Exploring the genetics of lithium response in bipolar disorders.

BACKGROUND: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. RESULTS: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. CONCLUSIONS: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Phenotypic clustering of bipolar disorder supports stratification by lithium responsiveness over diagnostic subtypes.

INTRODUCTION: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. METHODS: We included adult patients with BD-I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. RESULTS: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). CONCLUSIONS: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples.

Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Factores determinantes de la satisfacción del paciente en tratamiento renal sustitutivo / Factors determining patient satisfaction in kidney replacement treatment

El interés de los profesionales de enfermería se ha centrado siempre en prestar cuidados de calidad, sería errónea esta concepción sin tener en cuenta la opinión de los pacientes. Los objetivos del estudio son: 1. Determinar el grado de satisfacción y capacidad funcional de los pacientes en diálisis, valorando si existe diferencia según el tratamiento sustitutivo que realicen. 2. Identificar los aspectos del proceso asistencial que generan mayor satisfacción. Estudio descriptivo transversal a todos los pacientes de la unidad en marzo-abril 2005. Se administró el cuestionario SERVQHOS modificado. Se utilizó el índice de Karnosky para medir el grado de autonomía. Para el análisis de datos se utilizó el programa SPSS obteniendo las frecuencias y medias de puntación en cada ítem. Se utilizó el Alpha de Cronbach para el análisis de fiabilidad. Mediante análisis factorial se identificaron los atributos determinantes dela satisfacción. Se analizaron 77 cuestionarios. Tasa de respuesta del 95%. Las características demográficas son las siguientes: de los pacientes encuestados HD/DP55/22, el 65/85 % de los pacientes eran hombres. Edad media 68,8±14 / 54,6±12,4 años. El alpha de Cronbach fue de 0,95/0,90. El grado de satisfacción de los pacientes de HD es 3,28, en los de DP 3,68. No se ha encontrado correlación entre la capacidad funcional y la satisfacción de los pacientes en diálisis. Las variables que determinan el grado de satisfacción de los pacientes en HD son aquellas relacionadas con la atención que reciben. En DP están relacionadas con la responsabilidad de asumirla técnica (AU)

The interest of nursing professionals has always been focused on providing quality care. This focus would be incorrect if it failed to take into account patients’ opinions. The objectives of the study are: 1. To determine the degree of satisfaction and functional capacity of patients on dialysis, evaluating whether there is a difference depending on there placement treatment they receive, and 2. To identify the aspects of the care process that generate greatest satisfaction. Transversal descriptive study of all the patients in the unit in March-April 2005. The modified SERVQHOS questionnaire was administered. The Karnofsky index was used to measure the degree of autonomy. To analyse the data the SPSS program was used, obtaining score frequencies and averages on each item. Cronbach’s Alpha was used to analyse reliability. The attributes that determined satisfaction were identified using factorial analysis. A total of 77 questionnaires were analysed. Response rate of 95%. The demographic characteristics are as follows: of the patients surveyed HD/PD 55/22, 65/85 % of the patients were men. Average age 68.8±14 / 54.6±12.4 years. Cronbach’s Alpha was 0.95/0.90. The degree of satisfaction is 3.28 in HD patients, and 3.68 in PD patients. No correlation was found between functional capacity and the satisfaction of patients on dialysis. The variables that determine the degree of satisfaction of patients on HD are those related to the attention they receive. In DP they are related to the responsibility of undertaking the technique (AU)