Anderson G.,CRC |
Maes M.,Piyavate Hospital |
Berk M.,Deakin University |
Berk M.,Orygen Youth Health Research Center |
And 2 more authors.
Medical Hypotheses | Year: 2012
Background: Somatization is a multisomatoform disorder characterized by medically unexplained, functional or psychosomatic symptoms. Similar somatic symptoms are key components of depression and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Methods: This paper reviews the evidence that such symptoms are organically based. We use the term " physio-somatic" to describe these symptoms. Results: Inflammation, cell-mediated immune (CMI) activation and alterations in the tryptophan catabolite (TRYCAT) pathway are associated with the physio-somatic symptoms of depression, ME/CFS and/or somatization. Proinflammatory cytokines, decreased tryptophan and aberrations in TRYCATs may cause physio-somatic symptoms, such as fatigue, autonomic symptoms, hyperalgesia and somatic presentations. Conclusions: The data suggest co-ordinated and interacting biological pathways driving the occurrence of physio-somatic symptoms across these three disorders, giving a biologically validated " pathway phenotype" . These data have far-reaching implications for DSM-IV diagnostic conceptualizations of somatization (and ME/CFS) suggesting the presence of an emerging organic explanation. Future research should focus on the role of immune regulation, and co-ordination, of neuronal activity and, through larger data sets, ultimately creating new, biologically validated classification rules. These data have implications for the development of novel therapies utilizing these insights, buttressing the role of psychotherapy in psychosomatic presentations. © 2012 Elsevier Ltd.
Maes M.,Maes Clinics at TRIA |
Berk M.,Deakin University |
Berk M.,Orygen Youth Health Research Center |
Berk M.,The Mental Health Research Institute of Victoria |
And 7 more authors.
BMC Medicine | Year: 2012
It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers. © 2012 Maes et al; licensee BioMed Central Ltd.
Fullerton J.M.,Neuroscience Research Australia |
Fullerton J.M.,University of New South Wales |
Tiwari Y.,Neuroscience Research Australia |
Tiwari Y.,University of New South Wales |
And 9 more authors.
Bipolar Disorders | Year: 2010
Objectives: There is a growing body of evidence implicating oxidative stress and the glutathione system in the pathogenesis of major psychiatric illnesses, including schizophrenia and bipolar disorder. Here we investigate whether genes involved in oxidative stress regulation are associated with increased risk for bipolar disorder. Methods: Four candidate genes were selected a priori from two different steps in the oxidative stress pathway, specifically the synthesis of glutathione [catalytic subunit of glutamate cysteine ligase (GCLC) and regulatory subunit of glutamate cysteine ligase (GCLM)] and the removal of reactive oxygen species [superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3)]. Haplotype tagging and functional nucleotide polymorphisms were selected in each gene and tested for association with bipolar disorder under narrow (n = 240) and broad (n = 325) phenotypic models, compared to healthy controls (n = 392, comprising 166 psychiatrically assessed unaffected controls plus 226 healthy individuals). Results: Single marker association analysis did not reveal significant association with bipolar disorder; however, haplotypes in the SOD2 gene showed nominal association (global χ2 = 8.94, p = 0.03; broad model). Interaction analysis revealed a significant interaction between SOD2 and GPX3 haplotypes, which further increases risk for bipolar disorder (odds ratio = 2.247, χ2 = 9.526, p = 0.002, corrected p = 0.029). Conclusions: Further characterization of the SOD2 and GPX3 interaction using larger cohorts is required to determine the role of these oxidative pathway genes as risk factors for bipolar disorder. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.
The Mental Health Research Institute Of Victoria | Date: 2012-11-09
The present invention relates generally to a method of modulating glutathione metabolism in the central nervous system of mammals and to agents for use therein. More particularly, the present invention relates to a method of up-regulating glutathione metabolism in the central nervous system by up-regulating levels of glutathione precursor molecules. The method of the present invention is particularly useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate central nervous system oxidation homeostasis including, but not limited to, schizophrenia.
Pasco J.A.,Deakin University |
Pasco J.A.,University of Melbourne |
Jacka F.N.,Deakin University |
Jacka F.N.,University of Melbourne |
And 12 more authors.
Complementary Therapies in Medicine | Year: 2012
Objectives and methods: Alterations in redox biology are established in depression; however, there are no prospective epidemiological data on redox-active selenium in depression. We aimed to determine if low levels of dietary selenium are associated with an increased risk for . de novo major depressive disorder (MDD). In this nested case-control study, women aged 20 years or more were identified from a randomly selected cohort being followed prospectively for the Geelong Osteoporosis Study. Cases were individuals with incident MDD, identified using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no such history. Dietary selenium intake was measured using a food frequency questionnaire at baseline, together with anthropometric and lifestyle measures. Results: Eighteen women who developed . de novo MDD were classified as cases; there were 298 controls. Low dietary selenium intakes increased the likelihood of developing MDD; OR 2.74 (95%CI 0.95-7.89). After adjusting for age and SES, compared with a high selenium intake, a low intake (<8.9. μg/MJ/day) was associated with an approximate trebling of the likelihood for developing . de novo MDD; OR 2.95 (95%CI 1.00-8.72). Smoking, alcohol consumption and physical activity did not confound the association. Conclusion: These data suggest that lower dietary selenium intakes are associated with an increased risk of subsequent . de novo MDD. We propose that selenium's function as an antioxidant, and as a constituent of selenoproteins that are important in redox homeostasis, warrants further investigation as a risk factor for depression, and suggest a potentially novel modifiable factor in the primary prevention and management of depression. © 2012 Elsevier Ltd.