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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.

Beside somatic strains of congenital heart diseases (CHD), affected children often show developmental impairments in the long term. Ventricular septal defect (VSD) is the most common congenital heart defect and early surgical repair is associated with positive somatic outcomes. However, psychological adjustment is of lifelong relevance. We investigated 24 children with a surgically-corrected isolated VSD and their mothers from primary school (6–9 years) to adolescence (10–14 years) and compared them to controls. Both times, mothers reported child internalizing/externalizing problems, mothers and children rated child quality of life, and children performed neurodevelopmental tests. Adolescents also rated internalizing/externalizing problems themselves, and their hair cortisol levels were analyzed. Maternal anxiety and proactive parenting behavior were considered as moderators. Results revealed no group differences in child neurodevelopment (language, cognition), externalizing problems, and cortisol levels at any time. In reports from mothers, internalizing problems (depression, anxiety) were elevated in children with a VSD at both times—when mothers reported anxiety symptoms themselves. In adolescent reports, VSD patients’ quality of life was increased and internalizing problems were decreased—proactive parenting behavior went along with decreased symptoms in VSD-affected adolescents and with increased symptoms in controls. The findings pronounce the crucial role of parenting behavior and the influence of maternal anxieties on child mental health after surgical VSD repair and might highlight the need for parent-centered interventions.

Confinement due to the COVID-19 pandemic imposes a burden on adolescents worldwide and may seriously impact patients with an eating disorder (ED). The current FRanconian Anorexia Nervosa during COVID-19 (FRANCO) study explored (1) perceived change of depressive and ED symptomology during lockdown, (2) the role of social media, and (3) coping strategies of anorexia nervosa (AN) patients and clinical as well as healthy comparison groups. From June 2021 to September 2021, 222 female adolescents (19 with AN, 20 with depression, 45 with a self-reported psychiatric disorder (SRPD), and 138 controls) aged 11.2 to 18.9 years completed a one-time anonymous survey retrospectively reporting back on ED and depressive symptomology before and during the pandemic, the impact of social media, and coping strategies. A reduced quality of life (QoL) due to confinement was observed in almost half of female adolescents. All groups reported a significant perceived increase of disordered eating, overeating, anxiety, and depressive symptoms and emotion-regulation problems. In AN patients, significantly higher percentual deterioration of disordered eating and anxiety and depressive symptoms was found. For controls, a younger age and higher susceptibility of the sociocultural body image significantly correlated with increased disordered eating. Large-scale media literacy interventions are recommended.

BACKGROUND Drinking alcohol during pregnancy is considered a risk factor for child development; however, child biomarkers of prenatal alcohol exposure have been rarely studied. We examined whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with child cortisol concentrations at primary school age. METHODS For 137 children, prenatal alcohol exposure was operationalized by the meconium biomarker EtG and by maternal self-reports during pregnancy. Two EtG cut-offs (EtG ≥10 ng/g and EtG ≥112 ng/g) were applied. Cortisol concentrations were measured in saliva and hair samples. RESULTS Children with EtG ≥10 ng/g showed significantly reduced hair cortisol concentrations (HCCs) (p = .050, ηp2 = 0.042). For children with EtG ≥112 ng/g, the cortisol awakening response (CAR) was significantly decreased (p = .025, ηp2 = 0.070). These effects were also present in correlational analyses with continuous EtG data, speaking for partly dose-dependent effects. Especially, within the EtG ≥112 ng/g group, the basal (CAR: rp = -.642, p = .120) and cumulative (HCC: rp = -.660, p = .107) cortisol parameters were associated with child emotional symptoms at medium effect size. CONCLUSIONS The present study showed both the biological association of intrauterine alcohol exposure with the cortisol stress system, partly dose-dependent, and the functional association with emotional and behavioral symptoms.

Zusammenfassung. Schlafstörungen sind im Erwachsenen- wie auch im Kindes- und Jugendalter weit verbreitet. Kinder und Jugendliche in kinder- und jugendpsychiatrischer (KJP) Behandlung sind insbesondere davon betroffen. Die kognitive Verhaltenstherapie ist die Behandlung der ersten Wahl bei Schlafstörungen, der eine standardisierte Schlafdiagnostik vorangehen sollte. Im deutschsprachigen Raum fehlen bislang systematische Untersuchungen zur Schlafdiagnostik im teilstationären (TK) KJP-Setting. Für N = 46 Kinder/Jugendliche in TK-KJP-Behandlung wurde ein Schlafprotokoll (7 Tage), ein Schlafanamneseschema (Eltern & Kind/Jugendlicher) sowie ein klinisches Urteil zum Schlafverhalten (Diagnostiker_in) erhoben. Zudem wurde die Eltern-, Selbst- und klinische Beurteilung der psychischen Störung erfasst. Bei 52 % der Kinder/Jugendlichen wurden Schlafauffälligkeiten (= Schlafstörungssymptome im Rahmen komorbider Störungen) oder Schlafstörungen festgestellt, insbesondere Einschlafstörungen oder Ein- und Durchschlafstörungen (26 %). Zudem berichteten 33 % Albträume. Das Schlafverhalten korrelierte signifikant mit externalen Auffälligkeiten (r = .38 bis .61, p = 02 bis .04), auch beeinflussten Geschlecht (weiblich: p = .01 bis ≤ .001, |d| = 1.57 bis 2.50) und Alter (Ältere: p = .05, |d| = 0.78) das Schlafverhalten signifikant. Es scheinen insbesondere externale Auffälligkeiten einen Zusammenhang zu Schlafstörungen in der teilstationären Population aufzuweisen. Für die systematische Diagnostik der im TK-KJP-Setting vielfach vorliegenden Schlafauffälligkeiten, empfiehlt sich zusammenfassend ein Multi-Informant-Multi-Method-Vorgehen mit einer anschließenden individualisierten kognitiven Verhaltenstherapie der Schlafstörungen – gehäuft bei externalen Auffälligkeiten. Abstract. Sleep disorders are common in adults as well as children and adolescents. Children and adolescents in psychiatric treatment (CAP) are especially affected by sleep problems. Cognitive behavioral therapy represents the first-line treatment, preceded by a standardized procedure for sleep diagnostics. To date, no study has investigated sleep behavior in CAP day clinics in Germany. In this study, N = 46 children/adolescents receiving CAP treatment in a day clinic completed a sleep diary (7 days) and a sleep anamnesis scheme with the help of their parents, and their sleep behavior was assessed by a clinician. Furthermore, a parent- and a self-report questionnaire plus a clinical assessment of the mental disorders in the children/adolescents were collected. 52 % of the children/ adolescents exhibited sleep disorders or sleep abnormalities (= sleep disorder symptoms in the context of comorbid disorders), in particular problems falling asleep or to falling asleep and sleeping through the night (26 %). In addition, 33 % reported having nightmares. Their sleep behavior correlated significantly with their external behavior problems (r = .38 .61, p = .02-.04); their sex (female: p = .01–≤ .001, |d| = 1.57–2.50) and their age (older: p = .05, |d| = .78) also significantly influenced sleep behavior. Particularly external behavior problems were associated with sleep problems in this day-care population. In summary, a multi-method-multi-informant procedure should be established for the systematic diagnostics of sleep abnormalities, together with individualized cognitive-behavioral therapy of sleep problems, especially in patients with external behavior problems.

Anorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder‐compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food‐related conditioned responses and the influence of conditioned low‐calorie and high‐calorie food stimuli on instrumental responding for different foods. A Pavlovian‐to‐instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE‐Q, EDI‐2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low‐ and high‐calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low‐calorie food increased with increasing severity of eating disorder psychopathology suggesting weight‐loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward‐associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss.

Differential effects of blue- and red-enriched light on attention and sleep have been primarily described in adults. In our cross-over study in typically developing adolescents (11-17 years old), we found attention enhancing effects of blue- compared to red-enriched light in the morning (high intensity of ca. 1000 lx, short duration:1 h) in two of three attention tasks: e.g. better performance in math tests and reduced reaction time variability in a computerized attention test. In our pilot study, actigraphy measures of sleep indicated slight benefits for red- compared to blue-enriched light in the evening: tendencies toward a lower number of phases with movement activity after sleep onset in the complete sample and shorter sleep onset latency in a subgroup with later evening exposure times. These findings point to the relevance of light concepts regarding attention and sleep in typically developing adolescents. Such concepts should be developed and tested further in attention demanding contexts (at school) and for therapeutic purposes in adolescents with impaired attention or impaired circadian rhythms.

Background Dipeptidyl peptidase 4 (DPP4, CD26) is a moonlighting enzyme responsible for the proteolytic inactivation of neuropeptide Y (NPY), a peptide known for its anxiolytic effect in the central nervous system. Our previous work revealed a stress-resilient phenotype and a potentiation of short-term fear extinction in a congenic rat model deficient for DPP4 activity (DPP4mut). Here, we investigated neuroendocrine mechanisms underlying the phenotype of the DPP4mut animals. We studied the function of the hypothalamus–pituitary–adrenal (HPA) axis including the expression levels of its key genes and explored the possibility of structural NPY system changes. Methods and results We find decreased expression of Nr3c1 (glucocorticoid receptor - GR) and Fkbp5 (FK506 binding protein 5) in the amygdala and the hypothalamus of the DPP4mut rats, as well as the lower stress-induced peripheral corticosterone (CORT) levels. We detect no significant alterations in basal and DEX-induced CORT levels in the DPP4mut animals. The abundance of NPY-ergic neurons in the basolateral amygdala, dentate gyrus and hippocampus did not differ between the DPP4mut and their wild type littermates. Conclusion DPP4mut rats show blunted CORT response in line with their lower behavioral stress-response profile. These results are consistent with the hypothesis that increased central NPY levels elevate the threshold of stress response. We suggest that changes in the expression levels of key HPA axis genes (Nr3c1 and Fkbp5) are a consequence of the altered stress-perception of DPP4mut animals, thus further contributing to the stress-resilient phenotype.

BACKGROUND As a marker of cumulative cortisol activity, hair cortisol has received attention in clinical and methodological research. Currently, it is a common practice to relate the hair cortisol concentration (HCC) to hair weight. This article explores the hair protein concentration (HPC) as another possible reference value for HCC. METHODS For n = 18 hair samples cut from the posterior vertex, the HCC, HPC, and hair sample weight were determined, and the cortisol-to-weight and cortisol-to-protein ratios were calculated. Correlations were analyzed between the HCC, HPC, and hair sample weight as well as between the cortisol-to-weight and cortisol-to-protein ratios. Hair sample weight and HPC were included as independent variables in a stepwise linear regression model to predict HCC. RESULTS The HCC and HPC did not correlate significantly (r = 0.393, P = 0.106); however, the correlation between HCC and hair sample weight was significant (r = 0.520, P = 0.027). The HPC and hair sample weight (r = 0.605, P = 0.008) as well as the cortisol-to-weight and cortisol-to-protein ratios (r = 0.858, P < 0.000) showed a high correlation. The hair sample weight was the better predictor of the HCC (β = 0.520, P = 0.027) than HPC (β = 0.125, P = 0.657). CONCLUSIONS The results indicate that the hair sample weight is the more suitable reference value for the HCC. Thus, the standard cortisol-to-weight ratio should be used as the preferred expression for the cumulative cortisol activity measured in the scalp hair. However, calculating the cortisol-to-protein ratio can be considered as an alternative if the hair sample weight is not available.

ObjectiveDifferent components of body image processing seem to be reflected by different neural mechanisms. A core symptom of Anorexia nervosa (AN) is a disturbance of body image with correlates found on a neural level. The present study focusses at the neural processing of visual body stimuli of different weight categories in adolescent and adult AN patients.Method33 adolescents aged 12–18 years (15 AN patients, 18 control participants) and 36 adult women (19 AN patients, 17 control participants) underwent functional magnetic resonance imaging (fMRI) while performing a perceptive and an affective body image task involving photographic stimuli of women belonging to different BMI categories.ResultsDifferential effects on activation depending on the BMI of the women shown in the pictures were found in frontal brain regions, the thalamus, caudate and the fusiform gyrus. Group effects differentiating between AN patients and control participants were seen mainly in the caudate and insula.DiscussionDuring a perceptive task, diminished activation of regions involved in perceptive and evaluative functions as well as emotional reasoning was seen in AN. During evaluation of the neural processing in an affective task there was a tendency towards activation differences reflecting reduced ability of size estimation and impaired integration of visual and body perception with emotions.

ObjectiveTo elucidate the mechanisms of how snack foods may induce non-homeostatic food intake, we used resting state functional magnetic resonance imaging (fMRI), as resting state networks can individually adapt to experience after short time exposures. In addition, we used graph theoretical analysis together with machine learning techniques (support vector machine) to identifying biomarkers that can categorize between high-caloric (potato chips) vs. low-caloric (zucchini) food stimulation.MethodsSeventeen healthy human subjects with body mass index (BMI) 19 to 27 underwent 2 different fMRI sessions where an initial resting state scan was acquired, followed by visual presentation of different images of potato chips and zucchini. There was then a 5-minute pause to ingest food (day 1=potato chips, day 3=zucchini), followed by a second resting state scan. fMRI data were further analyzed using graph theory analysis and support vector machine techniques.ResultsPotato chips vs. zucchini stimulation led to significant connectivity changes. The support vector machine was able to accurately categorize the 2 types of food stimuli with 100% accuracy. Visual, auditory, and somatosensory structures, as well as thalamus, insula, and basal ganglia were found to be important for food classification. After potato chips consumption, the BMI was associated with the path length and degree in nucleus accumbens, middle temporal gyrus, and thalamus.ConclusionThe results suggest that high vs. low caloric food stimulation in healthy individuals can induce significant changes in resting state networks. These changes can be detected using graph theory measures in conjunction with support vector machine. Additionally, we found that the BMI affects the response of the nucleus accumbens when high caloric food is consumed.

Zusammenfassung. Eltern-Kind-Interaktionen erfolgen natürlicherweise bidirektional. In der Folge sollte kinder- und jugendpsychiatrische / -psychotherapeutische (KJP–) Behandlung individuums- und kontextzentrierte Interventionen berücksichtigen. Dafür wurde eine dimensionale Erhebung elterlicher Belastung, wie sie mittels des Eltern-Belastungs-Inventars (EBI; Tröster, 2011 ) möglich ist, untersucht. Für N = 166 zu einem KJP-Erstkontakt vorstellige Kinder und Jugendliche (11 – 18 Jahre) wurden KJP-relevante Merkmale (inkl. kritischer Lebensereignisse), die elterliche Belastung (EBI) und drei Messungen der kindseitigen Symptomatik betrachtet (1. Elternurteil, 2. Selbsturteil, 3. klinisches Urteil). Zusätzlich wurde die Elternsicht auf die KJP-Behandlung als Be- oder Entlastung analysiert. Die Ergebnisse zeigen eine auffällig hohe elterliche Belastung. Diese Belastung korrelierte signifikant mit kritischen Lebensereignissen sowie mit dem Elternurteil. Verglichen mit dem Selbst- und dem klinischen Urteil erwies sich nur das Elternurteil als hoch signifikanter Prädiktor elterlicher Belastung, die für verschiedene KJP-Merkmale variierte. Die Inanspruchnahme der KJP-Behandlung wurde seitens der Eltern zumeist als Entlastung erlebt. Das EBI erlaubt folglich die Beschreibung eltern- bzw. familienbezogener Belastungen aus dimensionaler Perspektive, die eine fundierte kontextzentrierte Behandlungsplanung unterstützt.

(1) This longitudinal study aimed to investigate the link between prenatal alcohol exposure and prenatal maternal depression with the offspring’s low-grade inflammatory status. (2) Prenatal alcohol exposure was determined via maternal self-report during the 3rd trimester of pregnancy (self-report+: n = 29) and the meconium alcohol metabolite Ethyl Glucuronide (EtG), collected at birth (≥30 ng/g: n = 23). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for prenatal maternal depressive symptoms during the 3rd trimester (≥10: n = 35). Fifteen years later, 122 adolescents (M = 13.32 years, 48.4% female) provided blood samples for the analysis of high sensitivity C-reactive protein (hsCRP, M = 0.91, SD = 1.28). (3) Higher hsCRP levels were found in EtG positive adolescents (p = 0.036, ηp2 = 0.04) and an inverse non-significant dose–response relation with hsCRP (r = −0.35, p = 0.113). For maternal self-reported prenatal alcohol consumption (p = 0.780, ηp2 = 0.00) and prenatal depressive symptoms (p = 0.360, ηp2 = 0.01) no differences for hsCRP levels between the affected and unaffected groups were found. (4) Adolescents with prenatal alcohol exposure are at risk for low-grade systemic inflammation. The EtG biomarker may be more accurate compared to self-reports. The findings suggest that prenatal maternal depression does not evoke low-grade systemic inflammation.

Background Alcohol intake during pregnancy is considered to be a risk factor for child development. Child biomarkers of intrauterine alcohol exposure have been rarely studied. We investigated whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with cognitive development, ADHD-related behaviour and neurophysiological markers of attention and executive control of children at primary-school age. Methods Mothers provided self-report on prenatal alcohol consumption during their 3rd trimester. Meconium samples were collected at birth. A total of 44 children with a meconium EtG above the detection limit (≥10 ng/g) and 44 nonexposed matched controls were compared. A second threshold (≥154 ng/g) was applied to study the dose effects. When children reached primary-school age, mothers rated ADHD-related behaviour, child cognitive development was measured using an IQ test battery, and event-related potentials were recorded during a cued go/nogo task. Results Children in both EtG-positive groups allocated fewer attentional resources than controls to the go/nogo task (reduced P3 component in go-trials). Children with a meconium EtG above 154 ng/g were also found to have an IQ that was six points lower than the other groups. Within the EtG ≥ 154 ng/g group, there was a positive correlation between EtG value and ADHD-related behaviour. These significant effects were not observed in relation to the maternal self-report data. Conclusions Associations between EtG and cognitive deficits, attentional resource capacity and ADHD-related behaviour could be documented with effects that were partially dose-dependent. In addition to maternal self-reports, this biomarker of intrauterine alcohol exposure may be considered as a predictor of child development.

Zusammenfassung. Fragestellung: Elternangaben werden regelhaft in die Diagnostik psychisch und verhaltensauffälliger Kinder und Jugendlicher einbezogen. Ihre Zuverlässigkeit steht jedoch aufgrund von Belastungen der Eltern und einer so verzerrten Wahrnehmung der kindseitigen Symptomatik infrage. Methodik: Für N = 68 zu einem kinder- und jugendpsychiatrischen/-psychotherapeutischen Erstkontakt vorstellige Kinder und Jugendliche (Alter: 11–18 Jahre) wurden je ein Eltern- und ein klinisches Urteil erhoben (internalisierende, externalisierende Auffälligkeiten, Gesamtproblemwert). Zusätzlich wurde die elterliche Belastung mittels des Eltern-Belastungs-Inventars (EBI, Tröster, 2011) erfasst (kind- und elternbezogene Belastung, Gesamtbelastungswert). Ergebnisse: Für auffällig belastete Eltern fanden sich in Mittelwertvergleichen größere Differenzen aus Eltern- und klinischem Urteil als für unauffällig belastete Eltern. Korrelationen zeigten zudem, dass eine höhere elterliche Belastung mit größeren Urteilsdifferenzen einhergeht. Die multiple Regression belegte dabei die Vorhersagekraft kindbezogener elterlicher Belastung für die Urteilsdifferenz. Genannte Ergebnisse gelten für internalisierende und externalisierende Auffälligkeiten sowie für den Gesamtproblemwert. Schlussfolgerungen: Elterliche Belastung sollte systematisch erfasst werden, um Elternangaben kritischer zu reflektieren und deren Einbezug in diagnostische und therapeutische Entscheidungen sorgfältiger abzuwägen.

Studies have shown that child development is negatively affected by prenatal depression. A dysregulated hypothalamic-pituitary-adrenal axis in the pregnant woman, passed to the fetus, is one discussed key mechanism. Studies, investigating primary-school age children, have found effects on antisocial behavior. Effects on internalizing symptoms were not found, but the analysis did not distinguish between anxiety and depression symptoms. Additionally, until now, no objective test data operationalizing social-emotional competencies have been included. The present study examined: 1.Whether the effects on child externalizing symptoms could be replicated; 2. If there are specific effects on child internalizing symptoms, separated for anxiety and depression; and 3. Are child clinical symptoms reflected in reductions in social-emotional competencies. A sample of 61 prenatally depressed and 143 prenatally not-depressed women and their 6–9 year old children were compared, controlling for key confounders in both the perinatal period and in middle childhood. Children of prenatally depressed mothers had more antisocial behavior and depression symptoms reported by their mothers. The prediction of antisocial behavior scores tended to be more significant for boys than for girls. Child anxiety symptoms were primarily explained by current maternal depressive symptoms. Children of prenatally depressed mothers also showed a reduction in social-emotional competencies, specifically regarding the ability to interpret complex social situations. This study showed that, even in a non-clinical sample, there are distinct effects of prenatal depression on child externalizing and internalizing symptoms which are accompanied by reductions in specific social-emotional competencies. These results emphasize that treatment for depressed pregnant women and/or early support for affected families is worthwhile. Additional work is required to identify the underlying biological mechanisms.

Because chronic stress is an important risk factor for anxiety states and depressive disorders, we studied hypothalamus-pituitary-adrenal (HPA) axis and sympathetic system activity via changes in cortisol and alpha amylase activity levels in pediatric generalized anxiety disorder (GAD) patients (n = 26) with comorbid depression and a healthy comparison group (n = 26). Morning plasma cortisol and diurnal profiles of salivary cortisol and salivary alpha amylase (sAA) activity were assessed, also reactivity of HPA-axis, sAA activity, and heart rate following a psychosocial stressor (Trier Social Stress Test for children). GAD patients with comorbid depression showed increased morning plasma and salivary cortisol levels, ameliorating throughout in-patient treatment, and higher sAA activity in their diurnal profile. Both HPA and sympathetic activity positively correlated with the severity of anxiety and depression. We also demonstrated a blunted HPA and sympathetic response to acute stress in patients. This pattern of neuroendocrine and sympathetic changes seems to be distinct from the one previously reported in pediatric patients with only social anxiety or depressive disorders. We propose morning plasma and saliva cortisol levels as potential physiological indicators for supporting the evaluation of symptoms' severity and treatment progress in children with GAD and comorbid depressive disorder.

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.

Maternal posttraumatic stress disorder (PTSD) following trauma exposure during pregnancy is associated with an increased risk of affective disorders in children. To investigate the mechanisms by which prenatal trauma and/or maternal PTSD affect brain development and behavior we established a mouse model of prenatal traumatic (PT) experience based on the application of an electric foot shock to C57Bl/6N female mice on the gestational day 12 during their pregnancy. The model is based on a previously validated animal model of PTSD. We found high anxiety levels and poor maternal care along with reduced serum prolactin and increased corticosterone levels in dams following maternal trauma (MT). PT-pups were born smaller and stayed smaller throughout their life. We show increased time and frequency of ultrasonic calls in PT-pups when separated from the mothers on the postnatal day (PND) 9. Cross-fostering experiments reveal lower anxiety levels in PT pups raised by healthy mothers as compared to trauma-naive pups raised by MT-dams. Importantly, the combination of prenatal trauma and being raised by a traumatized mother leads to: (1) the highest corticosterone levels in pups, (2) longest USV-call time and (3) highest anxiety levels in comparison to other experimental groups. Our data indicates a distinct change in maternal care following MT which is possibly associated with trauma-induced decrease in prolactin levels. Furthermore, we show that maternal behavior is crucial for the development of the offspring anxiety and specific aspects in maternal care overwrite to a significant extend the effects of in utero and postnatal environment. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1254-1265, 2016.

In Anorexia nervosa (AN) attentional biases towards, as well as away from, food cues have been found using different paradigms. In the current study, adult and adolescent AN patients and control participants performed two tasks while their eye movements were recorded. The tasks involved viewing and rating: 1. Single photographs of food items; 2. Pairs of pictures consisting of one picture of high calorie and one of low calorie food. Girls and women suffering from AN rated pictures of high calorie food as more negative than control participants. In the task showing single food pictures, reduced fixation times within Regions of Interest of low calorie food were seen in AN; during the task using picture pairs, a visual attentional bias towards low calorie and away from high calorie stimuli for AN was demonstrated. There is evidence for heightened visual attentional capture by high calorie stimuli when presented alone as well as attraction of attention by low calorie stimuli when shown next to high calorie stimuli, possibly facilitated by avoidance of the latter. Different attentional mechanisms seem to be activated when only one stimulus is shown compared to when two stimuli are competing for the viewer's attention.

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.

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.

This study aimed to evaluate the effects of the bacterial lipopolysaccharide (LPS) exposure during early pregnancy on anxiety-related behaviour of both pregnant female mice and their male offspring. Pregnant NMRI mice were treated with subcutaneous injections of LPS (30, 60, 120, 240 and 480 μg/kg) on the tenth gestational day of pregnancy. Pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6 and corticosterone levels, were measured in maternal serum 1.5h following the LPS injections. Baseline anxiety levels of pregnant mice (1.5h after LPS administration) and their male offspring (at postnatal days 60-70) were investigated with the elevated plus maze (EPM) test. In addition, anxiety levels in the offspring were measured after 2h restraint stress or TNF-α (10 μg/kg) administration. Our results demonstrate that LPS administration induces anxiety-like behaviour and a significant increase in cytokines and corticosterone levels in maternal serum. However, in male offspring, prenatal LPS administration has no significant effects on serum cytokines and corticosterone secretion with an exception of the lowest LPS dose that slightly reduced corticosterone levels. Interestingly, prenatal LPS treatment seemed to decrease the baseline anxiety levels, while pretreatment with restraint stress or TNF-α abolished this anxiolytic effects. In summary, our results suggest that prenatal exposure to LPS during early pregnancy may result in reduced baseline anxiety in adult male offspring.

In attention-deficit/hyperactivity disorder (ADHD), a reduced phasic alerting response (event-related potential component P3 to cue stimuli) has been reported for different subtypes and task types in a series of studies. In order to get a refined picture of this attentional deficit, which is based on the analysis of averaged event-related potentials, we studied the distribution of single-trial cue-P3 amplitudes and the relation between the cue-P3 and the neural state (EEG spectral analysis) when expecting the stimulus. Brain electrical activity was recorded in children of different ADHD subtypes (combined type, predominantly inattentive) and typically developing children while conducting the attention network test. In children with ADHD of the combined type, smaller cue-P3 amplitudes in the averaged signal were due to a larger portion of single trials with reduced cue-P3 amplitudes whereas maximum amplitudes did not differ from typically developing children. In this ADHD subtype, larger activity in the upper theta/lower alpha range (5.5-10.5Hz) was strongly associated with the range (difference between 0.9 quantile and 0.1 quantile) of the cue-P3 amplitude in single trials (correlation coefficient r=0.77) indicating a suboptimal neural state before stimulus presentation. In children with ADHD of the predominantly inattentive subtype, single-trial P3 amplitudes were comparable at lower quantiles but maximum amplitudes were reduced. This result pattern indicates an intact triggering of the cue-P3 but a reduced capacity of resource allocation for the predominantly inattentive subtype. Though findings are limited by a relative small sample size, the cue-P3 may be considered as a neurophysiological marker of alerting deficits in ADHD reflecting different underlying mechanisms in ADHD subtypes.

Knowledge about the core neural mechanisms of attention-deficit hyperactivity disorder, a pathophysiologically heterogeneous psychiatric disorder starting in childhood, is still limited. Progress may be achieved by combining different methods and levels of investigation. In the present study, we investigated neural mechanisms of motor control in 19 children with attention-deficit hyperactivity disorder (aged 9–14 years) and 21 age-matched typically developing children by relating neural markers of attention and response control (using event-related potentials) and measures of motor excitability/inhibition (evoked by transcranial magnetic stimulation). Thus, an interplay of processes at a subsecond scale could be studied. Using a monetary incentives-based cued Go/No-Go task, parameters that are well-known to be reduced in attention-deficit hyperactivity disorder were analysed: event-related potential components P3 (following cue stimuli; in Go and No-Go trials) and contingent negative variation as well as the transcranial magnetic stimulation-based short-interval intracortical inhibition measured at different latencies in Go and No-Go trials. For patient and control groups, different associations were obtained between performance, event-related potential and transcranial magnetic stimulation measures. In children with attention-deficit hyperactivity disorder, the P3 amplitude in Go trials was not correlated with reaction time measures but with short-interval intracortical inhibition at rest (r = 0.56, P = 0.01). In No-Go trials, P3 and short-interval intracortical inhibition after inhibiting the response (at 500 ms post-stimulus) were correlated in these children only (r = 0.62; P = 0.008). A classification rate of 90% was achieved when using short-interval intracortical inhibition (measured shortly before the occurrence of a Go or No-Go stimulus) and the amplitude of the P3 in cue trials as input features in a linear discriminant analysis. Findings indicate deviant neural implementation of motor control in children with attention-deficit hyperactivity disorder reflecting compensatory cognitive mechanisms as a result of a basal motor cortical inhibitory deficit (reduced activation of inhibitory intracortical interneurons). Both deviant inhibitory and attentional processes, which are not related to each other, seem to be characteristic for attention-deficit hyperactivity disorder at the neural level in motor control tasks. The underlying neural mechanisms, which are probably not restricted to the motor cortex and the posterior attention network, may play a key role in the pathophysiology of this child psychiatric disorder. The high classification rate can further be interpreted as a step towards the development of neural markers. In summary, the bimodal neurophysiological concept may contribute to developing an integrative framework for attention-deficit hyperactivity disorder.

Die Exzitabilität des motorischen Systems kann mittels der transkraniellen Magnetstimulation (TMS) untersucht werden. In dieser Arbeit wird ein Überblick über methodische Weiterentwicklungen und Forschungsergebnisse im Bereich der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) der vergangenen Jahre gegeben. Es werden verschiedene TMS-Parameter vorgestellt, die unter anderem die Funktion von Interneuronen im Motorkortex abbilden und neurophysiologische Inhibitionsmarker für ADHS darstellen könnten. Dies gilt insbesondere für die sogenannte intrakortikale Inhibition, die bei Kindern mit stark ausgeprägter hyperaktiver/impulsiver Symptomatik in Ruhe ähnlich gering wie kurz vor der Durchführung einer Bewegung ausfällt. Durch die Ableitung von TMS-evozierten Potentialen im EEG können Exzitabilitätsprozesse prinzipiell auch in nicht-motorischen Arealen untersucht werden. Die Effekte von Methylphenidat auf die Exzitabilität des motorischen Systems lassen sich im Sinne eines «Fine-Tunings» interpretieren, wobei diese überwiegend dopaminergen Effekte auch von genetischen Parametern (DAT1 Transporter) abhängen. Ein detaillierter Blick auf die Organisation motorischer Kontrolle ist durch eine kombinierte Messung von TMS-Parametern und ereignisbezogenen Potentialen möglich. Mit diesem Ansatz konnten bei Kindern mit ADHS eine unterschiedliche Implementierung bzw. mögliche kompensatorische Mechanismen (unter Beteiligung des präfrontalen Kortex) aufgezeigt werden. Diese Befunde, die zu einem besseren Verständnis von Hyperaktivität/Impulsivität, Inhibitionsmechanismen und motorischer Kontrolle bei ADHS sowie den Wirkmechanismen medikamentöser Therapie beitragen, unterstreichen die Bedeutung der TMS als neurophysiologische Methode zur Erforschung von ADHS.

Information from parents is regularly used in the diagnostic process of children and adolescents with psychiatric symptoms. But the reliability of this information is debatable, because the parents’ own stress can distort their perceptions of the child’s symptoms.For each of N = 68 children and adolescents (11–18 years) who were using mental health services for the first time, we evaluated the ratings of a parent and a professional clinician (internalizing, externalizing symptoms, total-problem score). In addition, parenting stress was scored on the Eltern-Belastungs-Inventars (EBI, Tröster, 2011), which measures both child-related stress and parent-related stress as well as total stress.Highly stressed parent ratings differed more from the clinicians’ ratings than the ratings of less stressed parents. Additionally, correlations showed that higher parenting stress resulted in larger differences between the parent’s and the clinician’s assessments. Multiple regressions proved the predictive value of child-caused parenting stress for these differences. These results apply for internalizing symptoms, externalizing symptoms, and total-problem score.Parenting stress should be evaluated systematically in order to carefully assess the value of the information from parents and to determine how it should be included in diagnostic and therapeutical decisions.

Neurofeedback (NF) is increasingly used as a therapy for attention-deficit/hyperactivity disorder (ADHD), however behavioral improvements require 20 plus training sessions. More economic evaluation strategies are needed to test methodological optimizations and mechanisms of action. In healthy adults, neuroplastic effects have been demonstrated directly after a single session of NF training. The aim of our study was to test the feasibility of short-term theta/beta NF in children with ADHD and to learn more about the mechanisms underlying this protocol. Children with ADHD conducted two theta/beta NF sessions. In the first half of the sessions, three NF trials (puzzles as feedback animations) were run with pre- and post-reading and picture search tasks. A significant decrease of the theta/beta ratio (TBR), driven by a decrease of theta activity, was found in the NF trials of the second session demonstrating rapid and successful neuroregulation by children with ADHD. For pre-post comparisons, children were split into good vs. poor regulator groups based on the slope of their TBR over the NF trials. For the reading task, significant EEG changes were seen for the theta band from pre- to post-NF depending on individual neuroregulation ability. This neuroplastic effect was not restricted to the feedback electrode Cz, but appeared as a generalized pattern, maximal over midline and right-hemisphere electrodes. Our findings indicate that short-term NF may be a valuable and economical tool to study the neuroplastic mechanisms of targeted NF protocols in clinical disorders, such as theta/beta training in children with ADHD.

We present a novel system to automatically diagnose reading disorders. The system is based on a speech recognition engine with a module for prosodic analysis. The reading disorder test is based on eight different subtests. In each of the subtests, the system achieves a recognition accuracy of at least 95%. As in the perceptual version of the test, the results of the subtests are then joined into a final test result to determine whether the child has a reading disorder. In the final classification stage, the system identifies 98.3% of the 120 children correctly. In the future, our system will facilitate the clinical evaluation of reading disorders.