Effect of anticholinergic medication on positive and negative symptoms in medication-free schizophrenic patients

Tandon, Rajiv; Mann, Nancy A.; Eisner, William; Coppard, Nancy

doi:10.1016/0165-1781(90)90092-j

Cited by 54 publications

(17 citation statements)

References 26 publications

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“…Several potential biases and confounding factors of earlier studies (Tandon et al 1990b(Tandon et al , 1992a were eliminated. We employed a double-blind, placebo-crossover design, randomizing the order of active drug versus placebo in drug-free schizophrenic patients, and compared the effects of biperiden with an active placebo, glycopyrrolate (which has peripheral anticholinergic activity, but is devoid of central anticholinergic activity).…”

Section: Study Design Symptom Studymentioning

confidence: 99%

“…We studied the effects of 2 days of treatment with biperiden, a relatively specific M 1 antimuscarinic/anticholinergic agent, on positive and negative symptoms in 15 medication-free (minimum 2 weeks) schizophrenic patients (Tandon et al 1990b). In this study, patients received 4-mg biperiden on night 1, two doses of 4-mg biperiden the next day, and a 4-mg biperiden dose the morning of day 3.…”

Section: Treatment Of Negative Symptoms Of Schizophrenia With Trihexymentioning

confidence: 99%

“…Consequently, we studied the effects of anticholinergic modulation on schizophrenic symptoms in drug-free patients. Some earlier studies had indicated that anticholinergics may antagonize the therapeutic effects of neuroleptics on positive symptoms (Singh and Kay 1979;Johnstone et al 1983;Singh et al 1987;Haase 1965;Johnstone et al 1988;Chouinard et al 1987), but controlled studies on the effects of anticholinergic drugs in medication-free schizophrenic patients were lacking.We studied the effects of 2 days of treatment with biperiden, a relatively specific M 1 antimuscarinic/anticholinergic agent, on positive and negative symptoms in 15 medication-free (minimum 2 weeks) schizophrenic patients (Tandon et al 1990b). In this study, patients received 4-mg biperiden on night 1, two doses of 4-mg biperiden the next day, and a 4-mg biperiden dose the morning of day 3.…”

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confidence: 99%

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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: Study Design Symptom Studymentioning

confidence: 99%

Section: Treatment Of Negative Symptoms Of Schizophrenia With Trihexymentioning

confidence: 99%

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confidence: 99%

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

Tandon

Taylor

DeQuardo

et al. 1999

Neuropsychopharmacology

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“…Antimuscarinic psychosis can be alleviated by antipsychotic drugs (APDs) (Gopel et al, 2002;Perry et al, 1978) as well as by acetylcholinesterase (AChE) inhibitors (Brown et al, 2004;Gopel et al, 2002;Granacher and Baldessarini, 1975;Nogue et al, 1991;Perry et al, 1978). Conversely, muscarinic antagonists used to reduce extrapyramidal side effects associated with APDs (Tandon, 1999) have been reported to exacerbate schizophrenia symptoms and to interfere with the therapeutic effects of APDs (Johnstone et al, 1983;Lo and Tsai, 1996;Kay, 1975, 1979;Tandon et al, 1990). These findings, taken together with postmortem and neuroimaging findings of cholinergic alterations in the brains of schizophrenia patients (eg Crook et al, 2001;Dean et al, 1996;Garcia-Rill et al, 1995;Karson et al, 1991;Raedler et al, 2003;Zavitsanou et al, 2005), have led to a growing interest in the involvement of the cholinergic system in this disorder (eg Hyde and Crook, 2001;Sarter et al, 2005;Tandon et al, 1992;Weiner et al, 2004;Yeomans, 1995).…”

Section: Introductionmentioning

confidence: 99%

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

Barak

Weiner

2006

Neuropsychopharmacol

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The fact that muscarinic antagonists may evoke a psychotic state ('antimuscarinic psychosis'), along with findings of cholinergic alterations in schizophrenia, have kindled an interest in the involvement of the cholinergic system in this disorder. Latent inhibition (LI) is a crossspecies phenomenon manifested as a poorer conditioning of a stimulus seen when the stage of conditioning is preceded by a stage of repeated nonreinforced pre-exposure to that stimulus, and is considered to index the capacity to ignore irrelevant stimuli. Amphetamine-induced LI disruption and its reversal by antipsychotic drugs (APDs) is a well-established model of positive symptoms of schizophrenia. Here, we tested whether the muscarinic antagonist scopolamine would disrupt LI and whether such disruption would be reversed by APDs and by the acetylcholinesterase inhibitor physostigmine. The results showed that scopolamine at doses of 0.15 and 0.5 mg/kg disrupted LI, and that this effect was due to the action of the drug in the pre-exposure stage, suggesting a role of muscarinic transmission in attentional processes underlying LI. Both the typical and the atypical APDs, haloperidol and clozapine, reversed scopolamine-induced LI disruption when given in conditioning or in both stages, but not in pre-exposure, indicating that the mechanism of antipsychotic action in this model is independent of the mechanism of action of the propsychotic drug. Scopolamine-induced LI disruption was reversed by physostigmine (0.05 and 0.15 mg/kg), which was ineffective in reversing amphetamine-induced LI disruption, pointing to distinct mechanisms underlying LI disruption by these two propsychotic drugs. The latter was further supported by the finding that unlike amphetamine, the LI-disrupting doses of scopolamine did not affect activity levels. We propose scopolamine-induced LI disruption as a model of cholinergic-related positive symptoms in schizophrenia. Neuropsychopharmacology (2007) 32, 989-999.

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“…The chin and eye leads record EMG and eye movements, respectively, during various stages of sleep (middle and bottom records). Time, ms some patients with schizophrenia [19]. Indeed, Karson et al [20], looking at histochemically labeled cells within this region at autopsy, have found nearly twice the num ber of cholinergic neurons within the PPN of chronic schizophrenics when compared to normal and to nonschi zophrenic psychiatric controls.…”

Section: Pathological Correlatesmentioning

confidence: 99%

The <i>P1: </i>Insights into Attention and Arousal

Boop

García‐Rill²,

Dykman³

et al. 1994

Pediatr Neurosurg

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The authors provide evidence that four mesencephalic nuclei, two of which are cholinergic and two of which are catecholaminergic, serve as oscillators capable of modulating a number of interrelated rhythmic functions. These include sleep-wake cycles, locomotion, blood pressure, respiratory rate, heart rate, mastication, micturition, and saccadic eye movements. The P1 auditory evoked potential is generated by ascendiung cholinergic projections from one of these nuclei, the pedunculopontine nucleus, and thus serves as a clinical tool to monitor the integrity of this system.

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Effect of anticholinergic medication on positive and negative symptoms in medication-free schizophrenic patients

Cited by 54 publications

References 26 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

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

The <i>P1: </i>Insights into Attention and Arousal

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