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Psychiatric drugs, including antipsychotics and antidepressants, are widely prescribed, even in young and adolescent populations at early or subthreshold disease stages. However, their impact on brain structure remains elusive. Elucidating the relationship between psychotropic medication and structural brain changes could enhance the understanding of the potential benefits and risks associated with such treatment.
Objectives
Investigation of the associations between psychiatric drug intake and longitudinal grey matter volume (GMV) changes in a transdiagnostic sample of young individuals at early stages of psychosis or depression using an unbiased data-driven approach.
Methods
The study sample comprised 247 participants (mean [SD] age = 25.06 [6.13] years, 50.61% male), consisting of young, minimally medicated individuals at clinical high-risk states for psychosis, individuals with recent-onset depression or psychosis, and healthy control individuals. Structural magnetic resonance imaging was used to obtain whole-brain voxel-wise GMV for all participants at two timepoints (mean [SD] time between scans = 11.15 [4.93] months). The multivariate sparse partial least squares (SPLS) algorithm (Monteiro et al. JNMEDT 2016; 271:182-194) was embedded in a nested cross-validation framework to identify parsimonious associations between the cumulative intake of psychiatric drugs, including commonly prescribed antipsychotics and antidepressants, and change in GMV between both timepoints, while additionally factoring in age, sex, and diagnosis. Furthermore, we correlated the retrieved SPLS results to personality domains (NEO-FFI) and childhood trauma (CTQ).
Results
SPLS analysis revealed significant associations between the antipsychotic classes of benzamides, butyrophenones and thioxanthenes and longitudinal GMV decreases in cortical regions including the insula, posterior superior temporal sulcus as well as cingulate, postcentral, precentral, orbital and frontal gyri (Figure 1A-C). These brain regions corresponded most closely to the dorsal and ventral attention, somatomotor, salience and default network (Figure 1D). Furthermore, the medication signature was negatively associated with the personality domains extraversion, agreeableness and conscientiousness and positively associated with the CTQ domains emotional and physical neglect.
Image:
Conclusions
Psychiatric drug intake over a period of one year was linked to distinct GMV reductions in key cortical hubs. These patterns were already visible in young individuals at early or subthreshold stages of mental illness and were further linked to childhood neglect and personality traits. Hence, a better and more in-depth understanding of the structural brain implications of medicating young and adolescent individuals might lead to more cautious, sustainable and targeted treatment strategies.
Community health workers and promotoras (CHW/Ps) have a fundamental role in facilitating research with communities. However, no national standard training exists as part of the CHW/P job role. We developed and evaluated a culturally- and linguistically tailored online research best practices course for CHW/Ps to meet this gap.
Methods:
After the research best practices course was developed, we advertised the opportunity to CHW/Ps nationwide to complete the training online in English or Spanish. Following course completion, CHW/Ps received an online survey to rate their skills in community-engaged research and their perceptions of the course using Likert scales of agreement. A qualitative content analysis was conducted on open-ended response data.
Results:
104 CHW/Ps completed the English or Spanish course (n = 52 for each language; mean age 42 years SD ± 12); 88% of individuals identified as female and 56% identified as Hispanic, Latino, or Spaniard. 96%–100% of respondents reported improvement in various skills. Nearly all CHW/Ps (97%) agreed the course was relevant to their work, and 96% felt the training was useful. Qualitative themes related to working more effectively as a result of training included enhanced skills, increased resources, and building bridges between communities and researchers.
Discussion:
The CHW/P research best practices course was rated as useful and relevant by CHW/Ps, particularly for communicating about research with community members. This course can be a professional development resource for CHW/Ps and could serve as the foundation for a national standardized training on their role related to research best practices.
To examine: (1) cross-sectional and longitudinal associations between measures of food insecurity (FI; household status and youth-reported) and intuitive eating (IE) from adolescence to emerging adulthood; and (2) the association between FI persistence and IE in emerging adulthood.
Design:
Longitudinal population-based study. Young people reported IE and FI (two items from the US Household Food Security Module) in adolescence and emerging adulthood. Parents provided data on household FI via the six-item US Household Food Security Module in adolescence.
Setting:
Adolescents (Mage = 14·3 ± 2 years) and their parents, recruited from Minneapolis/St. Paul public schools in 2009–2010 and again in 2017–2018 as emerging adults (Mage = 22·1 ± 2 years).
Participants:
The analytic sample (n 1372; 53·1 % female, 46·9 % male) was diverse across race/ethnicity (19·8 % Asian, 28·5 % Black, 16·6 % Latinx, 14·7 % Multiracial/Other and 19·9 % White) and socio-economic status (58·6 % low/lower middle, 16·8 % middle and 21·0 % upper middle/high).
Results:
In cross-sectional analyses, youth-reported FI was associated with lower IE during adolescence (P = 0·02) and emerging adulthood (P < 0·001). Longitudinally, household FI, but not adolescent experience of FI, was associated with lower IE in emerging adulthood (P = 0·01). Those who remained food-insecure (P = 0·05) or became food-insecure (P = 0·02) had lower IE in emerging adulthood than those remaining food-secure. All effect sizes were small.
Conclusions:
Results suggest FI may exert immediate and potentially lasting impacts on IE. As evidence suggests IE is an adaptive approach conferring benefits beyond eating, it would be valuable for interventions to address social and structural barriers that could impede IE.
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Background: Transthyretin Amyloidosis (ATTR) is a common cause of both cardiomyopathy and carpal tunnel syndrome, with many patients needing carpal tunnel release (CTR). Although tafamidis is now an approved treatment of ATTR cardiomyopathy, insurers in most provinces require biopsy confirmation of amyloidosis. Endomyocardial biopsy is often the chosen approach due to optimal sensitivity, albeit with risk of serious adverse events such as stroke, cardiac tamponade, and arrhythmias. CTR may present an ideal opportunity for obtaining amyloidosis biopsy confirmation. Methods: ATTR patients undergoing CTR had biopsy of their transverse carpal ligament (TCL) and/or flexor tenosynovium to assess the sensitivity of both sites for biopsy confirmation of amyloidosis. Results: Twelve patients consecutively underwent biopsies during CTR, with 4 (33%) having bilateral CTR and biopsy. Among 16 TCL biopsies and 14 tenosynovium biopsies, 100% demonstrated amyloid deposition. Another patient had isolated tenosynovium biopsy without CTR and also demonstrated amyloidosis. There were no serious adverse events, and 1/13 (8%) had wound dehiscence requiring repeat suturing. Conclusions: Biopsy of the TCL and/or tenosynovium during CTR is safe, cost-effective, and sensitive, and may represent an alternative to endomyocardial biopsy in patients requiring tissue confirmation for tafamidis approval. ATTR patients eligible for tafamidis may benefit from early neurology assessment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.
Social Media Statement: Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.
We hypothesized that healthcare workers (HCWs) with high-risk exposures outside the healthcare system would have less asymptomatic coronavirus 2019 (COVID-19) disease and more symptoms than those without such exposures.
Design:
A longitudinal point prevalence study was conducted during August 17–September 4, 2020 (period 1) and during December 2–23, 2020 (period 2).
Setting:
Community based teaching health system.
Participants:
All HCWs were invited to participate. Among HCWs who acquired COVID-19, logistic regression models were used to evaluate the adjusted odds of asymptomatic disease using high-risk exposure outside the healthcare system as the explanatory variable. The number of symptoms between exposure groups was evaluated with the Wilcoxon rank-sum test. The risk of seropositivity among all HCS by work exposure was evaluated during both periods.
Interventions:
Survey and serological testing.
Result:
Seroprevalence increased from 1.9% (95% confidence interval [CI], 1.2%–2.6%) to 13.7% (95% CI, 11.9%–15.5%) during the study. Only during period 2 did HCWs with the highest work exposure (versus low exposure) have an increased risk of seropositivity (risk difference [RD], 7%; 95% CI, 1%–13%). Participants who had a high-risk exposure outside of work (compared to those without) had a decreased probability of asymptomatic disease (odds ratio [OR], 0.38; 95% CI, 0.16–0.86) and demonstrated more symptoms (median 3 [IQR, 2–6] vs 1 [IQR, 0–4]; P = .001).
Conclusions:
Healthcare-acquired COVID-19 increases the probability of asymptomatic or mild COVID-19 disease compared to community-acquired disease. This finding suggests that infection prevention strategies (including masks and eye protection) may be mitigating inoculum and supports the variolation theory in COVID-19.
Serotonergic neurotransmission plays a key role in seasonal changes of mood and behaviour. Higher serotonin transporter availability in healthy human subjects in times of lesser light has been reported in recent studies. Furthermore, seasonal alterations of postsynaptic serotonin-1A receptors have been suggested by a recent animal study. Following that, this study aimed at identifying seasonal alterations of serotonin-1A receptor binding in the living human brain.
Methods
Thirty-six healthy, drug-naïve subjects were investigated using PET and the specific tracer [carbonyl-11C]WAY-100635. Regional serotonin-1A receptor binding (5-HT1A BPND) was related to the individual exposure to global radiation. Furthermore, the subjects were divided into two groups depending on individual exposure to global radiation, and the group differences in regional 5-HT1A BPND were determined.
Results
Correlation analysis controlled for age and gender revealed highly significant positive correlations between regional postsynaptic 5-HT1A BPND and global radiation accumulated for 5 days (r=.32 to .48, p=.030 to .002). Highly significant differences in 5-HT1A BPND binding between subjects with low compared to high exposure to global radiation were revealed (T=-2.63 to -3.77, p .013 to .001). 20% to 30% lower 5-HT1A BPND was found in the subject group exposed to lower amount of global radiation.
Conclusion
Seasonal factors such as exposure to global radiation influence postsynaptic serotonin-1A receptor binding in various brain regions in healthy human subjects. In combination with seasonal alterations in serotonin turnover and 5-HTT availability revealed in recent studies, our results provide an essential contribution of molecular mechanisms in seasonal changes of human serotonergic neurotransmission.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Methods
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
Results
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Conclusions
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
We analyzed the inner 320 × 535 pc2 of the elliptical galaxy NGC 1052 with integral field spectroscopy, both in the optical and in the near-infrared (NIR). The stellar population analysis revealed a dominance of old stellar populations from the optical data, and an intermediate-age ring from NIR data. When combining optical+NIR data, optical results were favoured. The emission-line analysis revealed five kinematic components, where two of them are unresolved and probably associated with the active galactic nucleus (AGN), one is associated with large-scale shocks, one with the radio jets, and the last could be explained by either a bipolar outflow, rotation in an eccentric disc or a combination of a disc and large-scale gas bubbles. Our results also indicate that the emission within the galaxy is caused by a combination of shocks and photoionization by the AGN.
The impact of haematozoan infection on host fitness has received substantial attention since Hamilton and Zuk posited that parasites are important drivers of sexual selection. However, short-term studies testing the assumption that these parasites consistently reduce host fitness in the wild have produced contradictory results. To address this complex issue, we conducted a long-term study examining the relationship between naturally occurring infection with Haemoproteus and Plasmodium, and lifetime reproductive success and survival of Mountain White-crowned Sparrows. Specifically, we tested the hypothesis that birds infected with haematozoan parasites have reduced survival (as determined by overwinter return rates) and reproductive success. Contrary to expectation, there was no relationship between Haemoproteus and Plasmodium infection and reproduction or survival in males, nor was there a relationship between Plasmodium infection and reproduction in females. Interestingly, Haemoproteus-infected females had significantly higher overwinter return rates and these females fledged more than twice as many chicks during their lifetimes as did uninfected females. We discuss the impact of parasitic infections on host fitness in light of these findings and suggest that, in the case of less virulent pathogens, investment in excessive immune defence may decrease lifetime reproduction.
This paper gives a bird's-eye view of the various ingredients that make up a modern, model-checking-based approach to performability evaluation: Markov reward models, temporal logics and continuous stochastic logic, model-checking algorithms, bisimulation and the handling of non-determinism. A short historical account as well as a large case study complete this picture. In this way, we show convincingly that the smart combination of performability evaluation with stochastic model-checking techniques, developed over the last decade, provides a powerful and unified method of performability evaluation, thereby combining the advantages of earlier approaches.
To evaluate residual tumour occurrence after vestibular schwannoma surgery, based on intra-operative registration and magnetic resonance imaging one year post-operatively.
Methods:
Patients undergoing translabyrinthine surgery for vestibular schwannoma in Denmark between 1976 and 2008 were registered in a national database covering 5.5 million inhabitants.
Results:
Translabyrinthine surgery was undertaken on 1143 patients. Of these, 978 had total, 140 near-total and 25 subtotal tumour excision, as assessed intra-operatively by the surgeon. One year after surgery, 65 per cent of small tumour remnants and 11 per cent of large tumour remnants were not visible on magnetic resonance imaging. The mean pre-operative size was significantly smaller for totally excised tumours, compared with near-totally and subtotally excised tumours. Revision surgery was performed for 14 patients (1.2 per cent), of whom 2 had received total, 5 near-total and 6 subtotal excisions initially.
Conclusion:
Most residual tumours disappear spontaneously, probably due to devascularisation. Few patients with a small residual vestibular schwannoma will require revision surgery or secondary radiotherapy.