Predicting lithium response (LiR) in bipolar disorder (BD) may inform treatment planning, but phenotypic heterogeneity complicates discovery of genomic markers. We hypothesized that patients with "exemplary phenotypes"-those whose clinical features are reliably associated with LiR and non-response (LiNR)-are more genetically separable than those with less exemplary phenotypes. Using clinical data collected from people with BD (n = 1266 across 7 centers; 34.7% responders), we computed a "clinical exemplar score," which measures the degree to which a subject's clinical phenotype is reliably predictive of LiR/LiNR. For patients whose genotypes were available (n = 321), we evaluated whether a subgroup of responders/non-responders with the top 25% of clinical exemplar scores (the "best clinical exemplars") were more accurately classified based on genetic data, compared to a subgroup with the lowest 25% of clinical exemplar scores (the "poor clinical exemplars"). On average, the best clinical exemplars of LiR had a later illness onset, completely episodic clinical course, absence of rapid cycling and psychosis, and few psychiatric comorbidities. The best clinical exemplars of LiR and LiNR were genetically separable with an area under the receiver operating characteristic curve of 0.88 (IQR [0.83, 0.98]), compared to 0.66 [0.61, 0.80] (p = 0.0032) among poor clinical exemplars. Variants in the Alzheimer's amyloid-secretase pathway, along with G-protein-coupled receptor, muscarinic acetylcholine, and histamine H1R signaling pathways were informative predictors. This study must be replicated on larger samples and extended to predict response to other mood stabilizers.
Článek popisuje kazuistiku mladé ženy s tachykardií s úzkými komplexy, u které byla provedena nefarmakologická kardioverze pomocí vagového manévru. Studie potvrzují, že vagové manévry jsou přínosným postupem první volby ke zvrácení supraventrikulárních tachyarytmií nejen v přednemocniční péči. Léčba modifikovaným Valsalvovým manévrem (VM) je pro ukončení (paroxysmální) supraventrikulární tachykardie signifikantně účinnější než standardní VM a je prakticky nejúčinnější z vagových manévrů. Při standartním VM se jedná o usilovný výdech při zavřené hlasové štěrbině. U modifikovaného VM se provádí usilovné exspirium nejčastěji proti odporu pístu injekční stříkačky zajišťující určitou standardizaci úsilí. V popsaném případu byl modifikovaný manévr využit u mladé ženy se supraventrikulární tachykardii (180 pulsů/min) s výsledným obnovením sinusového rytmu.
The article describes the case of a young woman with narrow complex tachycardia, in whom non-pharmacological cardioversion – the Valsalva manoeuvre (VM) – was used. Studies confirm that vagal manoeuvres are a generally recommended first-choice approach to reversing supraventricular tachyarrhythmia not only in pre-hospital care and that, for paroxysmal supraventricular tachycardia, treatment with modified VM is significantly more effective than the stan-dard VM and is virtually the most effective of all vagal manoeuvres. In the standard VM the patient exhales forcefully against a closed glottis. In the modified VM, the patient exhales against resistance (most commonly a syringe plunger). In our case, the normalisation of the rhythm in supraventricular tachycardia (180 pulses/min) was used successfully in a young woman, who recovered sinus rhythm.
- MeSH
- dospělí MeSH
- lidé MeSH
- tachykardie * terapie MeSH
- urgentní zdravotnické služby metody MeSH
- Valsalvův manévr MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- dospělí MeSH
- lidé MeSH
- supraventrikulární tachykardie * diagnóza terapie MeSH
- urgentní zdravotnické služby MeSH
- Valsalvův manévr * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: ADHD and alcoholism are psychiatric diseases with pathophysiology related to dopamine system. DAT1 belongs to the SLC6 family of transporters and is involved in the regulation of extracellular dopamine levels. A 40 bp variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1/SLC6A3 gene was previously reported to be associated with various phenotypes involving disturbed regulation of dopaminergic neurotransmission. METHODS: A total of 1312 subjects were included and genotyped for 40 bp VNTR polymorphism of DAT1/SLC6A3 gene in this study (441 alcoholics, 400 non-alcoholic controls, 218 ADHD children and 253 non ADHD children). Using miRBase software, we have performed a computer analysis of VNTR part of DAT1 gene for presence of miRNA binding sites. RESULTS: We have found significant relationships between ADHD and the 40 bp VNTR polymorphisms of DAT1/SLC6A3 gene (P < 0.01). The 9/9 genotype appeared to reduce the risk of ADHD about 0.4-fold (p < 0.04). We also noted an occurrence of rare genotypes in ADHD (frequency different from controls at p < 0.01). No association between alcoholism and genotype frequencies of 40 bp VNTR polymorphism of DAT1/SLC6A3 gene has been detected. CONCLUSIONS: We have found an association between 40 bp VNTR polymorphism of DAT1/SLC6A3 gene and ADHD in the Czech population; in a broad agreement with studies in other population samples. Furthermore, we detected rare genotypes 8/10, 7/10 and 10/11 present in ADHD boys only and identified miRNAs that should be looked at as potential novel targets in the research on ADHD.
- MeSH
- 3' nepřekládaná oblast genetika MeSH
- alkoholismus epidemiologie genetika MeSH
- dítě MeSH
- dospělí MeSH
- epigeneze genetická MeSH
- genotyp MeSH
- hyperkinetická porucha epidemiologie genetika MeSH
- impulzivní chování MeSH
- lidé středního věku MeSH
- lidé MeSH
- minisatelitní repetice genetika MeSH
- mladiství MeSH
- neuropsychologické testy MeSH
- počítačová simulace MeSH
- proteiny přenášející dopamin přes plazmatickou membránu genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- psychiatrie MeSH
- Publikační typ
- biografie MeSH
Brain-derived neurotrophic factor (BDNF) is a protein encoded, in humans, by BDNF gene on chromosome 11. BDNF protects adult neurons and promotes growth and differentiation during ontogenetic development but the nature and magnitude of its effects could be influenced by functional polymorphisms. The BDNF polymorphism Val66Met (rs6265) has been studied in the context of etiology of mental diseases including alcoholism. Alcoholism - a complex disorder known to be linked to several genes - has multiple manifestations, including sensory deficits such as those affecting vision. In the present study we examined a relationship between the Val66Met polymorphism, alcohol dependence and colour vision deficiency (CVD) in 167 alcohol-dependent men and 289 control male subjects. Statistical analysis revealed that almost half (about 48%) of the alcohol dependent men had a CVD. In addition we found that CVD was significantly associated (P=0.005) with the Val66Met polymorphism. The A allele containing 66Met promotes BDNF expression and this may protect humans against CVD induced by long-term excessive alcohol intake. The present findings indicate that alcohol-induced CVD does not depend solely on excessive alcohol consumption but is significantly influenced by genetic predisposition in the form of a specific BDNF polymorphism.
- MeSH
- alely MeSH
- alkoholismus komplikace genetika MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozkový neurotrofický faktor genetika MeSH
- poruchy barevného vidění komplikace genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- psychiatrie MeSH
- sexuologie MeSH
- Publikační typ
- biografie MeSH
- O autorovi
- Raboch, Jiří, 1951- Autorita
