Schizophrenia and addiction
Schizophrenia is a chronic mental disorder characterized by severe disruptions in thought processes, perceptions, emotional responsiveness, and social interactions, affecting about 1% of the population, typically emerging in adolescence or early adulthood. It is marked by symptoms such as delusions and hallucinations and is associated with dysfunction in brain systems, particularly involving dopamine and glutamate. The disorder can significantly impair cognitive functioning, and individuals may also experience a range of negative symptoms.
A notable concern is the high comorbidity between schizophrenia and substance use disorders (SUD), with studies indicating that 40-60% of those with schizophrenia also struggle with SUD. Common substances misused include nicotine, alcohol, cannabis, and cocaine. Factors such as younger age at diagnosis, male gender, and lower levels of negative symptoms increase the risk of developing SUD among individuals with schizophrenia. This dual diagnosis complicates treatment, often leading to worse health outcomes, including deteriorating mental health and increased hospitalizations.
Integrated treatment approaches, which address both conditions concurrently, are recommended, with clozapine being a notably studied antipsychotic that may help relieve symptoms associated with both schizophrenia and substance abuse. The relationship between schizophrenia and addiction is thought to involve disturbances in the brain's reward pathways, particularly relating to dopamine signaling. Understanding and addressing these connections is essential for improving treatment outcomes and the overall quality of life for those affected.
Schizophrenia and addiction
DEFINITION: Schizophrenia is a severe mental disorder characterized by impaired functioning in cognition, perception, emotions, and behavior. In its acute stage, it manifests as psychosis. Schizophrenia is highly associated with substance abuse, and the link between the two is thought to be disturbances in signaling pathways involved in the brain’s rewards system.
Background
Schizophrenia is a chronic and often severe mental disorder. Affecting approximately 1 percent of the population, schizophrenia usually develops during adolescence or early adulthood. Patients are diagnosed as having paranoid, catatonic, disorganized, undifferentiated, or residual schizophrenia, according to their positive symptoms (exaggerations of normal functioning) and negative symptoms (deficiencies in normal functioning). The hallmark of the disease is psychosis, wherein the person with schizophrenia loses touch with reality (and experiences delusions and hallucinations).
The complexities of schizophrenia are yet to be fully unraveled, and the psychiatric community still grapples with what constitutes psychosis. There is mounting evidence that malfunctioning dopamine and glutamate systems in the brain play a major role in the development of schizophrenia. Studies also suggest that genetic, environmental, and social factors may also contribute to development of the disorder.
Biological and Genetic Factors in Schizophrenia
Unlike many other psychiatric disorders, schizophrenia impairs multiple areas of brain functioning. Since the mid-twentieth century, technological advances have enabled neuroscientists to study the brain more fully, shedding light on the structural and genetic variants seen in schizophrenia.
Through a variety of dynamic imaging and brain mapping techniques, researchers have found that persons with schizophrenia have various anomalies in brain structure and morphology, displaying abnormalities such as loss of gray and white matter, enlargement of the ventricles, and displacement of other structures. Persons with schizophrenia also show disturbances in neurotransmission, particularly in the glutamate and dopamine signaling pathways.
The availability of genome-wide association studies has made the search for genetic markers of complex diseases a reality. The most likely candidate genes associated with schizophrenia have been located on chromosomes 1 (DISC1 and RG542), 6 (DTNBP1), 7 (GRM3), 8 (NRG1), 13 (DAOA), 17 (PPP1R1B), and 22 (COMT). Most of these genes make proteins involved in dopamine or glutamate signaling; others are growth factors involved in nerve development.
The bulk of these structural and genetic aberrations correlate with known functional impairment in persons with schizophrenia—namely, deficits in cognitive and executive functioning, information processing, verbal memory, planning, and self-awareness.
The Schizophrenia and Addiction Connection
Researchers have been investigating the relationship between substance use disorder (SUD) and schizophrenia since about 1980. Studies have shown that 40 to 60 percent of people with a diagnosis of a schizophrenia spectrum disorder also have a diagnosis of SUD. Despite the health hazards, 50 to 90 percent of people with schizophrenia also smoke cigarettes. Aside from nicotine, the most frequently used substances are alcohol, cannabis (marijuana) and cocaine.
In persons with schizophrenia, risk factors for developing SUD are younger age, male gender, earlier onset of the disease, and lower level of negative symptoms. Persons with comorbid schizophrenia and SUD have worsening signs of illness, including deteriorating function over time, reduced memory and attention, decreased adherence to medications, higher rates of relapse, increased frequency of hospitalizations, decreased employment opportunities, and increased rates of homelessness.
Integrated treatment in which the substance abuse and schizophrenia are treated simultaneously is recommended for persons with a dual diagnosis. Of the atypical antipsychotic agents, clozapine has been the drug more thoroughly studied for use in dual diagnosis. The drug has been shown to reduce psychotic symptoms seen in both schizophrenia and substance abuse and to reduce rates of substance abuse.
The reasons for the comorbidity between schizophrenia and substance abuse are not entirely understood, but there is growing evidence that this comorbidity is caused by disturbances in signaling pathways involved in the brain’s rewards system. The dopamine system is involved in several brain functions, including attention, executive function, working memory, and reward mechanisms, and it has been studied extensively for its role in schizophrenia, psychosis, and substance abuse.
The basis for the dopamine theory in schizophrenia is that the manifestation of psychosis arises from imbalances in dopaminergic neuronal pathways, evidenced by increased dopamine production and release observed in the brains of unmedicated patients during a psychotic episode. Dysfunction in the regulation of dopamine levels and signal transduction of dopamine receptors causes excess release of dopamine, which is thought to be the primary trigger of schizophrenic psychosis.
The role of the dopamine system in addiction has been clearly demonstrated. One function of the dopaminergic neuronal pathway is to connect the nucleus accumbens (NAC), a collection of neurons in the basal forebrain, with the ventral tegmental area (VTA), a brain structure involved in reward mechanisms and motivation. Most psychotropic drugs increase dopamine levels in the NAC and appear to transmit the rewarding effects of the drug by activating dopamine cells in the VTA, especially on initial use. This intensifies the motivation for repeated use and fosters addiction.
Another connection between schizophrenia and SUD is incentive salience, a concept initially used in the context of drug addiction and later applied to schizophrenic psychosis to describe a person’s motivational state in regard to a particular experience. Medical experts hypothesized that dopamine mediates the attribution of incentive salience to conditioned cues that predict reward, and that dopamine activation appears to be sufficient to enhance cue-triggered incentive salience. In schizophrenia, dopaminergic neurons attribute incentive salience to irrelevant stimuli, indicating that the attribution of salience to reward-predicting stimuli is impaired and that this dysfunction contributes to delusion formation.
However, it is now known that, although dopamine is necessary for normal wanting, dopamine release is not directly rewarding but reflects more of an error in reward prediction. In other words, when the actual reward exceeds the predicted reward, the positive difference between the two is reflected in increased dopamine firing. Conversely, dopamine firing is reduced when expectations are higher than outcomes. When the difference is zero (actual and expected reward are the same), no dopamine is released, indicating that it is independent of “consuming” the reward.
Schizophrenia is a life-long disorder with a high burden of illness, compounded by the great emotional toll it has on patients, families, hospitals, and communities. Added to these burdens is the tendency for patients with schizophrenia to use and become addicted to substances of abuse. For these reasons, significant research has attempted to provide a better understanding of the disorder and work toward more effective treatments or even a cure. According to the National Institute of Mental Health in 2024, psychosocial treatments help people find solutions to everyday challenges and manage symptoms in daily life. These treatments are often used with antipsychotic medication.
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