• Factors predicting adherence with psychiatric follow-up appointments for patients assessed by the liaison psychiatric team in the emergency department.

      Agyapong, Vincent I O; Rogers, Cathy; Machale, Siobhan; Cotter, David; St. Patrick's University Hospital, Dublin, Ireland. israelhans@hotmail.com (2010)
      Several factors may predict adherence with psychiatric follow-up appointment for patients seen in the emergency department (ED) by liaison psychiatric teams. Awareness of these factors would allow for interventions targeted at vulnerable groups.
    • Gender differences in outcome at 2-year follow-up of treated bipolar and depressed alcoholics.

      Farren, Conor K; Snee, Laura; McElroy, Sharon; Department of Addiction Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin 8, Ireland. cfarren@stpatsmail.com (2011-09)
      Alcohol dependence and affective disorders are significant health problems, and their co-occurrence is mutually detrimental. There are few long-term studies on the impact of treatment on the prognosis of these comorbid disorders. We wished to study if the impact of effective inpatient integrated treatment for these co-occurring disorders was maintained 2 years after discharge from the hospital.
    • Gender differences in the association between childhood abuse and psychosis.

      Fisher, Helen; Morgan, Craig; Dazzan, Paola; Craig, Thomas K; Morgan, Kevin; Hutchinson, Gerard; Jones, Peter B; Doody, Gillian A; Pariante, Carmine; McGuffin, Peter; et al. (2009-04)
      Studies demonstrating an association between childhood trauma and psychosis in adulthood have not systematically explored gender differences.
    • Genomic organization and promoter cloning of the human X11α gene APBA1.

      Chai, Ka-Ho; McLoughlin, Declan M; Chan, Ting Fung; Chan, Ho Yin Edwin; Lau, Kwok-Fai; Biochemistry Program, School Life Sciences, The Chinese University of Hong Kong , Shatin, New Territories, Hong Kong SAR. (2012-05)
      X11α is a brain specific multi-modular protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). Aggregation of amyloid-β peptide (Aβ), an APP cleavage product, is believed to be central to the pathogenesis of Alzheimer's disease. Recently, overexpression of X11α has been shown to reduce Aβ generation and to ameliorate memory deficit in a transgenic mouse model of Alzheimer's disease. Therefore, manipulating the expression level of X11α may provide a novel route for the treatment of Alzheimer's disease. Human X11α is encoded by the gene APBA1. As evidence suggests that X11α expression can be regulated at transcription level, we have determined the gene structure and cloned the promoter of APBA1. APBA1 spans over 244 kb on chromosome 9 and is composed of 13 exons and has multiple transcription start sites. A putative APBA1 promoter has been identified upstream of exon 1 and functional analysis revealed that this is highly active in neurons. By deletion analysis, the minimal promoter was found to be located between -224 and +14, a GC-rich region that contains a functional Sp3 binding site. In neurons, overexpression of Sp3 stimulates the APBA1 promoter while an Sp3 inhibitor suppresses the promoter activity. Moreover, inhibition of Sp3 reduces endogenous X11α expression and promotes the generation of Aβ. Our findings reveal that Sp3 play an essential role in APBA1 transcription.
    • Illicit substance use and its correlates in first episode psychosis.

      Mazzoncini, R; Donoghue, K; Hart, J; Morgan, C; Doody, G A; Dazzan, P; Jones, P B; Morgan, K; Murray, R M; Fearon, P; et al. (2010-05)
      To determine if substance use (particularly cannabis) is more frequent among first episode psychosis patients and associated with a more problematic clinical presentation.
    • Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study.

      Mourao-Miranda, J; Reinders, A A T S; Rocha-Rego, V; Lappin, J; Rondina, J; Morgan, C; Morgan, K D; Fearon, P; Jones, P B; Doody, G A; et al. (2012-05)
      To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode.
    • Initial diagnosis and treatment in first-episode psychosis: can an operationalized diagnostic classification system enhance treating clinicians' diagnosis and the treatment chosen?

      Coentre, Ricardo; Blanco, Pablo; Fontes, Silvina; Power, Paddy; Lambeth Early Onset Service, SouthLondon and Maudsley NHS Trust, London, UK. ricardo.coentre@netc.pt (2011-05)
      Diagnosis during the initial stages of first-episode psychosis is particularly challenging but crucial in deciding on treatment. This is compounded by important differences in the two major classification systems, International Classification of Diseases, 10th revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). We aimed to compare the concordance between an operationalized diagnosis using Operational Criteria Checklist (OPCRIT) and treating clinician-generated diagnosis in first episode psychosis diagnosis and its correlation with treatment prescribed.
    • Insight, grey matter and cognitive function in first-onset psychosis.

      Morgan, Kevin D; Dazzan, Paola; Morgan, Craig; Lappin, Julia; Hutchinson, Gerard; Suckling, John; Fearon, Paul; Jones, Peter B; Leff, Julian; Murray, Robin M; et al. (2010-08)
      Several studies have suggested that neuropsychological and structural brain deficits are implicated in poor insight. Few insight studies however have combined neurocognitive and structural neuroanatomical measures.
    • Lemur tyrosine kinase-2 signalling regulates kinesin-1 light chain-2 phosphorylation and binding of Smad2 cargo.

      Manser, C; Guillot, F; Vagnoni, A; Davies, J; Lau, K-F; McLoughlin, D M; De Vos, K J; Miller, C C J; Department of Neuroscience P037, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, London, UK. (2012-05-31)
      A recent genome-wide association study identified the gene encoding lemur tyrosine kinase-2 (LMTK2) as a susceptibility gene for prostate cancer. The identified genetic alteration is within intron 9, but the mechanisms by which LMTK2 may impact upon prostate cancer are not clear because the functions of LMTK2 are poorly understood. Here, we show that LMTK2 regulates a known pathway that controls phosphorylation of kinesin-1 light chain-2 (KLC2) by glycogen synthase kinase-3β (GSK3β). KLC2 phosphorylation by GSK3β induces the release of cargo from KLC2. LMTK2 signals via protein phosphatase-1C (PP1C) to increase inhibitory phosphorylation of GSK3β on serine-9 that reduces KLC2 phosphorylation and promotes binding of the known KLC2 cargo Smad2. Smad2 signals to the nucleus in response to transforming growth factor-β (TGFβ) receptor stimulation and transport of Smad2 by kinesin-1 is required for this signalling. We show that small interfering RNA loss of LMTK2 not only reduces binding of Smad2 to KLC2, but also inhibits TGFβ-induced Smad2 signalling. Thus, LMTK2 may regulate the activity of kinesin-1 motor function and Smad2 signalling.
    • Length of stay of general psychiatric inpatients in the United States: systematic review.

      Tulloch, Alex D; Fearon, Paul; David, Anthony S; Department of Psychiatry, Institute of Psychiatry, Kings College London, De Crespigny Park, London, SE5 8AF, UK, alexander.d.tulloch@kcl.ac.uk. (2011-05)
      Psychiatric length of stay (LOS) has reduced but is still longer than for physical disorders. Inpatient costs are 16% of total mental health spending. Regression analyses of the determinants of LOS for US adult psychiatric inpatients were systematically reviewed. Most studies predated recent LOS reductions. Psychosis, female gender and larger hospital size were associated with longer LOS, while discharge against medical advice, prospective payment, being married, being detained and either younger or middle age were associated with shorter LOS. Associations appeared consistent, especially where sample size was above 3,000. Updated studies should be adequately powered and include the variables above.
    • Long-term maternal recall of obstetric complications in schizophrenia research.

      Walshe, Muriel; McDonald, Colm; Boydell, Jane; Zhao, Jing Hua; Kravariti, Eugenia; Touloupoulou, Timothea; Fearon, Paul; Bramon, Elvira; Murray, Robin M; Allin, Matthew; et al. (2011-05-30)
      Obstetric complications (OCs) are consistently implicated in the aetiology of schizophrenia. Information about OCs is often gathered retrospectively, from maternal interview. It has been suggested that mothers of people with schizophrenia may not be accurate in their recollection of obstetric events. We assessed the validity of long term maternal recall by comparing maternal ratings of OCs with those obtained from medical records in a sample of mothers of offspring affected and unaffected with psychotic illness. Obstetric records were retrieved for 30 subjects affected with psychosis and 40 of their unaffected relatives. The Lewis-Murray scale of OCs was completed by maternal interview for each subject blind to the obstetric records. There was substantial agreement between maternal recall and birth records for the summary score of "definite" OCs, birth weight, and most of the individual items rated, with the exception of antepartum haemorrhage. There were no significant differences in the validity of recall or in errors of commission by mothers for affected and unaffected offspring. These findings indicate that several complications of pregnancy and delivery are accurately recalled by mother's decades after they occurred. Furthermore, there is no indication that mothers are less accurate in recalling OCs for their affected offspring than their unaffected offspring. When comparing women with and without recall errors, we found those with recall errors to have significantly worse verbal memory than women without such errors. Assessing the cognition of participants in retrospective studies may allow future studies to increase the reliability of their data.
    • Measuring consistency of autobiographical memory recall in depression.

      Semkovska, Maria; Noone, Martha; Carton, Mary; McLoughlin, Declan M; Department of Psychiatry, Trinity College, Dublin, Ireland. semkovsm@tcd.ie (2012-05-15)
      Autobiographical amnesia assessments in depression need to account for normal changes in consistency over time, contribution of mood and type of memories measured. We report herein validation studies of the Columbia Autobiographical Memory Interview - Short Form (CAMI-SF), exclusively used in depressed patients receiving electroconvulsive therapy (ECT) but without previous published report of normative data. The CAMI-SF was administered twice with a 6-month interval to 44 healthy volunteers to obtain normative data for retrieval consistency of its Semantic, Episodic-Extended and Episodic-Specific components and assess their reliability and validity. Healthy volunteers showed significant large decreases in retrieval consistency on all components. The Semantic and Episodic-Specific components demonstrated substantial construct validity. We then assessed CAMI-SF retrieval consistencies over a 2-month interval in 30 severely depressed patients never treated with ECT compared with healthy controls (n=19). On initial assessment, depressed patients produced less episodic-specific memories than controls. Both groups showed equivalent amounts of consistency loss over a 2-month interval on all components. At reassessment, only patients with persisting depressive symptoms were distinguishable from controls on episodic-specific memories retrieved. Research quantifying retrograde amnesia following ECT for depression needs to control for normal loss in consistency over time and contribution of persisting depressive symptoms.
    • Mental health matters

      St Patrick's University Hospital (St Patrick's University Hospital, 2008-12-02)
    • Mental health matters

      St Patrick's University Hospital (St Patrick's University Hospital, 2008-02-12)
    • Mental health services: the way forward: the perspectives of young people and parents

      Buckley, Sarah; Gavin, Blainid; Noctor, Colman; Devitt, Catherine; Guerin, Suzanne; The Way Forward Project Team (St Patrick's University Hospital, 2012-09)
    • Methohexitone, propofol and etomidate in electroconvulsive therapy for depression: a naturalistic comparison study.

      Eranti, Savithasri V; Mogg, Andrew J; Pluck, Graham C; Landau, Sabine; McLoughlin, Declan M; King's College London, Institute of Psychiatry, London, UK. (2009-02)
      Methohexitone has been the most widely used anaesthetic for electroconvulsive therapy (ECT). However, recent scarcity and erratic availability has led to use of other anaesthetics with differing effects upon ECT. We compared treatment parameters and response to ECT in patients anaesthetised with different anaesthetics in a routine clinical setting.
    • Migration and psychosis

      Fearon, P; St. Patrick's University Hospital, Dublin (2009)
    • Mobile phone text message interventions in psychiatry - what are the possibilities?

      I.O. Agyapong, Vincent; K. Farren, Conor; M. McLoughlin, Declan (2011-02)
    • Neurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments.

      Yates, Darran M; Manser, Catherine; De Vos, Kurt J; Shaw, Christopher E; McLoughlin, Declan M; Miller, Christopher C J; MRC Centre for Neurodegeneration Research, Department of Neuroscience P037, Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE58AF, UK. (2009-04)
      Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.
    • Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis.

      Semkovska, Maria; McLoughlin, Declan M; Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, St. Patrick's University Hospital, Ireland. (2010-09-15)
      Electroconvulsive therapy (ECT) is the most acutely effective treatment for depression, but is limited by cognitive side effects. However, research on their persistence, severity, and pattern is inconsistent. We aimed to quantify ECT-associated cognitive changes, specify their pattern, and determine progression.