Psychiatry - Research Publications
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ItemChronic adrenocorticotrophic hormone treatment alters tricyclic antidepressant efficacy and prefrontal monoamine tissue levels(ELSEVIER, 2013-04-01)Several animal models are currently utilised in the investigation of major depressive disorder; however, each is validated by its response to antidepressant pharmacotherapy. Few animal models consider the notion of antidepressant treatment resistance. Chronic daily administration of adrenocorticotropic hormone (ACTH) or corticosterone can alter behavioural responses to antidepressants, effectively blocking antidepressant efficacy. Herein, we demonstrate that ACTH-(1-24) (100μg/day; 14 days) blocks the immobility-reducing 'antidepressant' effects of a single dose of imipramine (10mg/kg) in the forced swim test. This finding was accompanied by altered monoamine tissue levels in the prefrontal cortex (PFC) 1h after exposure to the acute stress of the forced swim test. PFC tissue from ACTH pre-treated animals contained significantly higher serotonin, noradrenaline and adrenaline concentrations relative to saline pre-treated controls. Conversely, dopamine levels were significantly decreased. Altered plasma corticosterone responses to ACTH injections were observed over the treatment course. Measures were taken on treatment days 1, 4, 8, 11, 14 and 15. ACTH administration initially enhanced plasma corticosterone levels, however, these normalised to levels consistent with control animals by day 14. No differences in corticosterone levels were observed across the treatment time course in saline-treated animals. Taken together these results indicate that pre-treatment with ACTH (100μg/day; 14 days) blocks the antidepressant effects of imipramine (10mg/kg), significantly alters key PFC monoamine responses to stress and downregulates glucocorticoid responses. These results suggest that chronic ACTH treatment is a promising paradigm for elucidation of mechanisms mediating antidepressant treatment resistance.
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ItemPharmacological management of unipolar depression(WILEY, 2013-05-01)
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ItemSystematic Review of the Effectiveness of Pharmacologic Interventions to Improve Quality of Life and Well-being in People With Dementia(ELSEVIER SCIENCE INC, 2013-02-01)OBJECTIVE: To review systematically, for the first time, the effectiveness of all pharmacologic interventions to improve quality of life and well-being in people with dementia. DESIGN: Systematic review and meta-analysis. METHODS: We systematically reviewed the 15 randomized controlled trials and one review that fitted predetermined criteria. We included studies that reported the outcomes quality of life, well-being, happiness, or pleasure. MEASUREMENTS: We rated the validity of studies using a checklist. We calculated mean differences between intervention and control groups at follow-up. RESULTS: None of the evaluated trials reported a significant benefit to quality of life or well-being for people with dementia when comparing those taking a drug or its comparator at follow-up (pooled weighted mean difference: 0.18 [95% confidence interval: -0.82 to 0.46]). CONCLUSION: We found no consistent evidence that any drug improves quality of life in people with dementia. We recommend that all dementia trials should include quality of life as an outcome, as this is important to patients, and cannot be presumed from improvements in cognition or other symptomatic outcomes, especially if the latter are small.
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ItemChanges in long term neural connectivity following psychological trauma(ELSEVIER IRELAND LTD, 2009-02-01)OBJECTIVE: Neural connectivity differences between adults reporting childhood, adulthood or no history of trauma were examined. METHODS: A total of 39 participants completed the Post-traumatic Stress Diagnostic Scale (PDS; Foa EB. Post-traumatic Stress Diagnostic Scale (PDS) Manual. Minneapolis, MN: National Computer Systems, 1995), a Word Memory Task (WMT; [McNally RJ, Metzger LJ, Lasko NB, Clancy SA, Pitman RK. Directed forgetting of trauma cues in adult survivors of childhood sexual abuse with and without post-traumatic stress disorder. J Abnorm Psychol 1998;107:596-601]) and EEG analysis. Intelligence was not assessed during the study. RESULTS: As predicted, those with childhood trauma had significantly higher EEG coherence than those with either adulthood trauma or no past trauma. CONCLUSIONS: Significant differences were observed over frontal, central, temporal and parietal areas. Evidence was found suggesting that childhood psychological trauma may have a lasting impact on neuronal connectivity. SIGNIFICANCE: This is the first study to demonstrate the suspected long term effect of trauma over central, temporal and parietal areas. Long term neural correlates of childhood and adult trauma appear to suggest information processing differences--differences that may, eventually, lead to better interventions following trauma.