Assessing the Clinical Efficacy of a Virtual Reality Tool for the Treatment of Obesity: Randomized Controlled Trial.

BACKGROUND: Virtual reality (VR) interventions, based on cognitive behavioral therapy principles, have been proven effective as complementary tools in managing obesity and have been associated with promoting healthy behaviors and addressing body image concerns. However, they have not fully addressed certain underlying causes of obesity, such as a lack of motivation to change, low self-efficacy, and the impact of weight stigma interiorization, which often impede treatment adherence and long-term lifestyle habit changes. To tackle these concerns, this study introduces the VR self-counseling paradigm, which incorporates embodiment and body-swapping techniques, along with motivational strategies, to help people living with obesity effectively address some of the root causes of their condition. OBJECTIVE: This study aims to assess the clinical efficacy of ConVRself (Virtual Reality self-talk), a VR platform that allows participants to engage in motivational self-conversations. METHODS: A randomized controlled trial was conducted with 68 participants from the bariatric surgery waiting list from the obesity unit of the Vall d'Hebron University Hospital in Barcelona, Spain. Participants were assigned to 1 of 3 groups: a control group (CG), which only received treatment as usual from the obesity unit; experimental group 1 (EG1), which, after intensive motivational interviewing training, engaged in 4 sessions of VR-based self-conversations with ConVRself, and underwent embodiment and body-swapping techniques; and experimental group 2 (EG2), which engaged in 4 VR-based sessions led by a virtual counselor with a prerecorded discourse, and only underwent the embodiment technique. In the case of both EG1 and EG2, the VR interventions were assisted by a clinical researcher. Readiness to change habits, eating habits, and psychological variables, as well as adherence and satisfaction with ConVRself were measured at baseline, after the intervention, 1 week after the intervention, and 4 weeks after the intervention. RESULTS: Regarding the primary outcomes, EG1 (24/68, 35%) and EG2 (22/68, 32%) showed significant improvements in confidence to lose weight compared to the CG (22/68, 32%) at all assessment points (ß=-.16; P=.02). Similarly, EG1 demonstrated a significant increase after the intervention in readiness to exercise more compared to the CG (ß=-.17; P=.03). Regarding the secondary outcomes, EG1 participants showed a significant reduction in uncontrolled eating (ß=.71; P=.01) and emotional eating (ß=.29; P=.03) compared to the CG participants, as well as in their anxiety levels compared to EG2 and CG participants (ß=.65; P=.01). In addition, participants from the experimental groups reported high adherence and satisfaction with the VR platform (EG1: mean 59.82, SD 4.00; EG2: mean 58.43, SD 5.22; d=0.30, 95% CI -0.30 to 0.89). CONCLUSIONS: This study revealed that using VR self-conversations, based on motivational interviewing principles, may have benefits in helping people with obesity to enhance their readiness to change habits and self-efficacy, as well as reduce dysfunctional eating behaviors and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT05094557; https://www.clinicaltrials.gov/study/NCT05094557.

Comparing nurses attending a specialised mental health programme with and without substance use disorder: a retrospective, observational study in Spain.

OBJECTIVES: To analyse the differences between nurses with and without substance use disorders (SUDs) admitted to a specialised mental health programme. DESIGN: Retrospective, observational study. SETTING: Specialised mental health treatment programme for nurses in Catalonia, Spain. PARTICIPANTS: 1091 nurses admitted to the programme from 2000 to 2021. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOMES: Sociodemographic, occupational and clinical variables were analysed. Diagnoses followed Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision criteria. RESULTS: Most nurses admitted to the programme were women (88%, n=960) and came voluntarily (92.1%, n=1005). The mean age at admission was 45 (SD=10.4) years. The most common diagnoses were adjustment disorders (36.6%, n=399), unipolar mood disorders (25.8%, n=282), anxiety disorders (16.4%, n=179) and SUDs (13.8%, n=151). Only 19.2% (n=209) of the sample were hospitalised during their first treatment episode. After multivariate analysis, suffering from a SUD was significantly associated with being a man (OR=4.12; 95% CI 2.49 to 6.82), coming after a directed referral (OR=4.55; 95% CI 2.5 to 7.69), being on sick leave at admission (OR=2.21; 95% CI 1.42 to 3.45) and needing hospitalisation at the beginning of their treatment (OR=12.5; 95% CI 8.3 to 20). CONCLUSIONS: Nurses with SUDs have greater resistance to voluntarily asking for help from specialised mental health treatment programmes and have greater clinical severity compared with those without addictions. SUDs are also more frequent among men. More actions are needed to help prevent and promote earlier help-seeking behaviours among nurses with this type of mental disorder.

ADHD Rating Scale (ADHD-RS): Validation in Spanish in adult population according to the DSM-5.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, with an estimated prevalence in adulthood of 2.5-3.4%. The Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) is an 18-item self-administered scale that assesses attention deficit and hyperactivity/impulsivity symptoms of ADHD in adults. This study aims to validate the ADHD-RS in Spanish according to the diagnostic criteria established by the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). MATERIALS AND METHODS: A sample of 441 adult patients (mean age 33.34±11.37 years) was included, 396 subjects were diagnosed with ADHD (mean age 33.17±11.18 years), and 45 were controls (mean age 35.40±12.33 years). The clinical diagnosis of ADHD was established according to the DSM-5 criteria. The ADHD-RS was subsequently administered to all participants. A logistic regression study evaluated the model in terms of sensitivity, specificity, positive predictive value, and negative predictive value. The Kaiser-Meyer-Olkin (KMO) measure was performed to assess the adequacy of the data set, and to determine whether factor analysis was applicable, Bartlett's sphericity test was performed. Principal component analysis was used, using the Varimax orthogonal rotation method, which minimizes the number of variables with high loads on each factor, obtaining two factors and thus, simplifying their interpretation. RESULTS: The cut-off point that best discriminates the combined presentation of ADHD was 24 points, with a sensitivity of 94.78%, a specificity of 84.79%, a PPV (positive predictive value) of 93.74%, and an NPV (negative predictive value) of 78.33, with an area under the curve (AUC) of 0.85, and a kappa coefficient of 0.86. Regarding inattentive ADHD, the cut-off point that best discriminates was 21 points, with a sensitivity of 92.56%, a specificity of 76.26%, a PPV of 92.01%, an NPV of 78.33%, an AUC of 0.90, and a kappa coefficient of 0.87. Different cut-off values in the two subgroups suggests that a differentiated cut-off point for the inattentive and combined presentations may be an adequate assessment strategy for ADHD in adulthood. CONCLUSIONS: The Spanish version of the ADHD-RS is a valid instrument to evaluate ADHD in adults according to the diagnostic criteria established by the DSM-5. Differentiated cut-off points for the inattentive and combined presentations discriminate more accurately than a single cut-off point.

Emotion regulation and emotion dysregulation in children and adolescents with Autism Spectrum Disorder: A meta-analysis of evaluation and intervention studies.

Children and adolescents with Autism Spectrum Disorder (ASD) often experience challenges in emotion regulation (ER) and emotion dysregulation (ED) which can interfere with their adaptive functioning. This study aimed to systematically review and meta-analyze the evidence on ER/ED in children and/or adolescents with ASD, examining its relationship with the following variables: internalizing and externalizing symptoms, cognitive function and social skills, and the effectiveness of non-pharmacological interventions addressing ER difficulties. Both electronic and manual searches were conducted to identify potential studies. Fifty-five studies were included in the meta-analysis. A statistically significant between-group difference was found, suggesting greater ER/ED challenges in the ASD group. Also, the ASD group showed more maladaptive ER strategies and fewer adaptive ER strategies compared to the non-ASD participants. Additionally, more severe ASD and poorer social skills were associated with greater ED and poorer ER skills, respectivelly. Furthermore, there was a significant correlation between internalizing symptomatology and both adaptive and maladaptive ER strategies. Studies of non-pharmacological interventions showed significant improvement in both ER and ED. These results imply that assessing ER/ED in children and adolescents with ASD should be part of the evaluation process, and it should also be a focal point for intervention in this population.

Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders.

We characterized the genetic architecture of the attention-deficit hyperactivity disorder-substance use disorder (ADHD-SUD) relationship by investigating genetic correlation, causality, pleiotropy, and common polygenic risk. Summary statistics from genome-wide association studies (GWAS) were used to investigate ADHD (Neff = 51,568), cannabis use disorder (CanUD, Neff = 161,053), opioid use disorder (OUD, Neff = 57,120), problematic alcohol use (PAU, Neff = 502,272), and problematic tobacco use (PTU, Neff = 97,836). ADHD, CanUD, and OUD GWAS meta-analyses included cohorts with case definitions based on different diagnostic criteria. PAU GWAS combined information related to alcohol use disorder, alcohol dependence, and the items related to alcohol problematic consequences assessed by the alcohol use disorders identification test. PTU GWAS was generated a multi-trait analysis including information regarding Fagerström Test for Nicotine Dependence and cigarettes per day. Linkage disequilibrium score regression analyses indicated positive genetic correlation with CanUD, OUD, PAU, and PTU. Genomic structural equation modeling showed that these genetic correlations were related to two latent factors: one including ADHD, CanUD, and PTU and the other with OUD and PAU. The evidence of a causal effect of PAU and PTU on ADHD was stronger than the reverse in the two-sample Mendelian randomization analysis. Conversely, similar strength of evidence was found between ADHD and CanUD. CADM2 rs62250713 was a pleiotropic SNP between ADHD and all SUDs. We found seven, one, and twenty-eight pleiotropic variants between ADHD and CanUD, PAU, and PTU, respectively. Finally, OUD, CanUD, and PAU PRS were associated with increased odds of ADHD. Our findings demonstrated the contribution of multiple pleiotropic mechanisms to the comorbidity between ADHD and SUDs.

Abstinence duration and psychopathology among addiction outpatients during 18 months of COVID-19.

Background: The COVID-19 pandemic has impacted the mental health of patients with substance use disorder (SUD). However, few longitudinal studies have been done which examine associations between the pandemic, SUD patients' mental health and their drug use. Objectives: This study aimed to examine duration of abstinence according to psychiatric status among SUD outpatients followed-up for 18 months from the pandemic related lockdown. Methods: A follow-up study of 316 SUD outpatients was undertaken. Sociodemographic features, and clinical and consumption related variables were recorded. Pre, during and post lockdown information was evaluated. Abstinence/substance use was monitored at the patient's scheduled follow-up appointments, and psychiatric disorders and psychological variables were revaluated at 18 months. Results: Survival analyses were used to compare the duration of abstinence (in months) from the beginning of the lockdown. It was observed that 70% of patients consumed the main substance for which they were being treated at some point during the follow-up. Men, younger patients, those with more symptoms of anxiety and personality disorders, and patients who experienced increased craving during follow-up, showed shorter duration of abstinence. While patients who had previously maintained at least one year of abstinence, achieved better results. Conclusions: During the first year and a half of the pandemic, SUD outpatients presented alterations in mental health, such us anxiety, depression and maladaptive personality traits and a high rate of relapse. For this reason, despite the health and social crisis and their restrictive measures, a comprehensive treatment should be ensured.

Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome.

The association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade inflammation has been explored in children but rarely in adults. Inflammation is characteristic of some, but not all, patients with ADHD and might be influenced by ADHD medication but also lifestyle factors including nutrition, smoking, and stress. It is also still unclear if any specific symptoms are related to inflammation. Therefore, we assessed 96 inflammatory proteins in a deeply phenotyped cohort of 126 adult ADHD participants with a stable medication status using OLINK technology. A data-based, unsupervised hierarchical clustering method could identify two distinct biotypes within the 126 ADHD participants based on their inflammatory profile: a higher inflammatory potential (HIP) and a lower inflammatory protein potential (LIP) group. Biological processes that differed strongest between groups were related to the NF-κB pathway, chemokine signaling, IL-17 signaling, metabolic alterations, and chemokine attraction. A comparison of sample characteristics revealed that the HIP group was more likely to have higher levels of chronic stress (p < 0.001), a higher clinical global impression scale score (p = 0.030), and a higher risk for suicide (p = 0.032). Medication status did not influence protein levels significantly (p ≥ 0.074), but psychotropic co-medication (p ≤ 0.009) did. In conclusion, our data suggest the presence of two distinct biotypes in adults with ADHD. Higher levels of inflammatory proteins in ADHD are linked to higher levels of chronic perceived stress in a linear fashion. Further research on inflammation in adults with ADHD should take stress levels into account.

Brain Functional Correlates of Recall of Life Events in Medication-Naïve Adolescents with Borderline Personality Disorder.

INTRODUCTION: Recall of autobiographical events has been found to be impaired in borderline personality disorder (BPD), but few studies have examined if this impairment has brain functional correlates. This study evaluated brain functional alterations during autobiographical recall using medication-naive adolescent patients to avoid potential confounding effects of treatment. METHODS: Thirty-two adolescent female patients with BPD who were never-medicated and without psychiatric comorbidity and 33 matched healthy females underwent fMRI while they viewed individualized cue words that evoked autobiographical memories. Control conditions included viewing non-memory-evoking cues and a low-level baseline (cross-fixation). RESULTS: During autobiographical recall, in comparison to the low-level baseline, the BPD patients showed increased brain activity in regions including the posterior hippocampus, the lingual and calcarine cortex, and the precuneus compared to the healthy controls. The BPD patients also showed a failure to deactivate the right dorsolateral prefrontal cortex during autobiographical recall. No patient-control differences were found when memory-evoking words were compared to non-memory-evoking words. DISCUSSION/CONCLUSIONS: This study finds evidence of hippocampal/lingual/calcarine/precuneus hyperactivation to stimuli that evoke autobiographical memories in patients with BPD. As the changes were seen in never-treated patients without other comorbidities, they could be considered intrinsic to the disorder. Our study also adds to existing evidence for failure of deactivation in BPD, this time outside the default mode network.

Treating Treatment-resistant Depression with Esketamine Nasal Spray When All Therapeutic Options Have Been Exhausted: Clinical Experience from a Spanish Cohort of Expanded Use.

Objective: : Treatment Resistant Depression (TRD) is commonly defined as the lack of response to two or more anti-depressants with different mechanisms of action. Up to 30% of patients diagnosed with major depressive disorder might be considered to present TRD. The objective of this study was to assess the effectiveness and tolerability of esketamine in patients diagnosed with TRD, who were referred to our program after exhausting all available treatments. A secondary objective consisted in researching the relationship between response and previous use of electroconvulsive therapy. Methods: : A prospective, observational study was carried out in patients enrolled in the expanded use of esketamine in our center. They received esketamine prior to its marketing authorisation, for therapeutic purposes. Sixteen subjects were analyzed. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS). Patients were followed up to 4 months after the administration. Results: : Esketamine showed a rapid, robust effect in improving depressive symptoms, with no specific correlation between outcome and any demographic or clinical traits evaluated. No differences were found between patients that previously received Electroconvulsive Therapy, and those that didn't. 10 out of 16 patients responded (＞ 50% change in baseline MADRS scores), but only five achieved remission (＜ 12 points in the global MADRS score). We provide some recommendations, based on clinical experience, to improve tolerability and adherence, and to manage adverse effects. Conclusion: : Results suggest that esketamine is a safe, effective and rapid-acting option for TRD. More studies are needed to properly assess predictors of response outcome.

Transcriptomic risk scores for attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. We performed a transcriptome-wide association study (TWAS) using the latest genome-wide association study (GWAS) meta-analysis, in 38,691 individuals with ADHD and 186,843 controls, and 14 gene-expression reference panels across multiple brain tissues and whole blood. Based on TWAS results, we selected subsets of genes and constructed transcriptomic risk scores (TRSs) for the disorder in peripheral blood mononuclear cells of individuals with ADHD and controls. We found evidence of association between ADHD and TRSs constructed using expression profiles from multiple brain areas, with individuals with ADHD carrying a higher burden of TRSs than controls. TRSs were uncorrelated with the polygenic risk score (PRS) for ADHD and, in combination with PRS, improved significantly the proportion of variance explained over the PRS-only model. These results support the complementary predictive potential of genetic and transcriptomic profiles in blood and underscore the potential utility of gene expression for risk prediction and deeper insight in molecular mechanisms underlying ADHD.

Impact of the trait anxiety during pregnancy on birth weight: an observational cohort study.

To explore the effects of antenatal anxiety on fetal growth an observational cohort study was performed, including a cohort of 204 women with singleton pregnancies during the strict lockdown of the COVID-19 pandemic in 2020. Psychosocial factors, maternal demographics, obstetric outcomes, social support (Medical Outcomes Study Social Support Survey, MOS-SSS), and symptoms of anxiety (State-Trait Anxiety Inventory, STAIs and STAIt) and depression (Edinburgh Postpartum Depression Scale, EPDS) were studied as potential predictors of low birth weight. Main outcome measures were birth weight, head circumference and length. Results showed a negative correlation between STAIt score (trait anxiety) and birth weight percentile (r = -0.228, p = .047). In the univariate linear regression analysis, a lower maternal weight and BMI before pregnancy, parity, increased STAIt score and preterm birth below 37 weeks of gestation (p = .008, p = .015, p = .028, p = .047 and p = .022, respectively) were identified as predictive risk factors for low birth weight, whereas in the multivariate lineal regression analysis only a lower maternal weight before pregnancy and an increased STAIt score were independent predictors for low birth weight (p = .020, p = .049, respectively). To conclude, anxiety during pregnancy impacts birth weight, and specifically the trait anxiety, is a predictor for low birth weight.

Dog-Assisted Therapy vs Relaxation for Children and Adolescents with Fetal Alcohol Spectrum Disorder: A Randomized Controlled Study.

The rationale of this study was to evaluate the efficacy of Dog-assisted Therapy (DAT) in children and adolescents with Fetal Alcohol Spectrum Disorder (FASD). We conducted a randomized controlled trial in a cohort of 71 children and adolescents with FASD. Participants were randomly assigned either to DAT group (n = 38) or Relaxation Group (control group) (n = 33). Results revealed that participants who were assigned to the DAT group experienced significantly reduced externalizing symptoms (CBCL Externalizing Inattention: t (69) = 2.81, p = .007; d = 0.7); CBCL Opposition: t (69) = 2.54, p = .013; d = 0.6), reduced internalizing symptoms (CBCL Social problems: t (69) = 3.21, p = .002; d = 0.8) as well as improvements on social skills (SSIS-P Problem behavior: t (68) = 2.55, p = .013; d = 0.6), and quality of life (KidScreen Autonomy and Parents: t (51) = - 2.03, p = .047; d = 0.5) compared to the relaxation control group. The relaxation control group obtained significant differences between the pre- and post-treatment evaluation, diminishing withdraw symptoms (t (32) = 3.03, p = .005; d = 0.2). Results suggest that DAT and relaxation may be promising adjunctive treatments for children and adolescents with FASD.Clinical trial registration information: http://clinicaltrials.gov/ ; NCT04038164.

The impact of attention-deficit/hyperactivity disorder and specific learning disorders on academic performance in Spanish children from a low-middle- and a high-income population.

Introduction: Past research has demonstrated that attention-deficit/hyperactivity disorder (ADHD), specific learning disorders (SLD), and socioeconomic status (SES) affect a host of educational outcomes. However, there are no studies examining whether SES moderates the association between these neurodevelopmental disorders (ND) and the academic achievement of children and adolescents. The present investigation examined the impact of ADHD and SLD on academic performance in 1,287 Spanish students aged 5-17 from a low-middle (LM)- and a high-income population, when adjusted for comorbidity and demographic factors that may influence educational functioning. Methods: Parents completed a questionnaire regarding demographic data along with the Strengths and Difficulties Questionnaire. Additionally, teachers provided information on learning difficulties trough the Protocol for Detection and Management of Dyslexia. Teacher's Version. Academic performance across multiple domains (i.e., first language, foreign language, mathematics) was obtained from school records. ND were determined using standardized diagnostic methods based on the Diagnostic and Statistical Manual of Mental Disorders criteria. To examine the effects of ADHD and SLD on academic achievement and the potential moderating role of SES, a series of ordinal logistic regressions were conducted. Results: Emotional/behavioral problems, learning difficulties, and ND were more frequent among individuals from the LM-income population. After controlling for gender, age, parental divorce/separation, grade retention, frequency of screen use, and daily meals, both ADHD and SLD were associated with worse educational outcomes. Lower SES also increased the risk for academic impairment, although the interactions with ADHD or SLD were not significant. Conclusion: These findings indicate that ADHD and SLD exert a pervasive impact on academic performance across different socioeconomic backgrounds. Therefore, early detection and effective intervention strategies aimed at students with these ND are crucial to improve their educational functioning and mitigate the negative consequences related to academic problems.

Discrimination of Borderline Personality Disorder (BPD) and Attention-Deficit/Hyperactivity Disorder (ADHD) in adolescents: Spanish version of the Borderline Personality Features Scale for Children-11 Self-Report (BPFSC-11) Preliminary results.

BACKGROUND: Although the diagnosis of Borderline Personality Disorder (BPD) during adolescence has been questioned, many recent studies have confirmed its validity. However, some clinical manifestations of BPD could be identifiable in adolescents with other pathologies, such as Attention-Deficit/Hyperactivity Disorder (ADHD). The objective of the present study is to examine the capacity of the self-report Borderline Personality Features Scale Children-11 (BPFSC-11) to discriminate between BPD and ADHD adolescents. METHODS: One hundred and forty-five participants were grouped based on their diagnosis: 58 with BPD, 58 with ADHD, and 29 healthy volunteers as a control group. Between-group differences and the ROC curve were performed to test if the total score for the BPFSC-11 and/or its factors can significantly discriminate between BPD and other adolescent groups. RESULTS: The results show that the total BPFSC-11 score has good discriminant capacity among adolescents diagnosed with BPD, ADHD and healthy volunteers. However, different patterns of discriminative capacity were observed between the three groups for emotional dysregulation and impulsivity/recklessness factors. CONCLUSIONS: Our results support the hypothesis that the BPFSC-11 is an adequate instrument for discriminating between BPD and ADHD in adolescents, who can present significant psychopathological overlap. Tools to identify BPD in adolescence, as well as for better differential diagnosis, would improve the possibility of offering specific treatments targeting these populations.

Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. METHODS: We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. RESULTS: IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. CONCLUSIONS: These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.

Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan.

There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = -0.36, P = 1.41e-16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e-06; Beta = -0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes.

Clinical features and factors related to lifetime suicidal ideation and suicide attempts in patients who have had substance-induced psychosis across their lifetime.

Suicidal behaviors are common among patients with substance use disorders (SUD). However, the prevalence and clinical factors related to suicide behaviors among patients who have had substance-induced psychosis (SIP) is unknown. This study aims to explore the prevalence, clinical features, and factors related to lifetime suicidal ideation (SI) and suicide attempts (SA) in patients who have had SIP across their lifetime. A cross-sectional study was conducted in an outpatient center for addiction treatment between 01/01/2010 and 12/31/2021. 601 patients were evaluated with validated scales and questionnaires (79.03% males; M age 38.11±10.11 years). The prevalence of SI and SA was 55.4% and 33.6%, respectively. SI was independently related to any type of lifetime abuse, depressive spectrum disorders, benzodiazepine use disorder, borderline personality disorder, and the level of depressive symptoms. SA was independently associated with lifetime physical abuse, benzodiazepine use disorder, the number of psychotic symptoms, borderline personality disorder, and the level of depressive symptoms. The main factors related to SI and SA in those patients should be evaluated in daily clinical practice and considered in any approach to clinical practice as well as in health policies targeting suicide prevention.

Immunoregulatory and/or Anti-inflammatory Agents for the Management of Core and Associated Symptoms in Individuals with Autism Spectrum Disorder: A Narrative Review of Randomized, Placebo-Controlled Trials.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with a so far poorly understood underlying pathogenesis, and few effective therapies for core symptoms. Accumulating evidence supports an association between ASD and immune/inflammatory processes, arising as a possible pathway for new drug intervention. However, current literature on the efficacy of immunoregulatory/anti-inflammatory interventions on ASD symptoms is still limited. The aim of this narrative review was to summarize and discuss the latest evidence on the use of immunoregulatory and/or anti-inflammatory agents for the management of this condition. During the last 10 years, several randomized, placebo-controlled trials on the effectiveness of (add-on) treatment with prednisolone, pregnenolone, celecoxib, minocycline, N-acetylcysteine (NAC), sulforaphane (SFN), and/or omega-3 fatty acids have been performed. Overall, a beneficial effect of prednisolone, pregnenolone, celecoxib, and/or omega-3 fatty acids on several core symptoms, such as stereotyped behavior, was found. (Add-on) treatment with prednisolone, pregnenolone, celecoxib, minocycline, NAC, SFN, and/or omega-3 fatty acids was also associated with a significantly higher improvement in other symptoms, such as irritability, hyperactivity, and/or lethargy when compared with placebo. The mechanisms by which these agents exert their action and improve symptoms of ASD are not fully understood. Interestingly, studies have suggested that all these agents may suppress microglial/monocyte proinflammatory activation and also restore several immune cell imbalances (e.g., T regulatory/T helper-17 cell imbalances), decreasing the levels of proinflammatory cytokines, such as interleukin (IL)-6 and/or IL-17A, both in the blood and in the brain of individuals with ASD. Although encouraging, the performance of larger randomized placebo-controlled trials, including more homogeneous populations, dosages, and longer periods of follow-up, are urgently needed in order to confirm the findings and to provide stronger evidence.

Stress and coping strategies of families of pediatric solid organ transplant recipients in times of pandemic.

Objective: Pediatric solid organ transplantation (SOT) is a chronic condition that impacts the whole family system. The objective of this study is to evaluate psychopathology, family stress, and coping strategies in families of SOT recipients compared to families of healthy children and adolescents. Moreover, it analyzes if the stress related to the COVID-19 pandemic has had an additional impact on these families. Methods: The sample was recruited between May and July 2021, during the fourth and fifth wave of the pandemic in Spain. It consisted of 102 families, 51 with a pediatric recipient who had undergone a SOT (liver, kidney, heart, or lung) and 51 healthy controls, matched by child age and gender. A primary caregiver from each family answered an online sociodemographic questionnaire and different tests to evaluate family stress, depression, anxiety, coping strategies, and effects of the pandemic on the family. Results: Caregivers were mostly mothers (89.2%). Families of SOT recipients showed greater anxiety (U = 863.5, p = 0.003) and more total stress, stress related to childcare (t = -2.043; p = 0.045), and parent-child interaction stress (U = 355.5, p = 0.015). SOT families used more avoidance strategies, specifically denial (U = 889.5; p = 0.010) and abandonment of coping efforts (U = 1,013; p = 0.047), more religious strategies (U = 792.5; p = 0.031), and fewer social support coping strategies (t = 2.098; p = 0.038). No differences were found between groups in terms of exposure, impact, and distress more than 1 year after the start of the pandemic. Conclusion: SOT families showed clinical levels of anxiety, more parent-child interaction stress, more difficulties in taking care of their child, more avoidance and religious strategies, and less use of social support strategies, even 4 years after transplantation. The pandemic did not have an additional differential effect on SOT families. Caregivers of SOT patients can benefit from psychological interventions focused on parents' mental health, parent-child connectedness, skill building, and social support aid groups, with attention to multiculturalism and promoting a better balance between caregivers. There is a need for family interventions that are maintained over time. Strategies that offer this support to families through digital resources can facilitate adjustment to chronic illness, especially in pandemic times.

Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits. METHODS: We used genome-wide association study (GWAS) summary statistics for ADHD (n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD, we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results. RESULTS: Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR) = 0.966, 95% credible interval (CrI) = (0.954, 0.979)] and increased lifetime number of sexual partners [OR = 1.023, 95% CrI = (1.013, 1.033)]. We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), respectively] and time spent watching television [OR = 1.862, 95% CrI = (1.545, 2.246)], and evidence for a bidirectional effect for age of first sexual intercourse [beta = -0.058, 95% CrI = (-0.072, -0.044) and OR = 0.413, 95% CrI = (0.372, 0.457), respectively], odds of decreased age completed full-time education [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533), respectively] and years of schooling [beta = -0.036, 95% CrI = (-0.048, -0.024) and OR = 0.458, 95% CrI = (0.411, 0.511), respectively]. CONCLUSIONS: Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories.