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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., (©Marina Martin-Moratinos, Marcos Bella-Fernández, Maria Rodrigo-Yanguas, Carlos González-Tardón, Aaron Sújar, Chao Li, Ping Wang, Ana Royuela, Pilar Lopez-Garcia, Hilario Blasco-Fontecilla. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.02.2024.)

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., (©María Rodrigo-Yanguas, Marina Martín-Moratinos, Carlos González-Tardón, Fernando Sanchez-Sanchez, Ana Royuela, Marcos Bella-Fernández, Hilario Blasco-Fontecilla. Originally published in JMIR Serious Games (https://games.jmir.org), 24.04.2023.)

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.

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.", (©Aarón Sújar, Marina Martín-Moratinos, María Rodrigo-Yanguas, Marcos Bella-Fernández, Carlos González-Tardón, David Delgado-Gómez, Hilario Blasco-Fontecilla. Originally published in JMIR Serious Games (https://games.jmir.org), 01.08.2022.)

The use of new technologies has become widespread worldwide. There is increasing concern about "Internet addiction disorder" (IAD), "Internet gaming disorder" (IGD), and "Mobile phone addiction" (MPA). Attention Deficit Hyperactivity Disorder (ADHD) has been associated with IAD and IGD. However, evidence is lacking about the relationship between ADHD and MPA. Naturalistic case-control study. 112 patients (51 children with and 61 children without ADHD) between 7 and 17 years old were compared regarding IAD, IGD, and MPA. We used the TEA questionnaire for the assessment of executive function and ADHD (ATENTO), and the ADITEC questionnaire to get gender-differentiated information for IAD, IGD, and MPA. Female children scored higher on MPA (Mean ± Standard Deviation, M ± SD) (25.93 ±  17.64 vs. 14.77 ±  19.43, p=0.03), while male children scored higher on IGD (30.09 ± 21.65 vs. 12.51 ± 16.61, p < 10^-3). Severity of hyperactivity/impulsivity and IGD were moderately correlated (r=0.349, p=0.013), but the correlation disappeared after controlling for the impact on the social domain as measured by the ATENTO questionnaire (r=171, p=0.250). Most parents are concerned that their children may be addicted to IAD/IGD/MPA. Female gender is associated with MPA, while male gender is associated with IGD. ADHD is a risk factor for developing IAD and IGD. Combined type and predominantly hyperactive/impulsive ADHD are each associated with IGD. Good social adjustment protects against developing IGD. There are gender vulnerabilities for IAD/IGD/MPA. ADHD is a risk factor for IGD, but good social adjustment buffers this association.

Background: Mucosal secretory immunoglobulin A (s-IgA) is an antibody protein-complex that plays a crucial role in immune first defense against infection. Although different immune biomarkers have been associated with stress-related psychopathology, s-IgA remains poorly studied, especially in youth., Objectives: The present study investigated how s-IgA behaves in front of acute psychosocial stress in children and adolescents, including possible variability associated with developmental stage and history of childhood maltreatment (CM)., Methods: 94 children and adolescents from 7 to 17 years (54 with a current psychiatric diagnostic and 40 healthy controls) drawn from a larger Spanish study were explored (EPI-Young Stress Project). To assess biological reactivity, participants provided five saliva samples during an acute laboratory-based psychosocial stressor, the Trier Social Stress Test for Children (TSST-C). Samples were assayed for s-IgA, as well as for cortisol. Pubertal development was ascertained by Tanner stage and CM following TASSCV criteria., Results: We observed s-IgA fluctuations throughout the stressor, indicating the validity of TSST-C to stimulate s-IgA secretion (F(4,199) = 6.200, p <.001). Although s-IgA trajectories followed a reactivity and recovery pattern in adolescents, children exhibited no s-IgA response when faced with stress (F(4,197) = 3.406, p =.010). An interaction was found between s-IgA and CM (F(4,203) = 2.643, p =.035). Interestingly, an interaction between developmental stage, CM history and s-IgA reactivity was identified (F(12,343) = 2.036, p =.017); while children non-exposed to maltreatment exhibited no s-IgA changes to acute stress, children with a history of CM showed a similar response to adolescents, increasing their s-IgA levels after the psychosocial stressor., Conclusion: Acute psychosocial stress stimulates s-IgA secretion, but only after puberty. However, children with a history of maltreatment exhibited a response resembling that of adolescents, suggesting an early maturation of the immune system. Further studies are needed to clarify the validity of s-IgA as an acute stress biomarker, including additional measures during stress exposure., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (©Maria Rodrigo-Yanguas, Marina Martin-Moratinos, Angela Menendez-Garcia, Carlos Gonzalez-Tardon, Ana Royuela, Hilario Blasco-Fontecilla. Originally published in JMIR Serious Games (https://games.jmir.org), 01.09.2021.)

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.

Purpose of Review: The current serotonin-based biological model of suicidal behavior (SB) may be too simplistic. There is emerging evidence that other biomarkers and biological systems may be involved in SB pathophysiology. The literature on the endocannabinoid (EC) systems and SB is limited. The objective of the present article is to review all available information on the relationship between cannabinoid receptors (CB 1 and CB 2 receptors), and SB and/or psychological pain., Recent Findings: Our review is limited by the small number and heterogeneity of studies identified: (1) an autopsy study describing elevated levels of CB 1 receptor activity in the prefrontal cortex and suicide in both depression and alcoholism and (2) studies supporting the involvement of both CB 1 and CB 2 receptors in the regulation of neuropathic pain and stress-induced analgesia. We conclude that cannabinoid receptors, particularly CB 1 receptors, may become promising targets for the development of novel therapeutic tools for the treatment of SB.

Between 10 and 20 million people attempt suicide every year worldwide, and suicide attempts represent a major economic burden. Suicide attempters suffer from high rates of comorbidity, and comorbidity is the rule in suicide re-attempters. Comorbidity complicates treatment and prognosis and causes a more protracted course. In the present narrative review, we included these patterns of comorbidity: intra-Axis I disorders, intra-Axis II disorders, Axis I with Axis II disorders, and psychiatric with physical illnesses. We also briefly reviewed the patterns of comorbidity in suicide re-attempters. We concluded that comorbidity at different levels appears to be the rule in suicide attempters, particularly in those who re-attempt. However, several issues deserve further research regarding the patterns of comorbidity in suicide attempters.