• Unilateral brief-pulse electroconvulsive therapy and cognition: Effects of electrode placement, stimulus dosage and time.

      Semkovska, Maria; Keane, Deborah; Babalola, Oyemi; McLoughlin, Declan M; Department of Psychiatry, Trinity College Dublin, St Patrick's University Hospital, James's Street, Dublin 8, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, St Patrick's University Hospital, James's Street, Dublin 8, Ireland. (2010-11-23)
      To clarify advantages of unilateral electrode placement as an optimisation technique for electroconvulsive therapy (ECT) for depression, aims were to meta-analyse unilateral ECT effects on cognitive performance relative to: (1) bitemporal electrode placement, (2) electrical dosage, and (3) time interval between final treatment and cognitive reassessment. Relevant electronic databases were systematically searched through May 2009, using the terms: "electroconvulsive therapy" and ["cogniti∗", "neuropsycholog∗", "memory", "attention", "executive", "spatial", or "intellectual"]. Inclusion criteria were: independent study of depressed patients receiving unilateral or bitemporal brief-pulse ECT; within-subjects design; use of objective cognitive assessments; available mean electrical dosage for unilateral samples. Standardized pre-post ECT weighted effect sizes were computed and pooled within 16 cognitive domains by a mixed-effects model. Thirty-nine studies (1415 patients) were meta-analysed. Up to three days after final treatment, unilateral ECT was associated with significantly smaller decreases in global cognition, delayed verbal memory retrieval, and autobiographical memory, compared to bitemporal ECT. Significant publication bias was found for autobiographical memory, favouring reporting of larger percentage loss. Higher unilateral ECT electrical dosage predicted larger decreases in verbal learning, delayed verbal memory retrieval, visual recognition, and semantic memory retrieval. When retested more than three days after completing ECT, no significant differences remained between the two electrode placements; for unilateral ECT, electrical dosage no longer predicted cognitive performance whereas increasing interval between final treatment and retesting predicted growing improvement in some variables. This interval is a more useful long-term predictor of cognitive function than electrode placement or electrical dosage following unilateral ECT.
    • An update on the management of bipolar disorder

      Thekiso, T; Fearon, P (2011-05-19)
    • The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder.

      Fisher, H L; Jones, P B; Fearon, P; Craig, T K; Dazzan, P; Morgan, K; Hutchinson, G; Doody, G A; McGuffin, P; Leff, J; et al. (2010-12)
      Childhood adversity has been associated with onset of psychosis in adulthood but these studies have used only general definitions of this environmental risk indicator. Therefore, we sought to explore the prevalence of more specific adverse childhood experiences amongst those with and without psychotic disorders using detailed assessments in a large epidemiological case-control sample (AESOP).
    • An X11alpha/FSBP complex represses transcription of the GSK3beta gene promoter.

      Lau, Kwok-Fai; Perkinton, Michael S; Rodriguez, Lilia; McLoughlin, Declan M; Miller, Christopher C J; Department of Biochemistry Science, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR. kflau@cuhk.edu.hk (2010-08-04)
      X11alpha is a neuronal adaptor protein that interacts with the amyloid precursor protein (APP) through a centrally located phosphotyrosine binding domain to inhibit the production of Abeta peptide that is deposited in Alzheimer's disease brains. X11alpha also contains two C-terminal postsynaptic density-95, large discs, zona occludens 1 (PDZ) domains, and we show here that through its PDZ domains, X11alpha interacts with a novel transcription factor, fibrinogen silencer binding protein. Moreover, we show that an X11alpha/fibrinogen silencer binding protein complex signals to the nucleus to repress glycogen synthase kinase-3beta promoter activity. Glycogen synthase kinase-3beta is a favoured candidate kinase for phosphorylating tau in Alzheimer's disease. Our findings show a new function for X11alpha that may impact on Alzheimer's disease pathogenesis.
    • X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice.

      Mitchell, Jacqueline C; Ariff, Belall B; Yates, Darran M; Lau, Kwok-Fai; Perkinton, Michael S; Rogelj, Boris; Stephenson, John D; Miller, Christopher C J; McLoughlin, Declan M; MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London SE5 8AF, UK. (2009-12-01)
      Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer's disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer's disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer's disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer's disease.