What Can We Learn About Schizophrenia From Studying the Human Model, Drug-Induced Psychosis ?

Robin M. Murray, Alessandra Paparelli, Paul D. Morrison, Arianna Marconi, and Marta Di Forti

American Journal of Medical Genetics, Part B, 2013, 162B, 661–670.

Doi : 10.1002/ajmg.b.32177

 

When drug-induced psychoses were first identified in the mid- 20th century, schizophrenia was considered a discrete disease with a likely genetic cause. Consequently, drug-induced psychoses were not considered central to understanding schizophrenia as they were thought to be phenocopies rather than examples of the illness secondary to a particular known cause. However, now that we know that schizophrenia is a clinical syndrome with multiple component causes, then it is clear that the drug-induced psychoses have much to teach us. This article shows how the major neuropharmacological theories of schizophrenia have their origins in studies of the effects of drugs of abuse. Research into the effects of LSD initiated the serotonergic model; amphetamines the dopamine hypothesis, PCP and ketamine the glutamatergic hypothesis, while most recently the effects of cannabis have provoked interest in the role of endocannabinoids in schizophrenia. None of these models account for the complete picture of schizophrenia; rather the various drug models mimic different aspects of the illness. Determining the different molecular effects of those drugs whose pharmacological effects do and do not mimic the various aspects of schizophrenia has much to teach us concerning the pathogenesis of the illness.

Key words : psychosis; substances; schizophrenia; LSD; amphetamines

 

INTRODUCTION

We are delighted to contribute to this special issue honoring Ming Tsuang, for two reasons. Firstly because we work at the Institute of Psychiatry in London, where the young Dr. Tsuang arrived in the 1960s to study the genetics of psychiatric disorder.

He joined a number of (now) distinguished migrants to Eliot Slater’s unit [Gottesman and Shields, 1971] including Irving Gottesman and Leonard Heston, and studied sib-pairs where both had psychiatric disorder; this work was rewarded with a PhD in 1965.

The second reason for our delight is not one of geography but rather of topic because Ming Tsuang has had a long interest in the role of drug abuse in schizophrenia [Tsuang et al., 1982]. Of course, when he arrived in London, he joined a unit where schizophrenia was considered a discrete disease with a likely genetic cause; Slater, for example, considered that there was a single dominant schizophrenia gene [Gottesman and Shields, 1971]. Consequently, psychoses due to other causes such as temporal lobe epilepsy, even if phenomenologically identical to schizophrenia, were considered as phenocopies rather than examples of the disorder secondary to a particular cause. A great deal of information has subsequently accumulated but the picture presenting in the clinic, as opposed to that seen in the experimental setting, has not been widely acknowledged as telling us much about schizophrenia itself.

However, now schizophrenia is more appropriately viewed as at the extreme end of a continuum of psychosis where genetic and environmental risk factors combine to push the individual over a threshold into expressing the characteristic clinical syndrome [Stilo and Murray, 2010; Van Os et al., 2010]. It is time, therefore, to re-appraise the drug-induced psychoses, and how they can help us to understand schizophrenia.

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