Florey Institute for Neuroscience and Mental Health

Parkville, Australia

Florey Institute for Neuroscience and Mental Health

Parkville, Australia
SEARCH FILTERS
Time filter
Source Type

Nunes S.O.V.,State University Londrina | Vargas H.O.,State University Londrina | Prado E.,University of Melbourne | Barbosa D.S.,State University Londrina | And 8 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2013

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. © 2013 .


Moylan S.,Deakin University | Eyre H.A.,University of Adelaide | Eyre H.A.,James Cook University | Maes M.,Piyavate Hospital | And 6 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2013

Regular physical activity exerts positive effects on anxiety disorder symptoms, although the biological mechanisms underpinning this effect are incompletely understood. Numerous lines of evidence support inflammation and oxidative and nitrogen stress (O&NS) as important in the pathogenesis of mood and anxiety disorders, and physical activity is known to influence these same pathways. This paper reviews the inter-relationships between anxiety disorders, physical activity and inflammation and O&NS, to explore whether modulation of inflammation and O&NS may in part underpin the positive effect of physical activity on anxiety disorders. Numerous studies support the notion that physical activity operates as an anti-inflammatory and anti-O&NS agent which potentially exerts positive effects on neuroplasticity, the expression of neurotrophins and normal neuronal functions. These effects may therefore influence the expression and evolution of anxiety disorders. Further exploration of this area may elicit a deeper understanding of the pathogenesis of anxiety disorders, and inform the development of integrated programmes including PA specifically suited to the treatment and prevention of anxiety disorders and symptoms. © 2013 Elsevier Ltd.


Perry C.J.,Florey Institute for Neuroscience and Mental Health | Perry C.J.,University of Melbourne
Journal of Molecular Neuroscience | Year: 2016

Alcohol consumption triggers a neuroinflammatory response which, if prolonged, can lead to substantial volume loss in both gray and white matter. This brain injury is associated with characteristic cognitive deficits, and, in extreme cases, with dementia. Even mild cognitive impairment creates a significant hurdle for alcohol rehabilitation, because the domains that are affected tend to be those important for sustaining abstinence. Thus, cognitive decline induced by alcohol contributes to the persistence of alcoholism. Here, I present converging data from animal and clinical studies that show how alcohol affects the brain and behavior. Although there is currently no targeted treatment for overcoming alcohol-induced cognitive decline, emerging evidence suggests that physical activity is both protective and restorative. This is a potential avenue for future programs targeted at treating alcohol abuse. © 2016, Springer Science+Business Media New York.


Chanen A.M.,University of Melbourne | Chanen A.M.,Orygen Youth Health | Berk M.,Deakin University | Berk M.,University of Melbourne | Berk M.,Florey Institute for Neuroscience and Mental Health
Harvard Review of Psychiatry | Year: 2016

Borderline personality disorder (BPD) has been demonstrated to be a reliable and valid construct in young people (adolescents and young adults). Both borderline- and mood-related psychopathology become clinically apparent from puberty through to young adulthood, frequently co-occur, can reinforce one another, and can be difficult to differentiate clinically. This Gordian knot of overlapping clinical features, common risk factors, and precursors to both BPD andmood disorders complicates clinical assessment, prevention, and treatment. Regardless of whether an individual crosses an arbitrary diagnostic threshold, a considerable proportion of young people with borderline- and moodrelated psychopathology will develop significant and persistent functional, vocational, and interpersonal impairment and disability during this critical risk and developmental period. There is a clear need for early intervention, but spurious diagnostic certainty risks stigma, misapplication of diagnostic labels, inappropriate treatment, and unfavorable outcomes. This article aims to integrate early intervention for BPD and mood disorders in the clinical context of developmental and phenomenological change and evolution. “Clinical staging,” similar to disease staging in general medicine, is presented as a pragmatic, heuristic, and trans-diagnostic framework to guide prevention and intervention. It acknowledges that the early stages of these disorders cannot be disentangled sufficiently to allow for disorder-specific preventive measures and early interventions. Clinical staging defines an individual’s location along the continuum of the evolving temporal course of a disorder. Such staging aids differentiation of early or milder clinical phenomena from those that accompany illness progression and chronicity, and suggests the application of appropriate and proportionate intervention strategies. © 2016 President and Fellows of Harvard College.


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.


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.


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.

Loading Florey Institute for Neuroscience and Mental Health collaborators
Loading Florey Institute for Neuroscience and Mental Health collaborators