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Malhi G.S.,CADE Clinic | Malhi G.S.,University of Sydney | Hitching R.,CADE Clinic | Hitching R.,University of Sydney | And 9 more authors.
Acta Psychiatrica Scandinavica | Year: 2013

Objective: To be used in conjunction with 'Psychological management of unipolar depression' [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24-37] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review. Method: Using our previous Clinical Practice Guidelines [Malhi et al. Clinical practice recommendations for bipolar disorder. Acta Psychiatr Scand 2009;119(Suppl. 439):27-46] as a foundation, these clinician guidelines target key practical considerations when prescribing pharmacotherapy. A comprehensive review of the literature was conducted using electronic database searches (PubMed, MEDLINE), and the findings have been synthesized and integrated alongside clinical experience. Results: The pharmacotherapy of depression is an iterative process that often results in partial and non-response. Beyond the initiation of antidepressants, the options within widely used strategies, such as combining agents and switching between agents, are difficult to proscribe because of the paucity of pertinent research. However, there is some evidence for second-line strategies, and a non-prescriptive algorithm can be derived that is based broadly on principles rather than specific steps. Conclusion: Depression is by its very nature a heterogeneous illness that is consequently difficult to treat. Invariably, situation-specific factors often play a significant role and must be considered, especially in the case of partial and non-response. Consulting with colleagues and trialling alternate treatment paradigms are essential strategies in the management of depression. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd. Source

Rowe C.C.,Austin Health | Ellis K.A.,University of Melbourne | Ellis K.A.,The Mental Health Research Institute | Ellis K.A.,National Ageing Research Institute | And 21 more authors.
Neurobiology of Aging | Year: 2010

The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a participant of the worldwide Alzheimer's Disease Neuroimaging Initiative (ADNI), performed 11C-Pittsburgh Compound B (PiB) scans in 177 healthy controls (HC), 57 mild cognitive impairment (MCI) subjects, and 53 mild Alzheimer's disease (AD) patients. High PiB binding was present in 33% of HC (49% in ApoE-ε4 carriers vs 21% in noncarriers) and increased with age, most strongly in ε4 carriers. 18% of HC aged 60-69 had high PiB binding rising to 65% in those over 80 years. Subjective memory complaint was only associated with elevated PiB binding in ε4 carriers. There was no correlation with cognition in HC or MCI. PiB binding in AD was unrelated to age, hippocampal volume or memory. Beta-amyloid (Aβ) deposition seems almost inevitable with advanced age, amyloid burden is similar at all ages in AD, and secondary factors or downstream events appear to play a more direct role than total beta amyloid burden in hippocampal atrophy and cognitive decline. © 2010. Source

Fodero-Tavoletti M.T.,University of Melbourne | Brockschnieder D.,Bayer AG | Villemagne V.L.,Austin Health | Villemagne V.L.,The Mental Health Research Institute | And 11 more authors.
Nuclear Medicine and Biology | Year: 2012

Purpose: Amyloid-β (Aβ) plaques are a major pathological hallmark of Alzheimer's disease (AD). The noninvasive detection of Aβ plaques may increase the accuracy of clinical diagnosis as well as monitor therapeutic interventions. While [ 11C]-PiB is the most widely used Aβ positron emission tomography (PET) radiotracer, due to the short half-life of 11C (20min), its application is limited to centers with an on-site cyclotron and 11C radiochemistry expertise. Therefore, novel [ 18F] (half-life 110min)-labeled Aβ PET tracers have been developed. We have demonstrated that [ 18F]-florbetaben-PET can differentiate individuals diagnosed with AD from healthy elderly, Parkinson's disease and frontotemporal lobe dementia (FTLD-tau) patients. While [ 18F]-florbetaben-PET retention matched the reported postmortem distribution of Aβ plaques, the nature of [ 18F]-florbetaben binding to other pathological lesions comprising misfolded proteins needs further assessment. The objective of this study was to determine whether Florbetaben selectively binds to Aβ plaques in postmortem tissue specimens containing mixed pathological hallmarks (i.e., tau and α-synuclein aggregates). Method: Human AD, FTLD-tau and dementia with Lewy bodies (DLB) brain sections were analyzed by [ 18F]-florbetaben autoradiography and [ 3H]-florbetaben high-resolution emulsion autoradiography and [ 19F]-florbetaben fluorescence microscopy. Results: Both autoradiographical analyses demonstrated that Florbetaben exclusively bound Aβ plaques in AD brain sections at low nanomolar concentrations. Furthermore, at concentrations thousand-folds higher than those during a PET scan, [ 19F]-florbetaben did not bind to α-synuclein or tau aggregates in DLB and FTLD-tau brain sections, respectively. Detection of [ 19F]-florbetaben staining by fluorescence microscopy in several AD brain regions demonstrated that Florbetaben identified Aβ plaques in all brain regions examined. Conclusion: This study provides further evidence that [ 18F]-florbetaben-PET is a highly selective radiotracer to assess Aβ plaque deposition in the brain. © 2012 Elsevier Inc. Source

Dean B.,The Mental Health Research Institute | Dean B.,University of Melbourne | Boer S.,The Mental Health Research Institute | Scarr E.,The Mental Health Research Institute | And 10 more authors.
Open Neuropsychopharmacology Journal | Year: 2011

There are well validated rodent paradigms of schizophrenia which are based on environmental manipulation (e.g. altered rearing conditions) or drug challenges. These manipulations induce behavioural changes in rodents that are thought to involve neuronal circuitry similar to the ones that are affected by the pathophysiology of the disorder. This study has investigated whether three such rodent paradigms (isolation rearing, neonatal PCP treatment or sub-chronic PCP treatment) are associated with changes in muscarinic receptors (CHRMs) or ionotropic glutamate receptors, some of which have been reported to be altered in the CNS of subjects with schizophrenia. [3H]pirenzepine (CHRM1), [3H]4DAMP (CHRM1/CHRM3), [3H]MK801 (NMDA receptors) and [3H]kainate (kainate receptors; KAR) binding were measured using in situ radioligand binding and autoradiography. Isolation rearing caused widespread decreases in [3H]4DAMP (p = 0.01) and [3H]kainate binding (p = 0.03). Neonatal PCP caused widespread increases in [3H]4DAMP binding (p <0.0001), whereas sub-chronic PCP treatment caused widespread decreases in the binding of that radioligand (p < 0.002) and widespread increases in [3H]MK801 binding (p < 0.0001). There were no changes in [3H]pirenzepine binding to CHRM1 receptors in any paradigm or no significant within region changes in the binding of any radioligand. In conclusion, in the absence of any changes in CHRM1 receptors, our [3H]4DAMP and the binding of [3H]MK801 data would suggest that different rodent paradigms cause variable changes in levels of CHRM3 and KAR in the rat CNS. Our data raises the possibility that such changes may, in part, modulate the behavioural differences that have been observed after isolation rearing, neonatal PCP treatment or sub-chronic PCP treatment. © Dean et al. Source

Dean B.,The Mental Health Research Institute | Dean B.,University of Melbourne | Tawadros N.,The Mental Health Research Institute | Tawadros N.,University of Melbourne | And 4 more authors.
Journal of Affective Disorders | Year: 2010

Background: From studies in the periphery, changed levels of tumour necrosis factor (TNF) have been implicated in the pathophysiology of major depressive disorders (MDD). Therefore we decided to determine whether TNF was altered in the frontal cortex (Brodmann's areas (BA) 24 and 46) from 10 subjects with MDD and 10 control subjects. Methods: Tissue homogenates were prepared from the left hemisphere and levels of TNF trans-membrane (tmTNF) and TNF soluble (sTNF) forms measured by Western blots. Results: tmTNF was significantly increased in BA 46 (mean ± SEM: 7.70 ± 0.92 vs. 3.18 ± 0.87 Ratio Internal Control, p < 0.001), but not BA 24, from subjects with MDD, there was no change in levels of sTNF in either CNS region. Limitations: As the report of tmTNF in postmortem CNS from subjects with MDD, our findings need to be replicated in another group of cases. Conclusions: Our data supports the hypothesis that changes in pro-inflammatory pathways may be involved in the pathophysiology of MDD. Targeting these pathways may be a new approach to treating the disorder. © 2009 Elsevier B.V. All rights reserved. Source

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