Faculty Bibliography

We recorded hippocampal place cells in two spatial environments: a training environment in which rats underwent fear conditioning and a neutral control environment. Fear conditioning caused many place cells to alter (or remap) their preferred firing locations in the training environment, whereas most cells remained stable in the control environment. This finding indicates that aversive reinforcement can induce place cell remapping even when the environment itself remains unchanged. Furthermore, contextual fear conditioning caused significantly more remapping of place cells than auditory fear conditioning, suggesting that place cell remapping was related to the rat's learned fear of the environment. These results suggest that one possible function of place cell remapping may be to generate new spatial representations of a single environment, which could help the animal to discriminate among different motivational contexts within that environment

BACKGROUND: Previous studies found few abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function in prepubertal children with anxiety or depressive disorders. In this study, we combined data from two independent, consecutive studies to achieve a larger sample size. Our goal was to identify potential alterations in the circadian pattern of cortisol secretion in anxious or depressed children. METHODS: A total of 124 prepubertal subjects from two independent samples (76 with major depressive disorder, 31 with anxiety disorders, and 17 healthy control subjects) were studied. Blood samples collected for cortisol at hourly intervals over a 24-hour period were examined. Analyses were performed aligning cortisol samples by clock-time. Additional analyses aligning samples by sleep-onset time were performed with a subsample of subjects. RESULTS: In the combined sample, significant findings emerged that were previously undetected. Anxious children exhibited significantly lower nighttime cortisol levels and an initially sluggish rise in cortisol during the nighttime when compared with depressed and healthy control children. In contrast, depressed children did not show a clear-cut pattern of differences compared with healthy control children. CONCLUSIONS: Anxious children seem to exhibit an altered pattern of nighttime cortisol secretion, with an initially sluggish or delayed nocturnal rise before reaching similar peak levels of cortisol near the time of awakening. These findings suggest subtle alterations in HPA axis function in prepubertal children with anxiety disorders.

OBJECTIVE: To review the literature on the cognitive-behavioral treatment of children and adolescents with anxiety and depressive disorders within the conceptual framework of evidence-based medicine. METHOD: The psychiatric and psychological literature was systematically searched for controlled trials applying cognitive-behavioral treatment to pediatric anxiety and depressive disorders. RESULTS: For both anxiety and depression, substantial evidence supports the efficacy of problem-specific cognitive-behavioral interventions. Comparisons with wait-list, inactive control, and active control conditions suggest medium to large effects for symptom reduction in primary outcome domains. CONCLUSIONS: From an evidence-based perspective, cognitive-behavioral therapy is currently the treatment of choice for anxiety and depressive disorders in children and adolescents. Future research in this area will need to focus on comparing cognitive-behavioral psychotherapy with other treatments, component analyses, and the application of exportable protocol-driven treatments to divergent settings and patient populations

Having recently shown that extinction of conditioned fear depends on L-type voltage-gated calcium channels (LVGCCs), we have been seeking other protocols that require this unusual induction mechanism. We tested latent inhibition (LI) of fear, because LI resembles extinction except that cue exposures precede, rather than follow, cue-shock pairing. Systemic injections of two LVGCC inhibitors, nifedipine and diltiazem, before pre-exposure blocked LI completely with no evidence of state-dependent learning. The results indicate that extinction and LI share a common molecular requirement and may support the notion that LI, like extinction, is a form of inhibitory learning.

BACKGROUND: Specific features and diagnostic boundaries of childhood bipolar disorder (BD) remain controversial, and its differentiation from other disorders challenging, owing to high comorbidity with other common childhood disorders, and frequent lack of an episodic course typical of adult BD. METHODS: We repeatedly examined children meeting DSM-IV criteria for BD (excluding episode-duration requirements) and analyzed their clinical records to evaluate age-at-onset, family history, symptoms, course, and comorbidity. RESULTS: Of 82 juveniles (aged 10.6 +/- 3.6 years) diagnosed with BD, 90% had a family history of mood or substance-use disorders, but only 10% of patients had been diagnosed with BD. In 74%, psychopathology was recognized before age 3, usually as mood and sleep disturbances, hyperactivity, aggression, and anxiety. At onset, dysphoric-manic and mixed presentations were most common (48%), euphoric mania less (35%), and depression least (17%). Subtype diagnoses were: BP-I (52%) > BP-II (40%) > cyclothymia (7%). DSM episode-duration criteria were met in 52% of cases, and frequent shifts of mood and energy were common. LIMITATIONS: Partly retrospective study of clinically diagnosed referred outpatients without a comparison group. CONCLUSIONS: Pediatric BD is often mis- or undiagnosed, although it often manifests with mood lability and sleep disturbances early in life. DSM BD criteria inconsistent with clinical findings require revision for pediatric application.

OBJECTIVE: The use of placebo in the pediatric age group has come under increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a research forum. The purpose was to identify challenges and their solutions regarding the use of placebo in randomized controlled trials in pediatric psychopharmacology. METHOD: Workgroups focused on problems and solutions in five areas: ethics and human subjects, research design and statistics, partnering with consumers, U.S. Food and Drug Administration and pharmaceutical industry perspectives, and psychosocial treatments. RESULTS: In many but not all circumstances, inclusion of a placebo control is essential to meet the scientific goals of treatment outcome research. Innovative research designs; involvement of consumers in planning and implementing research; flexibility by industry, academia, the National Institutes of Health, and regulatory agencies acting in partnership; and concomitant use of evidence-based psychosocial services can and should assist in making placebo-controlled trials acceptable. CONCLUSIONS: Properly designed placebo-controlled trials remain necessary, ethical, and feasible.

OBJECTIVES: To better understand the predictors of parental discussions with pediatric care providers (pediatricians, psychologists/psychiatrists, social workers, early intervention providers, or other medical specialists) regarding early child behavior problems and to suggest strategies for eliciting early identification from parents in health care settings. DESIGN: A cross-sectional survey of parents of children from a representative healthy birth cohort. The survey included the Infant-Toddler Social Emotional Assessment, measurement of parental worry regarding problematic behavior, and demographic factors. SETTING: Fifteen urban and suburban towns in the northeastern United States. PARTICIPANTS: The study sample consisted of all parents of 11- to 39-month-olds (n = 269) who exceeded the 90th percentile on 1 or more Infant-Toddler Social Emotional Assessment problem domain scores (representing elevated problematic behavior symptoms) from an original sample of 1278. RESULTS: Few parents (17.7%) who reported elevated problematic behavior spoke to a provider about such problems. In adjusted models, speaking to a provider was associated with reported worry about behavior (odds ratio [OR], 3.47 [95% confidence interval (CI), 1.74-6.92]) and with low reported child social-emotional competence (OR, 2.68 [95% CI, 1.23-5.84]). In adjusted models, worry was most likely among parents who reported low child competence (OR, 2.18 [95% CI, 1.07-4.22]) and disruption in family routines attributed to the child's behavior (OR, 2.38 [95% CI, 1.31-4.33]). CONCLUSIONS: Parental worry is a robust predictor of help seeking among parents of children with behavioral problems. Further, lags in social competence contribute to both parental worry and help seeking. These findings, in conjunction with previous evidence that child behavior problems amenable to early intervention are often unidentified, suggest that systematic inquiry by health care providers about parental concerns is important in the identification of early emerging behavioral health problems.

Regulation of attention and promotion of behavioural flexibility are functions attributed to both the noradrenergic nucleus locus coeruleus (LC) and the prefrontal cortex (PFC). The PFC receives a large innervation from LC and small changes in catecholaminergic activity in PFC profoundly affect cognitive function. It is crucial to the understanding of learning-related plasticity, that the cognitive context driving LC neurons be determined and the relation to activity in PFC be elucidated. To this end simultaneous recordings were made from LC and prelimbic cortex (PL) during an odour-reward association task in the rat. Neuronal activity related to orientation of attention, reward predictability, reward itself, and changes in stimulus reinforcement contingencies, was measured. All LC neurons and a significant proportion of PL neurons were engaged during several aspects of a Go/NoGo task, especially after the signal for trial onset and CS+ presentation. LC activation was, however, more tightly aligned to the behavioural response than to the CS+ 22% of PL neurons were activated during the response-reward delay. This suggests that the activity of both these structures is related to reward anticipation. Finally, LC neurons exhibited rapid plasticity when the reward-contingency was modified. Within-trial response latencies were always shorter in LC than in PL and between-trial response adaptation in LC preceded that in PL by many trials. Identifying such temporal relationships is an essential step toward understanding how neuromodulatory inputs to forebrain networks might promote or permit experience-dependent plasticity in behavioural situations

Fear extinction refers to the ability to adapt as situations change by learning to suppress a previously learned fear. This process involves a gradual reduction in the capacity of a fear-conditioned stimulus to elicit fear by presenting the conditioned stimulus repeatedly on its own. Fear extinction is context-dependent and is generally considered to involve the establishment of inhibitory control of the prefrontal cortex over amygdala-based fear processes. In this paper, we review research progress on the neural basis of fear extinction with a focus on the role of the amygdala and the prefrontal cortex. We evaluate two competing hypotheses for how the medial prefrontal cortex inhibits amygdala output. In addition, we present new findings showing that lesions of the basal amygdala do not affect fear extinction. Based on this result, we propose an updated model for integrating hippocampal-based contextual information with prefrontal-amygdala circuitry

BACKGROUND: School bullying is the most common type of school violence. Victimization by or perpetration of school bullying has frequently been associated with a broad spectrum of behavioral, emotional, and social problems. OBJECTIVE: To investigate the prevalence and demographic characteristics of victims, perpetrators, and victim-perpetrators in a Korean middle school sample. METHODS: We evaluated 1756 middle school students in this cross-sectional study. Students provided demographic information and completed the Korean-Peer Nomination Inventory. Descriptive statistics and the Pearson chi(2) test were used. RESULTS: We found that 40% of all children participated in school bullying. By category, the prevalence of victims, perpetrators, and victim-perpetrators was 14%, 17%, and 9%, respectively. The most common subtypes of victimization were exclusion (23%), verbal abuse (22%), physical abuse (16%), and coercion (20%). Boys were more commonly involved in both school bullying and all 4 types of victimization. The prevalence of bullying was greater in students with either high or low socioeconomic status and in nonintact families. CONCLUSIONS: School bullying is highly prevalent in Korean middle school students. Demographic characteristics can help identify students at greater risk for participation in school bullying