Sex matters: Differences in prodromes, clinical and neuropsychological features in individuals with a first episode mania or psychosis.

OBJECTIVE: This study was aimed at identifying sex differences in patients presenting a first episode mania (FEM) or psychosis (FEP) to help shaping early treatment strategies focused on sex differences. METHODS: Patients with a FEM or FEP underwent a clinical, neuropsychological (neurocognitive functions and emotional intelligence) and functional assessment. Performance on those variables was compared between groups through general linear model, with sex and group (FEM vs FEP) as main effects and group by sex interactions. RESULTS: The total sample included 113 patients: FEM = 72 (45.83 % females) and FEP = 41 (46.34 % females). There were significant main effects for group (not for sex) for most of the clinical features (depressive, negative and positive symptoms) and psychosocial functioning (χ2 = 8.815, p = 0.003). As for neuropsychological performance, there were significant main effects for sex and group. Females performed better than males in verbal memory (χ2 = 9.038, p = 0.003) and obtained a higher emotional intelligence quotient (χ2 = 13.20, p < 0.001). On the contrary, males obtained better results in working memory (χ2 = 7.627, p = 0.006). FEP patients significantly underperformed FEM patients in most cognitive domains. There were significant group by sex interactions for few neuropsychological variables, namely processing speed (χ2 = 4.559, p = 0.033) and verbal fluency (χ2 = 8.913, p = 0.003). LIMITATIONS: Differences between sexes were evaluated, but the influence of gender was not considered. Retrospective evaluation of prodromes and substance use. No healthy control group comparator. CONCLUSION: The main finding is the presence of significant sex effect and group by sex interaction on specific neurocognitive cognition and emotional intelligence measures. Tailored sex-based early treatment strategies might be implemented.

A Suicide Attempt Multicomponent Intervention Treatment (SAMIT Program): study protocol for a multicentric randomised controlled trial.

BACKGROUND: Suicide has become a first-order public health concern, especially following the negative impact of COVID-19 on the mental health of the general population. Few studies have analysed the effects of early psychotherapeutic interventions on subjects who have attempted suicide, and even fewer have focused on those hospitalized in non-psychiatric units after a Medically Serious Suicide Attempt (MSSA). The main aim of this study is to describe the protocol designed to evaluate the effectiveness of individual psychological treatment for patients hospitalized after an MSSA. The secondary objectives of the study are: (1) to evaluate the impact on quality of life and other psychosocial variables of patients with a recent MSSA who receive early psychological intervention; (2) to analyse the biological, psychological, and clinical impact of early psychotherapeutic treatment on subjects hospitalized after an MSSA. METHODS: A longitudinal randomised controlled trial will be conducted with patients over 16 years of age admitted to two general hospitals. The case intervention group will enrol for 8-sessions of individual psychotherapy, Suicide Attempts Multi-component Intervention Treatment (SAMIT), combining Dialectical Behaviour Therapy (DBT), Mentalization-Based Therapy (MBT), and Narrative approaches, while the control group will receive a treatment-as-usual intervention (TAU). Longitudinal assessment will be conducted at baseline (before treatment), post-treatment, and 3, 6, and 12 months after. The main outcome variable will be re-attempting suicide during follow-up. DISCUSSION: Some psychotherapeutic interventions, usually implemented in outpatient, have proven to be effective in preventing suicidal behaviours. The combination of some of these may be a powerful treatment for preventing future SA in patients hospitalised after an MSSA, which is the most severely suicidal subgroup. Moreover, assessment of the biological, clinical and psychometric impact of this new intervention on patients during the first year after the attempt may help understand some of the multi-level factors associated with the effectiveness of psychotherapeutic interventions in MSSAs. The prevalence of high suicide rates requires the design of effective psychological interventions for their prevention, and also in order to design new pharmacological and psychological treatments. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06238414. Date of registration: 1st February 2024, final update is protocol version 3.0, 19th March 2024.

Childhood maltreatment and non-suicidal self-injury in adolescent population: A systematic review and meta-analysis.

BACKGROUND: Non-suicidal self-injury (NSSI) is highly prevalent among adolescents. However, knowledge about the possible factors that might precede and influence its development remains scarce. OBJECTIVE: Our goal is to examine the impact of adverse childhood events, and more specifically of different types of childhood maltreatment (CM) in adolescent NSSI. This involves performing a systematic review and meta-analysis of the different CM subtypes (physical and emotional neglect, physical and emotional abuse, sexual abuse) in clinical and non-clinical samples of adolescents with NSSI. PARTICIPANTS AND METHODS: A digital search of the PsycInfo, PubMed and Web of Science platforms for articles published up to June 2022 was performed. The search terms were "self harm", "non-suicidal self-injury", "childhood maltreatment" and "adolescents". RESULTS: Forty-six articles that fit the research objectives were included in the study, which covered a total of 1,505,430 adolescents, of whom 560,337 belonged to the NSSI group, while 945,093 were in the control group. The results describe strong positive associations between all CM subtypes and NSSI, especially with emotional abuse (odds ratio [OR] 2.91, 95 % CI 2.37-3.56) and sexual abuse (OR 2.72, 95 % CI 2.12-3.48), in clinical and non-clinical samples of adolescents. CONCLUSIONS: The experience of CM, and especially emotional and/or sexual abuse, seems to be associated with a greater risk of developing NSSI in adolescence. Therefore, early identification and detection of children who have suffered or are suffering these forms of CM are of vital importance for instigating psychotherapeutic treatments that can minimize the risk of developing NSSI in adolescence.

The gut-microbiome in adult Attention-deficit/hyperactivity disorder - A Meta-analysis.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that persists into adulthood in the majority of individuals. While the gut-microbiome seems to be relevant for ADHD, the few publications on gut-microbial alterations in ADHD are inconsistent, in the investigated phenotypes, sequencing method/region, preprocessing, statistical approaches, and findings. To identify gut-microbiome alterations in adult ADHD, robust across studies and statistical approaches, we harmonized bioinformatic pipelines and analyses of raw 16S rRNA sequencing data from four adult ADHD case-control studies (NADHD=312, NNoADHD=305). We investigated diversity and differential abundance of selected genera (logistic regression and ANOVA-like Differential Expression tool), corrected for age and sex, and meta-analyzed the study results. Converging results were investigated for association with hyperactive/impulsive and inattentive symptoms across all participants. Beta diversity was associated with ADHD diagnosis but showed significant heterogeneity between cohorts, despite harmonized analyses. Several genera were robustly associated with adult ADHD; e.g., Ruminococcus_torques_group (LogOdds=0.17, pfdr=4.42 × 10-2), which was more abundant in adults with ADHD, and Eubacterium_xylanophilum_group (LogOdds= -0.12, pfdr=6.9 × 10-3), which was less abundant in ADHD. Ruminococcus_torques_group was further associated with hyperactivity/impulsivity symptoms and Eisenbergiella with inattention and hyperactivity/impulsivity (pfdr<0.05). The literature points towards a role of these genera in inflammatory processes. Irreproducible results in the field of gut-microbiota research, due to between study heterogeneity and small sample sizes, stress the need for meta-analytic approaches and large sample sizes. While we robustly identified genera associated with adult ADHD, that might overall be considered beneficial or risk-conferring, functional studies are needed to shed light on these properties.

Sex differences in prolactin levels and clinical outcomes in patients with a first psychotic episode.

AIM: To analyze the clinical, neurocognitive, and functional impact of prolactin levels according to sex in patients with a First Episode Psychosis (FEP). METHODS: We measured prolactin levels in 221 non-affective FEP patients treated with antipsychotics (AP) and 224 healthy controls, at baseline and 2-year follow-up. We examined whether the relationships between clinical and functional variables were mediated by prolactin, controlling for antipsychotic use, according to sex. RESULTS: Prolactin levels were higher in patients when compared to controls at both time points. Baseline factors associated with prolactin were chlorpromazine equivalents, attention, and executive functioning. In the FEP group, prolactin levels were associated with functioning and diminished expression in males, and with working memory in females. Prolactin levels (p=0.0134) played a role as a mediator between negative symptomatology (p=0.086) and functional outcome (p=0.008) only in FEP male patients at baseline. CONCLUSIONS: Prolactin plays a role in the functionality and clinical symptomatology of FEP patients. Our results suggest that pharmacological counselling in patients with hyperprolactinemia at baseline and negative symptomatology might improve their functional and clinical outcomes.

Emotional intelligence and neurocognition profiles in first-episode psychosis: A two-year follow-up study.

Emotional intelligence (EI) and neurocognition (NC) impairments are common in first-episode psychosis (FEP), yet their evolution over time remains unclear. This study identified patient profiles in EI and NC performance in FEP. 98 adult FEP patients and 128 healthy controls (HCs) were tested on clinical, functional, EI, and NC variables at baseline and two-year follow-up (FUP). A repeated-measures ANOVA compared the effects of group (patients and HCs) and time on EI. Significant EI improvements were observed in both groups. Four groups were created based on NC and EI performance at baseline and FUP in patients: impairment in NC and EI, impairment in NC only, impairment in EI only, and no impairment. At FUP, patients impaired in NC and EI showed less cognitive reserve (CR), greater negative and positive symptoms, and poorer functional outcomes. At FUP, three group trajectories were identified: (I) maintain dual impairment (II) maintain no impairment or improve, (III) maintain sole impairment or worsen. The maintain dual impairment group had the lowest levels of CR. EI and NC impairments progress differently in FEP. Greater CR may protect against comorbid EI/NC impairment. Identifying these patient characteristics could contribute to the development of personalised interventions.

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.

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.

Disentangling heterogeneity in substance use disorder: Insights from genome-wide polygenic scores.

Substance use disorder (SUD) is a global health problem with a significant impact on individuals and society. The presentation of SUD is diverse, involving various substances, ages at onset, comorbid conditions, and disease trajectories. Current treatments for SUD struggle to address this heterogeneity, resulting in high relapse rates. SUD often co-occurs with other psychiatric and mental health-related conditions that contribute to the heterogeneity of the disorder and predispose to adverse disease trajectories. Family and genetic studies highlight the role of genetic and environmental factors in the course of SUD, and point to a shared genetic liability between SUDs and comorbid psychopathology. In this study, we aimed to disentangle SUD heterogeneity using a deeply phenotyped SUD cohort and polygenic scores (PGSs) for psychiatric disorders and related traits. We explored associations between PGSs and various SUD-related phenotypes, as well as PGS-environment interactions using information on lifetime emotional, physical, and/or sexual abuse. Our results identify clusters of individuals who exhibit differences in their phenotypic profile and reveal different patterns of associations between SUD-related phenotypes and the genetic liability for mental health-related traits, which may help explain part of the heterogeneity observed in SUD. In our SUD sample, we found associations linking the genetic liability for attention-deficit hyperactivity disorder (ADHD) with lower educational attainment, the genetic liability for post-traumatic stress disorder (PTSD) with higher rates of unemployment, the genetic liability for educational attainment with lower rates of criminal records and unemployment, and the genetic liability for well-being with lower rates of outpatient treatments and fewer problems related to family and social relationships. We also found evidence of PGS-environment interactions showing that genetic liability for suicide attempts worsened the psychiatric status in SUD individuals with a history of emotional physical and/or sexual abuse. Collectively, these data contribute to a better understanding of the role of genetic liability for mental health-related conditions and adverse life experiences in SUD heterogeneity.

Long-acting injectable buprenorphine in the real world: case report on dual disorders.

OBJECTIVES: Long-acting injectable buprenorphine (LAIB) has demonstrated a good profile for opioid use disorder (OUD) management. However, there is scarce information on LAIB in OUD patients with comorbid mental disorders (dual disorder patients). METHODS: We present a case report on OUD patients with a comorbid mental disorder who have received LAIB for at least 3 months. RESULTS: Two women and one man with OUD and another comorbid mental disorder were prescribed with LAIB ranging from three to twelve months. Good adherence and opioid abstinence were observed during the follow-up. Psychopathological issues related to comorbid mental disorders were stabilized. A deep discussion on LAIB in this profile of patients is conducted. CONCLUSIONS: LAIB in OUD patients with comorbid mental disorders may be a safe and well tolerated option, similar to OUD patients without comorbid mental disorders. LAIB's impact on psychopathological issues requires further high-quality research to understand the real impact of LAIB on OUD and comorbid mental disorders.

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.

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.

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.

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.

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.

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.

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.