Faculty Bibliography

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.

Much of the research on long-term potentiation (LTP) is motivated by the question of whether changes in synaptic strength similar to LTP underlie learning and memory. Here we discuss findings from studies on fear conditioning, a form of associative learning whose neural circuitry is relatively well understood, that may be particularly suited for addressing this question. We first review the evidence suggesting that fear conditioning is mediated by changes in synaptic strength at sensory inputs to the lateral nucleus of the amygdala. We then discuss several outstanding questions that will be important for future research on the role of synaptic plasticity in fear learning. The results gained from these studies may shed light not only on fear conditioning, but may also help unravel more general cellular mechanisms of learning and memory

BACKGROUND: There is uncertainty about the extent to which language skills are part of general intelligence and even more uncertainty on whether deprivation has differential effects on language and non-language skills. METHODS: Language and cognitive outcomes at 6 and 11 years of age were compared between a sample of 132 institution-reared Romanian children adopted into UK families under the age of 42 months, and a sample of 49 children adopted within the UK under the age of 6 months who had not experienced either institutional rearing or profound deprivation. RESULTS: The effects of institutional deprivation were basically similar for language and cognitive outcomes at age 6; in both there were few negative effects of deprivation if it ended before the age of 6 months and there was no linear association with duration of deprivation within the 6 to 42 month range. For the children over 18 months on arrival (range 18-42 months), the presence of even very minimal language skills (imitation of speech sounds) at the time of arrival was a strong beneficial prognostic factor for language and cognitive outcomes, but not for social/emotional/behavioural outcomes. Individual variations in adoptive parent characteristics were unrelated to differences in language or cognitive outcomes, possibly as a consequence of the limited variability in the adoptive family group. CONCLUSIONS: Minimal language probably indexes some form of cognitive reserve that, in turn, indexes the degree of institutional deprivation

Transient reductions in serotonin levels during tryptophan depletion (TD) are thought to impair reward processing in healthy volunteers, while another facet of the serotonergic system, the serotonin transporter (5-HTTLPR) short allele polymorphism, is implicated in augmented processing of aversive stimuli. We examined the impact and interactions of TD and the serotonin promoter polymorphism genotype on reward and punishment via two forms of instrumental learning: passive avoidance and response reversal. In this study, healthy volunteers (n=35) underwent rapid TD or control procedures and genotyping (n=26) of the 5-HTTLPR for long and short allele variants. In the passive avoidance task, tryptophan-depleted volunteers failed to respond sufficiently to rewarded stimuli compared to the control group. Additionally, long allele homozygous individuals (n=11) were slower to learn to avoid punished stimuli compared to short allele carriers (n=15). TD alone did not produce measurable deficits in probabilistic response reversal errors. However, a significant drug group by genotype interaction was found indicating that in comparison to short allele carriers, tryptophan-depleted individuals homozygous for the long allele failed to appropriately use punishment information to guide responding. These findings extend prior reports of impaired reward processing in TD to include instrumental learning. Furthermore, they demonstrate behavioral differences in responses to punishing stimuli between long allele homozygotes and short allele carriers when serotonin levels are acutely reduced.

BACKGROUND: Disinhibited attachment is an important sequel of an institutional rearing, but questions remain regarding its measurement, its persistence, the specificity of the association with institutional rearing and on whether or not it constitutes a meaningful disorder. METHOD: Children initially reared in profoundly depriving institutions in Romania and subsequently adopted into UK families were compared with respect to findings at 11 years with children who had not experienced institutional deprivation and who had been adopted within the UK before the age of 6 months. Measures included parental reports, a Strange Situation procedure modified for use in the home and systematic standardised investigator ratings of the children's behaviour. RESULTS: Disinhibited attachment, as reported by parents, showed a high degree of persistence from 6 to 11, but also a reduction over time in its frequency. Investigator ratings validated the parental reports but suggested that much of the fall in rate of disinhibited attachment was a function of the parental measure being less developmentally appropriate at 11 than it had been at 6. Disinhibited attachment was strongly associated with institutional rearing but there was not a significant increase in relation to duration of institutional deprivation beyond the age of 6 months. Mild, but not marked, disinhibited attachment was quite frequent in non-institutionalised adopted children but both the course and correlates indicated that its meaning was probably quite different. In the institution-reared children, disinhibited attachment was associated with a marked increase in service usage and associations with other forms of psychopathology. CONCLUSIONS: Disinhibited attachment constitutes a valid, and handicapping, clinical pattern that is strongly associated with an institutional rearing

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.

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.

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.

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.