Psychiatry - Research Publications
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ItemCingulate biochemistry in heroin users on substitution pharmacotherapy(SAGE PUBLICATIONS LTD, 2013-03)OBJECTIVE: High doses of opiate substitution pharmacotherapy are associated with greater treatment retention and lower illicit drug consumption, although the neurobiological bases of these benefits are poorly understood. Dysfunction of the anterior cingulate cortex (ACC) is associated with greater addiction severity and mood dysregulation in opiate users, such that the beneficial effects of substitution pharmacotherapy may relate to normalisation of ACC function. This study aimed to investigate the differential impact of methadone compared with buprenorphine on dorsal ACC biochemistry. A secondary aim was to explore the differential effects of methadone and buprenorphine on dorsal ACC biochemistry in relation to depressive symptoms. METHODS: Twenty-four heroin-dependent individuals stabilised on methadone (n=10) or buprenorphine (n=14) and 24 healthy controls were scanned using proton Magnetic Resonance Spectroscopy and compared for metabolite concentrations of N-acetylaspartate, glutamate/glutamine, and myo-inositol. RESULTS: (1) Methadone was associated with normalisation of dorsal ACC biochemistry (increased N-acetylaspartate and glutamate/glutamine levels, and decreased myo-inositol levels) in a dose-dependent manner; (2) buprenorphine-treated individuals had higher myo-inositol and glutamate/glutamine levels than methadone-treated patients in the right dorsal ACC; and (3) myo-inositol levels were positively correlated with depressive symptoms in participants stabilised on buprenorphine. CONCLUSIONS: These findings point to a beneficial role of high-dose methadone on dorsal ACC biochemistry, and suggest a link between elevated myo-inositol levels and depressive symptoms in the context of buprenorphine treatment.
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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)Objective To be used in conjunction with ‘Psychological management of unipolar depression’ [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24–37] and ‘Lifestyle management of unipolar depression’ [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38–54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review. Method Using our previous Clinical Practice Guidelines [Malhi et al. Clinical practice recommendations for bipolar disorder. Acta Psychiatr Scand 2009;119(Suppl. 439):27–46] as a foundation, these clinician guidelines target key practical considerations when prescribing pharmacotherapy. A comprehensive review of the literature was conducted using electronic database searches (PubMed, MEDLINE), and the findings have been synthesized and integrated alongside clinical experience. Results The pharmacotherapy of depression is an iterative process that often results in partial and non‐response. Beyond the initiation of antidepressants, the options within widely used strategies, such as combining agents and switching between agents, are difficult to proscribe because of the paucity of pertinent research. However, there is some evidence for second‐line strategies, and a non‐prescriptive algorithm can be derived that is based broadly on principles rather than specific steps. Conclusion Depression is by its very nature a heterogeneous illness that is consequently difficult to treat. Invariably, situation‐specific factors often play a significant role and must be considered, especially in the case of partial and non‐response. Consulting with colleagues and trialling alternate treatment paradigms are essential strategies in the management of depression.
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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.