoid subgroup.     

Plasma amine oxidase and clinical features of schizophrenia

Among 76 chronic schizophrenic patients, plasma amine oxidase activity was unrelated to paranoid/nonparanoid subtype, narrow/broad diagnostic criteria, prognosis, or age at onset. These clinical indices do not identify biological subtypes of schizophrenia with deviant plasma amine oxidase activity.     

Lithium treatment and kidney function. A survey of 237 patients in long-term treatment

Kidney function has been examined in 237 patients who in the autumn of 1977 were in lithium treatment at the Psychiatric Hospital in Risskov, most of them as outpatients. The average age was 42 years. The patients had been given lithium treatment for 0.5-17 years, mean duration 5 years. The mean lithium dosage was 33 mmol/day and the mean 12-hour serum lithium concentration 0.85 mmol/l. Glomerular filtration rate was assessed through determination of 24-hour creatinine clearance and serum creatinine, in some cases iothalamate clearance. Water excretion was assessed through determination of 24-hour urine volume and in some cases urine osmolality after 26 hours of fluid deprivation. Creatinine clearances, serum creatinine concentrations, and urine volumes were subjected to multiple regression analysis with various clinically relevant predictor variables. Affection of glomerular filtration rate was only moderate and progressed slowly. The data indicate that the risk of renal insufficiency and terminal azotemia is remote even when lithium is given for many years. A large number of the patients had altered water excretion with polyuria or lowered urine concentrating ability or both. Due to the extra fluid loss these patients are apt to develop dehydration, and they may then be in danger of lithium poisoning. We hypothesize that lithium-induced changes of kidney function may become less frequent and less pronounced if patients are maintained at serum lithium levels somewhat lower than those employed in the group studied here. We recommend careful monitoring of serum lithium levels, regular control of kidney function, and extra caution when physical illness or additional drug treatment may lead to disturbance of fluid and electrolyte balance.