Early childhood and adolescent risk factors for psychotic depression in a general population birth cohort sample

Background and purpose In the group of severe mental disorders, psychotic depression (PD) is essentially under-researched. Knowledge about the risk factors is scarce and this applies especially to early risk factors. Our aim was to study early childhood and adolescent risk factors of PD in a representative birth cohort sample with a follow-up of up to 50 years. Methods The study was carried out using the Northern Finland Birth Cohort 1966 (NFBC 1966). We used non-psychotic depression (NPD) (n = 746), schizophrenia (SZ) (n = 195), psychotic bipolar disorder (PBD) (n = 27), other psychoses (PNOS) (n = 136) and healthy controls (HC) (n = 8200) as comparison groups for PD (n = 58). We analysed several potential early risk factors from time of birth until the age of 16 years. Results The main finding was that parents' psychiatric illness [HR 3.59 (1.84-7.04)] was a risk factor and a high sports grade in school was a protective factor [HR 0.29 (0.11-0.73)] for PD also after adjusting for covariates in the multivariate Cox regression model. Parental psychotic illness was an especially strong risk factor for PD. The PD subjects had a parent with psychiatric illness significantly more often (p < 0.05) than NPD subjects. Differences between PD and other disorder groups were otherwise small. Conclusions A low sports grade in school may be a risk factor for PD. Psychiatric illnesses, especially psychoses, are common in the parents of PD subjects. A surprisingly low number of statistically significant risk factors may have resulted from the size of the PD sample and the underlying heterogeneity of the etiology of PD

Early exposure to social disadvantages and later life body mass index beyond genetic predisposition in three generations of Finnish birth cohorts

BackgroundThe study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI.MethodsWe studied participants of Helsinki Birth Cohort Study born in 1934-1944 (HBCS1934-1944, n=1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n=5807, NFBC1986, n=6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62years in HBCS1934-1944, at 46years in NFBC1966 and at 16years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex.ResultsThe association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (beta =0.79, 95% CI, 0.33, 1.25, p 0.22, 95% CI -0.91,1.35, p=0.700). In HBCS1934-1944 and NFBC1966, participants who had reduced their exposure to social disadvantage during the life-course had lower later life BMI than those who had increased their exposure (beta -1.34, [-2.37,-0.31], p=0.011; beta -0.46, [-0.89,-0.03], p=0.038, respectively).ConclusionsHigh social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.Peer reviewe

Hemodynamic responses to emotional speech in two-month-old infants imaged using diffuse optical tomography

Emotional speech is one of the principal forms of social communication in humans. In this study, we investigated neural processing of emotionalspeech (happy, angry, sad and neutral) in the left hemisphere of 21 two-month-old infants using diffuse optical tomography. Reconstructed total hemoglobin (HbT) images were analysed using adaptive voxel-based clustering and region-of-interest (ROI) analysis. We found a distributedhappy > neutral response within the temporo-parietal cortex, peakingin the anterior temporal cortex; a negative HbT response to emotional speech (the average of the emotional speech conditions angry in the anterior superior temporal sulcus (STS), happy > angry in the superior temporal gyrus and posterior superior temporal sulcus, angry </p

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Background: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. Conclusion: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern

Dermatitis and Aging-Related Barrier Dysfunction in Transgenic Mice Overexpressing an Epidermal-Targeted Claudin 6 Tail Deletion Mutant

The barrier function of the skin protects the mammalian body against infection, dehydration, UV irradiation and temperature fluctuation. Barrier function is reduced with the skin's intrinsic aging process, however the molecular mechanisms involved are unknown. We previously demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are essential in the development of the epidermis and that transgenic mice overexpressing Cldn6 in the suprabasal layers of the epidermis undergo a perturbed terminal differentiation program characterized in part by reduced barrier function. To dissect further the mechanisms by which Cldn6 acts during epithelial differentiation, we overexpressed a Cldn6 cytoplasmic tail deletion mutant in the suprabasal compartment of the transgenic mouse epidermis. Although there were no gross phenotypic abnormalities at birth, subtle epidermal anomalies were present that disappeared by one month of age, indicative of a robust injury response. However, with aging, epidermal changes with eventual chronic dermatitis appeared with a concomitant barrier dysfunction manifested in increased trans-epidermal water loss. Immunohistochemical analysis revealed aberrant suprabasal Cldn localization with marked down-regulation of Cldn1. Both the proliferative and terminal differentiation compartments were perturbed as evidenced by mislocalization of multiple epidermal markers. These results suggest that the normally robust injury response mechanism of the epidermis is lost in the aging Involucrin-Cldn6-CΔ196 transgenic epidermis, and provide a model for evaluation of aging-related skin changes

LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases

Consultocracy and its discontents : A critical typology and a call for a research agenda

Peer reviewe