Article

Comparison of psychotic bipolar disorder, schizoaffective disorder, and schizophrenia: An international, multisite study

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Abstract

Nosological distinctions among schizoaffective disorder (SA), bipolar I disorder with psychotic features (BDp), and schizophrenia (SZ) remain unresolved. We compared 2269 subjects with psychotic features in DSM-IV-TR diagnoses (1435 BDp, 463 SZ, 371 SA) from 8 collaborating international sites, by 12 sociodemographic and clinical measures, all between diagnostic pairs. In bivariate comparisons, SA was consistently intermediate between BDp and SZ for 11/12 features (except onset stressors), and SZ vs. BDp differed in all 12 factors. SA differed from both BDp and SZ in 9/12 factors: SA and BDp were similar in education and suicidal ideation or acts; SA and SZ were similar in education, onset stressors, and substance abuse. Meta-analytic comparisons of diagnostic pairs for 10 categorical factors indicated similar differences of SA from both SZ and BDp. Multivariate modeling indicated significantly independent differences between BDp and SZ (8 factors), SA vs. SZ (5), and BDp vs. SA (3). Measurement variance was similar for all diagnoses. SA was consistently intermediate between BDp and SZ. The three diagnostic groups ranked: BDp > SA > SZ related to lesser morbidity or disability. The findings are not consistent with a dyadic Kraepelinian categorization, although the considerable overlap among the three DSM-IV diagnostic groups indicates uncertain boundaries if they represent distinct disorders. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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... Substantial debate regarding the utility of categorical vs. dimensional classification in psychotic disorders continues across the psychosis spectrum and in disorders such as SZA in particular (1)(2)(3)(4)(5)(6). The Kraepelinian dichotomy draws a sharp boundary between BP and SZ; diagnoses that share characteristics of both disorders may be conceptualized as categorically separate disorders or may be considered to fall along a continuum in which someone may move toward one end or the other reflecting shifting symptom profiles (2,3). ...
... Substantial debate regarding the utility of categorical vs. dimensional classification in psychotic disorders continues across the psychosis spectrum and in disorders such as SZA in particular (1)(2)(3)(4)(5)(6). The Kraepelinian dichotomy draws a sharp boundary between BP and SZ; diagnoses that share characteristics of both disorders may be conceptualized as categorically separate disorders or may be considered to fall along a continuum in which someone may move toward one end or the other reflecting shifting symptom profiles (2,3). Nevertheless, clear evidence of the superiority of categorical vs. dimensional classification systems has not been demonstrated (7), and pre-defined categorization of diagnoses is commonly used in both clinical and research settings. ...
... SZA had a stability rate of 63.6% in our sample. As noted above, stability of the SZA classification has been highly variable across studies [1][2][3][4][5][6], which may reflect findings of (12, 13) shared and distinct phenomenological and genetic associations across the Kraeplinean divide (24). ...
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Psychiatric diagnosis is often treated as a stable construct both clinically and in research; however, some evidence suggests that diagnostic change may be common, which may impact research validity and clinical care. In the present study we examined diagnostic stability in individuals with psychosis over time. Participants with a diagnosis of any psychotic disorder ( n = 142) were assessed at two timepoints using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. We found a 25.4% diagnostic change rate across the total sample. People with an initial diagnosis of psychosis not otherwise specified and schizophreniform disorder had the highest rates of change, followed by those with schizophrenia and schizoaffective disorder; people with bipolar disorder had the lowest change rate. Most participants with an unstable initial diagnosis of schizophrenia, schizophreniform disorder, bipolar disorder, or psychosis not otherwise specified converted to a final diagnosis of schizoaffective disorder. Participants with an unstable initial diagnosis of schizoaffective disorder most frequently converted to a diagnosis of schizophrenia. Our findings suggest that diagnostic change is relatively common, occurring in approximately a quarter of patients. People with an initial diagnosis of schizophrenia-spectrum disorder were more likely to have a diagnostic change, suggesting a natural stability of some diagnoses more so than others.
... Most research to date on the association of psychosocial risk factors with psychosis has focused on SZ psychoses (Ayesa-Arriola et al., 2016;Compton, Kelley, & Ionescu, 2014;Crow, 1990;Jablensky, 2006 (Benabarre et al., 2001;Cannon, Jones, Gilvarry et al., 1997;Cheniaux, Landeira-Fernandez, Telles et al., 2008;Conus, Cotton, Schimmelmann, McGorry, & Lambert, 2007;Murray et al., 2004;Parellada, Castro-Fornieles, Gonzalez-Pinto et al., 2015;Strauss, Vertinski, Vogel, Ringdahl, & Allen, 2016;Tamminga, Ivleva, Keshavan et al., 2013;Tondo, Vázquez, Baethge et al., 2016). ...
... In this study, the baseline demographics of each diagnostic subgroup were generally in keeping with previous reports: the majority of patients with SZ were males (Benabarre et al., 2001;Cannon et al., 1997;Heslin et al., 2016;Hill et al., 2009;Mojtabai et al., 2000;Owoeye et al., 2013;Strauss et al., 2016;Tamminga et al., 2013;Tondo et al., 2016); MP patients were youngest at presentation but had achieved the highest level of education (Cannon et al., 1997;Mojtabai et al., 2000;Strauss et al., 2016;Tamminga et al., 2013) and MP patients had shorter DUP, a critical factor associated with better long-term outcomes and quality of life (Hill et al., 2009;Lloyd-Evans, Crosby, Stockton et al., 2011;Marshall et al., 2005). ...
... These results underscore the multifaceted aetiology of these conditions and demonstrate the degree of overlap between the subgroups. In this study, SZ patients often occupied an intermediate level between DP and MP patients, and previous research has already proposed SA disorder as the intermediate between SZ and MP (Benabarre et al., 2001;Parellada et al., 2015;Tamminga et al., 2013;Tondo et al., 2016). These findings contribute to the ongoing discussion concerning the existence of a psychosis spectrum (Crow, 1990;Van Os et al., 2009). ...
Article
Aim: To investigate the relationship between the presenting clinical and demographic characteristics in first-episode psychosis (FEP) patients with their clinical diagnostic grouping 1 year later. Methods: Data from 1014 first-presentation psychosis patients from seven London-based Early Intervention Services were extracted from the MiData audit database. Associations between clinical and demographic measures at presentation and clinical diagnosis made at 1 year were assessed with analysis of variance (ANOVA) and Chi-square tests. Results: The sample comprised 76% of patients with schizophrenia-spectrum diagnoses, 9% with manic psychoses (MP) and 6% with depressive psychoses. Compared to the other 2 groups, patients who were diagnosed as having MP were younger, with higher education and shorter duration of untreated psychosis, and had higher Young Mania Rating Scale scores at presentation and lower Positive and Negative Syndrome Scale (PANSS) negative scores. Patients diagnosed at 1 year as having depressive psychosis were older and more likely to be white, with the lowest PANSS positive scores at baseline. Patients diagnosed at 1 year as having schizophrenia spectrum diagnoses were more likely to be males. Patients in the 3 diagnostic subgroups of psychosis differed on both clinical and demographic characteristics at presentation. Conclusions: There were significant clinical and demographic differences at presentation between FEP patients who received different clinical diagnoses at 1 year. Future work should determine the extent to which these differences can be used to guide clinical care.
... For many people it follows a relapsing and remitting course, with periods of remission, interspersed with florid psychotic episodes and concurrent mood symptoms, either mania, mixed or depressive episodes. The classification of schizoaffective disorder as a separate condition to schizophrenia and bipolar affective disorder remains controversial, but it retains its place in diagnostic classification manuals as a standalone condition (APA 2013), with outcomes somewhere between those of schizophrenia and bipolar affective disorder (Harrow 2000; Marneros 2001; Mancuso 2014; Tondo 2016). Treatment-resistant schizoaffective disorder occurs in a minority of patients in which their response to antipsychotic medication or mood stabilisers, or both, is suboptimal. ...
... For these people, this means that persistent psychotic symptoms with accompanying affective change (hypomanic/manic or mixed or depressive) is the predominant clinical presentation, with poor functioning despite adequate treatment with antipsychotic medication or mood stabilisers , or both. There is no consensual definition of treatment resistance in schizoaffective disorder, making it difficult to estimate the number of treatment-resistant schizoaffective patients, but clinical experience indicates that some people with schizoaffective disorder demonstrate suboptimal clinical response at some point in the longitudinal course of their illness (Mancuso 2014; Tondo 2016). Treatment options are restricted, with clozapine the only drug with established efficacy in treatment-resistant schizophrenia (Kane 1988; Meltzer 1989; Wahlbeck 1999; Chakos 2001; McEvoy 2006 ), with emerging evidence for its effectiveness in treatmentresistant bipolar affective disorder (Li 2015), and it is similarly used in treatment-resistant schizoaffective disorder (McElroy 1991; Banov 1994; Ciapparelli 2003). ...
Article
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This is the protocol for a review and there is no abstract. The objectives are as follows: To systematically review the clinical effects, efficacy and safety of pharmacological augmentation for clozapine in treatment-resistant schizoaffective disorder. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
... El último planteo parte del supuesto de que la esquizofrenia y el trastorno del humor forman parte de un continuum en el cual estas dos patologías se encontrarían en los extremos, y el trastorno esquizoafectivo se ubicaría en un lugar intermedio. 8,21 Este planteo presenta cierta correlación con el Research Domain Criteria (RDoC) planteado por el Instituto Nacional de Salud Mental de Estados Unidos, el cual utiliza un enfoque dimensional y no categorial, determinando nuevas formas de clasificación psicopatológica basadas en dimensiones de comportamientos observables y análisis neurobiológicos. En este sentido, el trastorno esquizoafectivo se enmarca en un enfoque dimensional dentro de la escala esquizo-bipolar. ...
... Lo fundamental en cada trastorno es esa estructuración, ese todo singular que en cada uno constituye "el síntoma fundamental"». 21 De esta manera describe Casarotti cómo se vinculan los síntomas positivos con el diagnóstico fenomenológico-estructural. Agrega que solo este modo de lectura puede captar lo típico de cada déficit psíquico, en la variedad y en la atipía de sus manifestaciones. ...
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Resumen Desde su primera descripción, la enfermedad esquizoafectiva ha sufrido variaciones en cuanto a su forma de caracterización, lo que ha influido en su relevancia, aplicabilidad, validez e impacto en la práctica clínica. Hoy en día existe una discusión en torno al diagnóstico del trastorno esquizoafectivo, sustentada en la evidencia de su escasa confiabilidad y estabilidad temporal. Para comprender este debate es necesario detenerse sobre planteos actuales que afectan de manera transversal este diagnóstico, como el lugar de los manuales diagnósticos operacionales, las concep-ciones psicopatológicas de las psicosis crónicas y agudas, la determinación de la confiabilidad de los diagnósticos realizados, la presencia de trastornos longitudinales y transversales y la variedad de posiciones nosográficas. En este caso, se decide realizar una revisión narrativa sobre el surgimiento y la historia del trastorno esquizoafectivo, detallando los puntos de discu-sión actuales y planteando posibles alternativas para abordar esta problemática. Palabras clave trastorno esquizoafectivo nosografía validez diagnóstico psicopatología teoría órgano-dinámica Summary Ever since its first description, schizoaffective disorder has undergone variations in its characterization which have had an influence on its relevance, applicability, validity and impact in clinical practice. There is a discussion at present regarding the diagnosis of schizoaffective disorder, based on the evidence of its limited reliability and temporal stability. In order to understand this debate it is necessary to analyze present issues that transversally affect this diagnosis, such as the importance of operational diagnostic manuals, psychopathology of chronic and acute psychosis, reliability determination of previous diagnosis, longitudinal and transversal disorders and different nosographic theories. Authors make a narrative revision regarding the emergence and history of schizoaffective disorder, pointing out current discussions and suggesting possible alternatives when addressing this problem. Key words schizoaffective disorder nosography validity diagnosis psychopathology organodynamic theory Rev Psiquiatr Urug 2019; 83(1):20-32 Revisión S. Lema, R. Almada|Revista de Psiquiatría del Uruguay|Volumen 83 Nº 1 Octubre 2019|página 21 Introducción El diagnóstico en la medicina es un proceso de gran importancia; en psiquiatría, adquiere una particular complejidad. El diagnóstico en medicina en general es un proceso por el que se intenta someter a verificación científica la hipótesis de la per-tenencia de determinadas manifestaciones clínicas observadas en un paciente a una clase o a una dimensión, dentro de una determinada clasificación de referencia. 1 Las obras históricas como las de P. Laín Entralgo evidencian que el sustrato sólido de la medicina en su evolución ha sido la objetivación progresiva de formas clínicas típicas. 2 La identificación de formas clínicas y su diagnóstico han estado fundamentados principalmente en la nosología, la que es-tablece el vínculo entre las formas clínicas sindromáticas y su base patológica. En muchas ramas de la medicina la evolución de la nosografía y las clasificaciones se ha dado en consonancia con la evolución del desarrollo biotecnológico, que ha permitido discernir con mayor precisión la base fisiopatológica de las entidades clínicas. En psiquiatría subsiste sin embargo el problema de la distancia existente entre las manifestaciones psicopatológicas y su base, 3 distancia que implica que el proceso de identificación de formas clínicas típicas se encuentre menos influido por el conocimiento que se va generando a nivel de la base fisio-patológica de índole neurobiológica. Estas características determinan idas y venidas en cuanto a la identificación y deno-minación de las patologías, así como en cuanto a las clasificaciones de uso. Este proceso se ha visto influido a lo largo del tiempo, al igual que otro conjunto de fundamentos conceptua-les, por la existencia de cuerpos doctrinales y marcos teóricos que adoptan posiciones de dominio o de mayor influencia relativa. Así, por ejemplo, Casarotti señala que «el análisis histórico también revela que esa objetivación de las formas clínicas con sus reglas diagnós-ticas y pronósticas guarda estrecha relación y es inseparable de los cambiantes contextos de la teorización y de la praxis que caracterizan a cada etapa». 2 La noción de discontinuidad subyacente a tales «idas y venidas» se contrapone con una idea positivista de desarrollo constante, homogéneo, unidireccional y de acumulación y mejoría del conocimiento, según el cual podría asumirse que «lo último es lo más verdadero», noción que es cuestionada por el análisis histórico de la disciplina. 4 Según un análisis esquemático puede sos-tenerse que a lo largo de la historia las clasi-ficaciones en psiquiatría estuvieron guiadas primero por la búsqueda de formas clínicas que reflejaran la existencia de procesos etiológicos identificables, en el primer siglo de la discipli-na. Luego, con Kraepelin fundamentalmente, clasificaciones basadas en la descripción clínica observable y su evolución; más tarde, a partir de Bleuler, por la identificación y descripción de los procesos psicopatológicos subyacentes, hasta que en el último período han predomi-nado las clasificaciones criteriológicas que, mediante la utilización de criterios claros, simples y objetivos, pretenden la descripción sindromática de los cuadros clínicos que constituyeran diagnósticos fiables, evitando las referencias etiológicas y psicopatológicas. 1 Es en referencia a este último marco teórico que ha obtenido notoriedad en la nosografía psiquiátrica el trastorno esquizoafectivo. Nuestro objetivo en este caso es presentar las principales discusiones en torno a la validez y utilidad de esta categoría nosográfica. Metodología Para la realización de este trabajo se utilizó una combinación de métodos incluyendo una búsqueda de actualización, en conjunto con la utilización selectiva de autores de relevancia como fuente. Para la primera se utilizaron los descriptores «trastorno esquizoafectivo», «diagnóstico» y «revisión» en las bases de datos Scielo y Google Scholar, tanto en inglés como español, seleccionando entre los resul-tados obtenidos aquellos que resultaran más Revisión página 22|Volumen 83 Nº 1 Octubre 2019|Revista de Psiquiatría del Uruguay|Trastorno esquizoafectivo: un diagnóstico controversial informativos. El trabajo constituye revisión narrativa. Trastorno esquizoafectivo Los manuales diagnósticos actuales entien-den la realidad de la presencia de pacientes que presentan un solapamiento de «síntomas esquizofrénicos» y «reacciones afectivas», asignándoles un lugar particular que los discrimina de otras categorías. El lugar del trastorno esquizoafectivo ha variado en sus criterios diagnósticos y en su concepción. Considerando el Manual diagnóstico y es-tadístico de trastornos mentales (DSM) en un inicio, se consideraba esta presentación clínica como un subtipo dentro de la esquizo-frenia: DSM-I: reacción esquizofrénica, tipo esquizoafectivo; DSM-II: esquizofrenia, tipo esquizoafectivo excitado y depresivo. Luego, en la versión de 1980, el DSM-III establece el trastorno esquizoafectivo como una entidad nosológica particular, pero es el único diag-nóstico sin criterios operacionales explícitos. 5 En la revisión del DSM-III-R se establecen los criterios diagnósticos, que van a determinar una diferencia clara con la Clasificación inter-nacional de enfermedades (CIE), destacándose que la remisión sintomática interepisódica y la mejor evolución no fueron incluidas como criterios diagnósticos. Las siguientes revisiones no realizaron modificaciones significativas hasta el actual DSM-5. 6 Si bien el término «psicosis esquizoafectiva» fue establecido por Jacob Kasanin en 1933, ya existía la idea de identificar un tipo de presentación clínica que incluía los síntomas característicos de la esquizofrenia, pero sin la evolución deteriorante clásica de esta pa-tología (psicosis esquizofreniforme, psicosis cicloide, psicosis reactiva). Esta situación llevó a diferentes concepciones de esta nueva entidad nosológica, ya que el modelo dicotó-mico establecido por Emil Kraepelin dividía las psicosis entre la esquizofrenia (dementia praecox) y trastornos del humor (psicosis maníaco-depresiva), basándose en que estas categorías presentaban una etiología, hallazgos neuropatológicos y una evolución particular. 7 Como se desprende etimológicamente de su nombre, el trastorno esquizoafectivo sugiere una asociación entre esquizofrenia y síntomas de la esfera afectiva. 8 La descripción clínica realizada por Jacob Kasanin se centraba en pacientes con psicosis agudas que tenían una remisión completa en período de tiempo corto. 7 En esta descripción, a los nueve casos considerados se les describe características singulares, atípicas, que se apartan de los criterios formales de la esquizofrenia. Son pacientes jóvenes, con un adecuado ajuste social premórbido e inteligencia normal o superior, que presentan una psicosis de co-mienzo brusco, súbito, usualmente precedida por un estado de depresión latente y con el antecedente de un evento vital estresante significativo que actúa como desencadenante. Estos casos presentaron una compensación rápida e intensa y de duración limitada. Cursaron con inestabilidad emocional, dis-torsión de la realidad y en algunos casos con presencia de impresiones sensoriales falsas. Se recuperaron rápidamente y evolucionaron a largo plazo sin defecto. 9 La enfermedad esquizoafectiva sin embargo no adquiere un lugar de notoriedad en el uso de los psiquiatras sino hasta su designación como trastorno esquizoafectivo en los ma-nuales categoriales criteriológicos. Pese a su permanencia hasta las recientes ediciones, ha sido siempre una entidad cuestionada y sometida a la crítica. El DSM-III menciona al respecto: «se necesitarán investigaciones futuras para determinar si existe la necesidad de esta categoría y, de ser así, cómo se debe definir y cuál es su relación con la esquizo-frenia y el trastorno afectivo», mientras que el DSM-IV reconoce las dificultades en su aplicabilidad: «la categoría llena un agujero necesario e importante en el sistema de diag-nóstico, pero desafortunadamente no hace su trabajo muy bien». La discusión sobre la validez y utilidad de este diagnóstico puede organizarse en una serie de puntos clave. Revisión S. Lema, R. Almada|Revista de Psiquiatría del Uruguay|Volumen 83 Nº 1 Octubre 2019|página 23 1. Problemas que surgen de la comparación de las distintas versiones del DSM y la CIE
... El último planteo parte del supuesto de que la esquizofrenia y el trastorno del humor forman parte de un continuum en el cual estas dos patologías se encontrarían en los extremos, y el trastorno esquizoafectivo se ubicaría en un lugar intermedio. 8,21 Este planteo presenta cierta correlación con el Research Domain Criteria (RDoC) planteado por el Instituto Nacional de Salud Mental de Estados Unidos, el cual utiliza un enfoque dimensional y no categorial, determinando nuevas formas de clasificación psicopatológica basadas en dimensiones de comportamientos observables y análisis neurobiológicos. En este sentido, el trastorno esquizoafectivo se enmarca en un enfoque dimensional dentro de la escala esquizo-bipolar. ...
... Lo fundamental en cada trastorno es esa estructuración, ese todo singular que en cada uno constituye "el síntoma fundamental"». 21 De esta manera describe Casarotti cómo se vinculan los síntomas positivos con el diagnóstico fenomenológico-estructural. Agrega que solo este modo de lectura puede captar lo típico de cada déficit psíquico, en la variedad y en la atipía de sus manifestaciones. ...
Article
El desarrollo de los antipsicóticos ha cambiado el genio evolutivo de la esquizofrenia. La falta de cumplimiento terapéutico llevó al desarrollo de antipsicóticos de depósito a mediados de la década del sesenta del siglo pasado. Los primeros antipsicóticos de depósito fueron el enantato de flufenazina y el decanoato de flufenazina. Luego siguieron pipotiazina y haloperidol en depósito, y en la actualidad estamos asistiendo a un nuevo desarrollo de antipsicóticos de depósito de segunda generación. Los antipsicóticos de depósito han sido y son objeto de controversia en lo referente a eficacia seguridad y utilización. El presente trabajo tiene el objetivo de analizar aspectos de eficacia, seguridad y accesibilidad.
... Similarly, schizoaffective disorder (SAD) is a chronic and severe illness consisting on the concurrent presentation of symptoms of schizophrenia and affective disorders (depression and/or mania) . Actually, there is a still unresolved debate on nosological distinctions among schizoaffective disorder (SAD), BD-I with psychotic features and schizophrenia (SZ) ( Tondo et al., 2016 ). ...
Article
Long-Acting Injectable Antipsychotics (LAIs) are used to overcome non-compliance in psychoses, mainly schizophrenia spectrum disorders. We aimed to summarize available evidence of studies comparing the efficacy of LAIs to placebo or oral medications for Bipolar Disorder (BD) and/or Schizoaffective Disorder (SAD). We searched six databases from inception to 28-March-2018, using the strategy: long-acting antipsychotics AND (bipolar disorder OR schizoaffective disorder OR mania OR manic OR bipolar depression). We included peer-reviewed double-blind comparisons of LAIs for any clinical outcome occurrence in BD, or open mirror studies with same prospective as retrospective assessment periods. We excluded studies reporting on mixed schizophrenia/SAD populations without reporting results separately. The pooled records amounted to 642. After duplicate removal and inclusion/exclusion criteria application, we included 15 studies, 6 double-blind and 9 open, 13 assessing BD and 2 SAD. Depot neuroleptics prevented manic, but not depressive recurrences and may worsen depressive symptoms. Risperidone long-acting injectable was found to be effective in protecting from any mood/manic symptom compared to placebo, but not from depressive recurrences. Add-on or monotherapy paliperidone palmitate in SAD patients protected from psychotic, depressive, and manic symptoms. In patients with BD-I with a manic episode at study enrolment, aripiprazole monohydrate significantly delayed time to recurrence of manic episodes without inducing depressive episodes. LAIs are effective and well-tolerated maintenance treatments for BD and SAD. They showed better efficacy in preventing mania than depression. LAIs may be first-line for BD-I and SAD patients with a manic predominant polarity and with non-adherence problems.
... Many of the CR programs that have shown efficacy in patients with SZ have studied chronic patients who are able to attend sessions at community-based programs multiple times per week, due to high levels of disability and low instrumental role involvement (e.g., [24]). While patients with BD exhibit considerable disability, especially compared to premorbid functioning, patients with SZ or schizoaffective disorder (SZA) exhibit greater morbidity and disability on average [25], indicating that treatments requiring multiple weekly sessions at study sites may be unrealistic, especially for patients who are even partially engaged in work or school roles. With rapid advancements in online cognitive training programs, there is considerable potential for Internet-based treatments to improve access to training for patients. ...
Article
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Cognitive dysfunction is a major feature of bipolar disorder with psychosis and is strongly associated with functional outcomes. Computer-based cognitive remediation has shown promise in improving cognition in patients with schizophrenia. However, despite similar neurocognitive deficits between patients with schizophrenia and bipolar disorder, few studies have extended neuroscience-based cognitive remediation programs to this population. The Treatment to Enhance Cognition in Bipolar Disorder study is an investigator-initiated, parallel group, randomized, blinded clinical trial of an Internet-based cognitive remediation protocol for patients with bipolar disorder I with psychosis (n = 100). We also describe the development of our dose-matched active control paradigm. Both conditions involve 70 sessions of computer-based activities over 24 weeks. The control intervention was developed to mirror the treatment condition in dose and format but without the neuroplasticity-based task design and structure. All participants undergo neuropsychological and clinical assessment at baseline, after approximately 25 hours of study activities, post treatment, and after 6 months of no study contact to assess durability. Neuroimaging at baseline and post treatment are offered in an “opt-in” format. The primary outcomes are scores on the MATRICS battery; secondary and exploratory outcomes include measures of clinical symptoms, community functioning, and neuroimaging changes. Associations between change in cognitive measures and change in community functioning will be assessed. Baseline predictors of treatment response will be examined. The present study is the first we are aware of to implement an Internet-based cognitive remediation program in patients with bipolar disorder with psychosis and to develop a comparable web-based control paradigm. The mixed online and study-site format allows accessible treatment while providing weekly staff contact and bridging. Based on user-provided feedback, participant blinding is feasible. Trial registration ClinicalTrials.gov NCT01470781; 11 July 2011.
... Bipolar Disorder is a psychiatric condition, affecting about 1% of general population (5-6% considering extended criteria) (Merikangas et al., 2011), which, if not promptly treated, is associated with high disability (Altamura et al., 2011). Considering the course of illness, manic episodes represent a great challenge for clinicians (Dell'Osso et al., 2016) because during these phases patients may present psychotic symptoms (Tondo et al., 2016) and a severe cognitive impairment, particularly in executive functioning (Buoli et al., 2014a). In addition, manic episodes are characterized by impulsivity and disinhibition, which can be worsened by substance abuse and are associated with a high frequency of aggressive or risky behaviours (Large et al., 2011). ...
Article
Available antipsychotics show different efficacy on manic symptoms of bipolar patients, but few studies have investigated the speed of action of the various compounds. For this reason, purpose of the present paper was to compare antipsychotic mono-therapies in terms of speed of action in a sample of manic bipolar patients. In total, 155 bipolar patients, treated with antipsychotic mono-therapy and followed-up in Inpatient Psychiatry Clinic of University of Milan, were included in this single-blind comparative study. Clinical response was defined as a reduction of Young Mania Rating Scale (YMRS) scores ⩾50%, while remission as a YMRS score <10. After 4 days patients who had been treated with asenapine, were more likely to have achieved a clinical response than those in treatment with haloperidol ( p = 0.001). After 7 days, a more frequent clinical response was achieved by patients treated with asenapine than those who had been treated with haloperidol ( p < 0.001) or olanzapine ( p = 0.047). Asenapine appears to be faster in determining treatment response in manic patients compared with haloperidol and less markedly with olanzapine.
... Попытки отстоять нозологическую самостоятельность ШАР сводятся к теоретизированию. Авторы рассуждают о «взаимодействующем процессе», сочетающем генетические и конституциональнобиологические основы шизофрении и БАР [27,28,35,71,79,108,128], о передаче склонности к ШАР независимым путём [139]. Модель объясняет, почему «на срезе симптомы ШАР ближе к шизофреническому спектру, а течение напоминает биполярных пациентов» [32]. ...
Article
The article argues for the discrepancy between the artificial construction of «schizoaffective disorder» (SAD) and the principles of nosological diagnostics. The term of «acute schizoaffective psychoses», was introduced by Y. Kazanin in 1933, is still remain a controversial nosological unit. This diagnosis often made at the cut of a psychotic episode on a «dichotomous scale» by «weighing» schizophrenic and affective symptoms. In the history of the creation of the concept of SAD, there is a tendency towards reductionism and the search for universal manifestations. Each individual clinical case must be considered holistically. It is unacceptable to extract the individual signs (which does not fit syndromal structures) from general picture of the disease. However, this requirement is in contradiction with the current trends towards simplification, discreteness and loss of clinical thinking in currents classifications of diseases. The inadequacy of the available diagnostic approaches and criteria for distinguishing between SAD, bipolar disorder and schizophrenia leads to the fact that the patient’s diagnosis is based on the subjective preferences of a clinician, and during patient’s life can many times be changed. The results of the the phenotype and genotype of the corresponding disorders searching partially shed light on the features of the diagnosis; but at the same time, some researchers are artificially combine the discrete properties and coming to incorrect conclusions; often such an identity simply does not make sense. The authors join opinion of experts who suggesting the existence of a «third psychosis» or even several discrete forms of diseases, which, along with unrecognized attacks of bipolar psychosis and schizophrenia are still mistakenly dissolved in the dichotomous / dimensional hybrid SAD. Diagnostics, taking into account the follow-up, regularities of the course, pathophysiological changes and psychopathological structure, has not only clinical value, but is also responsible for the selection of effective treatment, correct preventive measures, affects the social status and, ultimately, the quality of life of the patient.
... Overlap among diagnostic groups is generally common in psychiatry and well known in Schizophrenia, for example, distinction between Schizoaffective disorder, Schizophrenia and Bipolar disorder with psychotic episodes are still debated in improving diagnostic tools [52] and deciding the best pharmacological treatments. Similarly, a clear differentiation between negative and depressive symptoms is also important in order to determine the best course of treatment for the negative symptoms of Schizophrenia. ...
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Background: Negative symptoms of schizophrenia show limited response to both typical and atypical antipsychotics. Repetitive transcranial magnetic stimulation applied over the prefrontal cortex (PFC) has been proposed as an adjuvant to pharmacological treatment of negative symptoms in schizophrenia, but whether the improvements obtained are specific to negative symptoms or attributable to antidepressant effects is still unclear. Objective: The aim of the present study is to determine to which extent the improvements in negative symptoms of schizophrenia obtained after high-frequency stimulation of the bilateral PFC using deep TMS (dTMS) are attributable to antidepressant effects. Methods: Repetitive dTMS was administered to the PFC in a cohort of 16 patients with schizophrenia under successful pharmacological control of positive symptoms and predominant negative symptoms. Patients were treated using high-frequency (18 Hz) bilateral stimulation applied over the lateral PFC bilaterally using Brainsway H-2 coil. The effects of dTMS on negative symptoms were measured using the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scales. We then compared the improvements in negative symptoms obtained in patients showing depressive symptoms (≥7 points) with those found in patients without depression (>7 points), as determined by the Calgary Scale for Depression. Results: Repetitive dTMS treatment induced significant improvements in negative symptoms as assessed using both Scale for the Assessment of Negative Symptoms and Positive and Negative Syndrome Scales. Comparison of the improvements obtained in patients with or without depression at the beginning of treatment revealed similar improvements in negative symptoms, irrespective of subjacent depression. Conclusions: Our data suggest that the beneficial effects of high frequency dTMS of the PFC cannot be attributed solely to its antidepressant effects.
... Shenton et al. 11 examined thought disorder in schizoaffective-manic, schizoaffective-depressed, and schizophrenic patients and judged that the thinking patters of the schizoaffective patients were similar to those with schizophrenia and concluded that schizoaffective disorder showed "a close resemblance to the schizophrenias." (p29) In an international, multisite study employing DSM-IV-TR diagnoses, Tondo et al. 12 studied 14,345 patients with a psychotic bipolar I disorder, 463 with schizophrenia, and 371 with a schizoaffective disorder, principally assessing sociodemographic and clinical factors, and judged that the schizoaffective patients were "intermediate" (p40) between the 2 other groups on most study variables and thus effectively viewed the condition as "mid-way" (p41) along a continuum between schizophrenia and bipolar disorder and thus "not consistent with the recent DSM-5 inclusion" (p40) of schizoaffective disorder among the schizophrenia-like disorders. Thus, such studies show 3 contrasting patterns: a closer alignment of schizoaffective disorder to bipolar disorder than to schizophrenia, the converse pattern, and its having intermediate status. ...
Article
Schizoaffective disorder has long been recognized and quite variably defined. It has been variably positioned as a discrete entity, a variant of either schizophrenia or of a mood disorder, as simply reflecting the co-occurrence of schizophrenia and a mood disorder, and effectively reflecting a diagnosis along a continuum linking schizophrenia and bipolar disorder. This article considers historical views, some empirical data that advance consideration of its status, and focuses on its classification in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). DSM-5 criteria seemingly weight it in the direction of a schizophrenic illness, as do some empirical studies, whereas the empirical literature examining the response to lithium links it more closely to bipolar disorder. It is suggested that DSM-5's B and C criteria are operationally unfeasible. Some suggestions are provided for a simpler definition.
... Psychodynamic models, as well, postulate that persecutory delusions are a defensive psychological reaction to conflicts or stresses that represent an intense hazard to the self [12]. In reacting to the said danger, there is an emotional withdrawal from close connections and an extreme struggle to keep the form of normality by defensive mechanisms such as projection [13]. ...
... This is nontrivial information for researchers and clinicians. Further, schizophrenia is characterized by higher morbidity and mortality than other DSM-5 psychosis categories (Tondo et al., 2016). While this contributes to pessimism, relabeling schizophrenia will not solve that problem: any new label will eventually acquire similar connotations until advances are made in identifying etiologic subtypes and effective treatments. ...
... It remains unclear, nevertheless, whether visual integration is affected in disorders in which psychosis is always present or highly prevalent, particularly those considered to be on the "schizophrenia-bipolar psychosis spectrum" (Keshavan et al., 2011). Bipolar disorder (BD) is a disorder frequently (>50%) affected by psychosis (Keck et al., 2003) and has substantial clinical, cognitive, neurobiological, and genetic overlap with schizophrenia (Brown, 2015;Hall et al., 2015;Pearlson, 2015;Pearlson and Ford, 2014;Tondo et al., 2015). Yet, no studies thus far have examined visual integration in BD. ...
Article
Impaired visual integration is well documented in schizophrenia and related to functional outcomes. However, it is unclear if this deficit is specific to schizophrenia, or characteristic of psychosis more broadly. To address this question, this study used a Bayesian model comparison approach to examine the evidence of three grouping models of visual integration performance in 116 individuals with schizophrenia (SZ), schizoaffective disorder (SA), bipolar disorder (BD) with or without a history of prominent psychosis (BDP+ and BDP-, respectively), or no psychiatric diagnosis (healthy controls; HC). We compared: (1) Psychosis Model (psychosis, non-psychosis), where the psychosis group included SZ, SA, and BDP+, and the non-psychosis group included BDP- and HC; (2) Schizophrenia Model (SZ, non-SZ); and (3) DSM Model (SZ, SA, BD, HC). The relationship between visual integration and general cognition was also explored. The Psychosis Model showed the strongest evidence, and visual integration was associated with general cognition in participants with psychosis. The results were consistent with the Research Domain Criteria (RDoC) framework, indicating that visual integration impairment is characteristic of psychosis and not specific to SZ or DSM categories, and may share similar disease pathways with observed neurocognitive deficits in psychotic disorders.
Article
Background: Psychotic disorders differ in their impact on psychosocial functioning. However, few studies have directly compared psychosocial functioning and its determinants between schizophrenia, schizoaffective disorder (SAD), bipolar disorder (BD), and major depressive disorder with psychotic features (psychotic MDD). Objective: We compared rates of independent living, employment, marriage, and having children between these diagnostic groups in a large national sample of participants with psychotic disorders in Finland. Methods: A cross-sectional substudy of participants (N = 9148) aged 18 to 65 years in the Finnish SUPER study, recruited nationwide from health- and social care settings and with advertisements. Psychosis diagnoses, age of onset, and hospitalizations were collected from healthcare registers. Participants were interviewed for psychosocial functioning. Associations of age of onset, hospitalizations, gender, and education with psychosocial functioning were analyzed using logistic regression models. Results: Of participants, 13.8% were employed or studying, 72.0% living independently and 32.5% had children. Overall, BD was associated with best, SAD and psychotic MDD with intermediate, and schizophrenia with worst level of psychosocial functioning. Greatest differences were found in independent living (OR 4.06 for BD vs. schizophrenia). In multivariate models, gender and number of hospitalizations predicted employment, marriage, and independent living in all diagnostic categories, and age of onset in some diagnostic categories. Conclusions: Level of functioning and psychosocial outcomes differed markedly between psychotic disorders, particularly in independent living. Outcomes were worst for schizophrenia and best for BD. Across all psychotic disorders, female gender and lifetime number of hospitalizations had strong independent associations with marriage, employment, and independent living.
Article
Background: Since the Iowa 500 study, residential and occupational status have been frequently used as indicators of everyday achievements in research on schizophrenia and bipolar disorder. The relationships of residential and occupational status with impairment in multiple domains including physical health indicators across these two diagnoses, however, have rarely been studied. We examined these relationships at the 20-year follow-up assessment of a first-admission sample. Methods: We included 146 participants with schizophrenia and 87 with bipolar disorder with psychosis who participated in the 20-year follow-up of the Suffolk County Mental Health Project. In addition to interviewer-based ratings of employment and residential independence, we examined self-reported impairment derived from the WHODAS, standard measures of current psychopathology, indicators of obesity, as well as performance-based measures of physical and cognitive functioning. Results: Participants with bipolar disorder were more likely to live independently and be gainfully employed; they also performed significantly better on each indicator of impairment apart from balance ability. In both groups, unemployment, but not residential independence, was associated with greater self-reported disability on the WHODAS. Residential independence, gainful employment, and subjective disability were also associated with better physical functioning. Across the two groups, psychiatric symptoms and physical functioning were the major determinants of subjective disability. Discussion: People with psychotic bipolar disorder were more likely to be gainfully employed and living independently than participants with schizophrenia but as a group, much less frequently than population standards. Interventions aimed at physical fitness may have the potential to improve both objective functioning and perceived disability.
Article
Objective To evaluate morbidity during long‐term follow‐up with clinical treatment of affective and schizoaffective disorder subjects followed from hospitalization for first major psychotic episodes. Methods We followed adult subjects systematically at regular intervals from hospitalization for first‐lifetime episodes of major affective and schizoaffective disorders with initial psychotic features. We compiled % of days with morbidity types from detailed records and life charts, reviewed earliest antecedent morbidities, compared both with final diagnoses and initial presenting illness types, and evaluated morbidity risk factors with regression modeling. Findings With final diagnoses of bipolar‐I (BD‐I, n = 216), schizoaffective (SzAffD, 71), and major depressive (MDD, 42) disorders, 329 subjects were followed for 4.47 [CI: 4.20–4.47] years. Initial episodes were mania (41.6%), mixed states (24.3%), depression (19.5%), or apparent nonaffective psychosis (14.6%). Antecedent morbidity presented 12.7 years before first episodes (ages: SzAffD ≤ BD‐I < MDD). Long‐term % of days ill ranked SzAffD (83.0%), MDD (57.8%), BD‐I (45.0%). Morbidity differed by diagnosis and first‐episode types, and was predicted by first episodes and suggested by antecedent illnesses. Long‐term wellness was greater with BD‐I diagnosis, first episode not mixed or psychotic nonaffective, rapid onset, and being older at first antecedents, but not follow‐up duration. Conclusions Initially, psychotic BD‐I, SzAffD, or MDD subjects followed for 4.47 years from first hospitalization experienced much illness, especially depressive or dysthymic, despite ongoing clinical treatment. Antecedent symptoms arose years before index first episodes; antecedents and first episode types predicted types and amounts of long‐term morbidity, which ranked: SzAffD > MDD > BD‐I.
Article
Objective: The purpose of this study was to determine if schizoaffective disorder in older adults is differentiated from schizophrenia and bipolar disorder with respect to community functioning, cognitive functioning, psychiatric symptoms, and service use. Design: Secondary analysis of baseline data collected from the Helping Older People Experience Success psychosocial skills training and health management study. Setting: Three community mental health centers in New Hampshire and Massachusetts. Participants: Adults over the age of 50 (N = 139, mean age: 59.7 years, SD: 7.4 years) with persistent functional impairment and a diagnosis of schizoaffective disorder (N = 52), schizophrenia (N = 51), or bipolar disorder (N = 36). Measurements: Health status (36-Item Short Form Health Survey [SF-36]), performance-based community living skills (UCSD Performance-Based Skills Assessment), neuropsychological functioning (Delis-Kaplan Executive Functioning subtests), psychiatric symptoms (Brief Psychiatric Rating Scale, Center for Epidemiologic Studies Depression Scale, Scale for the Assessment of Negative Symptoms), medical severity (Charlson comorbidity index), and acute service use. Results: Older adults with schizoaffective disorder had depressive symptoms of similar severity to bipolar disorder, and thought disorder symptoms of similar severity to schizophrenia. Schizoaffective disorder compared with schizophrenia was associated with better community functioning, but poorer subjective physical and mental health functioning as measured by the SF-36. Older adults with schizoaffective disorder had greater acute hospitalization compared with adults with schizophrenia, though their use of acute care services was comparable to individuals with bipolar disorder. Conclusions: Findings from this study suggest that schizoaffective disorder in older adults occupies a distinct profile from either schizophrenia or bipolar disorder with respect to community functional status, symptom profile, and acute services utilization.
Article
Background: There is growing evidence that neurocognitive function may be an endophenotype for mood disorders. The goal of this study is to examine the specificity and familiality of neurocognitive functioning across the full range of mood disorder subgroups, including Bipolar I (BP-I), Bipolar II (BP-II), Major Depressive Disorders (MDD), and controls in a community-based family study. Methods: A total of 310 participants from 137 families with mood spectrum disorders (n=151) and controls (n=159) completed the University of Pennsylvania's Computerized Neurocognitive Battery (CNB) that assessed the accuracy and speed of task performance across five domains. Mixed effects regression models tested association and familiality. Results: Compared to those without mood disorders, participants with BP-I had increased accuracy in complex cognition, while participants with MDD were more accurate in emotion recognition. There was also a significant familial association for accuracy of complex cognition. Mood disorder subgroups did not differ in performance speed in any of the domains. Limitations: The small number of BP-I cases, and family size limited the statistical power of these analyses, and the cross-sectional assessment of neurocognitive function precluded our ability to determine whether performance precedes or post dates onset of disorder. Conclusions: This is one of the few community-based family studies of potential neurocognitive endophenotypes that includes the full range of mood disorder subgroups. There were few differences in neurocognitive function except enhanced accuracy in specific domains among those with BP-I and MDD. The differential findings across specific mood disorder subgroups substantiate their heterogeneity in other biologic and endophenotypic domains.
Article
Background: Despite several previous attempts at subtyping schizophrenia, a typology that reflects neurobiological knowledge and reliably predicts course and outcome is lacking. We applied the system-specific concept of the Bern Psychopathology Scale (BPS) to generate a course typology based on three domains: language, affectivity, and motor behaviour. Sampling and methods: A cohort of 100 patients with schizophrenia or schizoaffective disorders according to DSM-IV criteria underwent psychopathological assessment, and all their available medical records were retrospectively analysed on the basis of the BPS. Results: Overall, 39% of the patients showed dominant abnormalities in only one domain, 37% in two domains, and 24% in all three domains. The motor domain was affected in the majority of patients (76%), followed by affectivity (63%) and language (46%). Eighty-six percent of patients showed a bipolar course pattern in at least one domain. Conclusions: In a retrospective analysis of 100 patient records we described system-specific course patterns of schizophrenia by using a neurobiologically informed psychopathological assessment. The results showed a surprisingly high proportion of bipolar courses and a pattern of pure and mixed subtypes, which speaks for an overlap of domains with regards to psychopathological symptoms. A limitation of this heuristic and retrospective approach is that it was largely based on clinical judgement. Prospective studies with more rigorous threshold definitions are needed to clarify the neurobiological and clinical implications of the proposed reorganization of psychotic disorders.
Article
Background: Affective syndrome is thought to be a key feature that differentiates schizophrenia from schizoaffective disorder (SA) and bipolar disorder with psychotic features (BDP). However genetic underpinnings of these differences remain unresolved. Objectives: We compared clinical variables of affective psychoses (SA, BDP and schizophrenia with affective symptoms (AFF SCZ)) and schizophrenia without affective symptoms (non-AFF SCZ) and searched for a genetic variant that may differentiate affective psychosis from non-AFF SCZ. Methods: A total of 2677 subjects, including 831 patients with affective psychosis, 785 patients with non-AFF SCZ and 1061 healthy controls, were used. Clinical symptoms were assessed with the PANSS. The sample was genotyped for 5-HTTLPR polymorphism of the serotonin transporter gene. Results: The diagnostic groups differed significantly on demographic and clinical variables. The percentage of men was higher, the current age and age at illness onset were lower in non-AFF SCZ and SA compared to AFF SCZ and BDP. The severity of positive and negative symptoms decreased significantly from group to group in the following manner: non-AFF SCZ>AFF SCZ>SA>BDP. There was the association between 5-HTTLPR polymorphism and affective psychosis (p=0.01). The frequency of the SS genotype was higher in the affective psychosis group compared to non-AFF SCZ and controls. No differences in the genotype distribution were identified between the non-AFF SCZ group and controls. Limitations: Difficulties in the differentiation between non-AFF SCZ and AFF SCZ or SA and between AFF SCZ and SA due to uncertain diagnostic boundaries between these conditions. Conclusions: SA is intermediate between non-AFF SCZ and BDP in the severity of positive and negative symptoms. The first episode patients, carriers of the SS genotype have a higher risk of developing affective psychosis than non-AFF SCZ. This finding carries implications for the prognosis of psychosis outcomes in the first-episode patients.
Article
Introduction: Bipolar disorder (BD) is considered to have a better outcome in comparison to schizophrenia. However, recent data dispute this notion. The current study aimed to compare the burden of patients with BD type I (BD-I) in remission with similar patients with schizophrenia (SZ) in remission. Materials and methods: Patients with schizophrenia (n=75) and BD-I (n=54) aged 18-64years were included in the study. The diagnosis was made with the SCID-I/P. Patients were assessed for sociodemographic variables, stigma, quality of life, disability, suicidality and current symptomatology. The statistical analysis included analysis of covariance (ANCOVA) and chi-square test. Results: ANCOVA with age at onset as a covariate and marital status and diagnosis as grouping variables returned no significant difference. Discussion: The results of the current study suggest that when in remission, BD-I patients do not differ from patients with schizophrenia with regards to stigma, quality of life, disability level and suicidality. Also, when in remission, they do not differ regarding the severity of their psychopathology.
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An increased rate of de novo copy number variants (CNVs) has been found in schizophrenia (SZ), autism and developmental delay. An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We used Illumina microarrays to genotype 368 BD probands, 76 SZ probands and all their parents. Copy number variants were called by PennCNV and filtered for frequency (<1%) and size (>10 kb). Putative de novo CNVs were validated with the z-score algorithm, manual inspection of log R ratios (LRR) and qPCR probes. We found 15 de novo CNVs in BD (4.1% rate) and 6 in SZ (7.9% rate). Combining results with previous studies and using a cut-off of >100 kb, the rate of de novo CNVs in BD was intermediate between controls and SZ: 1.5% in controls, 2.2% in BD and 4.3% in SZ. Only the differences between SZ and BD and SZ and controls were significant. The median size of de novo CNVs in BD (448 kb) was also intermediate between SZ (613 kb) and controls (338 kb), but only the comparison between SZ and controls was significant. Only one de novo CNV in BD was in a confirmed SZ locus (16p11.2). Sporadic or early onset cases were not more likely to have de novo CNVs. We conclude that de novo CNVs play a smaller role in BD compared with SZ. Patients with a positive family history can also harbour de novo mutations.
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In treated cohorts, individuals with bipolar disorder are more likely to report childhood adversities and recent stressors than individuals without bipolar disorder; similarly, in registry-based studies, childhood adversities are more common among individuals who later become hospitalized for bipolar disorder. Because these types of studies rely on treatment-seeking samples or hospital diagnoses, they leave unresolved the question of whether or not social experiences are involved in the etiology of bipolar disorder. We investigated the role of childhood adversities and adulthood stressors in liability for bipolar disorder using data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=33 375). We analyzed risk for initial-onset and recurrent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic episodes during the study's 3-year follow-up period. Childhood physical abuse and sexual maltreatment were associated with significantly higher risks of both first-onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI)=1.71, 2.91; OR for maltreatment: 2.10; CI=1.55, 2.83) and recurrent mania (OR for abuse: 1.55; CI=1.00, 2.40; OR for maltreatment: 1.60; CI=1.00, 2.55). In addition, past-year stressors in the domains of interpersonal instability and financial hardship were associated with a significantly higher risk of incident and recurrent mania. Exposure to childhood adversity potentiated the effects of recent stressors on adult mania. Our findings demonstrate a role of social experiences in the initial onset of bipolar disorder, as well as in its prospective course, and are consistent with etiologic models of bipolar disorder that implicate deficits in developmentally established stress-response pathways.Molecular Psychiatry advance online publication, 22 April 2014; doi:10.1038/mp.2014.36.
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This study examined hippocampal volume as a putative biomarker for psychotic illness in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) psychosis sample, contrasting manual tracing and semiautomated (FreeSurfer) region-of-interest outcomes. The study sample (n = 596) included probands with schizophrenia (SZ, n = 71), schizoaffective disorder (SAD, n = 70), and psychotic bipolar I disorder (BDP, n = 86); their first-degree relatives (SZ-Rel, n = 74; SAD-Rel, n = 62; BDP-Rel, n = 88); and healthy controls (HC, n = 145). Hippocampal volumes were derived from 3Tesla T1-weighted MPRAGE images using manual tracing/3DSlicer3.6.3 and semiautomated parcellation/FreeSurfer5.1,64bit. Volumetric outcomes from both methodologies were contrasted in HC and probands and relatives across the 3 diagnoses, using mixed-effect regression models (SAS9.3 Proc MIXED); Pearson correlations between manual tracing and FreeSurfer outcomes were computed. SZ (P = .0007–.02) and SAD (P = .003–.14) had lower hippocampal volumes compared with HC, whereas BDP showed normal volumes bilaterally (P = .18–.55). All relative groups had hippocampal volumes not different from controls (P = .12–.97) and higher than those observed in probands (P = .003–.09), except for FreeSurfer measures in bipolar probands vs relatives (P = .64–.99). Outcomes from manual tracing and FreeSurfer showed direct, moderate to strong, correlations (r = .51–.73, P < .05). These findings from a large psychosis sample support decreased hippocampal volume as a putative biomarker for schizophrenia and schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary disease processes and/or lifetime medication use. Manual tracing and semiautomated parcellation regional volumetric approaches may provide useful outcomes for defining measurable biomarkers underlying severe mental illness.
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To examine the effectiveness of switching patients to lurasidone using 3 different dosing strategies. Adults with DSM-IV-defined schizophrenia or schizoaffective disorder in a nonacute phase of illness were randomized to 1 of 3 lurasidone dosing regimens for the initial 2 weeks of the study: (1) 40 mg/d for 2 weeks; (2) 40 mg/d for 1 week, increased to 80 mg/d on day 8 for week 2 (up-titration group); and (3) 80 mg/d for 2 weeks. Lurasidone was then flexibly dosed (40-120 mg/d) for the subsequent 4 weeks of the study. The preswitch antipsychotic agent was tapered by day 7 to 50% of the original dose and discontinued by the end of week 2. Subjects were stratified on the basis of whether the primary preswitch antipsychotic medication was classified as "sedating" (olanzapine or quetiapine) or "nonsedating" (all other antipsychotics). The primary outcome measure was time to treatment failure, defined as any occurrence of insufficient clinical response, exacerbation of underlying disease, or discontinuation due to an adverse event. The study was conducted from June 2010 to May 2011. Of 240 subjects treated in this study, 86 (35.8%) were treated with an antecedent sedating antipsychotic, and 154 (64.2%) were treated with an antecedent nonsedating antipsychotic. Nineteen (7.9%) of the 240 patients experienced treatment failure. No clinically relevant differences were observed when the 3 randomized switch groups were compared. Treatment failure rates were 10/86 (11.6%) versus 9/154 (5.8%) among subjects who had been receiving a preswitch sedating versus nonsedating antipsychotic medication, respectively. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, glucose, insulin, lipids, or prolactin; mean improvements in weight and lipids were observed. Movement disorder rating scales did not demonstrate meaningful changes. The incidence of akathisia as an adverse event was 12.5%; only 1 subject (0.4%) discontinued due to akathisia. Switching patients to lurasidone can be successfully accomplished by starting at 40 mg/d for 2 weeks, or 80 mg/d for 2 weeks, or 40 mg/d for 1 week followed by 80 mg/d the second week. ClinicalTrials.gov identifier: NCT01143077.
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Circadian rhythm abnormalities in bipolar disorder (BD) have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies (GWAS). At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at three levels: essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD (major depression, schizophrenia, attention deficit/hyperactivity). Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies.
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Background: Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting. Method: We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill. Results: All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms. Conclusions: Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.
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A number of structural brain imaging studies and meta-analytic reviews have shown that multiple subtle brain abnormalities are consistently found in schizophrenia and bipolar disorder. Several studies suggest that schizophrenia and affective psychoses share a largely common pattern of brain abnormalities. Aim of the present study was to compare, by means of a meta-analytic approach, brain structural abnormalities, as detected by Magnetic Resonance Imaging (MRI), found at the onset of schizophrenia and bipolar disorder in order to address the question of the specificity of brain abnormalities across diagnostic groups. Forty-five studies were identified as suitable for analysis. In both schizophrenic and bipolar patients significant overall effect sizes were demonstrated for intracranial, whole brain, total grey and white matter volume reduction as well as for an increase of lateral ventricular volume at disease onset. Thus, the available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenia or bipolar disorder and that there is a significant overlap of brain abnormalities in affective and non-affective psychotic disorders at the onset of the disease. However, whole grey matter volume deficits and lateral ventricular enlargement appear to be more prominent in first-episode schizophrenia whereas white matter volume reduction seems more prominent in bipolar disorder. The common vs specific trajectories of brain pathomorphology in schizophrenia and bipolar disorder are discussed.
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Since stability of DSM-IV diagnoses of disorders with psychotic features requires validation, we evaluated psychotic patients followed systematically in the McLean-Harvard International First Episode Project. We diagnosed 517 patients hospitalized in a first psychotic illness by SCID-based criteria at baseline and at 24 months to assess stability of specific DSM-IV diagnoses. Among 500 patients (96.7%) completing the study, diagnoses remained stable in 77.6%, ranking as follows: bipolar I disorder (96.5%) > schizophrenia (75.0%) > delusional disorder (72.7%) > major depressive disorder (MDD), severe, with psychotic features (70.1%) > brief psychotic disorder (61.1%) > psychotic disorder not otherwise specified (NOS) (51.5%) > schizophreniform disorder (10.5%). Most changed diagnoses (22.4% of patients) were to schizoaffective disorder (53.6% of changes in 12.0% of subjects, from psychotic disorder NOS > schizophrenia > schizophreniform disorder = bipolar I disorder most recent episode mixed, severe, with psychotic features > MDD, severe, with psychotic features > delusional disorder > brief psychotic disorder > bipolar I disorder most recent episode manic, severe, with psychotic features). Second most changed diagnoses were to bipolar I disorder (25.9% of changes, 5.8% of subjects, from MDD, severe, with psychotic features > psychotic disorder NOS > brief psychotic disorder > schizophreniform disorder). Third most changed diagnoses were to schizophrenia (12.5% of changes, 2.8% of subjects, from schizophreniform disorder > psychotic disorder NOS > brief psychotic disorder = delusional disorder = MDD, severe, with psychotic features). These 3 categories accounted for 92.0% of changes. By logistic regression, diagnostic change was associated with nonaffective psychosis > auditory hallucinations > youth > male sex > gradual onset. Bipolar I disorder and schizophrenia were more stable diagnoses than delusional disorder or MDD, severe, with psychotic features, and much more than brief psychotic disorder, psychotic disorder NOS, or schizophreniform disorder. Diagnostic changes mainly involved emergence of affective symptoms and were predicted by several premorbid factors. The findings have implications for revisions of DSM and ICD.
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Use of psychotropic drugs has come to dominate clinical practice in psychiatry worldwide-perhaps owing largely to perceived simplicity, ease of use, and apparent efficiency, as well as apparent cost-effectiveness of such treatments. Nevertheless, medicinal treatments for patients with psychiatric disorders are but one component of comprehensive clinical care of complex human problems. Extensively updated since its second edition in 1985, Chemotherapy in Psychiatry, Third Edition, again addresses basic aspects of modern psychopharmacology and clinical applications of drugs used in the treatment of major psychiatric disorders, with major emphasis on psychotic, bipolar, and depressive disorders. The presentation covers descriptions of the main classes of psychotropic drugs, selected information concerning their known action mechanisms and metabolic disposition, and their clinical applications for acute illnesses and to prevent recurrences and long-term morbidity. Also covered are limitations and adverse effects of each type of agent, with emphasis on the fact that all psychotropic medicines have adverse effects that range from annoying to potentially lethal. Chemotherapy in Psychiatry, Third Edition, outlines the need to balance benefits and risks at the level of individual persons. Authoritative, and an important contribution to the literature, Chemotherapy in Psychiatry, Third Edition is an invaluable resource for physicians, scientists, trainees, and policymakers. © 2013 Springer Science+Business Media New York. All rights are reserved.
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Modern psychopharmacology has been evolving since the 1950s. Its contributions have been enormous and of fundamental importance to modern psychiatric therapeutics, encouraging and enabling the shift away from long-term institutional care, to brief inpatient interventions for crises, and reliance on ambulatory care. In addition, the clinical benefits provided by much of psychiatric chemotherapy, though typically incomplete, have stimulated decades of renewed efforts to develop a more biomedically based theoretical and academic psychiatry. In addition, the psychopharmaceutical industry has been especially successful in blending science and business to provide products of considerable social value.
Article
The Diagnostic and Statistical Manual of Mental Disorders (DSM) has provided diagnostic reliability across observers while neglecting biological validity. The current theme issue explores the boundaries between schizophrenia and bipolar disorder, using neuro-cognition, systems neuroscience, and genetics as points of departure to begin consideration of a biologically based reclassification of these illnesses. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
Article
Neuroimaging studies have generated a large body of knowledge regarding the neural correlates of schizophrenia (SZ) and bipolar disorder (BD). However, the initial goal of identifying disease-specific topographical mappings to localized brain regions or to distinct neural networks has not materialized and may be untenable. This contribution will argue that a systems neuroscience approach may prove more fruitful. The supporting evidence presented covers (a) brain structural, functional, and connectivity alterations and their implication for the clinical and cognitive manifestations of SZ and BD, (b) the prevailing system neuroscience models of the 2 disorders, and (c) key hypotheses likely to produce new insights into the mechanisms of underlying psychotic disorders.
Article
Treatment nonadherence in people with schizophrenia is associated with relapse and homelessness. Building on the usefulness of long-acting medication and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with DSM-IV-defined schizophrenia or schizoaffective disorder. Participants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence, as measured by the Tablets Routine Questionnaire, and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. The study was conducted from July 2010 to December 2012. The mean age of participants was 41.8 years (SD = 8.6); they were mainly minorities (90%, n = 27 African-American) and mainly single/never married (70%, n = 21). Most (97%, n = 29) had past or current substance abuse and had been incarcerated (97%, n = 29). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (at 6 months, 76%) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (P = .03). There were significant improvements in psychiatric symptoms (P < .001) and functioning (P < .001). Akathisia was a major side effect with LAI. While interpretation of findings must be tempered by the methodological limitations, CAE-L appears to be associated with improved adherence, symptoms, and functioning in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness. ClinicalTrials.gov identifier: NCT01152697.
Article
Schizoaffective disorder is viewed as a heterogeneous diagnosis among psychotic illnesses. Different diagnostic systems differ in their definition with DSM (-IIIR, -IV, and -V) providing a narrower definition than RDC and ICD-10. It is unclear whether this difference is reflected in patient samples diagnosed according to different diagnostic systems. Exploratory study based on a systematic review of studies of schizoaffective disorder samples diagnosed by either RDC and ICD-10 (group of "broad criteria") or DSM-IIIR and -IV ("narrow criteria"); comparison (by Mann-Whitney-U-tests) of key characteristics, such as age, number of hospitalizations, or scores in psychometric tests, between more broadly and more narrowly defined schizoaffective disorder samples using standard deviations as a measurement of heterogeneity as well as weighted means and percentages. To reduce selection bias only studies including schizoaffective patient samples together with affective disorder and schizophrenia samples were selected. 55 studies were included, 14 employing RDC, 4 ICD-10, 20 DSM-IIIR, and 17 DSM-IV. Thirteen characteristics were compared: patients diagnosed according to broader criteria had fewer previous hospitalizations (2.2 vs. 5.4) and were both less often male (42 vs. 51%) and married (21 vs. 40%). Heterogeneity was similar in both groups but slightly higher in RDC and ICD-10 samples than in DSM-IIIR and -IV-samples: +4% regarding demographic and clinical course data and +13% regarding psychometric tests (pooled SD). Secular trends and different designs may have confounded the results and limit generalizability. Some comparisons were underpowered. Differences in diagnostic criteria are reflected in key characteristics of samples. The association of larger heterogeneity with wider diagnostic criteria supports employing standard deviations as a measurement of heterogeneity.
Article
Studies of families and twins show the importance of genetic factors affecting susceptibility to bipolar disorder and suggest substantial genetic and phenotypic complexity. Robust and replicable genome-wide significant associations have recently been reported in genome-wide association studies at several common polymorphisms, including variants within the genes CACNA1C, ODZ4, and NCAN. Strong evidence exists for a polygenic contribution to risk (ie, many risk alleles of small effect). A notable finding is the overlap of susceptibility between bipolar disorder and schizophrenia for several individual risk alleles and for the polygenic risk. By contrast, genomic structural variation seems to play a smaller part in bipolar disorder than it does in schizophrenia. Together, these genetic findings suggest directions for future studies to delineate the aetiology and pathogenesis of bipolar disorder, indicate the need to re-evaluate our diagnostic classifications, and might eventually pave the way for major improvements in clinical management.
Article
Information on basic demographic and clinical characteristics of schizoaffective disorder is sparse and subject to sampling bias and low diagnostic reliability. In the present study we aimed to: (i) estimate the demographic and clinical descriptors in schizoaffective disorder patients and (ii) compare the findings with those with schizophrenia and bipolar disorder. To minimize sampling bias and low reliability, we systematically reviewed studies that simultaneously compared schizoaffective, schizophrenia, and bipolar disorder patients. We estimated demographic, clinical, and psychometric characteristics based on weighted pooling, and compared disorders by meta-analysis. We also estimated whether schizoaffective disorder is closer to schizophrenia or to bipolar disorder. We identified 50 studies that included 18312 patients. Most characteristics of the 2684 schizoaffective disorder patients fell between those of 4814 diagnosed with bipolar disorder and 10814 with schizophrenia. However, the schizoaffective group had the highest proportion of women (52%), had the youngest age at illness onset (23.3 ± 3.8 years), and had the highest standardized ratings of psychosis and depression. Differences in pooled parameters between schizoaffective versus schizophrenia and versus bipolar disorder subjects were similar. Values for patients with schizoaffective disorders mostly were intermediate between schizophrenia and bipolar disorder. However, the majority of studies showed schizoaffective patients to be more like schizophrenia than bipolar disorder patients in seven out of nine demographic and clinical categories as well as in five out of eight psychometric measures. These results remained similar when we restricted the analyses to studies with psychotic bipolar disorder patients only or to studies using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IIIR and DSM-IV only. The present study provided estimates of important characteristics of schizoaffective disorder – as balanced as possible in summarizing the findings from observational studies as unbiased as possible. The results did not support the hypothesis that schizoaffective disorder is primarily an affective disorder. The stronger resemblance of schizoaffective disorder to schizophrenia than to bipolar disorder needs further investigation.
Article
Objective Low diagnostic reliability, the need to meet criteria of two disorders, and its status as residual diagnosis in clinical practice led us to hypothesize that schizoaffective disorder (SAD) is characterized by considerable heterogeneity, particularly in comparison with schizophrenia (SZ) and bipolar disorder (BD). As this has not been investigated the aim of this study is to test whether heterogeneity is larger in SAD than in SZ and BD. Method Systematic search for studies simultaneously comparing all three diagnoses regarding demographic, clinical, psychometric (clinical rating scales and IQ tests), and biological parameters; comparison of heterogeneity as measured by standard deviation (SD). ResultsStandard deviation of SAD samples (N=47) was smaller than in both differential diagnoses. SDs were 7% higher in BD than in SAD (SZ: 2% higher); in studies employing DSM-IIIR/-IV pooled SD was 4% higher in BD (8% lower in SZ). Differences between diagnoses were limited to the comparison of SAD and BD, and became smaller when only psychotic BD was considered. Conclusion Heterogeneity of SZ and BD is not smaller than that of SAD. SAD seems not to be more diverse than other functional psychoses. Results are preliminary because of the novelty of the approach and to the small number of studies.
Article
Longitudinal studies of biological domains in bipolar disorder (BD) are crucial in determining if such baseline changes are progressive. We reviewed reported studies of longitudinal brain structural/functional magnetic resonance imaging (MRI) and neuropsychological changes in BD through November 2012. Longitudinal brain structural MRI studies suggest cortical and subcortical abnormalities within networks subserving emotional regulation. There is evidence of neuroprogressive loss of gray matter volume in prefrontal and anterior cingulate cortex and the subgenual region, with less consistent findings in temporal and subcortical regions. Abnormal amygdala neurodevelopment is noted in adolescent onset BD and possible changes in hippocampus require further evaluation. The fewer reported longitudinal functional MRI studies suggest neurobiological changes in activation patterns involving fronto-limbic circuitry which relate to different illness phase and mood states. Early onset paediatric/adolescent BD may signify a more malignant course of illness in which extensive and executive neurocognitive deficits are found early and may persist, with some potential for improvement during remission and perhaps with treatment. Future studies should include larger samples, combine investigational modalities, incorporate genetic profiles, consider standardisation of assessments and collaborative ventures across institutions, selection of more homogeneous subgroups and track neurobiological changes longer to clarify trajectories of changes.
Article
Die Beschäftigung mit Wilhelm Griesingers Werk ist weit über den psychiatriehistorischen Rahmen hinaus von besonderem Interesse für die aktuelle Debatte um das Selbstverständnis unseres Faches. Dies folgt vor allem daraus, dass Griesinger – der wohl am häufigsten verkürzt und undifferenziert rezipierte und kommentierte richtungsweisende psychiatrische Autor des 19. Jahrhunderts – den (auch damals schon) ungeliebten erkenntnistheoretischen Grundfragen des Faches nicht ausgewichen ist, sondern sie ideenreich und in ständigem Bezug zur klinischen und wissenschaftlichen Praxis erörtert hat. Thorough re-analysis of Wilhelm Griesinger's scientific work is very interesting not only from the historical point of view, but also with regard to the present-day debate about the role and self-image of psychiatry. In the literature, Griesinger's ideas are often reported in a rather undifferentiated and condensed manner. Therefore, it may be overlooked that he did not avoid getting involved with the principal epistemological issues of psychiatry (which were an unpopular topic in his time as well), but discussed them intensively and with a constant look at their relevance for clinical and research purposes.
Article
Schizoaffective disorder (SAD) is a chronic, severe and disabling illness consisting on the concurrent presentation of symptoms of schizophrenia and affective disorders (depression and/or mania). Evidence for the treatment of SAD mostly derives from studies based on mixed samples (i.e. schizophrenic and schizoaffective patients) or on extrapolations from studies on schizophrenia or bipolar disorder. The objective of the present review is to systematically consider and summarize the best evidence-based approaches to the treatment of SAD and extensively point out the gap between treatment research and clinical practice of this disorder. The complex problem of controlling the pleomorphic presentation of SAD's syndromic construct is reflected in the lack of evidence on key topics, including: diagnostic consistency, pharmacological approaches (mood stabilizers, antidepressants, both in acute and maintenance treatment as well as their possible combination), and the adjunctive role of psychosocial and biophysical interventions. Finally, treatment strategies for SAD, both unipolar and bipolar type, are proposed.
Article
To develop an individualized treatment plan that addresses both psychotic and affective symptoms in patients with schizoaffective disorder, clinicians can take several steps. First, clinicians can confirm the diagnosis. In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and in the International Classification of Diseases, Tenth Revision (ICD-10), schizoaffective disorder is defined differently, but, diagnostically, the disorder falls on a spectrum between bipolar disorder and schizophrenia and can be divided into bipolar and depressive types. Next, clinicians can evaluate predictors of outcome. Outcomes can be predicted by previous functioning, number of previous episodes, persistence of psychotic symptoms, and level of cognitive impairment. Then, clinicians can use evidence from clinical trials to guide selection of acute and maintenance phase treatment. Although data are limited, direct and indirect evidence from clinical trials support pharmacologic and psychoeducational interventions. In bipolar type schizoaffective disorder, evidence supports the use of an atypical antipsychotic and a mood stabilizer or atypical antipsychotic monotherapy. In the depressive type of the disorder, the combination of an atypical antipsychotic and an antidepressant is probably the best choice, but an atypical antipsychotic and a mood stabilizer could also be used. In both types of the disorder, patient psychoeducation can be beneficial in the maintenance phase of treatment. Adherence to treatment is essential for optimal outcome, and, besides patient psychoeducation, long-acting injectable antipsychotics and psychoeducation for caregivers may also improve adherence. In refractory cases, electroconvulsive therapy is an option.
Article
Schizoaffective disorder is a common diagnosis in mental health services. The present article aims to provide an overview of diagnostic reliability, symptomatology, outcome, neurobiology and treatment of schizoaffective disorder. Literature was identified by searches in "Medline" and "Cochrane Library". The diagnosis of schizoaffective disorder has a low reliability. There are marked differences between the current diagnostic systems. With respect to psychopathological symptoms, no clear boundaries were found between schizophrenia, schizoaffective disorder and affective disorders. Common neurobiological factors were found across the traditional diagnostic categories. Schizoaffective disorder according to ICD-10 criteria, but not to DSM-IV criteria, shows a more favorable outcome than schizophrenia. With regard to treatment, only a small and heterogeneous database exists. Due to the low reliability and questionable validity there is a substantial need for revision and unification of the current diagnostic concepts of schizoaffective disorder. If future diagnostic systems return to Kraepelin's dichotomous classification of non-organic psychosis or adopt a dimensional diagnostic approach, schizoaffective disorder will disappear from the psychiatric nomenclature. A nosological model with multiple diagnostic entities, however, would be compatible with retaining the diagnostic category of schizoaffective disorder.
Article
Schizophrenia (SZ) is a common and severe psychiatric disorder with both environmental and genetic risk factors, and a high heritability. After over 20 years of molecular genetics research, new molecular strategies, primarily genome-wide association studies (GWAS), have generated major tangible progress. This new data provides evidence for: (1) a number of chromosomal regions with common polymorphisms showing genome-wide association with SZ (the major histocompatibility complex, MHC, region at 6p22-p21; 18q21.2; and 2q32.1). The associated alleles present small odds ratios (the odds of a risk variant being present in cases vs. controls) and suggest causative involvement of gene regulatory mechanisms in SZ. (2) Polygenic inheritance. (3) Involvement of rare (<1%) and large (>100kb) copy number variants (CNVs). (4) A genetic overlap of SZ with autism and with bipolar disorder (BP) challenging the classical clinical classifications. Most new SZ findings (chromosomal regions and genes) have generated new biological leads. These new findings, however, still need to be translated into a better understanding of the underlying biology and into causal mechanisms. Furthermore, a considerable amount of heritability still remains unexplained (missing heritability). Deep resequencing for rare variants and system biology approaches (e.g., integrating DNA sequence and functional data) are expected to further improve our understanding of the genetic architecture of SZ and its underlying biology.
Article
To examine the effect of diagnosis, mood state, and anxiety on subjective wellbeing in patients with affective and non-affective psychotic disorders treated with quetiapine IR. 2175 patients with schizophrenia-spectrum (SZ, n=1681), schizoaffective (SA, n=249), and bipolar disorder (BPD, n=245) were treated with quetiapine over 6 months and assessed with the Clinical Global Impression-Severity of illness Scale (CGI-S) and the Subjective Wellbeing under Neuroleptic Treatment Scale (SWN-K). Diagnostic group differences and effects of mood state and anxiety on subjective wellbeing were analyzed using multi-factorial linear regression analysis and mixed models repeated measures. At baseline, despite similar CGI-S scores, significant SWN-K score differences between SZ (57.7 points), SA (64.1 points), and BPD (79.5 points) were detected. At baseline, depression (p<0.001) and anxiety (p<0.001) were independently associated with a worse and mania (p<0.001) with a better subjective wellbeing. Subjective wellbeing improved significantly in all groups (p<0.001; 27.6 points), and endpoint subjective wellbeing was not predicted by baseline depression or anxiety, but by endpoint depression and anxiety. Interventions to improve subjective wellbeing should take into account the course of mood state and anxiety. Assessment of subjective wellbeing and subjective quality of life in acute mania may need adapted tools.
Article
Whether schizophrenia and bipolar disorder are the clinical outcomes of discrete or shared causative processes is much debated in psychiatry. We aimed to assess genetic and environmental contributions to liability for schizophrenia, bipolar disorder, and their comorbidity. We linked the multi-generation register, which contains information about all children and their parents in Sweden, and the hospital discharge register, which includes all public psychiatric inpatient admissions in Sweden. We identified 9 009 202 unique individuals in more than 2 million nuclear families between 1973 and 2004. Risks for schizophrenia, bipolar disorder, and their comorbidity were assessed for biological and adoptive parents, offspring, full-siblings and half-siblings of probands with one of the diseases. We used a multivariate generalised linear mixed model for analysis of genetic and environmental contributions to liability for schizophrenia, bipolar disorder, and the comorbidity. First-degree relatives of probands with either schizophrenia (n=35 985) or bipolar disorder (n=40 487) were at increased risk of these disorders. Half-siblings had a significantly increased risk (schizophrenia: relative risk [RR] 3.6, 95% CI 2.3-5.5 for maternal half-siblings, and 2.7, 1.9-3.8 for paternal half-siblings; bipolar disorder: 4.5, 2.7-7.4 for maternal half-siblings, and 2.4, 1.4-4.1 for paternal half-siblings), but substantially lower than that of the full-siblings (schizophrenia: 9.0, 8.5-11.6; bipolar disorder: 7.9, 7.1-8.8). When relatives of probands with bipolar disorder were analysed, increased risks for schizophrenia existed for all relationships, including adopted children to biological parents with bipolar disorder. Heritability for schizophrenia and bipolar disorder was 64% and 59%, respectively. Shared environmental effects were small but substantial (schizophrenia: 4.5%, 4.4%-7.4%; bipolar disorder: 3.4%, 2.3%-6.2%) for both disorders. The comorbidity between disorders was mainly (63%) due to additive genetic effects common to both disorders. Similar to molecular genetic studies, we showed evidence that schizophrenia and bipolar disorder partly share a common genetic cause. These results challenge the current nosological dichotomy between schizophrenia and bipolar disorder, and are consistent with a reappraisal of these disorders as distinct diagnostic entities.
Article
This paper reminds the concept of a unitary nosological and pathogenic process that may be traced back to Joseph Guislain (1797-1860). The "phrénalgie initiale" was regarded as the initial stage of psychic illness by Guislain (Leçons orales, Ghent, 1852). That vision inspired the work of Wilhelm Griesinger (1817-1869) who further elaborated the concept of "Einheitspsychose" (Psychose unique--Unitary psychosis). That concept partially inspired Emil Kräpelin (1856-1926). Current classification systems like ICD-10 and DSM-III-R attempt to synthesize different views and the concept of unitary psychosis is actualized in the contemporary transnosography.
Article
1. A group of 9 cases is presented in which there is a blending of schizophrenic and affective symptoms. 2. The psychosis is characterized by a very sudden onset in a setting of marked emotional turmoil with a distortion of the outside world and presence of false sensory impressions in some cases. The psychosis lasts a few weeks to a few months and is followed by a recovery. 3. Our patients are young people, in the twenties or thirties, in excellent physical health, in whom there is usually a history of a previous attack in late adolescence.
Article
The lack of clinically homogenous cohorts of functional psychoses remains a major obstacle to further advances in biological psychiatry. In view of this fact, it seems appropriate to call attention to the teachings of the WernickeKleist-Leonhard school largely ignored by Anglo-American psychiatry. This classical school of thought represents a radical departure from the traditions of Kraepelin, Bleuler, and Schneider, wliich underpin current classifications of schizophrenic and affective psychoses. Although well-known for his work on aphasia, Carl Wernicke (1848-1905) is one of the undeservedly forgotten pioneers of biological psychiatry. Wernicke's efforts to explain psychiatric disorders with his "sejunction" hypothesis, a comprehensive neuropathological framework, were branded as "brain mythology" by Jaspers (Jaspers 1963) while paying tribute to Wernicke's contribution to descriptive psychopathology. Briefly, sejunction means disruption in the interconnections between different neural systems, thus giving rise to loss of function, hypeffunction, and parafunction. For instance, in the area of psychomotility, sejunction may result in akinesia (psychomotor retardation), hyperkinesia (motor excitement), or parakinesia (e.g., mannerisms, choreiform movements). Wernicke's hypothesis of psychic functions and their impairment is in keeping with the tenets of modem neuroscience, implying a dynamic interplay between different neural systems rather than assuming a one-to-one correspondence of psychic functions to morphological substrates. In the light of recent reappraisals of Wernicke's notions on the relationship between psychopathology and brain pathology (e.g., Franzek 1990), Jaspers' deprecating label does not seem to be justified.
Article
The validity and nosologic status of schizoaffective disorder is still a controversial issue. This study was conducted to analyze the demographic, clinical and prognostic variables that determine the validity of the diagnosis of schizoaffective disorder bipolar type. We analyzed and compared 138 outpatients: 67 with type I bipolar disorder, 34 with schizoaffective disorder bipolar type and 37 with schizophrenia. They were all diagnosed following research diagnostic criteria and assessed according to the Schedule for Affective Disorders and Schizophrenia. Schizoaffective unipolar patients were excluded. The results reaffirmed that, from the standpoints of demographics, clinical features and prognosis, schizoaffective disorders bipolar type can be classified as a phenotypic form at an intermediate point between bipolar I disorder and schizophrenia. These results emphasize the importance of longitudinal follow-up in the diagnosis and assessment of psychotic syndromes. Although cross-sectional symptoms were closer to the schizophrenia spectrum, the course of the illness resembled more that of bipolar patients, resulting in an intermediate outcome.
Article
Thorough re-analysis of Wilhelm Griesinger's scientific work is very interesting not only from the historical point of view, but also with regard to the present-day debate about the role and self-image of psychiatry. In the literature, Griesinger's ideas are often reported in a rather undifferentiated and condensed manner. Therefore, it may be overlooked that he did not avoid getting involved with the principal epistemological issues of psychiatry (which were an unpopular topic in his time as well), but discussed them intensively and with a constant look at their relevance for clinical and research purposes.
Article
To provide an overview of long-term treatment studies in schizoaffective disorder (SAD) and to draw conclusions for clinical decision-making. Literature was identified by searches in Medline, Embase, and the Cochrane Controlled Trials Register as well as a hand-search of handbook and journal articles. Studies were considered relevant if they reported on trials of at least 6 months duration and if they presented data for the SAD patients in particular. Thirty-nine studies met the criteria and 18 used modern diagnostic criteria, i. e., RDC, DSM-III-R, -IV, or ICD-10. The studies focused on lithium, anticonvulsants, and antipsychotics. The scientific evidence for prophylactic efficacy of the different substances is poor. Nevertheless, the data encourage the use of lithium and carbamazepine in primarily affective patients and clozapine in primarily schizophrenic patients and possibly in mainly affective patients as well. There is a considerable need for prospective and controlled studies on the long-term treatment of SAD. However, it seems to be useful to subtype the disorder of the patients into primarily affective vs. schizophrenic schizoaffective disorder and schizodepressive vs. schizobipolar and to treat accordingly.
Schizoaffective disorders are well established. Nevertheless, the definition in the International Classification of Diseases (ICD)-10 and the Diagnostic and Statistical Manual (DSM)-IV are insufficient. Critical review of the literature from Kahlbaum (1863) to the 21st century. Many authors have described people suddenly developing a disorder with both 'schizophrenic' and 'affective' symptoms. In DSM-IV and ICD-10, the schizoaffective disorder is defined as the concurrent occurrence of schizophrenic symptoms with a major affective disorder. However, there is no reason for a chronological distinction regarding the co-existence of schizophrenic and affective symptomatology. Moreover, longitudinal aspects are not included in the definitions. Two types of schizoaffective disorder must be distinguished: the 'concurrent' and the 'sequential' type. The first includes people having only a coincidence of schizophrenic and affective symptoms. The 'sequential' type is defined as the schizoaffective disorder under a longitudinal aspect subsuming disorders with a symptom change between different episodes. Consequences for further research are discussed in detail.
Article
The syndrome of manic-depressive insanity (MDI), as conceptualized by Emil Kraepelin a century ago, with later refinements, continues to dominate research and clinical practice with mood disorder patients. Current understanding of Kraepelin's views by Anglophones is heavily influenced by the late, highly developed, MDI concept represented in the 1921 partial English translation of the last complete edition of his textbook, the product of gradual development over several decades. We reviewed all nine editions and revisions of Kraepelin's Textbook (1883-1926) and other writings by him to document the evolution of his views of MDI, and characterized salient developments within biographical and historical contexts. We found support for the traditional impression that Kraepelin's clinical perception of similarities of various forms of periodic psychiatric disorders marked by fundamental dysregulation of excitation and inhibition of thought and behavior, as well as of mood--as distinct from chronic psychotic illnesses--encouraged his broad, mature concept of MDI. However, our findings indicate a complex evolution of Kraepelin's MDI concept in the 1880s and 1890s, his use of more creative and less empirical clinical methods than traditionally believed, and his considerable personal uncertainty about making clear distinctions among MDI, dementia praecox, intermediate conditions, and paranoid disorders--an uncertainty that persisted to the end of his career in the 1920s. Kraepelin responded to a compelling international need for diagnostic order in nineteenth-century psychiatry, and effectively promoted his diagnostic proposals with a widely used and influential textbook. Though his methods were less empirical than is usually realized, his legacy includes analysis of large clinical samples to describe psychopathology and illness-course, along with efforts to define psychobiologically coherent and clinically differentiable entities, as steps toward defining psychiatric syndromes. Modern international "neo-Kraepelinian" enthusiasm for descriptive, criterion-based diagnosis should be tempered by Kraepelin's own appreciation of the tentative and uncertain nature of psychiatric nosology, particularly in classifying illnesses with both affective and psychotic features.
Article
Schizoaffective disorder was named as a compromise diagnosis in 1933, and remains popular as judged by its place in the International Classification of Diseases and the Diagnostic and Statistical Manual of Mental Disorders, its frequent use in clinical practice, and its extensive discussion in the literature. Some, however, have questioned the validity of schizoaffective disorder as separate from psychotic mood disorder. We examined the literature to assess the rationale for the continuation of schizoaffective disorder as a legitimate diagnostic category. The diagnosis of schizoaffective disorder depends on the disease specificity of the diagnostic criteria for schizophrenia; however, the psychotic symptoms for schizophrenia, traditionally held as specific, can be accounted for by psychotic bipolar. Further, the interrater reliability for diagnosing schizoaffective disorder is very low. A recent and expanding body of comparative evidence from a wide range of clinical and basic science studies, especially genetic, reveals multiple similarities between schizoaffective disorder, schizophrenia and psychotic bipolar. Schizoaffective disorder unifies schizophrenia and bipolar, blurring the zones of rarity between them and suggesting that schizoaffective disorder is not a separate, 'bona-fide' disease. Patients diagnosed with schizoaffective disorder likely suffer from a psychotic mood disorder. The diagnosis of schizoaffective disorder, which can result in substandard treatment, should be eliminated from the diagnostic nomenclature.
Article
Since its first definition in the literature, schizoaffective disorder (SAD) has raised a considerable controversy regarding its clinical distinction from schizophrenia (SCH) and mood disorders (MD) as well as its validity as an independent nosological category. Investigate the validity of SAD as a discrete nosological category and its relationship with SCH and MD. A systematic literature review of clinical trial that compared SAD with SCH and/or MD patients was carried out throughout MEDLINE, psycINFO, Cochrane Library, SCIELO and LILACS databases. Evaluation of demographic characteristics, symptomatology, other clinical data, dexamethasone suppression test, neuroimage exams, response to treatment, evolution and family morbidity indicated that SAD occupies an intermediate position between SCH and MD. Literature review also failed to indicate a clear cut distinction between SAD and SCH or MD. Present analysis indicated that SAD cannot be interpreted as atypical forms of SCH or MD. SAD also does not appear to represent a SCH and MD comorbidity or yet an independent mental disorder. It is argued that SAD might constitute a heterogeneous group composed by both SCH and MD patients or a middle point of a continuum between SCH and MD.
Article
The authors determined whether diagnoses of cardiovascular disease (CVD) and CVD-related conditions differed by psychiatric diagnosis among male Veterans Administration patients from the mid-Atlantic region. Among 7,529 patients (mean age: 54.5 years), the prevalence of diagnoses ranged from 3.6% (stroke) to 35.4% (hypertension). Compared with schizophrenia patients, those with bipolar disorder were 19% more likely to have diabetes, 44% more likely to have coronary artery disease, and 18% more likely to have dyslipidemia, after adjustment. Clinical suspicion for CVD-related conditions, as well as risk-modification strategies, in patients with serious mental illness should incorporate differences in prevalence across specific psychiatric diagnoses.
Article
Difficulties surrounding the classification of mixed psychotic and affective syndromes continue to plague psychiatric nosology. This paper addresses the controversy regarding the diagnostic validity of schizoaffective disorder (SAD), a diagnosis that is used in both DSM-IV and ICD-10 and one that encroaches on both schizophrenia (SCZ) and bipolar disorder (BD). A systematic synthesis of clinical and empirical literature, including evidence from cognitive, neurobiological, genetic, and epidemiological research, was undertaken with the aim of evaluating the utility of the SAD classification. Distinctions between the diagnostic categories of SCZ, SAD and BD are not clearly demarcated by findings from neuropsychological, neuroimaging, molecular neurobiology, or genetic epidemiology studies. On the contrary, convergent evidence purports overlap across current diagnostic boundaries in the heritability and pathophysiology of psychotic and affective disorders. However, there are some disorder-specific findings. Schizoaffective disorder is a prototypic boundary condition that epitomizes the pitfalls of the current categorical classification system. Future revisions to the DSM should consider the implementation of one of two alternative models to account for individuals presenting with mixed psychotic and affective symptoms. These include the views that (i) SAD is a comorbid set of symptoms that occur as a by-product of two separate disorders (SCZ and BD) or, that (ii) SAD exists as the mid-point on a continuum between SCZ and BD, such that the incorporation of these two disorders onto one dimension may be a suitable alternative. Hence the category SAD should be omitted in future revisions of DSM, allowing the development of meaningful nomenclature that rests upon further rigorous investigation of differences and similarities between disorders.
Bipolar disorder, schizoaffective disorder and schizophrenia: epidemiologic, clinical and prognostic differences
  • A Benabarre
  • E Vieta
  • F Colom
  • Mart Inez-Ar An
  • A Reinares
  • M Gast O C
Benabarre A, Vieta E, Colom F, Mart ınez-Ar an A, Reinares M, Gast o C. Bipolar disorder, schizoaffective disorder and schizophrenia: epidemiologic, clinical and prognostic differences. Eur Psychiatry 2001;16:167-172.
Longitudinal neuroimaging and neuropsychological changes in bipolar disorder patients: review of the evidence
  • C S Lim
  • R J Baldessarini
  • E Vieta
  • M Yucil
  • E Bora
  • K Sim
Lim CS, Baldessarini RJ, Vieta E, Yucil M, Bora E, Sim K. Longitudinal neuroimaging and neuropsychological changes in bipolar disorder patients: review of the evidence. Neurosci Biobehav Rev 2013;37:418-435.