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The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC).
Participants were 27 children with AgCC and 32 TD children 8–16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure.
The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC.
This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.
For infants born in the contemporary era of neonatal care, little is known about adult mental health outcomes of extremely preterm birth (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g). This study aimed to compare attention deficit hyperactivity disorder (ADHD), anxiety, mood, and substance use disorder prevalence in young adults born EP/ELBW and normal birthweight (NBW; >2499 g) controls, and to compare change in prevalence of mental health symptoms and disorders from 18 to 25 years.
Participants were a prospective geographical cohort of 297 consecutive survivors born EP/ELBW during 1991–1992 and 260 NBW controls. At age 25 years, 174 EP/ELBW and 139 NBW participants completed the Adult ADHD Rating Scale, Structured Clinical Interview for DSM-IV Disorders, Beck Anxiety Inventory, and Center for Epidemiologic Studies Depression Scale-Revised. Data from follow-up at 18 years were also utilized. Multiple imputation was used to account for attrition.
Mental health outcomes at 25 years were similar between groups: prevalence rates were ADHD 7% v. 5%; anxiety 32% v. 27%; mood 38% v. 35%; substance use 12% v. 14% in the EP/ELBW and NBW groups, respectively. In both groups, ADHD declined between 18 and 25 years [odds ratio (OR) per year = 0.87, 95% confidence interval (CI) 0.79–0.95], and generalized anxiety disorder and major depressive episode became more common (OR 1.22, 95% CI 1.10–1.35 per year; OR 1.20, 95% CI 1.10–1.30 respectively).
This contemporary EP/ELBW cohort has comparable young adult mental health outcomes to controls, and similar patterns of change in mental health from late adolescence.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Children born very preterm (VP) are susceptible to a range of cognitive impairments, yet the effects of VP birth on long-term, episodic, and prospective memory remains unclear. This study examined episodic and prospective memory functioning in children born VP compared with their term-born counterparts at 13 years.
VP (n = 81: born <30 weeks’ gestation) and term (n = 26) groups were aged between 12 and 14 years. Children completed: (i) standardized verbal and visuospatial episodic memory tests; and (ii) an experimental time- and event-based prospective memory test that included short-term (within assessment session) and long-term (up to 1-week post-session) tasks. Parents completed a questionnaire assessing memory functions in everyday life.
The VP group performed worse on all measures of verbal and visuospatial episodic memory than the term group. While there were no group differences in event-based or long-term prospective memory, the VP group performed worse on time-based and short-term prospective memory tasks than term-born counterparts. Parents of children born VP reported more everyday memory difficulties than parents of children born at term, with parent-ratings indicating significantly elevated rates of everyday memory challenges in children born VP.
Children born VP warrant long-term surveillance, as challenges associated with VP birth include memory difficulties at 13 years. This study highlights the need for greater research and clinical attention into childhood functional memory outcomes.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus.
We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection.
Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data.
We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10−5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies.
We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.
MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.
VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.
Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.
ABSTRACT IMPACT: This study provides insight into how MED2 impacts the immune cells surrounding glioblastoma that help it to grow and spread; having a more complete understanding of how MED2 works will help us better develop therapies that may one day enter the clinic to improve patient outcomes in glioblastoma. OBJECTIVES/GOALS: The purpose of this study was to determine whether the phosphorylation state of the MED2 peptide impacts its biological activity in GBM and macrophages. MED2 variants include the phosphorylatable wild-type (MED2), pseudo-phosphorylated (MED2-PP), non-phosphorylatable (MED2-NP) and control length (CTL2) peptides. METHODS/STUDY POPULATION: MED2, MED2-NP, MED2-PP, and CTL2 were screened against a panel of molecularly characterized glioblastoma patient derived xenografts and IL4/13 stimulated M2-like THP-1 macrophages. The luminescent cell viability assay, CellTiter-Glo, was used to determine viability. RESULTS/ANTICIPATED RESULTS: The proneural lines XD456 and X1441 were highly sensitive to 5 µM MED2 and 5 µM MED2NP compared to 5 µM MED2PP (p<0.001). There was no statistically significant difference between untreated, 5 µM CTL2, and 5 µM MED2PP groups or between the MED2NP and MED2 treated groups. M2-like THP-1 macrophages were highly sensitive to 10 µM MED2NP compared to 10 µM CTL2 (p<0.01) and 10 µM MED2PP (p<0.01) No statistically significant difference was observed between untreated, 10 µM MED2, 10 µM MED2PP, and 10 µM CTL2 groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: The phosphorylation state of MED2 determines its toxicity. When MED2 is phosphorylated, it is nontoxic to GBM or M2-like macrophages. The non-phosphorylatable version is toxic to both GBM and M2-like macrophages. The wild-type peptide is toxic to GBM but not M2-like macrophages, suggesting that MED2 may be phosphorylated in M2-like macrophages.
To identify attention profiles at 7 and 13 years, and transitions in attention profiles over time in children born very preterm (VP; <30 weeks’ gestation) and full term (FT), and examine predictors of attention profiles and transitions.
Participants were 167 VP and 60 FT children, evaluated on profiles across five attention domains (selective, shifting and divided attention, processing speed, and behavioral attention) at 7 and 13 years using latent profile analyses. Transitions in profiles were assessed with contingency tables. For VP children, biological and social risk factors were tested as predictors with a multinomial logistic regression.
At 7 and 13 years, three distinct profiles of attentional functioning were identified. VP children were 2–3 times more likely to show poorer attention profiles compared with FT children. Transition patterns between 7 and 13 years were stable average, stable low, improving, and declining attention. VP children were two times less likely to have a stable average attention pattern and three times more likely to have stable low or improving attention patterns compared with FT children. Groups did not differ in declining attention patterns. For VP children, brain abnormalities on neonatal MRI and greater social risk at 7 years predicted stable low or changing attention patterns over time.
VP children show greater variability in attention profiles and transition patterns than FT children, with almost half of the VP children showing adverse attention patterns over time. Early brain pathology and social environment are markers for attentional functioning.
We have found a class of circular radio objects in the Evolutionary Map of the Universe Pilot Survey, using the Australian Square Kilometre Array Pathfinder telescope. The objects appear in radio images as circular edge-brightened discs, about one arcmin diameter, that are unlike other objects previously reported in the literature. We explore several possible mechanisms that might cause these objects, but none seems to be a compelling explanation.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.
Objectives: Preterm children demonstrate deficits in executive functions including inhibition, working memory, and cognitive flexibility; however, their goal setting abilities (planning, organization, strategic reasoning) remain unclear. This study compared goal setting abilities between very preterm (VP: <30 weeks/<1250 grams) and term born controls during late childhood. Additionally, early risk factors (neonatal brain abnormalities, medical complications, and sex) were examined in relationship to goal setting outcomes within the VP group. Methods: Participants included 177 VP and 61 full-term born control children aged 13 years. Goal setting was assessed using several measures of planning, organization, and strategic reasoning. Parents also completed the Behavior Rating Inventory of Executive Function. Regression models were performed to compare groups, with secondary analyses adjusting for potential confounders (sex and social risk), and excluding children with major neurosensory impairment and/or IQ<70. Within the VP group, regression models were performed to examine the relationship between brain abnormalities, medical complications, and sex, on goal setting scores. Results: The VP group demonstrated a clear pattern of impairment and inefficiency across goal setting measures, consistent with parental report, compared with their full-term born peers. Within the VP group, moderate/severe brain abnormalities on neonatal MRI predicted adverse goal setting outcomes at 13. Conclusions: Goal setting difficulties are a significant area of concern in VP children during late childhood. These difficulties are associated with neonatal brain abnormalities, and are likely to have functional consequences academically, socially and vocationally. (JINS, 2018, 24, 372–381)
Hypertension following primary coarctation repair affects up to a third of subjects. A number of studies suggest that future hypertension risk is reduced if primary repair is performed at a younger age.
The objective of this study was to evaluate the risk of future medical treatment for hypertension depending on age of primary coarctation repair.
This study was carried out at a tertiary paediatric cardiology referral centre. Retrospective database evaluation of children aged <16 years undergoing primary surgical coarctation repair between October, 2005 and October, 2014 was carried out. Patients with complex heart diseases were excluded. The following age groups were considered: neonate (⩽28 days), infant (>28 days and ⩽12 months), and children (>12 months). Main outcome measure is the need for long-term anti-hypertensive medication. The risk for re-coarctation was also evaluated.
A total of 87 patients were analysed: 60 neonates, 17 infants, 10 children. Among them, 6.7% neonates, 29.4% infants, and 40% children required long-term anti-hypertensive medications. Group differences were statistically significant (p=0.004). After adjustment for type of repair, the risk of long-term anti-hypertensive therapy was 4.5 (95% confidence interval 1.2–16.9, p=0.025) and 10.5 times (95% confidence interval 2.6–42.3, p=0.001) higher if primary repair was carried out in infancy and childhood, respectively, compared with neonates. Among all, 13 patients developed re-coarctation: 21.7% in the neonatal group, 5.9% in the infant group, and 20% in the child group. We could not demonstrate a significant difference between these proportions or calculate a reliable risk for developing re-coarctation.
Risk of medical treatment for hypertension was lowest when primary repair was carried out during the neonatal period, rising 10-fold if first operated on as a child. Knowing the likelihood of hypertension development depending on age of primary repair is useful for long-term surveillance and counselling.
Background: The evidence regarding whether co-morbid obsessive compulsive personality disorder (OCPD) is associated with treatment outcomes in obsessive compulsive disorder (OCD) is mixed, with some research indicating that OCPD is associated with poorer response, and some showing that it is associated with improved response. Aims: We sought to explore the role of OCPD diagnosis and the personality domain of conscientiousness on treatment outcomes for exposure and response prevention for OCD. Method: The impact of co-morbid OCPD and conscientiousness on treatment outcomes was examined in a clinical sample of 46 participants with OCD. Results: OCPD diagnosis and scores on conscientiousness were not associated with poorer post-treatment OCD severity, as indexed by Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, although the relative sample size of OCPD was small and thus generalizability is limited. Conclusion: This study found no evidence that OCPD or conscientiousness were associated with treatment outcomes for OCD. Further research with larger clinical samples is required.
Background: Perfectionism is strongly associated with obsessive compulsive disorder (OCD). Cognitive behavioural therapy for perfectionism (CBT-P) has been found to result in reductions in a range of symptoms in individuals with anxiety disorders, depression and eating disorders. Aim: To pilot-test the efficacy of group CBT for perfectionism in participants with OCD and elevated perfectionism. Method: Participants were randomized to receive immediate 8-week group CBT-P (n = 4) or an 8-week waitlist followed by CBT-P (n = 7). Results: Reliable reductions and a large effect size indicated that CBT-P was associated with improvements in perfectionism and OCD severity at post-test. However, these changes were not clinically significant and drop-out was high, resulting in a small final sample. Conclusions: CBT-P may be effective in reducing perfectionism and disorder-specific OCD symptoms. However, the high drop-out rate and lack of clinically significant findings suggest that further research needs to be conducted to determine the efficacy of CBT for perfectionism in OCD.