Prof Cyndi Shannon Weickert

TEAM LEADER PROFILE

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.

Projects Prof Cyndi Shannon Weickert is currently involved with

CURRENT PROJECTS

Raloxifene treatment in Maternal Immune Activation model of Schizophrenia

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.

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Raloxifene treatment in Maternal Immune Activation model of Schizophrenia

Identification and characterisation of ST8SIA2: a generalised mental illness susceptibility gene

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.

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Identification and characterisation of ST8SIA2: a generalised mental illness susceptibility gene

Neuregulin Dependent Neuronal Migration and Schizophrenia

The path to developing therapies to prevent schizophrenia involves research on how risk genes influence brain development and structure.

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Neuregulin Dependent Neuronal Migration and Schizophrenia

Enhancing Neurogenesis in Adult Primate Brain

Since brain disease often involves neuronal death, research into strategies to restore neuronal numbers could lead to improved function and recovery in patients.

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Enhancing Neurogenesis in Adult Primate Brain

RESEARCH TEAM

PUBLICATIONS

Overexpression of Neuregulin 1 Type III Confers Hippocampal mRNA Alterations and Schizophrenia-Like Behaviors in Mice.

Olaya JC, Heusner CL, Matsumoto M, Sinclair D, Kondo MA, Karl T, Shannon Weickert C

Neuregulin 1 (NRG1) is a schizophrenia candidate gene whose protein product is involved in neuronal migration, survival, and synaptic plasticity via production of specific isoforms. Importantly, NRG1 type III (NRG1 III) mRNA is increased in humans inheriting a schizophrenia risk haplotype for the NRG1 gene (HapICE), and NRG1 protein levels can be elevated in schizophrenia. The nature by which NRG1 type III overexpression results in schizophrenia-like behavior and brain pathology remains unclear, therefore we constructed a transgenic mouse with Nrg1 III overexpression in forebrain neurons (CamKII kinase+). Here, we demonstrate construct validity for this mouse model, as juvenile and adult Nrg1 III transgenic mice exhibit an overexpression of Nrg1 III mRNA and Nrg1 protein in multiple brain regions. Furthermore, Nrg1 III transgenic mice have face validity as they exhibit schizophrenia-relevant behavioral phenotypes including deficits in social preference, impaired fear-associated memory, and reduced prepulse inhibition. Additionally, microarray assay of hippocampal mRNA uncovered transcriptional alterations downstream of Nrg1 III overexpression, including changes in serotonin receptor 2C and angiotensin-converting enzyme. Transgenic mice did not exhibit other schizophrenia-relevant behaviors including hyperactivity, social withdrawal, or an increased vulnerability to the effects of MK-801 malate. Our results indicate that this novel Nrg1 III mouse is valid for modeling potential pathological mechanisms of some schizophrenia-like behaviors, for determining what other neurobiological changes may be downstream of elevated NRG1 III levels and for preclinically testing therapeutic strategies that may be specifically efficacious in patients with the NRG1 (HapICE) risk genotype.

Considering the role of adolescent sex steroids in schizophrenia.

Owens SJ, Murphy CE, Purves-Tyson TD, Weickert TW, Shannon Weickert C

Schizophrenia is a disabling illness that is typically first diagnosed during late adolescence to early adulthood, has an unremitting course, and is often treatment resistance. Many clinical aspects of the illness suggest that sex steroid-nervous system interactions may contribute to the onset and course of symptoms and the cognitive impairment displayed by men and women with schizophrenia. Here, we discuss the actions of estrogen and testosterone on the brain during adolescent development and in schizophrenia from the perspective of experimental studies in animals, human post-mortem studies, magnetic resonance imaging studies in living humans, and clinical trials of sex steroid based treatments. We present evidence of potential beneficial, as well as detrimental, effects of both testosterone and estrogen. We provide a rationale for the necessity to further elucidate sex steroid mechanisms of action at different ages, genders and brain regions to more fully understand the role of testosterone and estrogen in the pathophysiology of schizophrenia. The weight of the evidence suggests that sex steroid hormones influence mammalian brain function, including both cognition and emotion and that pharmaceutical agents aimed at sex steroid receptors appear to provide a novel treatment avenue to reduce symptoms and improve cognition in men and women with schizophrenia. This article is protected by copyright. All rights reserved.

Considering the role of adolescent sex steroids in schizophrenia.

Owens SJ, Murphy CE, Purves-Tyson TD, Weickert TW, Shannon Weickert C

Schizophrenia is a disabling illness that is typically first diagnosed during late adolescence to early adulthood, has an unremitting course, and is often treatment resistance. Many clinical aspects of the illness suggest that sex steroid-nervous system interactions may contribute to the onset and course of symptoms and the cognitive impairment displayed by men and women with schizophrenia. Here, we discuss the actions of estrogen and testosterone on the brain during adolescent development and in schizophrenia from the perspective of experimental studies in animals, human post-mortem studies, magnetic resonance imaging studies in living humans, and clinical trials of sex steroid based treatments. We present evidence of potential beneficial, as well as detrimental, effects of both testosterone and estrogen. We provide a rationale for the necessity to further elucidate sex steroid mechanisms of action at different ages, genders and brain regions to more fully understand the role of testosterone and estrogen in the pathophysiology of schizophrenia. The weight of the evidence suggests that sex steroid hormones influence mammalian brain function, including both cognition and emotion and that pharmaceutical agents aimed at sex steroid receptors appear to provide a novel treatment avenue to reduce symptoms and improve cognition in men and women with schizophrenia. This article is protected by copyright. All rights reserved.

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