Macquarie Group Foundation Chair of Schizophrenia Research, based at NeuRA and UNSW
Professor, School of Psychiatry, UNSW
+612 9399 1717
Cyndi’s research is focused on the molecular developmental neurobiology of schizophrenia. She earned a PhD in Biomedical Science at Mount Sinai School of Medicine, New York City and completed postdoctoral training at the National Institute of Mental Health rising to the level of Unit Chief of Molecules in the Neurobiology and Development of Schizophrenia Unit. Her awards include the Eli Lilly Young Investigator Award, NIH Fellows Award for Research Excellence, Independent Investigator Award and two Young Investigator Awards from NARSD. She has lectured throughout the world and contributed to over 150 publications.
Studying the molecular basis of raloxifene (a SERM) modulation of dopamine signalling in schizophrenia, which uses a maternal immune activation rodent model of schizophrenia to better understand how raloxifene brings about its effects.
Together with Professor Peter Schofield (NeuRA) and Professor Philip Mitchell (Black Dog Institute), our group is investigating the genetic contributors to bipolar disorder using Australian families with multiple individuals who have been diagnosed with the disorder.
The group previously identified a bipolar susceptibility locus located on chromosome 15 in a pooled analysis of 35 families. More detailed analysis of this region has identified a single gene, which confers an increased susceptibility to both bipolar disorder and schizophrenia, and has also been implicated as a risk factor for autism.
The group is now aiming to understand how alterations in ST8SIA2 translate into an increased genetic susceptibility by characterising alterations in the DNA, RNA and protein product of this gene and its interaction partners in patients with either bipolar disorder or schizophrenia.
CAITLIN MURPHY PhD student
DR DUNCAN SINCLAIR Postdoctoral Fellow
DEBORA ROTHMOND Senior Research Assistant
SHAN-YUAN TSAI-CHIN PhD student
DANNY BOERRIGTER Research assistant
ROXANNE CADIZ Technical assistant
YIRU ZHANG PhD student
KATE NAUDE Research assistant
JUAN OLAYA PhD student
DR MARI KONDO Postdoctoral Fellow
HELEN CAI PhD student
A large body of evidence indicates alterations in brain regional cellular energy metabolism and blood flow in schizophrenia. Among the different molecules regulating blood flow, vascular endothelial growth factor (VEGF) is generally accepted as the major factor involved in the process of angiogenesis. In the present study, we examined whether peripheral VEGF levels correlate with changes in the prefrontal cortex (PFC) volume in patients with schizophrenia and in healthy controls. Whole-blood samples were obtained from 96 people with schizophrenia or schizoaffective disorder and 83 healthy controls. Serum VEGF protein levels were analyzed by enzyme-linked immunosorbent assay, whereas quantitative PCR was performed to measure interleukin-6 (IL-6, a pro-inflammatory marker implicated in schizophrenia) mRNA levels in the blood samples. Structural magnetic resonance imaging scans were obtained using a 3T Achieva scanner on a subset of 59 people with schizophrenia or schizoaffective disorder and 65 healthy controls, and prefrontal volumes were obtained using FreeSurfer software. As compared with healthy controls, individuals with schizophrenia had a significant increase in log-transformed mean serum VEGF levels (t(177)=2.9, P=0.005). A significant inverse correlation (r=-0.40, P=0.002) between serum VEGF and total frontal pole volume was found in patients with schizophrenia/schizoaffective disorder. Moreover, we observed a significant positive association (r=0.24, P=0.03) between serum VEGF and IL-6 mRNA levels in patients with schizophrenia. These findings suggest an association between serum VEGF and inflammation, and that serum VEGF levels are related to structural abnormalities in the PFC of people with schizophrenia.
This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning, suggesting that plasma BDNF levels may reflect learning-related brain activity in healthy humans. The lack of relationship between plasma BDNF and task-related brain activity in patients suggests that circulating blood BDNF may not be indicative of learning-dependent brain activity in schizophrenia.
Although sex steroids are known to modulate brain dopamine, it is still unclear how testosterone modifies locomotor behaviour controlled, at least in part, by striatal dopamine in adolescent males. Our previous work suggests that increasing testosterone during adolescence may bias midbrain neurons to synthesise more dopamine. We hypothesised that baseline and amphetamine-induced locomotion would differ in adult males depending on testosterone exposure during adolescence. We hypothesised that concomitant stimulation of estrogen receptor signaling, through a selective estrogen receptor modulator (SERM), raloxifene, can counter testosterone effects on locomotion. Male Sprague-Dawley rats at postnatal day 45 were gonadectomised (G) or sham-operated (S) prior to the typical adolescent testosterone increase. Gonadectomised rats were either given testosterone replacement (T) or blank implants (B) for six weeks and sham-operated (i.e. intact or endogenous testosterone group) were given blank implants. Subgroups of sham-operated, gonadectomised and gonadectomised/testosterone-replaced rats were treated with raloxifene (R, 5mg/kg) or vehicle (V), daily for the final four weeks. There were six groups (SBV, GBV, GTV, SBR, GBR, GTR). Saline and amphetamine-induced (1.25mg/kg) locomotion in the open field was measured at PND85. Gonadectomy increased amphetamine-induced locomotion compared to rats with endogenous or with exogenous testosterone. Raloxifene increased amphetamine-induced locomotion in rats with either endogenous or exogenous testosterone. Amphetamine-induced locomotion was negatively correlated with testosterone and this relationship was abolished by raloxifene. Lack of testosterone during adolescence potentiates and testosterone exposure during adolescence attenuates amphetamine-induced locomotion. Treatment with raloxifene appears to potentiate amphetamine-induced locomotion and to have an opposite effect to that of testosterone in male rats.