NeuRA Magazine #20

NOVEL INSIGHTS INTO DOPAMINE DYSFUNCTION

Understanding how more precisely dopamine is changed in the brains of people with schizophrenia will help us to better understand the main path that leads to developing the disorder.

Dr Tertia Purves Tyson

While there are many roads leading to the development of schizophrenia, one often considered a final common pathway is the dysregulation of dopamine. Too much dopamine in particular region of the brain – the subcortex – contributes to the psychotic symptoms seen in schizophrenia.

Dopamine is a neurotransmitter that helps to control the brain’s reward and pleasure centre, and regulates our emotions. Antipsychotics are designed to block dopamine receptors, and reduce the amount of dopamine action in the brain. Unfortunately, antipsychotics do not work for everyone and have serious side effects.

A better understanding of how and where dopamine is changed in the brains of people with schizophrenia will help us to understand how to more accurately correct or prevent this disruption and thus help to design more targeted approaches to treatment.

A new study from the Schizophrenia Research Lab has identified molecular changes in the brains of people with schizophrenia, which offers support for and extends the dopamine hypothesis.

The new study from Dr Tertia Purves-Tyson compared tissue from deep in the brain (midbrain) of people with and without schizophrenia. This brain region has not previously been given the attention it deserves in schizophrenia research on human brains donated after death. The study found that the genes of molecules that are responsible for regulating the amount of dopamine and for regulating the reaction to dopamine (receptors) are altered in people with schizophrenia.

These alterations in gene expression implicate a new suspect as a major contributor to dopamine dysregulation, namely a massive decrease in dopamine transporter. This 66% reduction in this important molecule would mean that dopamine may be allowed to stay in the synapse longer than it should and suggests that novel treatments aimed at ramping up the synthesis and function of this in schizophrenia could be of benefit. To our knowledge, dopamine transporter has not been used as a treatment target ever before.

This study begins to address a vital knowledge gap in schizophrenia research with regards to how dopamine in the midbrain contributes to dopamine dysfunction. This will help us to better understand the dopamine dysregulation that is found in schizophrenia and, potentially, how we can better treat it.

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Abdominal muscle stimulation to improve bowel function in spinal cord injury

Bowel complications, resulting from impaired bowel function, are common for people living with a spinal cord injury (SCI). As a result, people with a SCI have high rates of bowel related illness, even compared with those with other neurological disorders. This includes high rates of abdominal pain, constipation, faecal incontinence and bloating. These problems lower the quality of life of people with a SCI and place a financial burden on the health system. A treatment that improves bowel function for people with a SCI should reduce illness, improve quality of life and lead to a large cost saving for health care providers. Bowel problems have traditionally been managed with manual and pharmacological interventions, such as digital rectal stimulation, enemas, and suppositories. These solutions are usually only partially effective, highlighting the need for improved interventions. The abdominal muscles are one of the major muscle groups used during defecation. Training the abdominal muscles should improve bowel function by increasing abdominal pressure. During our previous Abdominal FES research with people with a SCI, we observed that Abdominal FES appeared to lead to more consistent and effective bowel motion. However, this evidence remains anecdotal. As such, we are going to undertake a large randomised controlled trial to investigate the effectiveness of Abdominal FES to improve the bowel function of people with a SCI. This study will make use of a novel measurement system (SmartPill, Medtronic) that can be swallowed to measure whole gut and colonic transit time. We will also assess whether Abdominal FES can change constipation-related quality of life and the use of laxatives and manual procedures, as well as the frequency of defecation and the time taken. A positive outcome from this study is likely to lead to the rapid clinical translation of this technology for people living with a SCI.
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