Schizophrenia is a complex and severe mental health disorder with a heavy societal and economic burden. While it affects about 1 percent of the world’s population (including an estimated 3.2 million Americans), it is among the leading causes of disability. We know that a family history of schizophrenia can increase risk in some and genetics is believed to play a role in the disorder; yet the cause remains unknown.
Identifying schizophrenia biomarkers – which could lead to earlier diagnosis and guide the development of targeted therapies – has long been the goal of the scientific community. But to date, no reliable biomarkers for schizophrenia have been identified. A new consortium of industry, academic and regulatory stakeholders hopes to change that. The Event-related Potential (ERP) Biomarker Qualification Consortium was recently launched with the goal of qualifying ERPs, a specialized form of electroencephalogram (EEG), as biomarkers for schizophrenia.
If the consortium is successful, it could help streamline the development of new treatments for schizophrenia. It also may help researchers develop drugs that target the brain abnormalities associated with specific schizophrenia symptoms. This would be a needed advance toward precision medicine in psychiatry, and Lundbeck is proud to be a founding member of this consortium.
ERPs and their role in schizophrenia research
ERPs are measured brain responses to specific sensory, motor or cognitive stimuli. For example, if someone hears a single musical note over and over, then is exposed to a new tone of different frequency or intensity, the brain typically reacts to the new sound. Neurons in the brain circuits involved in attention, memory, awareness and reactivity recognize this “odd ball” tone and fire off new electrical signals. Those signals represent the ERP, which can be recorded via electrodes placed on the scalp and analyzed by computer.
Past research shows that when patients with schizophrenia are exposed to tones of varying frequencies, they typically demonstrate a reduced ERP response (in comparison with healthy adults). This may be because the brain circuits involved in critical information processing and cognitive skills are disrupted in schizophrenia. Cognitive impairment is a core symptom of schizophrenia, and many people with the disorder experience slow and disorganized thinking, difficulty expressing thoughts, and poor concentration and memory. There currently is no approved therapy for these symptoms, and cognitive impairment has a significant impact on people’s quality of life. ERPs provide a non-invasive means to directly measure the functional activity of brain circuits believed to be involved in cognitive skills, and the new consortium intends to further investigate that ERP process in people with schizophrenia.
Through well-designed and large-scale studies, we will seek to characterize and validate the atypical response anticipated in patients with schizophrenia. The ability to easily and reliably measure this new biomarker, and thoroughly understand its relevance to the clinical symptoms and function of patients could, speed research and development of treatments in schizophrenia.
Learn more about the ERP Biomarker Qualification Consortium here.
Why qualification matters
One of the main objectives of the new consortium is to qualify ERPs as a biomarker. When a biomarker is qualified, it means that the FDA accepts that the biomarker can be used to reliably provide supportive evidence to indicate a new therapy’s effectiveness. Qualifying the biomarker would allow researchers to use the ERP as an important outcome measure in drug development efforts including improving the sensitivity and reliability of critical clinical research trials.
Reducing the guesswork of schizophrenia trials
Lacking disease biomarkers, today we sometimes face challenges in replicating schizophrenia symptoms in our labs and early research. We may induce schizophrenia symptoms in pre-clinical research, but we can’t know with certainty if a mouse is experiencing psychosis. With ERPs, however, there is no guesswork. ERPs are seen in animal brains just as they are in human brains and can serve as a fundamental marker of how the brain processes information. This can help us understand with greater certainty if an investigational compound is likely to have the intended outcome before we bring the therapy to clinical trials. That could help reduce the number of failed trials and increase the likelihood of successful drug development that leads to effective new treatments.
Targeting disease pathology
Lundbeck has been at the leading edge of psychiatric research for more than 70 years, and today we are committed to further advancing brain health through biomarker discovery. Our research is aimed at uncovering and targeting the underlying mechanisms of brain diseases, and we’re doing this through our own projects and a variety of partnerships with leading academic and research institutions. Through these projects, and the new ERP consortium, we aim to increase the use of biomarkers and advance transformative therapies so that people living with schizophrenia and other complex brain disorders may have the chance to improve their functioning and quality of life.