Dopamine and Development: A Schizophrenic Predisposition

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1. SUMMARY

Schizophrenia is the most common psychotic disorder and currently affects around 200,000 Australians. Developmental risk factors such as prenatal hypoxia are associated with an increased risk of schizophrenia, although the neurobiological mechanisms by which this occurs are unknown. We propose that early environmental risk factors alter early brain development, giving rise to the same dopaminergic abnormalities that we see in schizophrenia. We have previously observed this with nutrient deficiencies and maternal infection, where early, unrelated risk factors for schizophrenia appear to act via a common convergent pathway of dopamine dysfunction. The purpose of my research is to understand how developmental risk factors for schizophrenia, namely prenatal hypoxia, result in schizophrenia-related dopaminergic changes and how a better understanding of this could potentiate more effective, targeted treatments for patients. 

2. BENEFIT

Patients with Schizophrenia experience hallucinations, delusions and disordered thinking which often leads to isolation, fear and additional health problems. Being highly associated with substance abuse and depression, Schizophrenic patients are 13 times more likely than the average Queenslander to take their own life (Heath 2017). Schizophrenia is the most common mental health disorder for hospital admission and the leading cause of hospital readmission (Chi, 2016). The effect of mental health on Queensland Hospitals is significant, where the average non-mental health patient will spend 4 days in hospital, mental health patients will spend 14 days in hospital (AIHW, 2019). Brisbane is currently the second highest region for overnight mental health related admissions in the nation (AIHW, 2019), where two-thirds of psychiatric patients require additional and on-going allied health including social work, physiotherapy and occupational therapy. 

Schizophrenia also poses a tremendous financial burden. Treating the vast majority of psychiatric patients is made possible by public funding from the health service budget (AIHW, 2019). With 90% of patients currently unemployed, schizophrenia costs the Australian government around $2.6 billion every year. It is without a doubt that poor treatment options are largely responsible for these saddening statistics.  

The available treatments provide some patients with temporary relief from their symptoms. However, for 50% of patients, antipsychotics do not treat their psychosis (Haddad and Correll, 2018). Our lack of understanding of the mechanisms by which this disease occurs has resulted in patients living their entire lives with debilitating and untreated symptoms.  

My laboratory primarily focuses on the role of dopamine in schizophrenia, where I am currently modelling prenatal hypoxia and quantifying changes in dopaminergic systems across important developmental time points. Prenatal hypoxia refers to insufficient oxygen to the foetus during gestation, which can occur from preeclampsia, smoking during pregnancy, iron deficiency anaemia and complications during labour. Hypoxia during pregnancy increases the foetus’ risk of developing schizophrenia 7-fold, compared to healthy controls (Zornber, 2000). I use immunohistochemistry to quantify different cellular and synaptic populations of dopamine neurons in embryonic brains to identify the influence that hypoxia has on the developing brain and the possible psychiatric implications of this. Current antipsychotic medications block dopamine D2-receptors however this is not where the fundamental abnormality in schizophrenia lies. It has been identified that schizophrenia is a disease of aberrant presynaptic dopamine function, for which no current medication is targeted, emphasising a dire need for further study into the dopaminergic mechanisms of early developmental insults in giving rise to schizophrenia. 

In studying how known risk factors for schizophrenia contribute to the disease, we are able to inform the community about the dangers of early risk factors, aid in prevention, early intervention and improve pharmaceutical treatment options.

3. ENGAGEMENT

I have always had a strong interest in scientific engagement, specifically with respect to the translation of research into clinical medicine, science communication and public health. My first experience in STEM engagement was being accepted into the National Youth Science Forum and London International Youth Science Forum in high school, at which time I led my schools state-level titrimetry team, was a staff student advisor for the ConoccoPhillips science experience, a member of Young Scientists Australia Queensland and partaking in The University of Queensland’s FEAST program. What I took from these early experiences was to actively seek out opportunities and be constantly involved in different avenues of science leadership, networking and professional development.

During my time as an undergraduate, I was a medical volunteer in emergency, intensive and critical care, I undertook observerships and shadowed physicians in every medical specialty to gain an understanding of how the public and private medical systems operate. This directed my interest specifically toward neuroscience and psychiatry. I travelled abroad to South-East Asia where I worked as a medical volunteer in a trauma hospital assisting in procedures, teaching English and engaging with other young scientific professionals from around the world. After studying in Japan as an exchange student I became privy to the importance of academic collaboration and translational research on a global scale.

Shortly after returning to Australia I became involved with United Nations Youth and a leader for the University of Adelaide’s Youth STEM Explorer program introducing disadvantaged children to different areas of science and where a career in STEM can lead. Additionally, I have worked on the assessment panel for the National Brain Bee, completed UQ’s LeadHERS program for women in leadership and entrepreneurship in the area of STEM as well as currently volunteer for the National Science Week coordination committee. I volunteered at the Translation Research symposium, the Mater/QBI research symposium and AAHMS Clinical Science Symposium facilitating events focused on scientific engagement, networking and promoting STEM to the wider community. I just recently became involved with YWAM Ships, an international medical outreach organisation providing education and medical care in developing countries. I feel as though ongoing engagement and an active involvement in STEM is imperative to becoming a well-rounded scientist, whether it be through industry collaboration, volunteering or academia I will always strive to be involved in the promotion and engagement of science and support my fellow women in STEM to advance in their respective fields.

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