Endofenotipos neurocognitivos potenciales para el trastorno bipolar: velocidad motora manual, memoria visual, velocidad de procesamiento

Antecedentes: Son pocas las investigaciones que se centran en el estudio de las disfunciones neurocognitivas en pacientes con trastorno bipolar (TB) como posibles marcadores de rasgo para esta enfermedad, menos aún son las que comparan el rendimiento motor, la memoria visual o la velocidad de procesamiento de la información, en estudios transversales o longitudinales, incluyendo a la vez, controles (CS) y familiares sanos de primer grado de los pacientes (TB-F); hasta la redacción de esta tesis, aunque el número va en aumento, en la investigación psiquiátrica el trastorno bipolar sigue ocupando un lugar secundario frente a la esquizofrenia, siendo insuficientes los estudios que buscan evidencias sobre posibles endofenotipos neurocognitivos de esta enfermedad mental. El objetivo de la presente tesis, en formato de “compendio de estudios”, es contribuir a esclarecer si tres de las disfunciones neurocognitivas menos estudiadas actualmente en el trastorno bipolar: 1) Velocidad Motora Manual (VMM), 2) Memoria Visual (MV) y 3) Velocidad de Procesamiento de la Información (VPI), podrían ser incluidas dentro del perfil endofenotípico de esta enfermedad mental, siguiendo los criterios tradicionalmente utilizados para su selección. Método: Se presentan separadamente 3 estudios, en cada uno de los cuales se siguió similar metodología investigativa, pero se utilizaron pruebas neurocognitivas diferentes: 1) Finger-Tapping Test (FTT), 2) Test de Copia y de Reproducción de Memoria de Figuras Geométricas Complejas (REY) y 3) subtest “Símbolos” o “Clave de Números” del WAIS (CN). Las evaluaciones se realizaron en tres tiempos investigativos a lo largo de cinco años, con tres grupos: pacientes con trastorno bipolar, sus familiares sanos de primer grado y controles sanos no relacionados genéticamente. La influencia de la edad sobre el desempeño de los participantes, en las pruebas, fue controlada con un modelo de regresión lineal sobre las medias de los CS. Las diferencias entre los grupos se compararon con un test ANOVA. Para determinar los endofenotipos, se creó y siguió una lista de verificación o protocolo, con los criterios de selección más utilizados en este campo de investigación. Resultados: En los tres estudios se observa que los pacientes siempre presentan peores rendimientos que los controles, manteniéndose estas diferencias a lo largo de los tres tiempos de estudio, con independencia de la mayoría de las variables sociodemográficas y clínicas. Las puntuaciones medias de los familiares, a pesar de presentar un comportamiento inestable, equiparándose a las de los pacientes en algunos momentos y en otros a las de los controles, siempre conservaron el mismo perfil o patrón intermedio (TB≤TB-F≤CS). Limitaciones: En el estudio 1 sólo se incluyeron sujetos diestros. En los estudios 2 y 3 se detectó una disminución importante en el número de casos de familiares en el tiempo 3, por lo cual fuera necesario excluir del análisis los resultados de este grupo de familiares en ese momento del estudio. Conclusiones: Los pacientes con trastorno bipolar presentan déficits cognitivos en la VMM, en la MV y en la VPI, con independencia de la mayoría de los factores sociodemográficos y clínicos. Los familiares de los pacientes presentan déficits en la VMM y en la MV en T1. Además, en todos los momentos y pruebas utilizadas, los rendimientos de los familiares presentan un perfil o patrón intermedio entre los rendimientos de los otros dos grupos. Teniendo en cuenta estos elementos y el cumplimiento de algunos otros de los criterios de la lista de verificación, podemos concluir que, los déficits en la velocidad de procesamiento de la información son un endofenotipo potencial, la disfunción en la velocidad motora manual es un endofenotipo bastante probable, y la memoria visual es de los tres, el más adecuado para ser incluido dentro del perfil endofenotípico del Trastorno Bipolar. Todo esto a la espera de nuevos estudios con resultados similares que apoyen estas conclusiones

Motor and Cognitive Performance in Patients with Liver Cirrhosis with Minimal Hepatic Encephalopathy

Minimal hepatic encephalopathy (MHE) is associated with mild cognitive impairment and frailty. This study aims to identify cognitive and motor differences in cirrhotic patients with and without MHE, and the correlations between motor signs and cognitive performance. Gait, balance, hand strength and motor speed performance were evaluated in 66 cirrhotic patients (38 without and 28 with MHE, according to the Psychometric Hepatic Encephalopathy Score (PHES). Cognitive performance was measured with the Mini-Mental State Examination, Verbal Fluency Test, Aprendizaje Verbal España-Complutense Test (TAVEC), Wechsler Adult Intelligence Scale III, Hamilton Depression and Anxiety Rating Scale and Functioning Assessment Short Test (FAST). MHE patients performed worse than patients without MHE in cognitive and autonomous functioning, learning and long-term memory, and verbal fluency. The same pattern was found in gait, center of pressure movement, variability of hand strength performance and hand motor speed. In MHE patients, high correlations were found between balance and FAST test, gait velocity and verbal skills, hand strength variability and anxiety and depression, and motor speed and FAST and TAVEC. MHE patients showed worse motor and cognitive performance than patients without MHE. MHE patients could have impaired movement control expressed as bradykinesia, and this reduced motor performance could correlate with cognitive performance

Visual memory dysfunction as a neurocognitive endophenotype in bipolar disorder patients and their unaffected relatives. Evidence from a 5-year follow-up Valencia study

BACKGROUND: Scarce research has focused on Visual Memory (VM) deficits as a possible neurocognitive endophenotype of bipolar disorder (BD). The main aim of this longitudinal, family study with healthy controls was to explore whether VM dysfunction represents a neurocognitive endophenotype of BD. METHODS: Assessment of VM by Rey-Osterrieth Complex Figure Test (ROCF) was carried out on a sample of 317 subjects, including 140 patients with BD, 60 unaffected first-degree relatives (BD-Rel), and 117 genetically-unrelated healthy controls (HC), on three occasions over a 5-year period (T1, T2, and T3). BD-Rel group scores were analyzed only at T1 and T2. RESULTS: Performance of BD patients was significantly worse than the HC group (p < 0.01). Performance of BD-Rel was also significantly different from HC scores at T1 (p < 0.01) and T2 (p?=?0.05), and showed an intermediate profile between the BD and HC groups. Only among BD patients, there were significant differences according to sex, with females performing worse than males (p?=?0.03). Regarding other variables, education represented significant differences only in average scores of BD-Rel group (p?=?0.01). LIMITATIONS: Important attrition in BD-Rel group over time was detected, which precluded analysis at T3. CONCLUSIONS: BD patients show significant deficits in VM that remain stable over time, even after controlling sociodemographic and clinical variables. Unaffected relatives also show stable deficits in VM. Accordingly, the deficit in VM could be considered a potential endophenotype of BD, which in turn may be useful as a predictor of the evolution of the disease. Further studies are needed to confirm these findings.VB-M is supported by the national grant PI16/01770 (PROBILIFE Study), from the ISCIII. RTS was supported in part by grant PROMETEOII/2015/021 from Generalitat Valenciana and the national grands PI14/00894, PI17/00719 and PIE14/00031 from ISCIII-FEDER. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Grip Strength, Neurocognition, and Social Functioning in People WithType-2 Diabetes Mellitus, Major Depressive Disorder, Bipolar Disorder, and Schizophrenia

[Background] Frailty is a common syndrome among older adults and patients with several comorbidities. Grip strength (GS) is a representative parameter of frailty because it is a valid indicator of current and long-term physical conditions in the general population and patients with severe mental illnesses (SMIs). Physical and cognitive capacities of people with SMIs are usually impaired; however, their relationship with frailty or social functioning have not been studied to date. The current study aimed to determine if GS is a valid predictor of changes in cognitive performance and social functioning in patients with type-2 diabetes mellitus and SMIs.[Methods] Assessments of social functioning, cognitive performance, and GS (measured with an electronic dynamometer) were conducted in 30 outpatients with type 2 diabetes mellitus, 35 with major depressive disorder, 42 with bipolar disorder, 30 with schizophrenia, and 28 healthy controls, twice during 1-year, follow-up period. Descriptive analyses were conducted using a one-way analysis of variance for continuous variables and the chi-squared test for categorical variables. Differences between groups for the motor, cognitive, and social variables at T1 and T2 were assessed using a one-way analysis of covariance, with sex and age as co-variates (p < 0.01). To test the predictive capacity of GS at baseline to explain the variance in cognitive performance and social functioning at T2, a linear regression analysis was performed (p < 0.05).[Results] Predictive relationships were found among GS when implicated with clinical, cognitive, and social variables. These relationships explained changes in cognitive performance after one year of follow-up; the variability percentage was 67.7%, in patients with type-2 diabetes mellitus and 89.1% in patients with schizophrenia. Baseline GS along with other variables, also predicted changes in social functioning in major depressive disorder, bipolar disorder, and schizophrenia, with variability percentages of 67.3, 36, and 59%, respectively.[Conclusion] GS combined with other variables significantly predicted changes in cognitive performance and social functioning in people with SMIs or type-2 diabetes mellitus. Interventions aimed to improve the overall physical conditions of patients who have poor GS could be a therapeutic option that confers positive effects on cognitive performance and social functioning.RT-S was supported in part by grant PROMETEOII/2015/021 from Generalitat Valenciana and the national grants PI14/00894 and PIE14/00031 from ISCIII-FEDER. RA-A is funded by a Miguel Servet contract from the Carlos III Health Institute (CP18/00003)