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Background: Pregnancy factors have been implicated in offspring oppositional-defiant disorder (ODD) and conduct disorder (CD) symptoms. Literature still holds notable limitations, such as studying only a restricted set of pregnancy factors, use of screening questionnaires which assess broadly defined outcome measures, and lack of control for disruptive behavior comorbidity and genetic confounds. We aimed to address these gaps by prospectively studying a broad range of pregnancy factors in relation to both offspring ODD and CD symptomatology in the Avon Longitudinal Study of Parent and Children., Methods: Outcomes were ODD and CD symptom scores at age 7;9 years using the Development and Well-Being Assessment interview. We analyzed maternal (N ≈ 6300) and teacher ratings (N ≈ 4400) of ODD and CD scores separately using negative binomial regression in multivariable models. Control variables included comorbid attention-deficit/hyperactivity disorder symptoms, ODD or CD symptoms as appropriate, and genetic risk scores based on an independent CD genome-wide association study., Results: Higher ODD symptom scores were linked to paracetamol use (IRR = 1.24 [98.3% confidence interval 1.05-1.47], P = 0.002, teacher ratings) and life events stress (IRR = 1.22 [1.07-1.39], P = 0.002, maternal ratings) during pregnancy. Higher CD symptom scores were linked to maternal smoking (IRR = 1.33 [1.18-1.51], P < 0.001, maternal ratings), life events stress (IRR = 1.24 [1.11-1.38], P < 0.001, maternal ratings) and depressive symptoms (IRR = 1.14 [1.01-1.30], P = 0.006, maternal ratings) during pregnancy., Conclusions: Common and potentially preventable pregnancy risk factors were independently related to both offspring ODD and CD symptomatology in children from the general population. Future studies should further address genetic confounds and confounding by environmental factors later in life., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Cross-sectional studies have indicated impaired neurodevelopment with elevated drinking water manganese concentrations (W-Mn), but potential susceptible exposure windows are unknown., Objectives: We prospectively evaluated the effects of W-Mn, from fetal life to school age, on children's cognitive abilities and behavior., Methods: We assessed cognitive abilities and behavior in 1,265 ten-year-old children in rural Bangladesh using the Wechsler Intelligence Scale for Children (WISC-IV) and the Strengths and Difficulties Questionnaire (SDQ), respectively. Manganese in drinking water used during pregnancy and by the children at 5 y and 10 y was measured using inductively coupled plasma mass spectrometry., Results: The median W-Mn was 0.20 mg/L (range 0.001–6.6) during pregnancy and 0.34mg/L (<0.001–8.7) at 10 y. In multivariable-adjusted linear regression analyses, restricted to children with low arsenic (As) exposure, none of the W-Mn exposures was associated with the children’s cognitive abilities. Stratifying by gender (p for interaction in general <0.081) showed that prenatal W-Mn (3 mg/L) was positively associated with cognitive ability measures in girls but not in boys. W-Mn at all time points was associated with an increased risk of conduct problems, particularly in boys (range 24–43% per mg/L). At the same time, the prenatal W-Mn was associated with a decreased risk of emotional problems [odds ratio (OR)=0.39 (95% CI: 0.19, 0.82)] in boys. In girls, W-Mn was mainly associated with low prosocial scores [prenatal W-Mn: OR=1.48 (95% CI: 1.06, 1.88)]., Conclusions: Elevated prenatal W-Mn exposure was positively associated with cognitive function in girls, whereas boys appeared to be unaffected. Early life W-Mn exposure appeared to adversely affect children's behavior. https://doi.org/10.1289/EHP631.

Background: Heavy alcohol use during pregnancy can cause considerable developmental problems for children, but effects of light-moderate drinking are uncertain. This study examined possible effects of moderate drinking in pregnancy on children's conduct problems using a Mendelian randomisation design to improve causal inference., Methods: A prospective cohort study (ALSPAC) followed children from their mother's pregnancy to age 13 years. Analyses were based on 3,544 children whose mothers self-reported either not drinking alcohol during pregnancy or drinking up to six units per week without binge drinking. Children's conduct problem trajectories were classified as low risk, childhood-limited, adolescence-onset or early-onset-persistent, using six repeated measures of the Strengths and Difficulties Questionnaire between ages 4-13 years. Variants of alcohol-metabolising genes in children were used to create an instrumental variable for Mendelian randomisation analysis., Results: Children's genotype scores were associated with early-onset-persistent conduct problems (OR = 1.29, 95% CI = 1.04-1.60, p = .020) if mothers drank moderately in pregnancy, but not if mothers abstained from drinking (OR = 0.94, CI = 0.72-1.25, p = .688). Children's genotype scores did not predict childhood-limited or adolescence-onset conduct problems., Conclusions: This quasi-experimental study suggests that moderate alcohol drinking in pregnancy contributes to increased risk for children's early-onset-persistent conduct problems, but not childhood-limited or adolescence-onset conduct problems., (© 2015 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: It remains uncertain whether exposure to lower doses of alcohol is damaging to the developing fetus. The present study aimed to investigate associations for boys and girls between prenatal exposure to binge drinking and lower doses of alcohol in pregnancy, and parent-reported behavioural and emotional development at age seven., Methods: This study used data from the Danish National Birth Cohort. Associations between cumulated alcohol exposure and binge drinking from full pregnancy and parent scores on the Strengths and Difficulties Questionnaire (SDQ) measured at age seven were investigated. The SDQ was used as continuous externalising/internalising scores, and as above/below cut-off for the specific scales of hyperactivity/inattention, conduct, emotional and peer problems. Inclusion criteria were information on alcohol exposure from three interviews, SDQ scores at age seven and being born full term (n=37 152)., Results: Controlling for relevant confounders, small positive associations were observed between binge drinking and internalising (relative change in mean: 1.04-1.06), externalising scores (relative change in mean: 1.01-1.07), and conduct scores (OR 1.12 to 1.23) for boys. No associations were observed with lower doses of alcohol., Conclusions: Exposure to binge drinking is weakly associated with impaired behavioural and emotional development measured at age seven. Large differences in background characteristics were observed between the groups defined by cumulated alcohol exposure, leaving the interpretations of findings uncertain.

Caffeine is the most widely used psychoactive substance in the world and currently the only one legally available to children and adolescents. The sale and use of caffeinated beverages has increased markedly among adolescents during the last decade. However, research on caffeine use and behaviors among adolescents is scarce. We investigate the relationship between adolescent caffeine use and self-reported violent behaviors and conduct disorders in a population-based cross-sectional sample of 3,747 10th grade students (15-16 years of age, 50.2 % girls) who were enrolled in the Icelandic national education system during February 2012. Through a series of multiple regression models, while controlling for background factors, Attention Deficit Hyperactivity Disorder symptoms and current medication and peer delinquency, and including measures on substance use, our findings show robust additive explanatory power of caffeine for both violent behaviors and conduct disorders. In addition, the association of caffeine to the outcomes is significantly stronger for girls than boys for both violent behaviors and conduct disorders. Future studies are needed to examine to what extent, if at all, these relationships are causal. Indication of causal connections between caffeine consumption and negative outcomes such as those reported here would call into question the acceptability of current policies concerning the availability of caffeine to adolescents and the targeting of adolescence in the marketing of caffeine products.

Background: Prenatal exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) has been associated with impaired performance on attention tasks in previous studies, but the extent to which these cognitive deficits translate into behavioral problems in the classroom and attention deficit/hyperactivity disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood has been associated with ADHD and disruptive behaviors in several studies., Objectives: In this study we examined the relation of developmental exposure to MeHg, PCBs, and Pb to behavioral problems at school age in Inuit children exposed through their traditional diet., Methods: In a prospective longitudinal study conducted in the Canadian Arctic, exposure to contaminants was measured at birth and at school age. An assessment of child behavior (n = 279; mean age = 11.3 years) was obtained from the child's classroom teacher on the Teacher Report Form (TRF) from the Child Behavior Checklist, and the Disruptive Behavior Disorders Rating Scale (DBD)., Results: Cord blood mercury concentrations were associated with higher TRF symptom scores for attention problems and DBD scores consistent with ADHD. Current blood Pb concentrations were associated with higher TRF symptom scores for externalizing problems and with symptoms of ADHD (hyperactive-impulsive type) based on the DBD., Conclusions: To our knowledge, this study is the first to identify an association between prenatal MeHg and ADHD symptomatology in childhood and the first to replicate previously reported associations between low-level childhood Pb exposure and ADHD in a population exposed to Pb primarily from dietary sources.

Background and Objective: Human studies that have investigated the association between caffeine intake during pregnancy and offspring's behavioral outcomes are scant and inconclusive. We prospectively investigated the association between maternal caffeine intake during pregnancy and children's problem behavior at age 5 to 6 years. Mediation by fetal growth restriction and gestational age as well as effect modification by the child's gender and maternal smoking was tested., Methods: In a community based multiethnic birth cohort, dietary caffeine intake (coffee, caffeinated tea, and cola) was measured (maternal self-report, n = 8202) around the 16th week of gestation. At age 5, children's overall problem behavior, emotional problems, conduct problems, hyperactivity/inattention problems, peer relationship problems, and prosocial behavior were rated by both mother and teacher (n = 3439) with the Strengths and Difficulties Questionnaire. Analyses were adjusted for maternal age, ethnicity, cohabitant status, education, smoking and alcohol consumption during pregnancy, child's gender, family size, and prenatal maternal anxiety., Results: Caffeine intake was not associated with a higher risk for behavior problems or with suboptimal prosocial behavior. No evidence was found for mediation by fetal growth restriction or gestational age, nor for effect modification by the child's gender., Conclusions: Results did not provide evidence for developmental programming influences of intrauterine exposure to caffeine on offspring's problem behavior at age 5. Present results give no indication to advise pregnant women to reduce their caffeine intake to prevent behavior problems in their children.

Unlabelled: Optimal methods to predict risk of aberrant drug-related behaviors before initiation of opioids for chronic noncancer pain and to identify aberrant behaviors after therapy is initiated are uncertain. We systematically reviewed published literature identified through searches of Ovid MEDLINE and the Cochrane databases through July 2008. Diagnostic test characteristics and accompanying confidence intervals were calculated with data extracted from the studies. Four prospective studies evaluated diagnostic accuracy of risk prediction instruments. Two higher-quality derivation studies found that high scores on the Screener and Opioid Assessment for Patients with Pain (SOAPP) Version 1 and the Revised SOAPP (SOAPP-R) instruments weakly increased the likelihood for future aberrant drug-related behaviors (positive likelihood ratios [PLR], 2.90 [95% CI, 1.91 to 4.39] and 2.50 [95% CI, 1.93 to 3.24], respectively). Low scores on the SOAPP Version 1 moderately decreased the likelihood for aberrant drug-related behaviors (negative likelihood ratio [NLR], 0.13 [95% CI, 0.05 to 0.34]) and low scores on the SOAPP-R weakly decreased the likelihood (NLR, 0.29 [95% CI, 0.18 to 0.46]), but estimates are too imprecise to determine if there is a difference between these instruments. One lower-quality study found that categorization as high risk using the Opioid Risk Tool strongly increased the likelihood for future aberrant drug-related behaviors (PLR, 14.3 [95% CI, 5.35 to 38.4]) and classification as low risk strongly decreased the likelihood (PLR, 0.08 [95% CI, 0.01 to 0.62]). Nine studies evaluated monitoring instruments for identification of aberrant drug-related behaviors in patients on opioid therapy. One higher-quality derivation study found higher scores on the Current Opioid Misuse Measure (COMM) weakly increased the likelihood of current aberrant drug-related behaviors (PLR, 2.77 [95% CI, 2.06 to 3.72]) and lower scores weakly decreased the likelihood (NLR, 0.35 [95% CI, 0.24 to 0.52]). In 8 studies of other monitoring instruments, diagnostic accuracy was poor, results were difficult to interpret due to methodological shortcomings, or standard diagnostic test characteristics were not reported. Definitions for aberrant drug-related behaviors were not standardized across studies and did not account for seriousness of identified behaviors. No reliable evidence exists on accuracy of urine drug screening, pill counts, or prescription drug monitoring programs; or clinical outcomes associated with different assessment or monitoring strategies., Perspective: Evidence on prediction and identification of aberrant drug-related behaviors is limited. Although several screening instruments may be useful, evidence is sparse and primarily based on derivation studies, and methodological shortcomings exist in all studies. Research that performs external validation, uses standardized definitions for clinically relevant aberrant drug-related behaviors, and evaluates clinical outcomes associated with different assessment and monitoring strategies is needed.

Objective: The purpose of this study was to examine the association of tobacco smoke and environmental lead exposure with conduct disorder (CD)., Methods: The National Health and Nutrition Examination Survey (NHANES) 2001-2004 is a nationally representative cross-sectional sample of the noninstitutionalized U.S. population. We examined the association of prenatal tobacco, postnatal tobacco, and environmental lead exposure with CD in children 8-15 years of age (n = 3,081). We measured prenatal tobacco exposure by parent report of cigarette use during pregnancy, and postnatal tobacco using serum cotinine levels. We assessed lead exposure using current blood lead concentration. Parents completed the Diagnostic Interview Schedule for Children to determine whether their children met criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV ) for CD., Results: Overall, 2.06% of children met DSM-IV criteria for CD in the past year, equivalent to 560,000 U.S. children 8-15 years of age. After adjustment, prenatal tobacco exposure was associated with increased odds for CD [odds ratio (OR) = 3.00; 95% confidence interval (CI), 1.36-6.63]. Increased blood lead levels (fourth vs. first quartile) and serum cotinine levels (fifth vs. first quintile) were associated with an 8.64-fold (95% CI, 1.87-40.04) and 9.15-fold (95% CI, 1.47-6.90) increased odds of meeting DSM-IV CD criteria. Increasing serum cotinine levels and blood lead levels were also associated with increased prevalence of CD symptoms (symptom count ratio, lead: 1.73; 95% CI, 1.23-2.43; symptom count ratio, cotinine: 1.97; 95% CI, 1.15-3.40)., Conclusions: These results suggest that prenatal tobacco exposure and environmental lead exposure contribute substantially to CD in U.S. children.

As atypical antipsychotics are increasingly used in the treatment of childhood behavioural disorders either as monotherapy or in combination with other medications, there is a need to know more about their safety, in particular during switching to and from methylphenidate treatment, as antipsychotics and methylphenidate have opposing effects on dopaminergic neurotransmission. This report is about three cases of children who developed severe adverse reactions during switching from risperidone to methylphenidate. The first patient was a 6-year-old boy, diagnosed with attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). He developed severe hyperactivity and agitation on taking methylphenidate after the discontinuation of risperidone treatment. The second patient was a girl of 6, already on risperidone for ADHD and borderline intellectual functioning when referred. She displayed severe hyperactivity, agitation and irritability upon switching to methylphenidate medication. The third patient was a 15-year-old female adolescent with a similar clinical course as the previous patients. In all the cases described here, it is only with the discontinuation of methylphenidate that the adverse reactions resolved and readministration of methylphenidate in two patients did not produce any adverse effect after a drug-free interval. Functional regulation of certain neuroreceptors during risperidone treatment may lead to altered behavioural responses upon switching to methylphenidate. Thus, a drug-free interval is recommended in order to prevent adverse reactions.

Background: Little is known about the characteristics of people with intellectual disabilities (IDs) who misuse substances and how such problems impinge upon their well-being. The aim of this paper is to describe how alcohol and drugs affect the health of people with IDs., Methods: A questionnaire was forwarded to all the community ID teams and mainstream addiction teams across Northern Ireland: 67 substance users with IDs and substantial substance-related problems were identified., Results: Alcohol was found to be the main substance to be misused, with one-fifth of the substance users also found to be using a combination of illicit drugs and/or prescribed medication. Nearly three-quarters of the sample were found to be hazardously using alcohol for more than 5 years. Being male and young, having a borderline/mild ID, living independently and having a mental health problem were found to be risk factors for developing a 'substance related problem'. Various problematic behaviours were identified, including aggression, erratic mood changes, sexual exploitation, difficulties in maintaining relationships and loss of daily routine., Conclusions: The findings of this study suggest that greater emphasis needs to be placed upon the early identification of this hidden population by primary and secondary healthcare personnel, and also ID personnel. Such early identification may also diminish the long-established patterns of use and associated related-behaviours that have been reported within this paper.

Adverse effects of benzodiazepines are well known since the first one was used in 1958 (chlordiazepoxide). The literature collects study-cases or rarely controlled studies concerning side effects or paradoxical reactions to benzodiazepines. They mostly described drowsiness and behavioral disinhibition, including increased well-being feeling but also hostility, rage access with feeling of invulnerability, serious crimes and sometimes homicides. Delusional, manic, confusional or depressive states are also pointed out. Rate for aggressive behaviour is 0.3 to 0.7% but distinction should be done between accidental or "idiosyncratic" reaction and voluntary sought disinhibition, clearly more frequent. No benzodiazepine has any specificity for these adverse effects but pharmacology, doses, associated drugs (or alcohol) and psychopathology interact to produce hazardous psychic states. Pharmacology: GABA induces a decrease in serotonin compound and vigilance. Pharmacokinetic: first dose effect or over-dose effect, short half-life, lipophily, affinity, digestive absorption, active metabolites interact. Psychopathology: age, alcohol association, psychological status (high initial level of hostility, impulsivity, frustration, personality disorder and depressive status). External conditions: chronic illness, affective and professional frustrations, physical or psychic exhaustion contribute also. Some benzodiazepines (flunitrazepam, diazepam, clorazepate, triazolam, alprazolam, lorazepam, for example) are more often concerned for pharmacokinetics characteristics but also prescription habits. Forensic aspects should be considered in case of homicide. Especially, reality of benzodiazepines consumption and awareness of the potential paradoxical reaction should be precisely evaluated. Special focus on voluntary induced disinhibition has to be done for forensic considerations. Relationship but also crime facilitations are sometimes consciously sought. Some benzodiazepines have already been identified for this use: flunitrazepam, clorazepate but also triazolam and temazepam in UK, alprazolam in USA. Flunitrazepam is prohibited in USA and considered as narcotics in France. A Swedish study showed that violent acts were more frequent and serious in juvenile offenders taking flunitrazepam/alcohol than other young offenders staying in the same correctional institution. They recommended classification of flunitrazepam as narcotic. A study from Belgium with drug addicts concluded in the same way and asked for an increased information of professionals and a more efficient control of the delivery. Before concluding to idiosyncratic effect, and then possibly to penal irresponsibility, the forensic approach should consider: firstly the reality of the benzodiazepines absorption and implication in committing violence (urine test, chronology, amnesia); secondly, the association of unusual behaviour and converging circumstances (pharmacological, pharmacokinetic, psychopathology, external conditions); thirdly the consumer's knowledge of the disinhibition effect. In our prison practice, we have to be particularly cautious as population frequently associates personality disorder, drug addiction and high level of frustration related to penitential context. Special information should be given to inmates when benzodiazepines are prescribed, but more extensively, a preventive strategy should be adopted in general population.