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
ISABELLA JACOMB Research Assistant
RUTH WELLS Visiting Research Assistant
ALICE ZHEN Research Assistant : firstname.lastname@example.org
CYNTHIA LEE PhD Candidate
HINA SALIMUDDIN Honours Student : email@example.com
MELANIE MORA Honours Student : firstname.lastname@example.org
The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265 influences learning and may represent a risk factor for schizophrenia. Healthy people with high schizotypal personality traits display cognitive deficits that are similar to but not as severe as those observed in schizophrenia and they can be studied without confounds of antipsychotics or chronic illness. How genetic variation in BDNF may impact learning in individuals falling along the schizophrenia spectrum is unknown. We predicted that schizotypal personality traits would influence learning and that schizotypal personality-based differences in learning would vary depending on the BDNF val66met genotype. Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire (SPQ) and a probabilistic association learning test. Blood samples were genotyped for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype (val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables and probabilistic association learning as the dependent variable. Participants with low SPQ scores (fewer schizotypal personality traits) showed significantly better learning than those with high SPQ scores. BDNF met-carriers displaying few schizotypal personality traits performed best, whereas BDNF met-carriers displaying high schizotypal personality traits performed worst. Thus, the BDNF val66met polymorphism appears to influence probabilistic association learning differently depending on the extent of schizotypal personality traits displayed.
Blockade of N-methyl-D-aspartate receptors (NMDARs) produces behavior in healthy people that is similar to the psychotic symptoms and cognitive deficits of schizophrenia and can exacerbate symptoms in people with schizophrenia. However, an endogenous brain disruption of NMDARs has not been clearly established in schizophrenia. We measured mRNA transcripts for five NMDAR subunit mRNAs and protein for the NR1 subunit in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and control (n=74) brains. Five NMDAR single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia were tested for association with NMDAR mRNAs in postmortem brain and for association with cognitive ability in an antemortem cohort of 101 healthy controls and 48 people with schizophrenia. The NR1 subunit (mRNA and protein) and NR2C mRNA were decreased in postmortem brain from people with schizophrenia (P=0.004, P=0.01 and P=0.01, respectively). In the antemortem cohort, the minor allele of NR2B rs1805502 (T5988C) was associated with significantly lower reasoning ability in schizophrenia. In the postmortem brain, the NR2B rs1805502 (T5988C) C allele was associated with reduced expression of NR1 mRNA and protein in schizophrenia. Reduction in NR1 and NR2C in the DLPFC of people with schizophrenia may lead to altered NMDAR stoichiometry and provides compelling evidence for an endogenous NMDAR deficit in schizophrenia. Genetic variation in the NR2B gene predicts reduced levels of the obligatory NR1 subunit, suggesting a novel mechanism by which the NR2B SNP may negatively influence other NMDAR subunit expression and reasoning ability in schizophrenia.
The results suggest that circulating sex steroids may modulate cognitive deficits associated with schizophrenia.