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Abstract Background Perinatal markers of prenatal development are associated with offspring psychiatric symptoms. However, there is little research investigating the specificity of perinatal markers for the development of specific disorders. This study aimed to explore if perinatal markers are specifically associated with adolescent substance use disorder (SUDs). Methods Adolescent participants from two study centers, one for SUD patients (n = 196) and one for general psychopathology (n = 307), were recruited for participation. Since the SUD participants presented with a number of comorbid disorders, we performed a 1-on-1 matching procedure, based on age, gender, and specific pattern of comorbid disorders. This procedure resulted in n = 51 participants from each group. From all participants and their mothers we recorded perinatal markers (mode of birth, weeks of completed pregnancy, birth weight, Apgar score after 5 min) as well as intelligence quotient (IQ). The SUD sample additionally filled out the Youth Safe Report (YSR) as well as the PQ-16 and the DUDIT. We aimed to distinguish the two groups (SUD sample vs. general psychiatric sample) based on the perinatal variables via a logistic regression analysis. Additionally, linear regressions were performed for the total group and the subgroups to assess the relationship between perinatal variables and IQ, YSR, DUDIT and PQ-16. Results The perinatal variables were not able to predict group membership (X 2 [4] = 4.77, p = .312, Cox & Snell R² = 0.053). Odds ratios indicated a small increase in probability to belonging to the general psychiatric sample instead of the SUD sample if birth was completed via C-section. After Bonferroni-correction, the linear regression models showed no relation between perinatal markers and IQ (p = .60, R² = 0.068), YSR (p = .09, R² = 0.121), DUDIT (p = .65, R² = 0.020), and PQ-16 (p = .73, R² =0.021). Conclusion Perinatal markers were not able to distinguish SUD patients from patients with diverse psychopathologies. This pattern contradicts previous findings, perhaps because our chosen markers reflect general processes instead of specific mechanistic explanations. Future studies should take care to investigate specific prenatal markers and associate them with psychopathology on the symptom level.

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.

Family influences on child quality of life (QoL) are increasingly understood. Parenting behavior and parent individual psychopathology are among the established predictors of offspring mental health. However, literature often addresses these factors as ‘parental’, lacking further gender-specific differentiation while predominantly studying maternal aspects. Social and biological fathers are still underrepresented in family research. The aim of this study was to analyze paternal contributions to child well-being. A total of 197 father/mother-dyads gave a standardized self-report on parenting behavior and their own psychopathology at child primary school age (t1; 6–10 y). Ratings were compared mutually and associated with child self-rated QoL at t1 and adolescence (t2; 12–14 y). Fathers and mothers differed in psychopathology and most parenting behavior dimensions (positive parenting, involvement, responsible parenting, poor monitoring, and corporal punishment). Father psychopathology made a relevant predictive contribution to girls’ QoL at t2. Boys’ t1 QoL was significantly influenced by maternal parenting factors (positivity and corporal punishment). Compared to mothers, fathers are faced with different individual stressors; paternal parenting behavior is different, while fathers’ influences are significant, particularly for daughters. Father-addressed pre- and intervention programs in child psychotherapeutic treatment are of high relevance.

Abstract In our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.

Pregnancy anamnesis is a crucial part of child and adolescent psychiatry diagnostics. In previous works, the reliability of retrospective maternal self-report on perinatal characteristics was heterogeneous. This prospective longitudinal study aimed to evaluate women’s recall of prenatal events in a within-subject design. A sample of 241 women gave a self-report on prenatal alcohol, smoking, partnership quality, pregnancy satisfaction, and obstetric complications during the 3rd trimester (t0), childhood (t1, 6–10 y), and adolescence (t2, 12–14 y). The intra-individual agreement was examined. The t0–t1–(t2) agreement was poor to substantial; this was highest for smoking and worst for obstetric complications, followed by alcohol (Fleiss’ κ = 0.719 to −0.051). There were significant t0–t1–(t2) differences for all pregnancy variables (p < 0.017), except for 3rd trimester satisfaction (p = 0.256). For alcohol (t0 25.8%, t1 17.4%, t2 41.0%) and smoking (t0 11.9%, t1 16.4%, t2 22.6%), the highest self-reported rates were found during adolescence. During childhood, fewer obstetric complications (t0 84.9%, t1 42.2%) and worse partnerships were reported (t0 M = 8.86, t1 M = 7.89). Thought to be due to social stigmata and memory effects, pregnancy self-reports cannot be precisely reproduced. Creating a respectful and trusting atmosphere is essential for mothers to give honest self-reports that are in the best interest of their children.

In anorexia nervosa, aberrant emotional reactions toward body stimuli have been discussed. We investigated heart rate as a physiological marker when viewing body stimuli and hypothesized altered HR reactions toward those highly significant and emotional stimuli in anorexia nervosa. In total, 37 anorexia nervosa patients and 43 control participants viewed pictures of women of five different weight categories, while their cardiac activity was recorded. R-R intervals following picture onset were determined, and means were calculated for three distinct time periods. The overall change in HR relative to baseline across all picture categories was greater in the patient group than in the control group (significant effect of “group”, p = 0.002, partial η2 = 0.120). A significant decrease in HR 2 to 8 s after picture presentation was found for pictures of women of extreme weight in both participant groups (significant “category ∗ time segment interaction”, p = 0.01, partial η2 = 0.037) and correlated with scores of sociocultural attitudes toward the appearance for the extremely underweight category (r = −0.33, p = 0.005). Therefore, differential HR reactions for anorexia nervosa patients and control participants were found for body stimuli in general. The highest HR decelerations in response to pictures of strongly underweight and overweight women may reflect emotional processes such as anxiety due to social comparison.

Background/AimDetermining C-reactive protein (CRP) by non-invasive methods is of great interest for research addressing inflammation in young people. However, direct comparisons of such methods applied in children and adolescents are lacking so far. This study aimed to evaluate the association between CRP measured in dried blood spots (DBS CRP) and in saliva (sCRP), two less invasive alternatives to venipuncture, in 12- to 14-year-old adolescents. To evaluate the validity of both measurements in the context of biobehavioral studies, the potential of DBS CRP and sCRP to discriminate between defined BMI subgroups was assessed.Materials and MethodsCRP levels in DBS and saliva collected from 87 healthy adolescents (M = 13.25 years, SD = 0.30, 51.7% females) were determined using high sensitive CRP ELISA for serum and salivary CRP ELISA, respectively. Characteristics and correlation of both measurements were assessed for the total sample and for three subgroups classified by BMI percentile ranges (A: ≤ 25; B: 26–74; C: ≥ 75).ResultsIn the total sample, DBS CRP and sCRP were significantly associated (r = 0.59, p < 0.001). Splitting the sample into BMI-dependent subgroups revealed similarly strong associations of DBS CRP with sCRP for all three groups (A: r = 0.51; B: r = 0.61; C: r = 0.53). However, comparing the mean CRP values per BMI subgroup, one-way ANOVA reported significant differences for DBS CRP, but not for sCRP mean values.ConclusionsThe significant correlation of DBS CRP with sCRP was independent of the investigated BMI range groups, yet BMI-dependent distinction was only provided by DBS CRP mean values. Overall, our results suggest that DBS CRP is likely to reflect systemic inflammation more precisely. Salivary CRP can be alternatively determined in studies with adolescents when conditions require it, given the oral health status is assessed. Considering that DBS CRP and sCRP share only 35% of common variance, further studies should examine their specific validity.

Abstract 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.

Here, we explore the effects of prenatal alcohol exposure (PAE) in adolescence. We investigated associations between meconium ethyl glucoronide (EtG) and facial malformation. For 129 children (66/63 male/female; M = 13.3, SD = 0.32, 12–14 years), PAE was implemented by newborn meconium EtG and maternal self-reports during the third trimester. Cognitive development was operationalized by standardized scores (WISC V). The EtG cut-off values were set at ≥10 ng/g (n = 32, 24.8% EtG10+) and ≥112 ng/g (n = 20, 15.5% EtG112+). The craniofacial shape was measured using FAS Facial Photographic Analysis Software. EtG10+− and EtG112+-affected children exhibited a shorter palpebral fissure length (p = 0.031/p = 0.055). Lip circularity was smaller in EtG112+-affected children (p = 0.026). Maternal self-reports were not associated (p > 0.164). Lip circularity correlated with fluid reasoning (EtG10+ p = 0.031; EtG112+ p = 0.298) and working memory (EtG10+ p = 0.084; EtG112+ p = 0.144). The present study demonstrates visible effects of the facial phenotype in exposed adolescents. Facial malformation was associated with a child’s cognitive performance in the alcohol-exposed group. The EtG biomarker was a better predictor than maternal self-reports.

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.

IntroductionVentricular 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.Methods26 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.ResultsDiurnal 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

A constant preoccupation with food and restrictive eating are main symptoms of anorexia nervosa (AN). Imaging studies revealed aberrant neural activation patterns in brain regions processing hedonic and reward reactions as well as-potentially aversive-emotions. An imbalance between so called "bottom-up" and "top-down" control areas is discussed. The present study is focusing on neural processing of disease-specific food stimuli and emotional stimuli and its developmental course in adolescent and adult AN patients and could offer new insight into differential mechanisms underlying shorter or more chronic disease.33 adolescents aged 12-18 years (15 AN patients, 18 control participants) and 32 adult women (16 AN patients, 16 control participants) underwent functional magnetic resonance imaging (fMRI, 3T high-field scanner) while watching pictures of high and low-calorie food and affective stimuli. Afterwards, they rated subjective valence of each picture. FMRI data analysis was performed using a region of interest based approach.Pictures of high-calorie food items were rated more negatively by AN patients. Differences in activation between patients and controls were found in "bottom up" and "top down" control areas for food stimuli and in several emotion processing regions for affective stimuli which were more pronounced in adolescents than in adults.A differential pattern was seen for food stimuli compared to generally emotion eliciting stimuli. Adolescents with AN show reduced processing of affective stimuli and enhanced activation of regions involved in "bottom up" reward processing and "top down" control as well as the insula with regard to food stimuli with a focus on brain regions which underlie changes during adolescent development. In adults less clear and less specific activation differences were present, pointing towards a high impact that regions undergoing maturation might have on AN symptoms.

In children with ADHD, different neurofeedback (NF) protocols have been applied, with the most prominent differentiation between EEG frequency-band (e.g. theta / beta) training and training of slow cortical potentials (SCPs). However, beyond distinctions between such basic NF variables, there are also competing assumptions about mechanisms of action (e.g., acquisition of regulation capability, generalization to daily life behavior).In the present article, we provide a framework for NF models and suppose two hypothetical models, which we call conditioning-and-repairing model and skill-acquisition model, reflecting extreme poles within this framework. We argue that the underlying model has an impact not only on how NF is applied but also on the selection of evaluation strategies and suggest using evaluation strategies beyond beaten paths of pharmacological research. Reflecting available studies, we address to what extent different views are supported by empirical data. We hypothesize that different models may hold true depending on the processes and behaviors to be addressed by a certain NF protocol. For example, the skill-acquisition model is supported by recent findings as an adequate explanatory framework for the mechanisms of action of SCP training in ADHD.In conclusion, evaluation and interpretation of NF trials in ADHD should be based on the underlying model and the way training is applied, which, in turn, should be stated explicitly in study reports.

Objective: In children with attention-deficit/hyperactivity disorder (ADHD), an increased theta/beta ratio in the resting EEG typically serves as a rationale to conduct theta/beta neurofeedback training. However, this finding is increasingly challenged. As neurofeedback may rather target an active than a passive state, we studied the EEG in a condition that requires attention.Methods: In children with ADHD of the DSM-IV combined type (ADHD-C; N=15) and of the predominantly inattentive type (ADHD-I; N=9) and in typically developing children (N=19), EEG spectral analysis was conducted for segments during the attention network test without processing of stimuli and overt behavior. Frontal (F3, Fz, F4), central (C3, Cz, C4) and parietal (P3, Pz, P4) electrodes were included in the statistical analysis. To investigate if EEG spectral parameters are related to performance measures, correlation coefficients were calculated.Results: Particularly in the ADHD-C group, higher theta and alpha activity was found with the most prominent effect in the upper-theta/lower-alpha (5.5-10.5 Hz) range. In the ADHD-I group, a significantly higher theta/beta ratio was observed at single electrodes (F3, Fz) and a tendency for a higher theta/beta ratio when considering all electrodes (large effect size). Higher 5.5-10.5 Hz activity was associated with higher reaction time variability with the effect most prominent in the ADHD-C group. A higher theta/beta ratio was associated with higher reaction times, particularly in the ADHD-I group.Conclusions: 1. In an attention demanding period, children with ADHD are characterized by an underactivated state in the EEG with subtype-specific differences. 2. The functional relevance of related EEG parameters is indicated by associations with performance (reaction time) measures. 3. Findings provide a rationale for applying NF protocols targeting theta (and alpha) activity and the theta/beta ratio in subgroups of children with ADHD.

Neurofeedback (NF) is being successfully applied, among others, in children with ADHD and as a peak performance training in healthy subjects. However, the neuronal mechanisms mediating a successful NF training have not yet been sufficiently uncovered for both theta/beta (T/B), and slow cortical potential (SCP) training, two protocols established in NF in ADHD. In the present randomized controlled investigation in adults without a clinical diagnosis (n = 59), the specificity of the effects of these two NF protocols on attentional processes, and motor system excitability were to be examined, focusing on the underlying neuronal mechanisms. NF training consisted of 10 double sessions, and self-regulation skills were analyzed. Pre- and post-training assessments encompassed performance and event-related potential measures during an attention task, and motor system excitability assessed by transcranial magnetic stimulation. Some NF protocol specific effects have been obtained. However, due to the limited sample size medium effects didn’t reach the level of significance. Self-regulation abilities during negativity trials of the SCP training were associated with increased contingent negative variation amplitudes, indicating improved resource allocation during cognitive preparation. Theta/beta training was associated with increased response speed and decreased target-P3 amplitudes after successful theta/beta regulation suggested reduced attentional resources necessary for stimulus evaluation. Motor system excitability effects after theta/beta training paralleled the effects of methylphenidate. Overall, our results are limited by the non-sufficiently acquired self-regulation skills, but some specific effects between good and poor learners could be described. Future studies with larger sample sizes and sufficient acquisition of self-regulation skills are needed to further evaluate the protocol specific effects on attention and motor system excitability reported.

Short interval intracortical inhibition (SICI) of motor cortex, measured by transcranial magnetic stimulation (TMS) in a passive (resting) condition, has been suggested as a neurophysiological marker of hyperactivity in attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to determine motor excitability in a go/nogo task at stages of response preparation, activation and suppression in children with ADHD, depending on the level of hyperactivity and impulsivity. Motor evoked potentials were recorded in 29 typically developing children and 43 children with ADHD (subdivided in two groups with higher and lower levels of hyperactivity/impulsivity; H/I-high and H/I-low). In the H/I-high group, SICI was markedly reduced in the resting condition and during response preparation. Though these children were able to increase SICI when inhibiting a response, SICI was still reduced compared to typically developing children. Interestingly, SICI at rest and during response activation were comparable, which may be associated with their hypermotoric behaviour. In the H/I-low group, response activation was accompanied by a pronounced decrease of SICI, indicating reduced motor control in the context of a fast motor response. In summary, different excitability patterns were obtained for the three groups allowing a better understanding of dysfunctional response activation and inhibition processes within the motor cortex in children with ADHD.