Faculty Bibliography

BACKGROUND: Family-based evidence for association at serotonin system genes SLC6A4, HTR1B, HTR2A, and brain-derived neurotrophic factor (BDNF) has been previously reported in obsessive-compulsive disorder (OCD). Early-onset OCD is a more familial form of the disorder. METHODS: We used the transmission-disequilibrium test of association at common polymorphisms in each of these genes in 54 parent-child trios ascertained through probands with early-onset OCD. RESULTS: No evidence for association was detected at any of the polymorphisms in the entire set of subjects. Nominally significant association was found at the HTR2A rs6311 polymorphism in subjects with tic disorder and OCD (p = .05), replicating a previous finding in Tourette syndrome and OCD. Nominally significant association was also found for the SLC6A4 HT transporter gene-linked polymorphic region (5-HTTLPR) polymorphism for female subjects (p = .03). Neither association would remain significant after statistical correction for multiple testing. Despite no individual study reporting replication, a pooled analysis of five replication studies of the SLC6A4 5-HTTLPR polymorphism supports association (p = .02). CONCLUSIONS: Low power across individual association studies in OCD may lead to a false acceptance of the null hypothesis. Accumulation of evidence from multiple studies will be necessary to evaluate the potential role for these genes in contributing to susceptibility to OCD

The intestinal epithelium functions to absorb nutrients and to protect the organism against microbes. To prevent autoimmune attack on this vital tissue, T cell tolerance to intestinal self-antigens must be established. Central tolerance mechanisms involve medullary thymic epithelial cells (mTECs), which use endogenously expressed peripheral-tissue antigens (PTAs) to delete self-reactive thymocytes. The prevailing model for the induction of peripheral tolerance involves cross-presentation of tissue antigens by quiescent dendritic cells. Here we show that lymph node stromal cells present endogenously expressed PTAs to T cells. Moreover, antigen presentation by lymph node stroma is sufficient to induce primary activation and subsequent tolerance among CD8(+) T cells. Thus, lymph node stromal cells are functionally akin to mTECs and provide a direct strategy for purging the peripheral repertoire of self-reactive T cells.

This study describes the relation between sleep problems and psychiatric symptoms in preschool-age children (3 to 5 years old) with pervasive developmental disorder and a community-based sample of children attending early childhood programs. Parents completed the Early Childhood Inventory-4, a Diagnostic and Statistical Manual of Mental Disorders (fourth edition)-referenced rating scale for 2 samples: children with pervasive developmental disorder (n = 112) and nondisabled youngsters (n = 497). Although children with pervasive developmental disorder had a significantly greater number and severity of sleep problems than the community preschoolers did, sleep-disturbed children in both samples exhibited more severe behavioral difficulties-primarily symptoms of attention-deficit hyperactivity disorder and oppositional defiant disorder-than did children without sleep problems. Sleep problems are an indicator of similar comorbid psychiatric symptoms in both children with and without pervasive developmental disorder, which suggests commonalities in their etiology

OBJECTIVE: To provide an overview of diffusion tensor imaging (DTI) and its application to the study of white matter in the developing brain in both healthy and clinical samples. METHOD: The development of DTI and its application to brain imaging of white matter tracts is discussed. Forty-eight studies using DTI to examine diffusion properties of the developing brain are reviewed in the context of the structural magnetic resonance imaging literature. Reports of how brain diffusion properties are affected in pediatric clinical samples and how they relate to cognitive and behavioral phenotypes are reviewed. RESULTS: DTI has been used successfully to describe white matter development in pediatric samples. Changes in white matter diffusion properties are consistent across studies, with anisotropy increasing and overall diffusion decreasing with age. Diffusion measures in relevant white matter regions correlate with behavioral measures in healthy children and in clinical pediatric samples. CONCLUSIONS: DTI is an important tool for providing a more detailed picture of developing white matter than can be obtained with conventional magnetic resonance imaging alone.

Seven hundred and thirty-two parents reported when and how their infants learned to climb stairs. Children typically mastered stair ascent (mean age=10.97 months) several months after crawling onset and several weeks prior to descent (mean age=12.53 months). Most infants (94%) crawled upstairs the first time they ascended independently. Most infants (76%) turned around and backed at initial descent. Other descent strategies included scooting down sitting, walking, and sliding down face first. Children with stairs in their home were more likely to learn to ascend stairs at a younger age, devise backing as a descent strategy, and be explicitly taught to descend by their parents than children without stairs in their home. However, all infants learned to descend stairs at the same age, regardless of the presence of stairs in their home. Parents' teaching strategies and infants' access to stairs worked together to constrain development and to influence the acquisition of stair climbing milestones.

OBJECTIVE: Individuals with panic disorder perceive panic attacks as unpredictable. Because predictability is fundamental to Pavlovian conditioning, failure to predict panic attacks could be due to a basic deficit in conditioning. The present study examined trace eyeblink conditioning in order to test the hypothesis that individuals with panic disorder are impaired in associative learning tasks that depend on declarative memory. METHOD: Delay and trace eyeblink conditioning were tested in separate experimental sessions in 19 individuals meeting DSM-IV criteria for panic disorder and 19 sex- and age-matched healthy comparison subjects. In the delay paradigm, a mild puff was delivered to the eye at the end of a 500-msec tone; in the trace paradigm, the puff was delivered after a 700-msec empty "trace" interval that followed the end of the tone. RESULTS: Patients and comparison subjects showed similar rates of conditioned responses in the delay paradigm, but patients showed reduced rates of conditioned responses in the trace paradigm. CONCLUSIONS: These results suggest that individuals with panic disorder suffer from a deficit in declarative associative learning. Such a deficit points to impaired hippocampal function that may disrupt cognitive processing of internal and external cues predictive of a panic attack.

OBJECTIVE: Researchers disagree as to whether irritability is a diagnostic indicator for pediatric mania in bipolar disorder. The authors compared the behavioral and psychophysiological correlates of irritability among children with severe mood dysregulation (i.e., nonepisodic irritability and hyperarousal without episodes of euphoric mood) and narrow-phenotype bipolar disorder (i.e., a history of at least one manic or hypomanic episode with euphoric mood) as well as those with no diagnosis (i.e., healthy comparison children). METHOD: Subjects with severe mood dysregulation (N=21) or narrow-phenotype bipolar disorder (N=35) and comparison subjects (N=26) completed the affective Posner task, an attentional task that manipulated emotional demands and induced frustration. Mood response, behavior (reaction time and accuracy), and brain activity (event-related potentials) were measured. RESULTS: The severe mood dysregulation and narrow-phenotype bipolar disorder groups both reported significantly more arousal than comparison subjects during frustration, but behavioral and psychophysiological performance differed between the patient groups. In the frustration condition, children with narrow-phenotype bipolar disorder had lower P3 amplitude than children with severe mood dysregulation or comparison subjects, reflecting impairments in executive attention. Regardless of emotional context, children with severe mood dysregulation had lower N1 event-related potential amplitude than comparison subjects or children with narrow-phenotype bipolar disorder, reflecting impairments in the initial stages of attention. Post hoc analyses demonstrated that the N1 deficit in children with severe mood dysregulation is associated with oppositional defiant disorder symptom severity. CONCLUSIONS: Results indicate that while irritability is an important feature of severe mood dysregulation and narrow-phenotype bipolar disorder, the pathophysiology of irritability may differ among the groups and is influenced by oppositional defiant disorder severity.

We assessed detainee abuse acceptance and variables associated with it. Outpatients from a veterans' hospital were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Three questionnaire versions differed in the final line of each version's scenarios, describing abuse either as: soldier initiated, superior ordered, or wrong by a "whistleblower" soldier. Three hundred fifty-one veterans participated, 80% with service during the Vietnam War. Zero tolerance for abuse--"completely unacceptable" regardless of who the detainee was--increased with abuse severity (16% for exposure, 31% for humiliation, and 48% for rape of detainee) and with soldier initiation. The strongest, most consistently significant odds were of depressed veterans, veterans with comorbid depression/post-traumatic stress disorder, and men being approximately 2, 3, and 4 to 20 times more tolerant of abuse than those without depression/post-traumatic stress disorder and women, respectively. There may be potential value to using similar scenario-based questionnaires to study active duty military perceptions of detainee abuse. Results may inform prevention policies.

INTRODUCTION: Although mental health problems are increasing in the primary care sector, the prevalence of mental health problems in families presenting for nonpsychiatric complaints in the emergency department (ED) setting is generally unknown. As such, we set out to assess the frequency of mental health concerns and associated risk factors in children presenting for care in a pediatric ED. METHODS: A total of 411 mother-child dyads were randomly selected during a 2-year period from the less acute area of a large pediatric ED. Mothers were interviewed for child mental health concerns using structured diagnostic instruments. Mothers were also interviewed for their own mental health symptoms. Risk factor analysis for the outcome of a pediatric mental health concern was performed using bivariate and multivariate techniques. RESULTS: Of all children, 45% met criteria for a mental health concern, with 23% of all children meeting criteria for two or more mental health concerns; 21% of mothers screened positive for a mental health problem themselves. Once adjusted, children whose mothers' screened positive for a mental illness were more likely to have a mental health concern themselves. CONCLUSION: There is a large burden of mental health concerns in children and their mothers presenting to the ED for medical care. Efficiently and accurately identifying mental illness in children presenting to a pediatric ED is the first step in the intervention process for a population that might otherwise slip through the system