Special Lecture

  1. Special Lecture
  2. NP Special Lecture
  3. Clinical Research Educational Seminar
  4. Symposiums
  5. Prize for encouragement of the society
  6. Abroad
  7. Lunceon Seminar
  8. Evening Seminar
  9. Oral Abstracts
  10. Poster Abstracts

SL-1

Oxidative and immune biomarkers as targets for novel therapies

Michael Berk1,2,3,4,5
  1. Deakin University, School of Medicine, Geelong Australia,
  2. Barwon Health, Geelong, Australia,
  3. Orygen Youth Health Research Centre,
  4. The Florey Institute for Neuroscience and Mental Health,
  5. The Department of Psychiatry, University of Melbourne, Australia

There is abundant evidence that inflammatory and oxidative processes, altered neurogenesis and mitochondrial dysfunction play a role in the neuroprogression of mood and psychotic disorders. There is evidence of increased inflammatory activity across most major neuropsychiatric disorders. The brain is the most metabolically active tissue, and disruptions in mitochondrial energy generation are now well described in mood and psychotic disorders. Administration of proinflammatory cytokines is amongst the best models of depression. The consequences of inflammatory and oxidative stress include lipid peroxidation, DNA fragmentation protein carbonylation and an increased vulnerability to apoptosis. Inflammatory and oxidative stress leads to decreased BDNF and other trophic factors. Established antidepressants and mood stabilisers including lithium and valproate alter immune markers and additionally have a role in ameliorating oxidative stress. N-acetyl cysteine (NAC) is a precursor of glutathione, has anti-inflammatory properties and has been shown to reverse animal models of oxidative stress and mitochondrial dysfunction. Clinical data shows a significant benefit of NAC in psychosis, especially on negative symptoms, and on measures of depression, quality of life and functioning in mood disorders. Equally, statins, aspirin and NSAIDS have diverse roles in inflammatory modulation, and there is data that these agents may reduce risk for mood disorders. Such biomarker data have the potential to lead to the development of other novel therapies outside of traditional monoamine targets.

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SL-2

Stress and cognition: A critical role for the prefrontal cortex

Anthony G. Phillips1,2

  1. CINP President,
  2. Department of Psychiatry, University of British Columbia, Vancouver, Canada

Excessive stress is recognized as a major contributor to many neuropsychiatric conditions ranging from major depression to post-traumatic stress disorder. Indeed, disruption of cognitive and executive functions within the medial prefrontal cortex
(mPFC), by both chronic and acute stress, may constitute core features of these neuropsychiatric disorders. Following a review of evidence linking stress to mental illness, we will focus on hormonal and neurochemical mechanisms by which prolonged acute stress can disrupt cognitive functions mediated by the mPFC. Acute stress enhances dopamine efflux in the rat mPFC and this is reduced by blockade of glucocorticoid receptors in the mPFC but not in the ventral tegmental area (VTA). DA neurons in the VTA receive excitatory input from and send reciprocal projections to the mPFC. Blockade of prefrontal glucocorticoid receptors reduced activity of descending glutamatergic input to the VTA, thereby attenuating stress-evoked dopamine efflux in the mPFC. Acute tail-pinch stress also causes a significant increase in glutamate efflux in the VTA. Blockade of prefrontal glucocorticoid receptors with the selective antagonist CORT 108297 attenuates stress-evoked glutamate efflux in the VTA along with DA efflux in the mPFC. Furthermore, blockade of ionotrophic glutamate receptors in the VTA attenuates stress-evoked DA efflux in the mPFC. Taken together, our data indicate that glucocorticoids act locally within the mPFC to modulate mesocortical DA efflux by potentiation of glutamatergic drive onto dopamine neurons in the VTA.
Stress-enhanced dopamine efflux in the mPFC impairs cognitive functions. Notably, stress-induced impairments in cognition are attenuated by blockade of glucocorticoid receptors in the prefrontal cortex. The ability to update and modify previously learned behavioral responses in a changing environment is essential for optimizing reward and coping with adverse events. Valid models of cognitive flexibility include set-shifting and reversal learning and we show that exposure to acute stress significantly disrupts set-shifting but not reversal learning. These data indicate that acute stress impairs mPFC-dependent cognition selectively by disrupting inhibition the a previously relevant cognitive strategy. Together, these data support the use of glucocorticoid receptor antagonists as a valid target for treating impaired cognition in neuropsychiatric conditions influenced by the experience of adverse stress.

 

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  1. Special Lecture
  2. NP Special Lecture
  3. Clinical Research Educational Seminar
  4. Symposiums
  5. Prize for encouragement of the society
  6. Abroad
  7. Lunceon Seminar
  8. Evening Seminar
  9. Oral Abstracts
  10. Poster Abstracts