Individuals with adverse childhood experiences explore less and underweight reward feedback.

Adverse childhood experiences (ACEs) are extreme stressors that lead to negative psychosocial outcomes in adulthood. Nonhuman animals explore less after exposure to early stress. Therefore, in this preregistered study, we hypothesized that reduced exploration following ACEs would also be evident in human adults. Further, we predicted that adults with ACEs, in a foraging task, would adopt a decision-making policy that relies on the most-recent reward feedback, a rational strategy for unstable environments. We analyzed data from 145 adult participants, 47 with four or more ACEs and 98 with fewer than four ACEs. In the foraging task, participants evaluated the trade-off between exploiting a known patch with diminishing rewards and exploring a novel one with a fresh distribution of rewards. Using computational modeling, we quantified the degree to which participants' decisions weighted recent feedback. As predicted, participants with ACEs explored less. However, contrary to our hypothesis, they underweighted recent feedback. These unexpected findings indicate that early adversity may dampen reward sensitivity. Our results may help to identify cognitive mechanisms that link childhood trauma to the onset of psychopathology.

Refuting the myth of a 'tsunami' of mental ill-health in populations affected by COVID-19: evidence that response to the pandemic is heterogeneous, not homogeneous.

BACKGROUND: The current study argues that population prevalence estimates for mental health disorders, or changes in mean scores over time, may not adequately reflect the heterogeneity in mental health response to the COVID-19 pandemic within the population. METHODS: The COVID-19 Psychological Research Consortium (C19PRC) Study is a longitudinal, nationally representative, online survey of UK adults. The current study analysed data from its first three waves of data collection: Wave 1 (March 2020, N = 2025), Wave 2 (April 2020, N = 1406) and Wave 3 (July 2020, N = 1166). Anxiety-depression was measured using the Patient Health Questionnaire Anxiety and Depression Scale (a composite measure of the PHQ-9 and GAD-7) and COVID-19-related posttraumatic stress disorder (PTSD) with the International Trauma Questionnaire. Changes in mental health outcomes were modelled across the three waves. Latent class growth analysis was used to identify subgroups of individuals with different trajectories of change in anxiety-depression and COVID-19 PTSD. Latent class membership was regressed on baseline characteristics. RESULTS: Overall prevalence of anxiety-depression remained stable, while COVID-19 PTSD reduced between Waves 2 and 3. Heterogeneity in mental health response was found, and hypothesised classes reflecting (i) stability, (ii) improvement and (iii) deterioration in mental health were identified. Psychological factors were most likely to differentiate the improving, deteriorating and high-stable classes from the low-stable mental health trajectories. CONCLUSIONS: A low-stable profile characterised by little-to-no psychological distress ('resilient' class) was the most common trajectory for both anxiety-depression and COVID-19 PTSD. Monitoring these trajectories is necessary moving forward, in particular for the ~30% of individuals with increasing anxiety-depression levels.

Metabolomics and NMR.

The purpose of this manuscript will be to convince the reader to dive deeper into NMR spectroscopy and prevent the technique from being just another "black-box" in the lab. We will try to concisely highlight interesting topics and supply additional references for further exploration at each stage. The advantages of delving into the technique will be shown. The secondary objective, i.e., avoiding common problems before starting, will hopefully then become clear. Lastly, we will emphasize the spectrometer information needed for manuscript reporting to allow reproduction of results and confirm findings.

Measurement invariance of the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) across four European countries during the COVID-19 pandemic.

BACKGROUND: The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) are self-report measures of major depressive disorder and generalised anxiety disorder. The primary aim of this study was to test for differential item functioning (DIF) on the PHQ-9 and GAD-7 items based on age, sex (males and females), and country. METHOD: Data from nationally representative surveys in UK, Ireland, Spain, and Italy (combined N = 6,054) were used to fit confirmatory factor analytic and multiple-indictor multiple-causes models. RESULTS: Spain and Italy had higher latent variable means than the UK and Ireland for both anxiety and depression, but there was no evidence for differential items functioning. CONCLUSIONS: The PHQ-9 and GAD-7 scores were found to be unidimensional, reliable, and largely free of DIF in data from four large nationally representative samples of the general population in the UK, Ireland, Italy and Spain.

Modelling the complexity of pandemic-related lifestyle quality change and mental health: an analysis of a nationally representative UK general population sample.

PURPOSE: The COVID-19 pandemic has affected the way many individuals go about their daily lives. This study attempted to model the complexity of change in lifestyle quality as a result of the COVID-19 pandemic and its context within the UK adult population. METHODS: Data from the COVID-19 Psychological Research Consortium Study (Wave 3, July 2020; N = 1166) were utilised. A measure of COVID-19-related lifestyle change captured how individuals' lifestyle quality had been altered as a consequence of the pandemic. Exploratory factor analysis and latent profile analysis were used to identify distinct lifestyle quality change subgroups, while multinomial logistic regression analysis was employed to describe class membership. RESULTS: Five lifestyle dimensions, reflecting partner relationships, health, family and friend relations, personal and social activities, and work life, were identified by the EFA, and seven classes characterised by distinct patterns of change across these dimensions emerged from the LPA: (1) better overall (3.3%), (2) worse except partner relations (6.0%), (3) worse overall (2.5%), (4) better relationships (9.5%), (5) better except partner relations (4.3%), (6) no different (67.9%), and (7) worse partner relations only (6.5%). Predictor variables differentiated membership of classes. Notably, classes 3 and 7 were associated with poorer mental health (COVID-19 related PTSD and suicidal ideation). CONCLUSIONS: Four months into the pandemic, most individuals' lifestyle quality remained largely unaffected by the crisis. Concerningly however, a substantial minority (15%) experienced worsened lifestyles compared to before the pandemic. In particular, a pronounced deterioration in partner relations seemed to constitute the more severe pandemic-related lifestyle change.

Are adolescents more optimal decision-makers in novel environments? Examining the benefits of heightened exploration in a patch foraging paradigm.

Adolescence is a period of heightened exploration relative to adulthood and childhood. This predisposition has been linked with negative behaviours related to risk-taking, including dangerous driving, substance misuse and risky sexual practices. However, recent models have argued that adolescents' heightened exploration serves a functional purpose within the lifespan, allowing adolescents to develop experiential knowledge of their surroundings. Yet, there is limited evidence that heightened exploration in adolescence is associated with positive outcomes. To address this, the present pre-registered study utilised a foraging paradigm with a sample of adolescents aged 16-17 (N = 68) and of adults aged 21 and above (N = 69). Participants completed a patch foraging task, which required them to choose between exploiting a known resource which gradually yields fewer rewards, and exploring a novel, unknown resource with a fresh distribution of rewards. Findings demonstrated that adolescents explored more than adults, which - in the context of the current task-represented more optimal patch foraging behaviour. These findings indicate that adolescents' heightened exploration can be beneficial, as they were able to effectively navigate unknown environments and accrue rewards more successfully than adults. This provides evidence that heightened exploration in adolescence, relative to adulthood, can lead to positive outcomes and contributes to our understanding of the role increased novelty-seeking plays at this point in the lifespan.

NMR as a "Gold Standard" Method in Drug Design and Discovery.

Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a "gold standard" platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development.

Looking for Mr(s) Right: Decision bias can prevent us from finding the most attractive face.

In realistic and challenging decision contexts, people may show biases that prevent them from choosing their favored options. For example, astronomer Johannes Kepler famously interviewed several candidate fiancées sequentially, but was rejected when attempting to return to a previous candidate. Similarly, we examined human performance on searches for attractive faces through fixed-length sequences by adapting optimal stopping computational theory developed from behavioral ecology and economics. Although economics studies have repeatedly found that participants sample too few options before choosing the best-ranked number from a series, we instead found overlong searches with many sequences ending without choice. Participants employed irrationally high choice thresholds, compared to the more lax, realistic standards of a Bayesian ideal observer, which achieved better-ranked faces. We consider several computational accounts and find that participants most resemble a Bayesian model that decides based on altered attractiveness values. These values may produce starkly different biases in the facial attractiveness domain than in other decision domains.

Measles, magic and misidentifications: a defence of the two-factor theory of delusions.

Corlett (Corlett, P. (this issue). Factor one, familiarity and frontal cortex: A challenge to the two-factor theory of delusions. Cognitive Neuropsychiatry) provides a robust critique of the two-factor theory of delusions. The heart of his critique is two challenges he derives from a paper by Tranel and Damasio (Tranel, D., & Damasio, H. (1994). Neuroanatomical correlates of electrodermal skin conductance responses. Psychophysiology, 31(5), 427-438), who illuminate the autonomic responses and brain damage of four patients often cited in support of the two-factor theory of Capgras delusion. I defend the two-factor theory against Corlett's two key challenges, arguing that his first challenge has been previously addressed, and that his second challenge is overstated. In my view, these challenges do not negate the two-factor account. Nevertheless, two-factor theorists - and computational psychiatrists - should continue to devise and test falsifiable predictions of their respective theories.

Explaining delusional beliefs: a hybrid model.

Introduction: In this paper we present and defend a hybrid theory of the development of delusions that incorporates the central ideas of two influential (yet sometimes bitterly opposing) theoretical approaches to delusions-the two-factor theory and the prediction error theory. Method: After introducing the central ideas of the two-factor theory and the prediction error theory, we describe the motivations for our conciliatory project, explain the theoretical details of the hybrid theory we propose, and answer potential objections to our proposal. Results: According to the hybrid theory we advance, the first factor of a delusion is physically grounded in an abnormal prediction error, and the second factor is physically grounded in the overestimation of the precision of the abnormal prediction error. Against anticipated objections, we argue that the hybrid theory is internally coherent, and that it constitutes a genuine hybrid between the two-factor theory and the prediction error theory. Conclusion: A rapprochement between the two-factor theory and the prediction error theory is both possible and desirable. In particular, our hybrid theory provides a parsimonious and unified account of delusions, whether monothematic or polythematic, across a wide variety of medical conditions.

Long TE STEAM and PRESS for estimating fat olefinic/methyl ratios and relative ω-3 fat content at 3T.

BACKGROUND: Fat olefinic/methyl ratios provide a measure of fat unsaturation. The methyl resonance linewidth is altered with the presence of ω-3 fat. PURPOSE: To optimize stimulated echo acquisition mode (STEAM) and point resolved spectroscopy (PRESS) echo times (TE) at 3T to 1) improve olefinic/methyl ratios and 2) enable relative ω-3 fat content assessment. STUDY TYPE: Technical development on phantoms and healthy volunteers. POPULATION: Nine edible oils and four healthy volunteers (tibial bone marrow). FIELD STRENGTH/SEQUENCE: STEAM (mixing time = 20 msec) and PRESS sequences at 3T. High-resolution oil spectra at 16.5T. ASSESSMENT: 3T STEAM and PRESS olefinic/methyl ratios as a function of TE were compared to 16.5T measures for the oils, and to a literature-deduced value for tibial bone marrow. Oil methyl linewidths were calculated at each TE to investigate correlation with expected ω-3 fatty acid content. STATISTICAL TESTS: Percent differences were calculated between oil olefinic/methyl ratios obtained at 3T and 16.5T. Linear regression R2 values measured correlation of methyl linewidth to ω-3 content. RESULTS: STEAM, TE = 120 msec, resulted in average oil olefinic/methyl ratios that differ by about -4.8% compared to high-resolution ratios. Tibial bone marrow olefinic/methyl ratios differ by -1.8% compared with literature-obtained ratios. PRESS, TE = 180 msec, resulted in oil ratios that differ by 7.8% and tibial bone marrow ratios that differ by 0.2%. A TE of 160 msec for both STEAM and PRESS enabled relative levels of oil ω-3 fatty acid content to be estimated (R2 values ≥0.9). DATA CONCLUSION: STEAM, TE = 120 msec (mixing time = 20 msec), and PRESS, TE = 180 msec, optimally estimated olefinic/methyl ratios. STEAM and PRESS, TE = 160 msec, enable relative oil ω-3 fatty acid estimation from methyl linewidths. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017.

Rituals Improve Children's Ability to Delay Gratification.

To be accepted into social groups, individuals must internalize and reproduce appropriate group conventions, such as rituals. The copying of such rigid and socially stipulated behavioral sequences places heavy demands on executive function. Given previous research showing that challenging executive functioning improves it, it was hypothesized that engagement in ritualistic behaviors improves children's executive functioning, in turn improving their ability to delay gratification. A 3-month circle time games intervention with 210 schoolchildren (Mage  = 7.78 years, SD = 1.47) in two contrasting cultural environments (Slovakia and Vanuatu) was conducted. The intervention improved children's executive function and in turn their ability to delay gratification. Moreover, these effects were amplified when the intervention task was imbued with ritual, rather than instrumental, cues.

Insightful directed evolution of Escherichia coli quorum sensing promoter region of the lsrACDBFG operon: a tool for synthetic biology systems and protein expression.

Quorum sensing (QS) regulates many natural phenotypes (e.q. virulence, biofilm formation, antibiotic resistance), and its components, when incorporated into synthetic genetic circuits, enable user-directed phenotypes. We created a library of Escherichia coli lsr operon promoters using error-prone PCR (ePCR) and selected for promoters that provided E. coli with higher tetracycline resistance over the native promoter when placed upstream of the tet(C) gene. Among the fourteen clones identified, we found several mutations in the binding sites of QS repressor, LsrR. Using site-directed mutagenesis we restored all p-lsrR-box sites to the native sequence in order to maintain LsrR repression of the promoter, preserving the other mutations for analysis. Two promoter variants, EP01rec and EP14rec, were discovered exhibiting enhanced protein expression. In turn, these variants retained their ability to exhibit the LsrR-mediated QS switching activity. Their sequences suggest regulatory linkage between CytR (CRP repressor) and LsrR. These promoters improve upon the native system and exhibit advantages over synthetic QS promoters previously reported. Incorporation of these promoters will facilitate future applications of QS-regulation in synthetic biology and metabolic engineering.

Shamanism and the psychosis continuum.

Singh's cultural evolutionary theory of shamanism is impressive, but it does not explain why some people become shamans while others do not. We propose that individual differences in where people lie on a "psychosis continuum" could play an important causal role.

Do the folk actually hold folk-economic beliefs?

Boyer & Petersen (B&P) argue that folk-economic beliefs are widespread - shaped by evolved cognitive systems - and they offer exemplar beliefs to illustrate their thesis. In this commentary, we highlight evidence of substantial variation in one of these exemplars: beliefs about immigration. Contra claims by B&P, we argue that the balance of this evidence suggests the "folk" may actually hold positive beliefs about the economic impact of immigration.

Insights into the Mechanism of Action of the Two-Peptide Lantibiotic Lacticin 3147.

Lacticin 3147 is a two peptide lantibiotc (LtnA1 and LtnA2) that displays nanomolar activity against many Gram-positive bacteria. Lacticin 3147 may exert its antimicrobial effect by several mechanisms. Isothermal titration calorimetry experiments show that only LtnA1 binds to the peptidoglycan precursor lipid II, which could inhibit peptidoglycan biosynthesis. An experimentally supported model of the resulting complex suggests that the key binding partners are the C-terminus of LtnA1 and pyrophosphate of lipid II. A combination of in vivo and in vitro assays indicates that LtnA1 and LtnA2 can induce rapid membrane lysis without the need for lipid II binding. However, the presence of lipid II substantially increases the activity of lacticin 3147. Furthermore, studies with synthetic LtnA2 analogues containing either desmethyl- or oxa-lanthionine rings confirm that the precise geometry of these rings is essential for this synergistic activity.

Controlling localization of Escherichia coli populations using a two-part synthetic motility circuit: An accelerator and brake.

Probiotics, whether taken as capsules or consumed in foods, have been regarded as safe for human use by regulatory agencies. Being living cells, they serve as "tunable" factories for the synthesis of a vast array of beneficial molecules. The idea of reprogramming probiotics to act as controllable factories, producing potential therapeutic molecules under user-specified conditions, represents a new and powerful concept in drug synthesis and delivery. Probiotics that serve as drug delivery vehicles pose several challenges, one being targeting (as seen with nanoparticle approaches). Here, we employ synthetic biology to control swimming directionality in a process referred to as "pseudotaxis." Escherichia coli, absent the motility regulator cheZ, swim sporadically, missing the traditional "run" in the run:tumble swimming paradigm. Upon introduction of cheZ in trans and its signal-generated upregulation, engineered bacteria can be "programmed" to swim toward the source of the chemical cue. Here, engineered cells that encounter sufficient levels of the small signal molecule pyocyanin, produce an engineered CheZ and swim with programmed directionality. By incorporating a degradation tag at the C-terminus of CheZ, the cells stop running when they exit spaces containing pyocyanin. That is, the engineered CheZ modified with a C-terminal extension derived from the putative DNA-binding transcriptional regulator YbaQ (RREERAAKKVA) is consumed by the ClpXP protease machine at a rate sufficient to "brake" the cells when pyocyanin levels are too low. Through this process, we demonstrate that over time, these engineered E. coli accumulate in pyocyanin-rich locales. We suggest that such approaches may find utility in engineering probiotics so that their beneficial functions can be focused in areas of principal benefit.

The optimist within? Selective sampling and self-deception.

The nature and existence of self-deception is controversial. On a classic conception, self-deceived individuals carry two conflicting representations of reality. Proponents of an alternative, deflationary account dispute this, arguing that putative cases of self-deception simply reflect distorted information processing. To investigate these alternatives, we adapted a paradigm from the "crowd-within" literature. Participants provided two different estimates for each of a series of incentivized questions. Half of the questions were neutral in content, while half referred to undesirable future events. Whereas the first and second estimates for neutral questions did not differ systematically, second estimates for undesirable questions were more optimistic than first estimates. This result suggests that participants were sampling selectively from an internal probability distribution when providing estimates for undesirable events, implying they had access to a less rosy representation of their future prospects than their individual estimates conveyed. In short, self-deception is real.

Choosing the right level of analysis: Stereotypes shape social reality via collective action.

In his 2012 book Jussim argues that the self-fulfilling prophecy and expectancy effects of descriptive stereotypes are not potent shapers of social reality. However, his conclusion that descriptive stereotypes per se do not shape social reality is premature and overly reductionist. We review evidence that suggests descriptive stereotypes do have a substantial influence on social reality, by virtue of their influence on collective action.