Deficiencias mnésicas, ejecutivas y atencionales como endofenotipos neurocognitivos en el trastorno bipolar: una revisión.

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Title:	Deficiencias mnésicas, ejecutivas y atencionales como endofenotipos neurocognitivos en el trastorno bipolar: una revisión.
Authors:	Castañeda Franco, Marisol¹ castaneda@imp.edu.mx, Tirado Durán, Elsa¹
Source:	Salud Mental. mar/apr2008, Vol. 31 Issue 2, p145-150. 6p.
Subjects:	GENETICS of bipolar disorder, DISEASE complications, ATTENTION, MEMORY, NEUROPSYCHOLOGICAL tests, BRAIN imaging
Abstract (English):	Although many studies have demonstrated that bipolar disorder (BD) is heritable, the disorder's genetic basis remains elusive despite the substantial evidence. Hence, indicators of processes mediating between genotype and phenotype, known as endophenotypes, may be necessary to provide more information about this issue. Given that endophenotypes could provide information for elucidating the genetic underpinnings of BD, many studies have focused on one class of endophenotypic marker, the neuropsychological measures. In order for a cognitive measure to be considered an endophenotype, it has to 1. be highly heritable, 2. be associated with the illness, 3. be independent of the clinical state and, 4. the impairment must co-segregate with the illness within a family, with non-affected family members showing impairment relative to general population. In this sense, failures in attention, executive functions and verbal memory are the most consistently reported deficits with the characteristics for endophenotypes. With these factors in mind, the primary interest of this paper was to review the existing literature on neurocognitive functioning in BD as possible endophenotypes. Studies were identified by searching the major databases (MEDLINE and PSYCINFO) from 1990 to 2007 with the following key words: endophenotype, neurocognitive assessment, bipolar disorder, attention, memory, executive functions, neuropsychological assessment and neuroimaging. The titles and abstracts of the articles identified were examined and those that appeared to fullfil our inclusion criteria were retrieved. Articles were included if they met the following criteria: 1. included adult patients (aged: 16-65), 2. included a psychiatric or normal comparison group, 3. used well-established diagnostic criteria to ascertain diagnosis (DSM, 3rd. and 4th. eds.), 4. provided information about the clinical status of the patients being assessmed and 5. cognitive assessment was based on standardized or well established cognitive tasks. Declarative memory has been studied in BD patients through tests that imply learning of words and stories to evaluate immediate memory, delayed recall and recognition, also considering the kind of strategies that the patients use to evoke verbal material. It seems that BD patients in depressive phase present deficits in immediate memory and delayed recall, but recognition memory is preserved. This impairment is due to difficulties in the planning and evoking strategies used, associated to prefrontal dysfunction. In manic phase, the patients make a lot of irrelevant associations because the failure in the system to control impulses. In the absence of the depressive and maniac symptoms, patients continue with anomalies in memory. Euthymic patient can use a similar semantic clustering strategy so that they can recall and recognize fewer words than controls, suggesting impaired encoding of verbal information and there is lack of rapid forgetting, which suggests a relative absence of a storage deficit. Results of studies in declarative memory impairment in BD suggests that the impairments are consistent with deficits in learning, but do not appear to be related to different organizational strategies during learning, and do not appear to be secondary to clinical state. Rather, they are associated with the underlying pathophysiology of the illness. Regarding executive functions, patients with BD have deficiencies related to planning, organizational strategies, lack of control in the action, conceptual formation and cognitive flexibility. In depressive phase, patients have problems with concept formation, meanwhile the deficit in verbal fluency is due because they use phonemic rather than semantic clues.… [ABSTRACT FROM AUTHOR]
Abstract (Spanish):	En los últimos años se ha planteado la necesidad de identificar los procesos que median entre el genotipo y el fenotipo del Trastorno Bipolar (TB), dando importancia al estudio de los endofenotipos. Los endofenotipos tratan del fenotipo interno y que no se observa clínicamente, que se encuentra mas cercano a la etiología biológica de la enfermedad que sus signos y síntomas, y que se encuentra influenciado por uno o más genes susceptibles al trastorno. Para que un marcador pueda ser considerado como endofenotipo debe cubrir las siguientes características: 1) ser heredable, 2) estar asociado con la enfermedad, 3) ser independiente del estado clínico y 4) mostrar co-segregación familiar. Dentro de los métodos disponibles para identificar a los endofenotipos se encuentran las mediciones neuropsicológicas y cognitivas entre otras. Diversos autores han señalado la utilidad de identificar los endofenotipos neurocognitivos del TB para mejorar la capacidad de detección de los genes que predisponen a la aparición del trastorno y ayudar a una mejor definición de los criterios diagnósticos. En este sentido, se han señalado a las alteraciones en los dominios de atención selectiva, memoria verbal y funciones ejecutivas, como marcadores endofenotípicos más representativos del TB porque cumplen con los criterios antes mencionados. Por lo tanto, en el presente artículo se realizó una revisión de los estudios neuropsicológicos reportados en pacientes con TB en estos dominios cognitivos y la descripción de estas deficiencias, así como de los circuitos neuronales asociados con estas alteraciones. Se realizó una búsqueda de artículos en MEDLINE y psycINFO desde 1990 a 2007 con las siguientes palabras clave: endofenotipo, evaluación neuropsicológica, trastorno bipolar, atención, memoria, funciones ejecutivas, neurocognición y neuroimagen. Los títulos y resúmenes de los artículos identificados fueron examinados y se conservaron aquellos que cubrían nuestros criterios de inclusión. Los artículos se tomaron en cuenta si cubrían los siguientes criterios: 1) incluían pacientes adultos (edad: 16-65), 2) incluían un grupo de comparación psiquiátrico o normal, 3) utilizaban criterios diagnósticos bien establecidos para el diagnóstico (DSM 3a. y 4a. eds.), 4) describían información sobre el estado clínico del paciente al momento de la evaluación y 5) utilizaban evaluaciones cognitivas con tareas estandarizadas y bien establecidas. En relación a la memoria declarativa, los pacientes en un episodio depresivo muestran alteraciones en las pruebas de aprendizaje y de memoria de listas de palabras en las variables de recuerdo libre, tanto a corto como a largo plazo; estas subyacen a deficiencias en la planeación y en la memoria operativa o de trabajo, mismas que persisten después de la fase aguda de cualquier etapa de este padecimiento. Durante la manía se observa un pobre desempeño caracterizado por intrusiones y asociaciones verbales irrelevantes. Se ha señalado que durante la eutimia existen deficiencias asociadas con fallas en la codificación de la información y que no se deben al olvido o a deficiencias en su almacenamiento.… [ABSTRACT FROM AUTHOR]
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Database:	MedicLatina

Description
Abstract:	Although many studies have demonstrated that bipolar disorder (BD) is heritable, the disorder's genetic basis remains elusive despite the substantial evidence. Hence, indicators of processes mediating between genotype and phenotype, known as endophenotypes, may be necessary to provide more information about this issue. Given that endophenotypes could provide information for elucidating the genetic underpinnings of BD, many studies have focused on one class of endophenotypic marker, the neuropsychological measures. In order for a cognitive measure to be considered an endophenotype, it has to 1. be highly heritable, 2. be associated with the illness, 3. be independent of the clinical state and, 4. the impairment must co-segregate with the illness within a family, with non-affected family members showing impairment relative to general population. In this sense, failures in attention, executive functions and verbal memory are the most consistently reported deficits with the characteristics for endophenotypes. With these factors in mind, the primary interest of this paper was to review the existing literature on neurocognitive functioning in BD as possible endophenotypes. Studies were identified by searching the major databases (MEDLINE and PSYCINFO) from 1990 to 2007 with the following key words: endophenotype, neurocognitive assessment, bipolar disorder, attention, memory, executive functions, neuropsychological assessment and neuroimaging. The titles and abstracts of the articles identified were examined and those that appeared to fullfil our inclusion criteria were retrieved. Articles were included if they met the following criteria: 1. included adult patients (aged: 16-65), 2. included a psychiatric or normal comparison group, 3. used well-established diagnostic criteria to ascertain diagnosis (DSM, 3rd. and 4th. eds.), 4. provided information about the clinical status of the patients being assessmed and 5. cognitive assessment was based on standardized or well established cognitive tasks. Declarative memory has been studied in BD patients through tests that imply learning of words and stories to evaluate immediate memory, delayed recall and recognition, also considering the kind of strategies that the patients use to evoke verbal material. It seems that BD patients in depressive phase present deficits in immediate memory and delayed recall, but recognition memory is preserved. This impairment is due to difficulties in the planning and evoking strategies used, associated to prefrontal dysfunction. In manic phase, the patients make a lot of irrelevant associations because the failure in the system to control impulses. In the absence of the depressive and maniac symptoms, patients continue with anomalies in memory. Euthymic patient can use a similar semantic clustering strategy so that they can recall and recognize fewer words than controls, suggesting impaired encoding of verbal information and there is lack of rapid forgetting, which suggests a relative absence of a storage deficit. Results of studies in declarative memory impairment in BD suggests that the impairments are consistent with deficits in learning, but do not appear to be related to different organizational strategies during learning, and do not appear to be secondary to clinical state. Rather, they are associated with the underlying pathophysiology of the illness. Regarding executive functions, patients with BD have deficiencies related to planning, organizational strategies, lack of control in the action, conceptual formation and cognitive flexibility. In depressive phase, patients have problems with concept formation, meanwhile the deficit in verbal fluency is due because they use phonemic rather than semantic clues.… [ABSTRACT FROM AUTHOR]
ISSN:	01853325