Vectorial-based analysis of dual-tracer PET imaging: A proof of concept.

BACKGROUND: The diagnosis of neurological diseases is complicated since they often share similar symptoms and occur in different severity levels. Imaging techniques such as PET molecular imaging are helpful for an early and accurate diagnosis and, staging allowing a noninvasive evaluation of the disease. The combination of two radioligands in the same patient could be valuable to achieve these diagnostic goals; nevertheless, the imaging data obtained with two radioligands is commonly interpreted independently. This novel approach to combine the PET data of two radiopharmaceuticals, separately acquired in the same subject, is to obtain new quantitative metrics. PET images of patients with Parkinson's disease (PD) and healthy controls (HC) were analyzed. Voxel-by-voxel uptake is compared by combining the imaging data. Dual-tracer PET imaging analysis was tested with [11C]DTBZ-[11C]Raclopride as proof of concept. RESULTS: The new proposed metric based on a resultant vector is capable of efficiently discriminating healthy controls from PD patients (p < 0.0001) allowing the detection of slight changes in patients undergoing therapeutic approaches. Significant differences were found between HC and PD patients for the evaluated radiotracers. CONCLUSIONS: The resultant vector appears to deliver useful information that could be helpful to evaluate PD patients under treatment and to improve differential diagnoses.

Semiquantitative analysis of cerebral [18F]FDG-PET uptake in pediatric patients.

BACKGROUND: Glycolytic metabolism in the brain of pediatric patients, imaged with [18F]  fluorodeoxyglucose-positron emission tomography (FDG-PET) is incompletely characterized. OBJECTIVE: The purpose of the current study was to characterize [18F]FDG-PET brain uptake in a large sample of pediatric patients with non-central nervous system diseases as an alternative to healthy subjects to evaluate changes at different pediatric ages. MATERIALS AND METHODS: Seven hundred ninety-five [18F]FDG-PET examinations from children < 18 years of age without central nervous system diseases were included. Each brain image was spatially normalized, and the standardized uptake value (SUV) was obtained. The SUV and the SUV relative to different pseudo-references were explored as a function of age. RESULTS: At all evaluated ages, the occipital lobe showed the highest [18F]FDG uptake (0.27 ± 0.04 SUV/year), while the parietal lobe and brainstem had the lowest uptake (0.17 ± 0.02 SUV/year, for both regions). An increase [18F]FDG uptake was found for all brain regions until 12 years old, while no significant uptake differences were found between ages 13 (SUV = 5.39) to 17 years old (SUV = 5.52) (P < 0.0001 for the whole brain). A sex dependence was found in the SUVmean for the whole brain during adolescence (SUV 5.04-5.25 for males, 5.68-5.74 for females, P = 0.0264). Asymmetries in [18F]FDG uptake were found in the temporal and central regions during infancy. CONCLUSIONS: Brain glycolytic metabolism of [18F]FDG, measured through the SUVmean, increased with age until early adolescence (< 13 years old), showing differences across brain regions. Age, sex, and brain region influence [18F]FDG uptake, with significant hemispheric asymmetries for temporal and central regions.

Validity of the ADHD module of the Mini International Neuropsychiatric Interview PLUS for screening of adult ADHD in treatment seeking substance use disorder patients: ADHD screening with MINI-Plus.

OBJECTIVE: This study aims to assess the validity of the ADHD module of the Mini-International Neuropsychiatric Interview (MINI-Plus) in patients with substance use disorders (SUD), using the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID) as the external criterion. METHOD: A cross sectional international multi-center study in 10 countries was conducted in treatment seeking SUD patients. A sample of 1263 patients with both MINI-Plus and CAADID was analyzed to determine the psychometric properties of the MINI-Plus. RESULTS: According to the CAADID, 179 patients (14.2%) met criteria for adult ADHD, whereas according to the MINI-Plus 227 patients (18.0%) were identified as having adult ADHD. Sensitivity of the MINI-Plus ADHD module was 74%, specificity was 91%, positive predictive value was 60% and negative predictive value was 96%. Kappa was 0.60. CONCLUSION: The MINI-Plus has acceptable criterion validity for the screening of adult ADHD in treatment seeking SUD patients. SCIENTIFIC SIGNIFICANCE: On the basis of the results, The MINI-Plus may be used for the screening of ADHD in SUD patients.

Evaluación de la calidad del agua de la vereda Río Suárez de Puente Nacional, Santander / Water quality evaluation ot the rural area of Río Suárez of Puente Nacional, Santander

Resumen Objetivo. Determinar la calidad del agua que abastece a la población de la Vereda Rio Suarez del municipio de Puente Nacional por medio del cálculo del índice de riesgo de la calidad del agua (IRCA). Métodos. Se tomaron 10 muestras de diferentes puntos de la red de distribución del agua veredal, se realizó análisis físico-químico y microbiológico por técnica de filtración por membrana bajo parámetros del Instituto Nacional de Salud. Resultados. El análisis físico-químico mostró cuantificación de hierro elevado y nivel de turbiedad inadecuado lo que puede afectar el sabor y el aspecto del agua. El recuento de coliformes totales fue >300 UFC/100ml., con identificación de Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa y Enterococcus entre otras, habitantes de suelo y aguas que pueden ser causantes de infecciones gastrointestinales e infecciones urinarias, resultados que indican que el agua no es apta para consumo humano.

Abstract Objective. To determine the quality of the water that supplies the population of the Vereda Rio Suarez of the municipality of Puente Nacional through the calculation of the risk index of water quality (IRCA). Methods. 10 samples were taken from different points of the water distribution network, physical-chemical and microbiological analysis was performed by membrane filtration technique under parameters of the National Institute of Health. Results. The physical-chemical analysis showed high iron quantification and inadequate turbidity level that can affect the taste and appearance of the water. The total coliform count> 300 CFU / 100ml., with identification of Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa and Enterococcus among others that inhabit soils and waters and can cause gastrointestinal infections and urinary infections and is not suitable for human consumption.

[International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder]. / Internationale Konsenserklärung zu Screening, Diagnostik und Behandlung von Jugendlichen und Heranwachsenden mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung und gleichzeitigen Störungen durch Substanzgebrauch.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Abstract. Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. Conclusion: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

Transcriptome profiling in adult attention-deficit hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated heritability of around 70%. Although the largest genome-wide association study (GWAS) meta-analysis on ADHD identified independent loci conferring risk to the disorder, the molecular mechanisms underlying the genetic basis of the disorder remain to be elucidated. To explore ADHD biology, we ran a two-step transcriptome profiling in peripheral blood mononuclear cells (PBMCs) of 143 ADHD subjects and 169 healthy controls. Through this exploratory study we found eight differentially expressed genes in ADHD. These results highlight promising candidate genes and gene pathways for ADHD and support the use of peripheral tissues to assess gene expression signatures for ADHD.

Professional perception of clozapine use in patients with dual psychosis.

INTRODUCTION: Patients with psychotic disorders often have substance use disorders and other addictions. The objective of this study was to know the current treatment situation of these patients focusing on clozapine, which was proposed in most consensus as antipsychotic of first choice in this indication. MATERIAL AND METHODS: A survey with 14 questions on aspects related to the treatment and management of the dual disorders was developed, emphasizing the role of clozapine in this disease. RESULTS: The survey was answered by 199 experts in mental illnesses (90.5% physicians and 9.5% psychologists). A total of 88.4% of experts were able to prescribe clozapine, but the majority (89.4%) administered the drug to patients with resistant schizophrenia without considering a dual disorder. Only 30.8% considered the use of clozapine in patients with dual psychosis. The underutilization of clozapine in these patients was mainly attributed to controls of the pharmacovigilance plan, including frequent leukocyte count (57.1%), and lack of drug education (35.6%). The main measures proposed to increase its use are fewer blood tests (29.3%), more training (27.8%), and fewer administrative problems (25.1%). CONCLUSIONS: In order to improve the treatment of patients with dual psychosis, it is necessary to simplify the therapy and increase the training of professionals in the use of atypical antipsychotics, especially clozapine, designed to be the drug of choice in the main expert consensus.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder.

BACKGROUND: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. OBJECTIVE: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. METHOD: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. RESULTS: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. CONCLUSION: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

Percepción de los profesionales sobre el uso de la clozapina en pacientes con psicosis dual / Professional perception of clozapine use in patients with dual psychosis

INTRODUCCIÓN. Los pacientes con trastornos psicóticos presentan con frecuencia trastornos por uso de sustancias y otras adicciones. El objetivo de este estudio fue conocer la situación actual del tratamiento de estos pacientes con el foco puesto en la clozapina, que ha sido propuesta en la mayoría de los consensos como antipsicótico de primera elección en esta indicación. MATERIAL Y MÉTODOS. Se elaboró una encuesta con 14 preguntas sobre aspectos relacionados con el tratamiento y manejo de la patología dual, haciendo hincapié en el papel de la clozapina en esta enfermedad. RESULTADOS: La encuesta fue respondida por 199 exper-tos en enfermedades mentales (90,5% médicos y 9,5% psicólogos). Un 88,4% de los encuestados tenía posibilidad de prescribir la clozapina, pero la mayoría (89,4%) la administraba a pacientes con esquizofrenia resistente sin considerar una patología dual. Solo un 30,8% planteó el uso de la clozapina a pacientes con psicosis dual. La infrautilización de la clozapina en estos pacientes se atribuyó principalmente a los controles del plan de farmacovigilancia, incluido el recuento leucocitario frecuente (57,1%), y a la falta de formación sobre el fármaco (35,6%). Las principales medidas propuestas para incrementar su uso son tener que hacer menos controles hemáticos (29,3%), mayor formación (27,8%) y tener menos problemas administrativos (25,1%). CONCLUSIONES: Para mejorar el tratamiento de los pacientes con psicosis dual es necesario simplificar la terapia e incrementar la formación de los profesionales sobre el uso de antipsicóticos atípicos, especialmente la clozapina, considerada como el fármaco de elección en los principales consensos de expertos

INTRODUCTION: Patients with psychotic disorders often have substance use disorders and other addictions. The objective of this study was to know the current treatment situation of these patients focusing on clozapine, which was proposed in most consensus as antipsychotic of first choice in this indication. MATERIAL AND METHODS: A survey with 14 questions on aspects related to the treatment and management of the dual disorders was developed, emphasizing the role of clozapine in this disease. RESULTS: The survey was answered by 199 experts in mental illnesses (90.5% physicians and 9.5% psychologists). A total of 88.4% of experts were able to prescribe clozapine, but the majority (89.4%) administered the drug to patients with resistant schizophrenia without considering a dual dis-order. Only 30.8% considered the use of clozapine in patients with dual psychosis. The underutilization of clozapine in these patients was mainly attributed to controls of the pharmacovigilance plan, including frequent leukocyte count (57.1%), and lack of drug education (35.6%). The main measures proposed to increase its use are fewer blood tests (29.3%), more training (27.8%), and fewer administrative problems (25.1%). CONCLUSIONS: In order to improve the treatment of patients with dual psychosis, it is necessary to simplify the therapy and increase the training of professionals in the use of atypical antipsychotics, especially clozapine, designed to be the drug of choice in the main expert consensus

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.

Genome-wide analysis of emotional lability in adult attention deficit hyperactivity disorder (ADHD).

Emotional lability is strongly associated with Attention Deficit Hyperactivity Disorder (ADHD), represents a major source of impairment and predicts poor clinical outcome in ADHD. Given that no specific genes with a role in the co-occurrence of both conditions have been described, we conducted a GWAS of emotional lability in 563 adults with ADHD. Despite not reaching genome-wide significance, the results highlighted genes related with neurotransmission, cognitive function and a wide range of psychiatric disorders that have emotional lability as common clinical feature. By constructing polygenic risk scores on mood instability in the UK Biobank sample and assessing their association with emotional lability in our clinical dataset, we found suggestive evidence of common genetic variation contributing to emotional lability in general population and in clinically diagnosed ADHD. Although not conclusive, these tentative results are in agreement with previous studies that suggest emotion dysregulation as a transdiagnostic construct and highlight the need for further investigation to disentangle the genetic basis of mood instability in ADHD and co-occurring psychiatric disorders.

Cocaine relapse and health-related quality of life: a 23 weeks study.

INTRODUCTION: Cocaine dependence is a disorder where relapses are frequently presented and many factors are involved. Furthermore, cocaine dependence is associated with poor health-related quality of life (HRQoL) outcomes. This study aims to explore perceived HRQoL as an indicator of drug relapse in cocaine-dependent patients (CDP). SUBJECTS AND METHODS: A longitudinal study was carried out in CDP during 23 weeks. A consecutive sampling method was applied, 39 participants composed the initial sample (mean age 35.6 years), only 15 participants completed outpatient follow-up period. CDP were assessed with psychiatric and HRQoL instruments (SCID-I, SCID-II, BDI, STAI scale and SF-36) in different points of the study. The patients were followed up, and cocaine relapses were assessed. The sample was divided according with the relapse (early vs. late relapse). Data were compared and analyzed in order to evaluate whether HRQoL measure could be related to cocaine relapse. RESULTS: There are differences in perceived HRQoL measures between CDP with/without early relapse, especially in Mental health and Social functioning dimensions (p<0.05). Furthermore, Late/relapse-patients have higher improvement of HRQoL than patients with early relapse. CONCLUSIONS: Perceived HRQoL might predict early relapse and could be a possible predictor tool of potential future relapses. More research in this field is needed.

Recaída en el uso de cocaína y calidad de vida relacionada con la salud: un estudio de 23 semanas de seguimiento / Cocaine relapse and health-related quality of life: a 23 weeks study

Introducción. Las recaídas son frecuentes en la dependencia a cocaína, múltiples factores están involucrados en ellas. Además, la dependencia a cocaína se relaciona con un peor pronóstico en relación a la calidad de vida relacionada con la salud (CVRS). Este estudio explora la CVRS percibida como un indicador de recaída en pacientes con dependencia a cocaína. Metodología. Se llevó a cabo un estudio longitudinal en pacientes con dependencia a cocaína durante 23 semanas. En total 39 pacientes participaron (edad media 35,6 años), aunque solamente 15 completaron el periodo de seguimiento. Se utilizaron varias escalas e instrumentos psicométricos (SCID-I, SCID-II, BDI, STAI y la SF-36) en diferentes puntos del estudio. Los pacientes fueron seguidos y se evaluaron las recaídas. La muestra fue dividida de acuerdo con el momento de recaída (temprano vs. tardía). La información fue comparada y analizada para poder evaluar si la CVRS se podía relacionar con la recaída de cocaína. Resultados. Hubo diferencias en la CVRS percibida entre los pacientes con y sin recaída temprana, especialmente en las dimensiones de Salud Mental y Funcionamiento Social (p<0,05). Además, los pacientes con recaídas tardías presentaban una mejoría de la CVRS percibida si se comparaba con los que recaían de forma temprana. Conclusiones. La CVRS percibida podría predecir parcialmente las recaídas tempranas y su medición podría ser una herramienta para evaluar posibles recaídas en el futuro. Sin embargo, es necesaria más investigación en esta área

Introduction. Cocaine dependence is a disorder where relapses are frequently presented and many factors are involved. Furthermore, cocaine dependence is associated with poor health-related quality of life (HRQoL) outcomes. This study aims to explore perceived HRQoL as an indicator of drug relapse in cocaine-dependent patients (CDP). Subjects and Methods. A longitudinal study was carried out in CDP during 23 weeks. A consecutive sampling method was applied, 39 participants composed the initial sample (mean age 35.6 years), only 15 participants completed outpatient follow-up period. CDP were assessed with psychiatric and HRQoL instruments (SCID-I, SCID-II, BDI, STAI scale and SF-36) in different points of the study. The patients were followed up, and cocaine relapses were assessed. The sample was divided according with the relapse (early vs. late relapse). Data were compared and analyzed in order to evaluate whether HRQoL measure could be related to cocaine relapse. Results. There are differences in perceived HRQoL measures between CDP with/without early relapse, especially in Mental health and Social functioning dimensions (p<0.05). Furthermore, Late/relapse-patients have higher improvement of HRQoL than patients with early relapse. Conclusions. Perceived HRQoL might predict early relapse and could be a possible predictor tool of potential future relapses. More research in this field is needed

ADGRL3 (LPHN3) variants predict substance use disorder.

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.

Epigenetic signature for attention-deficit/hyperactivity disorder: identification of miR-26b-5p, miR-185-5p, and miR-191-5p as potential biomarkers in peripheral blood mononuclear cells.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood and persists into adulthood in 40-65% of cases. Given the polygenic and heterogeneous architecture of the disorder and the limited overlap between genetic studies, there is a growing interest in epigenetic mechanisms, such as microRNAs, that modulate gene expression and may contribute to the phenotype. We attempted to clarify the role of microRNAs in ADHD at a molecular level through the first genome-wide integrative study of microRNA and mRNA profiles in peripheral blood mononuclear cells of medication-naive individuals with ADHD and healthy controls. We identified 79 microRNAs showing aberrant expression levels in 56 ADHD cases and 69 controls, with three of them, miR-26b-5p, miR-185-5p, and miR-191-5p, being highly predictive for diagnostic status in an independent dataset of 44 ADHD cases and 46 controls. Investigation of downstream microRNA-mediated mechanisms underlying the disorder, which was focused on differentially expressed, experimentally validated target genes of the three highly predictive microRNAs, provided evidence for aberrant myo-inositol signaling in ADHD and indicated an enrichment of genes involved in neurological disease and psychological disorders. Our comprehensive study design reveals novel microRNA-mRNA expression profiles aberrant in ADHD, provides novel insights into microRNA-mediated mechanisms contributing to the disorder, and highlights promising candidate peripheral biomarkers.

Family Functioning and Parental Bonding During Childhood in Adults Diagnosed With ADHD.

OBJECTIVE: This work assesses family functioning, parental bonding, and the relationship between the two in adults diagnosed with ADHD. METHOD: The study used a retrospective, ex post facto design and consisted of 100 adult participants, who were distributed into two groups: with and without diagnosis of ADHD. Two family assessment instruments were applied: the Family Adaptability and Cohesion Evaluation Scale short spanish version (FACES-20esp)) and the Parental Bonding Instrument (PBI). The diagnosis of ADHD was done by using a semistructured interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria (Conners' Adult ADHD Diagnostic Interview for DSM-IV [CAADID]). RESULTS: The results showed that higher rigidity and lower emotional connection were significantly associated with ADHD family functioning. Regarding parental bonding, the results showed significant differences only in the care dimension, with the ADHD group reporting lower care than the control group. CONCLUSION: The results suggest that ADHD families present dysfunctional family functioning with a rigid, separated typology, and parental bonding based on control without affection.

Benzodiazepine Use Disorder and Cognitive Impairment in Older Patients: A Six-Month-Follow-Up Study in an Outpatient Unit in Barcelona.

OBJECTIVE: Adverse health effects including cognitive impairment have been described in older adults with benzodiazepine misuse, although the literature about this issue is scarce. The present study aimed to assess cognitive decline in older adults with benzodiazepine use disorder and changes in cognitive state at the 6-month follow-up, as well as whether patients achieved abstinence. METHOD: A 6-month follow-up longitudinal study was conducted in an outpatient drug center in Barcelona in a sample of older adults (≥65 years old) who had benzodiazepine use disorder. The sample was compared with an equivalent control group. A neuropsychological protocol was performed at baseline and after 6-month follow-up covering the most important cognitive domains. RESULTS: The final sample comprised 33 patients with an average age of 73.5 years. At baseline, patients presented impairment in several domains compared with the control group: visual immediate recall (p < .001), visual delayed recall (p < .001), copy (p < .001), working memory (p < .003), immediate verbal learning (p < .002), total words learned (p < .009), set switching (p < .001), verbal fluency (p < .007), speed processing (p < .002), solving problems (p < .006), nonverbal fluency (p < .004), and sustained attention in all three areas omissions (p < .001), variability (p < .001), and perseverance (p < .005). At 6-month follow-up, patients achieving abstinence showed improvement compared with patients in active consumption in visual delayed recall (p < .006), total words learned (p < .010), and verbal fluency (p < .013). CONCLUSIONS: Benzodiazepine misuse in older adults may produce negative effects on cognitive skills. Recovery of some of these cognitive deficits may be possible with benzodiazepine abstinence.

Sex differences in an old adult sample with substance use disorder: A 6 months follow-up study.

Substance use disorder (SUD) is a worldwide concern that has its own particularities regarding age and sex. This study aims to assess the differences between old SUD women and men regarding socio-demographics, clinical factors and outcomes. A 6-months follow-up longitudinal study was conducted in an outpatient center, on a convenience sample of 115 SUD old adults (≥65 years old, average age of 71.57). Descriptive, bivariate, and multivariate analyses were performed. Data showed statistical significant differences between men and women related to sociodemographic variables (marital status, coexistence, criminal records and stress factors), medical and psychiatric conditions (women suffer higher rates of depression and anxiety, with worse health-related quality of life), family records (women had more presence of family psychiatric records) and SUD related parameters (men tend to use more alcohol, had an early onset, consume higher doses, report more craving and more tobacco life use while women had higher rates of prescription drugs use). At 6-month follow-up, the whole sample showed excellent rates of adherence and abstinence, without sex differences. The study points out sex differences on several sociodemographic and clinical variables, indicating their specific needs. This research could facilitate better approaches by considering a sex perspective in SUD old adults.

Genome-wide association meta-analysis of age at first cannabis use.

BACKGROUND AND AIMS: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. METHODS: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. RESULTS: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2  > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. CONCLUSION: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.