SUNScholar - Browsing by Author "Emsley, Robin A."

Browsing by Author "Emsley, Robin A."

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Alcohol and brain damage
(HMPG, 1993) Emsley, Robin A.
Acoholism may constitute the major health problem in many pans of the world, with its effects on morbidiry and monality grossly underestimated in world health statistics.' Alcohol-related neuropsychiatric disorders constitute a particularly large and incapacitating subset of the medical complications of alcoholism.
Arginine vasopressin hypersecretion and impaired water excretion in psychiatric disorders
(Stellenbosch : Stellenbosch University, 1987) Emsley, Robin A.; Stellenbosch University. Faculty of . Dept. of .
Associations of premorbid adjustment with type and timing of childhood trauma in first-episode schizophrenia spectrum disorders
(AOSIS, 2021-06) Smit, Anna M.; Kilian, Sanja; Emsley, Robin A.; Luckhoff, Hilmar K.; Swartz, Leslie; Seedat, Soraya; Asmal, Laila
Background: Childhood trauma may contribute to poorer premorbid social and academic adjustment which may be a risk factor for schizophrenia. Aim: We explored the relationship between premorbid adjustment and childhood trauma, timing of childhood trauma’s moderating role as well as the association of clinical and treatment-related confounders with premorbid adjustment. Setting: We conducted a secondary analysis in 111 patients with first-episode schizophrenia (FES) disorders that formed part of two parent studies, EONKCS study (n =73) and the Shared Roots study (n =38). Methods: Type of childhood trauma was assessed with the Childhood Trauma Questionnaire, short-form and premorbid adjustment using the Premorbid Adjustment Scale. Timing of childhood trauma was assessed using the Life Events Checklist and life events timeline. Linear regression analyses were used to assess the moderating effect of timing of childhood trauma. Clinical and treatment-related confounders were entered into sequential hierarchical regression models to identify independent predictors of premorbid adjustment across key life stages. Results: Childhood physical neglect was associated with poorer premorbid academic functioning during childhood and early adolescence, and poorer premorbid social functioning during early and late adolescence. By hierarchical regression modelling (r2 = 0.13), higher physical neglect subscale scores (p = 0.011) independently predicted poorer premorbid social adjustment during early adolescence. Timing of childhood trauma did not moderate the relationship between childhood trauma and premorbid functioning. Conclusion: In patients with FES, childhood physical neglect may contribute to poorer premorbid social functioning during early adolescence. This may provide us with an opportunity to identify and treat at-risk individuals earlier.
A case of Ifufunyane : a Xhosa culture-bound syndrome
(Lippincott, Williams & Wilkins, 2005-11) Niehaus, Dana J. H.; Stein, Dan J.; Koen, Liezl; Lochner, Christine; Muller, Jacqueline E.; Mbanga, N. Irene; Emsley, Robin A.; Gorman, Jack M.
Clinicians and patients frequently have a different understanding and interpretation of the nature of an illness. While many reasons for these discrepancies can be postulated, differences in sociocultural background often play an important role—especially in the field of psychiatry. At our tertiary psychiatric hospital in South Africa, where standard Western teachings are followed, clinicians are often confronted by patients who have a markedly different interpretation of their psychiatric symptoms compared with the clinician’s perspective. For instance, “ifufunyane” (plural “amafufunyana”), a ritualized”“possession state,” often thought to result from witchcraft, is frequently reported by South African (Xhosa) patients with psychosis (including schizophrenia) and their families.
Chromosome 22q11 in a Xhosa schizophrenia population
(Health and Medical Publishing Group (HMPG), 2012-03) Koen, Liezl; Niehaus, Dana J. H.; Wright, Galen; Warnich, Louise; De Jong, Greetje; Emsley, Robin A.; Mall, Sumaya
Chromosome 22q11 aberrations substantially increase the risk for developing schizophrenia. Although micro-deletions in this region have been extensively investigated in different populations across the world, little is known of their prevalence in African subjects with schizophrenia. We screened 110 African Xhosa-speaking participants with schizophrenia for the presence of micro-deletions. As further verification for the presence or absence of 22q11 microdeletions, we screened 238 Xhosa schizophrenia patients and 240 healthy Xhosa individuals from a larger schizophrenia candidate 22q11 gene study using molecular analyses. Data from molecular and cytogenetic analyses confirmed the absence of 22q11 microdeletions in the Xhosa schizophrenia samples. Although the absence of chromosome 22q11 micro-deletions in this group of patients does not exclude the possibility that it may occur in Xhosa schizophrenia patients, we concluded an extremely low prevalence. Our findings suggest that unique susceptibility loci may be present in this group.
Cognitive-perceptual deficits and symptom correlates in first-episode schizophrenia
(AOSIS Publishing, 2017) Olivier, Riaan M.; Kilian, Sanja; Chiliza, Bonginkosi; Asmal, Laila; Oosthuizen, Petrus P.; Emsley, Robin A.; Kidd, Martin
Background: Thought disorder and visual-perceptual deficits have been well documented, but their relationships with clinical symptoms and cognitive function remain unclear. Cognitive-perceptual deficits may underscore clinical symptoms in schizophrenia patients. Aim: This study aimed to explore how thought disorder and form perception are related with clinical symptoms and cognitive dysfunction in first-episode schizophrenia. Setting: Forty-two patients with a first-episode of schizophrenia, schizophreniform or schizoaffective disorder were recruited from community clinics and state hospitals in the Cape Town area. Methods: Patients were assessed at baseline with the Rorschach Perceptual Thinking Index (PTI), the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Cognitive Consensus Battery (MCCB). Spearman correlational analyses were conducted to investigate relationships between PTI scores, PANSS factor analysis-derived domain scores and MCCB composite and subscale scores. Multiple regression models explored these relationships further. Results: Unexpectedly, poor form perception (X- %) was inversely correlated with the severity of PANSS positive symptoms (r = -0.42, p = 0.02). Good form perception (XA%) correlated significantly with speed of processing (r = 0.59, p < 0.01), working memory (r = 0.48, p < 0.01) and visual learning (r = 0.55, p < 0.01). PTI measures of thought disorder did not correlate significantly with PANSS symptom scores or cognitive performance. Conclusions: Form perception is associated with positive symptoms and impairment in executive function during acute psychosis. These findings suggest that there may be clinical value in including sensory-perceptual processing tasks in cognitive remediation and social cognitive training programmes for schizophrenia patients.
Crisis discharges and readmission risk in acute psychiatric male inpatients
(BioMed Central, 2008-06) Niehaus, Dana J. H.; Koen, Liezl; Galal, Ushma; Dhansay, Khalid; Oosthuizen, Piet P.; Emsley, Robin A.; Jordaan, Esme
Background: Severe pressures on beds in psychiatric services have led to the implementation of an early ("crisis") discharge policy in the Western Cape, South Africa. The study examined the effect of this policy and length of hospital stay (LOS) on readmission rates in one psychiatric hospital in South Africa. Methods: Discharge summaries of adult male patients (n = 438) admitted to Stikland Psychiatric Hospital during 2004 were retrospectively examined. Each patient's clinical course was then analysed for the period between January 1st, 2004, and August 31st, 2006. Results: Although shorter LOS was associated with decreased readmission rates, the effect of crisis discharges was far more powerful. Patients discharged as usual had a far lower risk of readmission than those discharged due to bed pressures (i.e. crisis discharge). Conclusion: Increased risks associated with the early discharge policy necessitate the urgent review of the current management of bed shortages in this inpatient facility. The strengthening of community initiatives, particularly assertive outreach could be a way forward.
Efficacy and safety profile of paliperidone palmitate injections in the management of patients with schizophrenia : an evidence-based review
(Dove Medical Press, 2018) Emsley, Robin A.; Kilian, Sanja
The course of schizophrenia is characterized by multiple relapses, incomplete remission of symptoms, enduring cognitive deficits, and social and occupational functional impairments. Nonadherence to antipsychotic medication is a major determinant of this poor outcome. Long-acting injectable antipsychotics were developed specifically to address the nonadherence problem and are increasingly considered as an early treatment option, in an attempt to prevent accruing morbidity. This review focuses on paliperidone palmitate, the long-acting injectable (LAI) formulation of paliperidone. After considering the pharmacology of paliperidone palmitate, we review the randomized controlled trials, as well as pertinent observational, pragmatic studies for paliperidone once-monthly injections in schizophrenia. Finally, we review the recently introduced 3-monthly formulation of paliperidone palmitate. Taken together, the studies indicate that paliperidone palmitate (PP) has good efficacy compared with placebo and comparable with other antipsychotics including risperidone. The tolerability profile of PP is similar to that of risperidone, with the most important side effects being prolactin elevation, weight gain, and extrapyramidal symptoms. Advantages of PP include the extensive research database and clinical experience with paliperidone and its parent compound risperidone, the availability of different LAI formulations (once-monthly, 3-monthly, and perhaps even longer acting formulations in future), and the novel dose initiation procedure that provides rapid onset of action without the need for oral antipsychotic supplementation.
Factors moderating the relationship between childhood trauma and premorbid adjustment in first-episode schizophrenia
(Public Library of Science, 2017-01-20) Kilian, Sanja; Burns, J. K.; Seedat, S.; Asmal, L.; Chiliza, B.; Du Plessis, S.; Du Plessis, M. R.; Kidd, Michael; Emsley, Robin A.
Childhood trauma is a recognised risk factor for schizophrenia. It has been proposed that childhood trauma interferes with normal neurodevelopment, thereby establishing a biological vulnerability to schizophrenia. Poor premorbid adjustment is frequently a precursor to schizophrenia, and may be a manifestation of neurodevelopmental compromise. We investigated the relationship between childhood trauma and premorbid adjustment in 77 patients with first-episode schizophrenia spectrum disorders. We also investigated possible mediating roles for other selected risk factors in the relationship. We found several significant correlations between different trauma types and both social and academic premorbid adjustment from childhood to late adolescence. There were no significant moderating effects for family history of schizophrenia or family history of psychiatric disorder. History of obstetric complications, substance abuse and poor motor coordination weakened some of the associations between childhood trauma and premorbid adjustment, while poor sequencing of motor acts strengthened the association. Our results confirm previous studies indicating an association between childhood trauma and premorbid adjustment. Results indicate a general rather than specific association, apparent with different types of trauma, and affecting both social and academic components of premorbid adjustment across childhood, early and late adolescence. Further, our results suggest a complex interplay of various risk factors, supporting the notion of different pathways to psychosis.
Instruments measuring blunted affect in schizophrenia : a systematic review
(Public Library of Science, 2015-06) Kilian, Sanja; Asmal, Laila; Goosen, Anneke; Chiliza, Bonginkosi; Phahladira, Lebogang; Emsley, Robin A.
Blunted affect, also referred to as emotional blunting, is a prominent symptom of schizophrenia. Patients with blunted affect have difficulty in expressing their emotions. The work of Abrams and Taylor and their development of the Rating Scale for Emotional Blunting in the late 1970’s was an early indicator that blunted affect could indeed be assessed reliably. Since then, several new instruments assessing negative symptoms with subscales measuring blunted affect have been developed. In light of this, we aim to provide researchers and clinicians with a systematic review of the different instruments used to assess blunted affect by providing a comparison of the type, characteristics, administration and psychometric properties of these instruments. Studies reporting on the psychometric properties of instruments assessing blunted affect in patients with schizophrenia were included. Reviews and case studies were excluded. We reviewed 30 full-text articles and included 15 articles and 10 instruments in this systematic review. On average the instruments take 15–30 minutes to administer. We found that blunted affect items common across all instruments assess: gestures, facial expressions and vocal expressions. The CAINS Self-report Expression Subscale, had a low internal consistency score. This suggests that this sub-scale does not reliably assess patients’ self-reported blunted affect symptoms and is likely due to the nature of blunted affect. Instruments correlated minimally with instruments measuring positive symptoms and more importantly with depression suggesting that the instruments distinguish between seemingly similar symptoms.
Neurological soft signs, spontaneous and treatment emergent extrapyramidal syndromes in Black Africans with first episode schizophrenia
(Frontiers Media, 2018) Ojagbemi, Akin; Chiliza, Bonga; Bello, Toyin; Asmal, Laila; Esan, Oluyomi; Emsley, Robin A.; Gureje, Oye
Background: Very little is known about the relationship between spontaneous and treatment-induced motor syndromes in Africans with first episode schizophrenia. Objective: We investigated the association between spontaneous NSS and EPS, with treatment-induced EPS in a homogenous sample of Black Africans with first episode schizophrenia. Methods: We examined Xhosa (South Africa) and Yoruba (Nigeria) patients, using the Neurological Evaluation Scale and extrapyramidal symptoms scale before and at 3 months after exposure to low dose flupenthixol decanoate. Pearson's correlations and Linear regression models, controlling for duration of untreated psychosis (D.U.P) and premorbid adjustments, were used in examining associations. Results: Among 99 participants in the baseline sample, 91 (91.8%) and 20 (20.2%) had at least one definite NSS and EPS, respectively, before exposure to antipsychotics. Treatment-induced EPS were recorded in 34 (38.6%). Spontaneous EPS was associated with treatment-emergent Akathisia in participants with a longer D.U.P (r = 0.75, β = 0.70, p = 0.008). This association was specific for Parkinsonism (r = 0.75, β = 0.85, p = 0.008) and dyskinesia (r = 0.75, β = 1.70, p = 0.008). Conclusion: Similar to previous findings for tardive dyskinesia in studies implementing longer-term follow-up, spontaneous EPS may also predict short-term antipsychotic-induced EPS such as akathisia. These results may be important for early identification of patients at risk of treatment-induced Akathisia-linked psychomotor agitation in first episode schizophrenia.
The new-generation antipsychotics - integrating the neuropathology and pharmacology of schizophrenia
(Health & Medical Publishing Group, 1999) Harvey, Brian H.; Stein, Dan J.; Emsley, Robin A.
Despite a well-established role for dopamine (DA) in the neuropathology of schizophrenia, and the evidence of a hyperdopaminergic state in the schizophrenic brain, many questions still remain. Typical agents acting predominantly on DA D2 receptors are only partially effective. New data now indicate that the interaction between DA and the various DA receptors as well as DA interaction with other transmitter systems, are more critical in deciding the therapeutic success of an antipsychotic than actions on DA alone. These interactions are closely associated with what is being documented regarding the neuro-anatomy, neurobiology and neuropsychology of the disorder. There have been major advances in the understanding of the neuropathology of schizophrenia that, while not replacing the original DA hypothesis, have forced a re-evaluation of our understanding of the disorder. In this paper we present the biochemical and neuropathological basis for schizophrenia and discuss six new atypical antipsychotics according to these theories. Drugs reviewed include clozapine, risperidone, olanzapine, ziprasidone, sertindole and quetiapine. While not a comparative analysis of these drugs, this paper is an appraisal of how their pharmacology correlates with our present knowledge of the disorder and highlights differences among the drugs in this group. These agents therefore possess specifically designed qualities, to varying degrees, promising a significant improvement over earlier agents in terms of treating positive and negative symptoms, with a minimal risk of extrapyramidal symptoms (EPS). These qualities include an emphasis on D2 selectivity, D1/D2 balance, DA/serotonin (5HT) balance, D3/D4 selectivity, DA/acetylcholine (Ach) balance and glutamate (Glu)/gamma-aminobutyric acid (GABA) balance. The drugs are discussed with reference to these criteria. Targeted drug design has created a goal-directed strategy with which to treat schizophrenia. These new antipsychotics appear to have several distinct advantages over their predecessors, and should make a major contribution to the treatment of schizophrenia and the re-integration of these patients into society.
Once-monthly paliperidone palmitate in early stage schizophrenia – a retrospective, non-interventional 1-year study of patients with newly diagnosed schizophrenia
(Dove Medical Press, 2017) Emsley, Robin A.; Hargarter, Ludger; Bergmans, Paul; Uglesic, Boran; Sengul, Abdullah Cem; Petralia, Antonino; Khannanova, Angelina; Cherubin, Pierre; Schreiner, Andreas
Background: Long-acting antipsychotic therapy may be best suited for patients in the early stage of schizophrenia, when the most can be done before disease progression associated with poor adherence occurs. We explored the patterns of use of once-monthly paliperidone palmitate (PP1M), concomitant medication use, hospitalization, and clinical outcomes of adult, newly diagnosed patients with schizophrenia receiving continuous treatment with PP1M for at least 12 months. Methods: This was an international, multicenter, exploratory, retrospective chart review of medical records of adult patients who were newly diagnosed (not more than 1 year before initiation of PP1M treatment) with schizophrenia and who had received continuous treatment with PP1M for $12 months in naturalistic clinical settings. Results: A total of 84 (93.3%) patients were included in the analysis. All but one patient (98.8%, n=83) had received oral antipsychotic medication at least during the last month before the first PP1M administration. Three patients (3.6%) were newly hospitalized during the 12-month documentation period. The reason for hospitalization for all three was management of episode/relapse. A total of 79.2% of patients had a $20% improvement and 47.2% had a $50% improvement in Positive and Negative Syndrome Scale total score from baseline to endpoint. Half of patients (53.3%) showed a significant improvement, as reflected by an increase in Personal and Social Performance (PSP) total score of at least 7 points from baseline to endpoint (mean [SD] 11.9 [15.0] points; P,0.001). One quarter of patients (24.4%, n=11) moved from a PSP score of 31–70 (ie, moderate to marked functional impairment) at baseline to a PSP score of mild to no functional impairment (PSP score $71) at endpoint. Most adverse drug reactions were mild or moderate in severity. Conclusion: Continuous treatment with PP1M over 12 months was associated with statistically significant and clinically meaningful improvements in psychotic symptoms, disease severity, and functional outcomes in patients with schizophrenia.
Placebo controls in clinical trials : concerns about use in relapse prevention studies in schizophrenia
(BMJ Publishing Group, 2016) Emsley, Robin A.; Turoff, Sarah; Fleischhacker, W. Wolfgang; Galderisi, Silvana; Halpern, Lisa J.; McEvoy, Joseph P.; Schooler, Nina R.
ENGLISH SUMMARY : The use of placebos in clinical trials has major policy implications for ethical conduct across all of medicine and is relevant to clinicians, patients, drug development, and regulatory agencies. This article focuses on the use of placebos in relapse prevention studies in schizophrenia. However, the issues discussed are similar to those encountered in many other clinical trial situations. These include underestimating the risk of harm associated with trial participation, the risk of coercion, insufficient awareness of the risks by participants, and the risk of loss of trust between the patient and doctor. While the debate around using placebos in clinical trials of schizophrenia is long running, several developments make it imperative to readdress the topic. Firstly, new research has reported deleterious effects of relapse,1 challenging the previous assumption that relapse is not associated with a risk of lasting harm. Secondly, new questions have been raised about the need for maintenance treatment in schizophrenia.2 Thirdly, ethical standards have evolved, with reduced tolerance of exposure of participants to risk and greater respect of patient autonomy. Finally, and most importantly, recent publications from both the European Medicines Agency and US Food and Drug Administration continue to encourage the use of placebos in schizophrenia trials.
The potential role of regulatory genes (DNMT3A, HDAC5, and HDAC9) in antipsychotic treatment response in South African schizophrenia patients
(Frontiers Media, 2019-10-07) O’Connell, Kevin Sean; McGregor, Nathaniel Wade; Emsley, Robin A.; Seedat, Soraya; Warnich, Louise
ENGLISH ABSTRACT: Despite advances in pharmacogenetics, the majority of heritability for treatment response cannot be explained by common variation, suggesting that factors such as epigenetics may play a key role. Regulatory genes, such as those involved in DNA methylation and transcriptional repression, are therefore excellent candidates for investigating antipsychotic treatment response. This study explored the differential expression of regulatory genes between patients with schizophrenia (chronic and antipsychotic-naïve first-episode patients) and healthy controls in order to identify candidate genes for association with antipsychotic treatment response. Seven candidate differentially expressed genes were identified, and four variants within these genes were found to be significantly associated with treatment response (DNMT3A rs2304429, HDAC5 rs11079983, and HDAC9 rs1178119 and rs11764843). Further analyses revealed that two of these variants (rs2304429 and rs11079983) are predicted to alter the expression of specific genes (DNMT3A, ASB16, and ASB16-AS1) in brain regions previously implicated in schizophrenia and treatment response. These results may aid in the development of biomarkers for antipsychotic treatment response, as well as novel drug targets.
A retrospective chart review of the clinical and psychosocial profile of psychotic adolescents with co-morbid substance use disorders presenting to acute adolescent psychiatric services at Tygerberg Hospital
(2012) Lachman, Anusha; Nassen, Rene; Hawkridge, Sue; Emsley, Robin A.
ENGLISH ABSTRACT: Background. A large number of adolescents meet criteria for 'dual diagnosis' (a psychiatric disorder plus co-morbid substance use disorder (SUD)), which prolongs treatment response and complicates intervention strategies. The current service model in Cape Town divides the care of such patients into psychiatric treatment and a separate substance use intervention. Child and adolescent mental health services face the challenge of high rates of readmission of adolescents into psychiatric facilities before utilisation of community-based substance abuse services. Objective. There is a scarcity of available treatment guidelines for dual-diagnosis adolescents, and a lack of systematically documented epidemiological and clinical data in South African adolescent populations. Method. A retrospective chart review of adolescent psychiatric admissions to the Tygerberg Adolescent Psychiatric Unit during 2010 was conducted. Relevant epidemiological, clinical and demographic data for those presenting with a dual diagnosis (specifically psychotic disorders and SUD) was recorded. Results. Results suggest a high prevalence of SUD among adolescents presenting with a first-episode psychosis. Statistically significant correlations with lower levels of education were found in those with ongoing substance abuse (specifically cannabis and methamphetamine), and a significant relationship between choice of debut drug and ongoing drug use was also demonstrated. Risk factors for SUD (psychosocial adversities, childhood trauma, family and community exposure to substances, early debut drug ages), risky sexual behaviours, and clinical psychiatric profiles of adolescents with dual diagnosis are described. Conclusions. This cohort had an enhanced risk as a result of genetic vulnerability and environmental availability of substances, and the findings emphasise the differences in presentation, choice of drugs of abuse and psychosocial difficulties of adolescents with a dual diagnosis presenting to a psychiatric facility. We aim to influence role-players to provide more integrated services, and highlight the need for future prospective studies in this adolescent group to assist in improving outcomes.
Staff and bed distribution in public sector mental health services in the Eastern Cape Province, South Africa
(AOSIS Publishing, 2014-11) Sukeri, Kiran; Alonso-Betancourt, Orlando; Emsley, Robin A.
Background. The Eastern Cape Province of South Africa is a resource-limited province with a fragmented mental health service. Objective. To determine the current context of public sector mental health services in terms of staff and bed distribution, and how this corresponds to the population distribution in the province. Method. In this descriptive cross-sectional study, an audit questionnaire was submitted to all public sector mental health facilities. Norms and indicators were calculated at provincial and district level. This article investigates staff and bed distribution only. Results. Results demonstrated that within the province, only three of its seven districts have acute beds above the national baseline norm requirement of 13/100 000. The private mental health sector provides approximately double the number of medium- to long-stay beds available in the public sector. Only two regions have staff/population ratios above the baseline norm of 20/100 000. However, there are significant differences in this ratio among specific staff categories. There is an inequitable distribution of resources between the eastern and western regions of the province. When compared with the western regions, the eastern regions have poorer access to mental health facilities, human resources and non-governmental organisations. Conclusion. Owing to the inequitable distribution of resources, the provincial authorities urgently need to develop an equitable model of service delivery. The province has to address the absence of a reliable mental health information system.
Studies in the psychopathology, neurobiology and psychopharmacology of schizophrenia
(Stellenbosch : Stellenbosch University, 2008-03) Emsley, Robin A.; Stein, Dan; Stellenbosch University. Faculty of Health Sciences. Dept. of Psychiatry.
ENGLISH ABSTRACT: The overall aim of these studies was to investigate selected aspects of psychopathology, neurobiological abnormalities and treatment in schizophrenia. The following topics were researched: 1. Psychopathology: We explored the symptom structure of schizophrenia by means of principal components and factor analysis in two separate samples. a. The first study investigated the nature of symptoms in patients with a first-episode of schizophrenia, in a large cohort of patients who were participating in a multinational clinical trial. We compared our findings with similar analyses previously conducted in multi-episode schizophrenia patients. b. We then assessed the influence of culture on the symptom structure of schizophrenia by conducting a principal components and factor analysis of the symptom ratings in a large sample of South African Xhosa patients with schizophrenia, and comparing the results with those in other parts of the world. c. We investigated the occurrence of co-morbid depressive and anxiety symptoms, and their demographic and clinical correlates. The sample for this study comprised acutely psychotic patients who were participants in clinical drug trials conducted at our centre. d. To explore the relationships between obsessive-compulsive disorder and schizophrenia, we conducted a review of the relevant literature. 2. Neurobiological abnormalities: a. We performed a series of studies to investigate disorders of water homeostasis and vasopressin secretion in schizophrenia. To test the hypothesis that acutely psychotic patients have disordered regulation of water homeostasis, we applied a dynamic suppression test - a water loading test, with assessment of excretory capacity (including arginine vasopressin assay) in acutely psychotic patients. To evaluate whether a subset of patients with schizophrenia and co-morbid disordered water homeostasis sustained cerebral damage as a consequence of water intoxication we did the following experiment: We identified a cohort of subjects with schizophrenia and disordered water homeostasis and compared them with patients with schizophrenia without disordered water homeostasis in terms of cerebral ventricular size and cognitive function. To assess the prevalence of disordered water homeostasis in a long-term inpatient sample of psychiatric patients we conducted serum sodium screening tests. Those subjects with dilutional hyponatraemia were then further investigated for dysregulation of water homeostatic mechanisms. b. We studied neurological soft signs in a sample of subjects with first-episode schizophrenia followed up over a two year period. We investigated their occurrence, relationships to psychiatric symptoms and medication effects, their temporal stability and their outcome correlates. We also investigated their potential to predict outcome in schizophrenia 3. Treatment aspects A great deal of our work has focussed on the pharmacological treatment of schizophrenia. The following aspects of treatment are included in this thesis: a. Treatment effects on psychiatric symptoms: i. To assess the effects of ethnicity on treatment outcome in schizophrenia we compared the acute response to antipsychotic treatment in 3 ethnic groups, namely blacks, coloureds and whites. We included patients in this analysis who had participated in clinical trials in our department as well as the Department of Psychiatry in the University of the Free Sate. Patients had been treated under blinded conditions over a 6-week period. ii. After discussions with the late Dr David Horrobin, who had pioneered possible applications of the omega-3 fatty acids in the treatment of various psychiatric disorders, we became interested in further investigating the potential of this group of compounds as an affordable adjunct to treating schizophrenia. We assessed the antipsychotic potential of the omega-3 fatty acid, ethyl-eicosapentaenoic-acid (e-EPA) supplementation versus placebo supplementation in a small sample of subjects with schizophrenia who had been only partially responsive to antipsychotic treatment previously. We also conducted a review of the literature to evaluate the evidence for efficacy for the omega-3 fatty acids in schizophrenia according to published studies. b. Treatment effects on neurological abnormalities: i. In a single-blinded controlled study we compared a new generation antipsychotic to a conventional antipsychotic in the treatment of tardive dyskinesia (TD). This was a long-term (1 yr) study in patients with chronic schizophrenia and established tardive dyskinesia. ii. We also assessed the effect of omega-3 fatty acid (e-EPA) supplementation in treating TD. This was conducted in a larger sample (n=84) of patients with chronic schizophrenia and established TD. The blinded, placebo-controlled phase was 12 weeks. This was followed by an open-label extension for 40 weeks. c. Conventional versus new generation antipsychotic agents. Several evidence-based literature reviews of the efficacy and tolerability of the new generation of antipsychotics compared to the conventional agents were conducted. Some multinational, randomised, controlled clinical trials in which the author was principal investigator, are included in this thesis. Also, studies addressing patients with partial treatment refractoriness are included, as well as studies of the effects of antipsychotics on depressive symptoms, body mass and glycaemic control. Finally, we have included a pharmacoeconomic study comparing a conventional antipsychotic (haloperidol) with a new generation antipsychotic (quetiapine) in partially refractory patients in a South African setting. Findings and conclusions: 1. Psychopathology: Our studies demonstrated that the factor structure for the symptoms of schizophrenia is replicable across samples, and is not greatly influenced by ethnic and cultural factors. However, changes in the factor structures do occur over time. There are symptom domains that are present in first-episode schizophrenia but disappear as a distinct entity as the illness becomes chronic. Particularly, a motor component is evident in untreated patients, but disappears after initiation of treatment. We found that depression and anxiety are common co-morbid symptoms in schizophrenia, and have important clinical and outcome correlates. Depressive symptoms in the acute psychotic phase of schizophrenia are associated with a favourable prognosis and diminish as the symptoms of psychosis improve in response to antipsychotic treatment. However, persistent depressive symptoms are associated with a poorer prognosis, and require additional therapeutic intervention. 2. Neurobiological abnormalities: We investigated the occurrence of disordered water regulation in a population of psychiatric inpatients, and conducted further investigations on those identified, in order to establish mechanisms involved. Polydipsia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) were found to occur in a subset of patients with schizophrenia, and are associated with acute psychosis, as well as with some psychotropic medications. These patients are characterised by more severe cognitive impairment and evidence of cerebral atrophy. The condition can become life-threatening in the presence of other factors impeding water excretion, particularly thiazide diuretics. Neurological soft signs were investigated in a sample of patients with a first-episode of schizophrenia. These soft signs appear to be trait-like (present early in the illness, and stable over time), except for a motor sequencing factor. Patients performing poorly on this latter group of tests have a longer duration of untreated psychosis, and are at significant risk for developing TD. 3. Treatment aspects: Our studies suggest that there are important ethnic differences in antipsychotic treatment response, but that these differences could be explained by a number of environmental and biological factors. As was found with many studies worldwide, we found that the new generation antipsychotics have important efficacy and safety advantages over their predecessors. Risperidone was as effective as haloperidol in first-episode psychosis, but with a more favourable side-effect profile in terms of reduced extrapyramidal symptoms. Quetiapine treatment in partially refractory patients resulted in more responders compared to haloperidol, and fewer extrapyramidal symptoms. However, evidence of a different side-effect profile is emerging. Of particular concern is the finding that some of the new antispychotics cause weight gain, glucose intolerance and dyslipidaemias. We found that one novel antipsychotic, quetiapine, was not associated with significantly more weight gain or disordered glucose metabolism that a conventional agent, haloperidol. The omega-3 fatty acids, particularly EPA may have a role in the treatment of various psychiatric disorders. Our studies provided mixed results – the first found a significant beneficial effect on psychotic symptoms and dyskinesia scores for EPA supplementation, while the second failed to demonstrate a beneficial effect on TD or psychotic symptoms. We explored the early treatment response in first-episode psychosis and found, unlike that reported in multi-episode patients, some patients took a long time to respond. We also found that early treatment response was a significant predictor of later remission, as was duration of untreated psychosis, educational level and baseline excitement factor scores. Finally, our pharmacoeconomic study conducted for South African circumstances in patients with a partial response to conventional antipsychotic treatment showed cost-neutrality or cost-benefits for quetiapine compared with haloperidol treatment for direct costs.

Browsing by Author "Emsley, Robin A."

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