Cerebrospinal Fluid and Plasma Monoamine Metabolites and Their Relation to Psychosis

Pickar, David; Breier, Alan; Hsiao, John K.; Doran, Allen R.; Wolkowitz, Owen M.; Pato, Carlos N.; Konicki, P. Eric; Potter, William Z.

doi:10.1001/archpsyc.1990.01810190041006

Cited by 87 publications

(32 citation statements)

References 77 publications

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“…The slope of change in REM density following biperiden was inversely correlated to plasma HVA level in schizophrenic patients. Several studies have demonstrated the utility of plasma HVA levels as a measure of DA activity in the study of schizophrenia (Pickar et al 1990;Davila et al 1988;Sumiyoshi et al 1997). Because REM density is determined by the balance of cholinergic and catecholaminergic (in this case, dopaminergic) activity, our results suggest that the greater reduction in REM density (a measure of DA-ACh interactions) in schizophrenic patients following cholinergic blockade may be related to increased DA activity.…”

Section: Discussionmentioning

confidence: 58%

The Cholinergic System in Schizophrenia Reconsidered: Anticholinergic Modulation of Sleep and Symptom Profiles

Tandon

Taylor

DeQuardo

et al. 1999

Neuropsychopharmacology

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Receptors, Cholinergic; Receptors, muscarinic; Parasympathetic nervous system; Sleep, REM; Symptoms, positive; Symptoms, negative The dopamine (DA) hypothesis has dominated biochemical and pharmacological research on schizophrenia for about two decades. Although pharmacological data implicate increased DA activity in the pathogenesis of positive symptoms of schizophrenia, there is minimal association with negative symptoms (Crow 1980;Andreasen and Olsen 1982;Angrist et al. 1980). The poorly elucidated pathogenesis of negative symptoms and the unique properties of the atypical antipsychotic clozapine (Jibson and Tandon 1998) have encouraged a reappraisal of the role of the DA system in schizophrenia. Newer approaches to evaluating neurochemical abnormalities in schizophrenia include consideration of other neurotransmitter systems. Models of DA-serotonin (Meltzer 1989), DA-glutamate (Carlsson and Carlsson 1990), DA-acetylcholine (Tandon and Greden 1989), and DA-norepinephrine (van Kammen et al. 1990) interactions have been proposed. Although these models still accord DA a significant role in schizophrenia pathophysiology, they suggest that altered balance between DA and one (or more) of these other neurotransmitter systems may be the principal neurochemical abnormality related to the production of schizophrenic symptoms. Some of the earliest pharmacological treatments for schizophrenia included cholinergic agents (Cohen et al. 1944;Collard et al. 1946;Pfeiffer and Jenney 1957), and in the 1970s, several investigators suggested that cholinergic activity may be reduced in schizophrenia (Friedhoff and Alpert 1973;Janowsky et al. 1973;Davis et al. 1975;Singh and Kay 1979). There was no direct evidence of altered cholinergic functioning in schizophrenic patients, however, and pharmacological trials with cholinergic agents were generally ineffective (Rowntree et al. 1950;Gerlach et al. 1977;Davis and Berger 1978). With few exceptions (Johnstone et al. 1983;Singh et al. 1987), cholinergic mechanisms were increasingly considered irrelevant to the pathophysiology of schizophrenia and discussed predominantly with reference to the treatment of undesirable extrapyramidal side effects of neuroleptics (Richelson 1984). Indirect evidence from several lines of research, however, suggests that the cholinergic system may differentially influence positive and negative symptoms in schizophrenia (Tandon and Greden 1989).We and others have been conducting various studies to evaluate the role of the cholinergic system in schizophrenia, based on a primary hypothesis that DA-acetylcholine (ACh) interactions are of central importance in the production of positive and negative symptoms of schizophrenia (Tandon and Greden 1989;Tandon and Greden 1991). Based on available data and on observations of the course of positive and negative symptoms during the acute phase of the illness (Donlon and Blacker 1973;Docherty et al. 1978;Tandon et al. 1990a), we posited a role for disruption in DA-ACh balance in the expression of positive and negat...

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Section: Discussionmentioning

confidence: 58%

The Cholinergic System in Schizophrenia Reconsidered: Anticholinergic Modulation of Sleep and Symptom Profiles

Tandon

Taylor

DeQuardo

et al. 1999

Neuropsychopharmacology

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“…However, the changes in noradrenergic neurotransmission may simply be one correlate of an overall clinical improvement whose mechanism is unknown. While most work has focused on dopaminergic systems, there is significant evidence that norepinephrine may also modulate schizophrenic symptoms [49][50][51][52][53]. Typical neuroleptics have noradrenergic effects, treatment with these medications results in decreased noradrenergic activity, and baseline noradrenergic as well as dopaminergic levels can predict treatment response [54][55][56][57][58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Auditory P50 in Schizophrenics on Clozapine: Improved Gating Parallels Clinical Improvement and Changes in Plasma 3-Methoxy-4-Hydroxyphenylglycol

et al. 1999

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Schizophrenic patients have decreased inhibition of the P50 auditory evoked potential response to the second of two paired click stimuli delivered 500 ms apart. This deficit in inhibitory gating does not change during treatment with typical neuroleptics. We recently reported that neuroleptic-resistant schizophrenics had enhanced P50 gating after 1 month of clozapine treatment, if they responded with decreased clinical symptoms. This study reports the outcome of more prolonged treatment. Ten treatment-refractory schizophrenic patients were studied at baseline, after 1 month on clozapine, and again after 15 ± 6.1 (SD) months of clozapine treatment. Eight subjects reached a clinically stable improved state, at which time they had significantly improved P50 auditory gating. One patient had a return of impaired gating after stopping clozapine, as did another during a clinical relapse. Decreasing plasma 3-methoxy-4-hydroxyphenylglycol levels with clozapine treatment were correlated with improved P50 gating and improved Brief Bsychiatric Rating Scale-positive scores. This study provides further evidence that improved P50 gating in schizophrenic patients treated with clozapine coincides with clinical improvement and that this improvement can be sustained for at least 1 year.

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“…Low 5-hydroxyindoleacetic acid (5-HIAA), a serotoninergic metabolite, has been correlated with negative symptoms in one study [146]. More recently, three PET studies examined 5-HT1AR levels in vivo using [11C]WAY 100635 in patients with schizophrenia and healthy controls [147][148][149].…”

Section: Studies Of Associations Between Serotonin and Broadly Definementioning

confidence: 99%

Neurobiological background of negative symptoms

Galderisi

Merlotti

Mucci

2015

Eur Arch Psychiatry Clin Neurosci

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Studies investigating neurobiological bases of negative symptoms of schizophrenia failed to provide consistent findings, possibly due to the heterogeneity of this psychopathological construct. We tried to review the findings published to date investigating neurobiological abnormalities after reducing the heterogeneity of the negative symptoms construct. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, genetics and neurobiology of schizophrenia. We searched PubMed with the keywords "negative symptoms," "deficit schizophrenia," "persistent negative symptoms," "neurotransmissions," "neuroimaging" and "genetic." Additional articles were identified by manually checking the reference lists of the relevant publications. Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included. Structural and functional imaging studies addressed the issue of neurobiological background of negative symptoms from several perspectives (considering them as a unitary construct, focusing on primary and/or persistent negative symptoms and, more recently, clustering them into factors), but produced discrepant findings. The examined studies provided evidence suggesting that even primary and persistent negative symptoms include different psychopathological constructs, probably reflecting the dysfunction of different neurobiological substrates. Furthermore, they suggest that complex alterations in multiple neurotransmitter systems and genetic variants might influence the expression of negative symptoms in schizophrenia. On the whole, the reviewed findings, representing the distillation of a large body of disparate data, suggest that further deconstruction of negative symptomatology into more elementary components is needed to gain insight into underlying neurobiological mechanisms.

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Cerebrospinal Fluid and Plasma Monoamine Metabolites and Their Relation to Psychosis

Cited by 87 publications

References 77 publications

The Cholinergic System in Schizophrenia Reconsidered: Anticholinergic Modulation of Sleep and Symptom Profiles

The Cholinergic System in Schizophrenia Reconsidered: Anticholinergic Modulation of Sleep and Symptom Profiles

Auditory P50 in Schizophrenics on Clozapine: Improved Gating Parallels Clinical Improvement and Changes in Plasma 3-Methoxy-4-Hydroxyphenylglycol

Neurobiological background of negative symptoms

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