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Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
Joanna Leidenhag has written a ground-breaking book arguing that the concept of panpsychism can solve several problems facing present-day humans. It can motivate greater commitment to concern for earth's diverse environments and the life forms that inhabit them. And it can solve theological problems connected with human consciousness, notably, how consciousness and matter coexist and interact. This article summarizes and comments on Leidenhag's arguments, then suggests several paths forward for those inspired by Leidenhag's ideas and arguments who wish to explore them and related notions in greater depth.
Ingestion of mycoprotein stimulates skeletal muscle protein synthesis (MPS) rates to a greater extent than concentrated milk protein when matched for leucine content, potentially attributable to the wholefood nature of mycoprotein. We hypothesised that bolus ingestion of mycoprotein as part of its wholefood matrix would stimulate MPS rates to a greater extent compared with a leucine-matched bolus of protein concentrated from mycoprotein. Twenty-four healthy young (age, 21 ± 2 years; BMI, 24 ± 3 kg.m2) males received primed, continuous infusions of L-[ring-2H5]phenylalanine and completed a bout of unilateral resistance leg exercise before ingesting either 70 g mycoprotein (MYC; 31·4 g protein, 2·5 g leucine; n 12) or 38·2 g of a protein concentrate obtained from mycoprotein (PCM; 28·0 g protein, 2·5 g leucine; n 12). Blood and muscle samples (vastus lateralis) were taken pre- and (4 h) post-exercise/protein ingestion to assess postabsorptive and postprandial myofibrillar protein fractional synthetic rates (FSR) in resting and exercised muscle. Protein ingestion increased plasma essential amino acid and leucine concentrations (P < 0·0001), but more rapidly (both 60 v. 90 min; P < 0·0001) and to greater magnitudes (1367 v. 1346 μmol·l–1 and 298 v. 283 μmol·l–1, respectively; P < 0·0001) in PCM compared with MYC. Protein ingestion increased myofibrillar FSR (P < 0·0001) in both rested (MYC, Δ0·031 ± 0·007 %·h–1 and PCM, Δ0·020 ± 0·008 %·h–1) and exercised (MYC, Δ0·057 ± 0·011 %·h–1 and PCM, Δ0·058 ± 0·012 %·h–1) muscle, with no differences between conditions (P > 0·05). Mycoprotein ingestion results in equivalent postprandial stimulation of resting and post-exercise myofibrillar protein synthesis rates irrespective of whether it is consumed within or without its wholefood matrix.
Seabirds are declining globally and are one of the most threatened groups of birds. To halt or reverse this decline they need protection both on land and at sea, requiring site-based conservation initiatives based on seabird abundance and diversity. The Important Bird and Biodiversity Area (IBA) programme is a method of identifying the most important places for birds based on globally agreed standardised criteria and thresholds. However, while great strides have been made identifying terrestrial sites, at-sea identification is lacking. The Chagos Archipelago, central Indian Ocean, supports four terrestrial IBAs (tIBAs) and two proposed marine IBAs (mIBAs). The mIBAs are seaward extensions to breeding colonies based on outdated information and, other types of mIBA have not been explored. Here, we review the proposed seaward extension mIBAs using up-to-date seabird status and distribution information and, use global positioning system (GPS) tracking from Red-footed Booby Sula sula – one of the most widely distributed breeding seabirds on the archipelago – to identify any pelagic mIBAs. We demonstrate that due to overlapping boundaries of seaward extension to breeding colony and pelagic areas of importance there is a single mIBA in the central Indian Ocean that lays entirely within the Chagos Archipelago Marine Protected Area (MPA). Covering 62,379 km2 it constitutes ~10% of the MPA and if designated, would become the 11th largest mIBA in the world and 4th largest in the Indian Ocean. Our research strengthens the evidence of the benefits of large-scale MPAs for the protection of marine predators and provides a scientific foundation stone for marine biodiversity hotspot research in the central Indian Ocean.
The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.
Childhood maltreatment (CM) represents a potent risk factor for major depressive disorder (MDD), including poorer treatment response. Altered resting-state connectivity in the fronto-limbic system has been reported in maltreated individuals. However, previous results in smaller samples differ largely regarding localization and direction of effects.
We included healthy and depressed samples [n = 624 participants with MDD; n = 701 healthy control (HC) participants] that underwent resting-state functional MRI measurements and provided retrospective self-reports of maltreatment using the Childhood Trauma Questionnaire. A-priori defined regions of interest [ROI; amygdala, hippocampus, anterior cingulate cortex (ACC)] were used to calculate seed-to-voxel connectivities.
No significant associations between maltreatment and resting-state connectivity of any ROI were found across MDD and HC participants and no interaction effect with diagnosis became significant. Investigating MDD patients only yielded maltreatment-associated increased connectivity between the amygdala and dorsolateral frontal areas [pFDR < 0.001; η2partial = 0.050; 95%-CI (0.023–0.085)]. This effect was robust across various sensitivity analyses and was associated with concurrent and previous symptom severity. Particularly strong amygdala-frontal associations with maltreatment were observed in acutely depressed individuals [n = 264; pFDR < 0.001; η2partial = 0.091; 95%-CI (0.038–0.166)). Weaker evidence – not surviving correction for multiple ROI analyses – was found for altered supracallosal ACC connectivity in HC individuals associated with maltreatment.
The majority of previous resting-state connectivity correlates of CM could not be replicated in this large-scale study. The strongest evidence was found for clinically relevant maltreatment associations with altered adult amygdala-dorsolateral frontal connectivity in depression. Future studies should explore the relevance of this pathway for a maltreated subgroup of MDD patients.
Crops emit a variety of volatile organic compounds (VOCs) that serve as attractants or repellents for pests and their natural enemies. Crop rotations, off-farm chemical inputs, and mechanical and cultural tactics – collectively called cropping systems – alter soil nutrients, moisture content, and microbial communities, all of which have the potential to alter crop VOC emissions. Soil legacy effects of diversified cropping systems have been shown to enhance crop VOC emissions in greenhouse studies, but how they influence emissions under field conditions remains virtually unknown. To determine the effect of cropping systems on plant VOC emissions in the field, air samples were collected from the headspace of wheat (Triticum aestivum L. Judee) grown in simplified wheat-fallow rotations or diversified wheat-cover crop rotations where cover crops were terminated by grazing cattle. Across two growing seasons, wheat grown in rotation with fallow emitted greater amounts of Z-3-hexenyl acetate and β-ocimene, key attractants for wheat stem sawfly (Cephus cinctus Norton), a major pest of wheat. While overall VOC blends were relatively similar among cropping system during the first growing season, emissions varied substantially in the second year of this study where wheat grown in rotation with cover crops emitted substantially greater quantities of volatile compounds characteristic of abiotic stress. Below-average precipitation in the second growing season, in addition to reduced soil water content in cover crop rotations, suggests that cropping system effects on wheat VOCs may have been driven primarily by water availability, a major factor limiting crop growth in dryland agriculture. While the specific mechanisms driving changes in VOC emissions were not explicitly tested, this work shows that agricultural practices applied in one growing season can differentially influence crop VOC emissions in the next through soil legacy effects, illustrating additional avenues through which cropping systems may be leveraged to enhance pest management.
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.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
The Repugnant Conclusion is an implication of some approaches to population ethics. It states, in Derek Parfit's original formulation,
For any possible population of at least ten billion people, all with a very high quality of life, there must be some much larger imaginable population whose existence, if other things are equal, would be better, even though its members have lives that are barely worth living. (Parfit 1984: 388)
Roads affect wildlife in a variety of negative ways. Road ecology studies have mostly concentrated on areas in the northern hemisphere despite the potentially greater impact of roads on biodiversity in tropical habitats. Here, we examine 4 years (January 2016–December 2019) of opportunistic observations of mammalian roadkill along a road intersecting Jozani-Chwaka Bay National Park, Unguja, Zanzibar. In particular, we assess the impact of collisions on the population of an endemic primate, the Endangered Zanzibar red colobus Piliocolobus kirkii. Primates accounted for the majority of roadkill in this dataset. Monthly rainfall was not associated with roadkill frequency for mammals generally, nor for the Zanzibar red colobus. No single age–sex class of colobus was found dead more often than expected given their occurrence in the local population. The overall effect of roadkill on colobus populations in habitats fragmented by roads is unknown given the lack of accurate, long-term life history data for this species. Our findings suggest that mortality from collisions with vehicles in some groups of colobus is within the range of mortality rates other primates experience under natural predation. Unlike natural predators, however, vehicles do not kill selectively, so their impact on populations may differ. Although a comparison with historical accounts suggests that the installation of speedbumps along the road near the Park's entrance has led to a significant decrease in colobus roadkill, further actions to mitigate the impact of the road could bring substantial conservation benefits.
Despite evidence for the general effectiveness of psychological therapies, there exists substantial heterogeneity in patient outcomes. We aimed to identify factors associated with baseline severity of depression and anxiety symptoms, rate of symptomatic change over the course of therapy, and symptomatic recovery in a primary mental health care setting.
Using data from a service evaluation involving 35 527 patients in England's psychological and wellbeing [Improving Access to Psychological Therapies (IAPT)] services, we applied latent growth models to explore which routinely-collected sociodemographic, clinical, and therapeutic variables were associated with baseline symptom severity and rate of symptomatic change. We used a multilevel logit model to determine variables associated with symptomatic recovery.
Being female, younger, more functionally impaired, and more socioeconomically disadvantaged was associated with higher baseline severity of both depression and anxiety symptoms. Being older, less functionally impaired, and having more severe baseline symptomatology was associated with more rapid improvement of both depression and anxiety symptoms (male gender and greater socioeconomic disadvantage were further associated with rate of change for depression only). Therapy intensity and appointment frequency seemed to have no correlation with rate of symptomatic improvement. Patients with lower baseline symptom severity, less functional impairment, and older age had a greater likelihood of achieving symptomatic recovery (as defined by IAPT criteria).
We must continue to investigate how best to tailor psychotherapeutic interventions to fit patients’ needs. Patients who begin therapy with more severe depression and/or anxiety symptoms and poorer functioning merit special attention, as these characteristics may negatively impact recovery.
Influential theories predict that antidepressant medication and psychological therapies evoke distinct neural changes.
To test the convergence and divergence of antidepressant- and psychotherapy-evoked neural changes, and their overlap with the brain's affect network.
We employed a quantitative synthesis of three meta-analyses (n = 4206). First, we assessed the common and distinct neural changes evoked by antidepressant medication and psychotherapy, by contrasting two comparable meta-analyses reporting the neural effects of these treatments. Both meta-analyses included patients with affective disorders, including major depressive disorder, generalised anxiety disorder and panic disorder. The majority were assessed using negative-valence tasks during neuroimaging. Next, we assessed whether the neural changes evoked by antidepressants and psychotherapy overlapped with the brain's affect network, using data from a third meta-analysis of affect-based neural activation.
Neural changes from psychotherapy and antidepressant medication did not significantly converge on any region. Antidepressants evoked neural changes in the amygdala, whereas psychotherapy evoked anatomically distinct changes in the medial prefrontal cortex. Both psychotherapy- and antidepressant-related changes separately converged on regions of the affect network.
This supports the notion of treatment-specific brain effects of antidepressants and psychotherapy. Both treatments induce changes in the affect network, but our results suggest that their effects on affect processing occur via distinct proximal neurocognitive mechanisms of action.
Plant-derived proteins have been suggested to have less anabolic properties when compared with animal-derived proteins. Whether blends of plant- and animal-derived proteins can compensate for their lesser anabolic potential has not been assessed. The present study compares post-prandial muscle protein synthesis rates following the ingestion of milk protein with wheat protein or a blend of wheat plus milk protein in healthy, young males. In a randomised, double-blind, parallel-group design, 36 males (23 (sd 3) years) received a primed continuous L-[ring-13C6]-phenylalanine infusion after which they ingested 30 g milk protein (MILK), 30 g wheat protein (WHEAT) or a 30 g blend combining 15 g wheat plus 15 g milk protein (WHEAT+MILK). Blood and muscle biopsies were collected frequently for 5 h to assess post-prandial plasma amino acid profiles and subsequent myofibrillar protein synthesis rates. Ingestion of protein increased myofibrillar protein synthesis rates in all treatments (P < 0·001). Post-prandial myofibrillar protein synthesis rates did not differ between MILK v. WHEAT (0·053 (sd 0·013) v. 0·056 (sd 0·012) %·h−1, respectively; t test P = 0·56) or between MILK v. WHEAT+MILK (0·053 (sd 0·013) v. 0·059 (sd 0·025) %·h−1, respectively; t test P = 0·46). In conclusion, ingestion of 30 g milk protein, 30 g wheat protein or a blend of 15 g wheat plus 15 g milk protein increases muscle protein synthesis rates in young males. Furthermore, muscle protein synthesis rates following the ingestion of 30 g milk protein do not differ from rates observed after ingesting 30 g wheat protein or a blend with 15 g milk plus 15 g wheat protein in healthy, young males.
Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.
The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias.
A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses.
MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = −0.42) and underestimation (e.g. magical thinking, d = −0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition.
Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.
Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
OBJECTIVES/GOALS: The North Carolina Translational and Clinical Sciences Institute (NC TraCS) supports faculty and staff in carrying out clinical and translational research at UNC-Chapel Hill. To better understand customer satisfaction and impact, a survey was administered among NC TraCS users. METHODS/STUDY POPULATION: NC TraCS has 13 program areas that range from Biostatistics to Community and Stakeholder Engagement. These programs provide services to faculty, staff, students, and outside researchers in the area of clinical and translational science. A customer feedback survey was administered in Spring 2019 to anyone who had used at least one NC TraCS service between March 1st, 2017 and February 28th, 2019. A total of 856 survey invitations were sent. The survey included questions around users’ perception of the ease of access, helpfulness, outcome, and promptness of the services received using 6-point Likert scale. The survey also addressed career impact, communications, and suggestions for improvement. RESULTS/ANTICIPATED RESULTS: We received 268 responses, (31% response). Majority of respondents were satisfied with Overall Helpfulness (95%), Outcome of Service (96%), Ease of Access (93%), and Promptness of Service (90%). They also noted that their careers had at least slightly improved in the following areas: Mentorship (76%), Research Methods (75%), Skill Development (77%), Research Direction (71%) and Collaboration (80%). Furthermore, 96% responded positively to returning to TraCS. The feedback received was shared with service administrators and NC TraCS leadership to identify areas of improvement and further strengthen their services. Concerns, when present, were addressed by service directors or the overall PI’s. DISCUSSION/SIGNIFICANCE OF IMPACT: Need to communicate expectations to customers the expected turn-around time for help emerged as a clear take-away. In response, TraCS leadership is working to improve staffing and workflows for efficient service delivery including expectation management, especially among the most popular services.