Assoc Prof Tom Weickert

Rethinking schizophrenia in the context of normal neurodevelopment.

Catts VS, Fung SJ, Long LE, Joshi D, Vercammen A, Allen KM, Fillman SG, Rothmond DA, Sinclair D, Tiwari Y, Tsai SY, Weickert TW, Shannon Weickert C

Front Cell Neurosci. 2013 ;7():60. doi: 23720610. Epub 2013 May.

The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood, or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular, and behavioral events on a similar time line. We first consider the time at which human cognitive abilities such as selective attention, working memory, and inhibitory control mature, emphasizing that attainment of full adult potential is a process requiring decades. We review the timing of neurogenesis, neuronal migration, white matter changes (myelination), and synapse development. We consider how molecular changes in neurotransmitter signaling pathways are altered throughout life and how they may be concomitant with cellular and cognitive changes. We end with a consideration of how the response to drugs of abuse changes with age. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation, and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in adolescence. Updating our current understanding of post-natal neurodevelopment should aid researchers in interpreting gray matter changes and derailed neurodevelopmental processes that could underlie emergence of psychosis.

Considering the role of adolescent sex steroids in schizophrenia.

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

J. Neuroendocrinol.. 2017 Sep;():. doi: 28941299. Epub 2017 Sep.

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

J. Neuroendocrinol.. 2017 Sep;():. doi: 28941299. Epub 2017 Sep.

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.