Placental mitochondrial DNA content is associated with childhood intelligence

Background: Developmental processes in the placenta and the fetal brain are shaped by the similar biological signals. Evidence accumulates that adaptive responses of the placenta may influence central nervous system development. We hypothesize that placental mtDNA content at birth is associated with intelligence in childhood. In addition, we investigate if intra-pair differences in mtDNA content are associated with intra-pair differences in intelligence. Methods: Relative mtDNA content was measured using qPCR in placental tissue of 375 children of the East Flanders Prospective Twin Survey. Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) between 8 and 15 years old. We accounted for sex, gestational age, birth weight, birth year, zygosity and chorionicity, cord insertion, age at measurement, indicators of socioeconomic status, smoking during pregnancy, and urban environment. Results: In multivariable adjusted mixed modelling analysis, each doubling in placental mtDNA content was associated with 2.0 points (95% CI 0.02 to 3.9; p = 0.05) higher total and 2.3 points (95% CI 0.2 to 4.3; p = 0.03) higher performance IQ in childhood. We observed no association between mtDNA content and verbal intelligence. Intra-pair differences in mtDNA content and IQ were significantly (p = 0.01) correlated in monozygotic-monochorionic twin pairs, showing that the twin with the highest mtDNA content was 1.9 times more likely (p = 0.05) to have the highest IQ. This was not observed in dichorionic twin pairs. Conclusions: We provide the first evidence that placental mtDNA content is associated with childhood intelligence. This emphasizes the importance of placental mitochondrial function during in utero life on fetal brain development with long-lasting consequences

Psychiatric Diagnosis Revisited:Towards a System of Staging and Profiling Combining Nomothetic and Idiographic Parameters of Momentary Mental States

BACKGROUND: Mental disorders may be reducible to sets of symptoms, connected through systems of causal relations. A clinical staging model predicts that in earlier stages of illness, symptom expression is both non-specific and diffuse. With illness progression, more specific syndromes emerge. This paper addressed the hypothesis that connection strength and connection variability between mental states differ in the hypothesized direction across different stages of psychopathology. METHODS: In a general population sample of female siblings (mostly twins), the Experience Sampling Method was used to collect repeated measures of three momentary mental states (positive affect, negative affect and paranoia). Staging was operationalized across four levels of increasing severity of psychopathology, based on the total score of the Symptom Check List. Multilevel random regression was used to calculate inter- and intra-mental state connection strength and connection variability over time by modelling each momentary mental state at t as a function of the three momentary states at t-1, and by examining moderation by SCL-severity. RESULTS: Mental states impacted dynamically on each other over time, in interaction with SCL-severity groups. Thus, SCL-90 severity groups were characterized by progressively greater inter- and intra-mental state connection strength, and greater inter- and intra-mental state connection variability. CONCLUSION: Diagnosis in psychiatry can be described as stages of growing dynamic causal impact of mental states over time. This system achieves a mode of psychiatric diagnosis that combines nomothetic (group-based classification across stages) and idiographic (individual-specific psychopathological profiles) components of psychopathology at the level of momentary mental states impacting on each other over time

Cortisol dynamics in depression:Application of a continuous-time process model

Background: The temporal dynamics of cortisol may be altered in depression. Optimally studying these dynamics in daily life requires specific analytical methods. We used a continuous-time multilevel process model to study set point (rhythm-corrected mean), variability around this set point, and regulation strength (speed with which cortisol levels regulate back to the set point after any perturbation). We examined the generalizability of the parameters across two data sets with different sampling and assay methods, and the hypothesis that regulation strength, but not set point or variability thereof, would be altered in depressed, compared to non-depressed individuals. Methods: The first data set is a general population sample of female twins (n = 523), of which 21 were depressed, with saliva samples collected 10 times a day for 5 days. The second data set consists of pair-matched clinically depressed and non-depressed individuals (n = 30), who collected saliva samples 3 times a day for 30 days. Set point, regulation strength and variability were examined using a Bayesian multilevel Ornstein-Uhlenbeck (OU) process model. They were first compared between samples, and thereafter assessed within samples in relation to depression. Results: Set point and variability of salivary cortisol were twice as high in the female twin sample, compared to the pair-matched sample. The ratio between set point and variability, as well as regulation strength, which are relative measures and therefore less affected by the specific assay method, were similar across samples. The average regulation strength was high; after an increase in cortisol, cortisol levels would decrease by 63 % after 10 min, and by 95 % after 30 min, but depressed individuals of the pair-matched sample displayed an even faster regulation strength. Conclusions: The relative parameters of the two data sets. The results suggest that regulation strength is increased in depressed individuals. We recommend the presented methodology for future studies and call for replications with more diverse depressed populations

Unraveling the Role of Loneliness in Depression:The Relationship Between Daily Life Experience and Behavior

Objective: Focusing on temporal associations between momentary (or state) loneliness, appraisal of social company, and being alone in daily life may help elucidate mechanisms that contribute to the development of prolonged (or trait) loneliness and major depressive disorder (MDD). We aim to examine if (a) a self-reinforcing loop between loneliness, negative appraisals of social company, and being alone in daily life may contribute to trait loneliness; (b) this possible self-reinforcing loop may also contribute to the development of MDD, by testing differences in temporal relationships between these social elements in participants who did or did not develop MDD during follow-up; and (c) any of these social elements at baseline predicted a MDD at follow-up. Methods: A female general population sample (n = 417) participated in an experience sampling method (ESM) study. Time-lagged analyses between loneliness, appraisal of social company, and being alone were examined at baseline, and their associations with the development of MDD during 20 months follow-up were investigated. Results: State loneliness was followed by an increase in negative appraisals of social company and a higher frequency of being alone. Further, negative appraisals of social company were associated with a higher frequency of being alone afterward. Only the latter was significant in the transition to MDD group. Trait loneliness predicted MDD during follow-up. Conclusions: Avoiding social contact after appraising company more negatively may contribute to the development of MDD.</p

Telomere tracking from birth to adulthood and residential traffic exposure

Background: Telomere attrition is extremely rapid during the first years of life, while lifestyle during adulthood exerts a minor impact. This suggests that early life is an important period in the determination of telomere length. We investigated the importance of the early-life environment on both telomere tracking and adult telomere length. Methods: Among 184 twins of the East Flanders Prospective Twin Survey, telomere length in placental tissue and in buccal cells in young adulthood was measured. Residential addresses at birth and in young adulthood were geocoded and residential traffic and greenness exposure was determined. Results: We investigated individual telomere tracking from birth over a 20 year period (mean age (SD), 22.6 (3.1) years) in association with residential exposure to traffic and greenness. Telomere length in placental tissue and in buccal cells in young adulthood correlated positively (r = 0.31, P < 0.0001). Persons with higher placental telomere length at birth were more likely to have a stronger downward shift in telomere ranking over life (P < 0.0001). Maternal residential traffic exposure correlated inversely with telomere length at birth. Independent of birth placental telomere length, telomere ranking between birth and young adulthood was negatively and significantly associated with residential traffic exposure at the birth address, while traffic exposure at the residential address at adult age was not associated with telomere length. Conclusions: Longitudinal evidence of telomere length tracking from birth to adulthood shows inverse associations of residential traffic exposure in association with telomere length at birth as well as accelerated telomere shortening in the first two decades of life

Prediction of the Effect of Adaptation and Active HB Mechanics on Prestin-Based Amplification Using a Macroscopic Model of the Cochlea

Introduction: Negative social evaluation is associated with psychopathology. Given the frequency of evaluation through increasingly prevalent virtual social networks, increased understanding of the effects of this social evaluation is urgently required. Methods: A new digital social peer evaluation experiment (digi-SPEE) was developed to mimic everyday online social interactions between peers. Participants received mildly negative feedback on their appearance, intelligence, and congeniality. Two hundred and forty-one young people [58.9% female, aged 18.9 years (15 to 34)] from an ongoing novel general population twin study participated in this study. Positive affect (PA), negative affect (NA), implicit self-esteem, and cortisol were assessed before and after exposure to the social evaluation experiment. Results: The social evaluation experiment decreased PA (B=-5.25, p Conclusion: The digi-SPEE represents a social evaluation stressor that elicits biological and implicit and explicit mental changes that are relevant to mechanisms of psychopathology

The complex and dynamic interplay between self-esteem, belongingness and physical activity in daily life:An experience sampling study in adolescence and young adulthood

Physical activity has positive effects on self-esteem and sense of belongingness and vice versa. The experience sampling method allows for a level of analysis of the within-subject temporal dynamics of these interactions. We hypothesized that physical activity would predict prospective increases of self-esteem and belongingness in the flow of daily life, and vice versa. Additionally, we hypothesized that belongingness would predict self-esteem at the beep level. The study included 781 individuals (17.4 +/- 3.5 years; 59% female) who responded to 10 beeps daily for 6 days to items on physical activity, self-esteem and belongingness. Univariate and multivariate multilevel models were used to examine within-person prospective bidirectional associations. We found that physical activity predicted higher self-esteem and belongingness at t0+1. Participants who had a stronger increase of self-esteem following an increase in physical activity also had a concurrent stronger increase in belongingness. In contrast, self-esteem had no effect on physical activity at the next beep. Belongingness predicted self-esteem. We conclude that the interactions between physical activity, self-esteem and belongingness are complex and fluctuating in daily life. This has important implications for current theories describing the mental health benefits of physical activity

Childhood trauma, BDNF Val66Met and subclinical psychotic experiences. Attempt at replication in two independent samples

Childhood trauma exposure is a robust environmental risk factor for psychosis. However, not all exposed individuals develop psychotic symptoms later in life. The Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been suggested to moderate the psychosis-inducing effects of childhood trauma in clinical and nonclinical samples. Our study aimed to explore the interaction effect between childhood trauma and the BDNF Val66Met polymorphism on subclinical psychotic experiences (PEs). This was explored in two nonclinical independent samples: an undergraduate and technical-training school student sample (n = 808, sample 1) and a female twin sample (n = 621, sample 2). Results showed that childhood trauma was strongly associated with positive and negative PEs in nonclinical individuals. A BDNF Val66Met x childhood trauma effect on positive PEs was observed in both samples. These results were discordant in terms of risk allele: while in sample 1 Val allele carriers, especially males, were more vulnerable to the effects of childhood trauma regarding PEs, in sample 2 Met carriers presented higher PEs scores when exposed to childhood trauma, compared with Val carriers. Moreover, in sample 2, a significant interaction was also found in relation to negative PEs. Our study partially replicates previous findings and suggests that some individuals are more prone to develop PEs following childhood trauma because of a complex combination of multiple factors. Further studies including genetic, environmental and epigenetic factors may provide insights in this field