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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.
Methods:
Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.
Results:
Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).
Discussion:
Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.
Treatment guidelines recommend evidence-based psychological therapies for adults with intellectual disabilities with co-occurring anxiety or depression. No previous research has explored the effectiveness of these therapies in mainstream psychological therapy settings or outside specialist settings.
Aims
To evaluate the effectiveness of psychological therapies delivered in routine primary care settings for people with intellectual disability who are experiencing co-occurring depression or anxiety.
Method
This study used linked electronic healthcare records of 2 048 542 adults who received a course of NHS Talking Therapies for anxiety and depression in England between 2012 and 2019 to build a retrospective, observational cohort of individuals with intellectual disability, matched 1:2 with individuals without intellectual disability. Logistic regressions were used to compare metrics of symptom improvement and deterioration used in the national programme, on the basis of depression and anxiety measures collected before and at the last attended therapy session.
Results
The study included 6870 adults with intellectual disability and 2 041 672 adults without intellectual disability. In unadjusted analyses, symptoms improved on average for people with intellectual disability after a course of therapy, but these individuals experienced poorer outcomes compared with those without intellectual disability (reliable improvement 60.2% for people with intellectual disability v. 69.2% for people without intellectual disability, odds ratio 0.66, 95% CI 0.63–0.70; reliable deterioration 10.3% for people with intellectual disability v. 5.7% for those without intellectual disability, odds ratio 1.89, 95% CI 1.75–2.04). After propensity score matching, some differences were attenuated (reliable improvement, adjusted odds ratio 0.97, 95% CI 1.91–1.04), but some outcomes remained poorer for people with intellectual disability (reliable deterioration, adjusted odds ratio 1.28, 95% CI 1.16–1.42).
Conclusions
Evidence-based psychological therapies may be effective for adults with intellectual disability, but their outcomes may be similar to (for improvement and recovery) or poorer than (for deterioration) those for adults without intellectual disability. Future work should investigate the impact of adaptations of therapies for those with intellectual disability to make such interventions more effective and accessible for this population.
The antibiotic spectrum index (ASI) outcome quantifies antibiotic exposure based on spectrum of activity. Our objective was to examine ASI as an exploratory outcome in the context of a recent stewardship-focused, clinical trial in childhood pneumonia that originally used a binary guideline-concordant outcome.
Design:
Secondary analysis of a randomized clinical trial.
Setting:
Two tertiary pediatric hospitals.
Methods:
Encounters were randomly assigned to clinical decision support (CDS) or usual care treatment arm. The ASI was calculated by summing daily ASI scores for each unique antibiotic administered. It was evaluated as a continuous and ordinal measure: No Antibiotics (ASI = 0), Narrow (1-2), Intermediate (3-4), Broad (5-7), and Very Broad (≥8). Proportional odds regression modeled the ordinal ASI outcome in the first 24 hours by treatment arm and compared to the guideline-concordance outcome. Results were stratified by emergency department (ED) disposition. We also conducted a longitudinal, descriptive analysis of day-to-day ASI for those with in-hospital dispositions.
Results:
We included 1027 encounters, 549 (53%) were randomized to CDS and 478 (47%) usual care respectively. ASI Category did not differ by treatment arm overall (Odds Ratio: 0.88[95% Confidence Interval: 0.70,1.09]), which mirrored binary guideline-concordance. Mean ASI was lower for concordant encounters (2.1 vs 8.4, P < 0.001) and across all ED dispositions. In the longitudinal analysis, there were 1137 day-to-day ASI comparisons, with only 7% representing spectrum escalations.
Conclusions:
The ASI outcome yielded similar results to a dichotomous concordance outcome. However, ASI provided more granular insights into antibiotic prescribing, suggesting ASI may be a useful outcome measure in future stewardship-focused trials.
Current clinical guidelines for people at risk of heart disease in Australia recommend nutrition intervention in conjunction with pharmacotherapy(1). However, Australians living in rural and remote regions have less access to medical nutritional therapy (MNT) provided by Accredited Practising Dietitians (APDs) than their urban counterparts(2). The aim of the HealthyRHearts study was to trial the delivery of MNT by APDs using telehealth to eligible patients of General Practitioners (GPs) located in small to large rural towns in the Hunter New England region(3) of New South Wales, Australia. The study design was a 12-month pragmatic randomised controlled trial. The key outcome was reduced total cholesterol. The study was place-based, meaning many of the research team and APDs were based rurally, to ensure the context of the GPs and patients was already known. Eligible participants were those assessed as moderate-to-high risk of CVD by their GP. People in the intervention group received five MNT consults (totalling two hours) delivered via telehealth by APDs, and also answered a personalised nutrition questionnaire to guide their priorities and to support personalised dietary behaviour change during the counselling. Both intervention and control groups received usual care from their GP and were provided access to the Australian Eating Survey (Heart version), a 242-item online food frequency questionnaire with technology-supported personalised nutrition reports that evaluated intake relative to heart healthy eating principles. Of the 192 people who consented to participate, 132 were eligible due to their moderate-to-high risk. Pre-post participant medication use with a registered indication(4) for hypercholesterolemia, hypertension and glycemic control were documented according to class and strength (defined daily dose: DDD)(5). Nine GP practices (with 91 participants recruited) were randomised to the intervention group and seven practices (41 participants) were randomised to control. Intervention participants attended 4.3 ± 1.4 out of 5 dietetic consultations offered. Of the132 people with baseline clinical chemistry, 103 also provided a 12-month sample. Mean total cholesterol at baseline was 4.97 ± 1.13 mmol/L for both groups, with 12-m reduction of 0.26 ± 0.77 for intervention and 0.28 ± 0.79 for control (p = 0.90, unadjusted value). Median (IQR) number of medications for the intervention group was 2 (1–3) at both baseline and 12 months (p = 0.78) with 2 (1–3) and 3 (2–3) for the control group respectively. Combined DDD of all medications was 2.1 (0.5–3.8) and 2.5 (0.75–4.4) at baseline and 12 months (p = 0.77) for the intervention group and 2.7 (1.5–4.0) and 3.0 (2.0–4.5) for the control group (p = 0.30). Results suggest that medications were a significant contributor to the management of total cholesterol. Further analysis is required to evaluate changes in total cholesterol attributable to medication prescription relative to the MNT counselling received by the intervention group.
Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
Since cannabis was legalized in Canada in 2018, its use among older adults has increased. Although cannabis may exacerbate cognitive impairment, there are few studies on its use among older adults being evaluated for cognitive disorders.
Methods:
We analyzed data from 238 patients who attended a cognitive clinic between 2019 and 2023 and provided data on cannabis use. Health professionals collected information using a standardized case report form.
Results:
Cannabis use was reported by 23 out of 238 patients (9.7%): 12 took cannabis for recreation, 8 for medicinal purposes and 3 for both purposes. Compared to non-users, cannabis users were younger (mean ± SD 62.0 ± 7.5 vs 68.9 ± 9.5 years; p = 0.001), more likely to have a mood disorder (p < 0.05) and be current or former cigarette smokers (p < 0.05). There were no significant differences in sex, race or education. The proportion with dementia compared with pre-dementia cognitive states did not differ significantly in users compared with non-users. Cognitive test scores were similar in users compared with non-users (Montreal Cognitive Assessment: 20.4 ± 5.0 vs 20.7 ± 4.5, p = 0.81; Folstein Mini-Mental Status Exam: 24.5 ± 5.1 vs 26.0 ± 3.6, p = 0.25). The prevalence of insomnia, obstructive sleep apnea, anxiety disorders, alcohol use or psychotic disorders did not differ significantly.
Conclusion:
The prevalence of cannabis use among patients with cognitive concerns in this study was similar to the general Canadian population aged 65 and older. Further research is necessary to investigate patients’ motivations for use and explore the relationship between cannabis use and mood disorders and cognitive decline.
The recommended first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBTi), but access is limited. Telehealth- or internet-delivered CBTi are alternative ways to increase access. To date, these intervention modalities have never been compared within a single study. Further, few studies have examined (a) predictors of response to the different modalities, (b) whether successfully treating insomnia can result in improvement of health-related biomarkers, and (c) mechanisms of change in CBTi. This protocol was designed to compare the three CBTi modalities to each other and a waitlist control for adults aged 50–65 years (N = 100). Participants are randomly assigned to one of four study arms: in-person- (n = 30), telehealth- (n = 30) internet-delivered (n = 30) CBTi, or 12-week waitlist control (n = 10). Outcomes include self-reported insomnia symptom severity, polysomnography, circadian rhythms of activity and core body temperature, blood- and sweat-based biomarkers, cognitive functioning and magnetic resonance imaging.
Hand, foot and mouth disease (HFMD) is a contagious communicable disease, with a high incidence in children aged under 10 years. It is a mainly self-limiting disease but can also cause serious neurological or cardiopulmonary complications in some cases, which can lead to death. Little is known about the burden of HMFD on primary care health care services in the UK. The aim of this work was to describe trends in general practitioner (GP) consultations for HFMD in England from January 2017 to December 2022 using a syndromic surveillance network of GPs. Daily GP consultations for HFMD in England were extracted from 1 January 2017 to 31 December 2022. Mean weekly consultation rates per 100,000 population and 95% confidence intervals (CI) were calculated. Consultation rates and rate ratios (RR) were calculated by age group and sex. During the study period, the mean weekly consultation rate for HFMD (per 100,000 registered GP patients) was 1.53 (range of 0.27 to 2.47). In England, children aged 1–4 years old accounted for the largest affected population followed by children <1 years old. We observed a seasonal pattern of HFMD incidence during the non-COVID years, with a seasonal peak of mean weekly rates between months of September and December. HFMD is typically diagnosed clinically rather than through laboratory sampling. Therefore, the ability to look at the daily HFMD consultation rates provides an excellent epidemiological overview on disease trends. The use of a novel GP-in-hours surveillance system allowed a unique epidemiological insight into the recent trends of general practitioner consultations for HFMD. We demonstrate a male predominance of cases, the impact of the non-pharmaceutical interventions during the COVID-19 pandemic, and a change in the week in which the peak number of cases happens post-pandemic.
We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.
In Michigan, the COVID-19 pandemic severely impacted Black and Latinx communities. These communities experienced higher rates of exposure, hospitalizations, and deaths compared to Whites. We examine the impact of the pandemic and reasons for the higher burden on communities of color from the perspectives of Black and Latinx community members across four Michigan counties and discuss recommendations to better prepare for future public health emergencies.
Methods:
Using a community-based participatory research approach, we conducted semi-structured interviews (n = 40) with Black and Latinx individuals across the four counties. Interviews focused on knowledge related to the pandemic, the impact of the pandemic on their lives, sources of information, attitudes toward vaccination and participation in vaccine trials, and perspectives on the pandemic’s higher impact on communities of color.
Results:
Participants reported overwhelming effects of the pandemic in terms of worsened physical and mental health, financial difficulties, and lifestyle changes. They also reported some unexpected positive effects. They expressed awareness of the disproportionate burden among Black and Latinx populations and attributed this to a wide range of disparities in Social Determinants of Health. These included racism and systemic inequities, lack of access to information and language support, cultural practices, medical mistrust, and varied individual responses to the pandemic.
Conclusion:
Examining perspectives and experiences of those most impacted by the pandemic is essential for preparing for and effectively responding to public health emergencies in the future. Public health messaging and crisis response strategies must acknowledge the concerns and cultural needs of underrepresented populations.
Weeds are one of the greatest challenges to snap bean (Phaseolus vulgaris L.) production. Anecdotal observation posits certain species frequently escape the weed management system by the time of crop harvest, hereafter called residual weeds. The objectives of this work were to (1) quantify the residual weed community in snap bean grown for processing across the major growing regions in the United States and (2) investigate linkages between the density of residual weeds and their contributions to weed canopy cover. In surveys of 358 fields across the Northwest (NW), Midwest (MW), and Northeast (NE), residual weeds were observed in 95% of the fields. While a total of 109 species or species-groups were identified, one to three species dominated the residual weed community of individual fields in most cases. It was not uncommon to have >10 weeds m−2 with a weed canopy covering >5% of the field’s surface area. Some of the most abundant and problematic species or species-groups escaping control included amaranth species such as smooth pigweed (Amaranthus hybridus L.), Palmer amaranth (Amaranthus palmeri S. Watson), redroot pigweed (Amaranthus retroflexus L.), and waterhemp [Amaranthus tuberculatus (Moq.) Sauer]; common lambsquarters (Chenopodium album L.); large crabgrass [Digitaria sanguinalis (L.) Scop.]; and ivyleaf morningglory (Ipomoea hederacea Jacq.). Emerging threats include hophornbeam copperleaf (Acalypha ostryifolia Riddell) in the MW and sharppoint fluvellin [Kickxia elatine (L.) Dumort.] in the NW. Beyond crop losses due to weed interference, the weed canopy at harvest poses a risk to contaminating snap bean products with foreign material. Random forest modeling predicts the residual weed canopy is dominated by C. album, D. sanguinalis, carpetweed (Mollugo verticillata L.), I. hederacea, amaranth species, and A. ostryifolia. This is the first quantitative report on the weed community escaping control in U.S. snap bean production.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
We conducted a quantitative analysis of the microbial burden and prevalence of epidemiologically important pathogens (EIP) found on long-term care facilities (LTCF) environmental surfaces.
Methods:
Microbiological samples were collected using Rodac plates (25cm2/plate) from resident rooms and common areas in five LTCFs. EIP were defined as MRSA, VRE, C. difficile and multidrug-resistant (MDR) Gram-negative rods (GNRs).
Results:
Rooms of residents with reported colonization had much greater EIP counts per Rodac (8.32 CFU, 95% CI 8.05, 8.60) than rooms of non-colonized residents (0.78 CFU, 95% CI 0.70, 0.86). Sixty-five percent of the resident rooms and 50% of the common areas were positive for at least one EIP. If a resident was labeled by the facility as colonized with an EIP, we only found that EIP in 30% of the rooms. MRSA was the most common EIP recovered, followed by C. difficile and MDR-GNR.
Discussion:
We found frequent environmental contamination with EIP in LTCFs. Colonization status of a resident was a strong predictor of higher levels of EIP being recovered from his/her room.
From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.
Amaranthus species are problematic weeds in snap bean production systems. They reduce crop yields, and their stem fragments contaminate harvested pods. Knowledge of snap bean tolerance to different preemergence herbicides is limited; however, knowing this tolerance is essential for planning a reliable weed management system, breeding herbicide-tolerant cultivars, and registering herbicides for use on minor crops such as snap bean. Field trials were conducted in 2021 and 2022 to determine the tolerance of eight snap bean cultivars to preemergence herbicides with activity on Amaranthus species, including dimethenamid-P, flumioxazin, lactofen, metribuzin, saflufenacil, and sulfentrazone. Snap bean plant density (number of plants per square meter), plant biomass (grams per plant), and canopy biomass (grams per square meter) 21 d after treatment were used to assess crop tolerance to a range of herbicide rates. Linear mixed-effects regression models were fitted to quantify the relationships between preemergence herbicide rate and snap bean cultivar tolerance. Results indicated a high margin of crop safety with dimethenamid-P and lactofen for weed control in snap bean, and a low margin of crop safety with metribuzin and saflufenacil. Results indicated differential cultivar tolerance to flumioxazin and sulfentrazone, which could be driven by genetic variability among cultivars.
This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public–private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives’ involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic.
The expensive-tissue hypothesis (ETH) posited a brain–gut trade-off to explain how humans evolved large, costly brains. Versions of the ETH interrogating gut or other body tissues have been tested in non-human animals, but not humans. We collected brain and body composition data in 70 South Asian women and used structural equation modelling with instrumental variables, an approach that handles threats to causal inference including measurement error, unmeasured confounding and reverse causality. We tested a negative, causal effect of the latent construct ‘nutritional investment in brain tissues’ (MRI-derived brain volumes) on the construct ‘nutritional investment in lean body tissues’ (organ volume and skeletal muscle). We also predicted a negative causal effect of the brain latent on fat mass. We found negative causal estimates for both brain and lean tissue (−0.41, 95% CI, −1.13, 0.23) and brain and fat (−0.56, 95% CI, −2.46, 2.28). These results, although inconclusive, are consistent with theory and prior evidence of the brain trading off with lean and fat tissues, and they are an important step in assessing empirical evidence for the ETH in humans. Analyses using larger datasets, genetic data and causal modelling are required to build on these findings and expand the evidence base.