Explore the vast range of titles available.

Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.

Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.

Background Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic “smoking methylation pattern”, and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top “smoking methylation pattern” genes AHRR , MYO1G , GFI1 , CYP1A1 , and CNTNAP2 . The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 ( PIM1 ); cg25949550 ( CNTNAP2 ); and cg08699196 ( ITGB7 ). Sex-specific analyses revealed a mediating effect for cg25949550 ( CNTNAP2 ) in male newborns. Conclusion The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.

Clock genes govern circadian rhythms and shape the effect of alcohol use on the physiological system. Exposure to severe negative life events is related to both heavy drinking and disturbed circadian rhythmicity. The aim of this study was 1) to extend previous findings suggesting an association of a haplotype tagging single nucleotide polymorphism of PER2 gene with drinking patterns, and 2) to examine a possible role for an interaction of this gene with life stress in hazardous drinking. Data were collected as part of an epidemiological cohort study on the outcome of early risk factors followed since birth. At age 19 years, 268 young adults (126 males, 142 females) were genotyped for PER2 rs56013859 and were administered a 45-day alcohol timeline follow-back interview and the Alcohol Use Disorders Identification Test (AUDIT). Life stress was assessed as the number of severe negative life events during the past four years reported in a questionnaire and validated by interview. Individuals with the minor G allele of rs56013859 were found to be less engaged in alcohol use, drinking at only 72% of the days compared to homozygotes for the major A allele. Moreover, among regular drinkers, a gene x environment interaction emerged (p = .020). While no effects of genotype appeared under conditions of low stress, carriers of the G allele exhibited less hazardous drinking than those homozygous for the A allele when exposed to high stress. These findings may suggest a role of the circadian rhythm gene PER2 in both the drinking patterns of young adults and in moderating the impact of severe life stress on hazardous drinking in experienced alcohol users. However, in light of the likely burden of multiple tests, the nature of the measures used and the nominal evidence of interaction, replication is needed before drawing firm conclusions.

Reports of current ADHD symptoms in adults with a childhood diagnosis of ADHD are often discrepant: While one subgroup reports a particularly high level of current ADHD symptoms, another reports—in contrast—a very low level. The reasons for this difference remain unclear. Although sex might play a moderating role, it has not yet been examined in this regard. In an epidemiological cohort study from birth to young adulthood, childhood ADHD diagnoses were assessed at the ages of 4.5, 8, and 11 years based on parent ratings. Sex-specific development of ADHD symptoms was analyzed from the age of 15 to 25 years via self-reported ADHD symptoms in participants with (n = 47) and without childhood ADHD (n = 289) using a random coefficient regression model. The congruence between parent reports and adolescents’ self-ratings was examined, and the role of childhood ADHD diagnosis, childhood OCC/CD, and childhood internalizing disorder as possible sex-specific predictors of self-reported ADHD symptoms at age 25 years was investigated. With regard to self-reported ADHD symptoms, females with a childhood ADHD diagnosis reported significantly more ADHD symptoms compared to females without childhood ADHD and males with and without ADHD throughout adolescence and young adulthood. In contrast, males with childhood ADHD did not differ from control males either at age 15 or at age 25 years. Only in females did a childhood diagnosis of an externalizing disorder (ADHD and CD/ODD) predict self-reported ADHD symptoms by age 25 years. Our findings suggest that self-reports of young adults with a childhood diagnosis of ADHD are influenced by sex. Specifically, females with childhood ADHD report increased levels of ADHD symptoms upon reaching adulthood. To correctly evaluate symptoms and impairment in this subgroup, other, more objective, sources of information may be advisable, such as neurophysiological measures.

Evidence suggests that maternal care constitutes a protective factor for psychopathology which may be conditional on the level of family adversity. Given that psychopathology is frequently linked with social deficits and the amygdala with social functioning, we investigated the impact of early maternal care on amygdala function under high vs low familial risk for psychopathology. Amygdala activity and habituation during an emotional face-matching paradigm was analyzed in participants of an epidemiological cohort study followed since birth (n = 172, 25 years). Early mother-infant interaction was assessed during a standardized nursing and play setting at the age of three months. Information on familial risk during the offspring's childhood and on the participants' lifetime psychopathology was obtained with diagnostic interviews. An interaction between maternal stimulation and familial risk was found on amygdala habituation but not on activation, with higher maternal stimulation predicting stronger amygdala habituation in the familial risk group only. Furthermore, amygdala habituation correlated inversely with Attention Deficit Hyperactivity Disorder (ADHD) diagnoses. The findings underline the long-term importance of early maternal care on the offspring's socioemotional neurodevelopment and of interventions targeting maternal sensitivity early in life, particularly by increasing maternal interactive behavior in those with familial risk. (ZPID).

Child temperament as well as parenting behaviors have been linked to adolescent depression. Beyond their main effects, the interplay between these factors is of interest. For example, in an interactive model, a differential susceptibility of temperamental variants to parenting has been suggested. However, so far, the differential susceptibility hypothesis has mostly been studied with a focus on externalizing disorders. On the other hand, parenting may shape the child’s temperament and vice versa in a transactional process. In a prospective, longitudinal at-risk sample (163 boys, 176 girls), we assessed emotional (easy–difficult) and regulative (self-control) temperament at ages 4.5, and 8 years, respectively, as well as parenting quality at age 4.5 years using the HOME inventory. Hierarchical linear regression analysis was used to investigate the prediction of depressive symptoms at age 11, measured by the Child Depression Inventory, including interaction terms between the temperament variable and parenting. We additionally tested whether parenting was mediated by child temperament. As previously reported, both self-control and parenting were longitudinally associated with preadolescent depressive symptoms. There were no interactive effects between temperament and parenting. However, the effects of parenting were partly mediated by self-control. Our data do not support a differential susceptibility of temperamental variants in the development of preadolescent depression. However, our results are in line with the assumption that parenting may shape young children’s temperament, with positive parenting in the early childhood fostering the development of regulative temperament.

In this study, the association of aggressive behavior and personality traits with plasma cortisol levels was investigated in a high-risk community sample of adolescents. Plasma cortisol levels were collected in 245 fifteen-year-olds (118 males, 127 females) from an epidemiological cohort study of children at risk for psychopathology. Additionally, measures of reactive and proactive aggression, externalizing behavior and callous-unemotional together with impulsive personality features were assessed. Both subtypes of aggression as well as delinquent behavior and impulsive personality traits showed significant negative correlations with plasma cortisol levels. This association was observed in males, but not in females. In both gender groups, callous-unemotional traits were unrelated to plasma cortisol levels. This result suggests that the association between cortisol levels and aggression in adolescents is mediated rather by impulsivity than by unemotional or psychopathic traits.

Prenatal stress (PS) is an established risk factor in the etiology of mental disorders. Although mother–child interaction is the infant’s first important training in dealing with stress, little is yet known about the impact of PS on mother–infant dyadic behavior. The current study aimed to elucidate the prospective influence of psychological and physiological stresses during pregnancy on mother–infant dyadic behavior. Mother–infant interactions were videotaped at 6-month postpartum and coded into three dyadic patterns: (1) both positive; (2) infant protesting–mother positive; and (3) infant protesting–mother negative, using the infant and caregiver engagement phases. Exposure to PS was assessed during pregnancy using psychological (i.e., psychopathological, perceived, and psychosocial PS; n  = 164) and physiological stress measures (i.e., maternal cortisol; n  = 134). Group comparisons showed that psychosocial PS was predictive of mother–infant behavior at 6-month postpartum, indicating that dyads of prenatally high-stressed mothers exhibited significantly more positive interaction patterns (i.e., infant positive–mother positive) as compared to the prenatally low-stressed group. Physiological PS was unrelated to mother–infant behavior. These results suggest that mild psychosocial PS may be advantageous for positive mother–infant dyadic behavior, which is in accordance with the stress-inoculation model that assumes a beneficial effect of PS.

Reward processing is altered in various psychopathologies and has been shown to be susceptible to genetic and environmental influences. Here, we examined whether maternal care may buffer familial risk for psychiatric disorders in terms of reward processing. Functional magnetic resonance imaging during a monetary incentive delay task was acquired in participants of an epidemiological cohort study followed since birth (N = 172, 25 years). Early maternal stimulation was assessed during a standardized nursing/playing setting at the age of 3 months. Parental psychiatric disorders (familial risk) during childhood and the participants' previous psychopathology were assessed by diagnostic interview. With high familial risk, higher maternal stimulation was related to increasing activation in the caudate head, the supplementary motor area, the cingulum and the middle frontal gyrus during reward anticipation, with the opposite pattern found in individuals with no familial risk. In contrast, higher maternal stimulation was associated with decreasing caudate head activity during reward delivery and reduced levels of attention deficit hyperactivity disorder (ADHD) in the high-risk group. Decreased caudate head activity during reward anticipation and increased activity during delivery were linked to ADHD. These findings provide evidence of a long-term association of early maternal stimulation on both adult neurobiological systems of reward underlying externalizing behavior and ADHD during development.