Florey Institute for Neuroscience and Mental Health

Parkville, Australia

Florey Institute for Neuroscience and Mental Health

Parkville, Australia

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Sarris J.,University of Melbourne | Sarris J.,Swinburne University of Technology | O'Neil A.,Deakin University | O'Neil A.,Monash University | And 6 more authors.
BMC Psychiatry | Year: 2014

The prevalence of depression appears to have increased over the past three decades. While this may be an artefact of diagnostic practices, it is likely that there are factors about modernity that are contributing to this rise. There is now compelling evidence that a range of lifestyle factors are involved in the pathogenesis of depression. Many of these factors can potentially be modified, yet they receive little consideration in the contemporary treatment of depression, where medication and psychological intervention remain the first line treatments. " Lifestyle Medicine" provides a nexus between public health promotion and clinical treatments, involving the application of environmental, behavioural, and psychological principles to enhance physical and mental wellbeing. This may also provide opportunities for general health promotion and potential prevention of depression. In this paper we provide a narrative discussion of the major components of Lifestyle Medicine, consisting of the evidence-based adoption of physical activity or exercise, dietary modification, adequate relaxation/sleep and social interaction, use of mindfulness-based meditation techniques, and the reduction of recreational substances such as nicotine, drugs, and alcohol. We also discuss other potential lifestyle factors that have a more nascent evidence base, such as environmental issues (e.g. urbanisation, and exposure to air, water, noise, and chemical pollution), and the increasing human interface with technology. Clinical considerations are also outlined. While data supports that some of these individual elements are modifiers of overall mental health, and in many cases depression, rigorous research needs to address the long-term application of Lifestyle Medicine for depression prevention and management. Critically, studies exploring lifestyle modification involving multiple lifestyle elements are needed. While the judicious use of medication and psychological techniques are still advocated, due to the complexity of human illness/wellbeing, the emerging evidence encourages a more integrative approach for depression, and an acknowledgment that lifestyle modification should be a routine part of treatment and preventative efforts. © 2014 Sarris et al.; licensee BioMed Central Ltd.

Maixner W.,Royal Melbourne Hospital | Jackson G.D.,Florey Institute for Neuroscience and Mental Health | Harvey A.S.,University of Melbourne
Neurology | Year: 2012

Objective: We sought to identify intracranial EEG patterns characteristic of epileptogenic tubers and to understand the contribution of perituberal cortex. Methods: Twenty-three intracranial EEG monitoring studies were reviewed from 17 children aged 1.3-7.7 years with tuberous sclerosis complex and intractable multifocal epilepsy, 14 with a history of epileptic spasms. Interictal epileptiform discharges and ictal rhythms for 60 electroclinically distinct seizures (EDS) were analyzed in relation to 162 sampled tubers. Results: Localized, tuber-related, ictal rhythms were seen in 49/60 EDS, most commonly as lowvoltage fast activity recruiting to rhythmic spiking, then diffuse slowing or bursts of ripple range activity. Ictal onset in localized EDS involved only tubers in 57% and tubers with perituberal cortex in 31%. Ictal fast ripples (FR) noted at seizure onset in 15/38 localized EDS were confined to tubers in 73% and involved tuber with perituberal cortex in 27%. Intraictal activation occurred during seizure propagation in 19 localized EDS, being to tubers in 63%and to tuberswith perituberal cortex in 37%; 63% of activated tubers generated independent EDS. Trains of periodic sharp waves on an attenuated background were seen interictally at 36/162 tubers, with 67% of those tubers generating EDS (p 5 0.0001). Interictal FR, when present, involved tubers more commonly than perituberal cortex but were not associated with EDS. Conclusion: The study demonstrates interictal and ictal intracranial EEG findings characteristic of epileptogenic tubers, suggests that tubers play a greater role in seizure genesis than perituberal cortex, and suggests tuberectomy may be a sufficient surgical approach in a number of patients. © 2012 American Academy of Neurology.

Singh A.B.,Deakin University | Bousman C.A.,University of Melbourne | Bousman C.A.,Florey Institute for Neuroscience and Mental Health | Bousman C.A.,Swinburne University of Technology | And 5 more authors.
Current Opinion in Psychiatry | Year: 2014

PURPOSE OF REVIEW: This article reviews recent literature published over the period March 2012-August 2013 on antidepressant pharmacogenetics, with a focus on clinical translation and methodological challenges. RECENT FINDINGS: Recently, various polymorphisms associated with differential antidepressant efficacy, tolerability, and safety have emerged in association studies, but mixed findings, limited effect sizes, and poor control of confounders have prevented findings translating to practice. Although promising steps have been made, empirically robust clinically translatable pharmacogenetic tests are not yet established. The complex neurobiology of major depressive disorder (MDD) together with the evolving understanding of genetic processes present research challenges for clinical translation. SUMMARY: Early reports of clinical utility are published. The current evidence base for antidepressant pharmacogenetics is, however, not yet empirically robust enough to inform routine prescribing guidelines. Over the coming years, genetically guided versus unguided trials will help determine if antidepressant pharmacogenetics merits more widespread application. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Data-Franco J.,Hospital Santa Maria | Data-Franco J.,Deakin University | Berk M.,Deakin University | Berk M.,Florey Institute for Neuroscience and Mental Health | And 2 more authors.
Australian and New Zealand Journal of Psychiatry | Year: 2013

Objective: This paper aims to provide an overview on the nocebo effect, focusing on recognition - its phenomenology, at-risk demographic profiles, clinical situations and personality factors, as well as discriminating somatic symptoms in the general population from treatment-related adverse effects. Lastly, the paper addresses available evidence-based strategies for management and minimisation of the nocebo effect. Method: Data for this paper were identified by searching PubMed using the search terms "nocebo" and "nocebo effect", augmented by a manual search of the references of the key papers and the related literature. Results: The nocebo effect refers to non-pharmacodynamic, harmful or undesirable effects occurring after inactive treatment, a phenomenon that also occurs in the context of active therapy. Known drivers include classical conditioning and negative expectations concerning treatment. Recent meta-analyses have reported a considerable prevalence, ranging from 18% in the symptomatic treatment of migraine, to more than 74% in multiple sclerosis. Recognition of the nocebo-driven adverse effects presents a challenge, especially because of its non-specific nature and the similarity to the active medication's expected profile. Traits such as neuroticism, pessimism and type A personalities may predispose individuals to this phenomenon. Clinical management of the nocebo effect includes awareness and recognition, changing the manner of disclosure of potential drug-related adverse effects, shaping patients' expectations and enhancing the treatment alliance. Conclusion: The nocebo effect is a common, clinically significant, yet covert driver of clinical outcomes. Increased awareness of its features, as well as knowledge of strategies on how to manage it, are fundamental so that clinicians can mitigate its impact on clinical practice. © The Royal Australian and New Zealand College of Psychiatrists 2012.

Ayton S.,Florey Institute for Neuroscience and Mental Health | Lei P.,Florey Institute for Neuroscience and Mental Health | Duce J.A.,Florey Institute for Neuroscience and Mental Health | Wong B.X.W.,Florey Institute for Neuroscience and Mental Health | And 6 more authors.
Annals of Neurology | Year: 2013

Ceruloplasmin is an iron-export ferroxidase that is abundant in plasma and also expressed in glia. We found a ∼80% loss of ceruloplasmin ferroxidase activity in the substantia nigra of idiopathic Parkinson disease (PD) cases, which could contribute to the pro-oxidant iron accumulation that characterizes the pathology. Consistent with a role for ceruloplasmin in PD etiopathogenesis, ceruloplasmin knockout mice developed parkinsonism that was rescued by iron chelation. Additionally, peripheral infusion of ceruloplasmin attenuated neurodegeneration and nigral iron elevation in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine mouse model for PD. These findings show, in principle, that intravenous ceruloplasmin may have therapeutic potential in PD. © 2013 American Neurological Association.

Anderson G.,CRC Rm 30 | Berk M.,Deakin University | Berk M.,University of Melbourne | Berk M.,Orygen Youth Health Research Center | And 7 more authors.
CNS Drugs | Year: 2014

Accumulating data have led to a re-conceptualization of depression that emphasizes the role of immune-inflammatory processes, coupled to oxidative and nitrosative stress (O&NS). These in turn drive the production of neuroregulatory tryptophan catabolites (TRYCATs), driving tryptophan away from serotonin, melatonin, and N-acetylserotonin production, and contributing to central dysregulation. This revised perspective better encompasses the diverse range of biological changes occurring in depression and in doing so provides novel and readily attainable treatment targets, as well as potential screening investigations prior to treatment initiation. We briefly review the role that immune-inflammatory, O&NS, and TRYCAT pathways play in the etiology, course, and treatment of depression. We then discuss the pharmacological treatment implications arising from this, including the potentiation of currently available antidepressants by the adjunctive use of immune- and O&NS-targeted therapies. The use of such a frame of reference and the treatment benefits attained are likely to have wider implications and utility for depression-associated conditions, including the neuroinflammatory and (neuro)degenerative disorders. © 2013 Springer International Publishing Switzerland.

Evered L.,St Vincents Hospital | Silbert B.,St Vincents Hospital | Scott D.A.,St Vincents Hospital | Ames D.,National Ageing Research Institute | And 2 more authors.
Anesthesiology | Year: 2016

Background: Postoperative cognitive dysfunction (POCD) affects 16 to 21% of the elderly 3 months after anesthesia and surgery and is associated with adverse outcomes. The exact cause of POCD remains unknown. The authors hypothesized that elderly individuals with Alzheimer disease (AD) neuropathology, identified by cerebrospinal fluid (CSF) analysis, would have increased the risk for POCD. Methods: CSF samples were collected from 59 patients 60 yr or older who received combined spinal and general anesthesia for elective total hip replacement. Patients underwent neuropsychological testing preoperatively and at 7 days, 3 months, and 12 months postoperatively. POCD at 3 months and cognitive decline at 12 months were calculated by using the reliable change index. CSF amyloid β1- 42 (Aβ1- 42), total-tau, phosphorylated-tau, and neurofilament light were assayed with enzyme-linked immunosorbent assay methods. Results: POCD was identified in 5 of 57 patients (8.8%) at 3 months. For Aβ1- 42, 11 patients were below the cut-point for AD neuropathology of whom 3 were classified with POCD (27.3%; 95% CI, 6.0 to 61%), whereas of the 46 patients above the cut-point, 2 were classified with POCD (4.3%; 95% CI, 0.5 to 14.8%) (P = 0.01). There was no significant difference in the incidence of POCD in relation to the cut-points for any of the other analytes. Conclusions: Low CSF Aβ1- 42 may be a significant predictor of POCD at 3 months. This indicates that patients with AD neuropathology even in the absence of clinically detectable AD symptoms may be susceptible to POCD. © 2015 the American Society of Anesthesiologists, Inc.

Bartholomeusz C.F.,University of Melbourne | Ganella E.P.,University of Melbourne | Labuschagne I.,Australian Catholic University | Bousman C.,University of Melbourne | And 3 more authors.
Schizophrenia Research | Year: 2015

Impairments in social cognition and poor social functioning are core features of schizophrenia-spectrum disorders. In recent years, there has been a move towards developing new treatment strategies that specifically target social cognitive and social behavioural deficits. Oxytocin (OXT) is one such strategy that has gained increasing attention. There is a strong rationale for studying OXT in psychosis, from both an evolutionary perspective and neurodevelopmental-cognitive model of schizophrenia. Thus, the aim of this review was to critique and examine the observational and clinical oxytocin trial literature in schizophrenia-spectrum disorders. A handful of clinical trials suggest that OXT treatment may be beneficial for remediating social cognitive impairments, psychiatric symptoms, and improving social outcomes. However, inconsistencies exist in this literature, which may be explained by individual differences in the underlying neural response to OXT treatment and/or variation in the oxytocin and oxytocin receptor genes. Therefore, we additionally reviewed the evidence for structural and functional neural intermediate phenotypes in humans that link genetic variants to social behaviour/thinking, and discuss the implications of such interactions in the context of dysfunctional brain networks in schizophrenia. Factors that pose challenges for future OXT clinical research include the impact of age, sex, and ancestry, task-specific effects, bioavailability and pharmacokinetics, as well as neurotransmitter and drug interactions. While initial findings from OXT single dose/clinical trial studies are promising, more interdisciplinary research in both healthy and psychiatric populations is needed before determining whether OXT is a viable treatment option/adjunct for addressing poor illness outcomes in psychotic disorders. © 2015 Elsevier B.V.

Ghanizadeh A.,Shiraz University of Medical Sciences | Freeman R.D.,University of British Columbia | Berk M.,Deakin University | Berk M.,University of Melbourne | And 2 more authors.
Reviews on Recent Clinical Trials | Year: 2013

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children and adolescents. Stimulants are commonly prescribed for ADHD management. There is clinical trial evidence that some medications with noradrenergic properties such as atomoxetine are effective. It is of theoretical and practical importance if other agents with noradrenergic properties display a comparable pattern of efficacy. This paper is a systematic review of the efficacy and safety of venlafaxine for treating children and adolescents with ADHD. MEDLINE, Google scholar, Scopus, and Web of science (ISI) databases were electronically searched in July 2012, updated on November 2012. Time and language of publication were not exclusion criteria. Efficacy outcomes were assessed by a valid and reliable parent- and/or teacher-reported instrument to evaluate clinical symptoms. Adverse effects were also evaluated. There were three uncontrolled trials and only two double blind controlled clinical trials. Venlafaxine appeared effective for treating ADHD. The rates of some adverse effects of venlafaxine were less than those documented for methylphenidate. While one of the two small controlled trials did not find difference between venlafaxine ad methylphenidate, the other trial reported lower efficacy for venlafaxine. Headache, insomnia, and nausea were among the most common adverse effects. This systematic review provides preliminary support that venlafaxine may have short term utility in treating ADHD in children and adolescents. However, before recommending venlafaxine for treatment, more robust and larger clinical trials, in particular providing evidence of its long-term efficacy, safety and tolerability are required. © 2012 Bentham Science Publishers.

McIntyre R.S.,University of Toronto | Tohen M.,University of New Mexico | Berk M.,Deakin University | Berk M.,University of Melbourne | And 4 more authors.
Journal of Affective Disorders | Year: 2013

Background To describe the frequency of mixed specifier as proposed in DSM-5 in bipolar I patients with manic episodes, and to evaluate the effect of mixed specifier on symptom severity and treatment outcome. Methods This post-hoc analysis used proxies for DSM-5 mixed features specifier by using MADRS or PANSS items. Results Of the 960 patients analysed, 34%, 18% and 4.3% of patients, respectively, had ≥3 depressive features with mild (score ≥1 for MADRS items and ≥2 for PANSS item), moderate (score ≥2 MADRS, ≥3 PANSS) and severe (score ≥3 MADRS, ≥4 PANSS) symptoms. In patients with ≥3 depressive features and independent of treatment: MADRS remission (score ≤12) rate decreased with increasing severity (61-43%) and YMRS remission (score ≤12) was similar for mild and moderate patients (36-37%), but higher for severe (54%). In asenapine-treated patients, the MADRS remission rate was stable regardless of baseline depressive symptom severity (range 64-67%), whereas remission decreased with increasing severity with olanzapine (63-38%) and placebo (49-25%). Reduction in YMRS was significantly greater for asenapine compared with placebo at day 2 across the 3 severity cut-offs and continued to decrease throughout the treatment period. The difference between olanzapine and placebo was statistically significant in mild and moderate patients. Limitations Results are from post-hoc analyses. Conclusions These analyses support the validity of proposed DSM-5 criteria. They confirm that depressive features are frequent in bipolar patients with manic episodes. With increasing baseline severity of depressive features, treatment outcome was poorer with olanzapine and placebo, but remained stable with asenapine. © 2013 Elsevier B.V.

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