Current research suggests that schizophrenia is a neurodevelopmental disorder with an important dopamine component.Four decades of research have focused on the role of dopamine in schizophrenia, and it seems clear that excesses or deficiencies in dopamine can lead to symptoms of schizophrenia.
What Is the Dopamine Hypothesis of Schizophrenia?
The dopamine hypothesis of schizophrenia was one of the first neurobiological theories for this disease. The evidence for this theory comes from many sources, including post-mortem studies that have imbalances of dopamine as well as its metabolites in patients with schizophrenia. In addition, drugs that block the receptors for dopamine can help control schizophrenic symptoms.
How Does Dopamine Cause Schizophrenia Symptoms?
There are two types of schizophrenia symptoms that an excess of dopamine may cause: positive and negative. Positive symptoms include delusions and hallucinations. Negative symptoms include a decrease in social activity, emotional range, and cognitive function.
Positive Symptoms
Positive symptoms are those that appear to come from outside the person. These can include delusions, hallucinations, or thought disorders. Dopamine contributes to the development of positive symptoms through its effects on subtype-3A dopamine receptors (D3) of cortical neurons. The subtype-3A receptor is found in the prefrontal cortex, which controls planning and thinking, as well as other cortical areas. When these receptors are activated by dopamine, they overstimulate neurons. This can lead to all three types of positive symptoms. Evidence for this idea comes from studies that show that patients with schizophrenia have significantly lower levels of the D3 receptor than healthy people.
Negative Symptoms
While positive symptoms are those that appear to come from outside, negative symptoms appear to be internal. These include a decrease in social activity and emotional range, as well as cognitive deficits like poor problem solving or memory deficit. The mechanisms that contribute to negative symptoms are linked to dopamine levels in the limbic system. Dopamine excess leads to an increase in the activity of dopamine receptors, creating overstimulation similar to that seen in positive symptoms. Some researchers suggest that this overactivity decreases neuronal inhibition, leading to decreased social behavior and cognitive deficits.
Treatment Implications of the Dopamine Hypothesis
The dopamine hypothesis has important treatment implications. The vast majority of current antipsychotic medications target dopamine, and this makes sense given that these drugs were discovered through serendipitous observations of their effect on schizophrenia. The most important dopamine-affecting medications are the typical antipsychotics, which increase post-synaptic receptor stimulation by blocking dopamine receptors. Unfortunately, these medications produce a number of debilitating side effects, most notably extrapyramidal symptoms (EPS) like tardive dyskinesia. Newer second-generation antipsychotics have fewer side effects, but none are perfect. Treatment with dopamine agonists is a third possibility suggested by the dopamine hypothesis. Dopamine agonists stimulate post-synaptic dopamine receptors directly, and as such, they can be used to treat schizophrenia without producing EPS.
What Does This Mean for Patients?
Being diagnosed with schizophrenia can be extremely hard on patients and their families. It’s important that doctors and researchers continually investigate new treatments that could improve the lives of people living with this disorder. The best way for patients and their loved ones to navigate these issues is by staying informed and asking questions about any new or experimental treatments. They should also work with doctors to develop a personalized treatment plan that’s appropriate for their own needs.
Does Too Much Dopamine Cause Schizophrenia?
Increased activity of the mesolimbic pathway is related to positive symptoms of schizophrenia (delusions, hallucinations, etc.). This means that increasing the activity of dopamine receptors in this brain system could theoretically reduce delusions and hallucinations. As mentioned previously, this is what most modern medications do: they block post-synaptic dopamine receptors in order to reduce psychotic symptoms. Unfortunately, when scientists block all available dopamine receptors they also produce a number of debilitating side effects such as extrapyramidal symptoms (EPS) and tardive dyskinesia.
Is Dopamine High or Low in Schizophrenia?
The most common theory about the cause of schizophrenia is that there are too many dopamine receptors in certain parts of the brain, specifically the mesolimbic pathway. This causes an increase in mesolimbic activity which results in delusions, hallucinations, and other psychotic symptoms. Other research suggests that schizophrenia might be caused by a lack of dopamine activity in other parts of the brain. For example, scientists have discovered that the hippocampus is overactive in schizophrenia. Schizophrenia might also be characterized by low dopamine in the prefrontal cortex, but again the evidence is inconclusive. Some studies have found that patients with schizophrenia have elevated levels of dopamine in this region, while others suggest that there are too few dopamine receptors.
Implications of the Dopamine Hypothesis
It’s important to note that schizophrenia is a complex disorder. Even if dopamine hyperactivity is the primary cause, certain types of schizophrenia might be characterized by increased activity in certain brain areas while others are characterized by reduced activity in certain brain areas. Furthermore, it’s also possible that different patients will respond to treatment differently based on how their disease manifests.
Serotonin and Schizophrenia
Research also implicates serotonin as a regulator of dopamine release. Antipsychotic medications, including olanzapine and clozapine, reduce serotonin activity and increase dopamine activity. For example, olanzapine-induced reductions in serotonin metabolism were associated with significant improvements in negative and positive symptoms, but not cognitive deficits.
A Word From Verywell
Schizophrenia is a severe mental disorder that can be treated. If you or someone you know was recently diagnosed with schizophrenia, you might be wondering what the future holds. Healthcare professionals can help you manage your symptoms and chart a course for the best possible outcome. Sometimes, there may be periods of remission that allow you to live a productive life even when coping with schizophrenia. As new treatments are continually being developed, we can look forward to better options for people who suffer from this disorder in the future.
