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.
OBJECTIVE: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. METHOD: Our data are the largest existing sample of direct interview-based clinical data from lithium-treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR-as defined by the previously validated Alda scale-against 180 clinical predictors. RESULTS: Under appropriate cross-validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78-0.82) and a Cohen kappa of 0.46 (0.4-0.51). The model demonstrated a particularly low false-positive rate (specificity 0.91 [0.88-0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. CONCLUSION: Clinical data can inform out-of-sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between-site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between- and within-site heterogeneity, and further testing such models on new external datasets.
- MeSH
- antimanika terapeutické užití MeSH
- bipolární porucha farmakoterapie epidemiologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- plocha pod křivkou MeSH
- poruchy iniciace a udržování spánku epidemiologie MeSH
- pravidla klinického rozhodování * MeSH
- progrese nemoci MeSH
- rizikové faktory MeSH
- ROC křivka MeSH
- sloučeniny lithia terapeutické užití MeSH
- strojové učení * MeSH
- věk při počátku nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In the early stage of drug development the solubility of drug candidate is the most crucial physicochemical parameter to be defined for the selection of lead compound. Conventional shake flask method of solubility determination has now been replaced with more precise measurements like ultraviolet absorption, nephelometry, nuclear magnetic resonance and potentiometry. The development of a simple, rapid, sensitive and precise spectrophotometric method for the routine quantitative determination of samples will definitely reduce unnecessary tedious sample preparations and the cost of materials and labour. This article accounts for the measurement of solubility limit of few selected drugs by spectrophotometry using dilution technique. This has been done to optimize the method for rapid and convenient determination of drug solubility limit. Concentration of saturated solution of drug was determined from the absorbance versus concentration plots of various diluted solutions of drug as per Beer-Lambert law and was reported as drug solubility limit.
Recent findings indicate that conscious attention is related to large-scale information integration of various brain regions, including both hemispheres, that enables integration of parallel distributed modalities of processed information. There is also evidence that the level of information transference related to integration or splitting among brain regions, and between hemispheres, establishes a certain level of efficiency of the information processing. The level of information transference also may have modulatory influences on attentional capacity that are closely linked to the emotional arousal and autonomic response related to a stimulus. These findings suggest a hypothesis that changes in conscious attention, specifically during meditation could be reflected in the autonomic activity as the left-right information transference calculated from bilateral electrodermal activity (EDA). With the aim to compare conscious attention during meditation with other attentional states (resting state, Stroop task, and memory task), we performed bilateral EDA measurement in 7 healthy persons during resting state, Stroop task, neurofeedback memory test, and meditation. The results indicate that the information transference (ie, transinformation) is able to distinguish those attentional states, and that the highest level of the transinformation has been found during attentional processing related to meditation, indicating higher level of connectivity between left and right sides. Calculations other than pointwise transinformation (PTI) performed on EDA records, such as mean skin conductance level or laterality index, were not able to distinguish attentional states. The results suggest that PTI may present an interesting method useful for the assessment of information flow, related to neural functioning, that in the case of meditation may reflect typical integrative changes in the autonomic nervous system related to brain functions and focused attentional processing.
- MeSH
- dospělí MeSH
- elektroencefalografie * MeSH
- funkční lateralita fyziologie MeSH
- lidé MeSH
- mapování mozku MeSH
- meditace * MeSH
- modely neurologické MeSH
- neurofeedback MeSH
- paměť fyziologie MeSH
- pozornost fyziologie MeSH
- Stroopův test MeSH
- vědomí fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Caring for demented people has been associated with negative effect on caregiver health. One or more severe stress factors can precipitate brief reactive psychosis. METHODS: A 59-year-old Caucasian married woman with no prior psychosis has been caring for her severely demented husband for more than 3 years. She was treated for anxiety disorder and reaction to severe stress in our clinic for 1 year. RESULTS: Five days after husband's nursing home placement our patient developed the abnormal thought, that someone might tell her neighbours of her laziness and failures. She believed that she was under constant surveillance. These ideas grew rapidly into delusions and hallucinations. She was diagnosed as having transient psychosis with associated acute stress and was treated with risperidone. The psychosis lasted for two months. CONCLUSION: Careful differential diagnosis is necessary in the cases of transient psychosis. Psychotic symptoms in overloaded individuals may be more common than was previously thought.
- MeSH
- Alzheimerova nemoc ošetřování MeSH
- antipsychotika terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- manželé psychologie MeSH
- osoby pečující o pacienty psychologie MeSH
- psychický stres komplikace psychologie MeSH
- psychotické poruchy etiologie psychologie terapie MeSH
- risperidon terapeutické užití MeSH
- stupeň závažnosti nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Psychiatric genetics is a popular and much-discussed topic. Many candidate genes have been investigated in relation to psychiatric disorders and many connections have been found. The utilization of these investigations is currently at a theoretical level. Nevertheless, these findings of candidate genes will be important for further research and subsequent clinical use, for example in pharmacogenetics). Due to the rapidly growing number of empirical studies that provide profound analysis of different genes and their variants in different psychiatrical symptomatology, the field is highly divided, and providing a succinct overview is challenging. This article attempts to provide an up-to-date review of the most important and most discussed genes (mainly transporter and receptor genes) contributing to the etiology of psychiatric disorders.
- MeSH
- behaviorální genetika trendy MeSH
- duševní poruchy genetika MeSH
- genetická predispozice k nemoci MeSH
- lidé MeSH
- mozek - chemie genetika MeSH
- psychiatrie trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
