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Case study: Treating psychiatric disorders

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A long-established research team at our Manchester Pharmacy School is working on developing treatments for psychiatric disorders with drugs and other therapies, including exercise and cognitive remediation.

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Schizophrenia affects around 1% of the global population

Professor of Psychopharmacology Jo Neill has been conducting research for almost 30 years, specifically in the development of animal models of psychiatric disorders.

Her team collaborates with many scientists at the University, and from other institutions both in the UK and abroad. They also have several active collaborations with the pharmaceutical industry, which discover new drugs for her to test and assist in developing new models.

Schizophrenia

A particular focus of Professor Neill's on-going research is schizophrenia, which affects 1% of the global population.

Together with Dr Ben Grayson, she runs a small contract research organisation (CRO, b-neuro, b-neuro.com) testing the effects of new compounds to treat cognitive and behavioural disturbances that occur in schizophrenia and other disorders, a current unmet clinical need.

These aspects of the illness adversely affect the quality of patients’ lives, limiting their ability to work, have successful relationships and contribute to society.

Dr Mike Harte and Dr John Gigg also form an integral part of the team, which conducts experiments to determine mechanisms by which the drugs produce their effects.

Drugs and other therapies

Professor Neill has developed a series of tests in rats to assess learning and memory, mood and social behaviour of relevance to schizophrenia and other disorders, such as ADHD and Autism Spectrum Disorder (ASD).

One goal of her research is to identify whether drugs and other therapies can be developed that help prevent psychosis from occurring in the first place.

A further aim is to assess the benefits of non-drug interventions, such as exercise, cognitive remediation and social skills training.

As she explains: "The currently available drugs can control psychotic symptoms and do help many patients, but on the whole they do not do enough to improve quality of life for the patient. As such, pharmaceutical companies are searching for drugs to help improve cognition and overcome the negative symptoms associated with schizophrenia, and so improve quality of life for patients and their carers.

"It is likely that the most successful approach will be to combine drug treatment with exercise and cognitive therapies, providing a holistic approach to therapy."

The currently available drugs can control psychotic symptoms and do help many patients, but on the whole they do not do enough to improve quality of life for the patient. As such, pharmaceutical companies are searching for drugs to help improve cognition and overcome the negative symptoms associated with schizophrenia, and so improve quality of life for patients and their carers.

Professor Jo Neill / Professor of Psychopharmacology

Animal modelling

Professor Neill’s work centres around modelling aspects of mental illness in animals. The focus of her research is using and refining existing tests that take advantage of the natural behaviour of animals and their instincts, so she uses tests that are ethologically relevant.

"Our approach also aims to enhance animal welfare by maintaining rats in social environments, using food rewards, enrichment such as exercise and ethologically relevant tasks. We focus on subtle behavioural disturbances in the animals. Psychiatric illness is identified through alterations in behaviour resulting from disturbances of brain function."

She says that it is likely that these brain disturbances originate early in life, even before a person is born, and that that person will therefore react differently to environmental stressors as they are developing, thereby making them less resilient to the pressures and stress of growing up, particularly in the teenage years.

Assessment of whether a drug will work to restore cognitive function will typically begin with simple tests on the animal, such as recognition memory, and then progress towards more complex cognitive tests, while also looking at the social behaviour of the animal.

Cognition

Professor Neill's approach is to have different tests in the animals for each aspect of cognition affected in illness, eg attention and vigilance, decision making, problem solving and reasoning, speed of processing.

She takes the same approach to testing effects of drugs for negative symptoms, having tests for optimistic behaviour, mood, and sociability.

"Of course, human behaviour is remarkably complex and not all aspects can be mimicked in animals, but there is a surprising amount of human behaviours that do have an animal equivalent. The trick is understanding the species being studied and taking advantage of their motivations and abilities," she explains. "You have to treat the animal within the context of what you know about the species.

"For instance, we know that rats are a social species and that they use communication and smell extensively. We can therefore design appropriate tests in the laboratory to take advantage of this knowledge."