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.

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.

[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.

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.

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.

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.

Differences in the association between childhood trauma history and borderline personality disorder or attention deficit/hyperactivity disorder diagnoses in adulthood.

Common environmental etiological factors between borderline personality disorder (BPD) and attention deficit/hyperactivity disorder (ADHD) have not been fully studied. The main aim of this study was to investigate the relationship between childhood trauma histories, assessed by the Childhood Trauma Questionnaire-Short Form (CTQ-SF), with adult BPD, ADHD or BPD-ADHD diagnoses. Comorbid BPD-ADHD patients exhibited significantly higher clinical severity and higher scores in the Total Neglect Scale, compared to BPD and ADHD patients, and only a marginal difference was observed for Sexual Abuse when BPD and ADHD patients were compared. Physical Trauma Scales were associated with ADHD diagnosis, whereas Emotional Abuse and Sexual Abuse Scales were associated with BPD or BPD-ADHD diagnoses. The study findings support the association between experiencing traumatic events in childhood and a higher clinical severity of BPD in adulthood. Furthermore, physical trauma history in childhood could be associated with the persistence of ADHD in adulthood and emotional or sexual abuse with later development of BPD or comorbid BPD-ADHD. Whereas experiencing childhood traumas is associated with later development of more general psychopathology, our study supports that a specific type of traumatic event could increase the risk for the consolidation of a concrete psychiatric disorder in the trajectory from childhood to adulthood of vulnerable subjects.

Borderline Personality Disorder and Personality Inventory for DSM-5 (PID-5): Dimensional personality assessment with DSM-5.

INTRODUCTION: Borderline personality disorder (BPD) diagnosis has been considered highly controversial. The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) proposes an alternative hybrid diagnostic model for personality disorders (PD), and the Personality Inventory for DSM-5 (PID-5) has adequate psychometric properties and has been widely used for the assessment of the dimensional component. METHODS: Our aim was to analyze the utility of the personality traits presented in Section III of the DSM-5 for BPD diagnosis in an outpatient clinical sample, using the Spanish version of the PID-5. Two clinical samples were studied: BPD sample (n=84) and non-BPD sample (n=45). Between-sample differences in PID-5 scores were analyzed. RESULTS: The BPD sample obtained significantly higher scores in most PID-5 trait facets and domains. Specifically and after regression logistic analyses, in BPD patients, the domains of Negative Affectivity and Disinhibition, and the trait facets of emotional lability, [lack of] restricted affectivity, and impulsivity were more significantly associated with BPD. CONCLUSIONS: Although our findings are only partially consistent with the algorithm proposed by DSM-5, we consider that the combination of the PID-5 trait domains and facets could be useful for BPD dimensional diagnosis, and could further our understanding of BPD diagnosis complexity.

Impulsive clinical profile of Borderline Personality Disorder with comorbid Substance Use Disorder.

INTRODUCTION: Borderline Personality Disorder (BPD) is one of the Personality Disorder most frequently associated with Substance Use Disorder (SUD). According to different models, the Behavioral dysregulation-BPD subgroup has a higher prevalence of SUD and certain impulsivity behaviors than the other two subgroups. METHODS: Out of 156 BPD patients, 47 were in the Behavioral dysregulation-BPD subgroup, 55 in Affective dysregulation, and 54 in Disturbed relatedness. All patients completed the SCID-II for DSM-IV Axis II Disorders, SCID-I for DSM-IV Axis I Disorders, Barratt Impulsiveness Scale (BIS-11) and Revised Diagnostic Interview for Borderlines (DIB-R). RESULTS: In the comparison of the BPD subgroups, Behavioral dysregulation showed significantly more prevalence of SUD (alcohol and cocaine), and tendency for anxiolytics, higher impulsivity (DIB-R, but none in BIS-11), and higher number of suicide attempts and psychiatric admissions, although these was not significant in comparison with the other subgroups. CONCLUSIONS: This should be especially useful in the discrimination of BPD patients for different therapeutic approaches and prognoses.

Study of prevalence of Personality Disorders in inmate men sample with Substance Use Disorders using of PDQ-4+ Self-Report.

INTRODUCTION: The study focused on examining the prevalence of Personality Disorders (PD) in 51 male inmates diagnosed with Substance Use Disorders (SUDs) lifetime within a specialized unit at a prison. METHODS: The instruments administered included the Structured Clinical Interview for DSM-IV Axis I and the Personality Diagnostic Questionnaire-4+. RESULTS: The type of crime most frequently committed by the incarcerated was the robbery (76.5%), including robbery with violence. 45.1% of the patients screened positive for Antisocial PD, followed by 35.3% for Paranoid and 23.5% for Obsessive Compulsive PD. The results reflect a male inmate sample exhibiting a clinical profile characterized by SUDs and PD, with almost half of the total sample presenting Antisocial PD. CONCLUSIONS: The presence of Antisocial and Paranoid PD with SUD suggests a more complex personality profile, with a tendency to carry out more aggressive crimes, including robbery with violence. A more comprehensive PD assessment should be carried out in prison settings in order to identify dangerous individuals who are at risk of recidivism.

Relevant Differences in Perception and Knowledge of Professionals in Different Spanish Autonomous Communities Regarding Availability of Resources for Patients with Dual disorders.

OBJECTIVES: To assess the knowledge of health professionals attending patients with dual disorders about specific resources for patients with this condition in different Spanish regions. METHODS: Observational, cross-sectional, multicenter study to compare the perceptions of healthcare professionals (n=659) with reality regarding specific resources available for patients with dual disorders in Spain. The professionals completed an online questionnaire. Nineteen commissioners and managers responsible for national and regional substance abuse programs also completed the questionnaire. RESULTS: A representative sample of professionals from each community (553 centers in 235 Spanish cities) participated in the study. Most participants (93.2%) felt that specific resources for patients with dual disorders are needed. High percentages of professionals thought that there were no specific workshops (88.4%), subacute units (83.1%), day hospitals (82.8%), specific day centers (78.5%), or outpatient programs (73.2%) for patients with dual disorders. The real knowledge of professionals regarding the existence of specific resources varied according to the type of resource and autonomous community. The professionals generally underestimated the number of units available in their communities. CONCLUSIONS: There were clear differences in the real knowledge that healthcare professionals had about the resources available for patients with dual disorders in relation to the autonomous community where they were practicing. Actions are needed to harmonize knowledge nationally, for example, a single registry, white paper, or a national program for patients with dual disorders.

Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder.

BACKGROUND: Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress. METHODS: Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded. RESULTS: No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027). CONCLUSIONS: Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life.

Childhood trauma in Chronic Fatigue Syndrome: focus on personality disorders and psychopathology.

INTRODUCTION: Personality Disorders (PDs) and childhood traumatic experiences have been considered risk factors for Chronic Fatigue Syndrome (CFS). However, the relationship between these factors and their associated psychopathological impact has not been explored in this population. This study was designed to evaluate the association between different childhood traumas and the presence and number of PDs and current psychopathology in a sample of CFS patients. MATERIAL AND METHODS: For this purpose, 166 CFS patients were evaluated with the Personality Diagnostic Questionnaire-4+ (PDQ-4+) and the Child Trauma Questionnaire. Other instruments were used to assess the associated psychopathology and the impact of fatigue. RESULTS: Of the total sample, 55 (33.1%) presented childhood trauma, the most frequent of which were emotional neglect (21.7%) and emotional abuse (18.1%). Considering PD presence, 79 (47.6%) patients presented some PD. There were no differences in frequency of physical childhood trauma in patients with and without PD. However, patients with PD had more frequently experienced emotional childhood trauma (OR=2.18, p=0.034). Severity of childhood trauma was related to a higher number of PDs, more severe depressive symptoms (p=0.025) and suicide risk (p=0.001). Patients with PD and any childhood trauma presented more severe depressive and irritable symptoms and a higher suicide risk than those without any PD and non-childhood traumatic event. These patients' psychopathological symptoms were similar to those of patients with childhood trauma and without PD. CONCLUSIONS: These results suggest that emotional childhood trauma but not physical childhood trauma is related to higher frequency of PD presence. More severe childhood emotional and physical traumas are related to a higher number of PDs and to more severe psychopathological symptoms.

Frustrated expected reward induces differential transcriptional changes in the mouse brain.

Frustration represents a particular aspect of the addictive process that is related to loss of control when the expected reward is not obtained. We aim to study the consequences of frustrated expected reward on gene expression in the mouse brain. For this purpose, we used an operant model of frustration using palatable food as reward combined with microarrays. Transcriptomic profiles of frontal cortex, ventral striatum and hippocampus were analysed in five groups of mice: (1) positive control receiving palatable food and the cue light as conditioned stimulus; (2) frustrated group only receiving the cue light; (3) extinction learning group that did not receive palatable food nor the light; (4) negative control that never received the reinforcer nor the light during the whole experiment; and (5) yoked that received palatable food passively. Gene expression changes produced by frustration were revealed in the frontal cortex and ventral striatum, but not in the hippocampus. Most of the changes, such as the modification of the dopamine-DARPP-32 signalling pathway, were common in both areas and estimated to have neuronal origin. Extinction learning induced transcriptional changes only in the ventral striatum, with most genes showing down-regulation and without alteration in the dopamine-DARPP-32 signalling pathway. Active palatable food-seeking behaviour induced changes in gene expression in ventral striatum mainly affecting cell communication. In conclusion, frustration behaviour-induced changes in frontal cortex and ventral striatum mainly related to dopamine-DARPP-32 signalling that could play an important role in the loss of behavioural control during the addictive processes.

Regional analysis of health service utilisation by persons with borderline personality disorders: implications for evidence-informed policy.

BACKGROUND: Borderline Personality Disorder (BPD) has been associated with an intensive use of health resources and a high economic burden. AIMS OF THE STUDY: The aim of this study is to analyze the use of mental healthcare resources by BPD patients, to identify the information gaps on BPD at the regional health databases and to describe specific indicators and patterns of care utilization by persons with BPD in order to guide evidence-informed policy planning in Catalonia (Spain). METHODS: A multi-level cross-design synthesis approach was applied following a mixed quantitative-qualitative analysis to estimate the regional service utilisation of patients with BPD. This framing analysis included estimates based on all available data on the use of services combined with prior expert knowledge gathered through a nominal group of key stakeholders in this field. RESULTS: The estimated year prevalence of BPD was 0.7% but only 9.6% of all BPD patients in Catalonia had any contact with the health care system. Of those, less than half contacted mental health care. BPD represented 1.7% of the total care load in the community mental health centres. A significant information gap was identified in all the official databases and impeded their direct use for planning and resource allocation in BPD. Expert knowledge was required to estimate rates of care utilization at every level of care system (primary care, specialized outpatient care and hospital care). Nevertheless the high pattern of care utilization identified at the databases was accurate according to the experts. DISCUSSION: Detection of BPD was lower than expected in the local, regional and national databases and registries of Catalonia. Local data was judged highly inaccurate by experts in comparison to data available on other mental disorders in the same databases. IMPLICATIONS FOR HEALTH POLICY AND RESEARCH: Specific incentives should be implemented to improve the availability and accuracy of information on BPD at the regional databases. When present, BPD should be coded before other psychiatric disorders in clinical records and health databases. Mental health surveys and psychiatric epidemiological studies should specifically incorporate BPD in their inclusion criteria and further studies on the utilisation pattern of this disorder are needed, both locally and internationally.

Comorbid personality disorders in chronic fatigue syndrome patients: a marker of psychopathological severity.

INTRODUCTION: This study was designed to evaluate the presence of personality disorders (PDs) in Chronic Fatigue Syndrome (CFS) patients and to determine their influence on the severity of the associated psychopathology. METHODS: 132 CFS patients were assessed using SCID-I, Personality Diagnostic Questionnaire-4+ (PDQ-4+) with its Clinical Significance Scale, and Fatigue Impact Scale. The Beck Depression Inventory, Buss-Durkee Hostility Inventory and the State-Trait Anxiety Inventory were also administered. RESULTS: 48.5% patients presented PDs, being the most frequent the Obsessive-Compulsive and Avoidant ones. Patients with PDs had more depressive symptoms. Irritability, resentment, suspicion and guilt were the symptoms related with PDQ-4+ total score. CONCLUSIONS: According to these results, PDs may be frequent in CFS patients. This comorbidity is associated with a complex clinical profile, secondary to more severe psychiatric symptoms.

Substance Use among Medical Students: A Literature Review 1988- 2013.

The use of legal and illegal substances by medical students is a phenomenon that is only partially known. The aim of this paper was to review the literature published internationally in the last 25 years about the use of legal and illegal substances by medical students. A systematic search was made of MEDLINE and LILACS. One hundred and six manuscripts were evaluated, which included a population of 88,413 medical students. We validated 74,001 questionnaires, which represented 83.7% of responses. The methodology and the rigor of its application are not the same in all the publications. There are many regional variations, most studies being made in America and Europe. With the exception of alcohol in some areas of the Western world, medical students use substances less than university students in general and the general population. The substances used are mainly alcohol (24%), tobacco (17.2%), and cannabis (11.8%). The use of hypnotic and sedative drugs also is common (9.9%). The rate of use of stimulants is 7.7% and of cocaine, 2.1%; opiate use being very low (0.4%). In some parts of Latin America, up to 14.1% use inhalants. Students in the last years of school have a higher rate of substance use. The use of substances, except for hypnotics and sedatives, is more common among men than women. The use of substances by medical students is a phenomenon that should be evaluated systematically due to its prevalence and potential impact.

New suggestive genetic loci and biological pathways for attention function in adult attention-deficit/hyperactivity disorder.

Attention deficit is one of the core symptoms of the attention-deficit/hyperactivity disorder (ADHD). However, the specific genetic variants that may be associated with attention function in adult ADHD remain largely unknown. The present study aimed to identifying SNPs associated with attention function in adult ADHD and tested whether these associations were enriched for specific biological pathways. Commissions, hit-reaction time (HRT), the standard error of HRT (HRTSE), and intraindividual coefficient variability (ICV) of the Conners Continuous Performance Test (CPT-II) were assessed in 479 unmedicated adult ADHD individuals. A Genome-Wide Association Study (GWAS) was conducted for each outcome and, subsequently, gene set enrichment analyses were performed. Although no SNPs reached genome-wide significance (P < 5E-08), 27 loci showed suggestive evidence of association with the CPT outcomes (P < E-05). The most relevant associated SNP was located in the SORCS2 gene (P = 3.65E-07), previously associated with bipolar disorder (BP), Alzheimer disease (AD), and brain structure in elderly individuals. We detected other genes suggested to be involved in synaptic plasticity, cognitive function, neurological and neuropsychiatric disorders, and smoking behavior such as NUAK1, FGF20, NETO1, BTBD9, DLG2, TOP3B, and CHRNB4. Also, several of the pathways nominally associated with the CPT outcomes are relevant for ADHD such as the ubiquitin proteasome, neurodegenerative disorders, axon guidance, and AD amyloid secretase pathways. To our knowledge, this is the first GWAS and pathway analysis of attention function in patients with persistent ADHD. Overall, our findings reinforce the conceptualization of attention function as a potential endophenotype for studying the molecular basis of adult ADHD. © 2015 Wiley Periodicals, Inc.

Dopamine receptor DRD4 gene and stressful life events in persistent attention deficit hyperactivity disorder.

We performed a case-control association study in persistent ADHD considering eight candidate genes (DRD4, DAT1/SLC6A3, COMT, ADRA2A, CES1, CYP2D6, LPHN3, and OPRM1) and found additional evidence for the involvement of the Dup 120bp and VNTR 48bp functional variants within the dopamine receptor DRD4 gene in the etiology of adult ADHD. We subsequently investigated the interaction of stressful life events with these two DRD4 polymorphisms, and the impact of such events on the severity of ADHD symptomatology. The gene-by-environment analysis revealed an independent effect of stressful experiences on the severity of persistent ADHD, and a gene-by-environment interaction on the inattentive dimension of the disorder, where non carriers of the Dup 120bp (L) - VNTR 48bp (7R) haplotype were more sensitive to environmental adversity than carriers. These results are in agreement with previous works reporting a relationship between DRD4 and the effect of adverse experiences, which may explain the discordant findings in previous genetic studies and strengthen the importance of gene-by-environment interactions on the severity of ADHD. © 2015 Wiley Periodicals, Inc.