The cause of psychiatric disease
Grant number: 1002240 | Funding period: 2011 - 2016
The Applicant seeks to understand the causes of the schizophrenia, bipolar disorder and major depressive disorder, which affect over 20% of the Australian population. This research is important as drug design, based on chemical remodelling, has not significantly advanced initial breakthroughs in treating psychiatric disorders and there is now a widespread belief that new drugs will only come from understand their causes.
Related publications (42)
Altered levels of dopamine transporter in the frontal pole and the striatum in mood disorders: A postmortem study.
Hirotaka Sekiguchi, Geoff Pavey, Brian Dean
Dopamine dysregulation is known to play a major role in the pathophysiology of major depressive disorders (MDD) and bipolar disord..
An investigation into nicotinic receptor involvement in mood disorders uncovers novel depression candidate genes
Andrew Gibbons, Kate McPherson, Andrea Gogos, Brian Dean
BACKGROUND: We have previously reported reduced expression of the cholinergic autoreceptor CHRM2 in Brodmann's Area (BA) 24 of the..
The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder
Srisaiyini Kidnapillai, Chiara C Bortolasci, Madhara Udawela, Bruna Panizzutti, Briana Spolding, Timothy Connor, Andrew Sanigorski, Olivia M Dean, Tamsyn Crowley, Stephane Jamain, Laura Gray, Elizabeth Scarr, Marion Leboyer, Brian Dean, Michael Berk, Ken Walder
To create a gene expression signature (GES) to represent the biological effects of a combination of known drugs for bipolar disord..
Changed cortical risk gene expression in major depression and shared changes in cortical gene expression between major depression and bipolar disorders
Elizabeth Scarr, Madhara Udawela, Brian Dean
BACKGROUND: Mood disorders likely occur in someone with a genetic predisposition who encounters a deleterious environmental factor..
Changed frontal pole gene expression suggest altered interplay between neurotransmitter, developmental, and inflammatory pathways in schizophrenia
Elizabeth Scarr, Madhara Udawela, Brian Dean
Schizophrenia (Sz) probably occurs after genetically susceptible individuals encounter a deleterious environmental factor that tri..
Changed gene expression in subjects with schizophrenia and low cortical muscarinic M1 receptors predicts disrupted upstream pathways interacting with that receptor
E Scarr, M Udawela, EA Thomas, B Dean
We tested the hypothesis that, compared with subjects with no history of psychiatric illness (controls), changes in gene expressio..
Higher levels of different muscarinic receptors in the cortex and hippocampus from subjects with Alzheimer's disease
Elizabeth Scarr, Catriona McLean, Brian Dean
It has been suggest that drugs specifically targeting muscarinic receptors will be useful in treating Alzheimer's disease. We deci..
Muscarinic receptor binding changes in postmortem Parkinson's disease
Caitlin McOmish, Geoff Pavey, Catriona McLean, Malcolm Horne, Brian Dean, Elizabeth Scarr
Parkinson's disease (PD) is a devastating disorder, affecting approximately 2% of people aged 60 and above. It is marked by progre..
Fatty acid composition of the postmortem corpus callosum of patients with schizophrenia, bipolar disorder, or major depressive disorder
K Hamazaki, M Maekawa, T Toyota, B Dean, T Hamazaki, T Yoshikawa
BACKGROUND: Studies investigating the relationship between n-3 polyunsaturated fatty acid (PUFA) levels and psychiatric disorders ..
Analysis of induced pluripotent stem cells carrying 22q11.2 deletion
M Toyoshima, W Akamatsu, Y Okada, T Ohnishi, S Balan, Y Hisano, Y Iwayama, T Toyota, T Matsumoto, N Itasaka, S Sugiyama, M Tanaka, M Yano, B Dean, H Okano, T Yoshikawa
Given the complexity and heterogeneity of the genomic architecture underlying schizophrenia, molecular analyses of these patients ..
The distribution of muscarinic M1 receptors in the human hippocampus
Elizabeth Scarr, Myoung Suk Seo, Timothy Douglas Aumann, Gursharan Chana, Ian Paul Everall, Brian Dean
The muscarinic M1 receptor plays a significant role in cognition, probably by modulating information processing in key regions suc..
Validating reference genes using minimally transformed qpcr data: findings in human cortex and outcomes in schizophrenia
Brian Dean, Madhara Udawela, Elizabeth Scarr
BACKGROUND: It is common practice, when using quantitative real time polymerase chain reaction (qPCR), to normalise levels of mRNA..
Changes in BQCA Allosteric Modulation of [H-3]NMS Binding to Human Cortex within Schizophrenia and by Divalent Cations
Brian Dean, Shaun Hopper, P Jeffrey Conn, Elizabeth Scarr
Stimulation of the cortical muscarinic M1 receptor (CHRM1) is proposed as a treatment for schizophrenia, a hypothesis testable usi..
Changes in Muscarinic M2 Receptor Levels in the Cortex of Subjects with Bipolar Disorder and Major Depressive Disorder and in Rats after Treatment with Mood Stabilisers and Antidepressants
Andrew Stuart Gibbons, Won Je Jeon, Elizabeth Scarr, Brian Dean
BACKGROUND: Increasingly, data are implicating muscarinic receptors in the aetiology and treatment of mood disorders. This led us ..
Fatty acid composition and fatty acid binding protein expression in the postmortem frontal cortex of patients with schizophrenia: A case-control study
Kei Hamazaki, Motoko Maekawa, Tomoko Toyota, Yoshimi Iwayama, Brian Dean, Tomohito Hamazaki, Takeo Yoshikawa
BACKGROUND: Abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), have been found i..
Lower [3H]LY341495 binding to mGlu2/3 receptors in the anterior cingulate of subjects with major depressive disorder but not bipolar disorder or schizophrenia
Caitlin E McOmish, Geoff Pavey, Andrew Gibbons, Shaun Hopper, Madhara Udawela, Elizabeth Scarr, Brian Dean
INTRODUCTION: The glutamatergic system has recently been implicated in the pathogenesis and treatment of major depressive disorder..
Changes in cholinergic and glutamatergic markers in the striatum from a sub-set of subjects with schizophrenia
Brian Dean, Natalie Thomas, Chi-Yu Lai, Wei J Chen, Elizabeth Scarr
BACKGROUND/OBJECTIVES: Having separated a sub-group of people with schizophrenia based on a marked loss of cortical [(3)H]pirenzep..
The effect of a muscarinic receptor 1 gene variant on grey matter volume in schizophrenia
Vanessa L Cropley, Elizabeth Scarr, Alex Fornito, Paul Klauser, Chad A Bousman, Rodney Scott, Murray J Cairns, Paul A Tooney, Christos Pantelis, Brian Dean
Previous research has demonstrated that individuals with schizophrenia who are homozygous at the c.267C>A single nucleotide polymo..
Biomarkers for Psychiatry: The Journey from Fantasy to Fact, a Report of the 2013 CINP Think Tank
Elizabeth Scarr, Mark J Millan, Sabine Bahn, Alessandro Bertolino, Christoph W Turck, Shitij Kapur, Hans-Juergen Moeller, Brian Dean
BACKGROUND: A think tank sponsored by the Collegium Internationale Neuropsychopharmacologium (CINP) debated the status and prospec..
Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder
Kei Hamazaki, Motoko Maekawa, Tomoko Toyota, Brian Dean, Tomohito Hamazaki, Takeo Yoshikawa
Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, i..
Autophagy has a key role in the pathophysiology of schizophrenia
A Merenlender-Wagner, A Malishkevich, Z Shemer, M Udawela, A Gibbons, E Scarr, B Dean, J Levine, G Agam, I Gozes
Autophagy is a process preserving the balance between synthesis, degradation and recycling of cellular components and is therefore..
The Role of Muscarinic Receptors in the Pathophysiology of Mood Disorders: A Potential Novel Treatment?
Won Je Jeon, Brian Dean, Elizabeth Scarr, Andrew Gibbons
The central cholinergic system has been implicated in the pathophysiology of mood disorders. An imbalance in central cholinergic n..
Lower cortical serotonin 2A receptors in major depressive disorder, suicide and in rats after administration of imipramine
Brian Dean, Nahed Tawadros, Myoung Suk Seo, Won Je Jeon, Ian Everall, Elizabeth Scarr, Andrew Gibbons
We have attempted to replicate studies showing higher levels of serotonin 2A receptors (HTR2A) in the cortex of people with mood d..
Cholinergic muscarinic M-4 receptor gene polymorphisms: A potential risk factor and pharmacogenomic marker for schizophrenia
Elizabeth Scarr, Jung Yoon Um, Tiffany Frances Cowie, Brian Dean
Although schizophrenia is a widespread disorder of unknown aetiology, we have previously shown that muscarinic M4 receptor (CHRM4)..
Decreased cortical muscarinic M1 receptors in schizophrenia are associated with changes in gene promoter methylation, mRNA and gene targeting microRNA
E Scarr, JM Craig, MJ Cairns, MS Seo, JC Galati, NJ Beveridge, A Gibbons, S Juzva, B Weinrich, M Parkinson-Bates, AP Carroll, R Saffery, B Dean
Many studies have shown decreased cortical muscarinic M1 receptors (CHRM1) in schizophrenia (Sz), with one study showing Sz can be..
Mu opioid receptor availability in people with psychiatric disorders who died by suicide: a case control study
Elizabeth Scarr, Tammie Terese Money, Geoffrey Pavey, Jaclyn Neo, Brian Dean
BACKGROUND: Mu opioid receptors have previously been shown to be altered in people with affective disorders who died as a result o..
Muscarinic M1 receptor sequence: Preliminary studies on its effects on cognition and expression
Elizabeth Scarr, Suresh Sundram, Azita Deljo, Tiffany Francis Cowie, Andrew Stuart Gibbons, Susan Juzva, Andrew Mackinnon, Stephen J Wood, Renee Testa, Christos Pantelis, Brian Dean
It has been reported that people with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism of the choli..
Differential age- and disease-related effects on the expression of genes related to the arachidonic acid signaling pathway in schizophrenia
Bin Tang, Cristina Capitao, Brian Dean, Elizabeth A Thomas
We have previously identified differential effects of age on global brain gene expression profiles in subjects with schizophrenia ..
Altered neuronal markers following treatment with mood stabilizer and antipsychotic drugs indicate an increased likelihood of neurotransmitter release.
Elizabeth Scarr, Brian Dean
OBJECTIVE: Given the ability of mood stabilizers and antipsychotics to promote cell proliferation, we wanted to determine the effe..
AMPA receptor expression is increased post-mortem samples of the anterior cingulate from subjects with major depressive disorder
Andrew Stuart Gibbons, Lucy Brooks, Elizabeth Scarr, Brian Dean
BACKGROUND: Glutamate is thought to be involved in the pathophysiology of major depressive disorder and bipolar disorder; however,..
Understanding the role of inflammatory-related pathways in the pathophysiology and treatment of psychiatric disorders: evidence from human peripheral studies and CNS studies
Many lines of evidence now support the hypothesis that inflammation-related pathways are involved in the pathophysiology of psychi..