Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Abstract

Schizophrenia is a severe psychiatric disorder which is worsened substantially by substance abuse/addiction. Substance abuse affects nearly 50% of individuals with schizophrenia, extends across several drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants) and worsens overall functioning of patients. Prominent theories explaining schizophrenia and addiction comorbidity include the primary addiction hypothesis (i.e. schizophrenia susceptibility primes drug reward circuits, increasing drug addiction risk following drug exposure), the two-hit hypothesis (i.e. drug abuse and other genetic and/or environmental risk factors contribute to schizophrenia development) and the self-medication hypothesis (i.e. drug use alleviates schizophrenia symptoms). Animal models can be used to evaluate the utility and validity of these theories. Since this literature was last reviewed by Ng and colleagues in 2013 [Neurosci Biobehav Rev, 37(5)], significant advances have been made to our understanding of schizophrenia and substance abuse comorbidity. Here we review advances in the field since 2013, focussing on two key questions: 1) Does schizophrenia susceptibility increase susceptibility to drug addiction (assessing the primary addiction hypothesis), and 2) Do abused drugs exacerbate or ameliorate schizophrenia symptoms (assessing the two-hit hypothesis and the self-medication hypothesis). We addressed these questions using data from several schizophrenia preclinical models (e.g. genetic, lesion, neurodevelopmental, pharmacological) across drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants). We conclude that addiction-like behaviour is present in several preclinical schizophrenia models, and drugs of abuse can exacerbate but also ameliorate schizophrenia-relevant behaviours. These behavioural changes are associated with altered receptor system function (e.g. dopaminergic, glutamatergic, GABAergic) critically implicated in schizophrenia and addiction pathology.

Cannabis Use in Inpatients With Schizophrenia Spectrum Disorders at a Community Hospital

“…This belief is prevalent and increasing among all age groups [1,5]. Among people with schizophrenia, cannabis has always been more prevalent than in the general population [6,7]. Currently, usage is also increasing among people with schizophrenia [8].…”

“…Several reasons have been mentioned for the considerable use of cannabis among schizophrenia patients. They include self-medication such as to reduce anxiety and improve sleep which are the primary illness effects, and to improve socialization [6,7]. Neurobiologically, theories to consider include what Menne et al described as a complex bidirectional relationship [7].…”

“…They include self-medication such as to reduce anxiety and improve sleep which are the primary illness effects, and to improve socialization [6,7]. Neurobiologically, theories to consider include what Menne et al described as a complex bidirectional relationship [7]. In this regard, it is thought that individuals who develop schizophrenia are also predisposed to substance use.…”

“…Therefore, chronic use begins and develops after disease onset. This hypothesis proposes that this relationship subsists on the shared dopaminergic pathway of substance use and schizophrenia [7]. Another major reason that has been proposed for substance use generally among patients with psychotic disorders is the effect of environmental factors [7].…”

“…This hypothesis proposes that this relationship subsists on the shared dopaminergic pathway of substance use and schizophrenia [7]. Another major reason that has been proposed for substance use generally among patients with psychotic disorders is the effect of environmental factors [7]. These factors include privation, decline in functioning and a disproportionate exposure to dangerous situations which accumulate to increase the predisposition of schizophrenic patients to use substances [7].…”