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.
- MeSH
- bipolární porucha * farmakoterapie genetika MeSH
- celogenomová asociační studie MeSH
- fokální adheze MeSH
- fosfatidylinositol-3-kinasy genetika MeSH
- lidé MeSH
- lithium * farmakologie terapeutické užití MeSH
- multiomika MeSH
- protoonkogenní proteiny c-akt genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylinositol-3-kinasy MeSH
- lithium * MeSH
- protoonkogenní proteiny c-akt MeSH
Current literature reveals no increased risk for adverse non-hereditary health outcomes in the offspring of childhood cancer survivors (CCS), yet survivors reported concerns regarding their offspring's health. To investigate how the fear of cancer development in offspring influences parental behavior related to health and prevention, survey reports from 256 European adult CCS and 256 age- and sex-matched siblings who participated in a multicenter study on offspring health were analyzed in the present study. Analyses of covariance and chi-square tests were conducted to test for differences between CCS and siblings in outcome variables (all related to healthy parenting behavior). CCS reported higher fear levels (p = 0.044, Partial η2 = 0.01) and less alcohol consumption (p = 0.011, Phi = 0.12) and smoking (p = 0.022, Phi = 0.11) during pregnancy than siblings. In survivor families, children were breastfed less often (p < 0.001, Phi = 0.18). Partial correlation analyses showed that CCS' fear levels decreased with increasing age (r = -0.16, p = 0.014), time since oncological therapy (r = -0.19, p = 0.003), and number of children (r = -0.21, p = 0.001). Overall, due to their own experiences with cancer, many CCS harbor misperceptions regarding the health outcomes of their offspring. Although the fear decreases with increasing distance from the active disease, any fear should be taken seriously, even if unfounded, and combated through targeted educational measures.
- Klíčová slova
- childhood cancer, fear, health-related behavior, offspring health, survivor,
- Publikační typ
- časopisecké články MeSH
Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor.
- Klíčová slova
- Bipolar disorder, COVID-19, Infectious diseases, Systematic review, Vaccination,
- MeSH
- bipolární porucha * epidemiologie MeSH
- COVID-19 * MeSH
- infekční nemoci MeSH
- kontrola infekčních nemocí MeSH
- lidé MeSH
- pandemie MeSH
- SARS-CoV-2 MeSH
- vakcíny * aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
- Názvy látek
- vakcíny * MeSH
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
- MeSH
- bipolární porucha genetika MeSH
- celogenomová asociační studie * MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- genom lidský MeSH
- hlavní histokompatibilní komplex genetika MeSH
- lidé MeSH
- lidské chromozomy genetika MeSH
- lokus kvantitativního znaku genetika MeSH
- multifaktoriální dědičnost genetika MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- Research Support, N.I.H., Extramural MeSH
This narrative review summarizes and discusses the implications of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and the upcoming International Classification of Diseases (ICD)-11 classification systems on the prevalence of bipolar disorder and on the validity of the DSM-5 diagnosis of bipolar disorder according to the Robin and Guze criteria of diagnostic validity. Here we review and discuss current data on the prevalence of bipolar disorder diagnosed according to DSM-5 versus DSM-IV, and data on characteristics of bipolar disorder in the two diagnostic systems in relation to extended Robin and Guze criteria: 1) clinical presentation, 2) associations with para-clinical data such as brain imaging and blood-based biomarkers, 3) delimitation from other disorders, 4) associations with family history / genetics, 5) prognosis and long-term follow-up, and 6) treatment effects. The review highlights that few studies have investigated consequences for the prevalence of the diagnosis of bipolar disorder and for the validity of the diagnosis. Findings from these studies suggest a substantial decrease in the point prevalence of a diagnosis of bipolar with DSM-5 compared with DSM-IV, ranging from 30-50%, but a smaller decrease in the prevalence during lifetime, corresponding to a 6% reduction. It is concluded that it is likely that the use of DSM-5 and ICD-11 will result in diagnostic delay and delayed early intervention in bipolar disorder. Finally, we recommend areas for future research.
- Klíčová slova
- Bipolar disorder;DSM-5;ICD-11;Validity of diagnosis;Diagnostic delay;Delayed early intervention,
- MeSH
- bipolární porucha * diagnóza epidemiologie MeSH
- Diagnostický a statistický manuál mentálních poruch MeSH
- lidé MeSH
- mezinárodní klasifikace nemocí MeSH
- opožděná diagnóza MeSH
- prevalence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.
- MeSH
- bipolární porucha farmakoterapie genetika MeSH
- celogenomová asociační studie MeSH
- fenotyp MeSH
- genetická variace MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- receptory GDNF genetika MeSH
- sloučeniny lithia terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Názvy látek
- GFRA2 protein, human MeSH Prohlížeč
- receptory GDNF MeSH
- sloučeniny lithia MeSH
