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Moylan S.,Deakin University | Maes M.,Piyavate Hospital | Wray N.R.,University of Queensland | Berk M.,Deakin University | And 3 more authors.
Molecular Psychiatry

In some patients with major depressive disorder (MDD), individual illness characteristics appear consistent with those of a neuroprogressive illness. Features of neuroprogression include poorer symptomatic, treatment and functional outcomes in patients with earlier disease onset and increased number and length of depressive episodes. In such patients, longer and more frequent depressive episodes appear to increase vulnerability for further episodes, precipitating an accelerating and progressive illness course leading to functional decline. Evidence from clinical, biochemical and neuroimaging studies appear to support this model and are informing novel therapeutic approaches. This paper reviews current knowledge of the neuroprogressive processes that may occur in MDD, including structural brain consequences and potential molecular mechanisms including the role of neurotransmitter systems, inflammatory, oxidative and nitrosative stress pathways, neurotrophins and regulation of neurogenesis, cortisol and the hypothalamic-pituitary-adrenal axis modulation, mitochondrial dysfunction and epigenetic and dietary influences. Evidence-based novel treatments informed by this knowledge are discussed. © 2013 Macmillan Publishers Limited All rights reserved. Source

Ruangkanchanasetr P.,Phramongkutklao Hospital | Mahanonda N.,Perfect Heart Institute | Raungratanaamporn O.,Perfect Heart Institute | Ruckpanich P.,Perfect Heart Institute | And 7 more authors.
BMC Nephrology

Background: Enhanced external counterpulsation (EECP) enhances coronary perfusion and reduces left ventricular afterload. However, the role of EECP on renal function in cardiac patients is unknown. Our aim was to assess renal function determined by serum cystatin C in cardiac patients before and after EECP treatment. Methods. A prospective observational longitudinal study was conducted in order to evaluate renal function using serum cystatin C (Cys C) and estimated glomerular filtration rate (GFR) after 35 sessions of EECP treatment in 30 patients with chronic stable angina and/or heart failure. The median (IQR) time for follow-up period after starting EECP treatment was 16 (10-24) months. Results: Cys C significantly declined from 1.00 (0.78-1.31) to 0.94 (0.77-1.27) mg/L (p < 0.001) and estimated GFR increased from 70.47 (43.88-89.41) to 76.27 (49.02-91.46) mL/min/1.73 m§ssup§2§esup§ (p = 0.006) after EECP treatment. Subgroup analysis showed that patients with baseline GFR <60 mL/min/1.73 m§ssup§2§esup§ or NT-proBNP >125 pg/mL had a significant decrease in Cys C when compared to other groups (p < 0.01). Conclusions: The study demonstrated that EECP could improve long-term renal function in cardiac patients especially in cases with declined renal function or with high NT-proBNP. Trial registration. The study was registered in the clinical trial as International Standard Randomized Controlled Trial Number ISRCTN11560035. © 2013 Ruangkanchanasetr et al.; licensee BioMed Central Ltd. Source

Anderson G.,CRC | Maes M.,Piyavate Hospital
Metabolic Brain Disease

This paper reviews melatonin as an overlooked factor in the developmental etiology and maintenance of schizophrenia; the neuroimmune and oxidative pathophysiology of schizophrenia; specific symptoms in schizophrenia, including sleep disturbance; circadian rhythms; and side effects of antipsychotics, including tardive dyskinesia and metabolic syndrome. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this review using keywords: schizophrenia, psychosis, tardive dyskinesia, antipsychotics, metabolic syndrome, drug side effects and melatonin. Articles were selected on the basis of relevance to the etiology, course and treatment of schizophrenia. Melatonin levels and melatonin circadian rhythm are significantly decreased in schizophrenic patients. The adjunctive use of melatonin in schizophrenia may augment the efficacy of antipsychotics through its anti-inflammatory and antioxidative effects. Further, melatoninwould be expected to improve sleep disorders in schizophrenia and side effects of anti-psychotics, such as tardive dyskinesia, metaboilic syndrome and hypertension. It is proposed that melatonin also impacts on the tryptophan catabolic pathway via its effect on stress response and cortisol secretion, thereby impacting on cortex associated cognition, amygdala associated affect and striatal motivational processing. The secretion of melatonin is decreased in schizophrenia, contributing to its etiology, pathophysiology and management. Melatonin is likely to have impacts on the metabolic side effects of anti-psychotics that contribute to subsequent decreases in life-expectancy. © Springer Science+Business Media, LLC 2012. Source

Kubera M.,Polish Academy of Sciences | Curzytek K.,Polish Academy of Sciences | Duda W.,Polish Academy of Sciences | Leskiewicz M.,Polish Academy of Sciences | And 12 more authors.
Brain, Behavior, and Immunity

Chronic activation of immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways plays an important role in the pathophysiology of clinical depression. Increased IgA responses directed against LPS of gram-negative bacteria, indicating increased bacterial translocation, may be one of the drivers underpinning these pathways. There is a strong association between signs of bacterial translocation and chronicity of depression and O&NS, but not pro-inflammatory cytokines.The aims of the present study were to: (1) develop a new neurobehavioral model of (chronic) depression (anhedonic behavior) that may reflect chronic LPS stimulation and is associated with increased oxidative stress, and (2) to delineate the effects of fluoxetine on this new depression model.We established that in female mice repeated LPS injections once daily for 5. days (from 750. μg/kg to a maximal dose 1250. μg/kg; increasing doses for the first three days which were then gradually decreased on day 4 and 5) at a one-month interval and this repeated for 4 consecutive months induced chronic anhedonia (estimated by the preference to drink a 1% sucrose) lasting for at least 7. weeks. Chronic LPS administration significantly decreased thymus weight, proliferative activity of splenocytes, production of interferon (IFN)γ and interleukin-(IL)10, and increased superoxide and corticosterone production. Treatment with fluoxetine for 3. weeks abolished the neurobehavioral effects of LPS. The antidepressant effect of fluoxetine was accompanied by increased production of IL-10 and reduced superoxide and corticosterone production.Our results suggest that repeated intermittent LPS injections to female mice may be a useful model of chronic depression and in particular for the depressogenic effects of long standing activation of the toll-like receptor IV complex. © 2013 Elsevier Inc. Source

Jacka F.N.,Deakin University | Jacka F.N.,University of Melbourne | Maes M.,Piyavate Hospital | Pasco J.A.,Deakin University | And 6 more authors.
Journal of Affective Disorders

Background: There is an increasing recognition of the role of nutrition in depression and anxiety. Magnesium, folate and zinc have all been implicated in depressive illness, however there are few data on these nutrients in anxiety disorders and the data from population-studies are limited. Aims: In a large, randomly-selected, population-based sample of women, this study aimed to examine the relationship between the dietary intakes of these three micronutrients and clinically determined depressive and anxiety disorders and symptoms. Methods: Nutrient intakes were determined using a validated food frequency questionnaire. The General Health Questionnaire-12 measured psychological symptoms, and a clinical interview (Structured Clinical Interview for DSM-IV-TR, non-patient edition) assessed current depressive and anxiety disorders. Results: After adjustments for energy intake, each standard deviation increase in the intake of zinc, magnesium and folate was associated with reduced odds ratio (OR) for major depression/dysthymia (zinc: OR = 0.52, 95% confidence interval (CI) 0.31 to 0.88; magnesium: OR = 0.60, 95% CI 0.37 to 0.96; folate: OR = 0.66, 95% CI 0.45 to 0.97). There was also an inverse association between the intake of magnesium and zinc and GHQ-12 scores (zinc: zβ = - 0.16, 95% CI - 0.29 to - 0.04; magnesium: - 0.14, 95% CI - 0.26 to - 0.03). These relationships were not confounded by age, socioeconomic status, education or other health behaviours. There was no relationship observed between any nutrient and anxiety disorders. Conclusion: These results demonstrate an association between the dietary intakes of magnesium, folate and zinc and depressive illnesses, although reverse causality and/or confounding cannot be ruled out as explanations. © 2012 Elsevier B.V. Source

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