Browsing by Author "Koen L."
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- ItemAmisulpride as adjunct to clozapine in treatment-resistant schizophrenia and schizoaffective disorder: An open-label pilot study(2006) Koen L.; Niehaus D.J.; Schulte A.; Muller J.; Emsley R.; Oosthulzen P.Background. Although clozapine is the treatment of choice for treatment-resistant schizophrenia, many patients remain symptomatic despite adequate treatment with this medication. One suggested strategy to improve efficacy has been the addition of a potent D2 blocker such as amisulpride to treatment with clozapine. Methods. In this study, 20 subjects who were treatment-resistant to conventional antipsychotics and who were still symptomatic despite adequate treatment with clozapine received amisulpride as adjunctive treatment. After baseline assessment all subjects were titrated to amisulpride 400 mg per day and then reassessed after 8 weeks by a blinded rater. Results. Analysis showed statistically significant improvements in PANSS (Positive and Negative Symptom Scale) total score (t = 3.49, df = 18, p = 0.003), PANSS negative subscale score (t = 3.22, df = 18, p = 0.005), and PANSS depression factor score (t = 3.89, df = 19, p = 0.001). Discussion. This study suggests that addition of the second-generation antipsychotic amisulpride to a stable treatment regimen with clozapine may offer additional benefits in terms of negative and depressive symptoms.
- ItemApplicability and fairness of the oral examination in undergraduate psychiatry training in South Africa(2012) Niehaus D.J.H.; Jordaan E.; Koen L.; Mashile M; Mall S.Objective: There are several methods of evaluating medical students' performance, such as written examination, oral examination and objective structured clinical examination (OSCE). Many studies have focused on the reliability and validity of these methods but few studies have explored comparison between these methods. Psychiatry is the only subject at the University of Stellenbosch where the final assessment consists of solely an oral component. The aim of the study was to compare students' final overall and discipline specific examination marks (i.e. in the other subjects) with the examination marks in psychiatry, and to determine if content or structure (e,g. oral, written or OSCE format) of examination impacts more on the student performance in the examination. Method: 343 final year medical students were included. All undertook their psychiatry rotation at the University of Stellenbosch, South Africa during 2008 and 2009. Data of marks obtained in all the disciplines during 2008 and 2009 were collected and class marks were compared with their final examination marks across all disciplines. Bland-Altman plots were used to assess the level of agreement between the class and examination marks. Cases below the lower threshold were compared to all other cases across all disciplines. The odds ratio for group status was calculated for gender distribution of examiners. Results: The psychiatry class mark and final oral examination mark provided similar measures within a width of 31.5. Cases below the threshold had poorer performance in two other disciplines. The gender distribution of the examiners (female-female) significantly increased the odds ratio for poorer performance in the oral examination.Conclusion: The results suggest that a group of students underperform in their final examination independent of method of evaluation and that the gender of examiners impacts on examination marks. Therefore future research should focus on identifying and modifying factors (including choice of examiner combinations) that contribute to the poor performance of medical students in their final examination, in order to help students perform better. Gender distribution of examiners should also be considered when examinations are structured and designed.
- ItemAssociation of MB-COMT polymorphisms with schizophrenia-susceptibility and symptom severity in an African cohort(2012) Wright G.E.B.; Niehaus D.J.H.; van der Merwe L.; Koen L.; Korkie L.J.; Kinnear C.J.; Drogemoller B.I.; Warnich L.The catechol- O-methyltransferase (COMT) gene is an attractive schizophrenia candidate gene, encoding a catabolic dopamine enzyme. The enzyme exists as two distinct isoforms, with the membrane bound enzyme (i.e. MB-COMT) being predominantly expressed in the brain. Since African populations remain underrepresented in genetic/genomic research, we performed an association study to determine whether MB-COMT genetic variants are associated with schizophrenia-susceptibility and symptom severity in the South African Xhosa population.Fourteen candidate polymorphisms were selected by means of a literature search and in silico analyses and were subsequently genotyped in a cohort of 238 Xhosa schizophrenia patients and 240 healthy Xhosa controls. Genetic association was tested with schizophrenia-susceptibility as well as symptom severity within the patient group. Polymorphisms of interest were also analysed using functional assays.Two SNPs, rs2020917 (OR = 0.54, 95% CI 0.37-0.79; P= 0.0011) and rs737865 (OR = 0.52, 95% CI 0.36-0.74; P= 0.0002), in the P2 promoter region were significantly associated with schizophrenia as well as an increase (increase = 11.2%, 95% CI 3.7%-19.2%; P= 0.0031) in reporter gene expression. The minor alleles of these SNPs were underrepresented in the schizophrenia cohort, indicating a possible protective effect. The P2 region also formed part of a haplotype found to be associated with the severity of the negative symptoms of the disorder.The data generated by this study indicate that genetic variation of MB-COMT could be associated with schizophrenia and negative symptom severity in the Xhosa population and may therefore be one of the genomic loci contributing towards the disorder in the South African community. Future large-scale studies in other African schizophrenia populations are required to further elucidate the significance of these findings. © 2012 Elsevier Inc.
- ItemChanging the course of schizophrenia - Predictors of treatment outcome revisited(2007) Emsley R.; Oosthulzen P.; Niehaus D.; Koen L.; Chiliza B.Multiple factors play a role in determining the outcome of schizophrenia. However, the role of these factors is poorly understood, and research findings so far have been inconclusive and sometimes contradictory. Various demographic and baseline clinical factors have been reported to be associated with treatment outcome. Also, early symptom reduction after initiation of antipsychotic therapy is closely related to later treatment response. However, associations as such do not necessarily imply predictive value, and none of these factors can be regarded as clinically useful in predicting treatment outcome. This article discusses selected aspects of treatment outcome and its prediction in schizophrenia, focusing particularly on early treatment response, ethnicity, neurological soft signs, and the predictive value of a discriminant functional analysis model utilising a combination of putative predictors. Such a model holds promise, and it is to be hoped that future refinements will lead to a clinically useful model for predicting outcome.
- ItemClozapine-induced intestinal obstruction - A critical examination of four cases(2006) Seller C.; Koen L.; Niehaus D.J.H.[No abstract available]
- ItemConcordance of patient and clinical ratings of symptom severity and change of psychotic illness(2008) Rabinowitz J.; Levine S.Z.; Medori R.; Oosthuizen P.; Koen L.; Emsley R.[No abstract available]
- ItemDeficits in facial affect recognition in unaffected siblings of Xhosa schizophrenia patients: Evidence for a neurocognitive endophenotype(2008) Leppanen J.M.; Niehaus D.J.H.; Koen L.; Du Toit E.; Schoeman R.; Emsley R.The present study in an African Xhosa sample examined whether familial vulnerability to schizophrenia is associated with deficits in facial affect recognition. Healthy comparison subjects, unaffected siblings of schizophrenia patients, and schizophrenia patients were tested with a task requiring rapid recognition of matched positive (happy), negative (angry), and neutral facial expressions. Siblings and patients demonstrated impaired recognition of negative relative to positive facial expressions whereas comparison subjects recognized negative and positive expressions at an equal level of accuracy. These results suggest that deficits in the processing negative affect from social cues are transmitted in families and may represent a heritable endophenotype of schizophrenia. © 2007 Elsevier B.V. All rights reserved.
- ItemEmotional face processing deficit in schizophrenia: A replication study in a South African Xhosa population(2006) Leppanen J.M.; Niehaus D.J.H.; Koen L.; Du Toit E.; Schoeman R.; Emsley R.Schizophrenia is associated with a deficit in the recognition of negative emotions from facial expressions. The present study examined the universality of this finding by studying facial expression recognition in African Xhosa population. Forty-four Xhosa patients with schizophrenia and forty healthy controls were tested with a computerized task requiring rapid perceptual discrimination of matched positive (i.e. happy), negative (i.e. angry), and neutral faces. Patients were equally accurate as controls in recognizing happy faces but showed a marked impairment in recognition of angry faces. The impairment was particularly pronounced for high-intensity (open-mouth) angry faces. Patients also exhibited more false happy and angry responses to neutral faces than controls. No correlation between level of education or illness duration and emotion recognition was found but the deficit in the recognition of negative emotions was more pronounced in familial compared to non-familial cases of schizophrenia. These findings suggest that the deficit in the recognition of negative facial expressions may constitute a universal neurocognitive marker of schizophrenia. © 2006 Elsevier B.V. All rights reserved.
- ItemEscitalopram in the treatment of multisomatoform disorder: A double-blind, placebo-controlled trial(2008) Muller J.E.; Wentzel I.; Koen L.; Niehaus D.J.H.; Seedat S.; Stein D.J.Despite the prevalence of multisomatoform disorder (MSD), there are few controlled trials of its pharmacotherapy. The aim of this study was to compare the efficacy and safety of escitalopram (10-20 mg/day) with that of placebo in treating patients with MSD over a 12-week period. Fifty-one outpatients aged from 18 to 65 years, with multiple medically unexplained symptoms, were recruited. The primary efficacy measure was a change on the Patient Health Questionnaire-15 scores from baseline to endpoint. Secondary efficacy endpoints included the Clinical Global Impression-Improvement score, the psychic and somatic subscales of the Hamilton Anxiety Scale, Montgomery-Asberg Depression Rating Scale, the Visual Analogue Pain Rating Scale, the Scale for the Assessment of Illness Behaviour and the Sheehan Disability Scale. On the primary analysis of covariance, escitalopram-treated patients had significantly greater reductions in Patient Health Questionnaire scores (P<0.0001) compared with placebo at week 12. Significant separation from placebo occurred from week 6 onwards. Escitalopram was superior to placebo on all secondary outcome endpoints, with the exception of the Scale for the Assessment of Illness Behaviour. The medication was well tolerated. In conclusion, in this 12-week, randomized, placebo-controlled study, escitalopram (10-20 mg/day) was both effective and well tolerated in the treatment of patients with MSD. Compared with placebo, escitalopram was associated with lower symptom scores, increased response and remission rates, and improved functioning. © 2008 Lippincott Williams & Wilkins, Inc.
- ItemHoarding behaviour in Xhosa patients with schizophrenia - Prevalence and clinical presentation(2007) Ameer T.; Niehaus D.J.H.; Koen L.; Seller C.; Seedat S.Objective. Hoarding is commonly defined as the acquisition of and failure to discard possessions of little use or value, and is included as a symptom in the diagnostic criteria for obsessive compulsive personality disorder (OCPD) and obsessive compulsive disorder (OCD). However, it has also been observed in other clinical syndromes including schizophrenia. This study was conducted to investigate the prevalence and clinical presentation of hoarding behaviour in schizophrenia among Xhosa patients. Method. The sample consisted of 102 patients, recruited as part of a larger genetic study in the Cape Town metropole between November 2004 and January 2005, diagnosed with schizophrenia or schizoaffective disorders according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. They were screened for clinically significant hoarding symptoms. If these were present, additional information on the phenomenology was obtained by means of a structured questionnaire. The Mini International Neuropsychiatric Interview (MINI) (screen and full version), the Yale Brown Obsessive Compulsive Scale (Y-BOCS) Checklist, Y-BOCS, Clutter Image Rating Scale (CIRS) and a structured questionnaire on hoarding were administered. Results. Only four patients with schizophrenia were classified as hoarders. Although their clinical presentation resembled that of hoarders described elsewhere in the literature, they had low Y-BOCS scores and did not report other obsessive-compulsive symptoms. Conclusion. Our results suggest that hoarding behaviour is not common in Xhosa patients with schizophrenia. Further investigation of protective factors for hoarding behaviour in the Xhosa population is warranted.
- ItemPositive and negative symptoms in affected sib pairs with schizophrenia: Implications for genetic studies in an African Xhosa sample(2005) Niehaus D.J.H.; Koen L.; Laurent C.; Muller J.; Deleuze J.-F.; Mallet J.; Seller C.; Jordaan E.; Emsley R.Careful phenotyping and the identification of subtypes of schizophrenia can contribute significantly to the success of genetic studies in schizophrenia. The phenomenology of schizophrenia in affected sib pairs has been well-described in Caucasian populations, however a paucity of data exists for African populations. This study therefore investigated symptom dimensions in a sizeable group of affected Xhosa sib pairs as a means of evaluating the role of shared familial factors in the psychosis of schizophrenia. Five hundred and thirteen participants were interviewed with the Diagnostic Interview for Genetic Studies (DIGS), which included the Schedules for the Assessment of Negative and Positive symptoms (SANS/SAPS). One hundred and four sib pairs were then extracted (N = 208) for analysis of concordance for lifetime psychotic symptoms and an exploratory factor analysis of the SANS/SAPS. Concordance analysis of life-time symptoms indicated a significant concordance for olfactory hallucinations, persecutory delusions, jealousy, somatic, reference and control delusions as well as thought insertion and withdrawal. The factor analysis of the global scores of the SAPS and SANS revealed a five factor best-fit model and accounted for 92.5% of variance. The factors included a negative symptom factor, a positive symptom factor, a positive thought disorder and a bizarre behaviour component. The core symptomatology of schizophrenia in this sib pair sample was similar to that reported in Caucasian populations with the exception of higher rates of auditory hallucinations and delusions of persecution. In summary therefore; although the factor analysis only supported the concept of the universality of psychotic symptoms in schizophrenia, the concordance analysis of these symptoms did reveal hallucinations as well as delusions of control as possible candidates relevant for future research into genotype-phenotype relationships. © 2005 Elsevier B.V. All rights reserved.
- ItemPsychiatric genetics in South Africa: Cutting a rough diamond(2011) Wright G.E.B.; Niehaus D.J.H.; Koen L.; Drogemoller B.I.; Warnich L.Psychiatric disorders place a considerable healthcare burden on South African society. Incorporating genetic technologies into future treatment plans offers a potential mechanism to reduce this burden. This review focuses on psychiatric genetic research that has been performed in South African populations with regards to obsessive-compulsive disorder, schizophrenia and bipolar disorder. Preliminary findings from these studies suggest that data obtained in developed countries cannot necessarily be extrapolated to South African population groups. Psychiatric genetic studies in South Africa seem to involve relatively low-cost methodologies and only a limited number of large national collaborative studies. Future research in South Africa should therefore aim to incorporate highthroughput technologies into large scale psychiatric studies through the development of collaborations. On a global level, the vast majority of psychiatric genetic studies have been performed in non-African populations. South Africa, as the leading contributor to scientific research in Africa, may provide a foundation for addressing this disparity and strengthening psychiatric genetic research on the continent. Although the elucidation of the genetic architecture of psychiatric disorders has proved challenging, examining the unique genetic profiles found in South African populations could provide valuable insight into the genetics of psychiatric disorders.
- ItemRemission in first-episode psychosis: Predictor variables and symptom improvement patterns(2006) Emsley R.; Oosthuizen P.P.; Kidd M.; Koen L.; Niehaus D.J.H.; Turner H.J.Background: Previous attempts to identify clinically useful predictors of treatment outcome in schizophrenia have been hampered by methodological inconsistencies, including a lack of standardized outcome measures. Recently proposed operationally defined criteria for remission provide an opportunity to readdress this topic. Method: We applied the remission criteria to a sample of 57 subjects with first-episode psychosis (DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder), treated according to a fixed protocol in a prospective study. Subjects were recruited between April 1999 and January 2000 and were followed for 2 years. Various demographic, baseline clinical, and early-response variables were subjected to discriminant analysis for their ability to predict remission or nonremission. We also assessed the symptom improvement patterns over time and compared endpoint psychopathology in the remitters and nonremitters. Results: A model incorporating neurologic soft signs, 6-week treatment response, duration of untreated psychosis, marital status, and Positive and Negative Syndrome Scale excited factor baseline score was able to correctly predict 89% of the remitters and 86% of the nonremitters. Symptom reduction at 6 weeks, including core psychotic symptoms, was significant in both groups (remitters, p < .0001; nonremitters, p < .0001), although reduction was substantially greater in the remission group (p = .004). Thereafter, the remission group continued to improve (p < .01), while the nonremitting group failed to do so (p = .55). Considerable overlap of endpoint symptoms was observed, and depressive symptom scores were similar in remitters and nonremitters. Conclusion: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict treatment outcome. Persistent noncore psychotic symptoms in subjects meeting proposed remission criteria require further investigation.
- ItemRemission in patients with first-episode schizophrenia receiving assured antipsychotic medication: A study with risperidone long-acting injection(2008) Emsley R.; Oosthuizen P.; Koen L.; Niehaus D.J.H.; Medori R.; Rabinowitz J.Recently proposed criteria for remission by a 'Remission in Schizophrenia Working Group' have generated considerable interest. We assessed rates, predictors, and correlates of remission in a sample of patients with first-episode schizophrenia treated with injectable, long-acting risperidone. This allowed us to examine remission among patients known to be receiving medication. This was a single-site open-label study in which 50 newly diagnosed cases of schizophreniform disorder or schizophrenia aged 16 to 43 years were treated with injectable, long-acting risperidone 25-50 mg every 2 weeks for 2 years. Remission, according to Remission in Schizophrenia Working Group criteria, was achieved in 64% of the patients. Of those achieving remission, 97% maintained this status until study completion. Remission was associated with greater improvements in other symptom domains, insight, and social and occupational functioning. Patients in remission received lower doses of antipsychotic medication, had fewer extrapyramidal symptoms, and a more favorable attitude toward medication. The results of this open-label study suggest that a majority of first-episode patients who receive long-acting injectable antipsychotic medication may achieve sustained remission. Double-blind-controlled studies using long-acting injectable antipsychotics in early psychosis are warranted to further test this. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
- ItemSubjective awareness of tardive dyskinesia and insight in schizophrenia(2011) Emsley R.; Niehaus D.J.H.; Oosthuizen P.P.; Koen L.; Chiliza B.; Fincham D.Background: Lack of awareness of tardive dyskinesia (TD) and poor insight into mental illness are common in schizophrenia, raising the possibility that these phenomena are manifestations of a common underlying dysfunction. Methods: We investigated relationships between low awareness of TD and poor insight into mental illness in 130 patients with schizophrenia and TD. We also examined selected demographic and clinical correlates of these two phenomena. Results: Sixty-six (51%) patients had no or low awareness of TD and 94 (72%) had at least mild impairment of insight into their mental illness. Low awareness of TD was not significantly correlated with greater impairment of insight into mental illness. Regression analyses indicated that the Positive and Negative Syndrome Scale (PANSS) disorganised factor (β=0.72, t=11.88, p<0.01) accounted for 52% of the variance in insight into mental illness (adjusted R2=0.55) (F[2, 127]=81.00, p<0.01) and the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale score (β=0.47, t=6.80, p<0.01), PANSS disorganised factor (β=-0.26, t=-3.73, p<0.01), and ESRS parkinsonism subscale score (β=0.31, t=4.55, p<0.01) together accounted for 37% of the variance in awareness of TD (adjusted R2=0.37) (F[3, 126]=26.87, p<0.01). Conclusion: The two phenomena appear to be dissociated, and may be domain-specific. © 2010 Elsevier Masson SAS.
- ItemSymptom recurrence following intermittent treatment in first-episode schizophrenia successfully treated for 2 years: A 3-year open-label clinical study(2012) Emsley R.; Oosthuizen P.P.; Koen L.; Niehaus D.J.H.; Martinez G.Objective: An unanswered question in the management of schizophrenia is how long antipsychotic treatment should be continued after a single psychotic episode. In this study, we assessed the rates of symptom recurrence with intermittent treatment in patients with a first episode of DSM-IV-defined schizophrenia or related illness after 2 years of successful continuous treatment. We also investigated antecedents of recurrence, as well as demographic and baseline clinical predictors of early recurrence, and we compared the psychopathology of the recurrence episode with that of the first episode. Method: Outpatients in an academic psychiatric hospital setting (single site) who had responded well in an open-label study with risperidone long-acting injection were recruited for this intermittent treatment trial, and those who participated had their treatment tapered and discontinued over a period of up to 6 weeks, with follow-up for 3 years or until reemergence of symptoms. Open-label treatment with oral risperidone and risperidone long-acting injection was immediately reinstituted in the event of recurrence of symptoms. The study was conducted between February 2004 and March 2010. The primary outcome measure was symptom recurrence rate at 3 years. Results: Participants (N = 33) had a mean age ± SD of 28 ± 7.9 years and a mean baseline Positive and Negative Syndrome Scale total score ± SD of 44.8 ± 7.4 at study entry. Symptom recurrence rates were 79% at 12 months, 94% at 24 months, and 97% at 36 months. Onset of recurrence symptoms was fairly abrupt, and symptom severity returned to levels close to those of the first episode. No significant predictors of early recurrence were identified. Conclusions: Intermittent antipsychotic treatment, even after 2 years of successful treatment, may not be in the best interest of patients who have experienced a single psychotic episode. Trial Registration: ClinicalTrials.gov identifier: NCT00378092. © Copyright 2012 Physicians Postgraduate Press, Inc.
- ItemThe effects of eicosapentaenoic acid in tardive dyskinesia: A randomized, placebo-controlled trial(2006) Emsley R.; Niehaus D.J.H.; Koen L.; Oosthuizen P.P.; Turner H.J.; Carey P.; van Rensburg S.J.; Maritz J.S.; Murck H.Objective: Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. Method: This was a 12-week, double-blinded, randomized study of ethyl-EPA 2 g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. Results: Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences (p = 0.4). Response rates (≥ 30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) (p = 0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. Conclusions: This trial failed to demonstrate an antidyskinetic effect for ethyl-EPA 2 g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an antidyskinetic action. © 2006 Elsevier B.V. All rights reserved.