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

Cannabis use in male and female first episode of non-affective psychosis patients: long-term clinical, neuropsychological and functional differences

BACKGROUND: Numerous studies show the existence of a high prevalence of cannabis use among patients with psychosis. However, the differences between men and women who debut with a first episode of psychosis (FEP) regarding cannabis use have not been largely explored. The aim of this study was to identify the specific sex factors and differences in clinical evolution associated with cannabis use. METHOD: Sociodemographic characteristics at baseline were considered in our sample of FEP patients to find differences depending on sex and the use of cannabis. Clinical, functional and neurocognitive variables at baseline, 1-year, and 3-years follow-up were also explored. RESULTS: A total of 549 patients, of whom 43% (N = 236) were cannabis users, 79% (N = 186) male and 21% (N = 50) female, were included in the study. There was a clear relationship between being male and being a user of cannabis (OR = 5.6). Cannabis users were younger at illness onset. Longitudinal analysis showed that women significantly improved in all three dimensions of psychotic symptoms, both in the subgroup of cannabis users and in the non-users subgroup. Conversely, subgroups of men did not show improvement in the negative dimension. In cognitive function, only men presented a significant time by group interaction in processing speed, showing a greater improvement in the subgroup of cannabis users. CONCLUSION: Despite knowing that there is a relationship between cannabis use and psychosis, due to the high prevalence of cannabis use among male FEP patients, the results showed that there were very few differences in clinical and neurocognitive outcomes between men and women who used cannabis at the start of treatment compared to those who did not

Transdiagnostic neurocognitive deficits in patients with type 2 diabetes mellitus, major depressive disorder, bipolar disorder, and schizophrenia: a 1-year follow-up study

Background Neurocognition impairments are critical factors in patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), and also in those with somatic diseases such as type 2 diabetes mellitus (T2DM). Intriguingly, these severe mental illnesses are associated with an increased co-occurrence of diabetes (direct comorbidity). This study sought to investigate the neurocognition and social functioning across T2DM, MDD, BD, and SZ using a transdiagnostic and longitudinal approach. Methods A total of 165 participants, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HC), were assessed twice at a 1-year interval using a comprehensive, integrated test battery on neuropsychological and social functioning. Results Common neurocognitive impairments in somatic and psychiatric disorders were identified, including deficits in short-term memory and cognitive reserve (p < 0.01, η²p=0.08–0.31). Social functioning impairments were observed in almost all the disorders (p < 0.0001; η²p=0.29–0.49). Transdiagnostic deficits remained stable across the 1-year follow-up (p < 0.001; η²p=0.13–0.43) and could accurately differentiate individuals with somatic and psychiatric disorders (χ² = 48.0, p < 0.0001). Limitations The initial sample size was small, and high experimental mortality was observed after follow-up for one year. Conclusions This longitudinal study provides evidence of some possible overlap in neurocognition deficits across somatic and psychiatric diagnostic categories, such as T2DM, MDD, BD, and SZ, which have high comorbidity. This overlap may be a result of shared genetic and environmental etiological factors. The findings open promising avenues for research on transdiagnostic phenotypes of neurocognition in these disorders, in addition to their biological bases

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

Cannabis use in male and female first episode of non-affective psychosis patients: Long-term clinical, neuropsychological and functional differences

BACKGROUND: Numerous studies show the existence of a high prevalence of cannabis use among patients with psychosis. However, the differences between men and women who debut with a first episode of psychosis (FEP) regarding cannabis use have not been largely explored. The aim of this study was to identify the specific sex factors and differences in clinical evolution associated with cannabis use. METHOD: Sociodemographic characteristics at baseline were considered in our sample of FEP patients to find differences depending on sex and the use of cannabis. Clinical, functional and neurocognitive variables at baseline, 1-year, and 3-years follow-up were also explored. RESULTS: A total of 549 patients, of whom 43% (N = 236) were cannabis users, 79% (N = 186) male and 21% (N = 50) female, were included in the study. There was a clear relationship between being male and being a user of cannabis (OR = 5.6). Cannabis users were younger at illness onset. Longitudinal analysis showed that women significantly improved in all three dimensions of psychotic symptoms, both in the subgroup of cannabis users and in the non-users subgroup. Conversely, subgroups of men did not show improvement in the negative dimension. In cognitive function, only men presented a significant time by group interaction in processing speed, showing a greater improvement in the subgroup of cannabis users. CONCLUSION: Despite knowing that there is a relationship between cannabis use and psychosis, due to the high prevalence of cannabis use among male FEP patients, the results showed that there were very few differences in clinical and neurocognitive outcomes between men and women who used cannabis at the start of treatment compared to those who did not

Relevance of Sociodemographics and Clinical Tests in Single- and Dual-Task Conditions as Gait Speed Predictors of Parkinson&rsquo;s Disease

This cross-sectional study aimed to identify the patient characteristics and clinical test results that predict the functional gait speed of people with Parkinson&rsquo;s disease (PD). The impact of dual tasks on gait in Parkinson&rsquo;s disease (PD) reveals a lack of automaticity and increased cognitive demands. We explored which characteristics explained walking speed with and without dual-task interference and if they reflected the cognitive demands of the task. The preferred gait speed, stride length, and cadence were measured in individuals with PD through five conditions: single-task (ST) and visual, verbal, auditory, and motor dual-tasks (DTs). Sociodemographic and disease characteristics and the results from clinical tests such as the Dynamic Parkinson&rsquo;s Disease Gait Scale (DYPAGS), Frontal Assessment Battery (FAB), and Parkinson&rsquo;s Disease Questionnaire-39 (PDQ-39), among others, were also recorded. Two models of multiple regression analysis were used to explore the predictive value of outcomes concerning speed. In Model I, clinical results were included, and in Model II, spatiotemporal variables were added to the significant predictors of Model I. Forty PD patients (aged 66.72 (7.5) years) completed the assessments. All the models generated were significant (p &lt; 0.01). Models I and II accounted for 47% and 93% of the variance, respectively, in the single-task condition. A patient&rsquo;s gender, prescribed medication (drugs), academic level, and Hoehn and Yahr (H&amp;Y) stage, along with the FAB, DYPAGS, and PDQ-39 scores, were significant predictors of gait speed in Model I for the ST and DT conditions. In Model II, the H&amp;Y stage and prescribed medication (drugs), along with the FAB and DYPAGS scores, remained significant predictors. This research found that sociodemographics, the patient&rsquo;s stage disease, and their clinical test results contribute to their walking speed, highlighting the multifactorial nature of gait in demanding environments

Cannabis use in male and female first episode of non-affective psychosis patients: Long-term clinical, neuropsychological and functional differences

International audienceBackgroundNumerous studies show the existence of a high prevalence of cannabis use among patientswith psychosis. However, the differences between men and women who debut with a firstepisode of psychosis (FEP) regarding cannabis use have not been largely explored. Theaim of this study was to identify the specific sex factors and differences in clinical evolutionassociated with cannabis use.MethodSociodemographic characteristics at baseline were considered in our sample of FEPpatients to find differences depending on sex and the use of cannabis. Clinical, functionaland neurocognitive variables at baseline, 1-year, and 3-years follow-up were also explored.ResultsA total of 549 patients, of whom 43% (N = 236) were cannabis users, 79% (N = 186) maleand 21% (N = 50) female, were included in the study. There was a clear relationshipbetween being male and being a user of cannabis (OR = 5.6). Cannabis users wereyounger at illness onset. Longitudinal analysis showed that women significantly improved inall three dimensions of psychotic symptoms, both in the subgroup of cannabis users and inthe non-users subgroup. Conversely, subgroups of men did not show improvement in thenegative dimension. In cognitive function, only men presented a significant time by groupinteraction in processing speed, showing a greater improvement in the subgroup of cannabisusers

Cannabis use in male and female first episode of non-affective psychosis patients: long-term clinical, neuropsychological and functional differences

BACKGROUND: Numerous studies show the existence of a high prevalence of cannabis use among patients with psychosis. However, the differences between men and women who debut with a first episode of psychosis (FEP) regarding cannabis use have not been largely explored. The aim of this study was to identify the specific sex factors and differences in clinical evolution associated with cannabis use. METHOD: Sociodemographic characteristics at baseline were considered in our sample of FEP patients to find differences depending on sex and the use of cannabis. Clinical, functional and neurocognitive variables at baseline, 1-year, and 3-years follow-up were also explored. RESULTS: A total of 549 patients, of whom 43% (N = 236) were cannabis users, 79% (N = 186) male and 21% (N = 50) female, were included in the study. There was a clear relationship between being male and being a user of cannabis (OR = 5.6). Cannabis users were younger at illness onset. Longitudinal analysis showed that women significantly improved in all three dimensions of psychotic symptoms, both in the subgroup of cannabis users and in the non-users subgroup. Conversely, subgroups of men did not show improvement in the negative dimension. In cognitive function, only men presented a significant time by group interaction in processing speed, showing a greater improvement in the subgroup of cannabis users. CONCLUSION: Despite knowing that there is a relationship between cannabis use and psychosis, due to the high prevalence of cannabis use among male FEP patients, the results showed that there were very few differences in clinical and neurocognitive outcomes between men and women who used cannabis at the start of treatment compared to those who did not

Specific metabolic syndrome components predict cognition and social functioning in people with type 2 diabetes mellitus and severe mental disorders

Objective: Obesity and metabolic diseases such as metabolic syndrome (MetS) are more prevalent in people with type 2 diabetes mellitus (T2DM), major depres sive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). MetS com ponents might be associated with neurocognitive and functional impairments in these individuals. The predictive and discriminatory validity of MetS and its components regarding those outcomes were assessed from prospective and trans diagnostic perspectives. Methods: Metabolic syndrome components and neurocognitive and social func tioning were assessed in 165 subjects, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HCs). A posteriori, individuals were classified into two groups. The MetS group consisted of those who met at least three of the following criteria: abdominal obesity (AO), elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL), elevated blood pres sure (BP), and elevated fasting glucose (FPG); the remaining participants com prised the No-MetS group. Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed. Results: Cognitive impairment was significantly greater in the MetS group (n = 82) than in the No-MetS group (n = 83), with small effect sizes (p < 0.05; η²p = 0.02 – 0.03). In both groups, the most robust associations between MetS compo nents and neurocognitive and social functioning were observed with TG and FPG (p < 0.05). There was also evidence for a significant relationship between cogni tion and BP in the MetS group (p < 0.05). The combination of TG, FPG, elevated systolic BP and HDL best classified individuals with greater cognitive impairment (p < 0.001), and TG was the most accurate (p < 0.0001). Conclusions: Specific MetS components are significantly associated with cogni tive impairment across somatic and psychiatric disorders. Our findings provide further evidence on the summative effect of MetS components to predict cogni tion and social functioning and allow the identification of individuals with worse outcomes. Transdiagnostic, lifestyle-based therapeutic interventions targeted at that group hold the potential to improve health outcomes