Cognitive profiles in childhood and adolescence differ between adult psychotic and affective symptoms: a prospective birth cohort study

Background Differences between verbal and non-verbal cognitive development from childhood to adulthood may differentiate between those with and without psychotic symptoms and affective symptoms in later life. However, there has been no study exploring this in a population-based cohort. Method The sample was drawn from the MRC National Survey of Health and Development, and consisted of 2,384 study members with self-reported psychotic experiences and affective symptoms at age 53 years, and with complete cognitive data at ages 8 and 15 years. The association between verbal and non-verbal cognition at age 8 years and relative developmental lag from age 8 to 15 years, and both adult outcomes were tested with the covariates adjusted, and mutually adjusted for verbal and nonverbal cognition. Results Those with psychotic experiences (thought interference [n=433], strange experience [n=296], hallucination [n=88]) had lower cognition at both age 8 and 15 years in both verbal and non-verbal domains. After mutual adjustment, lower verbal cognition at age 8 years and greater verbal developmental lag were associated with higher likelihood of psychotic experiences within individuals, whereas there was no association between non-verbal cognition and any psychotic experience. In contrast, those with case-level affective symptoms (n=453) had lower non-verbal cognition at age 15, and greater developmental lag in non-verbal domain. After adjustment, lower non-verbal cognition at age 8 years and greater non-verbal developmental lag were associated with higher risk of case-level affective symptoms within individuals. Conclusions These results suggest that cognitive profiles in childhood and adolescence differentiate psychiatric disease spectra.SK was supported by the grants from JSPS KAKENHI Grant Number 25870143, 26118703, and Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation. MR is funded by the UK Medical Research Council [Unit Programme numbers MC UU 12019/3]. PJ is supported by Wellcome Trust grants 095844/Z/11/Z and 088869/Z/09/Z; National Institute for Health Research grant RP-PG-0606-1335; and by the NIHR Cambridge BRC and the NIHR CLAHRC East of England

Emotional bias training as a treatment for anxiety and depression: evidence from experimental medicine studies in healthy and medicated samples.

BACKGROUND: Anxiety and depression are leading causes of disability worldwide, yet individuals are often unable to access appropriate treatment. There is a need to develop effective interventions that can be delivered remotely. Previous research has suggested that emotional processing biases are a potential target for intervention, and these may be altered through brief training programs. METHODS: We report two experimental medicine studies of emotional bias training in two samples: individuals from the general population (n = 522) and individuals currently taking antidepressants to treat anxiety or depression (n = 212). Participants, recruited online, completed four sessions of EBT from their own home. Mental health and cognitive functioning outcomes were assessed at baseline, immediately post-training, and at 2-week follow-up. RESULTS: In both studies, our intervention successfully trained participants to perceive ambiguous social information more positively. This persisted at a 2-week follow-up. There was no clear evidence that this change in emotional processing transferred to improvements in symptoms in the primary analyses. However, in both studies, there was weak evidence for improved quality of life following EBT amongst individuals with more depressive symptoms at baseline. No clear evidence of transfer effects was observed for self-reported daily stress, anhedonia or depressive symptoms. Exploratory analyses suggested that younger participants reported greater treatment gains. CONCLUSIONS: These studies demonstrate the effectiveness of delivering a multi-session online training program to promote lasting cognitive changes. Given the inconsistent evidence for transfer effects, EBT requires further development before it can be considered as a treatment for anxiety and depression

Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders.

Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations.This work was supported by the Wellcome Trust [088869/Z/09/Z to M.R., P.B.J., D.G, and T. J. C,]; Medical Research Council [MC_UU_12019/1 and MC_UU_12019/3 to A.W, D.G., M.R]. Dr. Barnett is an employee of Cambridge Cognition, Ltd. This work forms part of the NIHR CLAHRC EoE that PBJ directs and the NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by NPG

Smoking in pregnancy, adolescent mental health and cognitive performance in young adult offspring: results from a matched sample within a Finnish cohort

$\textbf{Background:}$ The association between prenatal exposure to maternal cigarette smoking (PEMCS) and adult cognition is debated, including if there are differences according to sex. We aimed to determine if there are associations between PEMCS and cognition in early adulthood in men and women and examine if observed associations were mediated by adolescent mental health factors that are associated with cognition, namely psychotic-like experiences (PLEs), inattention and hyperactivity, and other externalizing behaviors. $\textbf{Methods:}$ Participants were 471 individuals drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986) followed up from pregnancy and birth to early adulthood; individuals with PEMCS were matched with those without PEMCS by socioeconomic and demographic factors. Cognitive performance in adulthood was assessed with a range of tests and their association with PEMCS was measured by sex using hierarchical linear regression, unadjusted and then controlling for potential confounders, mediators and moderators, including adolescent mental health factors. $\textbf{Results:}$ There were no associations between PEMCS and cognitive scores in females. In males, there were associations with vocabulary (beta = -0.444, 95% CI: -0.783, -0.104) and matrix reasoning (beta = -0.379, 95% CI: -0.711, -0.047). $\textbf{Conclusions:}$ While associations between PEMCS and cognition were limited, observed findings with measures of general intelligence in males contribute to suggestions of differences in response to PEMCS by sex. Furthermore, observed associations may be partly mediated by earlier inattention and hyperactivity. Findings add support to efforts aimed to eliminate smoking in pregnancy.The Northern Finland Birth Cohort 1986 is funded by the University of Oulu, University Hospital of Oulu, Academy of Finland, Sigrid Juselius Foundation, European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000- 01643), and NIH/NIMH (5R01MH63706:02). Cambridge Cognition Ltd. provided support in the form of salaries for author Jennifer H. Barnett

Non-overshooting stabilisation via state and output feedback

The concept of “strong stability” of LTI systems has been introduced in a recent paper [KHP2]. This is a stronger notion of stability compared to alternative definitions (e.g. stability in the sense of Lyapunov, asymptotic stability), which allows the analysis and design of control systems with non-overshooting response in the state-space for arbitrary initial conditions. The paper reviews the notion of “strong stability” [KHP2] and introduces the problem of non-overshooting stabilization. It is shown that non-overshooting stabilization under dynamic and static output feedback are, in a certain sense, equivalent problems. Thus, we turn our attention to static non-overshooting stabilization problems under state-feedback, output injection and output feedback. After developing a number of preliminary results, we give a geometric interpretation to the problem in terms of the intersection of an affine hyperplane and the interior of an open convex cone. A solution to the problem is finally obtained via Linear Matrix Inequalities, along with the complete parametrization of the optimal solution set

Assessing Deaf Cultural Competency of Physicians and Medical Students

The Medical Students, Cancer Control, and the Deaf Community Training program (DCT) intended to create physicians who were culturally competent to care for deaf patients were evaluated. DCT medical students (n = 22), UCSD medical faculty (n = 131), and non-DCT medical students (n = 211) were anonymously surveyed about their perceptions related to deaf patients, deaf cultural competency, and interpreter use. The faculty and non-DCT medical students displayed less knowledge than the DCT students. These findings suggest that training medical students in deaf cultural competency can significantly increase their capacity to care for community members and reduce the health disparities experienced by this community

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

<b>Background</b> Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. <p></p> <b>Methods</b> 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. <p></p> <b>Results</b> People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. <p></p> <b>Conclusion</b> People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation