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Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.
Methods
This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes. Cognitive function was measured by the Perceived Deficits Questionnaire (PDQ-5), the Digit Symbol Substitution Test (DSST), and the Trail Making Test Part B (TMT-B). Depression symptom severity was measured by the Montgomery–Åsberg Depression Rating Scale (MADRS). Workplace function was measured by the Sheehan Disability Scale (SDS) work–school item.
Results
When co-varying for BMI, age, and sex, the association between MADRS and SDS work scores was partially mediated by PDQ-5 total scores and DSST total scores, but not DSST error scores and TMT-B time.
Limitations
This study was insufficiently powered to perform sub-group analyses to identify distinctions between MDD and BD populations as well as between antidepressant agents.
Conclusions
These findings suggest that cognitive impairment in adults with MDD and BD is a critical mediator of workplace function and reinforces its importance as a therapeutic target.
Pharmacogenomic (PGx) testing identifies individual genetic variation that may inform medication treatment. Sentiment and barriers may limit PGx testing. Here we compare confidence in utilizing PGx testing and barriers to implementation by type of provider and treatment condition as identified in a survey.
Methods
Healthcare providers in the primary care setting were targeted between November 2022 and February 2023 via the Medscape Members paid market research program. The survey included 5 demographic, 5 multiple-choice, and 4 multi-component five-point Likert scale questions to assess PGx sentiments, use, and education in mental health (e.g., depression) and primary care (e.g., cardiovascular disease) conditions. Responses were descriptively compared.
Results
Of 305 U.S. provider respondents [40% nurse practitioners (NPs), 33% frontline MDs/DOs, 3% physician assistants (PAs), 24% other], 32% of NPs/PAs and 29% of MDs/DOs had used PGx testing for mental health conditions. The major barriers to adopt PGx testing were similar for mental health and primary care conditions yet differed by provider type. NPs/PAs (72-77%) were more concerned with patient cost than MDs/DOs (46-55%), whereas MDs/DOs were more concerned with evidence of clinical utility (54-59%) than NPs/PAs (40-42%). In respondents who use PGx testing, MDs/DOs reported slightly more confidence utilizing PGx than NPs/PAs. For both groups, confidence in using PGx for mental health conditions was somewhat greater than for non-mental health conditions.
Conclusions
These data illuminate the implementation barriers and confidence levels of clinicians utilizing PGx testing. Increasing awareness around patient cost and evidence of clinical utility for PGx testing may improve utilization.
Pharmacogenomic (PGx) testing identifies individual genetic variation that may inform medication treatment. Lack of awareness and education may be barriers to implementing routine PGx testing. To characterize current PGx testing utilization and educational needs we conducted a survey of various provider types.
Methods
Healthcare providers in the primary care setting were targeted between November 2022 and February 2023 via the Medscape Members paid market research program. The survey included 5 demographic, 5 multiple-choice, and 4 multi-component five-point Likert scale questions to assess PGx sentiments, use, and education in mental health (e.g., depression) and primary care (e.g., cardiovascular disease) conditions. Responses were descriptively compared.
Results
Of 305 U.S. provider respondents [40% nurse practitioners (NPs), 33% frontline MDs/DOs, 3% physician assistants (PAs), 24% other], most indicated that they “don’t use” (44-49%) or “have never heard of” (19-20%) PGx testing for mental health conditions. The most helpful sources to learn about PGx testing were accredited CE/CME activities (55-61%) and peer-reviewed publications (57-59%). Most NPs/PAs preferred webinars (62%) or online learning portal (57%) formats. MDs/DOs had no preference for webinars or learning portals over conferences, written materials, or academic presentations (45-47%). NPs/PAs were more interested in learning about PGx testing than MDs/DOs (4.29/5 vs. 3.96/5 average score).
Conclusions
These data reveal awareness level and desired learning opportunities for PGx testing between types of healthcare providers. Education should be tailored to meet providers’ preferred learning formats and information sources, such as offering CE/CME through an online learning portal.
The global population and status of Snowy Owls Bubo scandiacus are particularly challenging to assess because individuals are irruptive and nomadic, and the breeding range is restricted to the remote circumpolar Arctic tundra. The International Union for Conservation of Nature (IUCN) uplisted the Snowy Owl to “Vulnerable” in 2017 because the suggested population estimates appeared considerably lower than historical estimates, and it recommended actions to clarify the population size, structure, and trends. Here we present a broad review and status assessment, an effort led by the International Snowy Owl Working Group (ISOWG) and researchers from around the world, to estimate population trends and the current global status of the Snowy Owl. We use long-term breeding data, genetic studies, satellite-GPS tracking, and survival estimates to assess current population trends at several monitoring sites in the Arctic and we review the ecology and threats throughout the Snowy Owl range. An assessment of the available data suggests that current estimates of a worldwide population of 14,000–28,000 breeding adults are plausible. Our assessment of population trends at five long-term monitoring sites suggests that breeding populations of Snowy Owls in the Arctic have decreased by more than 30% over the past three generations and the species should continue to be categorised as Vulnerable under the IUCN Red List Criterion A2. We offer research recommendations to improve our understanding of Snowy Owl biology and future population assessments in a changing world.
To understand healthcare workers’ (HCWs) beliefs and practices toward blood culture (BCx) use.
Design:
Cross-sectional electronic survey and semi-structured interviews.
Setting:
Academic hospitals in the United States.
Participants:
HCWs involved in BCx ordering and collection in adult intensive care units (ICU) and wards.
Methods:
We administered an anonymous electronic survey to HCWs and conducted semi-structured interviews with unit staff and quality improvement (QI) leaders in these institutions to understand their perspectives regarding BCx stewardship between February and November 2023.
Results:
Of 314 HCWs who responded to the survey, most (67.4%) were physicians and were involved in BCx ordering (82.3%). Most survey respondents reported that clinicians had a low threshold to culture patients for fever (84.4%) and agreed they could safely reduce the number of BCx obtained in their units (65%). However, only half of them believed BCx was overused. Although most made BCx decisions as a team (74.1%), a minority reported these team discussions occurred daily (42.4%). A third of respondents reported not usually collecting the correct volume per BCx bottle, half were unaware of the improved sensitivity of 2 BCx sets, and most were unsure of the nationally recommended BCx contamination threshold (87.5%). Knowledge regarding the utility of BCx for common infections was limited.
Conclusions:
HCWs’ understanding of best collection practices and yield of BCx was limited.
Extant literature reveals how patients of marginalized social identities, socioeconomic status (SES), and medical experiences – especially patients of color and older adults – are underrepresented in cancer clinical trials (CCTs). Emerging evidence increasingly indicates CCT underrepresentation among patients of lower SES or rural origin, sexual and gender minorities, and patients with comorbid disability. This review applies an intersectional perspective to characterizing CCT representativeness across race and ethnicity, age, sexual and gender identity, SES, and disability. Four databases were systematically queried for articles addressing CCT participation inequities across these marginalizing indicators, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. One hundred one articles were included in a qualitative evaluation of CCT representativeness within each target population in the context of their intersectional impacts on participation. Findings corroborate strong evidence of CCT underrepresentation among patients of color, older age, lower SES, rural origin, and comorbid disabling conditions while highlighting systemic limitations in data available to characterize representativeness. Results emphasize how observed inequities interactively manifest through the compounding effects of minoritized social identity, inequitable economic conditions, and marginalizing medical experiences. Recommendations are discussed to more accurately quantify CCT participation inequities across underserved cancer populations and understand their underpinning mechanisms.
The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
Past studies indicate daily increases in estrogen across the menstrual cycle protect against binge-eating (BE) phenotypes (e.g. emotional eating), whereas increases in progesterone enhance risk. Two previous studies from our laboratory suggest these associations could be due to differential genomic effects of estrogen and progesterone. However, these prior studies were unable to directly model effects of daily changes in hormones on etiologic risk, instead relying on menstrual cycle phase or mean hormone levels. The current study used newly modified twin models to examine, for the first time, the effects of daily changes in estradiol and progesterone on genetic/environmental influences on emotional eating in our archival twin sample assessed across 45 consecutive days.
Methods
Participants included 468 female twins from the Michigan State University Twin Registry. Daily emotional eating was assessed with the Dutch Eating Behavior Questionnaire, and daily saliva samples were assayed for ovarian hormone levels. Modified genotype × environment interaction models examined daily changes in genetic/environmental effects across hormone levels.
Results
Findings revealed differential effects of daily changes in hormones on etiologic risk, with increasing genetic influences across progesterone levels, and increasing shared environmental influences at the highest estradiol levels. Results were consistent across primary analyses examining all study days and sensitivity analyses within menstrual cycle phases.
Conclusions
Findings are significant in being the first to identify changes in etiologic risk for BE symptoms across daily hormone levels and highlighting novel mechanisms (e.g. hormone threshold effects, regulation of conserved genes) that may contribute to the etiology of BE.
Achieving equitable healthcare access is a global challenge. Improving whole-population mental health and reducing the global burden of mental disorders is a key recommendation of the 2018 Lancet Global Mental Health Commission, which proposed monitoring national indicators, including the proportion of people with severe mental disorders who are service-users. This study aims to derive an equity indicator from national datasets integrating need, service utilisation and socioeconomic status, and demonstrate its utility in identifying gaps in mental health service use amongst those with the greatest need, thereby guiding equitable healthcare delivery.
Methods
We present a case study of a universal health insurance scheme (Medicare) in Australia. We developed the equity indicator using three national datasets. Geographic areas were linked to an area-based socioeconomic deprivation quintile (Census 2016). Per geographic area, we estimated the number with a mental healthcare need using scores ≥30 on the Kessler-10 (Australian National Health Surveys 2015 and 2018), and obtained the number of services used, defined as mental health-related contacts with general practitioners and mental health professionals (Medicare administrative data 2015–2019). We divided the number of services by the population with an estimated mental healthcare need and averaged these use-rates across each socioeconomic deprivation quintile. The equity indicator is the ratio of the use-rates in the least versus most deprived quintiles.
Results
Those estimated to have the greatest need for mental healthcare in 2019 ranged between 8.2% in the most disadvantaged area quintile (Q1) and 2.4% in the least (Q5), corresponding to a proportional increase of 27.7% in Q1 and 19.5% in Q5 since 2015. Equity-indicator-adjusted service rates of 4.2 (3.8–4.6) and 23.9 (22.4–25.4) showed that individuals with the highest need for care residing in Q1 areas received a stark 6 times fewer services compared to their Q5 counterparts, producing an equity indicator of 6.
Conclusions
As the global prevalence of common mental disorders may be increasing, it is crucial to calculate robust indicators evaluating the equity of mental health service use. In this Australian case study, we developed an equity indicator enabling the direct comparison of geographic areas with different need profiles. The results revealed striking inequities that persisted despite publicly-funded universal healthcare, recent service reforms and being a high-income country. This study demonstrates the importance and feasibility of generating such an indicator to inform and empower communities, healthcare providers and policymakers to pursue equitable service provision.
The population of adults with single-ventricle congenital heart disease (CHD) is growing. This study explores their lived experiences through an adult developmental psychology framework.
Methods:
Individuals aged 18 and older with single-ventricle CHD participated in Experience Group sessions and 1:1 interviews. Sessions were transcribed and analysed thematically. Themes were categorized by developmental domains and age group.
Results:
Of the 29 participants, 18 (62%) were female, 10 (35%) were emerging (18–29 years), 13 (45%) were established (30–45 years), and 6 (21%) were midlife adults (46–60 years). Emerging adults expressed reluctance to initiate romantic relationships and fear of burdening partners, while established adults reported strong relationships with partners deeply involved in caregiving. Emerging adults struggled with finding fulfilling work that meets their health needs, whereas established and midlife adults faced unemployment or early retirement due to health limits. Family dynamics shifted, with established and midlife adults educating their children to become caregivers. Physical limitations and low self-rated health were consistent across life stages, and midlife adults did not worry about traditional chronic conditions. Mental health concerns, including anxiety and depression, persisted across all life stages, but resiliency and positive affect were also evident.
Conclusion:
Adults with single-ventricle CHD experience developmental milestones differently, indicating the need for early anticipatory guidance in these domains to achieve optimal outcomes in adulthood.
Youth in sub-Saharan Africa (SSA) face limited access to professional mental health resources. A comprehensive assessment of the prevalence of mental disorders would build an understanding of the scope of the need.
We conducted systematic searches in PsycInfo, Pubmed, AfriBib and Africa Journals Online to identify prevalence rates for five disorders (anxiety, depression, conduct disorder, attention problems and post-traumatic stress) among SSA youth with a mean age of less than 19 years. We calculated a random-effects pooled prevalence for each disorder and assessed possible moderators.
The meta-analysis included 63 studies with 55,071 participants. We found the following pooled prevalence rates: 12.53% post-traumatic stress disorder (PTSD), 15.27% depression, 6.55% attention-deficit hyperactivity disorder, 11.78% anxiety and 9.76% conduct disorder. We found high heterogeneity across the studies, which may have resulted from differences in samples or measurement tools. Reported prevalence rates were not explained by the sample (i.e., special or general population), but whether the psychometric tool was validated for SSA youth affected the reported prevalence of PTSD and anxiety. In a meta-regression, prevalence rates were associated with the disorder type, with a higher prevalence of depression and PTSD. We found the mean age significantly moderated the prevalence in univariate meta-regression, with increased age correlated with greater prevalence.
Our findings suggest there is a need to explore reasons for varying prevalence rates further and to develop interventions that support youth mental health in SSA, particularly interventions for depression and PTSD. Limitations included a lack of standardization in psychometric tools and limited reporting on research methods, which influenced quality rating. Importantly, the search only considered studies published in English and was conducted 2 years ago. Although recent estimates reported slightly higher than our prevalence estimates, these reviews together highlight the prevalence and importance of youth mental health difficulties in SSA.
Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.
Methods
Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.
Results
Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.
Conclusions
While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.
Structure-switching aptamers have become ubiquitous in several applications, notably in analytical devices such as biosensors, due to their ease of supporting strong signaling. Aside from their ability to bind specifically with their respective target, this class of aptamers also undergoes a conformational rearrangement upon target recognition. While several well-studied and early-developed aptamers (e.g., cocaine, ATP, and thrombin) have been found to have this structure-switching property, the vast majority do not. As a result, it is common to try to engineer aptamers into switches. This proves challenging in part because of the difficulty in obtaining structural and functional information about aptamers. In response, we review various readily available biophysical characterization tools that are capable of assessing structure switching of aptamers. In doing so, we delve into the fundamentals of these different techniques and detail how they have been utilized in characterizing structure-switching aptamers. While each of these biophysical techniques alone has utility, their real power to demonstrate the occurrence of structural change with ligand binding is when multiple techniques are used. We hope that through a deeper understanding of these techniques, researchers will be better able to acquire biophysical information about their aptamer–ligand systems and accelerate the translation of aptamers into biosensors.
Major depressive disorder (MDD) is a tremendous global disease burden and the leading cause of disability worldwide. Unfortunately, individuals diagnosed with MDD typically experience a delayed response to traditional antidepressants and many do not adequately respond to pharmacotherapy, even after multiple trials. The critical need for novel antidepressant treatments has led to a recent resurgence in the clinical application of psychedelics, and intravenous ketamine, which has been investigated as a rapid-acting treatment for treatment resistant depression (TRD) as well acute suicidal ideation and behavior. However, variations in the type and quality of experimental design as well as a range of treatment outcomes in clinical trials of ketamine make interpretation of this large body of literature challenging.
Objectives
This umbrella review aims to advance our understanding of the effectiveness of intravenous ketamine as a pharmacotherapy for TRD by providing a systematic, quantitative, large-scale synthesis of the empirical literature.
Methods
We performed a comprehensive PubMed search for peer-reviewed meta-analyses of primary studies of intravenous ketamine used in the treatment of TRD. Meta-analysis and primary studies were then screened by two independent coding teams according to pre-established inclusion criteria as well as PRISMA and METRICS guidelines. We then employed metaumbrella, a statistical package developed in R, to perform effect size calculations and conversions as well as statistical tests.
Results
In a large-scale analysis of 1,182 participants across 51 primary studies, repeated-dose administration of intravenous ketamine demonstrated statistically significant effects (p<0.05) compared to placebo-controlled as well as other experimental conditions in patients with TRD, as measured by standardized clinician-administered and self-report depression symptom severity scales.
Conclusions
This study provides large-scale, quantitative support for the effectiveness of intravenous, repeated-dose ketamine as a therapy for TRD and a report of the relative effectiveness of several treatment parameters across a large and rapidly growing literature. Future investigations should use similar analytic tools to examine evidence-stratified conditions and the comparative effectiveness of other routes of administration and treatment schedules as well as the moderating influence of other clinical and demographic variables on the effectiveness of ketamine on TRD and suicidal ideation and behavior.
There has been rapidly growing interest in understanding the pharmaceutical and clinical properties of psychedelic and dissociative drugs, with a particular focus on ketamine. This compound, long known for its anesthetic and dissociative properties, has garnered attention due to its potential to rapidly alleviate symptoms of depression, especially in individuals with treatment-resistant depression (TRD) or acute suicidal ideation or behavior. However, while ketamine’s psychopharmacological effects are increasingly well-documented, the specific patterns of its neural impact remain a subject of exploration and basic questions remain about its effects on functional activation in both clinical and healthy populations.
Objectives
This meta-analysis seeks to contribute to the evolving landscape of neuroscience research on dissociative drugs such as ketamine by comprehensively examining the effects of acute ketamine administration on neural activation, as measured by functional magnetic resonance imaging (fMRI), in healthy participants.
Methods
We conducted a meta-analysis of existing fMRI activation studies of ketamine using multilevel kernel density analysis (MKDA). Following a comprehensive PubMed search, we quantitatively synthesized all published primary fMRI whole-brain activation studies of the effects of ketamine in healthy subjects with no overlapping samples (N=18). This approach also incorporated ensemble thresholding (α=0.05-0.0001) to minimize cluster-size detection bias and Monte Carlo simulations to correct for multiple comparisons.
Results
Our meta-analysis revealed statistically significant (p<0.05-0.0001; FWE-corrected) alterations in neural activation in multiple cortical and subcortical regions following the administration of ketamine to healthy participants (N=306).
Conclusions
These results offer valuable insights into the functional neuroanatomical effects caused by acute ketamine administration. These findings may also inform development of therapeutic applications of ketamine for various psychiatric and neurological conditions. Future studies should investigate the neural effects of ketamine administration, including both short-term and long-term effects, in clinical populations and their relation to clinical and functional improvements.
Bipolar I disorder (BD-I) is a chronic and recurrent mood disorder characterized by alternating episodes of depression and mania; it is also associated with substantial morbidity and mortality and with clinically significant functional impairments. While previous studies have used functional magnetic resonance imaging (fMRI) to examine neural abnormalities associated with BD-I, they have yielded mixed findings, perhaps due to differences in sampling and experimental design, including highly variable mood states at the time of scan.
Objectives
The purpose of this study is to advance our understanding of the neural basis of BD-I and mania, as measured by fMRI activation studies, and to inform the development of more effective brain-based diagnostic systems and clinical treatments.
Methods
We conducted a large-scale meta-analysis of whole-brain fMRI activation studies that compared participants with BD-I, assessed during a manic episode, to age-matched healthy controls. Following PRISMA guidelines, we conducted a comprehensive PubMed literature search using two independent coding teams to evaluate primary studies according to pre-established inclusion criteria. We then used multilevel kernel density analysis (MKDA), a well-established, voxel-wise, whole-brain, meta-analytic approach, to quantitatively synthesize all qualifying primary fMRI activation studies of mania. We used ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias, and 10,000 Monte Carlo simulations to correct for multiple comparisons.
Results
We found that participants with BD-I (N=2,042), during an active episode of mania and relative to age-matched healthy controls (N=1,764), exhibit a pattern of significantly (p<0.05-0.0001; FWE-corrected) different activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
This study supports the formulation of a robust neural basis for BD-I during manic episodes and advances our understanding of the pattern of abnormal activation in this disorder. These results may inform the development of novel brain-based clinical tools for bipolar disorder such as diagnostic biomarkers, non-invasive brain stimulation, and treatment-matching protocols. Future studies should compare the neural signatures of BD-I to other related disorders to facilitate the development of protocols for differential diagnosis and improve treatment outcomes in patients with BD-I.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric condition that frequently originates in early development and is associated with a variety of functional impairments. Despite a large functional neuroimaging literature on ADHD, our understanding of the neural basis of this disorder remains limited, and existing primary studies on the topic include somewhat divergent results.
Objectives
The present meta-analysis aims to advance our understanding of the neural basis of ADHD by identifying the most statistically robust patterns of abnormal neural activation throughout the whole-brain in individuals diagnosed with ADHD compared to age-matched healthy controls.
Methods
We conducted a meta-analysis of task-based functional magnetic resonance imaging (fMRI) activation studies of ADHD. This included, according to PRISMA guidelines, a comprehensive PubMed search and predetermined inclusion criteria as well as two independent coding teams who evaluated studies and included all task-based, whole-brain, fMRI activation studies that compared participants diagnosed with ADHD to age-matched healthy controls. We then performed multilevel kernel density analysis (MKDA) a well-established, whole-brain, voxelwise approach that quantitatively combines existing primary fMRI studies, with ensemble thresholding (p<0.05-0.0001) and multiple comparisons correction.
Results
Participants diagnosed with ADHD (N=1,550), relative to age-matched healthy controls (N=1,340), exhibited statistically significant (p<0.05-0.0001; FWE-corrected) patterns of abnormal activation in multiple brains of the cerebral cortex and basal ganglia across a variety of cognitive control tasks.
Conclusions
This study advances our understanding of the neural basis of ADHD and may aid in the development of new brain-based clinical interventions as well as diagnostic tools and treatment matching protocols for patients with ADHD. Future studies should also investigate the similarities and differences in neural signatures between ADHD and other highly comorbid psychiatric disorders.
Fructose-containing sugars can exaggerate postprandial lipaemia and stimulate hepatic de novo lipogenesis (DNL) when compared to glucose-based carbohydrates(1). Galactose has recently been shown to increase postprandial lipaemia compared to glucose(2), but mechanisms remain uncharacterised. The aim of this study was to assess the effect and mechanisms of lactose-induced lipaemia.
Twenty-four non-obese adults (12 male and 12 female) completed three trials in a randomised, crossover design (28 ± 7-day washout). During trials, participants consumed test drinks containing 50 g fat with 100 g of carbohydrate. The control carbohydrate was a glucose polymer (maltodextrin), the experimental carbohydrate was galactose-containing carbohydrate (lactose) and the active comparator was fructose-containing carbohydrate (sucrose). Hepatic DNL was assessed by the 2H2O method and [U-13C]-palmitate was added to the test drink to trace the fate of the ingested fat. Blood and breath samples were taken to determine plasma metabolite and hormone concentrations, in addition to plasma and breath 2H and 13C enrichments. Data were converted into incremental under the curve (iAUC) and were checked for normality by visual inspection of residuals. Differences between trials were assessed by one-way ANOVA. Where a main effect of trial was detected, post- hoc t-tests were performed to determine which trials differed from lactose according to the principle of closed-loop testing.
The plasma triacylglycerol iAUC (mean ± SD) in response to maltodextrin was 51 ± 68 mmol/L*360 min. Following lactose ingestion, plasma triacylglycerol iAUC increased to 98 ± 88 mmol/L*360 min (p<0.001 vs maltodextrin), which was comparable to sucrose [90 ± 95 mmol/L*360 min (p=0.41 vs lactose)]. Hepatic DNL in response to maltodextrin was 6.6 ± 3.0%. Following ingestion of lactose, hepatic DNL increased to 12.4 ± 6.9% (p=0.02 vs maltodextrin), which was comparable to sucrose [12.2 ± 6.9% (p=0.96 vs lactose)]. Exhaled 13CO2 in response to maltodextrin was 10.4 ± 4.1 mmol/kgFFM*360 min. Following ingestion of lactose, exhaled 13CO2 was 8.8 ± 4.9 mmol/kgFFM*360 min (p=0.09 vs maltodextrin), which was lower than sucrose [11.1 ± 3.9 mmol/kgFFM*360 min (p=0.01 vs lactose)].
These data are consistent with the hypothesis that hepatic de novo lipogenesis contributes to both lactose and sucrose-induced lipaemia and provide a rationale to investigate the longer-term effects of lactose and sucrose on metabolism.
Medical researchers are increasingly prioritizing the inclusion of underserved communities in clinical studies. However, mere inclusion is not enough. People from underserved communities frequently experience chronic stress that may lead to accelerated biological aging and early morbidity and mortality. It is our hope and intent that the medical community come together to engineer improved health outcomes for vulnerable populations. Here, we introduce Health Equity Engineering (HEE), a comprehensive scientific framework to guide research on the development of tools to identify individuals at risk of poor health outcomes due to chronic stress, the integration of these tools within existing healthcare system infrastructures, and a robust assessment of their effectiveness and sustainability. HEE is anchored in the premise that strategic intervention at the individual level, tailored to the needs of the most at-risk people, can pave the way for achieving equitable health standards at a broader population level. HEE provides a scientific framework guiding health equity research to equip the medical community with a robust set of tools to enhance health equity for current and future generations.