Prevalence and Clinical Picture of Diamine Oxidase Gene Variants in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent neurodevelopmental disorder worldwide. The diamine oxidase enzyme (DAO) is responsible for the histamine gastrointestinal degradation. Its deficient functioning may implicate an excess of histamine in the body. The excess of histamine (histamine intolerance, HIT) has been related with a growing number of diseases and pseudo-allergic symptomatology. However, data on the relationship between the DAO enzyme, HIT, and ADHD are lacking. The main objective of this pilot is to study the prevalence of the four most relevant SNP variants of the AOC1 gene affecting DAO enzyme functionality in a sample of patients diagnosed with ADHD attending child and adolescent mental health services. Methods: In a cohort of 303 participants, we measured the SNP variants of the AOC1 gene. Results: The prevalence of having at least one minor dysfunctional allele was 78.8%. No relationship between ADHD severity and DAO deficiency was found. However, some AOC1 gene variants associated with DAO deficiency were related to several meaningful medical comorbidities. Furthermore, we found a strong association between DAO activity and the intelligence quotient, particularly in working memory. Conclusions: Some SNP variants of the AOC1 gene associated with DAO deficiency are related to some medical comorbidities and cognitive dysfunction in ADHD children and adolescents. Studies including patients with other diagnoses and healthy controls and bigger samples are warranted to confirm our preliminary results.

Biomarcadores sanguíneos, de orina y conductas autolesivas e intentos de suicidio repetidos en los adolescentes / Blood and urine biomarkers and repeated self-injurious behaviors and suicide attempts in adolescents

Hay evidencia parcial de que los niveles elevados de la β-endorfina sanguínea se asocian a la adicción suicida en los adultos, pero apenas hay datos sobre los adolescentes. La β-endorfina sanguínea, con un importante papel en los mecanismos de gestión de las adicciones, puede inducir euforia y felicidad, recompensar y reforzar el comportamiento suicida. Para probar si los grandes repetidores de intentos de suicidio (5 o más intentos de suicidio) y de conductas autolesivas (20 o más episodios de autolesiones) tienen unos niveles de biomarcadores más elevados, se selecciona una muestra de 43 pacientes de entre 12 y 17 años que acuden al Servicio de Urgencias Psiquiátricas en el Hospital Universitario Puerta de Hierro Majadahonda. Diez presentan 5 o más intentos de suicidio, 35 presentan 20 o más episodios autolesivos y 10 presentan ambas características, y la mayoría de los adolescentes cumplían criterios de adicción para autolesiones y suicidio. Los resultados sugieren que todos los pacientes que presentaban adicción al suicidio también presentaban adicción a la autolesión. Los niveles de ACTH, cortisol y β-endorfina sanguíneos y de cortisol en orina fueron muy elevados, pero no diferenciaban a los grandes repetidores del resto de adolescentes. (AU)

There is partial evidence that elevated levels of blood β-endorphin are associated with suicidal addiction in adults, but hardly any data on adolescents. Blood β-endorphin, with an important role in addiction management mechanisms, can induce euphoria and happiness, reward and reinforce suicidal behavior. To test whether high repeaters of suicide attempts (5 or more suicide attempts) and self-injurious behaviors (20 or more episodes of self-injury) have higher biomarker levels, a sample of 43 patients aged 12-17 years attending the Psychiatric Emergency Department at the Hospital Universitario Puerta de Hierro Majadahonda is recruited. Ten present 5 or more suicide attempts, 35 present 20 or more self-injurious episodes and 10 present both characteristics, and most of the adolescents meet addiction criteria for self-injury and suicide. The results suggest that all patients with addiction to suicide also had addiction to self-injury. Blood ACTH, cortisol and β-endorphin and urine cortisol levels were very elevated, but did not differentiate heavy repeaters from the rest of the adolescents. (AU)

Effectiveness of a Serious Video Game (MOON) for Attention Deficit Hyperactivity Disorder: Protocol for a Randomized Clinical Trial.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood and adolescence, with a prevalence of 5% and associated difficulties and worse prognosis if undetected. Multimodal treatment is the treatment of choice. However, sometimes treatment can be insufficient or have drawbacks. OBJECTIVE: This study protocol aims to demonstrate the effectiveness of cognitive training through the serious video game The Secret Trail of Moon (MOON) in improving emotional regulation in people with ADHD. METHODS: This is a prospective, unicenter, randomized, unblinded, pre- and postintervention study. The groups will be randomized (MOON vs control) via an electronic case report form. The MOON intervention will be performed 2 times per week for 10 weeks (30 minutes per session). The first 5 weeks (10 sessions) will be conducted face-to-face at the Puerta de Hierro University Hospital, and the remaining weeks will be conducted via the internet at the participants' homes. The total sample consists of 152 patients aged between 7 and 18 years. All participants have a clinical diagnosis of ADHD under pharmacological treatment. Data collection will be used to obtain demographic and clinical data. The data will be recorded using REDCap. Measures will be made through clinical scales for parents and objective tests of cognitive functioning in patients. Additional information on academic performance will be collected. The study has a power greater than 80% to detect differences. Student t test, 2-factor analysis of variance (ANOVA), and Mann-Whitney analyses will be performed according to each variable's characteristics. RESULTS: The study was approved by the Research Ethics Committee of the Puerta de Hierro University Hospital on December 14, 2022. As of September 26, 2023, we have enrolled 62 participants, and 31 participants have completed the study. This clinical trial was funded by the Comunidad de Madrid (IND2020/BMD-17544). The approximate completion date is March 2024. CONCLUSIONS: Serious video games such as MOON can be motivational tools that complement multimodal treatment for ADHD. TRIAL REGISTRATION: ClinicalTrials.gov; NCT06006871; https://clinicaltrials.gov/study/NCT06006871. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53191.

Assessment of ADHD Subtypes Using Motion Tracking Recognition Based on Stroop Color-Word Tests.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder known for its significant heterogeneity and varied symptom presentation. Describing the different subtypes as predominantly inattentive (ADHD-I), combined (ADHD-C), and hyperactive-impulsive (ADHD-H) relies primarily on clinical observations, which can be subjective. To address the need for more objective diagnostic methods, this pilot study implemented a Microsoft Kinect-based Stroop Color-Word Test (KSWCT) with the objective of investigating the potential differences in executive function and motor control between different subtypes in a group of children and adolescents with ADHD. A series of linear mixture modeling were used to encompass the performance accuracy, reaction times, and extraneous movements during the tests. Our findings suggested that age plays a critical role, and older subjects showed improvements in KSWCT performance; however, no significant divergence in activity level between the subtypes (ADHD-I and ADHD-H/C) was established. Patients with ADHD-H/C showed tendencies toward deficits in motor planning and executive control, exhibited by shorter reaction times for incorrect responses and more difficulty suppressing erroneous responses. This study provides preliminary evidence of unique executive characteristics among ADHD subtypes, advances our understanding of the heterogeneity of the disorder, and lays the foundation for the development of refined and objective diagnostic tools for ADHD.

Differences in Ex-Gaussian Parameters from Response Time Distributions Between Individuals with and Without Attention Deficit/Hyperactivity Disorder: A Meta-analysis.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood and adolescence. Differences in reaction times (RT) in cognitive tasks have been consistently observed between ADHD and typical participants. Instead of estimating means and standard deviations, fitting non-symmetrical distributions like the ex-Gaussian, characterized by three parameters (µ, σ, and τ), account for the whole RT distributions. A meta-analysis is performed with all the available literature using ex-Gaussian distributions for comparisons between individuals with ADHD and controls. Results show that τ and σ are generally greater for ADHD samples, while µ tends to be larger for typical groups but only for younger ages. Differences in τ are also moderated by ADHD subtypes. τ and σ show, respectively, quadratic and linear relationships with inter-stimulus intervals from Continuous Performance Test and Go/No Go tasks. Furthermore, tasks and cognitive domains influence the three parameters. Interpretations of ex-Gaussian parameters and clinical implications of these findings are also discussed. Fitting ex-Gaussian distributions to RT data is a useful way to explore differences between individuals with ADHD and healthy controls.

The Relationship between Subjective Aging and Cognition in Elderly People: A Systematic Review.

There is a growing body of evidence on the effects of subjective aging on health, well-being and quality of life. This review aims to synthesize findings about the link between subjective aging and cognition and cognitive decline. Furthermore, it provides an examination of variation sources such as subjective aging construct, cognitive domains, measures employed, age and moderator variables. A systematic search was performed in PubMed, PsychInfo and Web of Science, as well as grey literature searches in Google Scholar, OpenGrey, WorldCat and NDLTD, which resulted in 59 reports being included. Subjective aging is a relevant construct in the explanation and prediction of cognitive aging and cognitive decline in elderly adults. More positive views about own aging and self-perceptions of aging, as well as a younger subjective age, were consistently related to better cognition and lower risk of cognitive decline. However, there were differences due to subjective aging subdimensions and cognitive domains, as well as an effect of age. Additionally, there were concerns about the content validity of some measures employed, such as the Philadelphia Geriatric Center Morale Scale for subjective aging and the Mini Mental State Examination for global cognition. Further studies should employ longitudinal designs with a process-based approach to cognition and precise subjective aging measures.

Effects of Music on Attention-Deficit/Hyperactivity Disorder (ADHD) and Potential Application in Serious Video Games: Systematic Review.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has a considerable impact on an individual's daily life. Some difficulties with timing deficits may be associated with deficiencies in attention, reading, language skills, or executive function. Music therapy, either active (playing an instrument) or passive (listening to music) has demonstrated its efficacy in reducing symptomatology in many disorders. Video games may prove to be a useful assessment and treatment tool in compensating for the difficulties with multimodal treatment in ADHD. OBJECTIVE: The aim of the study is to (1) analyze the evidence that music is beneficial in reducing the symptomatology of ADHD using systematic review and (2) propose the application of music in video games following music therapy strategies. METHODS: Searches were conducted in PubMed, Embase, PsycINFO, Cochrane, and gray literature (Google Scholar and WorldCat). We used the following search syntax: ((music[Title/Abstract]) or (music therapy[Title/Abstract])) and (attention deficit disorder[MeSH or thesaurus term]). RESULTS: Of the 70 records identified, 17 provided findings that music can be beneficial in various domains of ADHD. Active music therapy improves hemispheric synchrony, social skills, aggressivity, and impulsivity. Passive music therapy improves academic skills like arithmetic, drawing, and reading comprehension, as well as attention and disruptive behaviors. The effects depend on the music genre, tempo, or task difficulty. Music in video games was generally found to be beneficial for people with ADHD. Music improves immersion and flow while playing video games. Using rhythm may also improve timing skills and immersion in patients with ADHD. Regarding the proposed application of aspects of music to therapeutic video games for ADHD, some paradigms in timing and music therapy were considered in the proposed design of video games. CONCLUSIONS: Improving ADHD treatment through the application of music in video games is proposed. TRIAL REGISTRATION: PROSPERO CRD42021288226; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=288226.

Effectiveness of a Personalized, Chess-Based Training Serious Video Game in the Treatment of Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder: Randomized Controlled Trial.

BACKGROUND: Compared with traditional approaches, gaming strategies are promising interventions for the treatment of attention-deficit/hyperactivity disorder (ADHD). We developed a serious game, The Secret Trail of Moon (TSTM), for ADHD treatment. OBJECTIVE: The main objective of this clinical trial was to demonstrate the effectiveness of an add-on, either TSTM or Therapeutic Chess (TC), in previously optimally drug-titrated, clinically stable patients with ADHD. METHODS: This study is a prospective, unicentric, randomized clinical trial in clinically stable patients with ADHD, aged 12 to 22 years. The TSTM (n=35) and TC groups (n=34) performed 12 weekly sessions of their respective treatments. The control group (CG) patients (n=35) were called by phone every week, but they received no cognitive intervention. The primary end point was the change from baseline to end point in the parent "Behavior Rating Inventory of Executive Function-2" (BRIEF-2; patients' parents) in the per-protocol population (31 serious videogame: 24 TC and 34 CG). RESULTS: Our study failed to probe clear-cut improvements in the global score of the BRIEF-2. However, the TC group showed improvements in measures of emotional control, emotional regulation, and inattention. The TSTM group showed improvements in measures of emotional regulation, inattention, and school context. CONCLUSIONS: TSTM and TC did not improve executive function symptoms, but they improved ADHD symptomatology related to emotional regulation. Further studies with bigger samples are required to confirm these preliminary findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04355065; https://clinicaltrials.gov/ct2/show/NCT04355065.

Comparing Differences between Two Groups of Adolescents Hospitalized for Self-Harming Behaviors with and without Personality Disorders.

Self-harm (non-suicidal self-injury (NSSI) and suicidal behavior (SB)) is frequent display during adolescence. Patients with personality disorders (PDs) frequently self-harm. However, few studies have focused on the role of PDs in self-harming adolescents. In this study, we collected 79 adolescents hospitalized due to self-harm (88.6% female; 78.5% Caucasian) and divided them into two groups, with or without a diagnosis of PD. The socio-demographic and psychological-clinical data were collected through a structured interview by clinicians. Univariate, subgroup, and multiple logistic regression analyses were performed. Univariate analysis showed that adolescents with a PD and self-harm had (1) an older age at hospitalization (p < 0.01); (2) experienced physical and sexual abuse (p = 0.05, and p < 0.01, respectively); (3) ADHD (p = 0.05); (4) a greater number of SA (p < 0.01); and (5) probability of being a major NSSI patient (>20 lifetime NSSI episodes) (p < 0.01). After multivariate stratified analysis, the results indicated that an older age, and particularly major NSSI status were predictors of PD diagnosis. Early identification and a better understanding of the characteristics of adolescent PDs can assist clinicians in intervening earlier and developing more rational treatment strategies to reduce the long-term effects of PDs.

Traditional bullying and cyberbullying in the digital age and its associated mental health problems in children and adolescents: a meta-analysis.

Bullying is a risk factor for the physical and mental health of adolescents. The advent of new technologies has resulted in a brand-new type of bullying, cyberbullying (CB). The co-occurring effects of cyberbullying and traditional bullying(TB) forms of bullying on adolescent mental health are unclear. We performed a meta-analysis to explore the unique and combined effects of CB and TB on adverse psychological outcomes in victims by conducting a joint study of both types of bullying. By doing so, we provide the basis for a comprehensive community bullying prevention program. The database PubMed, PsyclNFO, and Web of Science were searched for studies from 2010 to 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed for data abstraction, and the NIH tool was used to evaluate study-level risk of bias. 42 studies with 266,888 participants were identified. Random-Effect models were used for our study. The moderator analysis was used to explore the moderator of prevalence. Studies with three groups of victims (TB only, CB only, and Both) and two groups of victims (TB and CB) were compared in subgroup analysis. The mean victimization rate was 24.32% (95% CI 20.32-28.83%) for TB and 11.10% (95% CI 9.12-13.44%) for CB. Roughly one-third of TB victims were also victimized by CB. Conversely, only about one-third of CB victims were free from TB. The estimated ORs for depression, suicidal ideation, suicide attempts, and self-harm in the three-group (TB only, CB only and Both) analysis were: depression [TB only: 3.33 (2.22-5.00); CB only: 3.38 (2.57-4.46); Both: 5.30 (2.43-11.56)]; suicidal ideations [TB only: 3.08 (2.12-4.46); CB only: 3.52 (2.38-5.20); Both: 6.64 (4.14-10.64)]; self-harm [TB only: 2.70 (1.86-3.91); CB only: 3.57 (3.20-3.98); Both: 5.57 (2.11-16.00)]; and suicide attempts: [TB only: 2.61 (1.50-4.55); CB only: 3.52 (2.50-4.98); Both: 7.82 (3.83-15.93)]. TB and CB victimization among youth are a matter of public health concern. Victimization appears to be a marker of greater psychopathological severity, particularly suicide-related issues.

Effectivity of Saffron Extract (Saffr'Activ) on Treatment for Children and Adolescents with Attention Deficit/Hyperactivity Disorder (ADHD): A Clinical Effectivity Study.

Attention Deficit/Hyperactivity Disorder is the most prevalent neurodevelopmental disorder worldwide. Choice treatment includes psychostimulants, but parents tend to be reluctant to administer them due to side effects, and alternatives are needed. Saffron extract is a natural stimulant that has been proven safe and effective for treating a variety of mental disorders. This study compares the efficacy of saffron and the usual treatment with methylphenidate, using objective and pen-and-paper tests. We performed a non-randomized clinical trial with two groups, methylphenidate (n = 27) and saffron (n = 36), in children and adolescents aged 7 to 17. Results show that the efficacy of saffron is comparable to that of methylphenidate. Saffron is more effective for treating hyperactivity symptoms, while methylphenidate is more effective for inattention symptoms.

Biosignature of self-injury behaviors in adolescence: Role of ß-endorphin in an acute inpatient unit.

Self-injurious behavior (SIB) (either non-suicidal self-injury, NSSI; or suicide attempts, SA) is a common reason for adolescent psychiatric emergency hospitalizations. Altered basal serum ß-endorphin (BE) levels have been reported in adults with a history of SIB, but information is lacking in adolescents. We analyzed the psychoclinical profile and serum BE level of 39 adolescents admitted to the acute unit at a hospital in Spain due to SIB. The Mean (SD) serum BE level was high (190.53 ± 74.83). Regarding time sequence, the onset age of NSSI and SA were related (p < 0.001). The older the onset age of NSSI, the shorter the transition between NSSI and the onset of SA behavior (p = 0.05), but this difference does not lead the variation of BE (p = 0.81). Patients diagnosed with depression had lower serum BE levels than adolescents with other diagnoses (p = 0.03). Although adolescents who seem to be addicted to SIB had higher levels of BE, this finding was not statistically significant. The relationship between serum BE levels and SIB in adolescents requires further investigation.

Developing Serious Video Games to Treat Attention Deficit Hyperactivity Disorder: Tutorial Guide.

Video game-based therapeutic interventions have demonstrated some effectiveness in decreasing the symptoms of attention deficit hyperactivity disorder (ADHD). Compared with more traditional strategies within the multimodal treatment of ADHD, video games have certain advantages such as being comfortable, flexible, and cost-efficient. However, establishing the most appropriate type(s) of video games that should be used for this treatment remains a matter of debate, including the commercial existing video games or serious video games that are specifically constructed to target specific disorders. This guide represents a starting point for developing serious video games aimed at treating ADHD. We summarize the key points that need to be addressed to generate an effective and motivating game-based treatment. Following recommendations from the literature to create game-based treatments, we describe the development stages of a serious video game for treating ADHD. Game design should consider the interests of future users; game mechanics should be based on cognitive exercises; and therapeutic mechanisms must include the control of difficulty, engagement, motivation, time constraints, and reinforcement. To elaborate upon this guide, we performed a narrative review focused on the use of video games for the treatment of ADHD, and were inspired by our own experience during the development of the game "The Secret Trail of Moon."

A Virtual Reality Game (The Secret Trail of Moon) for Treating Attention-Deficit/Hyperactivity Disorder: Development and Usability Study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) affects between 4% and 8% of children worldwide. The treatment of choice is multimodal treatment. Multimodal interventions for ADHD may be improved by incorporating new treatments, such as treatment via serious video games. The Secret Trail of Moon (TSTM) is a virtual reality serious video game that was designed for cognitive training related to core ADHD symptoms and executive dysfunction. OBJECTIVE: We aimed to describe the development and usability of TSTM. METHODS: The usability study included 37 children and adolescents who tested TSTM during the early usability stage (preinclusion) of a randomized controlled clinical trial for testing the effectiveness of TSTM. Chi-square tests were performed to compare patients with ADHD (ADHD combined subtype vs inattentive subtype) and to compare frequent and infrequent video game players in the second study. We used SPSS version 20 for Macintosh (IBM Corporation). RESULTS: A total of 31/37 (86%) and 30/37 (83%) of participants liked playing TSTM and wanted to continue playing TSTM, respectively. Further, 5/37 (14%) of participants reported that they experienced either perceived dizziness or virtual reality motion sickness. We found no statistically significant differences after comparing the ADHD combined subtype to the inattentive subtype and frequent video game players to infrequent video game players. CONCLUSIONS: Serious video games, such as TSTM, may complement the current multimodal approach for treating ADHD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04355065; https://clinicaltrials.gov/ct2/show/NCT04355065.

A Virtual Reality Serious Videogame Versus Online Chess Augmentation in Patients with Attention Deficit Hyperactivity Disorder: A Randomized Clinical Trial.

Objective: Serious videogames and virtual reality (VR) have gained increasing interest for treating attention deficit hyperactivity disorder (ADHD). "The Secret Trail of Moon" (TSTM) study is a clinical trial devoted to testing the efficacy of TSTM, a VR serious videogame developed to train in five major cognitive skills usually compromised in patients with ADHD. This study is a three-arm nonequality trial comparing TSTM to online chess training and a control group (CG). This study aims to demonstrate that augmentation with either TSTM or online chess is efficacious in clinically drug-stable patients with ADHD. Materials and Methods: This study is prospective, unicentric, and randomized with a CG. One hundred five patients with ADHD, ages 12-22 years old, and pharmacologically stable were enrolled. Patients were randomized into three groups: TSTM group, online chess group (therapeutic chess [TC]), and CG. Objective and subjective measures of the patient and parents are included. Patient visits differ for each group. TSTM group patients have 15 face-to-face visits: preinclusion visit, inclusion visit, 12 training visits, and final visit. TC and CG patients have 3 face-to-face visits (preinclusion, initial visit, and final visit) and 12 e-mail or phone communications during training (TC) or follow-up (CG group). This study was approved by the local Institutional Review Board (IRB). Results: Not applicable. This is a study protocol. Conclusion: This is the first study testing an augmentation strategy using either a serious videogame or chess in clinically drug-treated patients with ADHD. Using VR serious videogames present with several advantages over traditional videogames. Trial Registration: NCT04355065.