Processing of food stimuli in anorexia nervosa: An ERP-study comparing adolescents and adults.

BACKGROUND: Anorexia nervosa (AN) is associated with altered processing of disorder-relevant stimuli. Event-related potentials (ERP) - such as the Late Positive Potential (LPP) - give information about the underlying mechanisms of central nervous stimulus processing. METHODS: Patients with AN (22 adolescents, 23 adults) and healthy controls (HCs; 17 adolescents, 24 adults) were included. Neutral, low, and high calorie food-images were rated for valence and arousal; EEG activity was recorded and LPPs (early: 350-700 ms; late: 800-1200 ms) were extracted. Effects of patient status, age group, and stimulus category were analyzed via mixed 2 × 2 × 3-AN(C)OVAs. RESULTS: Patients with AN rated high calorie stimuli lower in valence and higher in arousal than HCs. Controlling for hunger, food stimuli elicited higher early LPPs than neutral ones in patients and HCs. For the late LPP, patients with AN showed larger amplitudes. CONCLUSION: Results suggest a highly automatic attentional bias towards low-calorie foods. Patients with AN seem to have more intense cognitive processing independent of stimulus material. More research is needed to validate and clarify differences between early and late LPP measures as well as the operationalization and relevance of hunger status.

Child neurodevelopment and mental health after surgical ventricular septal defect repair: risk and protective factors.

AIM: This case-control study examined the long-term consequences of surgical correction for ventricular septal defect (VSD; the most common congenital heart defect) in infancy. It assessed children who had undergone VSD surgery and the factors related to maternal conditions, surgery, and hospital stay. METHOD: Thirty-nine children (23 females, 16 males; age range 6y 1mo-9y 7mo [mean 7y 4mo, SD 1y]) with repaired isolated, non-syndromic, non-genetic VSD were compared with 39 typically developing children (22 females, 17 males; age range 6y-9y 2mo [mean 7y 3mo, SD 10mo]). The children completed behavioural tests of neurodevelopment and a quality of life (QoL) questionnaire. Mothers rated children's emotional/behavioural symptoms and QoL. Measures of maternal parenting behaviour and psychopathology were treated as moderators. RESULTS: Affected children showed reduced language skills (p=0.002) unless mothers reported high parenting behaviour subscale scores (p=0.04). Children's anxiety symptoms were elevated when mothers had anxiety symptoms (p=0.01). Longer hospital stay was associated with lower intelligence (p=0.003) and psychomotor scores (p=0.006). Longer scars predicted elevated child anxiety (p=0.008), and age at surgery and QoL were inversely related (p=0.01). INTERPRETATION: Impairments could be mitigated if VSD repair was performed early in life with a relatively small scar and uncomplicated hospital stay. This outcome depends on maternal parenting behaviour and anxiety symptoms. WHAT THIS PAPER ADDS: Children's cognitive and psychomotor development after surgical ventricular septal defect repair was unimpaired. Children showed no mental health restrictions when their mothers reported few anxiety symptoms themselves. Language impairments might be preventable by pro-active parenting. The outcome also depends on variables related to surgery and hospital stay.

Associations of prenatal depressive symptoms with DNA methylation of HPA axis-related genes and diurnal cortisol profiles in primary school-aged children.

Epigenetic DNA modifications in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are discussed as a mechanism underlying the association between prenatal depression and altered child HPA activity. In a longitudinal study, DNA methylation changes related to prenatal depressive symptoms were investigated in 167 children aged 6 to 9 years. At six candidate genes, 126 cytosine-guanine dinucleotides were considered without correcting for multiple testing due to the exploratory nature of the study. Further associations with the basal child HPA activity were examined. Children exposed to prenatal depressive symptoms exhibited lower bedtime cortisol (p = .003, ηp2 = 0.07) and a steeper diurnal slope (p = .023, ηp2 = 0.06). For total cortisol release, prenatal exposure was related to lower cortisol release in boys, and higher release in girls. Furthermore, prenatal depressive symptoms were associated with altered methylation in the glucocorticoid receptor gene (NR3C1), the mineralocorticoid receptor gene (NR3C2), and the serotonin receptor gene (SLC6A4), with some sex-specific effects (p = .012-.040, ηp2 = 0.03-0.04). In boys, prenatal depressive symptoms predicted bedtime cortisol mediated by NR3C2 methylation, indirect effect = -0.07, 95% confidence interval [-0.16, -0.02]. Results indicate relations of prenatal depressive symptoms to both child basal HPA activity and DNA methylation, partially fitting a mediation model, with exposed boys and girls being affected differently.

[Epigenetic modifications in children associated with maternal emotional stress during pregnancy]. / Affektive Belastungen der Mutter in der Schwangerschaft und assoziierte epigenetische Veränderungen beim Kind: Eine Übersicht.

Besides typical physical and hormonal changes during pregnancy, this life period is often associated with an increased emotional and mental stress for women. For the child, the time in utero is regarded as a critical developmental period since adverse stimuli during pregnancy can have lasting consequences for the fetal and postnatal health and development. Thus, prenatal depression, anxiety and stress are considered as risk factors for developmental delay, emotional and behavioral problems. Epigenetic modifications, especially modifications in DNA methylation, are discussed as a possible biological mechanism that could explain the association between prenatal emotional stress and altered developmental and health outcomes of the child. This review summarizes evidence for DNA methylation changes related to prenatal emotional stress from studies with a candidate-gene approach as well as epigenome-wide association studies. Problematic issues are discussed and recommendations for future research are presented.

A 10-Year-Old Girl's Dysfunctional 'Self-Help' in ADHD: Suppression of Hyperkinetic Symptoms via Self-Induced Weight Loss in the Context of Anorexia Nervosa-A Case Report.

Anorexia Nervosa (AN) and Attention Deficit Hyperactivity Disorder (ADHD) are frequent mental disorders in child and adolescent psychiatry. Comorbidity of these disorders is, however, rare among minors. Thus, little is known about their mutual impact on illness development as well as diagnostic and therapeutic influencing factors. We report the case of a 10-year old girl with AN and massive underweight. At the age of 5, ADHD had been diagnosed. Application of ADHD-specific medication had been refused by her caregiver. As of 3rd grade, hyperkinetic symptoms were significantly reduced, which was later linked to beginning AN-induced weight loss. At inpatient admission, no clinically relevant ADHD-related symptoms were present. Accompanying weight gain, rather 'sudden' appearance of attention difficulties, motoric hyperactivity and impulsivity were reported, widely impairing our patient's schoolwork and further daily life. Methylphenidate medication showed good clinical response and tolerability. We hypothesize that the former massive underweight had suppressed ADHD-specific behaviour. AN with significant weight loss could possibly mask hyperkinetic symptoms in children. Thus, sufficient clinical diagnostics and intense monitoring during ED treatment are required. Physicians and therapists should be sensitized for interactions in the joint occurrence of these mental disorders among minors.

Computer Based Body Exposure in Adolescents With Anorexia Nervosa: A Study Protocol.

Body dissatisfaction is a core feature of eating disorders (EDs) and plays an essential role in the development and maintenance of anorexia nervosa (AN). In the current study, a computer based body exposure intervention is conducted and evaluated regarding short-term effects on body dissatisfaction, psychopathology, viewing patterns, and stress reactivity. Within a randomized controlled trial (RCT) female adolescents and young women with AN are either receiving the intervention or treatment as usual (TAU). Furthermore, in a transdiagnostic approach, a highly body-dissatisfied group of clinical control participants obtaining the intervention will be surveyed to identify AN-specific processes. The standardized four-session body exposure intervention using photographs of the own body is adapted from a manualized body image treatment program for computer use. Psychopathology (body dissatisfaction, body image avoidance, body checking, depression, anxiety) is assessed via standardized questionnaires before and after the intervention. During each session, attentional biases regarding one's own body are measured via eye tracking, stress levels are measured via subjective ratings, heart rate variability, as well as salivary cortisol and alpha amylase. Between- and within-subject effects will be assessed. The pilot study aims to identify short-term effects of the intervention on body dissatisfaction and attentional bias, as well as to investigate the potential underlying mechanism of physiological habituation.

Anxiety Is Associated With DPPIV Alterations in Children With Selective Mutism and Social Anxiety Disorder: A Pilot Study.

Background: Both selective mutism (SM) and social anxiety disorder (SAD) are severe pediatric anxiety disorders with the common trait of behavioral inhibition (BI). The underlying pathophysiology of these disorders remains poorly understood, however converging evidence suggests that alterations in several peripheral molecular pathways might be involved. In a pilot study, we investigated alterations in plasma molecular markers (dipeptidyl peptidase-4 [DPPIV], interleukin-6 [IL-6], tumor necrosis factor-ß [TNF-ß] and neuropeptide-Y [NPY]) in children with SM, SAD, and healthy controls, as well as the correlation of these markers to symptom severity. Methods: We included 51 children and adolescents (aged 5-18 years; n = 29 girls): n = 20 children in the SM-, n = 16 in the SAD- and n = 15 in the control-group (CG). Peripheral blood samples were analyzed for DPPIV, IL-6, TNF-ß, and NPY concentrations. Diverse psychometric measures were used for BI, anxiety, and mutism symptoms. Results: Lower DPPIV-levels were correlated with more anxiety symptoms. However, we could not find a difference in any molecular marker between the patients with SAD and SM in comparison to the CG. Conclusion: DPPIV is proposed as relevant marker for child and adolescent anxiety. Investigating the pathophysiology of SM and SAD focusing on state and trait variables as anxiety or BI might help better understanding the underlying mechanisms of these disorders. Further studies with especially larger cohorts are needed to validate the current pilot-findings.

Genome-Wide DNA Methylation Patterns in Children Exposed to Nonpharmacologically Treated Prenatal Depressive Symptoms: Results From 2 Independent Cohorts.

BACKGROUND: Maternal depressive symptoms are a common phenomenon during pregnancy and are related to negative outcomes for child development and health. Modifications in child DNA methylation are discussed as an underlying mechanism for the association between prenatal depressive symptoms and alterations in child outcomes. However, formerly reported genome-wide associations have yet to be replicated. METHODS: In an epigenome-wide association study (EWAS), alterations of DNA methylation related to maternal prenatal depressive symptoms were investigated in buccal cell samples from 174 children (n = 52 exposed to prenatal depressive symptoms; 6-9 years old) of the German longitudinal study FRAMES-FRANCES. Whole blood samples from the independent, age-comparable ARIES subsample of the ARIES/ALSPAC study (n = 641; n = 159 exposed to prenatal depressive symptoms; 7-8 years old) were examined as a confirmation sample. Depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. DNA methylation was analyzed with the Infinium Human Methylation 450k BeadChip. Modifications in single CpGs, regions, and biological pathways were investigated. Results were adjusted for age and birth outcomes as well as postnatal and current maternal depressive symptoms. Analyses were performed for the whole sample as well as separated for sex. RESULTS: The EWAS yielded no differentially methylated CpG or region as well as no accordance between samples withstanding correction for multiple testing. In pathway analyses, no overlapping functional domain was found to be enriched for either sample. A comparison of current and former findings suggests some overlapping methylation modifications from infancy to childhood. Results suggest that there might be sex-specific differential methylation, which should be further investigated in additional studies. CONCLUSIONS: The current, mainly nonsignificant, results challenge the assumption of consistent modifications of DNA methylation in children exposed to prenatal depressive symptoms. Despite the relatively small sample size used in this study, this lack of significant results may reflect diverse issues of environmental epigenetic studies, which need to be addressed in future research.

Salivary and hair cortisol as biomarkers of emotional and behavioral symptoms in 6-9 year old children.

The aim of the present work is to investigate the association of salivary and cumulative cortisol levels with emotional and behavioral symptoms in a Franconian Cognition and Emotion Studies (FRANCES) general population cohort of 158 6- to 9 year old children. Salivary cortisol values were measured by one-day diurnal cortisol profile, whereas cumulative cortisol was estimated via one-month hair cortisol concentrations (rHCC). Nearly all significant associations of clinical symptoms with child cortisol indices were age dependent: We report emotional symptoms being associated with lower rHCC in younger children (6.06-7.54 years). In older children (7.55-9.41 years) behavioral problems were further associated with higher rHCC and lower salivary cortisol awakening responses. In summary, child clinical symptoms were stronger associated with markers of hair cortisol compared to salivary cortisol. To picture developmental mechanisms, we suggest longitudinal designs for cortisol measures of stress systems in children and adolescents.

Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children.

Prenatal alcohol exposure (PAE) is known to elicit a broad range of systemic effects, including neurophysiological alterations that result in adverse behavioral and cognitive outcomes. However, molecular pathways underlying these long-term intrauterine effects remain to be investigated. Here, we tested a hypothesis that PAE may lead to epigenetic alterations to the DNA resulting in attentional and cognitive alterations of the children. We report the results of the study that included 156 primary school children of the Franconian Cognition and Emotion Studies (FRANCES) cohort which were tested for an objective marker of PAE, ethyl glucuronide (EtG) in meconium at birth. Thirty-two newborns were found to be exposed to alcohol with EtG values above 30 ng/g (EtG+). Previously we described PAE being associated with lower IQ and smaller amplitude of the event-related potential component P3 in go trials (Go-P3), which indicates a reduced capacity of attentional resources. Whole-genome methylation analysis of the buccal cell DNA revealed 193 differentially methylated genes in children with positive meconium EtG, that were clustered into groups involved in epigenetic modifications, neurodegeneration, neurodevelopment, axon guidance and neuronal excitability. Furthermore, we detected mediation effects of the methylation changes in DPP10 and SLC16A9 genes on the EtG related cognitive and attention-related deficits. Our results suggest that system-wide epigenetic changes are involved in long-term effects of PAE. In particular, we show an epigenetic mediation of PAE effects on cognition and attention-related processes.

Long-term Associations of an Early Corrected Ventricular Septal Defect and Stress Systems of Child and Mother at Primary School Age.

INTRODUCTION: Ventricular septal defect (VSD) is the most common congenital heart defect, with larger VSDs typically being corrected with an open-heart surgery during infancy. Long-term consequences of a VSD-corrective surgery on stress systems of child and mother are still unknown. The aim of the present study is to investigate the associations of an early corrected VSD and diurnal cortisol release of child and mother. METHODS: 26 children (12 boys) between 6 and 9 years old, who underwent surgery for an isolated VSD within the first 3 years of life, and their mothers participated in the study. Their diurnal cortisol profiles were compared to a sex-, age-, and socioeconomic status-matched healthy control group. Within the VSD group, associations between cortisol and characteristics of surgery and hospitalization were investigated. Child and mother psychopathological symptoms were considered as a possible interfering mechanism of altered cortisol profiles. RESULTS: Diurnal cortisol profiles of children with an early corrected VSD did not differ from those of controls. However, mothers of affected children exhibited higher cortisol levels in the morning (p < 0.001, [Formula: see text]) and a steeper diurnal cortisol slope (p = 0.016, [Formula: see text]) than mothers of healthy children. CONCLUSION: Results indicate a favorable development of children with an early corrected VSD, in terms of comparable diurnal cortisol profiles with healthy controls, according to a comparable mother-rated psychopathology. Mothers of affected children reveal altered diurnal cortisol levels, without differences in self-rated psychopathology. This divergence should be clarified in future research.

Attention, cognitive control and motivation in ADHD: Linking event-related brain potentials and DNA methylation patterns in boys at early school age.

In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings. Performance and event-related potential measures (inter alia Cue-P3 and Nogo-P3), which were recorded in a motivational go/nogo task, indicated diminished attentional orienting, reduced inhibitory response control and a larger motivational effect on performance in ADHD already at this relatively young age. Methylation patterns were analysed in buccal cell DNA with the Illumina HumanMethylation 450K array. For CpG sites at genes of the dopaminergic (COMT, ANKK1) and the neurotrophic (BDNF, NGFR) system, associations with the Nogo-P3 as well as ADHD symptom severity were found suggesting that these systems are involved in response control deficits in ADHD. Methylation effects related to both functional aspects and ADHD behaviour were also observed for DPP10 and TPH2. Epigenetic mechanisms may play a role in ADHD-associated deficits but findings need to be replicated in larger samples and are limited by the fact that only peripheral methylation could be considered.