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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 | Year: 2013

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.

Morris G.,Tir Na Nog | Berk M.,Deakin University | Berk M.,Orygen Youth Health Research Center | Berk M.,University of Melbourne | Berk M.,Royal Melbourne Hospital
BMC Medicine | Year: 2015

Background: Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson's disease, schizophrenia, depression, autism, and chronic fatigue syndrome. Discussion: While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson's disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines. Summary: This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders. © Berk and Morris; licensee BioMed Central.

McGorry P.,University of Melbourne | McGorry P.,Orygen Youth Health Research Center
Schizophrenia Bulletin | Year: 2011

There is an urgent need and a global opportunity to rethink not only the dominant research paradigms in etiological research but also to invest in less constrained strategies which cut across the existing diagnostic silos to seek out common risk factors, late as well as early neurodevelopmental processes, pathophysiologies, and novel treatment strategies. The high-quality research presented in this special issue of Schizophrenia Bulletin makes a compelling case for such a rethink. While there is still a genuine disconnect between our understanding of the complex and dramatic brain changes that occur during the transition to adulthood and the concurrent surge in incidence of mental ill-health, there is no doubt that a much more serious focus on the perionset stage of clinical disorders in young people with their rapidly evolving brains, social environments, and life trajectories could be extremely productive. Research access to these early stages of illness would be catalyzed by the widespread construction of engaging stigma-free portals and clinical scaffolding appropriate for young people in the 21st century. The latter are urgently required to supersede traditional models of care, which have served both patients and families so poorly, and equally have failed to unlock a deeper understanding of the origins and progression of potentially serious mental disorders. © The Author 2009.

Jacka F.N.,Deakin University | Jacka F.N.,University of Melbourne | Mykletun A.,Norwegian Institute of Public Health | Mykletun A.,University of New South Wales | And 3 more authors.
BMC Medicine | Year: 2012

There is a need for the development of effective universal preventive approaches to the common mental disorders, depression and anxiety, at a population level. Poor diet, physical inactivity and smoking have long been recognized as key contributors to the high prevalence noncommunicable diseases. However, there are now an increasing number of studies suggesting that the same modifiable lifestyle behaviors are also risk factors for common mental disorders. In this paper we point to the emerging data regarding lifestyle risk factors for common mental disorders, with a particular focus on and critique of the newest evidence regarding diet quality. On the basis of this most recent evidence, we consequently argue for the inclusion of depression and anxiety in the ranks of the high prevalence noncommunicable diseases influenced by habitual lifestyle practices. We believe that it is both feasible and timely to begin to develop effective, sustainable, population-level prevention initiatives for the common mental illnesses that build on the established and developing approaches to the noncommunicable somatic diseases. © 2012 Jacka et al; licensee BioMed Central Ltd.

Killackey E.,Orygen Youth Health Research Center
Early Intervention in Psychiatry | Year: 2010

Aim: Unemployment is the major disability faced by people with psychotic illness. Unemployment rates of 75-95% are found among those with schizophrenia. Unemployment is associated with poorer social and economic inclusion, greater symptomatology, decreased autonomy and generally poorer life functioning. Unemployment also makes up over half of the total costs associated with psychotic illness.Methods: A meeting was convened in London in June 2008. Invitees to this meeting included people from the USA, Canada and the UK interested in vocational intervention in early psychosis from either a research, clinical, economic or policy point of view. From this meeting a larger group - the International First Episode Vocational Recovery (iFEVR) group - has developed an international consensus statement about vocational recovery in first episode psychosis.Results: The document is a basic statement of the rights of young people with psychosis to pursue employment, education and training; the evidence which exists to help them do this; and ways in which individuals, organizations and governments can assist the attainment of these ends.Conclusion: It is hoped that the Meaningful Lives consensus statement will increase the focus on the area of functional recovery and lift it to be seen in parallel with symptomatic recovery in the approach to treating early psychosis. © 2010 Blackwell Publishing Asia Pty Ltd.

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