The role of early childhood psychological factors in determining risk for enuresis at school age in a UK cohort

There is evidence for a link between psychological factors and bedwetting, but the direction of this association is unclear. Using data on 8769 children from the Avon Longitudinal Study of Parents and Children, we examined whether difficult temperament (Toddler Temperament Scale at 24 months; Emotionality Activity Sociability Questionnaire at 38 months) and psychological problems (Revised Rutter Parent Scale for Preschool Children at 42 months) are linked to bedwetting at school age. We examined the association between these risk factors and different patterns of bedwetting from 4 to 9 years using multinomial regression. Difficult temperament and psychological problems in early childhood were associated with increased odds of bedwetting at 4–9 years. The strongest associations were most often found for the pattern of bedwetting that was both frequent (at least twice a week) and persistent (up to age 9) e.g. the temperament traits of ‘adaptability’ and ‘mood’ were associated with a 33 % increase (95 % confidence interval = 1.14–1.55) and a 27 % increase (1.10–1.47) respectively in the odds of persistent and frequent bedwetting per one standard deviation increase in risk score. Early behaviour problems (e.g. conduct problems [1.43 (1.25, 1.63)] and hyperactivity [1.29 (1.11, 1.50), p < 0.001]) were also associated with frequent and persistent bedwetting, but there was less evidence that early emotional difficulties were risk factors for bedwetting. Adjustment for confounders did not alter these conclusions. The presence of difficult temperament and behaviour problems in early childhood might help to identify children who will continue to experience bedwetting at school age. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00787-015-0756-7) contains supplementary material, which is available to authorized users

Omega-3 and Omega-6 Fatty acids and risk of psychotic outcomes in the ALSPAC birth cohort

Background Long chain polyunsaturated fatty acid (PUFA) levels have been implicated in the pathology of psychotic disorders. We investigated the relationship between childhood PUFA levels and later psychotic experiences (PE's) in a large birth cohort. Methods Plasma levels of Ω-3 and Ω-6 fatty acids (FA's) were assayed at ages 7 and 16 years. PE's were assessed at ages 12 and 18 years using a semi-structured interview. Primary outcome was any PE's at 18 years; sensitivity analyses examined incident PE's between ages 12 and 18 years, persistent PE's (at 12 and 18) and psychotic disorder at 18 years. Genetic instruments for Ω-3 and Ω-6 were derived and used in a multivariable Mendelian Randomization analysis. Results Higher levels of Ω-6 FA's AA, OA and AdA at age 7 years were weakly associated with a reduced risk for PE's at 18 years, however, effect sizes were small and attenuated after adjusting for confounders (strongest evidence for OA; adjusted OR, 0.842; 95% CI, 0.711, 0.998; p, 0.048). Total Ω-6 levels at age 16 years were associated with an increased odds of psychotic disorder at age 18 years. However, there was no association between Ω-6/Ω-3 ratio and psychosis outcomes, nor with genetic instruments of total Ω-3 or Ω-6 levels. Conclusions There is no strong evidence that total plasma Ω-3 FA levels or Ω-6/Ω-3 ratios in childhood and mid-adolescence are associated with increased risk for PE's or psychotic disorder, but very marginal evidence that alterations in the Ω-6 pathway at developmental time points might influence risk2

How does childhood maltreatment influence cardiovascular disease?:A sequential causal mediation analysis

BACKGROUND: Childhood maltreatment has been consistently associated with cardiovascular disease (CVD). However, the mechanisms of this relationship are not yet fully understood. We explored the relative contribution of anxiety/depression, smoking, body mass index (BMI) and inflammation (C-reactive protein, CRP) to the association between childhood maltreatment and CVD in men and women aged 40–69 years in the UK. METHODS: We used data from 40 596 men and 59 511 women from UK Biobank. To estimate the indirect effects of childhood maltreatment (physical, sexual and emotional abuse, and emotional and physical neglect) on incident CVD via each of the mediators, we applied a sequential mediation approach. RESULTS: All forms of maltreatment were associated with increased CVD risk [hazard ratios (HRs) ranging from 1.09 to 1.27]. Together, anxiety/depression, smoking, BMI and inflammation (indexed by CRP) mediated 26–90% of the association between childhood maltreatment and CVD, and the contribution of these mediators differed by type of maltreatment and sex. Anxiety/depression mediated the largest proportion of the association of sexual abuse, emotional abuse and emotional neglect with CVD (accounting for 16–43% of the total effect), especially in women. In men, BMI contributed the most to the indirect effect of associations of physical abuse and physical neglect with CVD; in women, anxiety/depression and BMI had similar contributions. CONCLUSIONS: These findings add to the understanding of how childhood maltreatment affects CVD risk and identify modifiable mediating factors that could potentially reduce the burden of CVD in people exposed to maltreatment in early life

A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation

Genetic variation in SLC12A5 which encodes KCC2, the neuron‐specific cation‐chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co‐segregating variant (KCC2‐R952H) in an Australian family with febrile seizures. We show that KCC2‐R952H reduces neuronal Cl− extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2‐R952H which likely contributes to the functional deficits. Our data suggest that KCC2‐R952H is a bona fide susceptibility variant for febrile seizures.Peer reviewe

Longitudinal associations between adolescent psychotic experiences and depressive symptoms

BACKGROUND: Psychotic experiences are prevalent in community samples and are highly correlated with depressive symptoms. This study aimed to investigate the longitudinal associations between psychotic experiences and depressive symptoms between adolescence and young adulthood. METHOD: Prospective cohort study with a 6 year follow-up in a community sample of 7632 adolescents and young adults. Depressive symptoms were assessed with the Short Moods and Feelings Questionnaire and psychotic experiences with a semi-structured clinical interview at 12 and 18 years. Longitudinal and cross-sectional associations were investigated with regression and structural equation models. RESULTS: Depressive symptoms and psychotic experiences were associated at each time-point (12 years r = 0.486 [95% CI 0.457, 0.515]; 18 years r = 0.286 [95% CI 0.233, 0.339]) and there were longitudinal within-phenotype associations (depressive symptoms r = 0.252 [95% CI 0.205, 0.299]; psychotic experiences r = 0.662 [95% CI 0.595, 0.729]). There was an across-phenotype association between psychotic experiences at 12 and depressive symptoms at 18 r = 0.139 [95% CI 0.086, 0.192; p<0.001], but no association between depressive symptoms at 12 and psychotic experiences at 18 r = -0.022 [95% CI -0.032, 0.077; p = 0.891]. CONCLUSIONS: Longitudinal across-phenotype associations were substantially weaker than cross-sectional associations or within-phenotype longitudinal associations. Whilst psychotic experiences at 12 years were associated with a small increase in depression at 18 years, depression at 12 years was not associated with psychotic experiences at 18 years once across-phenotype cross-sectional and within-phenotype longitudinal associations were accounted for. This suggests that the biological mechanisms underlying depression at this age do not increase subsequent risk of psychotic experiences once they resolve

Prohibition Plebiscites on the Prairies: (Not-So) Direct Legislation and Liquor Control in Alberta, 1915 to 1932

Since its introduction into North America in the late nineteenth century, direct democracy, particularly in the form of direct legislation, has periodically piqued the interest of legal scholars. A handful of studies have examined the history of direct legislation in the United States and in Canada; however, these studies often fail to examine how direct legislation was actually used. Brief references might be given to which initiatives the voters attempted to secure via direct legislation, but the actual mechanics of the vote, and questions such as what the ballot said, for example, are typically overlooked

Single nucleotide variations in CLCN6 identified in patients with benign partial epilepsies in infancy and/or febrile seizures

Nucleotide alterations in the gene encoding proline-rich transmembrane protein 2 (PRRT2) have been identified in most patients with benign partial epilepsies in infancy (BPEI)/benign familial infantile epilepsy (BFIE). However, not all patients harbor these PRRT2 mutations, indicating the involvement of genes other than PRRT2. In this study, we performed whole exome sequencing analysis for a large family affected with PRRT2-unrelated BPEI. We identified a non-synonymous single nucleotide variation (SNV) in the voltage-sensitive chloride channel 6 gene (CLCN6). A cohort study of 48 BPEI patients without PRRT2 mutations revealed a different CLCN6 SNV in a patient, his sibling and his father who had a history of febrile seizures (FS) but not BPEI. Another study of 48 patients with FS identified an additional SNV in CLCN6. Chloride channels (CLCs) are involved in a multitude of physiologic processes and some members of the CLC family have been linked to inherited diseases. However, a phenotypic correlation has not been confirmed for CLCN6. Although we could not detect significant biological effects linked to the identified CLCN6 SNVs, further studies should investigate potential CLCN6 variants that may underlie the genetic susceptibility to convulsive disorders.Toshiyuki Yamamoto, Keiko Shimojima, Noriko Sangu, Yuta Komoike, Atsushi Ishii, Shinpei Abe, Shintaro Yamashita, Katsumi Imai, Tetsuo Kubota, Tatsuya Fukasawa, Tohru Okanishi, Hideo Enoki, Takuya Tanabe, Akira Saito, Toru Furukawa, Toshiaki Shimizu, Carol J. Milligan, Steven Petrou, Sarah E. Heron, Leanne M. Dibbens, Shinichi Hirose, Akihisa Okumur