Psychiatry - Research Publications
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ItemA randomised, controlled trial of a dietary intervention for adults with major depression (the "SMILES" trial): study protocol(BMC, 2013-04-15)BACKGROUND: Despite increased investment in its recognition and treatment, depression remains a substantial health and economic burden worldwide. Current treatment strategies generally focus on biological and psychological pathways, largely neglecting the role of lifestyle. There is emerging evidence to suggest that diet and nutrition play an important role in the risk, and the genesis, of depression. However, there are limited data regarding the therapeutic impact of dietary changes on existing mental illness. Using a randomised controlled trial design, we aim to investigate the efficacy and cost-efficacy of a dietary program for the treatment of Major Depressive Episodes (MDE). METHODS/DESIGN: One hundred and seventy six eligible participants suffering from current MDE are being randomised into a dietary intervention group or a social support group. Depression status is assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (Non Patient Edition) (SCID-I/NP). The intervention consists of 7 individual nutrition consulting sessions (of approximately 60 minutes), delivered by an Accredited Practising Dietitian (APD). Sessions commence within one week of baseline assessment. The intervention focuses on advocating a healthy diet based on the Australian Dietary Guidelines and the Dietary Guidelines for Adults in Greece. The control condition comprises a befriending protocol using the same visit schedule and length as the diet intervention. The study is being conducted at two locations in Victoria, Australia (a metropolitan and regional centre). Data collection occurs at baseline (pre-intervention), 3-months (post-intervention) and 6- months. The primary endpoint is MADRS scores at 3 months. A cost consequences analysis will determine the economic value of the intervention. DISCUSSION: If efficacious, this program could provide an alternative or adjunct treatment strategy for the management of this highly prevalent mental disorder; the benefits of which could extend to the management of common co-morbidities including cardiovascular disease (CVD), obesity, and type 2 diabetes. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820.
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ItemAspirin: a review of its neurobiological properties and therapeutic potential for mental illness(BMC, 2013-03-18)There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor-α and interleukin (IL)--6, but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.
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ItemDeserves a hearing? A case report of remitting tinnitus with N-acetyl cysteine(IN HOUSE PUBLICATIONS, 2013-07)
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ItemThe chemistry and biological activities of N-acetylcysteine(ELSEVIER, 2013-08)BACKGROUND: N-acetylcysteine (NAC) has been in clinical practice for several decades. It has been used as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication, doxorubicin cardiotoxicity, ischemia-reperfusion cardiac injury, acute respiratory distress syndrome, bronchitis, chemotherapy-induced toxicity, HIV/AIDS, heavy metal toxicity and psychiatric disorders. SCOPE OF REVIEW: The mechanisms underlying the therapeutic and clinical applications of NAC are complex and still unclear. The present review is focused on the chemistry of NAC and its interactions and functions at the organ, tissue and cellular levels in an attempt to bridge the gap between its recognized biological activities and chemistry. MAJOR CONCLUSIONS: The antioxidative activity of NAC as of other thiols can be attributed to its fast reactions with OH, NO2, CO3(-) and thiyl radicals as well as to restitution of impaired targets in vital cellular components. NAC reacts relatively slowly with superoxide, hydrogen-peroxide and peroxynitrite, which cast some doubt on the importance of these reactions under physiological conditions. The uniqueness of NAC is most probably due to efficient reduction of disulfide bonds in proteins thus altering their structures and disrupting their ligand bonding, competition with larger reducing molecules in sterically less accessible spaces, and serving as a precursor of cysteine for GSH synthesis. GENERAL SIGNIFICANCE: The outlined reactions only partially explain the diverse biological effects of NAC, and further studies are required for determining its ability to cross the cell membrane and the blood-brain barrier as well as elucidating its reactions with components of cell signaling pathways.
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ItemPutative neuroprotective agents in neuropsychiatric disorders(PERGAMON-ELSEVIER SCIENCE LTD, 2013-04-05)In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders.
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