Cheltenham Science Festival 2011 – Schizophrenia

The British Association for Psychopharmacology (BAP) organised a session at the 2011 Cheltenham Science Festival that explored Schizophrenia. The session, held in the town hall on 8th June, proved extremely popular with a ‘full house’. Professor Kathy Sykes, Festival Director, chaired the session that comprised presentations by three speakers, Marjorie Wallace, Dr Peter Haddad and Professor Gavin Reynolds. Following the presentations there was a lively question-and-answer session which continued in an informal manner in the ‘talking booth’. Members of the audience raised many pertinent questions and several discussed their personal experience of living with schizophrenia or having a relative who had been affected by the illness. These personal testimonies were extremely powerful and highlighted a range of issues including both positive and negative experiences of NHS care, stigma and how some sufferers had strived to successfully overcome their illness and lead as full a life as possible. The session was a great success both in terms of the number of attendees, the audience interaction and the quality of the presentations and discussion. A summary of the three presentations is provided below.

Marjorie Wallace CBE: The work of SANE

The session opened with a presentation by Marjorie Wallace, founder and Chief Executive of the charity SANE, who discussed her work with the charity over the last 25 years. She explained how SANE had been established in 1986 following public interest generated by a series of articles she had written on schizophrenia in The Times entitled ‘The Forgotten Illness’. Since that time the charity has gradually grown and now assists people not just with schizophrenia but those who suffer from any mental disorder.

SANE has three main aims. The first is to raise awareness about mental illness, reduce the associated stigma and to campaign for better mental health services. The second aim is to provide emotional support and information for sufferers of mental illness and their families. This is achieved through a national telephone helpline, support forums and an email service. These services are provided by trained volunteers who devote their time free of charge. The final aim is to support research into the causes and treatments of serious mental illness including schizophrenia, depression and bipolar disorder. In 2003 SANE founded the Prince of Wales International Centre for SANE Research in Oxford under the leadership of Professor Tim Crow.

The talk was illustrated with personal recollections of people who had influenced the development of SANE and key milestones in the organisation’s development. Marjorie Wallace highlighted the challenge of fund raising and thanked the patrons and supporters of SANE for their dedication over many years.

Dr Peter Haddad: Clinical aspects of schizophrenia

In the second session Dr Peter Haddad, Consultant Psychiatrist and Honorary Senior Lecturer at the University of Manchester, provided an overview of the clinical features and management of schizophrenia. He explained that schizophrenia is one of the most common serious mental illnesses with a life time risk of approximately 1%. It affects men and women equally, occurs in all countries of the world and most commonly starts when people are in their early twenties. It is classified as a psychotic illness as it is characterised by a loss of contact with reality.

The clinical course and impact on quality of life and functioning are very variable. A small proportion of people make a full recovery after a single psychotic episode and do not become ill again. At the other end of the specturm are a minority of people who do not recover from their first psychotic epsiode, have constant symptoms and require intensive help and support with daily activities, sometimes needing to live in supported accomodation. Inbetween these two extremes are the majority of sufferers who make a good recovery from their first psychotic episode but who experience further episodes of psychosis (‘relapses’) inbetween which symptoms are present to varying degrees. The illness can cause great suffering for the individual affected and their family. Many sufferers are unable to hold down paid employment though others are able to do so. Compared to the general population, people with schizophrenia have an increased risk of suicide and higher rates of many physical health problems including stroke and heart disease.

There is no diagnostic test for schizophrenia, rather it is clinical diagnosis based on the recognition of a characteristic pattern of symptoms. The symptoms are very varied but the most important are positive and negative symptoms. Positive symptoms, also termed psychotic symptoms, include delusions and hallucinations. Delusions are false beliefs that are held on inadequate grounds and which are totally resistant to reasoned argument. For example a sufferer may believe that his neighbours want to kidnap and harm him despite no objective evidence to support this. Hallucinations are perceptions that occur without a stimulus. The most common type of hallucination seen in schizophrenia is a person hearing voices despite the fact that in reality no-one is speaking (auditory hallucinations). Other psychotic symptoms that can occur in schizophrenia include the belief and experience that the sufferer can receive other peoples’ thoughts directly in their mind, that others can ‘pick-up’ and read their thoughts and that some outside force can control their behaviour or emotions. Not surprisingly, psychotic symptoms can be a terrifying experience for the sufferer. Negative symptoms represent a lack of function that one would usually expect to see in a healthy person. For example, a person with schizophrenia may appear emotionally ‘flat’, apathetic and show self neglect. Often it is the negative symptoms, rather than the more dramatic psychotic symptoms, that make schizophrenia such a disabling illness. As well as positive and negative symptoms, schizophrenia can cause many other symptoms including anxiety and depression but these have less diagnostic specificity.

Dr Haddad discussed clinical management and highlighted that this needs to be tailored to the individual. Most people with schizophrenia require care from a community mental health team that allows multidisciplinary input from a range of professionals including psychiatrists, psychologists, community psychiatric nurses, social workers, occupational therapists and support workers. Most care is provided in the community but psychotic relapses may require a period of inpatient care. Antipsychotic drugs are an essential part of treatment. They are effective for treating psychotic symptoms and also in preventing their recurrence, i.e. in reducing the risk of relapse. However they can cause a range of side effects including sedation, weight gain, sexual dysfunction, restlessness, stiffness and tremor. Expert management should enable medication side effects to be prevented or kept to a minimum. Rehabilitation and activity planning are important to treat negative symptoms. Talking treatments, incuding family interventions, have an important part to play in reducing the risk of relapse and treating resistant symptoms. There is much that sufferers can do themselves to help overcome their illness in terms of engaging fully with a wide range of treatments, keeping active and addressing other aspects of their lifestyle. Treatment very much needs to be a partnership between the sufferer, their family or carers and the treating team. A positive therapeutic alliance and ease of access to services are essential elements for good care.

Dr Haddad concluded by highlighting that schizophrenia poses many challenges for sufferers, their families and the professionals helping them, but great progress has been made in the last two decades. The available treatments and our understanding of the illness have both improved greatly during this time and further advances can be expected in the next decade.

Professor Gavin Reynolds: The underlying biology and mechanisms of antipsychotic action

Professor Gavin Reynolds, Past-President of the BAP and Honorary Professor at Sheffield Hallam University, started by emphasising how understanding the roles of certain neurotransmitters is central to what we know of the biology of schizophrenia and its treatment with antipsychotic drugs.

He then discussed the little we know about the genetic and environmental risk factors for the disease. Perhaps the biggest risk is having a close relative with schizophrenia: a first-degree relative with schizophrenia will increase risk by about 10 times. However there is no single genetic “cause” for the disease; rather there are multiple genetic factors that each impart a very small risk but when combined, perhaps in conjunction with environmental factors, then changes occur in the developing brain that may lead eventually to schizophrenia.

Thus genetic research has told us little about the causes of schizophrenia other than that it is complex and involves many genes. But there are parallels between the functions of these genes and what we are beginning to glean of the subtle differences seen in the brains of people with schizophrenia. This has emerged from studies both of the living brain, using imaging techniques, and of brains collected at post mortem, which enable us to study the cellular, subcellular and chemical make-up of brain tissue.  There have really been two converging approaches – one started from the structural differences seen in schizophrenia which point to a loss of brain tissue, while the other has developed from the so-called “dopamine hypothesis” of schizophrenia. The dopamine hypothesis proposes that there is an overactivity of this neurotransmitter in schizophrenia, formulated on the basis of two lines of evidence: one is that drugs such as amphetamine, which increase the levels of dopamine released by neurons, can cause psychosis similar to schizophrenia. The other is the finding that all drugs used to treat schizophrenia act by binding to specific dopamine receptors, blocking the effects of dopamine in the brain.

The problem with the dopamine hypothesis of schizophrenia is that there is very little evidence to support it as a cause of the disease. While modern imaging studies show that dopamine is stored in, and released from, neurons in greater quantities in people with symptoms of schizophrenia, there is no indication that this is the primary pathology of the disease. While an excess of dopamine might result in psychotic symptoms, the negative symptoms and cognitive problems of schizophrenia are not explained by dopamine hyperactivity.

Understanding the biology of schizophrenia has developed beyond the dopamine hypothesis due to the finding of a pathology of the disease – people with schizophrenia tend to have structural and cellular changes in the brain, particularly in certain regions that may relate to some of the symptoms. These findings are only clues as to what may be awry – schizophrenia can still occur without obvious brain tissue changes. But it has sparked an interest in understanding the underlying molecular changes that might relate to this pathology. Besides dopamine, two other neurotransmitters are particularly thought to be involved – GABA (gamma-aminobutyric acid) and glutamate. A deficit in a subset of GABA-containing neurons is a consistent finding in schizophrenia. Glutamate neurons provide the main driving force of brain activity, while inhibitory GABA and other neurotransmitters control and modulate this activity.

With an understanding of the possible roles of GABA and glutamate neurotransmitters in schizophrenia, we can see that drugs enhancing GABA neurotransmitter activity, or that control glutamate, might be effective in “normalising” the brain. Such drug treatments would allow us to get away from a focus on dopamine activity, and avoid the limitations resulting from this – the poor response of some symptoms and the unwanted side effects. Pharmaceutical companies are developing such drugs, and early trials for several new compounds are underway.

In parallel with these developments in drug treatment, there is an increasing focus on “personalised medicine”. Genetic factors can contribute to the effects of drugs, both on symptom response and the emergence of side effects. Thus we should eventually be able to use genetic testing to predict whether a patient is more or less likely to respond well to drug treatment, or to develop problematic side effects such as weight gain.

Additional Information
Further information on schizophrenia is available from various sources that include:

1. The Royal College of Psychiatrists. A range of public information leaflets on schizophrenia and related subjects is available at: https://www.rcpsych.ac.uk/mental-health/problems-disorders/schizophrenia

2. SANE. A Fact sheet on Schizophrenia produced by SANE is available at: http://www.sane.org.uk/uploads/schizophrenia.pdf

The website for SANE, which has details of other resources, is: http://www.sane.org.uk/

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