Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the general population.1 The 12-month prevalence of substance use disorders (SUDs) among the general US population is approximately 12% for alcohol(Drug information on alcohol) and 2% to 3% for illicit drugs.2 It is interesting to note that nearly 50% of people with schizophrenia also suffer from a comorbid substance-related illness during their lifetime.3 There are complex interactions between substance use and psychiatric disorders, including schizophrenia.4
Patients who receive a dual diagnosis—a psychiatric disorder and an SUD—are faced with serious challenges related to treatment and prognosis. Many clinicians focus solely on treating either the psychiatric illness or the SUD. This lack of integration of psychiatric and addiction treatment is a significant issue for dual-diagnosis patients; growing evidence suggests a poorer prognosis with nonintegrated treatment.5
Psychiatric illness appears to be a vulnerability factor for substance abuse, and because substance abuse can lead to an exacerbation of psychiatric symptoms, there is a critical need to understand the factors that influence both the onset and duration of substance abuse and psychiatric illness, particularly how they interact to influence prognosis.
The pathophysiology of schizophrenia
Schizophrenia is characterized by the disturbance of cognition and sometimes behavioral and emotional processes. Positive symptoms of schizophrenia can include hallucinations, paranoia, and delusions, while negative symptoms can include blunted affect, cognitive deficits, social avoidance, and anhedonia. Reductions in brain volume typically occur in patients with schizophrenia (as a function of the illness, medications, or both), primarily in the prefrontal cortex (PFC) and temporal lobes, which may contribute to the cognitive deficits commonly seen in patients.
There are 4 central dopamine(Drug information on dopamine) (DA) systems: mesolimbic, tuberoinfundibular, mesocortical, and nigrostriatal.6 The mesolimbic pathway projects from the ventral tegmental area and substantia nigra of the midbrain to the nucleus accumbens (NAc), olfactory tubercle, and amygdala.
The DA hypothesis may be insufficient to explain the complexity of schizophrenia. However, there is mounting evidence to support DA dysfunction in schizophrenia. In particular, schizophrenia appears to be associated with hyperactive subcortical mesolimbic DA pathways in the brain and deficient DA function in the PFC.7 Moreover, all effective antipsychotic medications are antagonists of the DA D2 receptor.8
Mesocortical DA modulates working memory and executive function, and dysregulation of this pathway may underlie some of the positive and negative symptoms associated with schizophrenia.9 The nigrostriatal pathway extends from the substantia nigra to the dorsal striatum via the median forebrain bundle, and overactivity of striatal DA release may be a key factor in the development of schizophrenia (Figure).10
DA influences motor activity and attention in humans and plays a critical role in stress.11 In animals that are subjected to stress, DA is released in the cortical and limbic areas of the brain and may exacerbate symptoms associated with schizophrenia that could be a result of too many demands on the already diminished population of dopamine neurons.12
The DA system also plays a large role in the reward- and pleasure-seeking system, particularly the D1 and D2 receptors. Many drugs of abuse block the function of the DA transporter, resulting in a large increase of DA in the synapse and increased D1 and D2 receptor signaling that mediates the reward pathway, usually in the NAc.13