Behavioral inhibition and disinhibition as hypothesized precursors to psychopathology: implications for pediatric bipolar disorder.

Attention has been devoted over the past two decades to the identification of temperamental risk factors for child psychopathology. These qualities, evident in toddlerhood or earlier, have the advantage of being measurable in standardized laboratory observations well before children reach the age of onset or diagnosis of psychiatric disorders. Our group's programmatic research over the past 15 years, and that of others, has provided evidence linking "behavioral inhibition to the unfamiliar" in toddlerhood or early childhood with later social anxiety disorder. In addition, recent results by our group have suggested that "behavioral disinhibition" in early childhood, measured by the same laboratory methods, may be linked with later disruptive behavior and comorbid mood disorders. In this article, we discuss our approach to the study of temperamental precursors to disorders in high-risk children, summarize the literature linking behavioral inhibition and disinhibition to later psychopathology, and suggest directions to take in applying this methodology to the search for temperamental precursors to pediatric bipolar disorder.     

Efficacy of a multimodal treatment for disruptive behavior disorders in children and adolescents: Focus on internalizing problems

Disruptive Behavior Disorders (DBDs) are among the most common reasons for youth referrals to mental health clinics. Aim of this study is to compare short and medium term efficacy of a multimodal treatment program (MTP), compared to community care (treatment-as-usual, TAU). The sample included 135 youths with DBDs (113 males, age range 9–15 years, mean age 12±2.5 years) were assigned either to a MTP (n=64), or addressed to community care for a TAU (n=71). Outcome measures were the Child Behaviour Checklist (CBCL) and the Children?s Global Assessment Scale (C-GAS). All subjects were assessed at the baseline (T0), after 1-year treatment (T1) and after a 2-year follow-up (T2). Compared with patients receiving TAU, youths in the MTP showed, both at T1 and T2, significantly lower scores on CBCL Externalizing Scale, Internalizing Scale, Anxious/Depressed, Social Problems, and Aggressive Behavior, and higher scores at the C-GAS. Improvement in Internalizing Scales was particularly evident, with a shift from the clinical to the non-clinical range. Rate of use of mental health services and scholastic failure were reduced in the MTP. It is suggested that the improvement of the Internalizing symptoms is a crucial component of the therapeutic process in this MTP.     

Clinical outcomes of laboratory-observed preschool behavioral disinhibition at five-year follow-up.

BACKGROUND: Behavioral disinhibition refers to a temperamental tendency to exhibit boldness, approach, and spontaneity in unfamiliar situations. We previously found it to be associated with childhood disruptive behavior and mood disorders, as well as with parental bipolar disorder. In the present study, our objective was to examine the diagnostic outcome in middle childhood of behavioral disinhibition assessed at preschool age among offspring at risk for anxiety and mood disorders. METHODS: The sample consisted of 284 children, including offspring of parents with panic disorder or major depression and comparison offspring of parents without these disorders, who had been assessed with laboratory observations of temperament at ages 21 months to 6 years. We reassessed 215 of the children (77%) at 5-year follow-up (mean age 9.6 years) with structured diagnostic interviews. RESULTS: Compared with noninhibited, nondisinhibited control subjects, behaviorally disinhibited children had higher lifetime rates of comorbid mood plus disruptive behavior disorders and higher current rates of any disruptive behavior disorder and of oppositional defiant disorder. CONCLUSIONS: Behavioral disinhibition appears to be a temperamental antecedent of disruptive behavior disorders and their comorbidity with mood disorders in middle childhood, which may be targeted for preventive intervention.     

Psychometric study of the test of variables of attention: preliminary findings on Taiwanese children with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common mental disorder in children. Unfortunately, reliable means of measuring attention and impulsivity to help with diagnoses are scarce. The test of variables of attention (TOVA) is a computer-administered continuous performance test measuring attention and impulsivity, designed to avoid confounding arising from language processing skills or short-term memory problems. Some evidence has indicated the TOVA can be useful in diagnosing ADHD. This study examines its validity and reliability in helping diagnose Taiwanese ADHD children. The study included 31 ADHD children (24 males, seven females) from a northern Taiwan children's hospital and 30 normal controls (18 males, 12 females) from the local community. The TOVA and the Child Behavior Checklist (CBCL) were administered to all children. TOVA scores for omissions, commissions, response time, response time variability, D' and ADHD scores were analyzed. Results showed a mean internal consistency of 0.81 for all six TOVA variables across conditions, with moderate convergent and discriminant validities. Groups showed significant differences in response time variability, D' and ADHD scores, with the normal group outperforming the ADHD group. Significant group differences were also found in all CBCL subscale scores except somatic complaints. The ADHD group obtained a clinically significant score on the hyperactivity subscale of the CBCL. The findings partially support the usefulness of the TOVA in assessing attention and impulsivity problems for a Taiwanese sample. Future studies should increase the sample size, use multiple measures, and collect behavior ratings from both parents and teachers.     

New medication strategies for comorbid substance use and bipolar affective disorders.

Comorbidity of substance abuse disorders (SUD) with bipolar disorders (BPD) is a serious treatment problem. Childhood BPD can be further complicated by comorbidity with attention-deficit/hyperactivity disorder (ADHD) and later SUD during adolescence. The aim of this article is to review the literature on pharmacotherapies for these patients. Developing the ideal pharmacotherapy for BPD and SUD can be informed by the role of gamma-aminobutyric acid (GABA) in the neurobiology of SUD. This ideal pharmacotherapy would have several key characteristics. These characteristics include treating the BPD, relieving withdrawal symptoms, and preventing relapse to SUD. The ideal medication should have low abuse liability, require infrequent dosing, be well tolerated, and have few side effects. A medication approaching this ideal is the GABA enhancer valproate. Adding atypical antipsychotic agents might not improve valproate's efficacy, but combining GABA medications with selective serotonin reuptake inhibitors holds promise for SUD with depression. Pemoline might be the best option for minimizing the risk of SUD complicating comorbid ADHD with BPD.     

Comorbidity for disruptive behavior disorders in psychiatrically hospitalized children

A variety of instruments were used to compare six groups of inpatient children: pure attention deficit disorder with hyperactivity (ADDH), pure conduct disorder (CD), pure oppositional defiant disorder (OD), ADDH+CD, and ADDH+OD, and a clinical control group who had no DBD diagnosis. Children with ADDH and CD or OD exhibited a greater degree of psychopathology. Children with CD and OD were more similar than different, indicating that perhaps a continuum of pathology exists between these diagnostic classifications.     

Pubertal influences on neural activation during risky decision-making in youth with ADHD and disruptive behavior disorders

ObjectiveRisk-taking during adolescence is a leading cause of mortality; Neuroscience research examining pubertal effects on decision-making is needed to better inform interventions, particularly among youth with attention-deficit/hyperactivity (ADHD) and disruptive behavior disorders (DBD), who are particularly prone to risky decision-making. We examined effects of pubertal development on risky decision-making and neural activation during decision-making among youth with ADHD/DBDs.MethodForty-six 11–12-year-olds (29.4% girls; 54.9% white; Tanner M(SD) = 2.08(1.32)) who met DSM-5 criteria for ADHD/DBD completed the Balloon Analog Risk Task (BART) during fMRI scanning. We examined effects of Tanner stage, sex, and age on risky decision-making (mean wager at which individuals stopped balloon inflation) and neural activation in the middle frontal gyrus and the ventral striatum during the choice and outcome phases of decision-making.ResultsThose in earlier pubertal stages made riskier decisions during the BART compared to those in later Tanner stages (β=-0.62, p = .02). Later pubertal stage was associated with greater activation in the left middle frontal gyrus (β=0.61, p = .03) during the choice phase and in the right ventral striatum in response to rewards (β=0.59, p = .03).ConclusionYouth with ADHD/DBD in later stages of puberty, regardless of age, show greater ventral striatal activation in response to rewards.     

A cross-cultural comparison between samples of Brazilian and German children with ADHD/HD using the Child Behavior Checklist

Introduction This study aims to assess cross-cultural similarities and differences in broadband psychopathology in two naturalistic clinical samples of children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) combined type according to DSM-IV criteria or with Hyperkinetic Disorder (HD) according to ICD-10 criteria. Methods We compared two clinical samples of children with ADHD combined type (Brazil, N = 248) and HD (Germany; N = 154) to controls (Brazil N = 71; Germany N = 135) using the Child Behavior Checklist (CBCL). ROC-curves (Receiver Operating Characteristic) were determined to evaluate the discriminating validity of the CBCL Attention Problem scale. A two-factorial ANOVA was computed across all 8 scales of the CBCL. Results Although Brazilian parents reported significantly higher scores on all CBCL scales than German parents (P < 0.05), a similar CBCL profile was detected in both cultures. Conclusion Despite the use of different diagnostic systems (DSM-IV vs. ICD-10) and the presence of other clinical differences, the similar broadband psychopathological profile of the CBCL in the two samples provides evidence that dimensional symptoms associated with the categorical diagnosis of ADHD combined type might be comparable in two clinical settings with diverse cultural background.     

盐酸托莫西汀对注意缺陷多动障碍儿童行为特征的影响

目的:探讨托莫西汀能否改善注意缺陷多动障碍(ADHD)患儿的行为问题.方法:评价65例ADHD患儿(男56例,女9例)在托莫西汀治疗前及治疗4周、8周的行为问题.使用Conners父母症状问卷(PSQ)及长处与困难问卷(SDQ)进行评定.结果:与治疗前相比,PSQ中冲动多动因子及多动指数在治疗第4周及第8周后均有明显改...     

Gender differences in a clinic-referred sample of Taiwanese attention-deficit/hyperactivity disorder children

The purpose of this study was to examine gender differences within a clinic-referred sample of 6-11-year-old Taiwanese children with attention-deficit/hyperactivity disorder (ADHD)- combined subtype. The subjects were 21 girls with a diagnosis of ADHD from the 4th edition of the Diagnostic and Statistical Manual and 21 age-matched boys with ADHD. Comparisons were made of behavioral ratings, cognitive profiles, and vigilance/attention assessments between these two groups. The results found ADHD girls and ADHD boys to be statistically indistinguishable on nearly all measures except the subtests of block design (P = 0.016), the discrepancy between Performance Intelligence Quotient and Verbal Intelligence Quotient (P = 0.019), and the discrepancy between fluid and crystallized IQ (P = 0.041). In the study samples, ADHD girls and ADHD boys were strikingly similar on a wide range of measures. ADHD boys and girls in clinics may be expected to show more similarities than differences in treatment needs. However, these results should be interpreted with caution since data were only from clinic-referred samples.     

Disruptive behavior disorders in children and adolescents with autism spectrum disorders: A review of the prevalence,presentation, and treatment

Children and adolescents with autism spectrum disorders (ASDs) often exhibit behaviors consistent with a disruptive behavior disorder (DBD) such as oppositional defiant disorder (ODD) or conduct disorder (CD). Understanding the relationship between ASDs and DBDs has important implications for clinicians and researchers. We reviewed 55 peer-reviewed articles published between 2000 and 2012 on the prevalence, phenomenology, or psychosocial treatments of DBDs in youth with ASDs. Prevalence estimates vary between 4% and 37% for ODD and 1% and 10% for CD. On the whole, approximately one in four children with an ASD meets diagnostic criteria for either ODD or CD. Most research on phenomenology has focused on distinguishing between DBDs and ASDs, rather than examining their co-occurrence. After the preschool years, the disorders can be reliably distinguished, but certain behaviors are more common among those with ASDs compared to their non-ASD counterparts. If one excludes medication trials and single-subject designs, there have been few treatment studies on DBDs in ASDs. Parent training has been the primary mode of psychosocial treatment and has some support for its efficacy. Overall, when it comes to DBDs, there has been a dearth of research using DSM-nosology in youth with ASDs.     

Sex differences in medial prefrontal and parietal cortex structure in children with disruptive behavior

Sex differences in brain structure in children with disruptive behavior disorders (DBD) remain poorly understood. This study examined sex differences in gray matter volume in children with DBD in a priori regions-of-interest implicated in the pathophysiology of disruptive behavior. We then conducted a whole-brain analysis of cortical thickness to examine sex differences in regions not included in our hypothesis. Exploratory analyses investigated unique associations between structure, and dimensional measures of severity of disruptive behavior and callous-unemotional traits. This cross-sectional study included 88 children with DBD (30 females) aged 8–16 years and 50 healthy controls (20 females). Structural MRI data were analyzed using surface-based morphometry to test for interactions between sex and group. Multiple-regression analyses tested for sex-specific associations between structure, callous-unemotional traits, and disruptive behavior severity. Boys with DBD showed reduced gray matter volume in the left ventromedial prefrontal cortex (vmPFC) and reduced cortical thickness in the supramarginal gyrus, but not girls compared to respective controls. Dimensional analyses revealed associations between sex, callous-unemotional traits, and disruptive behavior for amygdala and vmPFC volume, and ventrolateral prefrontal cortex cortical thickness. Sex-specific differences in prefrontal structures involved in emotion regulation may support identification of neural biomarkers of disruptive behavior to inform target-based treatments.     

Inhibitory deficits in ocular motor behavior in adults with attention-deficit/hyperactivity disorder.

BACKGROUNDS: Many of the symptoms of attention-deficit/hyperactivity disorder (ADHD) have been attributed to deficits in behavioral inhibition mediated by the frontostriatal system. The ability to suppress unwanted saccadic eye movements is mediated by prefrontal cortex-basal ganglia circuitry and thus constitutes a useful measure of inhibitory ability. METHODS: To evaluate the functional integrity of this circuitry in ADHD, adult ADHD subjects unmedicated for at least 48 hours and normal comparison adults were studied by means of a comprehensive battery of ocular motor paradigms. RESULTS: On a prosaccade task, in which subjects were required to generate saccades toward a peripheral visual target after a short stimulus-free interval, ADHD subjects generated significantly more of anticipatory (premature) saccades (reaction time <90 msec) and of saccades toward the target on catch trials, in which they were supposed to inhibit eye movements. On the antisaccade task, in which they were required to inhibit gazing toward the target while moving their eyes in the opposite direction, ADHD subjects made significantly more directional errors than normal adults. The performance of ADHD adults was consistent with deficits in saccadic inhibition. CONCLUSIONS: Given the recent evidence for the interdependence between the brain systems mediating visual attention and ocular motor behavior, these findings support the notion that deficits in inhibitory mechanisms might underlie the inattention characteristic of ADHD. These results also implicate abnormalities in prefrontal cortex-basal ganglia circuitry in ADHD.     

Cluster analysis of child behavior checklists of 6 to 11-year-old males with varying degrees of behavior disorders

Achenbach Child Behavior Checklist ratings were collected on boys aged 6 to 11 years screened as not having significant behavior problems, as clinic-referred boys, and as boys diagnosed as having Attention Deficit-Hyperactivity Disorder alone or together with Oppositional-Defiant Disorder or Conduct Disorder. Cluster analysis resulted in a classification system related to DSM-III-R classification of the boys and parent self-report of mildly antisocial acts. Clusters also enhanced the ability of the instrument to detect Attention Deficit Hyperactivity Disorder and disruptive behavior disorders.     

Childhood histories of attention-deficit hyperactivity disorders in Japanese methamphetamine and inhalant abusers: preliminary report

The present study examined childhood histories of attention-deficit hyperactivity disorder (ADHD) in 54 methamphetamine and 12 inhalant abusers using the Wender Utah Rating Scale. The inhalant abusers experienced initial drinking at a younger age than methamphetamine abusers (P=0.038). The Wender Utah Rating Scale score was significantly higher in the inhalant abusers than in the methamphetamine abusers (P=0.013) although 83.3% of inhalant and 55.6% of methamphetamine abusers had higher scores than the cut-off for ADHD. These findings suggest that drug abuse is associated with childhood ADHD, and that inhalant abusers have a higher incidence of childhood ADHD than methamphetamine abusers.