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Questions can be raised about the central status that evolutionarily ancient core knowledge systems are given in Spelke's otherwise very compelling theory. So, the existence of domain-general learning capacities has to be admitted, too, and no clear reason is provided to doubt the existence of uniquely human cognitive adaptations. All of these factors should be acknowledged when explaining human thought.
While the investigation of non-human economic decision-making is increasingly popular, it is not clear exactly what role it can play in settling debates in economics. This paper argues that—contrary to recent claims otherwise—data on animal decision-making do not help in (dis–)confirming economic theories of choice. Rather, such data help in spelling out the representationally proper domains of models of choice. To play this role, though, these data must be placed into phylogenetic comparative analyses: correlations with specific environmental features need to be assessed, and these correlations need to be corrected for the presence of phylogenetic signals.
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.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
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.
Results
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.
Conclusions
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.
Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.
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.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
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.
Results
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.
Conclusions
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.
We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (
${>}7 \times 10^{10} {\mathrm{M}}_\odot$
) central galaxies at
$0.25 < z <0.35$
in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics (
$0.6-0.8$
arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at
$0.25 < z <0.35$
, as well as hundreds of emission-line sources at
$z < 6$
. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at
$z\approx 0.3$
. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.
Methods
We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.
Results
Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.
Conclusions
Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.
To evaluate open-label treatment with olanzapine in patients with borderline personality disorder (BPD).
Methods:
In two concurrent studies, patients received 12 weeks of open-label olanzapine after completing 12-weeks of double-blind treatment with either olanzapine or placebo. Open-label olanzapine dosing started at 2.5 or 5mg/day and could be increased up to 20mg/day (Study 1) or 15mg/day (Study 2).
Results:
Mean ZAN-BPD total scores decreased from approximately 17 points to approximately 8-10 points during the acute phase. After 12 weeks of open-label olanzapine treatment, mean ZAN-BPD total scores were approximately 6-7 points. Patients treated with placebo during the acute phase and then open-label olanzapine showed changes in weight, prolactin, and other laboratory values similar in magnitude to those seen in acutely olanzapine-treated patients. Patients treated with olanzapine during the acute phase showed smaller changes in weight and laboratory values during the open-label extension.
Conclusions:
Overall BPD symptom severity was low by the end of the open-label olanzapine treatment period. The types of treatment emergent adverse events appeared to be consistent with those seen previously in patients treated with olanzapine. The direction and magnitude of effects on safety measures depended on the treatment received during the prior double-blind period.
Neuropsychological deficits are considered endophenotypes for schizophrenia, because they are not only found in patients but also in many of their unaffected relatives, albeit in attenuated form. It is not yet clear which of these deficits in relatives are related to genetic or to environmental causes. We tested effects of inferred genetic liability for schizophrenia on neurocognitive variables to address this problem.
Method:
Twenty-eight patients with schizophrenia, 129 non-affected biological parents and 143 matched controls were assessed with an extensive neuropsychological test battery including tests of attention, memory, executive functioning and motor soft signs. Twenty-two parents had an ancestral history of schizophrenia and therefore were hypothesized to be more likely than their spouses without such a history (n = 17) to carry a genetic risk for schizophrenia.
Results:
Unaffected parents of schizophrenic patients showed significant deficits in a wide array of neuropsychological tasks and task domains. However, comparison of more likely and less likely carriers of illness-related genes showed specifically attentional and executive functioning, but not memory, to vary with degree of inferred genetic loading.
Conclusions:
Attentional and executive (frontal) impairments vary with genetic loading for schizophrenia and can be considered true endophenotypes for this disorder. Consequently, these functions are particularly suited to evaluate the functional impact of candidate genes for schizophrenia in future studies.
Prolactin (PRL) data from adolescents treated with olanzapine are presented.
Methods:
Data from 454 adolescents (13-18, mean=15.9 yrs) with schizophrenia or bipolar mania were pooled from 4 olanzapine (2.5-20.0mg/day) studies (4-32 weeks; 2 double-blind, placebo-controlled studies [combined for acute phase endpoint PRL levels] with open-label extensions; 2 open-label studies). Age- and sex-specific Covance reference ranges defined normal PRL; categorical increases were based on multiples of the upper limit of normal (ULN). Baseline-to-endpoint PRL changes in adolescents were compared with data pooled from 84 olanzapine clinical trials in adults with schizophrenia or bipolar disorder.
Results:
Olanzapine-treated adolescents had mean PRL increases at both the acute (11.4μg/L) and open-label endpoints (4.7μg/L). Of those patients with normal PRL levels at baseline (N=311), high PRL occurred in 54.7% at anytime; 32.2% at endpoint. The percentage of patients in which PRL levels shifted from normal-to-abnormal was smaller at endpoint than at anytime during treatment; 26.7% shifted to a higher category. Among patients with normal baseline PRL, 32.7% remained <=1X ULN; 32.3% increased to 1¬<=2X; 6.0%, >2-<=3X; and 1.2%, >3X at anytime; 4.6% had at >=1 potentially PRL-related adverse event. Adolescents had significantly higher mean changes at endpoint (p=.004), and a greater incidence of high PRL levels at anytime during olanzapine treatment (p<.001) versus adults.
Conclusion:
Incidence of high PRL was significantly higher, and mean increases in PRL were significantly greater in adolescents versus adults. Mean increases and high PRL incidence were lower at the open-label compared with the acute phase endpoint.
Work in psychiatry can be strenuous – both in terms of caseload and the kind of work. Health care reforms have increased the pressure even further, amplifying the risk of burnout. Burnout research has been criticized for neglecting the perspective of those potentially at risk. This qualitative study seeks to throw light on the burnout literacy of mental health professionals and its implication on their help-seeking behaviour. It further seeks to identify the relevant mechanisms in transforming health literacy into action.
Methods
Focus groups were carried out with mental health providers (n=215) from different settings (in-patient/community-based), as well as professional groups. They addressed participants’ job strain and job-related resources, as well as their definition of what constitutes burnout, and what should be done about it. Group sessions were audio-taped, transcribed, and analysed by means of a qualitative procedure.
Results
Mental health professionals are well-informed about burnout. They perceive burnout as a multidimensional syndrome that affects professionals’ mental and physical health, job motivation, job performance as well as their relationship with their clients, and propose multiple intervention strategies. However, two major obstacles are described in translating their knowledge into practice: burnout (1) goes undetected for a long time and (2) has a stigma attached to it.
Conclusions
While mental health professionals’ burnout literacy is high, the social perception of burnout poses a serious barrier to early detection and treatment. Burnout prevention strategies should become an integral part of continuous medical education to ensure that mental health professionals can work effectively.
We examined the efficacy and safety of flexibly-dosed olanzapine for the treatment of borderline personality disorder (BPD).
Methods:
In this 12-week double-blind trial, patients 18-65 years of age with a diagnosis of DSM-IV BPD received olanzapine (2.5-20mg/day; N=155) or placebo (N=159). The primary efficacy measure was the change from baseline to last-observation carried forward endpoint (LOCF) on the Zanarini Rating Scale for BPD (ZAN-BPD) total score. Rate of response and time to response were also examined, with response defined as a >=50% reduction in ZAN-BPD total score.
Results:
Mean baseline ZAN-BPD total scores were indicative of moderate symptom severity (olanzapine 17.01 vs. placebo 17.70, p=0.156). Both treatment groups showed significant improvements in overall symptom severity, based on mean changes from baseline to LOCF endpoint in ZAN-BPD total score, but did not differ in the magnitude of improvement at endpoint (olanzapine -6.56 vs. placebo -6.25, p=.661). Response rates did not differ between treatment groups (olanzapine 64.7% vs. placebo 53.5%, p=.062); however, time to response was significantly shorter for the olanzapine treatment group (p=.022). Treatment-emergent adverse events reported significantly more frequently among olanzapine-treated patients included somnolence, sedation, increased appetite and weight increase. Mean weight change from baseline to endpoint was significantly different for olanzapine- relative to placebo-treated patients (2.86vs. -0.35kg, p<.001).
Conclusions:
Both the olanzapine- and placebo-treated patients showed significant but not statistically different improvement on overall symptoms of borderline personality disorder. The types of adverse events observed with olanzapine treatment were similar to those seen previously in adult populations.
Work in psychiatry can be highly rewarding, interesting, and challenging in a positive sense. On the other hand, we are confronted with an array of psychosocial stressors. Caring for others lies at the heart of our profession: the focus is on the needs of patients. And rightly so. Nevertheless, this involves the risk that providers' own needs get out of sight.
This course provides a forum for openly discussing work-related stress and coping strategies. Participants will learn to recognise their own “warning signs” of excessive stress, as well as develop strategies to successfully handle stressful situations, based on their own practical experiences. The course further addresses consequences of stress, such as the risk to develop physical health problems or burnout. Instruments to gauge one's own burnout risk and stress coping pattern will be available for a self-assessment.
Learning goals:
• Understanding stress mechanisms and our own reactions to stress.
• Noticing one's own stress level.
• Gauging the risk for burnout: Where do I stand?
• Coping with stress: What helps?
Methods
• Interactive teaching
• Exercises
• Group work
• Stress and burnout self assessment
• Guided discussion
Target group:
This course is open to all participants, but particularly addresses young psychiatrists. Young psychiatrists entering the field even experience elevated stressors. At the same time, starting out in the job is a good moment to develop self-care strategies – that are essential to maintain professional vitality and effectiveness in the long run.
The changes in metabolic parameters in olanzapine-treated adolescents were examined.
Methods:
Data from 454 adolescents (13–18, mean=15.9 years) with schizophrenia or bipolar I disorder were pooled from 4 olanzapine (2.5–20.0mg/day) studies (4–32 weeks). Changes in metabolic parameters in adolescents were compared with those of olanzapine-treated adults (pooled from 84 clinical trials); changes in weight and BMI were compared with US age- and sex-adjusted standardized growth curves.
Results:
Olanzapine-treated adolescents had significant increases from baseline-to-endpoint in fasting glucose (p=.021); total cholesterol, LDL, and triglycerides (p<.001); and significant decreases in HDL (p<.001). Significantly more adolescents gained >=7% of their baseline weight versus adults (65.1% vs. 35.6%, p<.001); mean change from baseline-to-endpoint in weight was significantly greater in adolescents (7.0 vs. 3.3kg, p<.001). Adolescents had significantly lower mean changes from baseline-to-endpoint in fasting glucose (0.3 vs. 0.1mmol/L, p=.002) and triglycerides (0.3 vs. 0.2mmol/L, p=.007) versus adults. Significantly more adults experienced treatment-emergent normal-to-high changes at anytime in fasting glucose (4.8% vs. 1.2%, p=.033), total cholesterol (6.9% vs. 1.1%, p=.001), LDL (5.8% vs. 1.5%, p=.014), and triglycerides (25.7% vs. 17.4%, p=.030). Compared with standardized growth curves, olanzapine-treated adolescents had greater increases from baseline-to-endpoint in weight (1.0 vs. 7.1kg, p<.001), height (0.5 vs. 0.7cm, p<.001), and BMI (0.2 vs. 2.2kg/m2, p<.001).
Conclusion:
Olanzapine-treated adolescents may gain significantly more weight compared with adults, but may have smaller changes in other metabolic parameters. Clinicians may want to consider both efficacy and changes in metabolic parameters when selecting treatment options for individual adolescent patients.
We examined the efficacy and safety of low vs. moderate olanzapine doses for the treatment of borderline personality disorder (BPD) in the largest controlled clinical trial ever conducted in this population.
Methods:
This 12-week, double-blind trial involved patients 18-65 years with a diagnosis of DSM-IV BPD randomized to receive 2.5mg/day olanzapine (N=150), 5-10mg/day olanzapine (N=148), or placebo (N=153). The primary efficacy measure was the change from baseline-to-endpoint (last-observation-carried-forward) on the Zanarini Rating Scale for BPD (ZAN-BPD) total score. Rate of response and time-to-response were also examined (response defined as a >=50% reduction in ZAN-BPD total score).
Results:
Mean baseline ZAN-BPD total scores ranged from 17.01 to 17.42, indicating moderate symptom severity. Treatment with OLZ5-10 was associated with significantly greater mean change from baseline-to-endpoint in ZAN-BPD total score than placebo (-8.50 vs. -6.79, p=.010). Response rates were significantly higher for OLZ5-10 (73.6%) than for OLZ2.5 (60.1%, p=.018) and placebo (57.8%, p=.006). Time-to-response was significantly shorter for OLZ5-10 than placebo (p=.028). Treatment-emergent adverse events seen more frequently in the olanzapine groups included somnolence, increased appetite, and weight gain. Mean weight change from baseline-to-endpoint was 2.09kg for OLZ 2.5, 3.17kg for OLZ5-10, and 0.02kg for placebo.
Conclusions:
The results of this study suggest that moderate doses of olanzapine (5-10mg/day) are effective in the treatment of overall borderline psychopathology. Also, the types of adverse events observed with olanzapine treatment were similar to those seen previously in adult populations.