Psychiatry - Research Publications

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    Deserves a hearing? A case report of remitting tinnitus with N-acetyl cysteine
    Dean, OM ; Jeavons, S ; Malhi, GS ; Cotton, SM ; Tanious, M ; Kohlmann, K ; Hewitt, K ; Moss, K ; Allwang, C ; Schapkaitz, I ; Robbins, J ; Dodd, S ; Bush, A ; Berk, M (IN HOUSE PUBLICATIONS, 2013-07)
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    Oxidative stress and inflammatory markers are associated with depression and nicotine dependence
    Vargas, HO ; Vargas Nunes, SO ; Pizzo de Castrob, MR ; Vargas, MM ; Barbosa, DS ; Bortolasci, CC ; Venugopal, K ; Dodd, S ; Berk, M (ELSEVIER IRELAND LTD, 2013-06-07)
    To determine if oxidative stress and inflammation are linked with major depressive disorder, nicotine dependence and both disorders combined. This study comprised 150 smokers and 191 never smokers. The instruments were: a socio-demographic questionnaire, diagnoses of mood disorder and nicotine dependence according to DSM-IV, (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Laboratory assessments included: nitric oxide metabolites (NOx), lipid hydroperoxides, malondialdehyde (MDA), total reactive antioxidant potential (TRAP), advanced oxidation protein products (AOPP), fibrinogen concentrations, homocysteine, erythrocytes sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP) were assayed from blood specimens. Statistically significant differences were found among depressed smokers who had more severe depressive symptoms, a higher risk of alcohol consumption, more suicide attempts, and more disability for work than non-depressed never smokers. Depressed smokers had significantly higher levels of NOx, fibrinogen, hs-CRP, AOPP, ESR and lower levels of TRAP compared to non-depressed never smokers. Depressed smokers had significant levels of oxidative stress and inflammatory biomarkers after adjusting for gender, age, years of education, disability for work, and laboratory measures. The levels of NOx, lipid hydroperoxides, AOPP, and fibrinogen were substantially higher, whereas levels of TRAP were lower in depressed smokers compared to non-depressed never smokers. (1) Depressed smokers exhibited altered concentrations of NOx, lipid hydroperoxides, AOPP, TRAP, and fibrinogen. (2) Depressed smokers were more unable to work, showed more severe depressive symptoms and attempted suicide more frequently.
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    The shared role of oxidative stress and inflammation in major depressive disorder and nicotine dependence
    Vargas Nunes, SO ; Vargas, HO ; Prado, E ; Barbosa, DS ; de Melo, LP ; Moylan, S ; Dodd, S ; Berk, M (PERGAMON-ELSEVIER SCIENCE LTD, 2013-09)
    Nicotine dependence is common in people with mood disorders; however the operative pathways are not well understood. This paper reviews the contribution of inflammation and oxidative stress pathways to the co-association of depressive disorder and nicotine dependence, including increased levels of pro-inflammatory cytokines, increased acute phase proteins, decreased levels of antioxidants and increased oxidative stress. These could be some of the potential pathophysiological mechanisms involved in neuroprogression. The shared inflammatory and oxidative stress pathways by which smoking may increase the risk for development of depressive disorders are in part mediated by increased levels of pro-inflammatory cytokines, diverse neurotransmitter systems, activation the hypothalamic-pituitary-adrenal (HPA) axis, microglial activation, increased production of oxidative stress and decreased levels of antioxidants. Depressive disorder and nicotine dependence are additionally linked imbalance between neuroprotective and neurodegenerative metabolites in the kynurenine pathway that contribute to neuroprogression. These pathways provide a mechanistic framework for understanding the interaction between nicotine dependence and depressive disorder.
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    Putative neuroprotective agents in neuropsychiatric disorders
    Dodd, S ; Maes, M ; Anderson, G ; Dean, OM ; Moylan, S ; Berk, M (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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    Biomarkers in bipolar disorder: A positional paper from the International Society for Bipolar Disorders Biomarkers Task Force
    Frey, BN ; Andreazza, AC ; Houenou, J ; Jamain, S ; Goldstein, BI ; Frye, MA ; Leboyer, M ; Berk, M ; Malhi, GS ; Lopez-Jaramillo, C ; Taylor, VH ; Dodd, S ; Frangou, S ; Hall, GB ; Fernandes, BS ; Kauer-Sant'Anna, M ; Yatham, LN ; Kapczinski, F ; Young, LT (SAGE PUBLICATIONS LTD, 2013-04)
    Although the etiology of bipolar disorder remains uncertain, multiple studies examining neuroimaging, peripheral markers and genetics have provided important insights into the pathophysiologic processes underlying bipolar disorder. Neuroimaging studies have consistently demonstrated loss of gray matter, as well as altered activation of subcortical, anterior temporal and ventral prefrontal regions in response to emotional stimuli in bipolar disorder. Genetics studies have identified several potential candidate genes associated with increased risk for developing bipolar disorder that involve circadian rhythm, neuronal development and calcium metabolism. Notably, several groups have found decreased levels of neurotrophic factors and increased pro-inflammatory cytokines and oxidative stress markers. Together these findings provide the background for the identification of potential biomarkers for vulnerability, disease expression and to help understand the course of illness and treatment response. In other areas of medicine, validated biomarkers now inform clinical decision-making. Although the findings reviewed herein hold promise, further research involving large collaborative studies is needed to validate these potential biomarkers prior to employing them for clinical purposes. Therefore, in this positional paper from the ISBD-BIONET (biomarkers network from the International Society for Bipolar Disorders), we will discuss our view of biomarkers for these three areas: neuroimaging, peripheral measurements and genetics; and conclude the paper with our position for the next steps in the search for biomarkers for bipolar disorder.
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    The sick role, illness cognitions and outcomes in bipolar disorder
    BERK, MICHAEL ; BERK, LESLEY ; DODD, SEETAL ; FITZGERALD, PAUL B ; de Castella, Anthony R ; Filia, Sachia ; FILIA, KATE ; Brnabic, Alan JM ; Kelin, Katerina ; Montgomery, William ; KULKARNI, JAYASHRI ; STAFFORD, LESLEY ( 2013)
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    Metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking N-acetyl-cysteine versus placebo
    DAS, PRITHA ; TANIOUS, MICHELLE ; FRITZ, KRISTINA ; DODD, SEETAL ; DEAN, OLIVIA ; BERK, MICHAEL ; MALHI, GIN S ( 2013)