Neurobiological and behavioral stress reactivity in children prenatally exposed to tobacco.

This study examined neurobiological and behavioral stress reactivity in children who had been prenatally exposed to tobacco. Neurobiological stress reactivity was measured using salivary cortisol and alpha-amylase levels at five different time points throughout a stressful neuropsychological test session, which involved a competition against a videotaped opponent. Participants (mean age: 10.6 years, SD 1.3) were 14 prenatally exposed (PE) children, 9 children with disruptive behavior problems (DBD), and 15 normal controls (NC). For cortisol responses, no significant differences between the three groups were observed. Normal controls, however, had significantly higher alpha-amylase levels than PE-children throughout the test session, and their alpha-amylase levels also increased throughout the session, whereas these remained low and stable for PE-children. Alpha-amylase levels and trajectory of PE-children were similar to those observed for DBD-children. PE-children also showed significantly increased behavioral stress reactivity compared to NC-children, and neurobiological and behavioral stress reactivity were inversely related in PE-children, again similar to what was observed for DBD-children. These results support the hypothesis that prenatal smoking may lead to long-lasting neurobiological and behavioral changes in exposed offspring.

Social information processing in children and adolescents with neurofibromatosis type 1.

AIM: To examine social information processing in children and adolescents with neurofibromatosis type 1 (NF1). METHOD: Thirty-two children with NF1 (12 males, 20 females; mean age 12y 4mo, SD 4y) and 32 comparison children (12 males, 20 females; mean age 13y 1mo, SD 3y 11mo) completed face recognition, identification of facial emotions (IFE), and matching facial emotions (MFE) tasks. A series of general linear model analyses of variance were used to compare performance between children with NF1 and comparison children. RESULTS: Children with NF1 performed less accurately than comparison children in the face recognition task when faces were presented 'in profile' (p=0.05), when fearful expressions had to be identified in IFE (p=0.017), and across conditions in MFE (p=0.009). When quality of cognitive control (i.e. mean standardized scores on tasks measuring working memory and inhibitory control) was introduced to the analyses, differences in face recognition were no longer significant and differences in MFE were largely reduced (p=0.048). Differences in IFE between the comparison group and children with NF1 remained largely intact (fear: p=0.047). INTERPRETATION: Children with NF1 have problems in social information processing, which, in part, appear to be caused by cognitive control deficits. Some of the deficits, however, appear to be caused by deficient bottom-up processing of social signals (e.g. fear recognition).

Hot and cool forms of inhibitory control and externalizing behavior in children of mothers who smoked during pregnancy: an exploratory study.

This study examined whether children exposed to prenatal smoking show deficits in "hot" and/or "cool" executive functioning (EF). Hot EF is involved in regulation of affect and motivation, whereas cool EF is involved in handling abstract, decontextualized problems. Forty 7 to 9-year-old children (15 exposed to prenatal smoking, 25 non-exposed) performed two computerized tasks. The Sustained Attention Dots (SA-Dots) Task (as a measure of "cool" inhibitory control) requires 400 non-dominant hand and 200 dominant hand responses. Inhibitory control of the prepotent response is required for dominant hand responses. The Delay Frustration Task (DeFT) (as a measure of "hot" inhibitory control) consists of 55 simple maths exercises. On a number of trials delays are introduced before the next question appears on the screen. The extent of response-button pressing during delays indicates frustration-induced inhibitory control. Prenatally exposed children showed poorer inhibitory control in the DeFT than non-exposed children. A dose-response relationship was also observed. In addition, prenatally exposed children had significantly higher (dose-dependent) conduct problem- and hyperactivity-inattention scores. There were no significant group differences in inhibitory control scores from the SA-Dots. These results indicate that children exposed to prenatal smoking are at higher risk of hot but not cool executive function deficits.

Family-genetic study of executive functioning in attention-deficit/hyperactivity disorder: Evidence for an endophenotype?

This study examined familiality of attentional control and mental flexibility in multiplex attention-deficit/hyperactivity disorder (ADHD) families. The authors hypothesized that siblings of ADHD probands, although not behaviorally expressing ADHD, have deficits in these executive functions and that the performance of probands, unaffected siblings, and control participants are on a continuum. Participants (aged 6 to 17) were 25 ADHD probands with a family history of ADHD, their 25 unaffected siblings, and 48 control participants. The unaffected siblings did not differ from the ADHD probands on attentional control or on some measures of mental flexibility. Linear changes in performance across the groups reflected an intermediate position of the unaffected siblings between the probands and control participants. These results suggest that these executive functions may be suitable endophenotypes of ADHD.

Sustained attention and executive functioning performance in attention-deficit/hyperactivity disorder.

The aim of this study was to further refine the cognitive phenotype of attention-deficit/hyperactivity disorder (ADHD), with respect to the ability to sustain attention and executive functioning. Participants were 34 boys with ADHD (combined type) and 28 normal controls. The groups were closely matched for age and IQ. All participants were 12 years of age. Both groups performed a computerized sustained attention task and a response interference task. Measures related to speed, accuracy, and time on task were collected. We found that children with ADHD performed slower, less accurately, more impulsively, and with less stability than controls. Both groups produced more errors with increasing time on task, reflecting reduced vigilance. Importantly, no interaction with time on task was found. The overall pattern of results suggests that measures related to accuracy are more informative than measures related to speed of responding in refining the cognitive phenotype of ADHD.

Motor flexibility problems as a marker for genetic susceptibility to attention-deficit/hyperactivity disorder.

BACKGROUND: Since many children with attention-deficit/hyperactivity disorder (ADHD) have fine visuomotor problems that are already evident at a young age, motor dysfunctioning is investigated in family-genetic perspective. We hypothesized that if fine motor problems may be a marker for genetic susceptibility to ADHD, nonaffected siblings of ADHD probands would experience motor problems similar to those of their ADHD siblings. METHODS: Twenty-five carefully phenotyped ADHD probands with a family history of ADHD, their nonaffected siblings (n = 25), and 48 normal control subjects (aged 6 to 17) completed a motor fluency task and a motor flexibility task. The motor fluency task involved completion of a familiar, automatized trajectory, whereas the motor flexibility task required continuous adjustment of movement to complete an unpredictable random trajectory. RESULTS: On the motor fluency task, the performance of the nonaffected children was significantly better than that of the ADHD probands; strikingly, on the motor flexibility task, they performed as well as their ADHD siblings. CONCLUSIONS: Nonaffected siblings experience complex motor problems similar to their ADHD siblings but only in nonautomatized movements that require controlled processing. The results suggest that higher-order controlled motor deficits in ADHD may be associated with genetic susceptibility for ADHD.

Familial clustering of executive functioning in affected sibling pair families with ADHD.

OBJECTIVE: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. METHOD: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the Stroop test, go/no-go task, two different fine visuomotor tracking tasks, and a sustained-, divided-, and focused attention task. RESULTS: Significant correlations (r = 0.4) were found between siblings for response inhibition and attentional control and for fine visuomotor skills that made high demands on executive functioning. CONCLUSIONS: Response inhibition, higher order controlled fine visuomotor functioning, and attentional control seem to cluster in ADHD-affected siblings. This suggests that these aspects of executive dysfunctioning may reflect an endophenotype of ADHD. Measurement of these executive functions may facilitate the identification of genes involved in ADHD by forming more homogeneous subgroups.

Executive functioning in children: a comparison of hospitalised ODD and ODD/ADHD children and normal controls.

BACKGROUND: Deficits in executive functioning are supposed to have a predisposing influence on impulsive or aggressive behaviour. We tested the hypothesis that oppositional-defiant disorder (ODD) children with or without attention deficit hyperactivity disorder (ADHD) have problems in executive functioning. METHOD: Seventy-seven 7- to 12-year-old children (15 ODD, 26 ODD/ADHD, and 36 normal controls), all with normal IQ, completed 7 neuropsychological measures of executive functioning, assessing the abilities of set shifting, planning, working memory, inhibition/attention, and impulsivity. Some of these tasks involved the possibility of monetary rewards with a view to testing the prediction of a specific motivational inhibitory deficit. RESULTS: We found no evidence of deficits in working memory, planning, inhibition, or impulsivity. However, the ODD/ADHD group was worse than the normal control (NC) group in set shifting, and both the ODD and ODD/ADHD groups performed worse on a response perseveration task. Moreover, on the basis of one variable derived from a motivational inhibition task, 77% of the children could be correctly classified as ODD or NC. CONCLUSIONS: The findings do not support the hypothesis that ODD and ODD/ADHD children have a deficit in executive inhibitory control; rather, they emphasise that they have problems in regulating their behaviour under motivational inhibitory conditions.

Deficient response inhibition as a cognitive endophenotype of ADHD.

OBJECTIVE: To investigate whether a deficient response inhibition is a cognitive endophenotype of attention-deficit/hyperactivity disorder (ADHD). The authors hypothesized that nonaffected siblings of ADHD probands would have a response inhibition between that of ADHD probands and normal controls, although they resembled the controls at a behavioral level. METHOD: Participants were 25 ADHD probands with a family history of ADHD, their nonaffected siblings (n = 25), and 48 normal controls matched for age and IQ. All participants were between 6 and 17 years of age. The nonaffected siblings were compared with their ADHD siblings and with controls on measures reflecting different types of response inhibition. RESULTS: The nonaffected siblings had results similar to those of the ADHD probands, who differed from the controls on all inhibition measures (p <.05). CONCLUSIONS: Siblings of ADHD probands, while not behaviorally expressing the disorder, have ADHD-associated deficits in response inhibition. This suggests that subtyping based on measures of response inhibition can help identify genetic susceptibility to ADHD. Children with a genetic vulnerability to ADHD may have hidden cognitive deficits in the absence of manifest behavioral symptoms. Therefore, they should be monitored to detect possible learning problems.