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Background: For optimizing the validity of diagnoses of mental disorders, several sources of information should be used to assess psychopathological symptoms. Among these are relatives of patients with mental illness. The very low number of empirical studies examining the assessment of psychopathology by relatives of adult, nondemented mentally ill patients stands in significant contrast to the clinical importance of this source of information, however. Sampling and Methods: Using the Positive and Negative Syndrome Scale (PANSS), researchers asked 163 relatives of patients with the main clinical ICD-10 diagnosis of schizophrenic, recurrent depressive or bipolar disorders to rate the current symptoms of the patients at the time of outpatient community-oriented treatment. Results: On average, severity of symptoms was rated as absent or minimal, although anxiety, depression and passive/apathetic social as well as emotional withdrawal, motor retardation, poor attention, and disturbance of volition were clearly rated above the PANSS mean total score for all patients. A six-factor structure identified by factor analysis better illustrates the significant differences in the assessments of the three main diagnostic groups than the three established PANSS scales. With the exception of ‘problematic social behavior’, differences among the diagnostic groups appeared in all factors and were particularly pronounced for ‘delusional beliefs’ and ‘motor impairments’. Conclusions: The results of this study showed that the use of standardized instruments such as PANSS for the assessment of psychopathology by relatives is not only practical, but produces adequately reliable results. The use of PANSS for this purpose, however, requires interviewing of relatives by trained experts able to explain technical terms. Because this study did not sufficiently explore the validity of this approach, further research on this specific issue is urgently needed and should, for example, assess the concordance of ratings between professionals and relatives as well as correlation with suitable external criteria. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: For optimizing the validity of diagnoses of mental disorders, several sources of information should be used to assess psychopathological symptoms. Among these are relatives of patients with mental illness. The very low number of empirical studies examining the assessment of psychopathology by relatives of adult, nondemented mentally ill patients stands in significant contrast to the clinical importance of this source of information, however. Sampling and Methods: Using the Positive and Negative Syndrome Scale (PANSS), researchers asked 163 relatives of patients with the main clinical ICD-10 diagnosis of schizophrenic, recurrent depressive or bipolar disorders to rate the current symptoms of the patients at the time of outpatient community-oriented treatment. Results: On average, severity of symptoms was rated as absent or minimal, although anxiety, depression and passive/apathetic social as well as emotional withdrawal, motor retardation, poor attention, and disturbance of volition were clearly rated above the PANSS mean total score for all patients. A six-factor structure identified by factor analysis better illustrates the significant differences in the assessments of the three main diagnostic groups than the three established PANSS scales. With the exception of ‘problematic social behavior’, differences among the diagnostic groups appeared in all factors and were particularly pronounced for ‘delusional beliefs’ and ‘motor impairments’. Conclusions: The results of this study showed that the use of standardized instruments such as PANSS for the assessment of psychopathology by relatives is not only practical, but produces adequately reliable results. The use of PANSS for this purpose, however, requires interviewing of relatives by trained experts able to explain technical terms. Because this study did not sufficiently explore the validity of this approach, further research on this specific issue is urgently needed and should, for example, assess the concordance of ratings between professionals and relatives as well as correlation with suitable external criteria. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

La schizophrénie est une pathologie fréquente et grave qui touche environ 1% de la population adulte jeune et constitue un problème majeur de santé public. Son mode évolutif reste marqué par la chronicité et la fréquence des rechutes. Depuis les années 1950 l'apport des neuroleptiques, puis celui des neuroleptiques atypiques présentant une meilleure tolérance neurologique, a considérablement modifié la prise en charge des patients souffrant de schizophrénie. Toutefois, les effets latéraux des neuroleptiques ont toujours constitués une des principales limites de cet apport thérapeutique la seconde étant l'importance des non réponses au traitement voire des résistances. Le pourcentage d'échec au traitement en phase aigue reste encore très élevé sans que l'on soit capable de prédire le risque de non réponse en fonction du traitement choisi. En pratique clinique, le choix thérapeutique se fait souvent de façon empirique. L'utilisation de critères diagnostics fiables et harmonisés (DSMIV) ainsi que l'approche de la réponse au traitement à l'aide d'outils de mesures dimensionnels (PANSS, BPRS, CGI) ont permis de réaliser une progression majeure dans l'abord de la recherche clinique dans la schizophrénie. En particulier les critères associés au pronostic évolutif ont pu être mieux appréhendés. Des facteurs prédictifs cliniques et précliniques d'une mauvaise réponse au traitement chez les patients principalement traités par des neuroleptiques conventionnels ont été décrits : l'âge de début de la maladie, la durée d'évolution sans traitement et la gravité de l'atteinte pour des critères cliniques. La pharmacogénétique étudie les mécanismes d'origine génétique impliqués dans la réponse aux médicaments et permet de mettre en évidence des critères prédictifs individuels en termes d'efficacité des traitements. Les données pharmacogénétiques concernant la réponse aux neuroleptiques sont présentées au cours de ce travail à travers une revue de la littérature. Les travaux effectués dans ce domaine concernent en particulier les hypothèses pharmacodynamiques et les gènes impliqués dans la synthèse des récepteurs aux monoamines. Les carences méthodologiques des 1ères études réalisées; en particulier en termes d'homogénéité ethnique des populations étudiées et d'évaluation du phénotype, expliquent que peu de résultat soient répliqués à ce jour. Dans une cohorte de patients schizophrènes caucasiens traités par olanzapine ou rispéridone et évaluée prospectivement pour l'efficacité et la tolérance du traitement, nous avons recherché des critères cliniques et socio-démographiques permettant de prédire la réponse au traitement. L'âge précoce de début des troubles et la durée de la maladie sont des prédicteurs individuels de la mauvaise réponse au traitement. Nous avons également étudié l'implication de variants génétiques du transporteur de la noradrénaline, inhibé par l'olanzapine et la rispéridone, dans l'efficacité des traitements antipsychotiques. Nous avons observé l'implication de 2 polymorphismes de ce transporteur dans la décroissance des symptômes positifs sous traitement. Ces travaux ont permis de confirmer la difficulté de prédire la réponse au traitement dans la schizophrénie sans développer des marqueurs biologiques fiables. L'apport de la pharmacogénétique semble une voie essentielle dans cette perspective.

Objectiu: L'estudi pretén valorar en quina mesura la simptomatologia i el funcionament cognitiu poden predir el nivell de discapacitat de pacients comunitaris amb diagnòstic d'esquizofrènia. Mètode: Es van seleccionar aleatòriament 231 pacients comunitaris amb diagnòstic d'esquizofrènia (criteris DSM-IV) del registre informatitzat que recull tots els pacients en tractament en qualsevol dels 5 centres de Salut Mental de Sant Joan de Déu-Serveis de Salut Mental. Els pacients van ser avaluats en un primer moment amb l'Escala de les Síndromes Positiva i Negativa (PANSS) i un qüestionari sociodemogràfic que incloïa l'escala d'Avaluació de la Discapacitat (DAS) i l'escala d'Avaluació del Funcionament Global (GAF). Es va realitzar una segona avaluació a la qual es va afegir una bateria neuropsicològica que incorporava mesures de memòria verbal, atenció, memòria operativa i funció d'abstracció i flexibilitat. Amb la finalitat de descriure com s'estructurava la simptomatologia de la mostra es va realitzar una anàlisi de components principals amb rotació oblimin amb els ítems de la PANSS. Per a avaluar com es relacionaven els factors clínics, amb la discapacitat i el funcionament cognitiu es van calcular els coeficients de correlació de Pearson. Per a establir la capacitat predictiva de les variables clíniques, simptomatològiques i cognitives sobre el grau de discapacitat es van desenvolupar models de regressió lineal. Resultats: Els quatre components principals seleccionats explicaven un 56.22% de la variància i es van identificar com Negatiu (32.48%), Excitatiu (11.29%), Afectiu (7.45%) i Positiu (5.01%). Una gravetat major de la simptomatologia negativa es va associar amb majors dèficits cognitius. Totes les àrees de discapacitat llevat de la discapacitat en el funcionament ocupacional es van explicar parcialment per la dimensió negativa. Conclusió: Els dominis Positiu i negatiu són comuns en tots els resultats previs d'anàlisis de components principals. La simptomatologia negativa és la major font de discapacitat de la nostra mostra i també s'associa amb un pitjor funcionament cognitiu. / Objetivo: El estudio pretende valorar en qué medida la sintomatología y el funcionamiento cognitivo pueden predecir el nivel de discapacidad de pacientes comunitarios con diagnóstico de esquizofrenia. Método: Se seleccionaron aleatoriamente 231 pacientes comunitarios con diagnostico de esquizofrenia (criterios DSM-IV) del registro informatizado que recoge todos los pacientes en tratamiento en cualquiera de los 5 centros de Salud Mental de Sant Joan de Déu-Serveis de Salut Mental. Los pacientes fueron evaluados en un primer momento con la la Escala de los Síndromes Positivo y Negativo (PANSS), y un cuestionario socio demográfico que incluía la escala de Evaluación de la Discapacidad (DAS) y la escala de Evaluación del Funcionamiento Global (GAF). Se realizó una segunda evaluación a la que se añadió una batería neuropsicológica que incorporaba medidas de memoria verbal, atención, memoria operativa y función de abstracción y flexibilidad. Con la finalidad de describir como se estructuraba la sintomatología de la muestra se realizó un análisis de componentes principales con rotación oblimin con los ítems de la PANSS. Para evaluar como se relacionaban los factores clínicos, con la discapacidad y el funcionamiento cognitivo se calcularon los coeficientes de correlación de Pearson. Para establecer la capacidad predictiva de las variables clínicas, sintomatológicas y cognitivas sobre el grado de discapacidad de desarrollaron modelos de regresión lineal. Resultados: Los cuatro componentes principales seleccionados explicaban un 56.22% de la varianza y se identificaron como Negativo (32.48%), Excitativo (11.29%), Afectivo (7.45%) y Positivo (5.01%). Una gravedad mayor de la sintomatología negativa se asoció con mayores déficits cognitivos. Todas las áreas de discapacidad a excepción de la discapacidad en el funcionamiento ocupacional se explicaron parcialmente por la dimensión negativa. Conclusión: Los dominios Positivo y negativo son comunes en todos los resultados previos de análisis de componentes principales. La sintomatología negativa es la mayor fuente de discapacidad de nuestra muestra y también se asocia con un peor funcionamiento cognitivo. / Objective: The study aims to assess the load of symptoms and cognitive functioning when predicting disability of outpatients with diagnosis of schizophrenia. Method: 231 outpatients a diagnose of schizophrenia (DSM-IV criteria) were randomly selected from a computerized register that included all patients under treatment in any of the 5 Mental Health Centers of Sant Joan of Déu-Serveis of Salut Mental. Patients were assessed at baseline with the Positive and Negative Syndrome Scale (PANSS), and a sociodemographic questionnaire that included the Disability Assessment Scale (DAS) and the Global Assessment of Functioning Scale (GAF). A second evaluation which also included a neuropsychological battery was conducted. The battery included measures verbal memory, attention, operative memory and abstraction and flexibility functions. In order to describe how symptoms structured a principal component analyses with oblimin rotation was conducted with the PANSS items. To assess the associations between clinical factors, disability and cognitive functioning Pearson correlation coefficients were computed. In order to establish the predictive capacity of the cognitive, clinical and symptom variables on disability linear regression models were fitted. Results: The four principal components accounted for 56.22% of the variance. These factors were identified as Negative (32.48%), Excitement (11.29%), Affective (7.45%) and Positive (5.01%). More severity of negative symptoms was associated with worse cognitive functioning. All disability areas except for occupational disability were partially explained by the negative dimension. Conclusion: The Positive and negative components are common in all previous results of principal components analysis. Negative symptoms are the major source of disability of our sample and also associate with a worse cognitive functioning.

There is an increase in the prevalence of obesity among people with schizophrenia thought to be due in part to the weight enhancing side-effects of medications commonly used to treat the symptoms of schizophrenia. Despite the deleterious health effects associated with obesity and its impact on quality of life and medication compliance, little is known about body composition and energy expenditure in this clinical group. The primary purpose of this thesis was to enhance understanding of body composition and energy expenditure, particularly resting energy expenditure in men with schizophrenia who take atypical antipsychotic medications. Unique to this investigation is the evaluation of clinical tools used to predict body composition and energy expenditure against reference methodologies in men with schizophrenia. Further, given the known links between obesity and physical activity, an additional but less comprehensive component of the thesis was a consideration of total and activity energy expenditure in addition to the interaction between psychiatric symptoms, side-effects of antipsychotic medications and physical activity also occurred as part of this thesis. Collectively, the goals of this thesis were addressed through a series of studies – the first two studies were related to the measurement and characteristics of body composition in men with schizophrenia, while the third and fourth studies were related to the measurement and characteristics of resting energy expenditure in men with schizophrenia. The fifth and sixth studies the utilised doubly labelled water technique to quantify activity and total energy expenditure in a small group of men with schizophrenia and explored the use of accelerometry in this cohort. The final study briefly considered the impact of psychiatric symptoms and self-reported medication side-effects on objectively measured physical activity. In the first study, thirty-one male adults previously diagnosed with schizophrenia and sixteen healthy male controls were recruited. Estimates of body composition derived from an anthropometry-based equation and from bioelectric impedance analysis (BIA) using deuterium dilution as the reference methodology to determine total body water were compared. The study also determined the validity of equations commonly used to predict body composition from BIA in the men with schizophrenia. A further aim was to determine the superiority of either BIA or body mass index (BMI) as an indicator of obesity in this cohort. The inclusion of the control group, closely matched for age, body size and body composition demonstrated that there was no difference in the ability of body composition prediction methods to distinguish between fat and fat-free mass (FFM) in controls and men with schizophrenia when both groups had similar body composition. However this study indicated that an anthropometry-based equation previously used in people with schizophrenia was a poor predictor of body composition in this cohort, as evidenced by wide limits of agreement (25%) and systematic variation of the bias. In comparison, the best predictor of percentage body fat (%BF) in this group was gained when impedance values were used to predict percentage body fat via the equation published by Lukaski et al (1986). Although percentage body fat was underpredicted using the Lukaski et al. (1986) equation, the mean magnitude was relatively small (1.3%), with the limits of agreement approximately 13%. Linear regression analysis revealed that %BF predicted using the Lukaski et al. (1986) equation explained 25% more of the variance in percentage body fat than BMI. Further, this study also indicated that BIA was more sensitive than BMI in distinguishing between overweight and obesity in this cohort of men with schizophrenia. Because of the almost exclusive use of BMI as an indicator of obesity in people with schizophrenia, the level of excess body fat may be in excess of that previously indicated. The second study extended the examination of body composition in men with schizophrenia. In this study, the thirty-one participants with schizophrenia (age, 34.2 ± 5.7 years; BMI, 30.2 ± 5.7 kg/m2) were individually matched with sedentary controls by age, weight and BMI. Deuterium dilution was used to distinguish between FFM and fat mass. The previous study had indicated that while BIA was a suitable group measure for obesity, on an individual level the technique lacked the precision required for investigating body composition in men with schizophrenia. Waist circumference was used as an indicator of body fat distribution. The findings of this study indicated that in comparison with healthy sedentary controls of similar body size and age, men with schizophrenia had higher levels of body fat which was more centrally distributed. Percentage body fat was on average 4% higher and waist circumference, on average 5 cm greater in men with schizophrenia than the sedentary controls of the same age and BMI. Further, this study indicates that the use of BMI to predict body fat in men with schizophrenia will result in greater bias than when it is used to predict body fat in other sedentary men. Commonly used regression equations to predict energy requirements at rest are based on the relationships between weight and resting energy expenditure (REE) and in such equations, weight acts as a surrogate measure of FFM. The objectives of study three were to measure REE in a small group of men with schizophrenia who were taking the antipsychotic medication clozapine and to determine whether REE can be predicted with sufficient accuracy to substitute for the measurement of REE in the clinical and/or research settings. Body composition was determined using deuterium dilution and REE was measured using a Deltatrac Metabolic Cart via a ventilated hood. The male participants, (aged 28.0 ± 6.7 yrs, BMI 29.8 ± 6.8 kg/m2) were weight stable at the time of the study and had been taking clozapine for 20.5 ± 12.8 months, with doses of 450 ± 140 mg/day. Of the six prediction equations evaluated, the equation of Mifflin et al. (1990) with no systematic bias, the lowest bias and the lowest limits of agreement proved to be the most suitable equation to predict REE in this cohort. The overestimation of REE can be corrected for by deducting 160 kcal/day from the predicted REE value when using the Mifflin et al. (1990) equations. However, the magnitude of the error associated with the prediction of REE for an individual is 370 kcal/day. The findings of this study indicate that REE cannot be predicted with sufficient individual accuracy in men with schizophrenia, therefore it was necessary to measure rather than predict REE in subsequent studies. In the fourth study, indirect calorimetry (Deltatrac Metabolic Cart via ventilated hood) and deuterium dilution were used to accurately determine REE, respiratory quotient (RQ) and FFM in 31 men with schizophrenia and healthy sedentary controls individually matched for age and BMI. Data from this study indicated that gross REE was lower in men with schizophrenia than in healthy sedentary controls of a similar age and body size. However, there was no difference between the groups in REE when REE was adjusted for FFM using the mathematically correct method (analysis of covariance with FFM as the covariate). There was however a statistically and clinically significant difference in resting, fasted RQ between men with schizophrenia and controls, suggesting that RQ rather than REE may be an important correlate worthy of further investigation in men with schizophrenia who take antipsychotic medications. Studies five and six involved the application of the doubly labelled water (DLW) technique to accurately determine total energy expenditure (TEE) and activity energy expenditure (AEE) in a small group of men with schizophrenia who had been taking the atypical antipsychotic medication clozapine. The participants were those who took part in study three. The purpose of these studies was to assess the validity of a commercially available tri-axial accelerometer (RT3) for predicting free-living AEE and to investigate TEE and AEE in men with schizophrenia. There was poor agreement between AEE measured using DLW and AEE predicted using the RT3. However, using the RT3 to measure inactivity explained over two-thirds of the variance in AEE. This study found that the relationship between current AEE per kilogram of body weight and change from baseline weight in men taking clozapine was strong although not significant. The sedentary nature of the group of participants in this study was reflected in physical activity levels, (PAL, 1.39 ± 0.27), AEE (435 ±352 kcal/day) and TEE (2511 ± 606 kcal/day) that fell well short of values recommended by WHO (2000) for optimal health and to prevent weight gain. Given the increasing recognition of the importance of sedentary behaviour to weight gain in the general community, further examination of the unique contributing factors such as medication side effects and symptoms of mental illness to activity levels in this clinical group is warranted. The final study used accelerometry (RT3) to objectively measure activity in a group of 31 men with schizophrenia who had been taking atypical antipsychotic medications for more than four months. The purpose of this study was to explore the relationships between psychiatric symptomatology, side-effects of medication and physical activity. Accelerometry output was analysed to provide a measure of inactivity and moderate intensity activity (MIA). The well-validated and reliable standardised clinical interview, the Positive and Negative Syndrome Scale (PANSS) was used as a measure of psychiatric symptoms. Perceived side-effects of medication were assessed using the Liverpool University Neuroleptic Rating Side-Effects Scale (LUNSER). Surprisingly, there was no relationship reported between any measures of negative symptoms and physical inactivity. However, self-reported measures of medication side-effects relating to fatigue, sleepiness during the day and extrapyramidal symptoms explained 40% of the variance in inactivity. This study found significant relationships between some negative symptoms and moderate intensity activity. Despite the expectation that as symptoms of mental illness reduce, inactivity may diminish and moderate intensity activity will increase, it may not be surprising that in practice this is an overly simplistic view. It may be that measures of social functioning and possibly therefore cognition may be better predictors of physical activity than psychiatric symptomatology per se.