Thompson and colleagues14 recently reported that striatal DA release is increased in patients with schizophrenia, primarily in the precommissural caudate, and reduced in the ventral striatum in individuals with addiction. They measured the change in amphetamine-induced D2/3 receptor availability in both dual-diagnosis schizophrenia patients and in schizophrenia-only patients using positron emission tomography. Dual-diagnosis patients reported greater increases in happiness and energy following drug administration, but amphetamine reduced D2/3 receptor availability across both groups.
Schizophrenia and SUD
Many hypotheses have been put forth to explain the link between substance abuse and schizophrenia. The two hypotheses that we discuss are the self-medication hypothesis (SMH) and the addiction vulnerability hypothesis (AVH).15,16 The SMH posits that drugs of abuse relieve psychological suffering and that a person’s preference for a particular drug involves some degree of psychopharmacological specificity.17 By contrast, the AVH suggests that the of schizophrenia may increase vulnerability to drug reward and reinforcement, thus promoting concurrent expression of these disorders.16
The SMH entails relief of negative symptoms, such as anhedonia, depression, blunted affect, and neurocognitive deficits.15 This hypothesis claims that drug addiction is a secondary process, or a reaction, to schizophrenia; the dysfunctional leads to aversive symptoms and to self-medication. Khantzian17 suggested that “it is not so much a psychiatric condition that one self-medicates, but a wide range of subjective symptoms and states of distress that may or may not be associated with a psychiatric disorder.”
People with schizophrenia may be targeting the negative symptoms and/or motor adverse effects of antipsychotic medications. The SMH explains comorbid drug addiction through a negative reinforcement model, in which drugs may serve to reduce aversive symptoms associated with the psychiatric disorder.17
Over the past few decades, the SMH has drawn criticism. Since support for the SMH has focused on subjective, self-report measures, many researchers question the validity of this hypothesis. Amelioration of negative symptoms and adverse effects of medication is among the reasons Khantzian provides for individuals with schizophrenia who use drugs.17 Tobacco use is common in patients with schizophrenia, and nicotine(Drug information on nicotine) may alter nicotinic acetylcholine receptor abnormalities in schizophrenia.18
The effects of smoking abstinence on visuospatial working memory (VSWM; a cognitive process dependent in part on prefrontal DA) were examined in smokers with schizophrenia and smokers without schizophrenia (controls).19 Smoking abstinence in the schizophrenia group was associated with a decreased VSWM; in the control quitters, VSWM improved. The findings indicate that nicotine may have beneficial effects on cognition in smokers with schizophrenia. Although these data appear to support the SMH, it is important to note that cognition is subconscious and an individual with schizophrenia is unlikely to describe the effects of smoking on such unconscious processes.
Another shortcoming of the SMH is that when dual-diagnosis patients stop using their drug of choice, their psychiatric symptoms improve or remain unchanged rather than worsen after drug withdrawal is complete.4,20 Moreover, findings from prospective clinical trials suggest that patients with schizophrenia who quit smoking have no significant changes in positive and negative symptoms.21 Results from a retrospective study show that smokers with schizophrenia significantly decreased their reported daily cigarette use when they switched from neuroleptics to the atypical antipsychotic clozapine(Drug information on clozapine).22 If the SMH were supported, it would be expected that smokers would not decrease their daily smoking in response to medication (and may in fact increase smoking), since the SMH suggests that individuals use drugs to relieve medication adverse effects.
The AVH differs from the SMH in that it does not assume there are any beneficial (or detrimental) reasons for comorbid drug addiction. While the SMH posits that dual-diagnosis patients become addicted to relieve deficits, such as mood and anxiety symptoms, the AVH claims that dual-diagnosis patients become addicted to drugs despite the negative consequences of the drug.23