Samantha Owens

RESEARCHER PROFILE

PhD Student

+61 93991749


Samantha completed a Bachelor of Advanced Science at the University of New South Wales in 2012. She completed her honours project at the Schizophrenia Research Laboratory where she examined sex steroid modulation of dopamine signalling molecules in the nigrostriatal pathway of adolescent rats. Samantha returned to the Schizophrenia Research Laboratory in 2015 as a PhD candidate after travelling overseas. Her PhD project builds on her previous work and involves examining the dysregulation of both sex-steroid signalling and dopaminergic pathways and how this contributes to the pathophysiology of schizophrenia.

RESEARCH TEAM

PUBLICATIONS

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.

Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain.

Purves-Tyson TD, Owens SJ, Rothmond DA, Halliday GM, Double KL, Stevens J, McCrossin T, Shannon Weickert C

The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes. Gene expression of 12 dopamine-related molecules was examined in post-mortem midbrain (28 antipsychotic-treated schizophrenia cases/29 controls) using quantitative PCR. TH and the synaptic dopamine transporter (DAT) proteins were examined in post-mortem midbrain (26 antipsychotic-treated schizophrenia cases per 27 controls) using immunoblotting. TH and aromatic acid decarboxylase (AADC) mRNA and TH protein were unchanged in the midbrain in schizophrenia compared with controls. Dopamine receptor D2 short, vesicular monoamine transporter (VMAT2) and DAT mRNAs were significantly decreased in schizophrenia, with no change in DRD3 mRNA, DRD3nf mRNA and DAT protein between diagnostic groups. However, DAT protein was significantly increased in putatively treatment-resistant cases of schizophrenia compared to putatively treatment-responsive cases. Midbrain monoamine oxidase A (MAOA) mRNA was increased, whereas MAOB and catechol-O-methyl transferase mRNAs were unchanged in schizophrenia. We conclude that, whereas some mRNA changes are consistent with increased dopamine action (decreased DAT mRNA), others suggest reduced dopamine action (increased MAOA mRNA) in the midbrain in schizophrenia. Here, we identify a molecular signature of dopamine dysregulation in the midbrain in schizophrenia that mainly includes gene expression changes of molecules involved in dopamine synthesis and in regulating the time course of dopamine action.

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