Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Lessons learned from a multimodal sensor-based eHealth approach for treating pediatric obsessive-compulsive disorder

IntroductionThe present study investigates the feasibility and usability of a sensor-based eHealth treatment in psychotherapy for pediatric obsessive-compulsive disorder (OCD), and explores the promises and pitfalls of this novel approach. With eHealth interventions, therapy can be delivered in a patient's home environment, leading to a more ecologically valid symptom assessment and access to experts even in rural areas. Furthermore, sensors can help indicate a patient's emotional and physical state during treatment. Finally, using sensors during exposure with response prevention (E/RP) can help individualize therapy and prevent avoidance behavior.MethodsIn this study, we developed and subsequently evaluated a multimodal sensor-based eHealth intervention during 14 video sessions of cognitive-behavioral therapy (CBT) in 20 patients with OCD aged 12-18. During E/RP, we recorded eye movements and gaze direction via eye trackers, and an ECG chest strap captured heart rate (HR) to identify stress responses. Additionally, motion sensors detected approach and avoidance behavior.ResultsThe results indicate a promising application of sensor-supported therapy for pediatric OCD, such that the technology was well-accepted by the participants, and the therapeutic relationship was successfully established in the context of internet-based treatment. Patients, their parents, and the therapists all showed high levels of satisfaction with this form of therapy and rated the wearable approach in the home environment as helpful, with fewer OCD symptoms perceived at the end of the treatment.DiscussionThe goal of this study was to gain a better understanding of the psychological and physiological processes that occur in pediatric patients during exposure-based online treatment. In addition, 10 key considerations in preparing and conducting sensor-supported CBT for children and adolescents with OCD are explored at the end of the article. This approach has the potential to overcome limitations in eHealth interventions by allowing the real-time transmission of objective data to therapists, once challenges regarding technical support and hardware and software usability are addressed. Clinical Trial Registrationwww.ClinicalTrials.gov, identifier (NCT05291611)

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. In this study, we focussed on genetic variants of the Neuropeptide Y (NPY) system. NPY is one of the most abundant neuropeptides in the human brain with emerging evidence of capacity to modulate stress response, which is of high relevance in OCD. We focussed on tag-SNPs of NPY and its receptor gene NPY1R in a family-based approach. The sample comprised 86 patients (children and adolescents) with eoOCD with both their biological parents. However, this first study on genetic variants of the NPY-system could not confirm the association between the investigated SNPs and eoOCD. Based on the small sample size results have to be interpreted as preliminary and should be replicated in larger samples. However, also in an additional GWAS analysis in a large sample, we could not observe an associations between NPY and OCD. Overall, these preliminary results point to a minor role of NPY on the stress response of OCD

Internet-based psychotherapy in children with obsessive-compulsive disorder (OCD): protocol of a randomized controlled trial

Background: Obsessive-compulsive disorder (OCD) in children can lead to a huge burden on the concerned patients and their family members. While successful state-of-the art cognitive behavioral interventions exist, there is still a lack of available experts for treatment at home, where most symptoms manifest. Internet-based cognitive behavioral therapy (iCBT) could overcome these restrictions; however, studies about iCBT in children with OCD are rare and mostly target computerized self-help resources and only email contact with the therapist. Therefore, we intended to build up and to evaluate an iCBT approach for children with OCD, replacing successful elements of traditional in-office face-to-face CBT, with face-to-face teleconferences, online materials, and apps. Methods: With the help of a pilot feasibility study, we developed the iCBT consisting of 14 teleconference sessions with the child and parents. The sessions are supported by an app assessing daily and weekly symptoms and treatment course completed by children and parents. Additionally, we obtain heart rate and activity scores from the child via wristbands during several days and exposure sessions. Using a waiting list randomized control trial design, we aim to treat and analyze 20 children with OCD immediately after a diagnostic session whereas the control group of another set of 20 OCD patients will be treated after waiting period of 16 weeks. We will recruit 30 patients in each group to take account for potential dropouts. Outcomes for the treatment group are evaluated before randomization (baseline, t0), 16 weeks (end of treatment, t1), 32 weeks (follow-up 1, t2), and 48 weeks after randomization (follow-up 2, t3). For the waiting list group, outcomes are measured before the first randomization (baseline), at 16 weeks (waiting list period), 32 weeks (end of treatment), 48 weeks after the first randomization (follow-up I), and 64 weeks after the first randomization (follow-up II). Discussion: Based on our experience of feasibility during the pilot study, we were able to develop the iCBT approach and the current study will investigate treatment effectiveness. Building up an iCBT approach, resembling traditional in-office face-to-face therapy, may ensure the achievement of well-known therapy effect factors, the acceptance in both patients and clinicians, and the wide distribution within the health system. Trial registration: ClinicalTrials.gov NCT05037344 . Registered May 2019, last release August 13th, 2021

Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial

Background and hypotheses: In the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent studies failed to find a beneficial effect. The current study aimed to further investigate the effect of omega-3 PUFAs in UHR, to determine whether this line of research is worth pursuing. Study design: A double-blind, randomized, placebo-controlled study testing the efficacy of 6-month treatment with omega-3 PUFAs in 135 subjects at UHR for FEP, aged 13 to 20 years on the prevention of a transition to psychosis, followed up for 18 months post-treatment. The trial was conducted at 16 general hospitals and psychiatric specialty centers located in 8 European countries and Israel. Study results: There was no beneficial effect of treatment with omega-3 PUFAs compared to placebo; the rate of transition over 2 years did not differ between treatment arms nor was there a difference in change in symptom severity after 6-month treatment. Dropout rates and serious adverse events were similar across the groups. Conclusions: This is the third study that fails to replicate the original finding on the protective effect of omega-3 PUFAs in UHR subjects for transition to psychosis. The accumulating evidence therefore suggests that omega-3 PUFAs do not reduce transition rates to psychosis in those at increased risk at 2 years follow-up. Clinical trials: This trial is registered with ClinicalTrials.gov (NCT02597439; Study Details | Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe | ClinicalTrials.gov)

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder:The ENIGMA adventure

International audienc

Improving Mental Health in Childhood and Adolescence. The Role of the Youth Mental Health Infrastructure at the German Center for Mental Health (DZPG)

Hintergrund: Zum 1. Mai 2023 hat das Deutsche Zentrum für Psychische Gesundheit (DZPG – www.dzpg.org ) die Arbeit aufgenommen. Übergreifendes Ziel des DZPG ist die Optimierung von Forschungsbedingungen und die Schaffung von Infrastrukturen, um häufige psychische Störungen sowie psychisches Wohlbefinden besser zu verstehen, Interventionen und Prävention zu verbessern und versorgungsrelevante Ergebnisse schneller in die Praxis zu bringen. Die Youth-Mental-Health-Infrastruktur (YMH-INF), als eine von zwölf Infrastrukturen im DZPG, fokussiert Kinder, Jugendliche, ihre Familien und relevante Bezugspersonen in ihren Lebenswelten. Methode: Die partizipative Beteiligung aller relevanten Zielgruppen bei der Entwicklung der YMH-INF schlägt die Brücke zwischen Lebenswelt und Forschung (Translation-Rücktranslation). Es werden die Partizipationsniveaus „Interaktive Beratung“ und „Co-Entwicklung“ nach Sellars et al. (2021) umgesetzt und Möglichkeiten für eine volle „Partizipative Leitung“ geschaffen. Ergebnisse: Die Arbeit mit den partizipativen Räten und die konsequente Umsetzung der Partizipation tragen dazu bei, dass erzielte Ergebnisse gemeinsam getragen und disseminiert werden. Der Gewinn liegt in der dadurch erzielten hohen Akzeptanz. Diskussion und Schlussfolgerung: Der partizipative Ansatz erweist sich bislang als erfolgversprechende Basis, um darauf aufbauend mehr Evidenz in Schulen und Kindergärten/Kitas zu implementieren. Das Ziel der YMH-INF ist es, die Translation wissenschaftlicher Erkenntnisse schneller und nachhaltig in den Alltag von Kindern, Jugendlichen und ihren Familien zu bringen, um in den relevanten Lebenswelten ihre psychische Gesundheit zu verbessern. Kernfragen sind: Was schützt uns, macht und hält uns gesund? Was kann uns krank machen?Background: The German Centre for Mental Health (DZPG, www.dzpg.org ) started work on 1 May 2023. Its overarching goal is to optimize research conditions and create infrastructures to better understand common mental illnesses, improve interventions and prevention, and bring care-relevant results into practice more quickly. The Youth Mental Health Infrastructure (YMH-INF), one of nine infrastructures in the DZPG, focuses on children, adolescents, their families, and relevant caregivers in their living environments. Method: The participatory involvement of all relevant target groups in the development of the YMH-INF creates a bridge between the living environment and research (translation and back-translation). It implements the participation levels “interactive counseling” and “co-development” according to Sellars et al. (2021) and creates opportunities for full “participatory leadership.” Results: The cooperation with the councils and the consistent implementation of participation help ensure that the results achieved are jointly supported and disseminated. The benefit lies in a high level of acceptance achieved. Discussion and conclusion: To date, the participatory approach has proved to be a promising basis for implementing more evidence in schools and preschool facilities. The YMH-INF aims to translate scientific findings more quickly and sustainably into the everyday lives of children, young people, and their families to improve their mental health in relevant environments and to answer the questions: What protects us, makes us healthy, and keeps us healthy? What makes us ill

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

Objective Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study-wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.publishedVersio