• Early interventions for people with psychotic disorders

      Power, P; McGorry, PD; St. Patrick's University Hospital, Dublin (Oxford University Press, 2011)
    • The economic cost of pathways to care in first episode psychosis.

      Heslin, Margaret; McCrone, Paul; Flach, Clare; Fearon, Paul; Morgan, Kevin; Jones, Peter; Murray, Robin M; Dazzan, Paola; Doody, Gill; Morgan, Craig; et al. (2011)
      Few studies have examined the economic cost of psychoses other than schizophrenia and there have been no studies of the economic cost of pathways to care in patients with their first episode of psychosis. The aims of this study were to explore the economic cost of pathways to care in patients with a first episode of psychosis and to examine variation in costs. Data on pathways to care for first episode psychosis patients referred to specialist mental health services in south-east London and Nottingham between 1997-2000. Costs of pathway events were estimated and compared between diagnostic groups. The average costs for patients in south-east London were £54 (CI £33-£75) higher, compared to patients in Nottingham. Across both centres unemployed patients had £25 (CI £7-£43) higher average costs compared to employed patients. Higher costs were associated with being unemployed and living in south-east London and these differences could not be accounted for by any single factor. This should be considered when the National Health Service (NHS) is making decisions about funding.
    • Electroconvulsive therapy and nursing care.

      Kavanagh, Adam; McLoughlin, Declan M; Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, St Patrick's University Hospital, Dublin, Ireland. (2011-04-27)
      Modified electroconvulsive therapy (ECT) is a controlled medical procedure in which a seizure is induced in an anaesthetized patient to produce a therapeutic effect. ECT is the most acutely effective treatment available for affective disorders and is more effective than antidepressant drugs. Although in use for 70 years, ECT continues to attract controversy and there is considerable stigma associated with its use that often overshadows the empirical evidence for its effectiveness. One way to overcome this is for health professionals to be educated about contemporary ECT practice. Patients need to make informed decisions when consenting to ECT and this process can be influenced by preconceived ideas and scientific fact. It is, therefore, essential that nurses possess sufficient information to help patients make rational and informed treatment decisions and be able to care for both the clinical and psychological needs of patients treated with ECT. This review outlines the nursing role in ECT and summarizes the main aspects of contemporary ECT practice relevant to general and psychiatric nursing practice.
    • Electroconvulsive therapy, brain stimulation and neurosurgery for mental illness

      Dunne, R; McLoughlin, D.M.; St. Patrick's University Hospital, Dublin (Elsevier, 2010)
    • 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.