Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. It has been proposed that an increase in the concentration of the neuromodulator phenylethylamine at the post-synaptic dopamine receptor may be involved in the etiology of schizophrenia. If this increase is the case, a reduction in the CSF and/or serum concentrations of phenylacetic acid, its major metabolite, might be anticipated. 2. The authors have found in hospitalized Indian schizophrenic patients ingesting antipsychotic drugs, that the paranoid subgroup did indeed exhibit lower levels of unconjugated, conjugated and total phenylacetic acid in both serum and CSF.
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PMID:Phenylacetic acid in CSF and serum in Indian schizophrenic patients. 200 39

Lumbar cerebrospinal fluid concentrations of phenylacetic acid were significantly elevated in paranoid vs. nonparanoid schizophrenics. Further, phenylacetic acid concentrations were correlated with hostility. These results are consistent with the hypothesis that phenylethylamine, the proposed precursor of phenylacetic acid, plays a role in schizophrenia.
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PMID:CSF phenylacetic acid and hostility in paranoid schizophrenia. 261 81

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.
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PMID:Urinary trace amine excretion and platelet monoamine oxidase activity in schizophrenia. 362 9

Phenylethylamine (PEA) is an endogenous substance with amphetamine-like stimulant properties. On the basis of this ability an abnormal brain PEA metabolism has been proposed as an etiological factor in some forms of schizophrenia. In the present study 28 schizophrenic patients and 15 healthy controls were investigated. No significant difference from control values was found in PEA concentration in cerebrospinal fluid (CSF) of either untreated of neuroleptic-treated schizophrenics. However, 2 schizophrenics with highest BPRS scores had extremely high PES concentrations. Free phenylacetic acid (PAA), the major metabolite of PEA, was significantly decreased in ummedicated but not in drug-treated schizophrenics. Because of the assumed neuromodulatory properties of PEA, it is suggested that lowered PAA concentrations and the tendency for PEA to be elevated may imply that altered central neurotransmission occurs in certain forms of schizophrenia.
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PMID:Phenylethylamine and phenylacetic acid in CSF of schizophrenics and healthy controls. 613 17

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.
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PMID:Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man. 671 36

Cerebrospinal fluid levels of phenylacetic acid (CSF PAA) were obtained from normal controls and from drug-free psychiatric inpatients (schizophrenia, major depression, mania, and schizoaffective disorder). Post-treatment CSF PAA levels were obtained from 16 patients after 4 weeks of neuroleptic treatment. Phenylacetic acid levels were higher in women and were significantly correlated with age. There were no differences in CSF PAA levels between the various diagnostic groups and no difference between the paranoid and the nonparanoid subtypes of schizophrenia. CSF PAA was significantly correlated with several measures of psychopathology, especially the Brief Psychiatric Rating Scale hostility/suspiciousness factor. Neuroleptic treatment did not result in significant PAA changes. These findings are discussed in light of the amphetamine-like role ascribed to phenylethylamine, the precursor of PAA.
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PMID:Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral associations and response to neuroleptic treatment. 763 84

1. The evidence that phenylethylamine (PEA) plays a role in the etiology of schizophrenia is reviewed. 2. PEA shares structural and physiological similarities with the amphetamines, the administration of which can induce a schizophrenia-like psychosis. 3. While there are a number of reports of high urinary PEA excretion in schizophrenic patients, the measurement of PEA in other body fluids and the measurement of phenylacetic acid (the major metabolite of PEA) has resulted in inconsistent findings. 4. The use of neuroleptic medication is a major confounding variable in most of the clinical studies. If PEA does have a role in the etiology of schizophrenia, the mechanism may involve PEAs ability to amplify dopamine responses.
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PMID:Phenylethylamine and schizophrenia. 790 96

This study reports the application of Nile blue (NB), a farred oxazine label, as a precolumn derivatization reagent for the measurement of free levels of phenylacetic acid (PAA) in plasma. The measurement of PAA in psychiatric populations is important because it provides a marker for 2-phenylethylamine (PEA), which has been implicated in the pathogenesis of schizophrenia and major depression. PAA was derivatized with NB through an amide linkage in the presence of 2-chloro-1-methylpyridinium iodide (carboxylic acid activator, CMP) and triethylamine (base catalyst, TEA), respectively. The formation of the NB-PAA derivative was confirmed using normal phase and reversed phase thin-layer chromatography, reversed phase liquid chromatography, and electrospray mass spectrometry. The formation of the NB-PAA derivative was optimized using a sequential single factor approach. The optimal conditions for the formation and chromatographic separation of the derivative were determined to be 8.0 nmol/mL NB, 390 nmol/mL CMP, 2 mumol/mL TEA, a reaction time of 45 min, and a reaction temperature of 25 degrees C. This derivatization scheme was performed in a phase transfer catalysis mode that enabled the simultaneous extraction, preconcentration, and derivatization of the analyte in a single step. The limit of derivatization of PAA was determined to be 1.0 x 10(-9) M in phosphate-buffered saline, a PAA-free matrix. This derivatization was limited not by the kinetics of the reaction but by the chromatographic separation of the derivative from a side reaction product. The method was used to estimate endogenous free levels of PAA in human plasma samples. The levels of PAA in four sources of plasma were determined to be within 30-70 ng/mL using the method of standard addition and reflected levels that have been reported in the literature. The limit of detection of the derivative was determined to be 7.33 x 10(-11) M using a laboratory-constructed HPLC-VDLIF detector.
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PMID:Visible diode laser-induced fluorescence detection of phenylacetic acid in plasma derivatized with Nile blue and using precolumn phase transfer catalysis. 925 52

The effects of acute and repeated nicotine administration on the stress response of rat mesoprefrontal dopaminergic pathways were examined. Rats were given daily injections of nicotine (0.15 or 0.60 mg/kg, s.c., freebase) or saline for 4 days, then challenged with either nicotine or saline. A regimen of inescapable electrical footshocks or no footshocks was then administered. Thirty minutes after final injection, rats were sacrificed, brains removed and dopamine (DA) and its metabolite dihydroxy-O-phenylacetic acid (DOPAC) were extracted from medial prefrontal cortex (mPFC), nucleus accumbens septi (NAS) and dorsolateral striatum and quantified by high performance liquid chromatography with electrochemical detection. Acute administration of low dose nicotine (0.15 mg/kg) produced an increase in DA utilization (increased DOPAC/DA ratio) in mPFC and NAS, but not striatum. High dose nicotine (0.60 mg/kg) produced activation in NAS, but not mPFC or striatum. Repeated low dose nicotine pre-treatment produced tolerance to the effects of nicotine challenge in the mPFC, and reduced its effects in NAS. Footshock stress preferentially increased DA utilization in mPFC and associated footshock stress-induced immobility responses, and these were reduced by low, but not high, dose repeated nicotine pre-treatment. Further, a single dose of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (MCA) 30 min prior to nicotine challenge dose-dependently blocked the reduction of mesoprefrontal DA stress responsivity and immobility responses produced by repeated nicotine pre-treatment. These results indicate that: (1) there are dose-dependent differential effects of acute and repeated nicotine pre-exposure on regional DA utilization; (2) low, but not high, dose repeated nicotine reduces both the mesoprefrontal DA and behavioral effects of acute footshock stress; and (3) these effects of repeated nicotine may depend on mecamylamine-sensitive nAChR stimulation. These results may have relevance to acute stress and nicotine dependence, particularly in schizophrenic disorders, which have high prevalence rates of co-morbid nicotine dependence, stress-induced symptom exacerbation and prefrontal cortical dysfunction.
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PMID:Effects of repeated nicotine pre-treatment on mesoprefrontal dopaminergic and behavioral responses to acute footshock stress. 972 61