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Neuroprotection

Research Leader

Colin O' Donnell

Current Studies

Multi-centre Study of the Effect of Taurine on cognition and symptoms in 128 patients with first episode psychosis. 

(CI: Dr O’Donnell, RAs: Nguyen, Moral)

ORC was awarded a grant from the Stanley Medical Research Institute to examine taurine, an amino acid, as Taurine levels are are shown to be lowered in the cerebrospinal fluid of patients with schizophrenia. Among the many functions of Taurine that may be beneficial in first episode psychosis are membrane stabilisation, reactive-radical scavenging, oxidative stress and neurotransmission. This study is investigating the effects of taurine on cognition and symptomatology in a double blind randomized controlled trial in 128 young people experiencing their first psychotic episode. The trial is currently recruiting in OYH and Southern Health, RAPP’s first episode clinic in Dandenong. The additional site was set up to augment recruitment at OYH, EPPIC.

Vitamins in Psychosis

(CI: Dr O’Donnell, RAs: Papas, Moral)

The use of certain vitamins in human subjects is thought to effect levels of a naturally occurring substance, homocysteine.  In previous studies of patients with chronic illness it has been shown that homocysteine levels are raised.  Raised levels are thought to be neurotoxic causing impaired cognitive dysfunction.  The core aim of this study is to determine whether cognition can be enhanced in patients with stabilized psychosis by lowering their levels of homocysteine with the use of vitamins.  Recruitment is complete with a total of 120 first-episode psychosis patients randomised to a vitamin B pill (high dose folic acid with vitamins B6, B12) or placebo (double-blind placebo-controlled design) in addition to antipsychotic medication and standard treatment through OYH. Patients have undergone cognitive assessment and neuroimaging in addition to a battery of psychopathology testing.

Females improved significantly on both the primary outcome composite cognition score and on the secondary outcome depression scores, however no benefit was found for males, who, a priori we had considered more likely to benefit from homocysteine lowering. No effect was found for psychotic symptoms. The improvement in depressive symptoms as measured by the CDSS is consistent with the previous literature in depressive disorders that indicates a possible beneficial effect of folate supplementation on the symptoms of depression. These interesting results indicate a possible benefit in females, of folate augmentation/homocysteine lowering in the treatment of cognitive dysfunction associated with psychosis.

We have also completed and are conducting other neurobiological projects utilising the blood samples (around 200 patients plus controls) and phenotypic data collected from patients and normal healthy controls over the past 4 years during the course of the above 2 projects:

  1. Nutrition in first episode psychosis- We have completed the first phase of collecting food frequency questionnaires from a cohort of first episode patients and healthy controls. The second phase involves more in-depth face-to-face diet assessments with a sub-group to validate the food frequency questionnaire in our population. These interviews are being conducted by a dietician from the Royal Children’s Hospital and the data is being analyzed by food scientists, Prof Andrew Sinclair and Melanie Voerudin.
  2. Folate metabolism genetics- We have analyzed over 40 single nucleotide polymorphisms of the one carbon (folate) cycle. We found 5 new polymorphisms associated with psychosis. We have replicated our findings in a separate sample from the Murdoch Research Institute.
  3. Methylation Analysis- We collected blood samples from VIP participants at the beginning and the end of the VIP trial. We are analyzing these samples for methylation changes, in collaboration with the Murdoch Research Institute with the aid of a grant from the Jack Brockhoff institute.
  4. Autoimmune antibodies- In collaboration with the University of Melbourne, we are conducting preliminary work on the role of autoantibodies in schizophrenia.
  5. We have completed a compliance monitoring project utilizing electronic pill cap monitors, both for antipsychotics and for the use of trial medication.
  6. We are extending the above research to examine the influence of cytochrome polymorphisms on outcome and have received an investigator initiated grant from Janssen to examine these pharmacogenetic factors. Eli Lilly and Astra-Zeneca are also interested in funding this study and we have submitted further information to them for consideration.
  7. We have also completed a study of the prevalence of folate, red blood cell folate, B12, B6 and homocysteine deficiencies, utilizing results from 1000 ORYGEN patients and 16,000 Controls. These results indicate that folate is significantly lower in schizophrenia, schizophreniform disorder and depressive disorder, and depression with psychosis compared to other diagnoses.
  8. We are also collaborating with Melbourne Neuropsychiatry Centre and have scanned participants from both the VIP and the ongoing Taurine study. Some initial results form these studies include a finding from DTI scanning that white matter changes evident in chronic schizophrenia are not present in early psychosis.

A naturalistic, prospective, single-centre, double-blinded, fixed-dose, randomised, four-week comparison study investigating efficacy, tolerability and safety of 200 versus 400mg quetiapine fumarate in 120 drug-naïve first-episode Psychosis patients aged 15–25 years

(CI: Dr Berger, RAs(past): McConchie, Kerr, Markulev)

Quetiapine has demonstrated clinical efficacy in patients with chronic schizophrenia at the dose range of 300–750mg per day. The primary aim is to compare the efficacy of two low doses of quetiapine in drug-naïve, first-episode psychosis patients. It is essentially a dose-finding study in first episode psychosis. To this end, the study is examining whether or not the provision of initial lower doses results in higher final maintenance doses, the increased likelihood of benzodiazepine use or more frequent changes to other antipsychotic medication. In addition to a number of psychopathological assessments and the administration of scales to measure side effects, consenting patients underwent serial neuroimaging. This will allow study of possible neuroprotective effects of quetiapine, which has been shown to possess these properties in laboratory studies.  This study’s recruitment and followup of 120 patients from the EPPIC program is now completed and has provided a large data set for the study of the effects of low dose therapy and neuroprotection.  Data analysis is now underway and a series of publications are planned.  A paper reporting the results of this study has been submitted to the Journal Neuropsychopharmacology and is under review.