Intentos de autolisis en pacientes bipolares I y II

El trastorno bipolar II, que se caracteriza por episodios depresivos graves y períodos de tiipomanía moderados que se suceden de forma espontánea, parece ser algo más que una forma leve de psicosis maníaco-depresiva. Los estudios anteriores indican que es una categoría de diagnóstico válida, diferente del transtorno bipolar I en aspectos genéticos, biológicos, clínicos y farmacológicos (Cassano et al., 1992; Menchón et al., 1993). Por estas razones, se ha distinguido como una entidad separada en el DSM-IV. No obstante, entre los diversos estudios que tratan aspectos importantes del trastorno bipolar II -como la edad de aparición, la frecuencia de los episodios y el comportamiento suicida- aparecen algunas diferencias. Ei riesgo de suicidio inherente a ambos subtipos es un tema especialmente controvertido (Lester, 1993). Algunos estudios atribuyen índices de intentos de suicidio al trastorno bipolar II. (Dunner et al., 1976; Stallone et al., 1980), pero otros no (Cassano et al., 1992; Coryell et al., 1987; Perugi et al., 1988). Además en diversos estudios sobre suicidio consumado se ha observado que los pacientes con trastorno bipolar II están sobrerrepresentados en el grupo de víctimas suicidas consecutivas (Rihmer et al., 1995). El objetivo de este estudio ha sido el de comprobar las características clínicas de los pacientes bipolares en comparación con el tipo bipolar I clásico (especialmente en relación a la conducta suicida)

Emotional intelligence: A comparison between patients after first episode mania and those suffering from chronic bipolar disorder type i

Deficits in emotional intelligence (EI) were detected in patients with Bipolar Disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. Methods: The Emotional Intelligence Quotient (EIQ) was calculated with the MayerSalovey-Caruso Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. Results: 184 subjects were included (FEM n=48, euthymic chronic BD type I n=75, HC n=61). BD patients performed significantly worse than HC on the EIQ (Mean Difference MD=10.09, Standard Error SE=3.14, p=0.004) and on the Understanding emotions branch (MD=7.46, SE=2.53, p=0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (β=-0.293, p=0.034) and verbal memory performance (β=0.374, p=0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. Conclusions: Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness

Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Bipolar afective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratifcation are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identifed genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × ­10−3; FDR< 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common infammatory/autoimmune processes, our fndings strongly suggest that HLA-mediated low infammatory background may contribute to the efcient response to Li in BD patients, while an infammatory status overriding Li anti-infammatory properties would favor a weak response

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD

Estudio de los cambios regionales en el flujo sanguíneo cerebral mediante tomografía por emisión de fotoón simple y su correlación neuropsicológica en el trastorno bipolar

[spa] Fundamentos: Para algunos trastornos psiquiátricos se ha podido establecer que existe relación entre las disfunciones cognitivas y las alteraciones en el FSCr. Para el trastorno bipolar (TB), distintos trabajos previos han sugerido que los pacientes con este trastorno presentan disfunciones cognitivas. Asimismo, en distintos estudios han sido halladas alteraciones en la distribución del flujo sanguíneo cerebral regional (FSCr) de estos pacientes. No obstante, no existe ningún trabajo publicado en que se haya estudiado la relación entre ambos tipos de marcadores en pacientes con TB. Objetivos: Determinar las posibles alteraciones en el rendimiento neuropsicológico y en el FSCr de los pacientes con TB, y establecer la relación entre ambos tipos de marcadores y con la psicopatología propia del trastorno. Pacientes y métodos: Se incluyeron 43 pacientes con TB (RDC) que se clasificaron según su fase en la enfermedad a partir de la puntuación obtenida en las escalas YMRS y HDRS en fase maníaca (n=7), hipomaníaca (n=8), depresiva (n=12) o eutímica (n=3), y 6 sujetos control. Se evaluó además el estado clínico mediante las escalas PANSS y GAF, la función cognitiva mediante los tests neuropsicológicos WAIS, WCST, Stroop, TMT, CVLT, WMS y FAS/COWAT, y se obtuvieron imágenes SPECT administrando el contraste radiológico 99mTc-HMPAO. Resultados: Las principales correlaciones halladas fueron entre: función ejecutiva (WCST) y FSCr de estriado, frontal, temporal, cerebelo, parietal y cingulado; función mnésica (WMS, WAIS-dígitos) y FSCr de estriado, frontal, temporal y parietal; tareas atencionales (Stroop) y FSCr de estriado, temporal media y parietal; aprendizaje verbal (CVLT) y FSCr de frontal, temporal posterior, cingulado y occipital; alteraciones psicomotoras (TMT) y FSCr de temporal anterior; empeoramiento intelectual (WAIS-Vocabulario) y FSCr de cerebelo y parietal. Conclusiones: Los resultados del estudio corroboran las hipótesis actuales que señalan la existencia de anomalías funcionales en estructuras fronto-subcorticales, cerebelo y sistema límbico en el TB

Analysis of the influence of microRNAs in lithium response in bipolar disorder

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted

Analysis of the influence of microRNAs in lithium response in bipolar disorder

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted

Intentos de autolisis en pacientes bipolares I y II

El trastorno bipolar II, que se caracteriza por episodios depresivos graves y períodos de tiipomanía moderados que se suceden de forma espontánea, parece ser algo más que una forma leve de psicosis maníaco-depresiva. Los estudios anteriores indican que es una categoría de diagnóstico válida, diferente del transtorno bipolar I en aspectos genéticos, biológicos, clínicos y farmacológicos (Cassano et al., 1992; Menchón et al., 1993). Por estas razones, se ha distinguido como una entidad separada en el DSM-IV. No obstante, entre los diversos estudios que tratan aspectos importantes del trastorno bipolar II -como la edad de aparición, la frecuencia de los episodios y el comportamiento suicida- aparecen algunas diferencias. Ei riesgo de suicidio inherente a ambos subtipos es un tema especialmente controvertido (Lester, 1993). Algunos estudios atribuyen índices de intentos de suicidio al trastorno bipolar II. (Dunner et al., 1976; Stallone et al., 1980), pero otros no (Cassano et al., 1992; Coryell et al., 1987; Perugi et al., 1988). Además en diversos estudios sobre suicidio consumado se ha observado que los pacientes con trastorno bipolar II están sobrerrepresentados en el grupo de víctimas suicidas consecutivas (Rihmer et al., 1995). El objetivo de este estudio ha sido el de comprobar las características clínicas de los pacientes bipolares en comparación con el tipo bipolar I clásico (especialmente en relación a la conducta suicida)

Intentos de autolisis en pacientes bipolares I y II

El trastorno bipolar II, que se caracteriza por episodios depresivos graves y períodos de tiipomanía moderados que se suceden de forma espontánea, parece ser algo más que una forma leve de psicosis maníaco-depresiva. Los estudios anteriores indican que es una categoría de diagnóstico válida, diferente del transtorno bipolar I en aspectos genéticos, biológicos, clínicos y farmacológicos (Cassano et al., 1992; Menchón et al., 1993). Por estas razones, se ha distinguido como una entidad separada en el DSM-IV. No obstante, entre los diversos estudios que tratan aspectos importantes del trastorno bipolar II -como la edad de aparición, la frecuencia de los episodios y el comportamiento suicida- aparecen algunas diferencias. Ei riesgo de suicidio inherente a ambos subtipos es un tema especialmente controvertido (Lester, 1993). Algunos estudios atribuyen índices de intentos de suicidio al trastorno bipolar II. (Dunner et al., 1976; Stallone et al., 1980), pero otros no (Cassano et al., 1992; Coryell et al., 1987; Perugi et al., 1988). Además en diversos estudios sobre suicidio consumado se ha observado que los pacientes con trastorno bipolar II están sobrerrepresentados en el grupo de víctimas suicidas consecutivas (Rihmer et al., 1995). El objetivo de este estudio ha sido el de comprobar las características clínicas de los pacientes bipolares en comparación con el tipo bipolar I clásico (especialmente en relación a la conducta suicida)