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)

The hypothesis that central biogenic amines may play a role in the pathophysiology of schizophrenia was originally based upon the fact that hallucinogenic and antipsychotic drugs have profound effects on central transmitter pathways where dopamine, noradrenaline and serotonin are involved. The structural similarities between hallucinogenic drugs such as amphetamine and mescaline, and catecholamines on the one hand and lysergic acid diethylamide (LSD) and indolamines such as serotonin on the other hand have by direct experimentation been shown to explain their important effects on the transmitter systems. The marked effect of several classes of chemically different antipsychotic drugs on central dopamine receptor function formed the basis for the dopamine hypothesis regarding the mechanisms of action of these drugs and also for the hypothesis that dopamine D2 receptor function played a significant role in the pathophysiology of schizophrenia. Direct experimental analysis of aminergic functions in the brain of schizophrenic patients, both during life and post mortem, has been and will for the foreseeable future continue to be a rational approach to the further elucidation of the validity of these hypotheses. Analysis of metabolite levels in the cerebrospinal fluid and plasma of schizophrenic patients has shown great variation in the results with reports of both elevated and reduced release of amines in the brains of schizophrenic patients. Analysis of the aminergic receptor structures in the postmortem human brain has relatively consistently revealed an increased density of D2 receptors in the major basal ganglia of schizophrenic patients. Whether these alterations represent a primary feature of brain structure in schizophrenia or a drug-induced effect still remains to be shown. Positron emission tomographic (PET) scan studies of D2 receptors in schizophrenia have demonstrated both increased densities and absence of change in the characteristics of D2 receptors in the patients as compared to matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoamines and schizophrenia. 197 95

Basal serum amino acids (including central monoamine precursors), central monoamines, and hormones were studied in schizophrenic patients (drug-naive; n = 20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic-withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What are the effects of neuroleptic treatment on these measures? (3) On which variables do drug-free and neuroleptic-treated patients differ? Because serum amino acid, central monoamine, and hormone levels were similar in drug-naive and drug-withdrawn patients, data from these groups ("drug-free") were combined and compared to those of healthy subjects and neuroleptic-treated patients. Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids were significantly lower in drug-free schizophrenic patients than in healthy subjects. Dopamine was increased, and melatonin and thyroid hormones were decreased in drug-free schizophrenic patients compared to healthy subjects. Norepinephrine, epinephrine, and prolactin were higher in neuroleptic-treated men compared to drug-free male patients or healthy men. These results are consistent with the hypothesis of dopaminergic overactivity in schizophrenia, which might be caused by altered amino acid precursor availability and could be related to the decrease in melatonin and reduction in thyroid hormone levels.
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PMID:Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects. 198 23

Absence of skin conductance response (SCR) is a psychophysiological sign frequently observed among schizophrenic patients. This alteration of electrodermal activity can be reproduced in cats and rats by intraventricular administration of 6-hydroxydopamine (6-OHDA), a neurotoxin selectively destroying catecholamine neurons. The finding appears to be quite consistent with the catecholamine hypothesis of schizophrenia. To determine which catecholamine system--the dopamine (DA) or the noradrenaline (NA)--is responsible for the induction of this abnormality, the same dose of 6-OHDA was microinjected to either the ventral tegmental area (VTA, n = 3), through which most DA fibers ascend, or to the ascending noradrenergic bundle (ANB, n = 3), through which most NA fibers ascend. Four cats remained intact as a control for later brain catecholamine estimation. The skin conductance of all pretreatment intact cats (n = 10) showed not only spontaneous fluctuations but also SCRs to auditory stimuli (5 kHz, 100 dB, 1 sec) which habituated with repetition. In contrast, ANB-lesioned cats showed a complete abolition of auditory SCRs, few spontaneous fluctuations, and a low basal skin conductance level. These abnormalities were statistically significant. On the other hand, no change was found in the skin conductance activity of the VTA-lesioned cats. Catecholamine estimation after the experiment confirmed selective destruction of the appropriate system corresponding to each type of lesion. These findings are discussed in the context of the DA or NA theory of schizophrenia, and involvement of the NA system in the pathogenesis of this illness is suggested.
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PMID:Skin conductance response after 6-hydroxydopamine lesion of central noradrenaline system in cats. 216 23

B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine), a candidate for selective dopamine (DA) autoreceptor agonist activity, was tested for its interactions with biochemical parameters of brain dopaminergic, noradrenergic and serotoninergic systems as measured in ventriculocisternal perfusates of chloralose-anaesthetized cats. DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA) and 5-hydroxyindolic acid (5-HIAA) were measured in samples of 30 min collection periods by high-pressure liquid chromatography with electrochemical detection. B-HT 920, in the dose range of 0.03-1 mg/kg i.v., promptly inhibited the efflux of DA and DOPAC in a dose-dependent manner. The 1 mg/kg dose of B-HT 920 reduced the DA levels below 25% of control levels for the whole length of the experiments. The HVA levels were reduced less and in a protracted manner. Only the highest dose of B-HT 920 tested (1 mg/kg) had a significant effect on the level of NA (marked, prompt reduction) and 5-HIAA (delayed, moderate reduction), reflecting its well known alpha 2-adrenoceptor agonist property. The effects of B-HT 920 on the dopaminergic indices were DA receptor-mediated as they were reversed by a low dose (0.05 mg/kg i.v.) of haloperidol. In contrast, the alpha 2-adrenoceptor blocking drug, idazoxan, 4 mg/kg i.v., while it reversed the NA and 5-HIAA reductions did not modify the effect of B-HT 920 on DA, DOPAC and HVA. Thus B-HT 920, in the dose range between 0.03-0.1 mg/kg, selectively affected brain dopaminergic parameters. Our experiments demonstrated that B-HT 920 causes an effective, long lasting and selective suppression of extracellular brain DA levels in vivo. B-HT 920 represents a promising compound for clinical use in pathological conditions known to be ameliorated by a reduction of brain DA activity, such as Huntington's disease, mania and schizophrenia.
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PMID:The dopamine autoreceptor agonist, B-HT 920, preferentially reduces brain dopamine release in vivo: biochemical indices of brain dopamine, noradrenaline and serotonin in ventriculocisternal perfusates in the cat. 246 28

The therapeutic efficacy and target symptoms of maprotiline were tested by administering it in addition to conventional neuroleptic treatment for 10 weeks to a total of 32 chronic schizophrenic patients who showed no, or only partial, response to the neuroleptic medication. The final global improvement rating was 68.8% for all patients. Average therapeutic doses administered were 150 mg per day. Changes in psychotic symptoms were assessed by the Brief Psychiatric Rating Scale (BPRS), Psychiatric Evaluating scale (PES), and the Scale for the Assessment of Negative Symptoms (SANS). All mean improvement rates of these rating scales were observed at the 2nd week after the start of treatment, and maprotiline produced a marked amelioration in negative symptoms such as decreased spontaneity, blunted affect, emotional withdrawal, impaired work or recreation, etc. The incidence of side-effects was 37.5%. Constipation was the most frequently occurring side-effect. Neither side-effects nor laboratory test results were serious enough to discontinue the trial, except in the case of one chronic patient who showed acute exacerbation of symptoms due to maprotiline-induced insomnia, elation and hallucination. These results suggest that maprotiline improves the negative symptoms of schizophrenia by a noradrenaline potentiating action not demonstrated by dopaminergic or serotonergic reward systems.
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PMID:Effect of maprotiline combined with conventional neuroleptics against negative symptoms of chronic schizophrenia. 257 Jun 87

For two decades it has been hypothesized that schizophrenia and depression are related to alterations in the activity of specific neurotransmitters in brain; to a great extent, these theories are based on the assumed mode of action of antipsychotic and antidepressant drugs. With the available knowledge of how panic anxiety can be effectively treated (and elicited) with drugs, it is now reasonable to formulate hypotheses also regarding the contribution of central neurotransmitters to the generation of panic. As will be discussed in this brief review, three substances seem to be of particular importance in this context: serotonin, noradrenaline and GABA. In view of this concept, the putative mode of action of the atypical benzodiazepine derivative alprazolam, which in contrast to other benzodiazepines has been attributed effectiveness in the treatment of panic, will also be discussed.
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PMID:Brain neurotransmission in panic disorder. 289 Feb 66

beta Phenylethylamine (PEA) is an endogenous amine that resembles amphetamine in chemical structure and has been identified in human and other mammalian brains and in many peripheral tissues. Although PEA exists in much smaller amounts than monoamines, the mode of action of PEA as a neuromodulator is of special interest. In this paper the author reviews animal and clinical studies on PEA. The first section deals the methods for the determination of PEA in mammalian brains and human urine. PEA is reliably measured using spectrofluorometric, gas chromatographic-mass spectrometric methods. The second chapter reviews the changes in animal behavior elicited by PEA. The administration of PEA induces stereotypy and increased motor activity in animals. The third part reviews the effect of PEA on dopamine, noradrenaline, serotonin and tyramine metabolism in mammalian brains. The fourth chapter examines recent clinical evidence suggesting a role for PEA in schizophrenia and affective disorders.
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PMID:[beta Phenylethylamine: psychopharmacological and clinical aspects]. 310 12

One important function of the catecholamine innervation of the cerebral cortex may be the control of attention. Of particular interest are the catecholamine projections to the cerebral cortex from the reticular formation, namely the dopamine neurons of the ventral tegmentum of the midbrain and the noradrenergic neurons of the locus coeruleus in the upper pons. Animal studies implicate noradrenaline and dopamine in a wide range of attention-related behaviours involving search and exploratory activity, distractibility, response rate, discriminability and the switching of attention. Most human studies come from the clinical literature relating to schizophrenia, Parkinson's disease and attention deficit disorder. An association has been claimed in each of these conditions between abnormal catecholamine activity (in particular dopamine) and attentional dysfunction. In particular, difficulty with the attachment of appropriate responses to environmental stimuli, akin to those observed in animals with lesions to central dopamine pathways, indicates a role for dopamine in response selection processes. Overall, the animal and human studies reviewed indicate a role for central noradrenaline and dopamine in the early and late processing of information, respectively.
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PMID:Catecholamines and attention. I: Animal and clinical studies. 332 64

Kinetic parameters KM and Vmax of the synaptosomal high-affinity dopamine (DA) and noradrenaline (NA) uptake were measured in the nucleus (n.) accumbens, n. caudatus and frontal cortex from post-mortem brains of schizophrenic patients and matched controls. Additionally, the 5-hydroxytryptamine (5 HT) uptake was determined in the n. accumbens of the same specimens. The KM and Vmax data of DA uptake were significantly elevated in the n. accumbens (KM to 253%, Vmax to 271%) and in the n. caudatus (KM to 201%, Vmax to 174%) of schizophrenics in comparison with controls. The kinetic parameters of the NA uptake increased similarly in the n. accumbens and n. caudatus of schizophrenics in comparison with controls. The alterations in DA and NA uptake kinetics do not seem to be primarily dependent on neuroleptic medication. On the other hand, DA and NA uptake in the frontal cortex as well as 5 HT uptake in the n. accumbens was unchanged. The results are compatible with the hypothesis that both DA and NA transmission systems are changed in schizophrenia. They give a first indication of presynaptic functional alterations in schizophrenia.
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PMID:Studies in postmortem dopamine uptake. II. Alterations of the synaptosomal catecholamine uptake in postmortem brain regions in schizophrenia. 355 42

Cerebrospinal fluid (CSF), thyrotropin releasing hormone (TRH), CSF-vasopressin (AVP), plasma-AVP, CSF-osmolality, plasma-osmolality, CSF-adrenaline (A) and -noradrenaline (NA) were measured in psychiatric patients and controls. Psychiatric patients were classified according to ICD-9 and grouped into endogenous depression, non-endogenous depression, mania and schizophrenia. The depressive groups were classified according to the Newcastle Rating Scale for Depression 1965. Severity of disease was quantified by BRMES, BRMS and BPRS. No difference in CSF-TRH levels was seen among the different diagnostic groups and controls. A positive correlation between CSF-TRH and CSF-A was demonstrated. CSF-AVP concentrations were significantly lowered in both endogenous and non-endogenous depression; no correlation with CSF-A or -NA was seen. Neither did any difference between plasma levels of AVP, plasma-osmolality or CSF-osmolality appear among the groups investigated.
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PMID:Cerebrospinal fluid vasopressin--changes in depression. 393 7


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