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Schizophrenia is a mental illness that emerges in adolescence or young adulthood and affects approximately 1 in 100 people in Australia and worldwide. It causes difficulties in thinking and unusual experiences such as hearing unpleasant voices or having false and sometimes bizarre beliefs. People with schizophrenia often avoid family and friends, lack motivation and are often unable to work.

While the exact causes are not known, we believe that genetic and environmental influences combine to create abnormal changes in brain development that cause the symptoms of schizophrenia.

Current treatments are designed to suppress these symptoms and do not target the cause of the disorder. These drugs only partially relieve symptoms and can produce unwanted side effects.

We are currently investigating several new treatments, including a medication that targets a hormone receptor in the brain, as well as transcranial Direct Current Stimulation, a very mild form of electrical stimulation applied to the scalp to stimulate brain activity and improve thinking.


Damien McDonell was a participant in the CASSI study. Click
here to read his story.

 

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Symptoms

Outward symptoms of schizophrenia usually become evident in adolescence or young adulthood. Women tend to have a slightly later age of onset.

A person with schizophrenia may initially appear withdrawn or depressed and later on express unusual thoughts or beliefs. At first, they are typically not aware of their symptoms and they do not understand that they are unwell.

Symptoms can be divided into two categories: positive symptoms (behaviour or feelings that people with schizophrenia experience but are not commonly observed in healthy people) and negative symptoms (behaviour or feelings that are missing in people with schizophrenia but are commonly observed in healthy people).

Positive symptoms include auditory hallucinations and delusions. Auditory hallucinations often take the form of one or more voices, perceived by the person with schizophrenia as someone speaking out loud. These voices often comment on the person’s behaviour and are often experienced as someone saying mean things about the person with schizophrenia.

Delusions, or continuous false beliefs, might include a belief that some unseen force is controlling your actions, that you are receiving special messages from the television, that people are out to harm you or that you can read other people’s minds.

The term ‘word salad’ has been used to describe the jumbled and confused thoughts and speech that is also symptomatic of schizophrenia.

Negative symptoms include a lack of emotion and motivation, minimal speech and deficits in the ability to think clearly.

Schizophrenia can appear to be somewhat different in different people. Some people experience more hallucinations and delusions, while others primarily experience disordered thoughts and speech. Some people also experience depression and mania (symptoms seen in people with bipolar disorder) which is characteristic of schizoaffective disorder.

While many of these symptoms are typically apparent during the unmedicated and ‘psychotic’ phase of the illness, with treatment some people with schizophrenia can also experience periods of stable mental health or variable degrees of symptom reduction; however, the 'negative' symptoms often persist even with current available treatments.

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Common causes 

While we don’t yet know exactly what causes schizophrenia, we believe that it’s most likely that several genes, together with environmental influences, that increase susceptibility to the disorder by causing the brain to develop abnormally at different stages of life – possibly before birth, or in early childhood and in adolescence.

Researchers have found a handful of genes that may be linked to schizophrenia. Some of these genes relate to a neurotransmitter called glutamate, which plays a major role in brain development. It’s been suggested that the glutamate system may not function properly in people with schizophrenia. Other candidate genes relate to another neurotransmitter called dopamine. It’s been shown that the dopamine system does not function properly in the brains of people with schizophrenia.

At Neuroscience Research Australia, Professor Cyndi Shannon Weickert, the Macquarie Group Chair of Schizophrenia Research, has discovered that people with schizophrenia are more likely to inherit a gene that codes for a faulty oestrogen receptor in the brain. Together with the Schofield Group, they are also investigating another gene that plays an important role in the development of neural connections in the brain during early development.

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Management

Diagnosis: At present, there is no biological test for schizophrenia. A diagnosis is made by a psychiatrist based on outward signs and symptoms of the disorder described above.

Some studies have suggested that people with schizophrenia develop enlarged ventricles, natural connected spaces in between the folds of the brain that carry cerebral spinal fluid, but this finding is not present in all people with schizophrenia.

Treatment: The primary treatment to relieve symptoms of schizophrenia are antipsychotic medications. Some examples of available medications are: risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone. Clozapine is sometimes used in patients who do not respond to other medications, but can have life-threatening complications in some people and must be monitored regularly.

Studies have suggested that the earlier a person is treated, the better their outcome. Early, consistent treatment with medication may prevent the severe, chronic debilitating form of this illness from developing.

Unfortunately, current medications don’t offer a total solution, or ‘cure’. Current treatments only suppress symptoms and do not treat the biological cause of the illness. In addition, some patients don’t respond well to medication or may have intolerable side effects. Some common side effects include weight gain and diabetic-like problems with glucose metabolism.

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About our research 

The Macquarie Group Chair of Schizophrenia Research, Professor Cyndi Shannon Weickert, and her research team aim to understand how genes and environments lead to biological changes in the brain during development to cause schizophrenia. A more complete knowledge of these causes can lead to new and more effective treatments aimed at the root of the problem in schizophrenia. Dr Tom Weickert’s research group takes discoveries from Cyndi Shannon Weickert’s lab to identify and test new treatments in clinical trials to reduce symptoms, improve thinking, and restore normal social function in people with schizophrenia.

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What we have discovered 

People with schizophrenia have difficulty planning tasks, problem solving, focusing attention, remembering information and interacting with others. Antipsychotic medication treatment may reduce some symptoms but they do not return people to their level of function before the illness. A relationship between antipsychotic medicine and genes may explain why some people with schizophrenia respond better to antipsychotic medication than other people.  We have discovered that some people with schizophrenia have a gene that does not allow the brain to respond to hormones during development which may put a person at risk for schizophrenia. These findings have allowed us to test new treatments aimed at improving the lives of people with schizophrenia and their families.

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Current projects 

Cognitive and Affective Symptoms of Schizophrenia Intervention (CASSI)
This clinical trial will test the effectiveness of a medication in reducing the symptoms of schizophrenia and improving daily function. Of all the symptoms associated with schizophrenia or schizoaffective disorder, problems with thinking and social interactions often do not respond to treatment. They are the most lasting and debilitating as they interfere with a person’s ability to function independently. This study aims to determine if a gene that makes a faulty hormone receptor in the brain is related to thinking problems in people with schizophrenia and if a hormone modulator medication (already approved for use to treat a different illness), taken in addition to a person’s current antipsychotic medication, can also improve thinking and social interactions in people with schizophrenia and schizoaffective disorder.
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A transcranial Direct Current Stimulation (tDCS) to improve thinking in people with schizophrenia and schizoaffective disorder
People with schizophrenia have difficulty thinking that is often caused by problems in the frontal region of the brain. These thinking problems do not usually improve with current antipsychotic medication treatment and they may be responsible for the inability to function normally in the community. tDCS is a very mild form of electrical stimulation that is applied by electrodes on the scalp to stimulate brain activity. Based on previous research showing that tDCS can improve thinking in healthy adults and in people with depression, this study will test if weak brain stimulation using tDCS to the frontal area of the brain will temporarily improve thinking problems in people with schizophrenia and schizoaffective disorder. The study is still in progress, but at present, we have measured significant improvement in the thinking of about half of the people with schizophrenia who have completed this trial.

A clinical trial of transcranial Direct Current Stimulation (tDCS) to reduce auditory hallucinations AND improve thinking in people with schizophrenia and schizoaffective disorder
Based on the success of our nearly completed tDCS study to improve thinking in people with schizophrenia and schizoaffective disorder (see above), we are beginning a new clinical trial of tDCS with the aim of improving thinking ability for a longer time and reducing the hearing of unwanted voices that often make critical comments on a person’s behaviour. The hearing of unwanted voices is one of the more frequent psychotic symptoms in people with schizophrenia and schizoaffective disorder. These voices are not completely eliminated by existing antipsychotic medication. Positioning of the electrodes over specific brain regions important for problem solving and hearing unwanted voices may improve thinking and reduce these unwanted voices in people with schizophrenia. This new trial also extends the tDCS treatments over a 4 week period to test how long these improvements will continue.
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Understanding the link between hormones and schizophrenia
There a many clues that sex and stress hormones may influence the symptoms of schizophrenia. Males are more likely to suffer more severely from schizophrenia than females. Women who suffer from schizophrenia have worse symptoms when their hormone levels of oestrogen are low. Psychotic symptoms can be reduced in women when they receive oestrogen replacement. In general, high life stress can bring on psychotic symptoms in both men and women. In this study we seek to gain a better understanding of the relationship among sex hormones (oestrogen and testosterone) and stress hormones (cortisol) and how these hormones may influence psychotic symptoms, brain activity and function. We especially want to know if increasing the sex hormones (that may be helpful) and decreasing the stress hormones (that can be harmful) will help reduce symptoms in people with schizophrenia.
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The nature of the link between cannabis and psychosis
The nature of the link between cannabis and psychosis has been questioned for decades. Australian survey data indicate that young people initiate cannabis use at an earlier age than in the 1980s, using more potent forms of cannabis. However, the majority of early users do not develop later psychotic disorders and there is an urgent need to clarify the impact of cannabis on the aetiology of schizophrenia. As cannabis is a mixture of different cannabinoids,Dr Tim Karl is looking at how these plant components impact on genetically induced schizophrenia-relevant behaviours in mouse models.

We are currently recruiting participants for some of the above studies.

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