Research Fellow, NeuRA
Associate Professor, School of Psychiatry, UNSW
+61 2 9399 1730
Assoc Prof Thomas Weickert received a BA in Biology from Kean University, USA and while at the Graduate School of the City University of New York (CUNY) where his studies focused on Cognition, he received an MA, an MPhil, and a PhD in Psychology. He was an Adjunct Lecturer in Psychology at Hunter College. He has received several undergraduate and graduate level academic and research awards. His dissertation work on memory deficits in healthy ageing and Alzheimer’s disease was conducted at the New York University Medical Center in Manhattan where he also worked as an assistant research scientist. He received an Intramural Research Training Award Fellowship to study cognitive deficits in schizophrenia at the National Institute of Mental Health in Bethesda, MD, USA. His research has resulted in over 45 peer-reviewed publications, which have over 1800 citations and appear in well-respected scientific journals. His first publication alone has generated over 300 citations. He is a co-author of chapters in two Psychiatry textbooks. He has been a research mentor to well over 20 students. He is a member of many scientific organisations. He is an Associate Editor of Frontiers in Psychiatry and a reviewer of grant applications and manuscripts submitted to many scientific journals. He has presented his work at many national and international scientific meetings.
DR DANIEL PELLEN Research Officer
DR CLIVE STANTON Visiting Research Officer
ELLEN JI PhD student
ISABELLA JACOMB Research Assistant
RUTH WELLS Visiting Research Assistant
CYNTHIA LEE Honours student
CAITLIN MURPHY Honours student
YIJUN GAO Honours student
SUN KIM ILP student
Evidence suggests that anomalous mismatch negativity (MMN) in schizophrenia is related to glutamatergic abnormalities, possibly involving N-methyl-d-aspartate (NMDA) receptors. Decreased cortical expressions of NMDA receptor subunits have been observed in schizophrenia, though not consistently. To aid with integration and interpretation of previous work, we performed a meta-analysis of effect sizes of mRNA or protein levels of the obligatory NR1 subunit in prefrontal cortex from people with schizophrenia. In schizophrenia compared to unaffected controls the pooled effect size was -0.64 (95% confidence interval: -1.08 to -0.20) for NR1 mRNA reduction and -0.44 (95% confidence interval: -0.80 to -0.07) for NR1 protein reduction. These results represent the first step to a deeper understanding of the region-specific, cell-specific, and stage-specific NMDA receptor hypofunction in schizophrenia, which could be linked to mismatch negativity deficits via transgenic and pharmacological animal models.
Cognitive deficits are prevalent in schizophrenia, and these deficits represent a disabling aspect of the illness for which there are no current effective treatments. Recent work has shown that sex hormone levels correlate with brain activity and cognitive abilities differentially in patients with schizophrenia relative to healthy control groups. There is emerging evidence suggesting that oestrogen-based therapies may be useful in reversing the cognitive deficits associated with schizophrenia. To date, the results from clinical trials using oestrogen-based therapies to reverse cognitive impairment in schizophrenia have shown that the selective oestrogen receptor modulator raloxifene may be useful to improve attention, memory, learning and the associated brain activity in chronically ill men and women with schizophrenia or schizoaffective disorder. While these findings of cognitive enhancement with a selective oestrogen receptor modulator in people with schizophrenia are encouraging, additional studies will be required to replicate the initial results, assess the time frame of treatment effects, identify biomarkers in subsets of patients who may be more likely to optimally respond to treatment, and identify a more precise mechanism of action, which may include anti-inflammatory effects of oestrogen-based treatments.
Sex hormones impact reward processing, which is dysfunctional in schizophrenia; however, the degree to which testosterone levels relate to reward-related brain activity in healthy men and the extent to which this relationship may be altered in men with schizophrenia has not been determined. We used functional magnetic resonance imaging (fMRI) to measure neural responses in the striatum during reward prediction-errors and hormone assays to measure testosterone and prolactin in serum. To determine if testosterone can have a direct effect on dopamine neurons, we also localized and measured androgen receptors in human midbrain with immunohistochemistry and quantitative PCR. We found correlations between testosterone and prediction-error related activity in the ventral striatum of healthy men, but not in men with schizophrenia, such that testosterone increased the size of positive and negative prediction-error related activity in a valence-specific manner. We also identified midbrain dopamine neurons that were androgen receptor immunoreactive, and found that androgen receptor (AR) mRNA was positively correlated with tyrosine hydroxylase (TH) mRNA in human male substantia nigra. The results suggest that sex steroid receptors can potentially influence midbrain dopamine biosynthesis, and higher levels of serum testosterone are linked to better discrimination of motivationally-relevant signals in the ventral striatum, putatively by modulation of the dopamine biosynthesis pathway via AR ligand binding. However, the normal relationship between serum testosterone and ventral striatum activity during reward learning appears to be disrupted in schizophrenia.