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.

The Sleep Disturbance Scale for Children: psychometric properties and prevalence of sleep disorders in Spanish children aged 6-16 years.

The present research aimed to investigate, for the first time, the validity and reliability of the Sleep Disturbance Scale for Children (SDSC) in a sample of 2733 Spanish children aged 6-16 years. We also described the prevalence and sociodemographic correlates of sleep disorder symptoms among young people, which had never been studied in Spain. Confirmatory factor analysis supported the original six-factor model and Cronbach's alpha for the total questionnaire was 0.82, which indicated good reliability. Moreover, all the SDSC subscales correlated positively and significantly with the total score (range = 0.41-0.70), thus showing convergent validity. Considering T-scores >70 as pathological, we identified at least one sleep disorder in 116 participants (4.24%), including disorders of excessive somnolence (DOES; 5.82%), sleep-wake transition disorders (SWTD; 5.27%), and disorders of initiating and maintaining sleep (DIMS; 5.09%) among the most common problems. Students in secondary education and those from families with a low socioeconomic status were more likely to have DIMS, disorders of arousal, and DOES. Subjects with clinically elevated levels of sleep breathing disorders were more frequently of foreign origin and from disadvantaged families. Boys and primary school students were more prone to sleep hyperhidrosis, while SWTD were overrepresented among children with a low socioeconomic status. According to our results, the Spanish version of the SDSC seems to be a good instrument for assessing sleep disturbances in school-age children and adolescents, which is essential to prevent the significant implications of poor sleeping on the overall welfare of young people.

Neurodevelopmental disorders among Spanish school-age children: prevalence and sociodemographic correlates.

BACKGROUND: Prevalence estimates of neurodevelopmental disorders (ND) are essential for treatment planning. However, epidemiological research has yielded highly variable rates across countries, including Spain. This study examined the prevalence and sociodemographic correlates of ND in a school sample of Spanish children and adolescents. METHODS: The Child Behaviour Checklist/Teacher's Report Form/Youth Self-Report and the Conners' Rating Scales were administered for screening purposes. Additionally, teachers provided information on reading and writing difficulties. Subjects who screened positive were interviewed for diagnostic confirmation according to the Diagnostic and Statistical Manual of Mental Disorders criteria. The final population comprised 6834 students aged 5-17. Multivariate analyses were performed to determine the influence of gender, age, educational stage, school type, socioeconomic status (SES), and ethnicity on the prevalence estimates. RESULTS: A total of 1249 (18.3%) subjects met criteria for at least one ND, although only 423 had already received a diagnosis. Specifically, the following prevalence rates were found: intellectual disabilities (ID), 0.63%; communication disorders, 1.05%; autism spectrum disorder (ASD), 0.70%; attention-deficit/hyperactivity disorder (ADHD), 9.92%; specific learning disorder (SLD), 10.0%; and motor disorders, 0.76%. Students of foreign origin and from low SES evidenced higher odds of having ID. Boys were more likely to display ASD or a motor disorder. Age, SES, and ethnicity were significant predictors for SLD, while communication disorders and ADHD were also associated with gender. CONCLUSIONS: The prevalence of ND among Spanish students is consistent with international studies. However, a substantial proportion had never been previously diagnosed, which emphasise the need for early detection and intervention programmes.

Genetic overlap and causality between substance use disorder and attention-deficit and hyperactivity disorder.

Substance use disorder (SUD) often co-occur at high prevalence with other psychiatric conditions. Among them, attention-deficit and hyperactivity disorder (ADHD) is present in almost one out of every four subjects with SUD and is associated with higher severity, more frequent polysubstance dependence and increased risk for other mental health problems in SUD patients. Despite studies suggesting a genetic basis in the co-occurrence of these two conditions, the genetic factors involved in the joint development of both disorders and the mechanisms mediating these causal relationships are still unknown. In this study, we tested whether the genetic liability to five SUD-related phenotypes share a common background in the general population and clinically diagnosed ADHD individuals from an in-house sample of 989 subjects and further explored the genetic overlap and the causal relationship between ADHD and SUD using pre-existing GWAS datasets. Our results confirm a common genetic background between ADHD and SUD and support the current literature on the causal effect of the liability to ADHD on the risk for SUD. We added novel findings on the effect of the liability of lifetime cannabis use on ADHD and found evidence of shared genetic background underlying SUD in general population and in ADHD, at least for lifetime cannabis use, alcohol dependence and smoking initiation. These findings are in agreement with the high comorbidity observed between ADHD and SUD and highlight the need to control for substance use in ADHD and to screen for ADHD comorbidity in all SUD patients to provide optimal clinical interventions.

Integral Treatment Programme for Addicted Physicians: Results from The Galatea Care Programme for Sick Physicians.

INTRODUCTION: Addictions among physicians are a matter of public health interest because of their negative impact on the physician's well-being and the potential risk of malpractice. Physicians' Health Programmes (PHP) have been developed in several countries to address this issue. Although they share some similarities, they differ in organisational and clinical aspects. OBJECTIVE: This study aimed to describe the clinical outcomes of the Integral Treatment Programme for Addicted Physicians of The Galatea Care Programme for Sick Physicians (PAIMM). METHODS: A prospective naturalistic longitudinal study was conducted using data from electronic medical records of 126 physicians registered at the Barcelona Medical Association-Council and admitted to the PAIMM between 2008 and 2016. All patients received addiction treatment supervised by a specialised team with individual visits (psychiatrist and psychologist), had regular and random drug screening, attended a 3-step intervention with 2 intensive initial phases and 2-5 year weekly group psychotherapy, and were monitored when they returned to practice. RESULTS: All admitted physicians completed the intensive intervention, and 87.3% were subsequently monitored. The mean treatment length was 48 months. Overall, 72.2% of sick physicians remained abstinent at last contact. Good adherence to follow-up psychotherapy groups predicted both lower risk of lapse during the treatment process and higher rates of abstinence at follow-up. CONCLUSIONS: Initial intensive treatment, long-term follow-up and drug screening, group therapy attendance, and a case management approach are common factors that may explain the positive clinical outcomes for physicians with addictions in treatment at PHPs, regardless of the country.

Dual diagnosis among medical residents: a systematic review. / Diagnóstico dual en médicos residentes: una revisión sistemática.

The post-graduate period as a resident doctor (MIR, in Spanish) is usually associated with high emotional distress due to new professional demands and to other psychosocial factors. The objective of this study is to determine the characteristics of dual diagnosis among MIRs. A systematic review was carried out in MEDLINE (PubMed), Web of Science and Google Scholar databases, selecting articles published in English and Spanish between 1984 and 2017. A total of 2,415 articles were obtained: 2,276 were excluded by their title, 105 by the abstract and 17 after a complete review of the article; 17 papers were finally included. The prevalence of depressive symptoms among MIRs ranges from 10.2% to 70%, while the prevalence of anxious symptoms varies from 13.2% to 33.9%, from 6.7% to 25% reported suicidal ideation, 20% hazardous drinking, 2%-13.4% self-prescribed psychotropics, and 2.7%-14% used other drugs. Most studies present important methodological limitations, thus complicating adequate understanding of the phenomenon. High variations in prevalence data are related to differences in the psychometric scales and to disparity in diagnosis criteria, among other limitations. However, most studies report that alcohol and drug use is correlated with severe distress among MIRs. More research is needed to ascertain the nature of dual diagnosis in this professional group in order to effectively prevent and treat its serious consequences.

El período de preparación como médico residente (en español, MIR) suele asociarse a una elevada sobrecarga emocional tanto por las nuevas exigencias profesionales como por otros factores psicosociales. El objetivo de este estudio es conocer las características del diagnóstico dual en los MIRs. Se llevó a cabo una revisión sistemática de las bases de datos MEDLINE (PubMed), Web of Science y Google Scholar, seleccionando artículos publicados en inglés y español entre 1984 y 2017. Se obtuvieron 2.415 artículos: se excluyeron 2.276 por título, 105 por el contenido del resumen y 17 por el contenido del artículo. En la revisión final se incluyeron 17 artículos. La prevalencia de clínica depresiva varía del 10,2% al 70%, de ansiedad entre 13,2% y 33,9%, de ideación suicida entre 6,7% y 25% mientras que el consumo de riesgo de alcohol se encuentra aproximadamente en torno al 20%, entre 2% y 13,4% se auto-prescriben medicamentos psicótropos y del 2,7% al 14% consumen otras sustancias. La mayoría de los estudios analizados adolecen de limitaciones metodológicas importantes lo que dificulta una adecuada comprensión del fenómeno. Las variaciones en las cifras de prevalencia tienen que ver con la disparidad de escalas y de criterios diagnósticos empleados, entre otros factores. Aún así, los estudios muestran que el consumo de alcohol y/u otras sustancias se correlacionan positivamente con el malestar emocional en los MIRs. Se hace necesario mejorar el conocimiento del diagnóstico dual en este grupo profesional para que se puedan prevenir y tratar sus consecuencias de manera más eficaz.

Women with compulsive buying or gambling disorder: Similar profiles for different behavioural addictions.

The aim of the present study was to examine the differences in sociodemographic and clinical characteristics of 104 women diagnosed with compulsive buying behaviour (CBB = 55) or gambling disorder (GD = 49) treated at three public hospitals unit specialized in behavioural addictions from January 2004 to December 2015. Significant between-group differences in sociodemographic variables were observed for cohabitation status (living with a partner or not) and educational level, with a higher percentage of women in the GD group cohabiting (х2 (1), p = .029). By contrast, the CBB group had a significantly higher educational level (х2 (1) = 7.4, p = .007). There were no significant differences between the groups in age of onset, age at treatment initiation, age at the onset of behavioural problems, or in the years elapsed until presenting addiction problems. However, there were significant between-group differences in the amount of money spent weekly (F (1.100) = 4.9, p = .028), with women in the CBB group spending on average €289.4/week (SD, 412.4) versus €151/week (SD, 141.23) in the GD group. The CBB group had significantly more depressive disorders compared to the GD group (х2(1) = 5.4, p = .020). In contrast, the GD group presented significantly more tobacco use than the CBB group (х2(1) = 1.19, p = .000). This study suggests that women with CBB or GD share more characteristics than differences and the treatment approaches must take into account gender related factors.

Dimensional Personality Assessment among a Chronic Fatigue Syndrome (CFS) sample with Personality Inventory for DSM-5 (PID-5).

INTRODUCTION: Personality Disorders (PD) are highly prevalent among Chronic Fatigue Syndrome (CFS) patients, but studies based on the DSM-5 are still scarce. Validated instruments have not yet been specifically used in CFS patients. Therefore, our aim was to analyze the differences in personality facets and domains profiles among CFS patients with and without a PD using the Personality Inventory for DSM-5 (PID-5). Additionally, we analyzed the ability of this instrument to predict PD in a sample of CFS patients. This instrument is validated for PDs, but not for CFS. METHODS: All of the 84 CFS patients were evaluated through a clinical interview and underwent psychopathological evaluation with the SCID I and SCID II. Dimensional personality facets and domains were evaluated with the PID-5, according to DSM-5. RESULTS: In our sample, 54 (64%) of the patients fulfilled the criteria of a PD. The most significant facets in CFS with PD in comparison to those patients without a PD were Separation Insecurity, Perseveration, Withdrawal, Depressivity, Rigid Perfectionism, Unusual Beliefs and Experiences. Negative Affectivity and Detachment were the two significant domains in CFS-PD patients. In the regression analyses, only Detachment and Rigid Perfectionism constituted a prognostic factor leading to high probability of an endorsed PD. Conclussion. According to these results, the PID-5 domains and facets could be adequate and useful to differentiate between PD and non-PD patients in clinical samples and suggest a more frequent dimensional personality profile in CFS patients.

Are patients with bipolar disorder and comorbid attention-deficit hyperactivity disorder more neurocognitively impaired?

OBJECTIVE: Research on neurocognitive impairment in adult patients with comorbid bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) is very scarce. This study assessed the neurocognitive profile of a comorbid group (BD+ADHD) compared with that of pure BD (pBD) group, pure ADHD (pADHD) group and healthy controls (HCs). METHODS: This was a three-site study comprising 229 subjects: 70 patients with pBD, 23 with BD+ADHD, 50 with pADHD, and 86 HCs. All patients with BD had been euthymic for at least 6 months. Neuropsychological performance was assessed using a comprehensive neurocognitive battery. RESULTS: Our results showed that all the clinical groups had poorer performance than the HCs in all the neurocognitive domains except for executive functions. No significant differences were observed between the pBD and BD+ADHD groups in any of the cognitive domains, with these two groups showing greater impairment than the pADHD group in executive functions and visual memory. CONCLUSIONS: Our results, although preliminary, suggest that the BD+ADHD group showed the same neurocognitive profile as pBD patients, most likely reflecting the same neurobiological basis. On the other hand, the pADHD group showed a more selective moderate impairment in attention.

Administrative prevalence of insomnia and associated clinical features in patients with addiction during active substance use.

INTRODUCTION: A bidirectional relation between substance use and insomnia has been described, although there are few studies examining insomnia in the population of people with addiction. The aim of this study was to describe the prevalence of insomnia during active substance use in patients with addiction and its associated clinical features. PATIENTS AND METHODS: Descriptive study in patients diagnosed with substance dependence disorder admitted to a Hospital Detoxification Unit. The existence of insomnia prior to admission was assessed using the Oviedo Sleep Questionnaire (OSQ). Demographic variables, consumptionrelated clinical variables, and diagnostic variables were collected and the SCID-I and -II (Structured Clinical Interview for DSM-IV) and CAADID (Conners’ Adult ADHD Diagnostic Interview for DSM-IV) were administered to evaluate the psychiatric diagnoses. Bivariate and multivariate analyses were made of the data. RESULTS: 481 patients (72.6% men, age 40.6±10.1 years) were enrolled. 64.3% of the patients reported insomnia during active substance use. The most common type of insomnia was fragmented nocturnal sleep (49.9%). The factors significantly associated with insomnia were polysubstance drug use, medical comorbidities (most notably, infectious diseases), anxiety disorder, personality disorder (particularly cluster C), a greater number of previous admissions for detoxication, and early age at onset of substance use. CONCLUSIONS: Insomnia is highly prevalent in patients with addiction during active use of the substance. Fragmented nocturnal sleep was the most common type of insomnia. Patients with addiction and comorbid anxiety disorder, medical comorbidity, and early onset of dependence were more likely to experience insomnia.

Motivational interviewing group at inpatient detoxification, its influence in maintaining abstinence and treatment retention after discharge.

The relapse rate after discharge from inpatient detoxification is high. The objective of this pilot study is to assess the sociodemographic, clinical and therapeutic factors associated with maintaining abstinence in patients who participated in a brief motivational interviewing group during admission for detoxification. A total of 46 patients, diagnosed substance dependent according to DSM -IV, and admitted to the Hospital Detoxification Unit, participated in a brief motivational interviewing group. Sociodemographic, clinical, motivation to change (University of Rhode Island Change Assessment, URICA) and satisfaction with the treatment group (Treatment Perceptions Questionnaire, CPT) data were collected. Abstinence and treatment retention two months after discharge were assessed by weekly telephone calls. A survival analysis was performed. Being male, having more cognitions of the maintenance stage of change at discharge, being satisfied with group therapy and therapist during hospitalization are associated with longer abstinence after discharge. The brief motivational interviewing group approach with patients admitted for detoxification is related to greater likelihood of maintaining abstinence and subsequent treatment retention.

La tasa de recaída en el consumo al alta de una Unidad de Desintoxicación Hospitalaria es elevada. El objetivo de este estudio piloto es valorar los factores sociodemográficos, clínicos y terapéuticos asociados al mantenimiento de la abstinencia de pacientes que han participado en un grupo psicoterapéutico breve de corte motivacional durante su ingreso para la desintoxicación.Un total de 46 pacientes con diagnóstico de trastorno por dependencia a sustancias, según DSM-IV, ingresados en Unidad de Desintoxicación Hospitalaria participaron en un grupo breve de corte motivacional. Se midieron variables sociodemográficas y clínicas, así como la motivación al cambio (University of Rhode Island Change Assessment, URICA) y la satisfacción con el tratamiento grupal (Cuestionario de Percepciones de Tratamiento, CPT). El mantenimiento de la abstinencia y la retención al tratamiento, dos meses tras el alta, se evaluaron mediante llamadas telefónicas semanales. Se realizó un análisis de supervivencia. Los resultados muestran que ser varón, tener cogniciones del estadio de mantenimiento del cambio al alta y tener una buena satisfacción con la terapia grupal y su terapeuta durante el ingreso, se asocia con mayor tiempo en abstinencia tras el alta. El abordaje psicoterapéutico grupal breve de corte motivacional, en pacientes ingresados para la desintoxicación, se relaciona con mayor probabilidad de mantenimiento de abstinencia y de retención al tratamiento posterior.

Neuroticism and impulsivity: their hierarchical organization in the personality characterization of drug-dependent patients from a decision tree learning perspective.

OBJECTIVE: Neuroticism and impulsivity are the personality variables most consistently associated with drug-dependent patients. To date, no data mining procedures have been applied to explore the differential role of personality variables in this population. METHODS: The personality profile of 336 drug-dependent patients was compared with that of a sample of community participants in the context of a decision tree learning approach using the Alternative Five Factor Model. The resulting discriminant model was cross-validated. RESULTS: Neuroticism and impulsivity were the most relevant variables in the resulting model, but their association appeared to be hierarchically organized. In the personality characterization of these patients, neuroticism became the main discriminant dimension, whereas impulsivity played a differential role, explained by means of an interaction effect. Decision tree learning models appear to be a heuristic theoretical and empirical approximation to the study of relevant variables, such as personality traits, in drug-dependency research.

An international perspective and review of cocaine-induced psychosis: a call to action.

Cocaine use can induce transient psychotic symptoms that include suspiciousness, paranoia, hallucinations, and other cocaine-related behaviors. In this commentary, the authors provide an international perspective while reviewing the recent advances in epidemiology, clinical features, and risk factors related to cocaine-induced psychosis exhibited by patients with cocaine use disorders. In some settings, the occurrence of cocaine-induced psychosis has been shown to be as high as 86.5%. Many risk factors have been linked with cocaine-induced psychosis, including the quantity of cocaine consumed, lifetime amount of cocaine use, onset of cocaine dependence, years of use, routes of administration, other substance use disorder comorbidity, weight, gender, comorbidity with other medical and mental health disorders, genetics, and pharmacological interactions. Research has shown that the evaluation of cocaine-induced psychosis in patients with cocaine use is clinically relevant, especially in those patients who consume high amounts of cocaine, have a cannabis dependence history, have antisocial personality disorder, use administration routes other than intranasal, or exhibit attention-deficit/hyperactivity disorder (ADHD) comorbidity. Currently, the literature lacks information regarding the evolution of cocaine dependence or cocaine-dependent patients' risk for developing schizophrenia or other psychotic disorders. Furthermore, clinicians still do not have an evidence-based pharmacological approach to management of cocaine dependence available to them. Additional research is also needed regarding risk factors such as neurobiological markers and personality traits. Finally, we recommend the development of an integrative model including all of the risk factors and protective factors for cocaine-induced psychosis.

Dual diagnosis among physicians: a clinical perspective.

Co-occurrence of mental disorders and substance use disorders (dual diagnosis) among doctors is a cause of serious concern due to its negative personal, professional, and social consequences. This work provides an overview of the prevalence of dual diagnosis among physicians, suggests a clinical etiological model to explain the development of dual diagnosis in doctors, and recommends some treatment strategies specifically for doctors. The most common presentation of dual diagnosis among doctors is the combination of alcohol use disorders and affective disorders. There are also high rates of self-medication with benzodiazepines, legal opiates, and amphetamines compared to the general population, and cannabis use disorders are increasing, mainly in young doctors. The prevalence of nicotine dependence varies from one country to another depending on the nature of public health policies. Emergency medicine physicians, psychiatrists, and anaesthesiologists are at higher risk for developing a substance use disorder compared with other doctors, perhaps because of their knowledge of and access to certain legal drugs. Two main pathways may lead doctors toward dual diagnosis: (a) the use of substances (often alcohol or self-prescribed drugs) as an unhealthy strategy to cope with their emotional or mental distress and (b) the use of substances for recreational or other purposes. In both cases, doctors tend to delay seeking help once a problem has been established, often for many years. Denial, minimization, and rationalization are common defense mechanisms, maybe because of the social stigma associated with mental or substance use disorders, the risk of losing employment/medical license, and a professional culture of perfectionism and denial of emotional needs or failures. Personal vulnerability interacts with these factors to increase the risk of a dual diagnosis developing in some individuals. When doctors with substance use disorders accept treatment in programs specifically designed for them (Physicians' Health Programs), they show better outcomes than the general population. However, physicians with dual diagnosis have more psychological distress and worse clinical prognosis than those with substance use disorders only. Future studies should contribute to a better comprehension of the risk and protective factors and the evidence-based treatment strategies for doctors with dual diagnosis.

Inpatient physicians and nurses with dual diagnosis: an exploratory study.

OBJECTIVE: This study explored the clinical features of physicians and nurses with dual diagnosis.   METHODS: We conducted a retrospective review of 150 medical records of physicians (n = 120) and nurses (n = 30) admitted from February 2008 to February 2011 to the Barcelona Psychiatric Inpatient Unit for Health Professionals. Routine intake included the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) and a clinical interview.   RESULTS: The mean age of participants was 48.59 (SD = 8.9) years and 57.3% were male. Patients experienced substance dependence with alcohol (n = 112, 74.7%), sedatives (n = 59, 39.3%), cocaine (n = 24, 16%), other stimulants (n = 15, 10%), and opiates other than heroin (n = 16, 10.7%). About 41% (n = 61) also met criteria for a mental health disorder, mainly major depressive disorder (n = 42, 28%), while 8% (n = 12) had attention deficit hyperactivity disorder. A high proportion of physicians (n = 95, 79.2%) and nurses (n = 25, 83.3%) had nicotine dependence. The most common comorbidity was alcohol dependence and major depressive disorder. No differences were found between groups in the prevalence of substance use disorders, mental health disorders, and dual diagnosis.   CONCLUSIONS: Dual diagnosis is a common condition among inpatient physicians and nurses with substance use disorders and its clinical presentation may be similar in both groups.

Patterns of Physical Activity of Adolescents With ADHD in the School Context: A Cross-Sectional Study for Clinical Practice.

OBJECTIVES: To describe the daily Physical Activity (PA) patterns of adolescents with Attention-deficit/hyperactivity disorder (ADHD), to analyze the differences in terms of PA patterns between adolescents with ADHD and those without ADHD, and to study the factors associated with achieving the daily PA recommendations. METHODS: The sample was composed of 778 adolescents who provided complete information on their PA patterns through the Physical Activity Questionnaire for Adolescents (PAQ-A). Of these, 97 had ADHD according to DSM-5 criteria. RESULTS: The results show that being a girl or being of foreign origin and having ADHD have an impact on the achievement of the recommended amount of daily PA. CONCLUSIONS: When promoting PA in adolescents with ADHD within the school environment, it is necessary to consider different domains and specific contexts of a school day, paying special attention to girls and adolescents with ADHD of immigrant origin.

Fine-mapping genomic loci refines bipolar disorder risk genes.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).

ADHD symptomatology in eating disorders: a secondary psychopathological measure of severity?

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has commonly been described in psychiatric disorders. Although several studies have found positive associations between abnormal eating patterns during childhood and ADHD, there is a lack of studies on ADHD and Eating Disorders (ED). The aims of this exploratory study were 1) to assess the ADHD symptoms level in ED and to ascertain whether there are differences among ED subtypes; 2) to analyze whether the presence of ADHD symptoms is associated with more severe eating disorder symptoms and greater general psychopathology; and 3) to assess whether the ADHD symptoms level is associated with specific temperament and character traits. METHODS: 191 female ED patients were included. Assessment was carried out with the EDI-2, ASRS-v1.1, the SCL-90-R and the TCI-R. RESULTS: The ADHD symptoms level was similar in bulimia, eating disorder not otherwise specified and binge eating subtypes, and lower in anorexic patients. Obsessiveness and Hostility were significantly positively associated with ADHD symptoms. A path model showed that ADHD was associated with high Novelty Seeking and low Self-Directedness, whereas ED severity was influenced by ADHD severity and low Self-Directedness. CONCLUSIONS: Bingeing/purging ED subtypes have a high ADHD symptoms level, also related with more severe eating, general and personality psychopathology.

The role of neuroticism, perfectionism and depression in chronic fatigue syndrome. A structural equation modeling approach.

OBJECTIVE: Previous studies have reported consistent associations between Neuroticism, maladaptive perfectionism and depression with severity of fatigue in Chronic Fatigue Syndrome (CFS). Depression has been considered a mediator factor between maladaptive perfectionism and fatigue severity, but no studies have explored the role of neuroticism in a comparable theoretical framework. This study aims to examine for the first time, the role of neuroticism, maladaptive perfectionism and depression on the severity of CFS, analyzing several explanation models. METHODS: A sample of 229 CFS patients were studied comparing four structural equation models, testing the role of mediation effect of depression severity in the association of Neuroticism and/or Maladaptive perfectionism on fatigue severity. RESULTS: The model considering depression severity as mediator factor between Neuroticism and fatigue severity is the only one of the explored models where all the structural modeling indexes have fitted satisfactorily (Chi square=27.01, p=0.079; RMSE=0.047, CFI=0.994; SRMR=0.033). Neuroticism is associated with CFS by the mediation effect of depression severity. This personality variable constitutes a more consistent factor than maladaptive perfectionism in the conceptualization of CFS severity.