Australian researchers develop new animal model of schizophrenia
Friday, May 10, 2019
Schizophrenia is devastating. This mental disorder, which often destroys families, disrupts thought processes, perceptions, emotional responsiveness, and social interactions.
Schizophrenia is a severe brain disorder that affects 1% of the population, or 24 million people worldwide, and is one of the top 15 leading causes of disability.Approximately half of those with schizophrenia have co-occurring mental and/or behavioral health disorders. Diagnosis is made on clinical information alone; there are no lab tests or imaging studies that confirm the diagnosis.
More than 15 new medications for the treatment of schizophrenia are currently in development by different biotech and pharmaceuticals companies.
The first generation or typical antipsychotics, such as haloperidol, chlorpromazine, and perphenazine, impose higher risks of extra-pyramidal side effects (EPS), such as dyskinesia and akathisia, with increasing amounts of dopamine blockade. These side effects must be weighed against the clinical benefit.
The second generation or atypical antipsychotics, such as risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and clozapine, carry a lower risk of EPS and may not worsen the negative symptoms of schizophrenia. These drugs are effective for the psychotic symptoms with fewer risks of EPS and tardive dyskinesia. But the risks of developing metabolic syndrome, hypertension, dyslipidemia, or glucose intolerance are significant; side effects are often what contribute to noncompliance, and understandably so.
The exact cause of schizophrenia remains unknown, but current research suggests that it is a multifactorial disease based in genetics, susceptibilities, and environment. Ultimately, better treatments are urgently needed.
Scientists have known that schizophrenia is associated with a pronounced change in the way the brain uses the neurotransmitter dopamine. In those with schizophrenia, dopamine production and signaling significantly increase in the dorsal or upper part of the striatum region of the brain, leading to symptoms of schizophrenia. However, researchers are unclear why excessive dopamine causes symptoms.
To address this, neuroscientists at The University of Queensland’s Brain Institute have developed a new animal model of schizophrenia where dopamine is specifically elevated at the dorsal striatum — a model that was inspired from animal models of Parkinson’s disease where dopamine is deficient.
The researchers delivered genetic constructs (that make dopamine) into the brain of rats, using a virus to target delivery onto dopamine neurons that project to the dorsal striatum. This caused the animals to mimic symptoms of schizophrenia.
The researchers plan to use this model to explore the changes in the brain’s circuitry that are altered or affected when elevated levels of dopamine are produced in the dorsal striatum, which could lead to treatments that may either diminish or prevent schizophrenia. Exploring the basic changes in the brain’s circuitry that are altered when elevated levels of dopamine are produced in the dorsal striatum will also help researchers better understand the basis of schizophrenia.
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