Generation of induced pluripotent stem cells from ADHD patients who do or do not respond to Methylphenidate treatment.

As a neurodevelopmental multifactorial disorder whose prevalence has been increasing worldwide, attention-deficit hyperactivity disorder (ADHD) is considered a public health concern. Methylphenidate (MPH) is the drug of choice for ADHD; however, not all patients respond fully to this treatment. Therefore, exploring the underlying molecular mechanisms involved in ADHD and potential novel therapeutic targets is crucial.

Hypomania-Checklist-33: risk stratification and factor structure in a mixed psychiatric adolescent sample.

Background: The 33-item Hypomania Checklist (HCL-33) has been shown to distinguish between adolescent bipolar disorder (BD) and unipolar depression. To investigate the utility of the HCL-33 as a screening tool in routine diagnostics, the frequency and psychopathological characteristics of detected individuals in a mixed psychiatric sample necessitate more examination.

Methods: The HCL-33, Children's Depression Inventory, Beck's Anxiety Inventory, and Strengths and Difficulties Questionnaire were completed by 285 children and adolescents (12-18 years) in a mixed psychiatric sample.

Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD.

Introduction: Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers.

Methods: Children and adolescents ( = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined.

Protocol for a Wnt reporter assay to measure its activity in human neural stem cells derived from induced pluripotent stem cells.

The canonical Wnt signaling is an essential pathway that regulates cellular proliferation, maturation, and differentiation during neurodevelopment and maintenance of adult tissue homeostasis. This pathway has been implicated with the pathophysiology of neuropsychiatric disorders and was associated with cognitive processes, such as learning and memory. However, the molecular investigation of the Wnt signaling in functional human neural cell lines might be challenging since brain biopsies are not possible and animal models may not represent the polygenic profile of some neurological and neurodevelopmental disorders.

Impact of the COVID-19 pandemic on mental health and family situation of clinically referred children and adolescents in Switzerland: results of a survey among mental health care professionals after 1 year of COVID-19.

The aim of this study was to assess the impact of the COVID-19 pandemic on mental well-being of clinically referred children and adolescents and on their families from the perspective of mental health care professionals in Switzerland during the first year of the pandemic. Psychiatrists and psychologists for children and adolescents participated in an anonymous survey conducted online in April/May 2021. The survey was completed by 454 mental health care professionals, most of them working in outpatient clinics for child and adolescent psychiatry or in independent practices.

Problematic use of digital media in children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder compared to controls. A meta-analysis.

Objective: Problematic use of digital media and problematic use of the internet (PUI) in particular are growing problems in the general population. Moreover, studies have shown links between PUI and symptoms of attention-deficit/hyperactivity disorder (ADHD). This meta-analysis investigated whether children and adolescents with ADHD are more often affected by PUI compared to control groups.

The Impact of the COVID-19 Pandemic on Mental Health Care of Children and Adolescents in Switzerland: Results of a Survey among Mental Health Care Professionals after One Year of COVID-19.

Background: To assess the impact of the COVID-19 pandemic on treatment demand and supply in children and adolescents with mental disorders during the first year of the pandemic from the perspective of child and adolescent psychiatrists and psychologists in Switzerland.

Methods: The survey was conducted anonymously, in German or French and online in April/May 2021. Mental health professionals working in child and adolescent psychiatry, psychotherapy services or independent practices were contacted by email.

Media use and emotional distress under COVID-19 lockdown in a clinical sample referred for internalizing disorders: A Swiss adolescents' perspective.

The COVID-19 outbreak has profoundly affected adolescents' life. Adolescents with pre-existing psychiatric disorders have been at particular risk of increased mental health problems and problematic media use. 178 patients, aged 12-18 years, referred before the COVID-19 outbreak to child and adolescent psychiatry, participated in an anonymous online survey on the impact of the lockdown on media use and mental well-being.

Media use before, during and after COVID-19 lockdown according to parents in a clinically referred sample in child and adolescent psychiatry: Results of an online survey in Switzerland.

Background: To investigate the consequences of COVID-19 lockdown on screen media use in children and adolescents with mental health problems, an online survey was conducted on leisure media use before, during and after the lockdown of spring 2020.

Method: Parents of patients (10-18 yrs) referred to child and adolescent psychiatry participated in an anonymous online survey, approximately six weeks after the first easing of lockdown measures. Parents rated the amount, the content and the psychological impact of their children's media use before, during and after the lockdown.

Personalized at-home neurofeedback compared to long-acting methylphenidate in children with ADHD: NEWROFEED, a European randomized noninferiority trial.

Background: Neurofeedback is considered a promising intervention for the treatment of attention-deficit hyperactivity disorder (ADHD). NEWROFEED is a prospective, multicentre, randomized (3:2), reference drug-controlled trial in children with ADHD aged between 7 and 13 years. The main objective of NEWROFEED was to demonstrate the noninferiority of personalized at-home neurofeedback (NF) training versus methylphenidate in the treatment of children with ADHD.

Impact of the COVID-19 lockdown on screen media use in patients referred for ADHD to child and adolescent psychiatry: an introduction to problematic use of the internet in ADHD and results of a survey.

The COVID-19 outbreak and lockdown have been associated with multiple consequences for mental health, including an excessive and potentially harmful increase in screen media use. The specific consequences for children, adolescents and young adults with ADHD are still unknown. In the first part of this study, a short review of problematic use of the internet (PUI) in ADHD is presented, showing that patients with ADHD are at risk for different aspects of PUI, such as excessive gaming or problematic social media use.

Generation of integration-free induced pluripotent stem cells from healthy individuals.

Ten human induced pluripotent stem cell (iPSC) lines have been derived from five healthy controls matched to a study including Attention-Deficit Hyperactivity Disorder patients (ADHD). Both female and male children and adolescents aged 6-18 years were recruited. Isolated keratinocyte cells from the participants were reprogrammed into iPSCs using non-integrating Sendai virus to deliver the reprogramming factors Oct3/4, Sox2, Klf4 and cMyc.

Generation of integration-free induced pluripotent stem cell lines from four pediatric ADHD patients.

Human induced pluripotent stem cell (iPSC) lines have been derived from four male patients with childhood attention-deficit hyperactivity disorder (ADHD). Children and adolescents between the ages 6 and 18 suffering from ADHD were recruited for this work. Isolated keratinocytes or peripheral blood mononuclear cells from the participants were reprogrammed into iPSCs using non-integrating Sendai virus to deliver the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc.

The stress-Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric neurodevelopmental disorders in children and adolescents. Although ADHD has been studied for nearly a century, the cause and pathophysiology of ADHD is yet largely unknown. However, findings from previous studies have resulted in the formation of a new hypothesis: Apart from the well-known multifactorial etiology of ADHD, recent evidence suggests that the interaction between genetic and environmental factors and especially Wnt- and mTOR-signaling pathways might have an important role in the pathophysiology of ADHD.

High-resolution chromosomal microarray analysis for copy-number variations in high-functioning autism reveals large aberration typical for intellectual disability.

Copy-number variants (CNVs), in particular rare, small and large ones (< 1% frequency) and those encompassing brain-related genes, have been shown to be associated with neurodevelopmental disorders like autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID). However, the vast majority of CNV findings lack specificity with respect to autistic or developmental-delay phenotypes. Therefore, the aim of the study was to investigate the size and frequency of CNVs in high-functioning ASD (HFA) without ID compared with a random population sample and with published findings in ASD and ID.

No Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents.

Obsessive-compulsive disorder (OCD) causes severe distress and is therefore counted by the World Health Organisation (WHO) as one of the 10 most impairing illnesses. There is evidence for a strong genetic underpinning especially in early onset OCD (eoOCD). Though several genes involved in neurotransmission have been reported as candidates, there is still a need to identify new pathways.

Association study and a systematic meta-analysis of the VNTR polymorphism in the 3'-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) has been postulated to associate with dopaminergic dysfunction, including the dopamine transporter (DAT1). Several meta-analyses showed small but significant association between the 10-repeat allele in the DAT1 gene in 3'-untranslated region variant number tandem repeat polymorphism and child and adolescent ADHD, whereas in adult ADHD the 9-repeat allele was suggested to confer as risk allele. Interestingly, recent evidence indicated that the long-allele variants (10 repeats and longer) might confer to lower expression of the transporter in comparison to the short-allele.

The involvement of the canonical Wnt-signaling receptor LRP5 and LRP6 gene variants with ADHD and sexual dimorphism: Association study and meta-analysis.

Wnt-signaling is one of the most abundant pathways involved in processes such as cell-proliferation, -polarity, and -differentiation. Altered Wnt-signaling has been linked with several neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) as well as with cognitive functions, learning and memory. Particularly, lipoprotein receptor-related protein 5 (LRP5) or LRP6 coreceptors, responsible in the activation of the canonical Wnt-pathway, were associated with cognitive alterations in psychiatric disorders.

Improved Generation of Induced Pluripotent Stem Cells From Hair Derived Keratinocytes - A Tool to Study Neurodevelopmental Disorders as ADHD.

In the last decade, there is an increasing application of induced pluripotent stem cells (iPSCs) for disease modeling. The iPSC technology enables the study of patient-specific neuronal cell lines to evaluate dysfunction at the cellular level and identify the responsible genetic factors. This approach might be particularly valuable for filling the gap of knowledge at the cellular and molecular levels underlying the pathophysiology of various neurodevelopmental and/or psychiatric disorders, such as attention-deficit hyperactivity disorder (ADHD).

CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.

The Contactin Associated Protein-like 2 (CNTNAP2) gene has been discussed to be associated with different symptoms of autism spectrum disorders (ASDs) and other neurodevelopmental disorders. We aimed to elucidate the genetic association of CNTNAP2 within high functioning ASD (HFA), focusing on autism specific symptoms and reducing intelligence related factors. Furthermore, we compared our findings conducting a meta-analysis in patients with ASD and HFA only.

Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel cell carcinomas: heterogeneity and indications for cadherin switching.

Aims: Merkel cell carcinomas (MCCs) are rare but aggressive tumours associated recently with Merkel cell polyomavirus (MCV). As development and progression of several types of carcinomas can be promoted by changes in cell adhesion proteins, the aim of this study was to examine homo- and heterotypic cell contacts of Merkel cells and MCCs.

Methods And Results: Merkel cells of healthy glabrous epidermis and 52 MCCs were analysed by double-label immunostaining, immunofluorescence and confocal microscopy.