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Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.
Shortages of personal protective equipment during the coronavirus disease 2019 (COVID-19) pandemic have led to the extended use or reuse of single-use respirators and surgical masks by frontline healthcare workers. The evidence base underpinning such practices warrants examination.
To synthesize current guidance and systematic review evidence on extended use, reuse, or reprocessing of single-use surgical masks or filtering face-piece respirators.
We used the World Health Organization, the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites to identify guidance. We used Medline, PubMed, Epistemonikos, Cochrane Database, and preprint servers for systematic reviews.
Two reviewers conducted screening and data extraction. The quality of included systematic reviews was appraised using AMSTAR-2. Findings were narratively synthesized.
In total, 6 guidance documents were identified. Levels of detail and consistency across documents varied. They included 4 high-quality systematic reviews: 3 focused on reprocessing (decontamination) of N95 respirators and 1 focused on reprocessing of surgical masks. Vaporized hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale.
Evidence on the impact of extended use and reuse of surgical masks and respirators is limited, and gaps and inconsistencies exist in current guidance. Where extended use or reuse is being practiced, healthcare organizations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance.
Categorical rubrics are the prevailing approach to personality disorder (PD) assessment and diagnosis. Diagnostic manuals, funding bodies, and training programs tend to follow this categorical model. Yet there is now abundant evidence that PD categories are impeding research progress on personality pathology. This chapter describes an emerging dimensional perspective on personality problems, the Hierarchical Taxonomy of Psychopathology (HiTOP). The HiTOP framework encapsulates factor analytically derived higher- and lower-order dimensions of personality pathology, ranging from an overarching general factor of psychopathology at the hierarchy’s apex to homogeneous maladaptive personality traits and acute symptoms at the base. This multi-level system bypasses aspects of categorical PD diagnoses that researchers find problematic (e.g., comorbidity, within-diagnosis heterogeneity, and insufficient coverage of personality problems encountered in the clinic). HiTOP has the potential to renew field-wide interest in PD and streamline social, psychological, and biological research on personality pathology.
The study aims to explore the views of consultant psychiatrists in Ireland on shared care between specialist psychiatric services and primary care.
A self-administered questionnaire was posted to all 470 consultant psychiatrists working in Ireland. Self addressed envelopes were included for the return of completed questionnaires. Data was analysed using descriptive statistics and ANOVA
213 questionnaires were returned giving a response rate of 45%. 47.9% of the respondents were male and 52.1% were female. Over all, 91% of respondents reported that they would support a general policy on shared care between primary care and specialised psychiatric services for patients who are stable on their treatment. However, 85% reported that they foresaw difficulties for patients in implementing such a policy, including: increased financial burden on some patients (66%), lack of adequate allied health professionals resources in primary care (60%) and GP's not adequately trained to provide psychiatric care (52%). Most psychiatrists did not feel comfortable to transfer the care of patients with schizophrenia or bipolar disorder to their GP's and Child psychiatrists were significantly less comfortable than other psychiatrists to discharge patients with Depression, Bipolar Disorder, Anxiety Disorder, Alcohol Dependency Syndrome and Personality Disorder into the care of GP's after they have been stabilised in their medication.
Although most psychiatrists in Ireland would support a policy of shared care, they identify several constraints which would currently hamper the effective implementation of a policy of active collaboration between primary care and specialised psychiatric services in Ireland.
The study aims to explore the views of primary care physicians in Ireland on shared care of psychiatric patients between primary and secondary services.
A self-administered questionnaire was posted to a random cross-section primary care physicians working in Ireland. Data were compiled and analyzed using descriptive statistics and analysis of variance.
145 out of 300 questionnaires were returned giving a response rate of 48%. Overall, 77.9% of respondents reported that they completed a psychiatric rotation as part of their general practice training. Most General Practitioners expressed confidence in their ability to recognize and manage psychiatric disorders in primary care (on a confidence scale of 1 to 5, mean was 3.97, SD 0.699). There was a statistically, significant difference in confidence scores between those who had took a rotation in psychiatry as part of their GP training and those who did not, with the former reporting higher scores (4.04 vs. 3.72, F = 1.801, t = 2.363, p = 0.02)Regarding shared care, 95.8% of GPs were in favour of a formal shared care policy; however 42.8% expressed reservations regarding the implications of implementing such a policy. The most frequently expressed concerns related to the lack of resources in primary care for psychiatric patients (55.9%), financial implications for some patients (48.3%), and concern over communication with psychiatric services (42%).
The majority of Primary Care physicians in Ireland would support a policy of shared care of psychiatric patients’; however they raise some concerns regarding practical implications of such a policy.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Optimal maternal polyunsaturated fatty acid (PUFA) status is essential for foetal development. The desaturase enzymes, encoded by the fatty acid desaturase (FADS) genes, are involved in the endogenous synthesis of long chain (LC)PUFA and influence maternal LCPUFA concentrations. The minor allele of various FADS SNPs has been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of the LCPUFA arachidonic acid (AA) and docosahexaenoic acid (DHA); however, there is limited research to date on the influence of FADS genotype on cord PUFA status. The aim of the current study was to investigate the influence of maternal and child genetic variation on cord blood PUFA status in a high fish-eating cohort.
Cord blood samples collected from mother-child pairs (n = 1088) taking part in the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Maternal (n = 1088) and child genotype (n = 592) were determined for the FADS SNPs rs174537, rs174561, rs174575, and rs3834458. Regression analysis determined associations between maternal and child FADS genotype and cord PUFA status. In all regression models, the major allele homozygote genotype for each SNP was used as the reference group.
Directions of significant associations were as predicted. In mothers, the minor allele homozygote genotype for SNPs rs174537, rs174561 and rs3834458 was associated with lower cord DHA and lower total n-3 PUFA when compared to the major allele homozygous genotype (p < 0.05 for all). The heterozygous genotype was associated with increased concentrations of LA compared to the reference genotype for rs174561 (p = 0.021) and rs383448 (p = 0.023). In children, the heterozygous genotype was associated with lower AA concentrations and lower cord n-6:n-3 ratio for all SNPs (p < 0.05 for all) compared to those with the major allele homozygous genotype. A lower cord AA:LA ratio was also observed for children heterozygous for rs174547, rs174561 and rs174575 (p < 0.05 for all). Contrary to expected, there were no associations between cord PUFA concentrations and child minor allele homozygous genotype.
The current study indicates that variation in maternal and child FADS genotype influences cord PUFA concentrations, despite the high intake of preformed dietary LCPUFA from fish in this population. The sample size for minor allele homozygous children was likely too small to observe any statistically significant associations in the current analysis. Further research is needed to determine whether increased dietary intake can compensate for lower PUFA status as a result of FADS genotype.
Diagnosis and classification for mental disorder are in flux. This transition has downstream consequences on the nature of clinical assessment in research and treatment settings. We begin this chapter by describing the prevailing categorical rubrics, which are the predominant guide to clinical assessment worldwide. These systems, despite their popularity, suffer from serious defects, which have prompted the development of alternate frameworks for conceptualization and assessment of psychopathology. We focus the remainder of the chapter on two prominent contenders to supplement, and perhaps eventually supplant, traditional categorical models. The Hierarchical Taxonomy of Psychopathology is an empirically derived system of the phenotypic dimensions of psychopathology and the Research Domain Criteria represent a biologically oriented approach to understanding risk processes implicated in mental disorder. We describe the promise and challenges facing these two emerging systems, and we speculate about how they will shape the future of clinical assessment.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Recovery is a key goal for individuals, and services’ recovery orientation can facilitate this process. The independent mental health sector is increasingly important in Ireland, particularly in counselling and suicide prevention. We aimed to evaluate Pieta House as a recovery-oriented service through clients’ self-rated recovery; and clients’ and therapists’ evaluation of the service.
Clients completing therapy over a 3-month period were invited to complete the Recovery Assessment Scale (RAS) and the Recovery Self Assessment-Revised (RSA-R). Therapists completed the RSA-R staff version.
Response rate was 36.7% for clients (n=88), 98% for therapists (n=49). Personal recovery was endorsed by 73.8% of clients, with highest agreement for factors ‘Willingness to Ask for Help’ (84.5%), and ‘Reliance on Others’ (82.1%). A smaller number agreed with factors ‘Personal Confidence and Hope’ (61.3%) and ‘No Domination by Symptoms’ (66.6%). Clients’ and therapists’ evaluation of the service showed high levels of agreement with factors of ‘Choice’ (90.9% clients, 100% therapists); ‘Life Goals’ (84.1% clients, 98% therapists) and ‘Individually Tailored Services’ (80.6% clients, 79.6% therapists). Client involvement in service management had the lowest level of agreement (36.4% clients, 30.6% therapists). Clients’ self-rated recovery correlated with their rating of the service (correlation value 0.993, p=0.01).
Clients’ self-rated recovery and the recovery orientation of Pieta House were rated highly, with areas for improvement in service user involvement, peer support and advocacy. The correlation of personal recovery and recovery orientation of the service may merit further study.
It has been suggested that offspring of parents with bipolar disorder are at increased risk for disruptive mood dysregulation disorder (DMDD), but the specificity of this association has not been established.
We examined the specificity of DMDD to family history by comparing offspring of parents with (a) bipolar disorder, (b) major depressive disorder and (c) a control group with no mood disorders.
We established lifetime diagnosis of DMDD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children for DSM-5 in 180 youth aged 6–18 years, including 58 offspring of parents with bipolar disorder, 82 offspring of parents with major depressive disorder and 40 control offspring.
Diagnostic criteria for DMDD were met in none of the offspring of parents with bipolar disorder, 6 of the offspring of parents with major depressive disorder and none of the control offspring. DMDD diagnosis was significantly associated with family history of major depressive disorder.
Our results suggest that DMDD is not specifically associated with a family history of bipolar disorder and may be associated with parental depression.
To describe and discuss the portrayal of psychiatric illness in film and theatre.
A review of psychiatric literature on psychiatric illness and stigma was carried out. This was combined with a review of selected films and plays. The dramatic function of mental illness, and the manner of its portrayal, were considered in a discursive manner.
From Ancient Greek theatre to modern film, psychiatric illness has been used to exemplify “otherness”. This has frequently had connotations of danger and violence, either to others or to societal norms. Occasionally psychiatric illness is depicted as transformative, or an understandable reaction to an insane environment, and there is a trend towards more nuanced depictions of mental illness. However, the disproportionate association of mental illness with violence and danger is reflected in the public's perception of mental illness, and contributes to self-stigmatisation.
Ongoing communication between psychiatry, service users and the arts may help to challenge the stereotype of “mad, bad and dangerous to know”.
The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.
Introduced accidentally from South America, deeproot sedge is rapidly expanding in a variety of habitats throughout the southeastern United States. Of particular concern is its rapid expansion, naturalization, and formation of monocultures in Texas coastal prairie, one of the most imperiled temperate ecoregions in North America. The objective of this research was to examine how deeproot sedge responds to prescribed fire, to the herbicide imazapic, and to treatment combinations of both. Combinations of prescribed fire and imazapic treatments and imazapic-only treatments effectively reduced deeproot sedge cover and frequency. However, plots exposed to dormant season fires (with no imazapic) had greater deeproot sedge cover after burn treatments were applied, indicating that coastal prairie management using only dormant season prescribed fire will not work toward reduction or management of this exotic invasive species. Although deeproot sedge cover was often reduced in fire–imazapic treatment combinations, it was still present in treatment plots. Moreover, desirable functional plant groups (i.e., native bunchgrasses) did not respond positively to the fire–imazapic treatments, but in some instances, woody plant coverage increased. Repeated, long-term approaches using integrated and coordinated efforts with multiple treatment options will be necessary to restore community structure to desired compositional levels. Such integrated approaches should be effective in reducing deeproot sedge frequency, cover, and extent to more manageable levels throughout its introduced geographic range.
Previous research supports gene–environment interactions for polymorphisms in the corticotropin hormone receptor 1 gene (CRHR1) and the serotonin transporter gene linked polymorphic region (5-HTTLPR) in predicting depression, but it has rarely considered genetic influences on stress sensitization processes, whereby early adversities (EA) increase depressive reactivity to proximal stressors later in life. The current study tested a gene–environment–environment interaction (G × E × E; specifically, gene–EA–proximal stress interaction) model of depression in a 20-year longitudinal study. Participants were assessed prospectively for EA up to age 5 and recent chronic stress and depressive symptoms at age 20 and genotyped for CRHR1 single nucleotide polymorphism rs110402 and 5-HTTLPR. EA predicted stronger associations between recent chronic stress and depression, and the effect was moderated by genes. CRHR1 A alleles and 5-HTTLPR short alleles were associated with greater stress sensitization (i.e., greater depressive reactivity to chronic stress for those also exposed to high levels of EA). The results are consistent with the notion that EA exposure results in neurobiological and cognitive–emotional consequences (e.g., altered hypothalamic–pituitary–adrenal axis functioning), leading to emotional distress in the face of recent stressors among those with certain genetic characteristics, although further research is needed to explore explanatory mechanisms.
The NIH Toolbox (NIHTB) Pattern Comparison Processing Speed Test was developed to assess processing speed within the NIHTB for the Assessment of Neurological Behavior and Function Cognition Battery (NIHTB-CB). This study highlights validation data collected in adults ages 18–85 on this measure and reports descriptive data, test–retest reliability, construct validity, and preliminary work creating a composite index of processing speed. Results indicated good test–retest reliability. There was also evidence for both convergent and discriminant validity; the Pattern Comparison Processing Speed Test demonstrated moderate significant correlations with other processing speed tests (i.e., WAIS-IV Coding, Symbol Search and Processing Speed Index), small significant correlations with measures of working memory (i.e., WAIS-IV Letter-Number Sequencing and PASAT), and non-significant correlations with a test of vocabulary comprehension (i.e., PPVT-IV). Finally, analyses comparing and combining scores on the NIHTB Pattern Comparison Processing Speed Test with other measures of simple reaction time from the NIHTB-CB indicated that a Processing Speed Composite score performed better than any test examined in isolation. The NIHTB Pattern Comparison Processing Speed Test exhibits several strengths: it is appropriate for use across the lifespan (ages, 3–85 years), it is short and easy to administer, and it has high construct validity. (JINS, 2014, 20, 1–12)
Native to temperate South America, deeproot sedge has naturalized throughout the southeastern United States. Often forming dense, homogenous stands, deeproot sedge has become widespread, invasive, and potentially harmful ecologically throughout the coastal prairie ecoregion of Texas. Possessing characteristics (rapid growth, generalized habitat requirements) of other weedy congeners (purple nutsedge and yellow nutsedge), its relatively recent expansion highlights the critical need to develop effective control techniques and strategies for this species throughout this endangered ecoregion. Research was performed to delineate total nonstructural carbohydrate (TNC) trends in deeproot sedge rhizomes for development of a phenologically based schedule for herbicide applications and mechanical treatments. Overall, TNC levels were greatest in May to August and lowest from October to January, regardless of study area. Apparently, deeproot sedge exerts little energy into seed production because TNC levels were continually replenished throughout the growing season. As such, foliar-herbicide application throughout the growing season should achieve total plant kill. Conversely, deeproot sedge rhizome TNC levels never fell below 30%, even during winter, which indicates that winter mechanical treatments or winter prescribed fires will not be effective because substantial rhizome reserves are present to support resprouting during the next growing season. Beyond a priori prevention, sequential herbicide applications combined with integrated, sequential, prescribed fire and herbicide treatments will be needed for long-term deeproot sedge control throughout its geographic range.