• The ethical issues surrounding consent and capacity

      Dornan, J; Kennedy, M; St. Patrick's University Hospital, Dublin (Irish Psychiatrist, 2010)
    • Ethnic identity, perceptions of disadvantage, and psychosis: findings from the ÆSOP study.

      Reininghaus, Ulrich; Craig, Thomas K J; Fisher, Helen L; Hutchinson, Gerard; Fearon, Paul; Morgan, Kevin; Dazzan, Paola; Doody, Gillian A; Jones, Peter B; Murray, Robin M; et al. (2010-12)
      Many studies have shown that rates of psychosis are elevated in the Black and minority ethnic (BME) population in the UK. One important, but relatively less researched explanation of these high rates may be social adversity associated with acculturation processes. Strong identification with an ethnic minority group subjected to social disadvantage may exert adverse effects on individuals from BME groups. Using data from a large epidemiological case-control study of first-episode psychosis, we aimed to investigate whether strong ethnic identification is a factor contributing to the excess of psychosis in BME groups compared with the White British, after adjustment for perceptions of disadvantage. All cases with a first episode of psychosis presenting to specialist mental health services within tightly defined catchment areas in London and Nottingham, UK, and geographically matched community controls were included in the study. Data were collected on socio-demographic and clinical characteristics, perceptions of disadvantage, and identification with one's own ethnic group. Analysis was performed on data from 139 cases and 234 controls. There was evidence that, as levels of ethnic identification increased, the odds of psychosis increased in the BME but not in the White British group, independent of potential confounders. However, the association between strong ethnic identity and psychosis in BME individuals was attenuated and non-significant when controlled for perceived disadvantage. Strong identification with an ethnic minority group may be a potential contributory factor of the high rates of psychosis in the BME population, the effects of which may be explained by perceptions of disadvantage.
    • Ethnicity, social disadvantage and psychotic-like experiences in a healthy population based sample.

      Morgan, C; Fisher, H; Hutchinson, G; Kirkbride, J; Craig, T K; Morgan, K; Dazzan, P; Boydell, J; Doody, G A; Jones, P B; et al. (2009-03)
      We sought to investigate the prevalence and social correlates of psychotic-like experiences in a general population sample of Black and White British subjects.
    • An evoked auditory response fMRI study of the effects of rTMS on putative AVH pathways in healthy volunteers.

      Tracy, D K; O'Daly, O; Joyce, D W; Michalopoulou, P G; Basit, B B; Dhillon, G; McLoughlin, D M; Shergill, S S; CSI Lab, Department of Psychological Medicine, The Institute of Psychiatry, King's College London, UK. d.tracy@iop.kcl.ac.uk (2010-01)
      Auditory verbal hallucinations (AVH) are the most prevalent symptom in schizophrenia. They are associated with increased activation within the temporoparietal cortices and are refractory to pharmacological and psychological treatment in approximately 25% of patients. Low frequency repetitive transcranial magnetic stimulation (rTMS) over the temporoparietal cortex has been demonstrated to be effective in reducing AVH in some patients, although results have varied. The cortical mechanism by which rTMS exerts its effects remain unknown, although data from the motor system is suggestive of a local cortical inhibitory effect. We explored neuroimaging differences in healthy volunteers between application of a clinically utilized rTMS protocol and a sham rTMS equivalent when undertaking a prosodic auditory task.
    • Examining evidence for neighbourhood variation in the duration of untreated psychosis.

      Kirkbride, J B; Lunn, D J; Morgan, C; Lappin, J M; Dazzan, P; Morgan, K; Fearon, P; Murray, R M; Jones, P B; Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. jbk25@cam.ac.uk;St. Patrick's University Hospital Dublin (2010-03)
      Family involvement in help-seeking is associated with a shorter duration of untreated psychoses [DUP], but it is unknown whether neighbourhood-level factors are also important.
    • Expression of the neuronal adaptor protein X11alpha protects against memory dysfunction in a transgenic mouse model of Alzheimer's disease.

      Mitchell, Jacqueline C; Perkinton, Michael S; Yates, Darran M; Lau, Kwok-Fai; Rogelj, Boris; Miller, Christopher C J; McLoughlin, Declan M; MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London, UK. (2010)
      X11alpha is a neuronal-specific adaptor protein that binds to the amyloid-beta protein precursor (AbetaPP). Overexpression of X11alpha reduces Abeta production but whether X11alpha also protects against Abeta-related memory dysfunction is not known. To test this possibility, we crossed X11alpha transgenic mice with AbetaPP-Tg2576 mice. AbetaPP-Tg2576 mice produce high levels of brain Abeta and develop age-related defects in memory function that correlate with increasing Abeta load. Overexpression of X11alpha alone had no detectable adverse effect upon behavior. However, X11alpha reduced brain Abeta levels and corrected spatial reference memory defects in aged X11alpha/AbetaPP double transgenics. Thus, X11alpha may be a therapeutic target for Alzheimer's disease.
    • Extra information about treatment is too much for the patient with psychosis.

      Kennedy, Miriam; Dornan, Julieanne; Rutledge, Emer; O'Neill, Helen; Kennedy, Harry G; Central Mental Hospital, Dublin, Ireland. (2011-04-27)
      Case law across jurisdictions requires ever more complete disclosure of material facts when obtaining consent to treatment.
    • 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)