Faculty Bibliography

Reports an error in 'Efficacy and Safety of Immediate-Release Methylphenidate Treatment for Preschoolers With ADHD' by Laurence Greenhill, Scott Kollins, Howard Abikoff, James McCracken, Mark Riddle, James Swanson, James McGough, Sharon Wigal, Tim Wigal, Benedetto Vitiello, Anne Skrobala, Kelly Posner, Jaswinder Ghuman, Charles Cunningham, Mark Davies, Shirley Chuang and Tom Cooper (Journal of the American Academy of Child & Adolescent Psychiatry, 2006[Nov], Vol 45[11], 1284-1293). The first sentence of the third paragraph of the Results section is incorrect (p. 1289). The sentence should read, 'For those preschoolers who completed titration (N = 147), blind ratings classified 7 (5%) preschoolers as nonresponders; 14 (10%) as placebo nonresponders; 24 (16%) as best responding to 1.25 mg t.i.d. (0.2 mg/kg/day); 26 (18%) as best responding to 2.5 mg t.i.d. (0.4 mg/kg/day); 30 (20%) as best responding to 5.0 mg t.i.d. (0.8 mg/kg/day); 36 (24%) as best responding to 7.5 mg t.i.d. (1.2 mg/kg/day); 7 (5%) as best responding to 10 mg t.i.d. (1.3 mg/kg/day); and 3 (2%) as having insufficient data.' (The following abstract of the original article appeared in record 2006-20746-002.) Objective: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). Method: The 8-phase, 70-week PATS protocol included two double-blind, controlled phases, a crossover-titration trial followed by a placebo-controlled parallel trial. The crossover-titration phase's primary efficacy measure was a combined score from the Swanson, Kotkin, Atkins, M-Flynn, and Pelham (SKAMP) plus the Conners, Loney, and Milich (CLAM) rating scales; the parallel phase's primary outcome measure was excellent response, based on composite scores on the Swanson, Nolan, and Pelham (SNAP) rating scale. Results: Of 303 preschoolers enrolled, 165 were randomized into the titration trial. Compared with placebo, significant decreases in ADHD symptoms were found on MPH at 2.5 mg (p < .01), 5 mg (p < .001), and 7.5 mg (p < .001) t.i.d. doses, but not for 1.25 mg (p < .06). The mean optimal MPH total daily dose for the entire group was 14.2 +or- 8.1 mg/day (0.7 +or- 0.4 mg/kg/day). For the preschoolers (n = 114) later randomized into the parallel phase, only 21% on best-dose MPH and 13% on placebo achieved MTA-defined categorical criterion for remission set for school-age children with ADHD. Conclusions: MPH-IR, delivered in 2.5-, 5-, and 7.5-mg doses t.i.d., produced significant reductions on ADHD symptom scales in preschoolers compared to placebo, although effect sizes (0.4-0.8) were smaller than those cited for school-age children on the same medication.

Infant joint attention has been observed to be related to social-emotional outcomes in at-risk children. To address whether this relation is also evident in typically developing children, 52 children were tested at 12, 15, 24, and 30 months to examine associations between infant joint attention and social outcomes. Twelve-month initiating and responding to joint attention were related to 30-month social competence and externalizing behavior, even when accounting for 15-month temperament ratings, 24-month cognition and language, and demographic variables. These results suggest that, in addition to associations with language and cognition, infant joint attention reflects robust aspects of development that are related to individual differences in the emergence of social and behavioral competence in childhood

OBJECTIVE: Conduct a randomized trial to test whether a cognitive behavioral intervention designed to decrease depressive symptoms produces subsequent decreases in bulimic and substance use symptoms. METHOD: Female participants (N = 145) with elevated depressive symptoms were randomly assigned to a 4-session depression intervention or a measurement-only condition and assessed through 6-month follow-up. RESULTS: Relative to control participants, intervention participants showed decreases in depressive symptoms. Intervention participants also showed significantly greater reductions in bulimic symptoms, but not substance use, and change in depressive symptoms mediated this effect for bulimic symptoms. CONCLUSION: The results provide experimental support for the theory that affect disturbances contribute to bulimic pathology, but do not support the affect regulation theory of substance use.

Serotonin reuptake inhibitors may increase symptoms of anxiety immediately following treatment initiation. The present study examined whether acute citalopram increased fear-potentiated startle to predictable and/or unpredictable shocks in healthy subjects. Eighteen healthy subjects each received two treatments, placebo and 20 mg citalopram in a crossover design. Participants were exposed to three conditions including one in which predictable aversive shocks were signaled by a cue, a second in which unpredictable shocks were anticipated, and a third in which no shocks were administered. Changes in aversive states were investigated using acoustic startle stimuli. Citalopram did not affect baseline startle. However, the phasic startle potentiation to the threat cue in the predictable condition was robustly increased by acute citalopram. The sustained startle potentiation in the unpredictable conditions was also increased by citalopram, but only when the drug was given during the first session. These results indicate that a single dose of citalopram is not anxiogenic in itself, but can exacerbate the expression of fear and anxiety.

CONTEXT: Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. OBJECTIVE: To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Fifteen adolescents with generalized anxiety disorder and 20 controls. MAIN OUTCOME MEASURES: Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention. RESULTS: While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P<.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex. CONCLUSIONS: This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.

OBJECTIVE: Deficits in motor inhibition may contribute to impulsivity and irritability in children with bipolar disorder. Studies of the neural circuitry engaged during failed motor inhibition in pediatric bipolar disorder may increase our understanding of the pathophysiology of the illness. The authors tested the hypothesis that children with bipolar disorder and comparison subjects would differ in ventral prefrontal cortex, striatal, and anterior cingulate activation during unsuccessful motor inhibition. They also compared activation in medicated versus unmedicated children with bipolar disorder and in children with bipolar disorder and attention deficit hyperactivity disorder (ADHD) versus those with bipolar disorder without ADHD. METHOD: The authors conducted an event-related functional magnetic resonance imaging study comparing neural activation in children with bipolar disorder and healthy comparison subjects while they performed a motor inhibition task. The study group included 26 children with bipolar disorder (13 unmedicated and 15 with ADHD) and 17 comparison subjects matched by age, gender, and IQ. RESULTS: On failed inhibitory trials, comparison subjects showed greater bilateral striatal and right ventral prefrontal cortex activation than did patients. These deficits were present in unmedicated patients, but the role of ADHD in mediating them was unclear. CONCLUSIONS: In relation to comparison subjects, children with bipolar disorder may have deficits in their ability to engage striatal structures and the right ventral prefrontal cortex during unsuccessful inhibition. Further research should ascertain the contribution of ADHD to these deficits and the role that such deficits may play in the emotional and behavioral dysregulation characteristic of bipolar disorder.

Objectives. In 2 studies, we aimed to describe the content of mothers' verbal warnings to their young children and to investigate whether mothers modify their warnings based on the type of dangerous situation and children's age. Study 1. Mothers of 12-, 18-, and 24-month-olds reported in a telephone interview the words and phrases they would use to prevent their children from falling, touching dangerous objects, ingesting poisonous substances, and running away. The words "no," "don't," and "stop" were the most frequent warnings across ages. Mothers also used warnings to elicit their children's attention, regulate children's location, modify children's actions, and to highlight the properties and consequences of specific dangers. The content, diversity and complexity of mothers' warnings varied with children's age and the type of dangerous situation. Study 2. We observed mothers in the laboratory as they warned their 12- and 18-month-old children not to walk down 50 degrees slopes. As in Study 1, mothers primarily relied on the words "no," "don't," and "stop," but again used warnings to elicit attention, regulate location, modify actions, and describe the danger. Mothers used more complex and diverse warnings with older versus younger children. Conclusions. Although simple warnings, such as 'no," "don't," and "stop" hold privileged status at all ages, mothers express a rich array of warnings that are attuned to children's age and the dangers of the situation.

Objective. We examined how parents' expectations about their infants' crawling ability and crawling attempts in a locomotor task affect parenting choices about ensuring infants' safety and providing appropriate challenges. Design. Mothers and fathers of 34 11-month-old infants adjusted a ramp to the steepest slopes they thought their infants could safely crawl down, would attempt to crawl down, and they would allow their infants to crawl down independently. Results. Most parents expected their infants to attempt slopes that were steeper than their ability and generally emphasized safety only by permitting infants to crawl down slopes that were within infants' expected ability. More fathers than mothers displayed parenting choices emphasizing challenge by allowing their infants to attempt slopes beyond their ability. Conclusions. Both mothers and fathers expected infants to attempt impossibly steep slopes, but mothers were more likely to adopt safety-oriented parenting choices. Wide disagreements within dyads and inconsistencies in individual parents' estimates might increase the chances of infants incurring injuries.

Three experiments investigated visual search for targets that differed from distractors in colour, size, or orientation. In one condition the target was defined by a conjunction of these features, while in the other condition the target was the odd one out. In all experiments, 6-7- and 9-10-year-old children were compared with young adults. Experiment 1 showed that children's search differed from adults' search in two ways. In conjunction searches children searched more slowly and took longer to reject trials when no target was present. In the odd-one-out experiments, 6-7-year-old children were slower to respond to size targets than to orientation targets, and slower for orientation targets than for colour targets. Both the other groups showed no difference in their rate of responding to colour and orientation. Experiments 2 and 3 highlighted that these results were not a function of either differential density across set sizes (Experiment 2) or discriminability of orientation and colour (Experiment 3). Across all three experiments, the results of both conjunction and odd-one-out searches highlighted a development in visual search from middle to late childhood

The proportionality of blood oxygen level-dependent (BOLD) response during a cognitive task and that from a hypercapnic challenge was investigated in cortical structures involved in working memory (WM). Breath holding (BH) following inspiration was used to induce a BOLD response characteristic of regional vasomotor reactivity but devoid of metabolic changes. BOLD effects measured during BH were used to normalize individual subject activations during WM, which effectively reduced the confounding influence of individual- and region-specific differences in hemodynamic responsivity common to both tasks. In a study of seven subjects, the BH calibration reduced intersubject variability in WM effect amplitude by 24.8% (P < 0.03). Reduced intersubject variability resulted in a 23.7% increase in group WM activation voxel extent significant at P < 0.001, with further increases at more stringent thresholds. Because the BH task does not require CO(2) inhalation or other invasive manipulations and is broadly applicable across cortical regions, the proposed approach is simple to implement and may be beneficial for use not only in quantitative group fMRI analyses, but also for multicenter and longitudinal studies.