Northwestern Medicine Scientists Make Groundbreaking Discovery on Antipsychotic Drugs and Schizophrenia Treatment
A recent study conducted by scientists at Northwestern Medicine has revealed a groundbreaking discovery that challenges our existing understanding of how antipsychotic drugs work in the treatment of schizophrenia. The research suggests that the interaction with D1 dopamine receptor-expressing neurons, rather than D2, better predicts the efficacy of these drugs in treating the symptoms of schizophrenia.
Schizophrenia affects millions of people in the United States, and the available antipsychotic drugs often come with numerous side effects and are ineffective for many individuals. As a result, there is a growing need for the development of more effective and better-tolerated drugs.
The Northwestern Medicine scientists have adopted an innovative approach to drug development for schizophrenia treatment. Traditionally, researchers have screened antipsychotic drug candidates based on their effects on mouse behavior. However, this new study demonstrates that observing the drugs’ interaction with a specific neuron type is a superior method for predicting their effectiveness in patients.
The researchers found that antipsychotic drugs, which work by inhibiting overactive dopamine that causes the symptoms of schizophrenia, actually interact with a different neuron than previously believed. It was originally assumed that these drugs acted on neurons expressing the D2 dopamine receptors, but the study discovered that it is the neighboring neurons with D1 receptors that respond to antipsychotics in a manner that predicts their clinical effect.
Lead investigator Jones Parker, an assistant professor of neuroscience at Northwestern University Feinberg School of Medicine, described this finding as a landmark that completely revises our understanding of the neural basis for psychosis. Furthermore, it opens up new possibilities for the development of drugs with fewer adverse side effects than those currently available.
The study, published in the journal Nature Neuroscience on July 13, sheds light on the role of dopamine in schizophrenia. Patients with schizophrenia have elevated dopamine levels in a brain region called the striatum, which contains two types of specialized neurons: D1 and D2. While experts had previously assumed that antipsychotics primarily targeted D2 receptor-expressing neurons, this research suggests that it is actually the D1 receptor-expressing neurons that respond to these drugs in a way that predicts their effectiveness.
The current treatments for schizophrenia, although effective for certain symptoms such as hallucinations and delusions, are inadequate for addressing other aspects of the disorder, such as cognitive and social deficits. Moreover, they are completely ineffective for more than 30% of patients with treatment-resistant schizophrenia. Additionally, these drugs have adverse side effects, including uncontrollable body movements and parkinsonism.
This new research provides novel insights into how antipsychotic drugs modulate the brain region associated with psychosis. By uncovering new therapeutic strategies, it paves the way for the development of more effective antipsychotics that can better address the diverse symptoms of schizophrenia.
The study, titled “Antipsychotic drug efficacy correlates with the modulation of D1 rather than D2 receptor-expressing striatal projection neurons,” was authored by Seongsik Yun, Ben Yang, Justin D. Anair, Madison M. Martin, Stefan W. Fleps, Arin Pamukcu, Nai-Hsing Yeh, Anis Contractor, Ann Kennedy, and Jones G. Parker. The research was supported by grants from the National Institutes of Health and the Whitehall Foundation.