Search

Abstract Background Perinatal depression affects 10–15% of mothers and approximately 5% of fathers. However, only a small number of affected individuals seek treatment. If left unrecognized and untreated, it can have negative long-term consequences for the family’s health, leading to subsequent high costs. Early treatment is crucial, yet there is a notable underdiagnosis and undertreatment. Affected individuals are often seen during this time, e.g. in paediatric practices, but not by specialists in mental health. Consequently, this study aims to increase detection and treatment rates of affected individuals by implementing a screening for depression and psychosocial stress in perinatal and postpartum parents within routine obstetric and paediatric care with subsequent advice and—if necessary—further referral to a mental health specialist. Methods UPlusE is a prospective, cluster-randomized controlled trial conducted in an outpatient setting. Obstetric and paediatric practices will be randomized into an intervention and control group (1:1 ratio). Practices and enrolling patients will be required to use specific smartphone apps (practice apps) for interaction. The screening will occur with the apps at each paediatric checkup up to the child’s age of 12 months, using the Edinburgh Postnatal Depression Scale (EPDS), KID-PROTEKT questionnaire, and the scale 1 (impaired bonding) of the Postpartum Bonding Questionnaire (PBQ-1). The goal is to screen 10,000 patients across Germany. Gynaecologists and paediatricians will receive certified training on peripartum depression. Participants in the intervention group with scores above cut-offs (EPDS ≥ 10, KID-PROTEKT ≥ 1, PBQ-1 ≥ 12) will receive counselling through their treating gynaecologists/paediatricians and will be provided with regional addresses for psychiatrists, psychotherapists, and “Frühe Hilfen” (early prevention) as well as family counselling centres, depending on symptom severity. At each screening, participants will be asked whether they sought support, where, and with whom (utilization). Utilization is the primary outcome. Discussion The screening is designed to reduce underdiagnosis to enable suitable support at an early stage (especially for those often overlooked, such as individuals with “high-functioning depression”) and hence to avoid manifestation of mental health problems in the whole family, especially infants who are exceptionally dependent on their parents and their well-being will benefit from this program. Trial registration German Clinical Trials Register, DRKS00033385. Registered on 15 January 2024.

Background: Child ADHD symptoms are highly prevalent in middle childhood, alongside impairment in social functioning. The parent–child relationship has been shown to play an important role; however, studies investigating specific facets of the parent–child relationship in ADHD symptomatology in middle childhood have been neglected. We assumed that higher ADHD symptoms were associated with both (1) lower maternal emotional availability (EA) and (2) lower child attachment security. Moreover, (3) we aimed to explore which specific EA dimensions were associated with ADHD symptoms. Methods: In a socio-pediatric clinic in Germany, 71 inpatient mother–child dyads (child age: M = 7.70, SD = 1.06; n = 54 boys) were assessed. Clinical data about child ADHD symptoms (Child Behavior Checklist 6–18 subscale “attention deficit/hyperactivity problems”), maternal EA (free play), and child attachment representation (Attachment Story Completion Task, GEV-B) were analyzed cross-sectionally. Results: Controlling for child oppositional behavior and sex, child ADHD symptoms were associated with overall maternal EA, and more specifically non-hostility, but not with child attachment representation. Conclusions: Our results imply that the role of parent–child interaction quality should be considered in the treatment of ADHD. Bidirectional effects cannot be ruled out.

Abstract Objectives To examine the impact of displacement experiences on 0- to 6-year-old children’s social-emotional and cognitive development, as well as influencing factors on reported outcomes. Study design We systematically searched MEDline, Psyndex, Cochrane Library, Web of Science, Elsevier, TandF, Oxford Journal of Refugee Studies, Journal of Immigrant & Refugee Studies, and Canada’s Journal on Refugees for existing literature regarding social-emotional and cognitive outcomes in children directly exposed to forced displacement due to political violence. Results were synthesized in the discussion and displayed using harvest plots. Results Our search generated 9,791 articles of which 32 were selected for review and evaluation according to NICE criteria. Included studies provided results for 6,878 forcibly displaced children. Measured outcomes were diverse and included areas such as peer relations, prosocial behavior, family functioning, play, intelligence, learning performance, and language development. Repeated exposure to adverse experiences, separation from parents, parental distress, as well as duration and quality of resettlement in the host country were reported as influencing factors in the reviewed studies. Conclusion As protective factors like secure and stable living conditions help to promote children’s development, we call for policies that enhance participation in the welcoming society for refugee families. Early integration with low-threshold access to health and educational facilities can help to mitigate the wide-ranging negative consequences of forced displacement on young children’s development.

Background/Objectives: Infant regulatory problems (RPs), i.e., crying, sleeping, and feeding problems, are associated with unfavorable outcomes in later childhood. RPs increased during the pandemic; however, their occurrence in the face of today’s societal challenges remains unclear. RPs are strongly linked to parenting stress and less positive parenting behaviors, but their interplay is less investigated. Methods: In this cross-sectional, questionnaire-based study (ntotal = 7039), we compared the incidences of crying, sleeping, and feeding problems in infants (0–2 years) in pandemic (npandemic = 1391) versus post-pandemic (npost-pandemic = 5648) samples in Germany. We also investigated the relationship between post-pandemic infant RPs and parenting behaviors with parenting stress as a potential mediator for fathers and mothers. Results: Crying/whining/sleeping problems (34.8%) and excessive crying (6.3%) were significantly more prevalent in the post-pandemic sample. In both mothers and fathers, infant RPs were significantly associated with less positive parenting behaviors. Parenting stress partially mediated this relationship. Conclusions: RPs in the post-pandemic era are even more prevalent than during the pandemic, highlighting the imperative for health care professionals to focus on infant mental health. Parenting stress emerges as an entry point for addressing the cycle of infant RPs and maladaptive behaviors in both fathers and mothers.

IntroductionExcessive crying, sleeping, and eating disorders are among the most prevalent mental health diagnoses in the first 3 years of life and involve significant health service use. Parents of infants with excessive crying/sleeping/eating disorders report high levels of stress, since they feel incapable of soothing and/or nurturing their baby. Infants' distress can lead to a breakdown in parents' mentalizing abilities and, more specifically, parental mind-mindedness in the parent-child interaction. Moreover, the signals of infants with excessive crying/sleeping/eating disorders tend to be equivocal and difficult to read. This also might contribute to lower parent-child interaction quality. Until now, parental mind-mindedness, which is regarded as a prerequisite for sensitivity, has not been investigated in mothers of infants with excessive crying/sleeping/eating disorders. We investigated whether mind-mindedness in mothers of infants with excessive crying, sleeping and/or eating disorders differed from a healthy control group. We supposed that mothers of infants with excessive crying/sleeping/eating disorders would use (1) less appropriate mind-related comments (AMRCs), and (2) more non-attuned mind-related comments (NAMRCs) than mothers in the control group.MethodsOur sample consisted of 44 mothers and their infants who were patients in a socio-paediatric clinic in Germany. The children were diagnosed with excessive crying, sleeping and/or eating disorders according to DC:0-5 (= clinical group). The control group was composed of 64 healthy children and their mothers. Maternal mind-mindedness was coded during a free-play interaction.ResultsResults showed that mothers of infants with excessive crying, sleeping and/or eating disorders used both more AMRCs (p = .029) as well as more NAMRCs (p = .006) than mothers in the control group.DiscussionThe findings are discussed in terms of implications for interventions (e.g., enhancing mind-mindedness trough video-feedback).

Background: There is a lack of evidence-based app guidance for parents of children with crying, sleeping, and feeding problems who are often highly burdened and not likely to seek professional help. A new psychoeducational app for parents providing scientifically sound information via text and videos, a diary function, selfcare strategies, a chat forum and a regional directory of specialized counseling centers may serve as a low-threshold intervention for this target group. Objective: We investigated how parents perceived the app in terms of the following: (1) overall impression and usability, (2) feedback on specific app functions regarding usefulness and (3) possible future improvements. Methods: Our clinical sample of N = 137 parents of children aged from 0 to 24 months was recruited from a cry baby outpatient clinic in Southern Germany between 2019 and 2022. A convergent parallel mixed methods design was used to collect and analyse cross-sectional data on app evaluation. After app use within the framework of a clinical trial, parents filled in an app evaluation questionnaire. Results: Most participants used the app at least once a week (86, 62.8 %) over an average period of 19.06 days (SD = 15.00). Participants rated overall impression and usability as good, and the informational texts, expert videos and regional register of counseling centers as appealing and useful. The diary function and chat forum were found to be helpful in theory, but improvements in implementation were requested, such as a timer function for the diary entry. Regarding future functionality, parents posed several suggestions such as the option to contact counseling centers directly via app, and the inclusion of the profile of their partners. Conclusions: Positive ratings of overall impression, usability, and specific app functions are important prerequisites for the app to be effective. App-based guidance for this target group should include easy-to-use information. The app is intended to serve as a secondary preventive low-threshold offer and to complement professional counseling.

BackgroundOver nearly three years, the COVID-19 pandemic has had a lasting impact on people's lives and mental health worldwide with its far-reaching restrictions and concerns about infections and other personal consequences. Families were particularly affected and showed increased stress and psychological problems. Long-term effects cannot be ruled out. So far, data on young families are sparse. The present longitudinal analysis (n = 932) of the CoronabaBY study investigated the development of parenting stress, parental affective symptoms, and child's mental health in young families with children aged 0–3 years in Germany as well as potential influencing factors.MethodsThe observational study includes two measurement points over the course of the pandemic (baseline and follow-up). Data was collected by app using standardized questionnaires.ResultsN = 932 participants, mainly mothers (94.7%) born in Germany (93.1%) with higher education (61.3% with at least high school diploma) and a comfortable financial situation participated in the longitudinal study. Children were on average 14.7 months old at baseline (SD: 12, range: 1–39 months). While the proportion of parents who perceived the pandemic as stressful decreased significantly from baseline (60%) to follow-up (52.3%), the proportion with parenting stress increased significantly (from 40.1% to 45.4%). Both parental and child mental health problems remained constant over time, with infants crying/feeding/sleeping problems ranging above pre-pandemic comparative data. Most predictive for high parenting stress at follow-up was high parenting stress at baseline. This was also true for parental affective symptoms (depression/anxiety) and child mental health problems.ConclusionsDespite faded pandemic restrictions, parents remained burdened. Support services do not appear to have been sufficient to help families out of their stressful situation. Our results indicate a need for action regarding low-threshold services that effectively reach affected families.Trial registrationThe study was pre-registered in OSF (https://osf.io/search/?q=tksh5&page=1).

Abstract Background Families with young children are particularly vulnerable for the stressors induced by the COVID-19 pandemic. However, studies on their psychosocial situation during the course of the crisis are still sparse. Methods In a comparison of three survey waves (wave I and III = high COVID-19 incidences), we cross-sectionally investigated the proportion of families (Ntotal = 2940) with children aged 0–3 years experiencing pandemic burden, parenting stress, and parental and child mental health problems in relation to COVID-19 incidences and restrictions in Southern Germany via validated questionnaires. Potential influencing factors were also explored. Results The number of parents with a high pandemic burden decreased over the course of the pandemic with a peak of 65.3% in wave I (significant changes except wave II versus III). Participants with high parenting stress significantly increased from 38.2% in wave I to 51.2% in wave III. The number of parents with symptoms of depression and anxiety remained constantly high with a maximum of 28.4% being affected. Infants with crying/sleeping problems increased significantly from 26.4% in wave I to 35.5% in wave III. Toddlers’ emotional and behavioral problems showed a peak of 23.9% in wave III (no significant changes). Increased family conflicts were the strongest predictor for parenting stress (ß = 0.355), maternal (ß = 0.305), infants’ (ß = 0.149) and toddlers’ (ß = 0.216) mental health problems during the pandemic. Conclusions Psychosocial stress factors in families with infants and toddlers remained highly pronounced and even partly increased irrespective of pandemic events. The findings suggest a staggered negative impact of pandemic-related factors on young children’s mental health. Promoting infants’ mental health as well as strengthening parental resources by reducing parenting stress should be a top healthcare priority in the aftermath of COVID-19. Trial registration The study was pre-registered in OSF ( https://osf.io/search/?q=tksh5&page=1 )

Abstract Background Cognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies. Methods Within this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I–III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV). Discussion The study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition. Trial registration The clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www.clinicaltrials.gov ; date of registration: 04/11/2018) and in EudraCT (number 2016–005022-10).

BackgroundThe use of digital media (e.g., smartphones, tablets, etc.) and the Internet have become omnipresent for every age group and are part of children’s and parents’ everyday life. Focusing on young children, the availability of media devices, their use as well as associated problems (e.g., in social, emotional and motor development) have increased in recent years. Of particular interest for prevention of these problems in early childhood is the relationship between the familial context (parental digital media use, Problematic Internet Use, school graduation, presence of siblings) and the digital media use of infants and toddlers. The present study’s goal was to describe media usage in 0–4-year-old children and to identify the potential relationship between familial context factors and child media usage.MethodsThe sample included N = 3,035 children aged 0 to 3;11 years (M = 17.37 months, SD = 13.68; 49.13% female). Recruitment took place within the framework of a restandardization study for a German developmental test. The parents of the participants answered a questionnaire on socio-demographics, on child media use, and on parental media use. Questions on parental media use included the full version of the Short Compulsive Internet Use Scale (S-CIUS).ResultsSignificant increases in media usage times with child age were identified, but no significant gender differences. A multiple regression analysis revealed that increasing maternal total media usage time, a higher parental S-CIUS score, lower school leaving certificate of both mother and father, and increasing child’s age led to higher child media usage time. Having siblings diminished young children’s media usage in this study. Having more than one child and having children aged over a year was associated with a higher parental S-CIUS score.ConclusionFamily factors such as maternal media use time, Problematic Internet Use and lower school graduation are significantly associated with young children’s digital media use. Parents should be aware of their personal influence on their children’s media use which might be due their role in terms of model learning.

Abstract Background Psychosocial stress during the COVID-19 pandemic is increasing particularly in parents. Although being specifically vulnerable to negative environmental exposures, research on psychosocial stress factors in infants’ and toddlers’ families during the pandemic is so far sparse. The CoronabaBY study investigates the perceived pandemic burden, parenting stress and parent and child mental health problems in families with children aged 0–3 years in Bavaria, Southern Germany. Further, the relationships between these psychosocial stressors are examined and sociodemographic characteristics that may be predictive of these factors will be explored. Methods Participants were cross-sectionally surveyed via smartphone app. Standardized questionnaires on perceived pandemic burden, parenting stress, parental symptoms of depression and anxiety, infants’ crying, sleeping and feeding problems or toddlers’ emotional and behavioral problems were applied. Results N = 991 parents (M age = 33.7 years, SD = 4.5; 93.7% mothers, 91.5% born in Germany) with infants (n = 554; M age = 5.9 months, SD = 3.0) or toddlers (n = 435; M age = 25.9 months, SD = 6.5) participated in the first half-year of 2021. Sixty-five percent of the parents perceived a high pandemic burden, 37.7% experienced parenting stress and 24.1% showed affective symptoms (anxiety: 30.1%, depression: 18.5%). Feeding problems, crying/ sleeping problems and multiple regulatory problems were found in 34.8%, 26.2% and 13.5% of the infants, respectively. Amongst toddlers, 8.5% showed noticeable behavior and emotional problems. Children`s mental health problems correlated moderately with parenting stress and parental affective symptoms and weakly with perceived pandemic burden. A lower financial status, higher parental education and increasing child age were significant but weak predictors for higher parenting stress, affective symptoms and higher psychological problems in children. Conclusions A majority of the surveyed families with infants and toddlers experience the pandemic as stressful. The main challenges are parental affective symptoms and limited resources for childcare due to parenting stress. Overall, infants and toddlers show similar levels of mental health problems when being compared to pre-pandemic studies, but staggered detrimental effects on children`s mental health might occur if the stressful conditions persist. This is already indicated by correlations between parental and child psychosocial stress factors.

BackgroundExcessive crying, sleeping, and feeding problems in early childhood are major stressors that can result in parents feeling socially isolated and having low self-efficacy. Affected children are a risk group for being maltreated and developing emotional and behavioral problems. Thus, the development of an innovative and interactive psychoeducational app for parents of children with crying, sleeping, and feeding problems may provide low-threshold access to scientifically based information and reduce negative outcomes in parents and children. ObjectiveWe aimed to investigate whether following the use of a newly developed psychoeducational app, the parents of children with crying, sleeping, or feeding problems experienced less parenting stress; gained more knowledge about crying, sleeping, and feeding problems; and perceived themselves as more self-effective and as better socially supported and whether their children’s symptoms decreased more than those of the parents who did not use the app. MethodsOur clinical sample consisted of 136 parents of children (aged 0-24 months) who contacted a cry baby outpatient clinic in Bavaria (Southern Germany) for an initial consultation. Using a randomized controlled design, families were randomly allocated to either an intervention group (IG; 73/136, 53.7%) or a waitlist control group (WCG; 63/136, 46.3%) during the usual waiting time until consultation. The IG was given a psychoeducational app that included evidence-based information via text and videos, a child behavior diary function, a parent chat forum and experience report, tips on relaxation, an emergency plan, and a regional directory of specialized counseling centers. Outcome variables were assessed using validated questionnaires at baseline test and posttest. Both groups were compared at posttest regarding changes in parenting stress (primary outcome) and secondary outcomes, namely knowledge about crying, sleeping, and feeding problems; perceived self-efficacy; perceived social support; and child symptoms. ResultsThe mean individual study duration was 23.41 (SD 10.42) days. The IG reported significantly lower levels of parenting stress (mean 83.18, SD 19.94) after app use compared with the WCG (mean 87.46, SD 16.67; P=.03; Cohen d=0.23). Furthermore, parents in the IG reported a higher level of knowledge about crying, sleeping, and feeding (mean 62.91, SD 4.30) than those in the WCG (mean 61.15, SD 4.46; P

Mental health problems in early childhood are common, but there is a lack of psychiatric research on this age group. DC:0-5 is a multiaxial classification system for mental disorders in early childhood, providing a framework for standardizing clinical practice and research. However, research on the validity of DC:0-5 is scarce. The Developmental Psychiatry Diagnostic Challenges Study (DePsy) is a multi-site, prospective clinical study including six German early childhood mental health (ECMH) clinics. The main objective of the study is to contribute to the validation of Axis I and Axis II of DC:0-5. A second aim of the study is to describe the population of the participating clinics regarding diagnoses, family context, and treatment outcomes. Additionally, the impact of environmental risk factors, including parental Adverse Childhood Experiences (ACEs) and media use, on child psychopathology and caregiver–child relationships will be examined. Over two years, patients aged 0.0–5.9 years old will be enrolled in the study. Assessments include ICD-10 and DC:0-5 diagnoses, developmental tests, video-based observations of caregiver—child interactions, and questionnaires on child psychopathology, media use, parental stress, and treatment satisfaction. Study results will promote the standardization of assessment and treatment in ECMH clinics aiming to improve the development of patients and their families.

Abstract Background Our goal was to accurately detect young children at risk for long-term psychiatric disturbances after potentially traumatic experiences in the course of relocation. In addition to detailed assessment of parent-rated parent and child symptomatology, we focused on disruptive behaviors in the education environment summarized as survival states, as these frequently lead to clinical referral. Methods We screened 52 refugee children aged 3–7 (M = 5.14 years, SD = 1.17) for symptoms of Posttraumatic Stress Disorder (PTSD) with the Child and Adolescent Trauma Screening (CATS) in parent rating. The parents’ mental health was assessed using the Refugee Health Screener (RHS-15). Furthermore, the child’s educators were asked to evaluate the pathological survival states of the child and we made a general assessment of the children’s symptoms with the Strengths and Difficulties Questionnaire (SDQ) rated by parents and educators. Children in the refugee sample completed a working memory learning task (Subtest Atlantis from the Kaufmann Assessment Battery for Children, KABC-II) and delivered saliva samples for testing of the cortisol level. Results The parental rating of their child’s PTSD symptoms was significantly related to their own mental well-being (r = .50, p

Abstract CREB (cyclic AMP response element binding protein) binding protein (CBP, CREBBP) is a ubiquitously expressed transcription coactivator with intrinsic histone acetyltransferase (KAT) activity. Germline mutations within the CBP gene are known to cause Rubinstein-Taybi syndrome (RSTS), a developmental disorder characterized by intellectual disability, specific facial features and physical anomalies. Here, we investigate mechanisms of CBP function during brain development in order to elucidate morphological and functional mechanisms underlying the development of RSTS. Due to the embryonic lethality of conventional CBP knockout mice, we employed a tissue specific knockout mouse model (hGFAP-cre::CBP Fl/Fl , mutant mouse) to achieve a homozygous deletion of CBP in neural precursor cells of the central nervous system. Our findings suggest that CBP plays a central role in brain size regulation, correct neural cell differentiation and neural precursor cell migration. We provide evidence that CBP is both important for stem cell viability within the ventricular germinal zone during embryonic development and for unhindered establishment of adult neurogenesis. Prominent histological findings in adult animals include a significantly smaller hippocampus with fewer neural stem cells. In the subventricular zone, we observe large cell aggregations at the beginning of the rostral migratory stream due to a migration deficit caused by impaired attraction from the CBP-deficient olfactory bulb. The cerebral cortex of mutant mice is characterized by a shorter dendrite length, a diminished spine number, and a relatively decreased number of mature spines as well as a reduced number of synapses. In conclusion, we provide evidence that CBP is important for neurogenesis, shaping neuronal morphology, neural connectivity and that it is involved in neuronal cell migration. These findings may help to understand the molecular basis of intellectual disability in RSTS patients and may be employed to establish treatment options to improve patients’ quality of life.

Neuronal plasticity is considered to be the neurophysiological correlate of learning and memory and changes in corticospinal excitability play a key role in the normal development of the central nervous system as well as in developmental disorders. In a previous study, it was shown that quadri-pulse theta burst stimulation (qTBS) can induce bidirectional changes in corticospinal excitability (1). There, a quadruple burst consisted of four single-sine-wave (SSW) pulses with a duration of 160 μs and inter-pulse intervals of 1.5 ms to match I-wave periodicity (666 Hz). In the present study, the pulse shape was modified applying double-sine-waves (DSW) rather than SSW pulses, while keeping the pulse duration at 160 μs. In two separate sessions, we reversed the current direction of the DSW pulse, so that its second component elicited either a mainly posterior-to-anterior (DSW PA-qTBS) or anterior-to-posterior (DSW AP-qTBS) directed current in the precentral gyrus. The after-effects of DSW qTBS on corticospinal excitability were examined in healthy individuals (n = 10) with single SSW TMS pulses. For single-pulse SSW TMS, the second component produced the same preferential current direction as DSW qTBS but had a suprathreshold intensity, thus eliciting motor evoked potentials (PA-MEP or AP-MEP). Single-pulse SSW TMS revealed bidirectional changes in corticospinal excitability after DSW qTBS, which depended on the preferentially induced current direction. DSW PA-qTBS at 666 Hz caused a stable increase in PA-MEP, whereas AP-qTBS at 666 Hz induced a transient decrease in AP-MEP. The sign of excitability following DSW qTBS at I-wave periodicity was opposite to the bidirectional changes after SSW qTBS. The results show that the pulse configuration and induced current direction determine the plasticity-effects of ultra-high frequency SSW and DSW qTBS at I-wave periodicity. These findings may offer new opportunities for short non-invasive brain stimulation protocols that are especially suited for stimulation in children and patients with neurological or neurodevelopmental disorders.

Thousands of refugees who have entered Europe experienced threatening conditions, potentially leading to post traumatic stress disorder (PTSD), which has to be detected and treated early to avoid chronic manifestation, especially in children. We aimed to evaluate and test suitable screening tools to detect PTSD in children. Syrian refugee children aged 4–14 years were examined using the PTSD-semi-structured interview, the Kinder-DIPS, and the Child Behavior Checklist (CBCL). The latter was evaluated as a potential screening tool for PTSD using (i) the CBCL-PTSD subscale and (ii) an alternative subscale consisting of a psychometrically guided selection of items with an appropriate correlation to PTSD and a sufficient prevalence (presence in more than 20% of the cases with PTSD). For both tools we calculated sensitivity, specificity, and a receiver operating characteristic (ROC) curve. Depending on the sum score of the items, the 20-item CBCL-PTSD subscale as used in previous studies yielded a maximal sensitivity of 85% and specificity of 76%. The psychometrically guided item selection resulted in a sensitivity of 85% and a specificity of 83%. The areas under the ROC curves were the same for both tools (0.9). Both subscales may be suitable as screening instrument for PTSD in refugee children, as they reveal a high sensitivity and specificity.

Sleep deprivation is believed to lead to homeostatic increases in synaptic strength and reduced inducibility of associative LTP, based mainly on findings from animal studies. Here, Kuhn et al. demonstrate similar sleep-dependent synaptic plasticity changes in humans along with altered plasma BDNF levels.

Patterned transcranial magnetic stimulation (TMS) such as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS) can induce changes in cortico-spinal excitability, commonly referred to as long-term potentiation (LTP)-like and long-term depression (LTD)-like effects in human motor cortex (M1). Here, we aimed to test the plasticity-inducing capabilities of a novel protocol that merged TBS and QPS. 360 bursts of quadri-pulse TBS (qTBS) were continuously given to M1 at 90% of active motor threshold (1440 full-sine pulses). In a first experiment, stimulation frequency of each burst was set to 666 Hz to mimic the rhythmicity of the descending cortico-spinal volleys that are elicited by TMS (i.e., I-wave periodicity). In a second experiment, burst frequency was set to 200 Hz to maximize postsynaptic Ca2+ influx using a temporal pattern unrelated to I-wave periodicity. The second phase of sinusoidal TMS pulses elicited either a posterior-anterior (PA) or anterior-posterior (AP) directed current in M1. Motor evoked potentials (MEPs) were recorded before and after qTBS to probe changes in cortico-spinal excitability. PA-qTBS at 666 Hz caused a decrease in PA-MEP amplitudes, whereas AP-qTBS at 666 Hz induced an increase in mean AP-MEP amplitudes. At a burst frequency of 200 Hz, PA-qTBS and AP-qTBS produced an increase in cortico-spinal excitability outlasting for at least 60 minutes in PA- and AP-MEP amplitudes, respectively. Continuous qTBS at 666 Hz or 200 Hz can induce lasting changes in cortico-spinal excitability. Induced current direction in the brain appears to be relevant when qTBS targets I-wave periodicity, corroborating that high-fidelity spike timing mechanisms are critical for inducing bi-directional plasticity in human M1.

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than full-sine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the half-segment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior-anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS.