Childhood IQ and risk of bipolar disorder in adulthood: prospective birth cohort study

Background: Intellectual ability may be an endophenotypic marker for bipolar disorder. Aims: Within a large birth cohort, we aimed to assess whether childhood IQ (including both verbal IQ (VIQ) and performance IQ (PIQ) subscales) was predictive of lifetime features of bipolar disorder assessed in young adulthood. Method: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large UK birth cohort, to test for an association between measures of childhood IQ at age 8 years and lifetime manic features assessed at age 22–23 years using the Hypomania Checklist-32 (HCL-32; n=1881 individuals). An ordinary least squares linear regression model was used, with normal childhood IQ (range 90–109) as the referent group. We adjusted analyses for confounding factors, including gender, ethnicity, handedness, maternal social class at recruitment, maternal age, maternal history of depression and maternal education. Results: There was a positive association between IQ at age 8 years and lifetime manic features at age 22–23 years (Pearson's correlation coefficient 0.159 (95% CI 0.120–0.198), P>0.001). Individuals in the lowest decile of manic features had a mean full-scale IQ (FSIQ) which was almost 10 points lower than those in the highest decile of manic features: mean FSIQ 100.71 (95% CI 98.74–102.6) v. 110.14 (95% CI 107.79–112.50), P>0.001. The association between IQ and manic features was present for FSIQ, VIQ and for PIQ but was strongest for VIQ. Conclusions: A higher childhood IQ score, and high VIQ in particular, may represent a marker of risk for the later development of bipolar disorder. This finding has implications for understanding of how liability to bipolar disorder may have been selected through generations. It will also inform future genetic studies at the interface of intelligence, creativity and bipolar disorder and is relevant to the developmental trajectory of bipolar disorder. It may also improve approaches to earlier detection and treatment of bipolar disorder in adolescents and young adults

Comparison between PI and PR current controllers in grid connected PV inverters

This paper presents a comparison between Proportional Integral (PI) and Proportional Resonant (PR) current controllers used in Grid Connected Photovoltaic (PV) Inverters. Both simulation and experimental results will be presented. A 3kW Grid- Connected PV Inverter was designed and constructed for this research.peer-reviewe

Design of PR current control with selective harmonic compensators using Matlab

This paper presents a procedure to design a Proportional Resonant (PR) current controller with additional PR selective harmonic compensators for Grid Connected Photovoltaic (PV) Inverters. The design of the PR current control and the harmonic compensators will be carried out using Matlab. Testing was carried out on a 3kW Grid- Connected PV Inverter which was designed and constructed for this research. Both simulation and experimental results will be presented.peer-reviewe

Borderline personality and attention-deficit hyperactivity traits in childhood are associated with hypomanic features in early adulthood

Background There is limited understanding of the symptomatic development of bipolar disorder from childhood to early adulthood. Aims We assessed whether borderline personality disorder traits, ADHD, and emotional, behavioural and social difficulties during childhood were associated with hypomania assessed in young adulthood. Method We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine associations between measures of childhood psychopathology and lifetime hypomanic features assessed at age 22–23 years using the Hypomania Checklist-32 (HCL-32; n = 3,372). We also conducted a factor analysis of the HCL to identify latent constructs underlying hypomania, and the extent to which childhood psychopathology was associated with these. Results We identified two factors of the HCL corresponding to energy/mood and risk-taking/irritability. There was evidence of association between childhood borderline personality disorder traits and both hypomania factors, with evidence that the association was stronger with the risk-taking/irritability factor. All individual borderline traits, with the exception of fear of abandonment, were associated with hypomania. There was also evidence of association between most other measures of childhood psychopathology (ADHD, hyperactivity, conduct problems, peer relationship problems and reduced prosocial behaviour) and the risk-taking/irritability factor, but much less consistent evidence of association with the energy/mood factor. Limitations The HCL cannot diagnose bipolar disorder and may be subject to reporting bias. Conclusions A broad range of childhood psychopathologies may represent early markers of risk for hypomania. Further studies are required to understand the mechanisms underlying these associations, and to inform earlier detection of bipolar disorder

Genetic risk for bipolar disorder and psychopathology from childhood to early adulthood

Background: Studying the phenotypic manifestations of increased genetic liability for Bipolar Disorder (BD) can increase understanding of this disorder. Aims: We assessed whether genetic risk for BD was associated with childhood psychopathology and features of hypomania in young adulthood within a large population-based birth cohort. Methods: We used data from the second Psychiatric Genetics Consortium Genome Wide Association Study (GWAS) for Bipolar Disorder to construct a polygenic risk score (PRS) for each individual in the Avon Longitudinal Study of Parents and Children (ALSPAC). Linear and logistic regression models were used to assess associations between the BD-PRS and emotional/behavioural difficulties, attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) traits in childhood, as well as hypomania in early adulthood (sample sizes from 2654 to 6111). Results: The BD-PRS was not associated with total hypomania score, but was weakly associated with a binary measure of hypomania (OR = 1.13, 95%CI 0.98,1.32; p = 0.097), and particularly at higher hypomania symptom thresholds (strongest evidence OR = 1.33, 95%CI 1.07, 1.65; p = 0.01). The BD-PRS was also associated with ADHD (OR = 1.31, 95%CI 1.10, 1.57; p = 0.018), but not with other childhood psychopathology. Limitations: The PRS only captures common genetic variation and currently explains a relatively small proportion of the variance for BD. Conclusions: The BD-PRS was associated with ADHD in childhood, and weakly with adult hypomania, but not with other psychopathology examined. Our findings suggest that genetic risk for BD does not appear to manifest in childhood to the same extent as schizophrenia genetic risk has been reported to do

Reduction of current harmonics in grid-connected PV inverters using harmonic compensation - conforming to IEEE and IEC standards

This paper deals with the reduction of harmonics generated by Grid-Connected PV Inverters to conform to the harmonic limits set by the IEEE and IEC standards. An analysis of the current harmonics present in the output current of a grid-connected inverter will be presented. The inverter will be current controlled by a Proportional-Resonant (PR) current controller. The design and testing of the PR current controller will be presented. This paper will also deal with the application of harmonic compensation to make the inverter compliant to the standards, by using selective harmonic compensators in addition to the Proportional-Resonant (PR) controller. Both simulation and experimental results will be presented. Testing was carried out on a Grid-Connected PV Inverter which was designed and constructed for this research.peer-reviewe

Paralleling of buck converters for DC microgrid operation

This paper presents the controller design of paralleled Buck converters using Droop Control to obtain common load sharing for DC Microgrid operation. Proportional Integral (PI) controllers are used to provide nested current and voltage control of the Buck converters. Droop control is applied to obtain load sharing between the paralleled converters. Then, a voltage restoration loop is applied utilizing another PI controller to restore the desired voltage in the dc microgrid, correcting any voltage deviations caused by the droop loop. The operation of the controllers is tested by simulating two paralleled Buck converters operated in the continuous current mode while sharing a common resistive load.peer-reviewe

Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants

Background UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors. Aims An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders. Method An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders. Results 157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation. Conclusions The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health

Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity

The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell-intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity

Investigating associations between genetic risk for bipolar disorder and cognitive functioning in childhood

Introduction Identifying phenotypic manifestations of genetic risk for bipolar disorder (BD) in childhood could increase our understanding of aetiological mechanisms. Aims To examine whether BD genetic risk is associated with childhood (age 8 years) cognitive function. Methods Using data from the Avon Longitudinal Study of Parents and Children, we examined associations between polygenic risk scores for BD (BD-PRS) derived using Psychiatric Genomics Consortium summary data at p-thresholds (PT) ≤0.01 (primary) and ≤0.5 (secondary) and several cognitive domains (sample sizes 5,613 to 5,936). We also examined whether associations were due to SNPs that have shared risk effects on schizophrenia (SZ). Results At PT≤0.01, the BD-PRS was associated with poorer executive functioning (ß= -0.03, 95%CI -0.06, -0.01; p = 0.013), and, more weakly with poorer processing speed (ß = -0.02, 95%CI -0.05, 0.02; p = 0.075). Evidence of association with both poorer processing speed (p = 0.016) and performance IQ (p = 0.018) was stronger at PT≤0.5. Associations with performance IQ and processing speed were primarily driven by genetic effects that are shared with SZ risk, but there was some evidence of bipolar-specific genetic effects on childhood executive functioning. Limitations The BD-PRS still explains only a small proportion of the variance for BD which will have reduced power to detect associations. Conclusions Genetic risk for BD manifests as impaired cognition in childhood, and this is driven by risk SNPs that are also shared with SZ genetic risk. Further elucidation of which cognitive domains are most affected by genetic risk for BD could help understanding of aetiology and improve prediction of BD