Faculty Bibliography

Attention deficit hyperactivity disorder (ADHD) is the most frequent psychiatric disorder in children, yet data are sparse on its pathophysiology. Particularly relevant are the dopamine transporters since these are the main targets of stimulant medications used for ADHD treatment. Though some imaging studies have shown increases in dopamine transporters in ADHD others have not and their role in the neurobiology of ADHD remains unclear. Here we investigate dopamine transporters in ADHD subjects with control of potentially confounding factors (previous medication and/or drug histories, comorbidity) and their association with clinical symptoms. Positron emission tomography and [11C]cocaine were used to measure dopamine transporters in 20 never medicated adults with ADHD and 25 controls. Dopamine transporters were lower in left caudate (13%, p < 0.05) and in left nucleus accumbens (p < 0.005) in ADHD subjects than in controls. In putamen dopamine transporters did not differ between groups but were associated with scores of inattention (Conners Adult Attention Rating Scale) both in ADHD subjects (p < 0.005) and in controls (p < 0.005). Thus, for a given transporter level the scores for inattention were on average five times greater in ADHD subjects than in controls. These results do not corroborate increases in dopamine transporters in ADHD subjects and show that in some they are reduced. It also provides evidence that dopamine transporter levels modulate attention but suggest that additional pathology (e.g., prefrontal or cingulostriatal pathways, noradrenergic neurotransmission) is necessary to account for the large differences in inattention observed between controls and ADHD subjects

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.

OBJECTIVE: No previous research has focused on psychosocial functioning in understanding how personality disorders compound the impairment caused by major depressive disorder over time. This report describes the effects of persistent and remitting comorbid personality disorders on the depressive status and functioning of patients with major depressive disorder over the course of 2 years. METHOD: Longitudinal data on functioning from the first 2 years of the Collaborative Longitudinal Personality Disorders Study were evaluated for 3 groups of subjects with major depressive disorder: subjects with major depressive disorder alone (N = 103), those with persistent comorbid personality disorders (N = 164), and those with comorbid personality disorders that remitted (N = 69). DSM-IV criteria were used for mood and personality disorder diagnoses. The data were gathered from September 1996 to August 2000 and from September 2001 to September 2004. RESULTS: Subjects whose personality disorders remitted were more likely than those with persisting personality disorders to have major depressive disorder remit. Social functioning, as measured by the Longitudinal Interval Follow-up Evaluation and the Global Assessment of Functioning, improved across a range of domains over time, with most gains occurring in the first 6 months of follow-up and with differential improvement by group. As hypothesized, subjects whose personality disorders remitted fared nearly as well as did subjects without personality disorders, whereas subjects whose personality disorders persisted functioned most poorly. CONCLUSIONS: Outcome research on major depressive disorder has often ignored Axis II disorders. Our data indicate that the longitudinal course of personality psychopathology meaningfully influences depressive outcome and psychosocial functioning in patients with major depressive disorder. The findings indicate the need to target both symptom relief and psychosocial functioning and to treat both personality and mood disorders in comorbid patients

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.

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

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.

Tetrachloroethylene is a solvent used in dry cleaning with reported neurotoxic effects. Using proportional hazard methods, we examined the relationship between parental occupation as a dry cleaner and risk for schizophrenia in a prospective population-based cohort of 88,829 offspring born in Jerusalem from 1964 through 1976, followed from birth to age 21-33 years. Of 144 offspring whose parents were dry cleaners, 4 developed schizophrenia. We observed an increased incidence of schizophrenia in offspring of parents who were dry cleaners (RR=3.4, 95% CI, 1.3-9.2, p=0.01). Tetrachloroethylene exposure warrants further investigation as a risk factor for schizophrenia