Prediction of lithium response using genomic data

Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using the largest existing genomic dataset in the lithium response literature (n = 2210 across 14 international sites; 29% responders), we evaluated the degree to which lithium response could be predicted based on 47,465 genotyped single nucleotide polymorphisms using a supervised ML approach. Under appropriate cross-validation procedures, lithium response could be predicted to above-chance levels in two constituent sites (Halifax, Cohen's kappa 0.15, 95% confidence interval, CI [0.07, 0.24]; and Würzburg, kappa 0.2 [0.1, 0.3]). Variants with shared importance in these models showed over-representation of postsynaptic membrane related genes. Lithium response was not predictable in the pooled dataset (kappa 0.02 [- 0.01, 0.04]), although non-trivial performance was achieved within a restricted dataset including only those patients followed prospectively (kappa 0.09 [0.04, 0.14]). Genomic classification of lithium response remains a promising but difficult task. Classification performance could potentially be improved by further harmonization of data collection procedures

Internet use by older adults with bipolar disorder: international survey results

Background: The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use by older adults with bipolar disorder as part of a larger survey project about information seeking. Methods: A paper-based survey about information seeking by patients with bipolar disorder was developed and translated into 12 languages. The survey was anonymous and completed between March 2014 and January 2016 by 1222 patients in 17 countries. All patients were diagnosed by a psychiatrist. General estimating equations were used to account for correlated data. Results: Overall, 47% of older adults (age 60 years or older) used the Internet versus 87% of younger adults (less than 60 years). More education and having symptoms that interfered with regular activities increased the odds of using the Internet, while being age 60 years or older decreased the odds. Data from 187 older adults and 1021 younger adults were included in the analysis excluding missing values. Conclusions: Older adults with bipolar disorder use the Internet much less frequently than younger adults. Many older adults do not use the Internet, and technology tools are suitable for some but not all older adults. As more health services are only available online, and more digital tools are developed, there is concern about growing health disparities based on age. Mental health experts should participate in determining the appropriate role for digital tools for older adults with bipolar disorder.We acknowledge support by the Open Access Publication Funds of the SLUB/TU Dresden (Grant No. IN-1502335)

Internet Use by Older Adults with Bipolar Disorder: International Survey Results

Background: The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use by older adults with bipolar disorder as part of a larger survey project about information seeking. Methods: A paper-based survey about information seeking by patients with bipolar disorder was developed and translated into 12 languages. The survey was anonymous and completed between March 2014 and January 2016 by 1222 patients in 17 countries. All patients were diagnosed by a psychiatrist. General estimating equations were used to account for correlated data. Results: Overall, 47% of older adults (age 60 years or older) used the Internet versus 87% of younger adults (less than 60 years). More education and having symptoms that interfered with regular activities increased the odds of using the Internet, while being age 60 years or older decreased the odds. Data from 187 older adults and 1021 younger adults were included in the analysis excluding missing values. Conclusions: Older adults with bipolar disorder use the Internet much less frequently than younger adults. Many older adults do not use the Internet, and technology tools are suitable for some but not all older adults. As more health services are only available online, and more digital tools are developed, there is concern about growing health disparities based on age. Mental health experts should participate in determining the appropriate role for digital tools for older adults with bipolar disorder

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed

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

Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters

Background: Concerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear. Methods: Accordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8–48 (mean 18) years and aged 20–89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea–nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling. Results: Overall, 29.5% of subjects experienced at least one low value of eGFR ( 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years. Limitations Control data for age-matched subjects not exposed to lithium were lacking. Conclusions: Long-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age

Association between solar insolation and a history of suicide attempts in bipolar I disorder

In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p <0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.Peer reviewe

Internet use by older adults with bipolar disorder: international survey results

Background: The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use by older adults with bipolar disorder as part of a larger survey project about information seeking. Methods: A paper-based survey about information seeking by patients with bipolar disorder was developed and translated into 12 languages. The survey was anonymous and completed between March 2014 and January 2016 by 1222 patients in 17 countries. All patients were diagnosed by a psychiatrist. General estimating equations were used to account for correlated data. Results: Overall, 47% of older adults (age 60 years or older) used the Internet versus 87% of younger adults (less than 60 years). More education and having symptoms that interfered with regular activities increased the odds of using the Internet, while being age 60 years or older decreased the odds. Data from 187 older adults and 1021 younger adults were included in the analysis excluding missing values. Conclusions: Older adults with bipolar disorder use the Internet much less frequently than younger adults. Many older adults do not use the Internet, and technology tools are suitable for some but not all older adults. As more health services are only available online, and more digital tools are developed, there is concern about growing health disparities based on age. Mental health experts should participate in determining the appropriate role for digital tools for older adults with bipolar disorder

Geochronology in South Australia

© 2008 Informa plcGeochronology studies in South Australia were developed in three Adelaide institutions. (i) University of Adelaide: (ia) Department of Geology and Mineralogy, where four single chemical measurements were reported in 1923-1955 and 14 lead-alpha measurements in 1961; MSID Rb-Sr work began in 1972 followed by zircon U-Pb about 1980 and Sm-Nd later; (ib) luminescence equipment was developed in the Department of Physics and is used to date recent sediments. (ii) Flinders University, where alpha spectrometry disequilibrium dating of recent sediments was active during 1972-2000; and (iii) AMDEL, which supplied a variable commercial service of K-Ar, Rb-Sr and zircon dating during period 1972-1999.J. A. Cooper, J. D. Foden, J. R. Prescott, H. H. Veeh & A. W. Web

Mixing and evaporation processes in an inverse estuary inferred from d2H and d18O

THE BOULEVARD, LANGFORD LANE,KIDLINGTON, OXFORD, ENGLAND, OX5 1G