Dissecting the polygenic contribution of attention-deficit/hyperactivity disorder and autism spectrum disorder on school performance by their relationship with educational attainment.

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are strongly associated with educational attainment (EA), but little is known about their genetic relationship with school performance and whether these links are explained, in part, by the genetic liability of EA. Here, we aim to dissect the polygenic contribution of ADHD and ASD to school performance, early manifestation of psychopathology and other psychiatric disorders and related traits by their relationship with EA. To do so, we tested the association of polygenic scores for EA, ADHD and ASD with school performance, assessed whether the contribution of the genetic liability of ADHD and ASD to school performance is influenced by the genetic liability of EA, and evaluated the role of EA in the genetic overlap between ADHD and ASD with early manifestation of psychopathology and other psychiatric disorders and related traits in a sample of 4,278 school-age children. The genetic liability for ADHD and ASD dissected by their relationship with EA show differences in their association with school performance and early manifestation of psychopathology, partly mediated by ADHD and ASD symptoms. Genetic variation with concordant effects in ASD and EA contributes to better school performance, while the genetic variation with discordant effects in ADHD or ASD and EA is associated with poor school performance and higher rates of emotional and behavioral problems. Our results strongly support the usage of the genetic load for EA to dissect the genetic and phenotypic heterogeneity of ADHD and ASD, which could help to fill the gap of knowledge of mechanisms underlying educational outcomes.

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.

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.

Spanish experts consensus on emergency psychiatric care in hospital emergency departments.

BACKGROUND: The demand for urgent psychiatric care is increasing, but in Spain there are no clear recommendations for emergency departments (ED) on how to optimize care for patients with psychiatric emergencies. We aimed to provide expert consensus recommendations on the requirements for general hospitals´ emergency departments to treat patients with urgent psychiatric symptoms. METHODS: We used a modified Delphi technique. A scientific committee compiled 36 statements based on literature search and clinical experience. The statements covered the organizational model, facilities, staffing, safety, patient interventions, and staff training. A panel of 38 psychiatry specialists with expertise in psychiatric emergencies evaluated the questionnaire in two rounds. RESULTS: After two rounds of voting, 30 out of 36 proposed items (83%) were agreed upon. The panel agreed that psychiatric emergencies should be managed in a general hospital, with dedicated facilities for patient assessment, direct supervision of patients at risk, and an observation unit run by the psychiatric service. In addition to the psychiatrist, the ED should have specialist nurses and security staff available 24/7. Social workers should also be readily available. ED and consulting rooms should be designed to ensure patient and staff safety. A triage system should be established for patients with psychiatric symptoms, with medical evaluation preceding psychiatric evaluation. Guidance on supplies, equipment, and staff training is also provided. CONCLUSION: All ED in general hospitals should have adequate resources to handle any psychiatric emergency. This paper provides recommendations on the minimum requirements to achieve this goal.

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.

Correlates of Control Preferences, Participation in Decision-making and Activation in Patients with Substance Use Disorder.

BACKGROUND: Treatment of Substance Use Disorder (SUD) is complex and therefore including patients in the therapeutic process is needed. Patient-Centered Care (PCC) and Shared Decision-Making (SDM) have been associated with greater satisfaction, self-control, and less substance use. However, correlates of SDM have not been investigated in this population. METHOD: A cross-sectional analysis was carried out in 214 SUD patients to identify sociodemographic, clinical and psychological correlates of preferences and perceptions about participation in SDM and degree of activation. The Control Preference Scale (CPS), the Shared Decision-Making Questionnaire (SDM-9-Q) and the Patient Activation Measure (PAM) were used to assess the PCC elements. Multinomial logistic regression was used to analyze the correlates of the CPS variables (preferred role, perceived role, and role matching). For SDM-9-Q and PAM, multilevel linear regression was used. RESULTS: Preferring an active role, compared to a shared one, was significantly associated with higher educational level, lower neuroticism, absence of affective and alcohol use disorders, and higher quality of life. Perceiving greater participation was significantly associated with not being a new patient, having fewer legal problems, higher severity of alcohol consumption, not presenting polydrug use and main substance use different than opioids or sedatives. Activation was associated with higher scores in the personality trait activity, a preference for an active role and greater perception of being involved in the decision process. CONCLUSIONS: Patients with milder clinical profiles prefer an active role compared to a shared one. Patients who prefer or perceive a shared or passive role did not show relevant differences. Greater activation was related to preference for an active role and the perception of having been involved in decisions.

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.

Emotional intelligence: a comparison between patients after first episode mania and those suffering from chronic bipolar disorder type I.

BACKGROUND: Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. METHODS: The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. RESULTS: In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (ß = -0.293, p = 0.034) and verbal memory performance (ß = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. CONCLUSIONS: Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.

Obstetric complications and cognition in schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Schizophrenia (SZ) is a complex brain disorder linked to cognitive and neurostructural abnormalities that involves genetic and environmental factors with obstetric complications (OCs) at birth conferring a high risk for the disease. Indeed, current research in the general population describes the deleterious effect of OCs on cognitive performance in adulthood. With this rationale, we aim to review the relationship between OCs and cognition in SZ and related psychotic disorders. METHODS: A systematic review and meta-analysis describing cognitive function and OCs in patients with SZ and related disorders were conducted. PubMed, EmBase, SCOPUS, and the Cochrane Library were systematically searched to identify eligible studies up to January 2022. We calculated the effect sizes (Hedges' g) of cognitive domains within each study and quantified the proportion of between-study variability using the I2 statistic. Homogeneity was assessed using the Q-statistic (X2). The study was registered on PROSPERO (CRD42018094238). RESULTS: A total of 4124 studies were retrieved, with 10 studies meeting inclusion criteria for the systematic review and eight for meta-analysis. SZ subjects with OCs showed poor verbal memory [Hedges' g = -0.89 (95% CI -1.41 to -0.37), p < 0.001] and working memory performance [Hedges' g = -1.47 (95% CI -2.89 to -0.06), p = 0.01] in a random-effect model compared to those without OCs. CONCLUSIONS: OCs appear to have a moderate impact on specific cognitive such as working memory and verbal memory. Our findings suggest that OCs are associated with brain development and might underlie the cognitive abnormalities described at onset of psychosis.

Prodromal phase: Differences in prodromal symptoms, risk factors and markers of vulnerability in first episode mania versus first episode psychosis with onset in late adolescence or adulthood.

OBJECTIVE: This study was aimed at identifying differences in the prodromal symptoms and their duration, risk factors and markers of vulnerability in patients presenting a first episode mania (FEM) or psychosis (FEP) with onset in late adolescence or adulthood in order to guide tailored treatment strategies. METHODS: Patients with a FEM or FEP underwent a clinical assessment. Prodromes were evaluated with the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R). Chi-squared tests were conducted to assess specific prodromal symptoms, risk factors or markers of vulnerability between groups. Significant prodromal symptoms were entered in a stepwise forward logistic regression model. The probabilities of a gradual versus rapid onset pattern of the prodromes were computed with logistic regression models. RESULTS: The total sample included 108 patients (FEM = 72, FEP = 36). Social isolation was associated with the prodromal stage of a FEP whilst Increased energy or goal-directed activity with the prodrome to a FEM. Physically slowed down presented the most gradual onset whilst Increased energy presented the most rapid. The presence of obstetric complications and difficulties in writing and reading during childhood were risk factors for FEP. As for markers of vulnerability, impairment in premorbid adjustment was characteristic of FEP patients. No specific risk factor or marker of vulnerability was identified for FEM. CONCLUSION: Early characteristics differentiating FEP from FEM were identified. These findings might help shape early identification and preventive intervention programmes.

COVID-19 Lockdown and Consumption Patterns among Substance Use Disorder Outpatients: A Multicentre Study.

INTRODUCTION: COVID-19 has had a great impact on mental health in the general population. However, few studies have focused on patients with substance use disorders (SUDs). This research aimed to compare the clinical status and substance use patterns of SUD outpatients, before and during confinement due to the COVID-19 pandemic. METHODS: This multicentre study recruited 588 patients (29.2% women; M age = 47.4 ± 11.7 years) in thirteen centres for addiction treatment in Catalonia, Spain. All subjects were evaluated with validated instruments and ad hoc questionnaires. The sample was divided into 3 groups according to how the substance consumption pattern changed during lockdown (maintained pattern, worsened pattern, and improved pattern). RESULTS: More than 62% of the patients maintained or worsened their consumption pattern during confinement, and about 38% improved throughout this time. Diverse factors were associated with the changes in pattern like age, addiction severity, psychological distress during lockdown, social and familial issues, and therapeutic variables. CONCLUSION: The home lockdown during the COVID-19 pandemic was associated with major implications for substance consumption and psychiatric distress among SUD outpatients. Considering this, the need to plan appropriate interventions in cases of similar health crises is highlighted.

A Multicenter Study on the Impact of Gender, Age, and Dual Diagnosis on Substance Consumption and Mental Health Status in Outpatients Treated for Substance Use Disorders During COVID-19 Lockdown.

Objective COVID-19 and lockdown measures impacted mental health globally and had a particular impact on patients with substance use disorders (SUD). However, the impact of gender, age, and dual diagnosis on consumption patterns and mental health during COVID-19 lockdown among patients with SUD has not been analyzed in depth. Therefore, this study aimed to examine substance use and mental health status during COVID-19 lockdown considering gender, age, and previous dual diagnosis in patients with SUD treated in different outpatient addiction clinics in Catalonia. Methods: Thirteen clinics participated and 588 patients were enrolled in the study, of whom 70.7% were men and 29.3% were women. The mean age was 48 ± 11.3 years, and 63.2% had dual diagnoses. Results: Men reported significantly more frequent alcohol and cocaine consumption during lockdown, while women experienced more anxiety and depressive symptoms. Younger patients more frequently reported consuming cocaine and cannabis, breaking the lockdown rule, worsened family relationships, and reduced incomes. Older patients more frequently reported maintaining abstinence. Previous dual diagnosis was more often associated with benzodiazepine use disorder, less active working during lockdown, and more anxiety and depressive symptoms than not having previous dual diagnosis. Conclusions: Both new psychiatric symptoms and general worsening of existing symptoms were frequent during the lockdown. Differences based on the gender, age, and dual diagnosis of outpatients treated for substance use disorders should be considered in the planning of protection measures such as home confinement.

Activation of the Monocyte/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade inflammation may be involved in the pathophysiology of this condition. However, studies investigating peripheral blood levels of immune cells, and/or of immune cell activation markers such as neopterin are lacking and have provided mixed findings. We performed a systematic review and meta-analysis of studies comparing total and differential white blood cell (WBC) counts, blood levels of lymphocyte subpopulations and of neopterin between individuals with ASD and typically developing (TD) controls (PROSPERO registration number: CRD CRD42019146472). Online searches covered publications from 1 January 1994 until 1 March 2022. Out of 1170 publication records identified, 25 studies were finally included. Random-effects meta-analyses were carried out, and sensitivity analyses were performed to control for potential moderators. Results: Individuals with ASD showed a significantly higher WBC count (k = 10, g = 0.29, p = 0.001, I2 = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I2 = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I2 = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I2 = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I2 = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I2 = 0%), compared to TD controls. Subjects with ASD were also characterized by a significantly higher neutrophil-to-lymphocyte ratio (NLR) (k = 4, g = 0.69, p = 0.040, I2 = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I2 = 97%) compared to TD controls. No significant differences were found with respect to the levels of lymphocytes, B cells, Th cells, Treg cells, and Th17 cells. Sensitivity analysis suggested that the findings for monocyte and neutrophil levels were robust, and independent of other factors, such as medication status, diagnostic criteria applied, and/or the difference in age or sex between subjects with ASD and TD controls. Taken together, our findings suggest the existence of a chronically (and systemically) activated inflammatory response system in, at least, a subgroup of individuals with ASD. This might have not only diagnostic, but also, therapeutic implications. However, larger longitudinal studies including more homogeneous samples and laboratory assessment methods and recording potential confounding factors such as body mass index, or the presence of comorbid psychiatric and/or medical conditions are urgently needed to confirm the findings.

Spanish validation of the Brief Problem Gambling Screen in patients with substance use disorders. / Validación al castellano de la escala Brief Problem Gambling Screen en pacientes con Trastorno por Uso de Sustancias.

Problematic Gambling or Gambling Disorder (GD) can act by initiating and maintaining the problem of substance addiction. Despite this, there are no rapid screening tools validated in Spanish. The Brief Problem Gambling Screen (BPGS) has proven to be one of the most sensitive tools for detecting GD and populations at risk. This study aims to validate the Spanish version of the original five-item BPGS. A sample of 100 Spanish-speaking adults with substance use disorder were recruited from an addiction treatment center. The participants were administered the Spanish version of BPGS. It showed strong item reliability properties (Ω = 0.93). Sensitivity and specificity values were excellent (0.93 each), also positive (0.7) and negative (0.99) predictive values suggest high discriminant power when compared to non-GD subjects. Statistically significant strong correlation with a gold-standard measure (Problem Gambling Severity Index) was found (r = 0.8, p < 0.01). Similar psychometric properties were found in at-risk gambler patients. In conclusion, the BPGS seems to be an adequate screening instrument in Spanish-speaking clinical population, and also identifies at-risk of GD subjects.

El juego patológico (JP) puede actuar iniciando y manteniendo el problema de la adicción a sustancias. A pesar de ello, no existen herramientas de cribado rápido validadas en español. La Breve evaluación del juego problemático (BPGS) ha demostrado ser una de las herramientas más sensibles para detectar JP y poblaciones en riesgo. Este estudio tiene como objetivo validar la versión en español de la BPGS original de cinco factores. Se reclutó una muestra de 100 adultos hispanohablantes con trastorno por uso de sustancias de un centro de tratamiento de adicciones. A los participantes se les administró la versión en español de la BPGS. El instrumento mostró propiedades de fiabilidad de los ítems evaluados (Ω = 0,93). Los valores de sensibilidad y especificidad fueron excelentes (0,93 cada uno), también los valores predictivos positivos (0,7) y negativos (0,99) sugieren un alto poder discriminante en comparación con los sujetos sin JP. Se encontró una fuerte correlación significativa con la medida gold-estándar (índice de severidad del juego problemático, PGSI) (r = 0,8, p < 0,01). Se encontraron propiedades psicométricas similares en pacientes en riesgo de JP. En conclusión, la BPGS parece un buen instrumento de cribado en la población clínica española, y también identifica a los sujetos en riesgo de desarrollar JP.

Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality.

Attention-deficit/hyperactivity disorder (ADHD) is a severely impairing neurodevelopmental disorder with a prevalence of 5% in children and adolescents and of 2.5% in adults. Comorbid conditions in ADHD play a key role in symptom progression, disorder course and outcome. ADHD is associated with a significantly increased risk for substance use, abuse and dependence. ADHD and cannabis use are partly determined by genetic factors; the heritability of ADHD is estimated at 70-80% and of cannabis use initiation at 40-48%. In this study, we used summary statistics from the largest available meta-analyses of genome-wide association studies (GWAS) of ADHD (n = 53,293) and lifetime cannabis use (n = 32,330) to gain insights into the genetic overlap and causal relationship of these two traits. We estimated their genetic correlation to be r2 = 0.29 (P = 1.63 × 10-5) and identified four new genome-wide significant loci in a cross-trait analysis: two in a single variant association analysis (rs145108385, P = 3.30 × 10-8 and rs4259397, P = 4.52 × 10-8) and two in a gene-based association analysis (WDPCP, P = 9.67 × 10-7 and ZNF251, P = 1.62 × 10-6). Using a two-sample Mendelian randomization approach we found support that ADHD is causal for lifetime cannabis use, with an odds ratio of 7.9 for cannabis use in individuals with ADHD in comparison to individuals without ADHD (95% CI (3.72, 15.51), P = 5.88 × 10-5). These results substantiate the temporal relationship between ADHD and future cannabis use and reinforce the need to consider substance misuse in the context of ADHD in clinical interventions.

Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a complex genetic background, hampering identification of underlying genetic risk factors. We hypothesized that combining linkage analysis and whole-exome sequencing (WES) in multi-generation pedigrees with multiple affected individuals can point toward novel ADHD genes. Three families with multiple ADHD-affected members (Ntotal = 70) and apparent dominant inheritance pattern were included in this study. Genotyping was performed in 37 family members, and WES was additionally carried out in 10 of those. Linkage analysis was performed using multi-point analysis in Superlink Online SNP 1.1. From prioritized linkage regions with a LOD score ≥ 2, a total of 24 genes harboring rare variants were selected. Those genes were taken forward and were jointly analyzed in gene-set analyses of exome-chip data using the MAGMA software in an independent sample of patients with persistent ADHD and healthy controls (N = 9365). The gene-set including all 24 genes together, and particularly the gene-set from one of the three families (12 genes), were significantly associated with persistent ADHD in this sample. Among the latter, gene-wide analysis for the AAED1 gene reached significance. A rare variant (rs151326868) within AAED1 segregated with ADHD in one of the families. The analytic strategy followed here is an effective approach for identifying novel ADHD risk genes. Additionally, this study suggests that both rare and more frequent variants in multiple genes act together in contributing to ADHD risk, even in individual multi-case families.

Impact of COVID-19 on Families of Pediatric Solid Organ Transplant Recipients.

OBJECTIVE: The COVID-19 pandemic and lockdown measures have had a clear psychological impact on families, and specifically those with children with chronic illnesses have reported greater overloads and exhaustion. The objective of this study was to evaluate the exposure, impact and experience of the pandemic on families of pediatric solid organ transplant (SOT) recipients compared to families of healthy children and adolescents. METHODS: We recruited 96 families, 48 with a pediatric SOT recipient and 48 healthy controls, matched by child age and gender. A primary caregiver from each family responded to an online sociodemographic questionnaire and the COVID-19 Exposure and Family Impact Survey (CEFIS), which explores the exposure, impact and experience of the pandemic and lockdown on families. RESULTS: Exposure to the pandemic was greater in families of healthy children and adolescents. The impact was mostly negative in both groups: caregivers reported increased anxiety (76%) and mood disturbances (71.9%) and hindered quality of sleep (64.6%) and health habits (58.3%). On the positive side, family relationships improved. Qualitatively, the SOT group positively perceived isolation and established hygienic measures as protective and destigmatizing, although they reported fear of virus transmission to their child. CONCLUSIONS: The psychological impact of the pandemic has been similar in both groups, although families of transplant recipients have protected themselves more, probably because they are used to prevention measures and they see contagion as a graver risk. Additionally, SOT recipients' families presented some idiosyncratic elements, especially a decrease in their perception of stigma associated with the medical condition.

Psychological impact and social support in pregnant women during lockdown due to SARS-CoV2 pandemic: A cohort study.

INTRODUCTION: Anxiety and depression during pregnancy can lead to adverse maternal and neonatal outcomes. The SARS CoV-2 pandemic, and the complete lockdown required during the first wave in most countries are stressors for pregnant women and can lead to anxiety and depression during pregnancy. The aim of this study was to explore depression and anxiety symptoms, and social support in pregnant women during the SARS CoV-2 lockdown, as well as to explore demographic risk factors. MATERIAL AND METHODS: A prospective cohort study was performed at Hospital Universitari Vall d'Hebron, Barcelona, including pregnant women attending the antenatal clinic during the SARS-CoV2 lockdown period. Three questionnaires were administered to study depression (EPDS), anxiety (STAI) and Social Support (MOS-SSS). STAI state (STAIs) described the actual state of anxiety and the STAI trait (STAIt) described the trait of anxiety. A cut-off of 10 for EPDS and 40 for STAI was considered to be clinically relevant. The main outcome measures were depression and anxiety symptoms. RESULTS: A total of 217 women were invited to participate, and 204 accepted (94%). From these, 164 filled in the EPDS, 109 STAI and 159 MOS-SSS questionnaires: 37.8% (95% confidence interval [CI] 30.5%-45.7%) (62/164) of women showed an EPDS result ≥10, 59.6% (95% CI 49.8%-68.8%) (65/109) a STAI state (STAIs) ≥40, and 58.7% (95% CI 48.9%-67.9%) (64/109) a STAI trait (STAIt) ≥40. Regression analysis showed that mental health disorder, Latin American origin and lack of social support were independent risk factors for anxiety symptoms in the STAIs (P = .032, P = .040 and P = .029, respectively). Regarding depressive symptoms, maternal body mass index, mental health disorders and social support were independent factors (P = .013, P = .015 and P = .000, respectively). CONCLUSIONS: A lockdown scenario during the first wave of the SARS-CoV 2 pandemic increased the symptoms of anxiety and depression among pregnant women, particularly affecting those with less social support.

Electrophysiological Brain Changes Associated With Cognitive Improvement in a Pediatric Attention Deficit Hyperactivity Disorder Digital Artificial Intelligence-Driven Intervention: Randomized Controlled Trial.

BACKGROUND: Cognitive stimulation therapy appears to show promising results in the rehabilitation of impaired cognitive processes in attention deficit hyperactivity disorder. OBJECTIVE: Encouraged by this evidence and the ever-increasing use of technology and artificial intelligence for therapeutic purposes, we examined whether cognitive stimulation therapy implemented on a mobile device and controlled by an artificial intelligence engine can be effective in the neurocognitive rehabilitation of these patients. METHODS: In this randomized study, 29 child participants (25 males) underwent training with a smart, digital, cognitive stimulation program (KAD_SCL_01) or with 3 commercial video games for 12 weeks, 3 days a week, 15 minutes a day. Participants completed a neuropsychological assessment and a preintervention and postintervention magnetoencephalography study in a resting state with their eyes closed. In addition, information on clinical symptoms was collected from the child´s legal guardians. RESULTS: In line with our main hypothesis, we found evidence that smart, digital, cognitive treatment results in improvements in inhibitory control performance. Improvements were also found in visuospatial working memory performance and in the cognitive flexibility, working memory, and behavior and general executive functioning behavioral clinical indexes in this group of participants. Finally, the improvements found in inhibitory control were related to increases in alpha-band power in all participants in the posterior regions, including 2 default mode network regions of the interest: the bilateral precuneus and the bilateral posterior cingulate cortex. However, only the participants who underwent cognitive stimulation intervention (KAD_SCL_01) showed a significant increase in this relationship. CONCLUSIONS: The results seem to indicate that smart, digital treatment can be effective in the inhibitory control and visuospatial working memory rehabilitation in patients with attention deficit hyperactivity disorder. Furthermore, the relation of the inhibitory control with alpha-band power changes could mean that these changes are a product of plasticity mechanisms or changes in the neuromodulatory dynamics. TRIAL REGISTRATION: ISRCTN Registry ISRCTN71041318; https://www.isrctn.com/ISRCTN71041318.

Catatonia Related to Cannabis and Synthetic Cannabinoids: A Review.

OBJECTIVE: Cannabis and synthetic cannabinoids (SC) are related to several neuropsychiatric symptoms and disorders, especially psychotic symptoms and disorders. Interestingly, catatonia-like symptoms associated with cannabis and SC have been generally neglected in research and scarcely described despite the clinical repercussions. Hence, this review aims to analyze current clinical publications on catatonia induced by cannabis or SC in a systematized way. Methods: A search using PRISMA guidelines was performed on three databases based on a specific inclusion and exclusion criteria. Results: 11 publications describing 14 patients (10 males; mean age 22.50 ± 6.67 years old) with catatonia apparently precipitated by the use of cannabis (n = 6) or SC (n = 8) were found. Clinical features and treatment are described and discussed. Conclusion: From a clinical perspective, cannabis and SC use may be related to catatonia-like symptoms and catatonia syndrome in the same way these substances (cannabis and SC) are related to induced-psychotic episodes. However, further research will be required to understand the exact nature of that relationship. Additionally, investigations focused on the clinical significance (i.e., prognosis, evolution, and outcomes) of catatonia-like symptoms induced by cannabis and SC use in patients are also needed.