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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Site-specific specimen preparation for atom probe tomography (APT) is a challenging task. Small features need to be located using a suitable imaging technique and captured within a volume of less than 0.01 μm3. Correlative microscopy has shown to be helpful for target preparation as well as to gain complementary information about the material. Current strategies developed in that direction can be highly time-consuming and not always ensure the correct site extraction in complex microstructures. In this work, we present a methodology to study grain boundaries and interfaces in martensitic steels by combining electron backscattered diffraction, transmission Kikuchi diffraction (TKD), and APT. Furthermore, we include the design of a sample holder that allows to perform TKD and scanning transmission electron microscopy on the specimen during preparation without breaking the vacuum of the scanning electron microscope/focused ion beam workstation. We show a case study where a prior austenite grain boundary is traced from the bulk material to the apex of the APT specimen. The presence of contamination due to the specimen exposure to the electron beam and the use of plasma cleaning to minimize it are discussed.
Somatic symptoms and anxiety symptoms are often disregarded in the detection of depression in primary care. The present investigation examined to what extent somatic and anxiety symptoms recorded with the Composite International Diagnostic Interview—Primary Health Care Version (CIDI—PHC) can improve the detection of depression as compared to the General Health Questionnaire—12-item version alone. Data from the World Health Organization study on Psychological Problems in General Health Care were used. The study sample consisted of primary care attenders from 15 centres from all over the world who underwent a psychiatric examination with the CIDI—PHC. Medically unexplained somatic symptoms (back pain, feelings of heaviness/lightness in parts of the body, periods of bodily weakness, seizures/convulsions, permanent tiredness, exhaustion after a minimum of effort) and—to a smaller extent—diverse anxiety symptoms (e.g. feelings of anxiousness/nervousness, feelings of tension, difficulties relaxing) significantly contributed to the detection of depression in a logistic regression analysis. The results confirm the observation that in primary care somatic symptoms play an important role in the manifestation of depressive disorders. The items investigated herein could prove beneficial for future depression screening instruments to improve the detection of depressive disorders in primary care.
After parasuicide there is a high risk of reattempts. However, it seems that patients who survived severe suicidal trauma recover well. Therefore, the outcome of patients with severe multiple blunt trauma as a result of a suicide attempt was investigated with respect to psychiatric and somatic health, quality of life (QOL) and suicide reattempt rates.
Patients who underwent a suicide attempt were isolated from a prospectively collected sample of trauma patients from a level I University Trauma Centre. Follow-up examination was performed 6.1 ± 3 years after the trauma. A physical and psychiatric examination was performed, using established psychiatric scales.
Twelve percent of severely injured patients were identified as suicide attempters (male/female: 37/28, mean age 38 ± 18 years, mean Injury Severity Score (ISS) 40 ± 15 points). A psychiatric diagnosis was present in 90% at the time of the suicide attempt. Twenty-one patients died during the hospital stay (32%) and six subjects died thereafter, none due to suicide. Thirty-five individuals were eligible for examination. None of them had reattempted suicide. Seventeen (48%) had good outcomes reflected by absent or ambulatory psychiatric treatment, employment, normal psychiatric findings and good psychosocial ability. An indeterminate outcome was determined in 24%. Predictive variables for an adverse outcome (10 patients, 28%) were found to be a diagnosis of schizophrenia, continued psychiatric treatment and being without employment.
Despite the seriousness of the suicide attempt, survivors recovered well in about half the cases with no further suicide attempt in any patient. An early psychiatric consultation already on the Intensive Care Unit (ICU) is recommended.
The Late Pennsylvanian (Kasimovian, early Stephanian) sub- to perimontaneous Souss basin, situated in the present-day southwestern High Atlas mountains of Morocco, contains the hitherto only known late Paleozoic entomofauna from North Africa, which is simultaneously also the southernmost Euramerican entomofauna. The present study provides descriptions, identifications, and revisions of several species belonging to the genera Phyloblatta and Anthracoblattina (family Phyloblattidae) and of the genus Compsoblatta (family Compsoblattidae). A relatively large number of well-preserved Phyloblatta forewings, compared with congeneric species from several insect localities in Europe and North America, permits insights into the individual, intraspecific, and interspecific variability of the venation pattern as indispensable base for the description of the new specimens and the revision of several older species. The Souss insect beds cover a wide range of potential habitats. They are situated in different paleogeographical positions within the Souss basin and scattered across a 900 m thick succession of sediments. The single insect beds represent different sedimentary and biotic subenvironments from swamps and mires to shallow and deep lakes within a fluvial-dominated megaenvironment.
The Moscow Syneclise on the East European Platform is an important area for the study of the continental biota of late Permian to Early Triassic age in continuous sections. This study attempts a taxonomic description of the late Permian conchostracan fauna of this area. The rich, new material was collected, bed by bed, during geological and paleontological excavations of lacustrine and fluvial deposits of the Obnora Formation and Vokhma Formation of the late Permian Zhukovian Regional Stage near the towns of Vyazniki and Gorokhovets. The conchostracan fauna of the Zhukovian Regional Stage consists predominantly of Pseudestheria and less frequently of Palaeolimnadiopsis. In the earliest Triassic Vokhmian Regional Stage, a more diverse fauna including Euestheria, Magniestheria, Cornia, Palaeolimnadiopsis, and Rossolimnadiopsis was already recorded. The preliminary taxonomic determination of the pseudestheriids from the Zhukovian Regional Stage is intended to serve as a prerequisite for future studies of late Permian conchostracan biostratigraphy on the regional to interregional scale.
Physical activity (PA) may be therapeutic for people with severe mental illness (SMI) who generally have low PA and experience numerous life style-related medical complications. We conducted a meta-review of PA interventions and their impact on health outcomes for people with SMI, including schizophrenia-spectrum disorders, major depressive disorder (MDD) and bipolar disorder. We searched major electronic databases until January 2018 for systematic reviews with/without meta-analysis that investigated PA for any SMI. We rated the quality of studies with the AMSTAR tool, grading the quality of evidence, and identifying gaps, future research needs and clinical practice recommendations. For MDD, consistent evidence indicated that PA can improve depressive symptoms versus control conditions, with effects comparable to those of antidepressants and psychotherapy. PA can also improve cardiorespiratory fitness and quality of life in people with MDD, although the impact on physical health outcomes was limited. There were no differences in adverse events versus control conditions. For MDD, larger effect sizes were seen when PA was delivered at moderate-vigorous intensity and supervised by an exercise specialist. For schizophrenia-spectrum disorders, evidence indicates that aerobic PA can reduce psychiatric symptoms, improves cognition and various subdomains, cardiorespiratory fitness, whilst evidence for the impact on anthropometric measures was inconsistent. There was a paucity of studies investigating PA in bipolar disorder, precluding any definitive recommendations. No cost effectiveness analyses in any SMI condition were identified. We make multiple recommendations to fill existing research gaps and increase the use of PA in routine clinical care aimed at improving psychiatric and medical outcomes.
This article examines how disease salience influences attitudes toward two types of humanitarian aid: sending foreign aid and housing refugees. Some have argued that disease salience increases levels of out-group prejudice through what is referred to as the behavioral immune system (BIS), and this increase in out-group prejudice works to shape policy attitudes. However, an alternative mechanism that may explain the effects of disease salience is contamination fear, which would suggest there is no group bias in the effects of disease threat. Existing work largely interprets opposition to policies that assist out-groups as evidence of out-group prejudice. We suggest it is necessary to separate measures of out-group animosity from opinions toward specific policies to determine whether increased out-group prejudice rather than fear of contamination is the mechanism by which disease salience impacts policy attitudes. Across two experiments, disease salience is shown to significantly decrease support for humanitarian aid, but only in the form of refugee support. Furthermore, there is converging evidence to suggest that any influence of disease salience on aid attitudes is not caused by a corresponding increase in xenophobia. We suggest that the mechanism by which disease threat influences policy attitudes is a general fear of contamination rather than xenophobia. These findings go against an important hypothesized mechanism of the BIS and have critical implications for the relationship between disease salience and attitudes toward transnational policies involving humanitarian aid.
We use numerical modelling of glacier mass balance combined with recent and past glacier extents to obtain information on Little Ice Age (LIA) climate in southeastern Tibet. We choose two glaciers that have been analysed in a previous study of equilibrium-line altitudes (ELA) and LIA glacier advances with remote-sensing approaches. We apply a physically based surface energy- and mass-balance model that is forced by dynamically downscaled global analysis data. The model is applied to two glacier stages mapped from satellite imagery, modern (1999) and LIA. Precipitation scaling factors (PSF) and air temperature offsets (ATO) are applied to reproduce recent ELA and glacier mass balance (MB) during the LIA. A sensitivity analysis is performed by applying seasonally varying gradients of precipitation and air temperature. The calculated glacier-wide MB estimate for the period 2000–12 is negative for both glaciers (–992±366 kgm–2 a–1 and –1053±258 kgm–2 a–1). Relating recent and LIA PSF/ATO sets suggests a LIA climate with ~8–25% increased precipitation and ~1–2.5°C lower mean air temperature than in the period 2000–12. The results only provide an order of magnitude because deviations in other input parameters are not considered.
Empathy is a basic human ability, and patients with schizophrenia show
dysfunctional empathic abilities on the behavioural and neural level.
These dysfunctions may precede the onset of illness; thus, it seems
mandatory to examine the empathic abilities in individuals at clinical
high risk for psychosis.
Using functional magnetic resonance imaging, we measured 15 individuals
at clinical high risk of psychosis (CHR group) and compared their empathy
performance with 15 healthy volunteers and 15 patients with
Behavioural data analysis indicated no significant deficit in the CHR
group. Functional data analysis revealed hyperactivation in a
frontotemporoparietal network including the amygdala in the CHR group
compared with the other two groups.
Despite normal behavioural performance, the CHR group activated the
neural empathy network differently and specifically showed
hyperactivation in regions critical for emotion processing. This could
suggest a compensatory mechanism reflecting emotional hypersensitivity or
dysfunctional emotion regulation. Further investigations should clarify
the role of these neural alterations for development and exacerbation of
Individuals with schizophrenia and people with depression both show
abnormal behavioural and neural responses when perceiving and responding
to emotional stimuli, but pathology-specific differences and
commonalities remain mostly unclear.
To directly compare empathic responses to dynamic multimodal emotional
stimuli in a group with schizophrenia and a group with depression, and to
investigate their neural correlates using functional magnetic resonance
The schizophrenia group (n = 20), the depression group
(n = 24) and a control group (n =
24) were presented with portrait-shot video clips expressing emotion
through three possible communication channels: facial expression, prosody
and content. Participants rated their own and the actor's emotional state
as an index of empathy.
Although no group differences were found in empathy ratings,
characteristic differences emerged in the fMRI activation patterns. The
schizophrenia group demonstrated aberrant activation patterns during the
neutral speech content condition in regions implicated in multimodal
integration and formation of semantic constructs. Those in the depression
group were most affected during conditions with trimodal emotional and
trimodal neutral stimuli, in key regions of the mentalising network.
Our findings reveal characteristic differences in patients with
schizophrenia compared with those with depression in their cortical
responses to dynamic affective stimuli. These differences indicate that
impairments in responding to emotional stimuli may be caused by
pathology-specific problems in social cognition.
Despite its increasing popularity in German political science, systematic reflection on the various methods that are used in policy analysis is still scarce. It is revealing that none of the current German textbooks on policy analysis includes a special chapter on methodology, yet the variety of methods that are applied in this sub-discipline is enormous. Many of the methods that are used in the social sciences in general and political science in particular are also used in policy analysis. Similar to other areas of empirical research, in policy analysis the various methods are also closely related to objects of research and its various dimensions (aggregate level, scope and numbers of entities that are under scrutiny) in the same way as methods are linked to particular theoretical frameworks that are guiding the research process (for instance, frameworks focusing on rational decisions, institutional arrangements or policy discourse) (Schneider and Janning, 2006).
Policy research can be done at various levels. In its early phase it concentrated mostly on the national and regional governmental level; however, since the 1990s policy analysis on the international level has also become increasingly popular.
At the most aggregate level policy analysis can deal with the level of governmental intervention into society (usually measured by governmental expenditure related to total economic activity [gross domestic product, GDP] in a given country) or governmental activity in a societal sector such as the educational system or the labour market. Most studies at this level compare many cases and apply statistical methods to explain, for instance, governmental activity by political variables such as party orientation of governments or the restricting effects of political institutions (large-N studies) (see Figure 5.1).
A different type of analysis is provided by Politikfeldanalyse (policy domain research) that is strongly influenced by political sociology where policy domains are conceived as sociopolitical sub-systems that are constituted by a variety of organisations involved in sectoral policy-making. Policy domain studies may focus on the emergence of a given policy area, and also on the various coordination mechanisms and regulatory pattern by which a given policy sub-system is governed. Policy domains can be studied with qualitative and quantitative methods.
Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms. Patients were randomly assigned under double-blind conditions to receive risperidone (n=143) or haloperidol (n=146) for 8 wk. The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale (PANSS) negative score between treatment groups; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores, and several other measures of psychopathology and general functioning. The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson–Angus Scale (SAS) compared between treatment groups. The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms. Secondary tolerability criteria were the other extrapyramidal symptoms, measured with the Hillside Akathisia Scale (HAS) and the Abnormal Involuntary Movement Scale (AIMS). The average mean daily doses were 3.8 mg (s.d.=1.5) for risperidone and 3.7 mg (s.d.=1.5) for haloperidol. There were similar, significant improvements in both treatment groups in the primary and secondary efficacy criteria. At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [SAS: risperidone 36.5% of patients; haloperidol 51.5% of patients; likelihood ratio test, χ2(1)=7.8, p=0.005]. There were significantly fewer drop-outs [risperidone n=55, drop-out rate=38.5%; haloperidol n=79, drop-out rate=54.1%, χ2(1)=7.1, p=0.009] and a longer non-discontinuation time [risperidone: average of 50.8 d to drop-out; haloperidol: average of 44.0 d to drop-out; log rank test, χ2(1)=6.4, p=0.011] in the risperidone group. Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia. Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients.
The isotopic composition of ancient wood has the potential to provide information about past environments. We analyzed the δ13C, δ18O, and δ2H of cellulose of conifer trees from several cross-sections at each of 9 sites around the Great Lakes region ranging from ∼4000 to 14,000 cal BP. Isotopic values of Picea, Pinus, and Thuja species seem interchangeable for δ18O and δ2H comparisons, but Thuja appears distinctly different from the other 2 in its δ13C composition. Isotopic results suggest that the 2 sites of near-Younger Dryas age experienced the coldest conditions, although the Gribben Basin site near the Laurentide ice sheet was relatively dry, whereas the Liverpool site 500 km south was moister. The spatial isotopic variability of 3 of the 4 sites of Two Creeks age shows evidence of an elevation effect, perhaps related to sites farther inland from the Lake Michigan shoreline experiencing warmer daytime growing season temperatures. Thus, despite floristic similarity across sites (wood samples at 7 of the sites being Picea), the isotopes appear to reflect environmental differences that might not be readily evident from a purely floristic interpretation of macrofossil or pollen identification.
Adherence to treatment guidelines enhances treatment outcome. However, in clinical practice many patients with depression do not receive appropriate treatment.
To evaluate the treatment of depression in in-patients of German psychiatric hospitals with respect to treatment outcome and adherence to guidelines.
We recruited 1202 in-patients with depression from ten different hospitals. Quality data concerning treatment were collected at admission, during the treatment course and at discharge.
The level of depression was significantly decreased and most patients were satisfied with treatment. Many aspects of the treatment routine adhered to guideline recommendations. Adherence to guidelines could be improved with respect to adjustment of antidepressant dosage, reduction of benzodiazepine prescription, enhanced use of electroconvulsive therapy and wider use of interpersonal therapy.
The study reveals a high standard of psychiatric treatment of in-patients with depression. Nevertheless there is still room for improvement. Differences between hospitals in adherence to guidelines indicates the need for individual application of quality management tools.