Intelligence in offspring born to women exposed to intimate partner violence: a population-based cohort study

Background: Intimate partner violence (IPV) is a risk factor for developmental problems in offspring. Despite a high prevalence of IPV in the UK and elsewhere, the longer-term outcomes of offspring born to exposed mothers remain under-researched. Methods: Population-based cohort study. We assessed IPV prevalence by type and timing for 3,153 mother-child pairs with complete data within our study population and examined associations between IPV and offspring IQ. We used multiple-imputation to evaluate bias due to our exclusion of observations with missing covariate data. Results: Nearly one in five mothers reported IPV during the study period, with 17.6% reporting emotional violence and 6.8% reporting physical violence. Taking into account potential confounders, the IQ scores of children born to mothers exposed to physical violence remained lower than those of maternally unexposed children (full-scale IQ = −2.8 points [95%CI −4.9 to −0.7], verbal IQ = −2.2 [95%CI −4.4 to −0.1], performance IQ = −2.7 [95%CI  −5.0 to −0.5]) and odds of below-average intelligence (IQ<90) remained increased for full-scale (OR 1.48 [95%CI 1.03 to 2.14] and performance IQ (OR 1.48 [95%CI 1.08 to 2.04]) but not verbal IQ (OR 1.06 [95%CI 0.69 to 1.64]). Most physical violence occurred postnatally, and relative odds were most substantial when mothers were exposed to violence across pre-/perinatal and postnatal study periods (OR performance IQ<90 = 2.97 [95%CI 1.30 to 6.82]). Conclusions: Maternal exposure to physical IPV is associated with lower offspring IQ at age 8. Associations persisted after adjusting for potential confounders and were driven by violence occurring postnatally

Cognitive function in soccer athletes determined by sleep disruption and self-reported health, yet not by decision-reinvestment

BackgroundSleep disruption (SD) increases sympathetic activity and cortisol secretion, and delays cognitive functions such as reaction-time (RT). Sympathetic activity of disturbed sleepers, is similar to those of so-called decision-reinvesters. Decision-reinvestment refers to traits in individuals with greater tendency to ruminate and reinvest in their decisions, with significant decrease in both motor-control and cognitive performance. Decision-making quality is a crucial attribute to athletic performance which relies on RT. Consequently, SD affects pitch-performance negatively, particularly in decision-reinvesters. This observational pilot-study examined the relationship between SD and cognitive function, perceived health, as well as reinvestment strategies. The hypothesis was that athletes with lower SD perceive their health better, report lower stress levels, perform better in cognitive tasks, and show lower tendency for decision-reinvestment.MethodsTwenty-one football player recorded their sleep with fit-trackers for 7 nights. Participants self-reported their mental and physical health, decision-reinvestment strategy, sleep behaviour, and perceived stress levels. Athletes then performed a set of cognitive tests to examine memory function (Backwards Corsi), selective attention (STROOP), and cognitive flexibility (Wisconsin Card Sorting Test, WCST). Normality was tested with a Shapiro-Wilk test, and analysed with a Pearson's or Spearman's correlation test.ResultsSignificant correlation appeared between extended sleep-interruptions and Backwards Corsi RT, r = 0.66, p = 0.010, as further in total sleep time and wellbeing r = 0.50, p = 0.029. A negative correlation exist in regard of pain scores and Backwards Corsi scores r = −0.57, p = 0.110. Physical health correlated with error-rates in the WCST, r = 0.69, p ≤ 0.001. Also, reinvestment negatively correlated with physical health, r = −0.80, p ≤ 0.001.ConclusionWellbeing relies on total sleep-time. Athletes with extended sleep-interruptions are slower in recalling memory, and those with greater reported pain have lower memory scores. Participants who rate physical health greater, have more error-rates in the WCST; indicating that cognitive flexibility is enhanced in individuals with inferior perceived health. However, individuals with lower physical health scores also have greater tendency to ruminate and reinvest in decisions, suggesting interrelation between reinvestment and physical health

Association of neuregulin 1 with schizophrenia confirmed in a Scottish population

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldRecently, we identified neuregulin 1 (NRG1) as a susceptibility gene for schizophrenia in the Icelandic population, by a combined linkage and association approach. Here, we report the first study evaluating the relevance of NRG1 to schizophrenia in a population outside Iceland. Markers representing a core at-risk haplotype found in Icelanders at the 5' end of the NRG1 gene were genotyped in 609 unrelated Scottish patients and 618 unrelated Scottish control individuals. This haplotype consisted of five SNP markers and two microsatellites, which all appear to be in strong linkage disequilibrium. For the Scottish patients and control subjects, haplotype frequencies were estimated by maximum likelihood, using the expectation-maximization algorithm. The frequency of the seven-marker haplotype among the Scottish patients was significantly greater than that among the control subjects (10.2% vs. 5.9%, P=.00031). The estimated risk ratio was 1.8, which is in keeping with our report of unrelated Icelandic patients (2.1). Three of the seven markers in the haplotype gave single-point P values ranging from .000064 to .0021 for the allele contributing to the at-risk haplotype. This direct replication of haplotype association in a second population further implicates NRG1 as a factor that contributes to the etiology of schizophrenia

HPA Axis Genetic Variation, Cortisol, and Psychosis in Major Depression

Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis over-activity in healthy controls and patients with severe forms of major depression has not been well explored but could explain risk for cortisol dysregulation. 95 participants were studied: 40 patients with psychotic major depression (PMD); 26 patients with nonpsychotic major depression (NPMD); and 29 healthy controls (HC). Collection of genetic material was added one third of the way into a larger study on cortisol, cognition, and psychosis in major depression. Subjects were assessed using the Brief Psychiatric Rating Scale, the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Blood was collected hourly for determination of cortisol from 6pm to 9am and for the assessment of alleles for 6 genes involved in HPA Axis regulation. Two of the 6 genes contributed significantly to cortisol levels, psychosis measures or depression severity. After accounting for age, depression, and psychosis, and medication status, only allelic variation for the glucocorticoid receptor gene (GR) accounted for significant variance for mean cortisol levels from 6pm to 1am (r2=.317) and from 1am to 9am (r2=.194). Interestingly, neither depression severity nor psychosis predicted cortisol variance. In addition, GR and corticotropin-releasing hormone receptor 1 (CRH-R1) contributed significantly to psychosis measures and CRH-R1 contributed significantly to depression severity rating

A randomised double-blind placebo-controlled trial of minocycline and/or Omega-3 fatty acids added to treatment as usual for At Risk Mental States (NAYAB): study protocol

Background The At Risk Mental State (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials that have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for ARMS that are available both in high, low and middle-income countries. Methods A six-month intervention study of minocycline and/or Omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. 320 consenting patients with capacity will be recruited from community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants to each study arm, and 236 will complete in total. We will determine whether the addition of minocycline and/or Omega-3 fatty acids to TAU attenuates rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy end-point is conversion to psychotic disorder at 12 months post study entry. Analysis will be by intention-to-treat, using analysis-of variance, chi-squared tests and adjusted odds ratios to assess between-group differences. Cox regression analyses will be used to analyse potential between-group differences in time-to-onset of psychosis. Discussion The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive are readily available in low/middle-income countries such as Pakistan, and if evidenced, may prove to be safe and effective for treating ARMS

Association of peripheral interleukin-6 with global cognitive decline in non-demented adults: a meta-analysis of prospective studies

Background: Elevated biomarkers of systemic inflammation have been reported in individuals with cognitive decline, however, most of the literature concerns cross-sectional analyses that have produced mixed results. This study investigates the aetiology of this association by performing meta-analyses on prospective studies investigating the relationship between baseline interleukin-6 (IL-6), an established marker of peripheral inflammation, with cognitive decline risk in non-demented adults at follow-up. Methods: We reviewed studies reporting peripheral IL-6 with future cognitive decline, up to February 2017 by searching the PubMed, Science Direct, Scopus and Google Scholar databases. Studies which contained odds ratios (ORs) for the association between circulating baseline IL-6 and longitudinal cognitive performance in non-demented community dwelling older adults were pooled in random-effects models. Results: The literature search retrieved 5,642 potential articles, of which 7 articles containing 8 independent ageing cohorts were eligible for review. Collectively, these studies included 15,828 participants at baseline. Those with high circulating IL-6 were 1.42 times more likely to experience global cognitive decline at follow-up, over a 2 – 7-year period, compared to those with low IL-6 (OR 1.42, 95% CI 1.18 – 1.70; p < 0.001). Subgroup and sensitivity analyses suggests that this association is independent of the study sample size, duration of follow-up and cognitive assessments used. Conclusions: These results add further evidence for the association between high peripheral inflammation, as measured by blood IL-6, and global cognitive decline. Measuring circulating IL-6 may be a useful indication for future cognitive health

Temporal trends in antidepressant prescribing to children in UK primary care, 2000–2015

Background The prevalence of antidepressant prescribing in children and adolescents increased steadily in the United States and parts of Europe between 2005 and 2012 despite regulatory safety warnings. Little is known about the characteristics of those being prescribed antidepressants for the first time. Methods A longitudinal study of antidepressant prescribing in 3–17 year olds was carried out using data from the UK Clinical Practice Research Datalink (CPRD) between 2000 and 2015. Changes in the incidence of first ever antidepressant prescriptions and the characteristics of those being prescribed them was examined. Results Incidence of first ever prescriptions nearly doubled between 2006 and 2015 rising from 1.60 (95%CI: 1.51, 1.69) to 3.12 (3.00, 3.25) per 1000 person years. Only 21% of the 1721 patients with incident prescriptions in 2015 could be linked to a depression diagnosis, with an additional 22% of prescriptions linked to alternative indications. The incidence of prescriptions linked to a depression diagnosis increased between 2012 and 2015, with an adjusted incidence rate ratio of 1.46 (1.26, 1.70). Antidepressant prescribing for depression and other indications has been increasing most rapidly in 15 to 17 year old females. Limitations Diagnoses are not directly linked to prescriptions in CPRD, so linkage must be inferred by temporal proximity. Conclusions Antidepressant prescribing in children increased between 2006 and 2015. This is, at least in part, due to a rise in alternative uses of antidepressants, including the treatment of anxiety, chronic pain and migraines

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

An investigation into the genetic basis of schizophrenia

Schizophrenia is a common and debilitating mental illness, affecting 1% of the population and affecting all ethnic groups (Wilkinson et al 1996).  It is a highly complex disorder containing genetic and environmental components (Birkett et al. 2000), making it difficult to identify those genes responsible for the development of schizophrenia using linkage alone.  This thesis presents work on three candidate genes Disrupted in Schizophrenia 1 (DISC1), Neuregulin 1 (NRG1) and 5-HT5A, using a case control approach to test for association between schizophrenia and the candidate genes, in the Scottish population.  All findings for 5-HT5A were negative. The exact function of DISC1 is unknown but it appears to have a role in neurodevelopment.  Acting in complex with NUDEL to affect neurite growth (Ozeki et al. 2003) and modifying Translin binding when intragenically spliced with TRAX (Chennathukuzhi et al. 2001).  Genotypic and haplotypic analysis of DISC1 using a combination of pooling and individual genotyping.  Led to the discovery of a novel nonsynonymous SNP A40961G located in exon 2 of DISC1 which shows significant association with schizophrenia (p = 0.000232, O.R. = 0.71861, n = 600).  Haplotypic analysis identified a 4 marker at-risk haplotype (p = 0.0010, O.R = 2.56, n = 200) containing the A40961G marker. NRG1 was investigated at the request of DeCode Genetics in order to replicate there positive at the 5’ end of NRG1 (p = 0.000087) (Stefansson et al. 2002). The genotyping was carried out blind of diagnosis by myself at DeCode Genetics, analysis was carried out independently.  The results confirmed the Icelandic findings for a 7 marker at-risk haplotype located at the 5’ end NRG1 (p = 0.00031).EThOS - Electronic Theses Online ServiceGBUnited Kingdo

I can do this, I’ll show you!: technical and clinical skill literacy and assessment in biomedical and physiological sciences

As academics, our aim is to design and deliver training programmes that enable students to gain the knowledge and skills needed for graduate career success (Steele et al., 2020). A survey of academics suggested three top skills for graduates to prosper; Communication, Critical Thinking and Problem Solving (McVitty and Andrews, 2021). However, student misidentification of acquisition and demonstration of these within their study programme, could lead to low confidence and inadequacies in evidencing these to employers upon completion of training (Bist and Mehta, 2020). We will describe our mechanism for technical skill literacy training and authentic assessment of technical skill competency, using direct observation of practice, clinical simulation and case-based learning. Our aim is to promote technical skills literacy and to provide graduates with a portfolio of evidence for a future employer/ further training provider