Faculty Bibliography

Clinician diagnoses of conduct disorder (CD) were compared to the diagnoses of CD generated by a structured interview against an observed criterion. Participants were 534 youth from a large residential program in the Midwest for delinquent youth. Rates of in-program CD behaviors were gathered from staff observations of the youth over a 9-month time period. Youth diagnosed with CD by the Diagnostic Interview Schedule for Children (DISC) displayed significantly more CD behaviors in the first 6 months of treatment compared to both youth without an externalizing disorder and youth diagnosed with CD by a clinician. Youth diagnosed with CD by a clinician had rates of CD identical to youth without an externalizing disorder. Clinicians may have weighted contextual information more heavily, as this group was significantly more likely to have an arrest record. Results support the use of structured interviews and provide evidence that typical clinician diagnoses may lack adequate validity

There are two basic types of bacterial communication systems--those in which the signal is directed solely at other organisms and those in which the signal is sensed by the producing organism as well. The former are involved primarily in conjugation; the latter in adaptation to the environment. Gram-positive bacteria use small peptides for both types of signaling, whereas Gram-negative bacteria use homoserine lactones. Since adaptation signals are autoinducers the response is population-density-dependent and has been referred to as 'quorum-sensing'. Gram-negative bacteria internalize the signals which act upon an intracellular receptor, whereas Gram-positive bacteria use them as ligands for the extracellular receptor of a two-component signaling module. In both cases, the signal activates a complex adaptation response involving many genes

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) occurs in as many as 4 percent of adults yet it is often not recognized in clinical settings because the presenting symptoms may resemble those seen in other disorders or because symptoms may be masked by commonly comorbid conditions such as anxiety and depression. OBJECTIVE: The purpose of this study was to examine the diagnostic utility of instruments commonly used in the assessment of adults presenting with symptoms of ADHD. METHODS: We reviewed several widely used self-report and laboratory measures and empirically examined the utility of the Brown Attention-Deficit Disorder Scale for Adults (Brown ADD Scale) and the Conners Continuous Performance Test (CPT) in differentially identifying adults with ADHD and those with other Axis I disorders. RESULTS: Ninety-three adults who self-referred to the ADHD program for adults at a university medical center participated in the study. Of these, 44 had ADHD combined subtype (ADHD-CB), and 26 had ADHD, predominantly inattentive subtype (ADHD-IA). Thirty-three non-ADHD adults diagnosed with Axis I mood or anxiety disorders comprised an "Other Psychiatric" group. Rates of comorbid disorders, including substance abuse, in the ADHD groups were typical of those reported in the adult ADHD literature. Data on the Brown ADD Scale and on the CPT were available for subsets of 61 and 46 participants, respectively. Analyses showed that the ADHD-CB, ADHD-IA, and Other Psychiatric groups all received mean scores in the clinical range on the Brown ADD Scale, with a trend toward even higher elevations in the two ADHD groups. Among 12 CPT variables assessed for the three groups, the mean scores on only two variables for the ADHD-IA group were clinically elevated. Neither the Brown ADD Scale nor CPT scores evinced sufficient sensitivity and specificity to qualify them to assist in differential diagnosis of ADHD vis-a-vis other, predominantly internalizing, psychiatric disorders. CONCLUSION: The results indicate a need for closer examination of executive and adaptive functioning in adults with ADHD compared with those with internalizing disorders in order to identify features that could assist in differential diagnosis.

OBJECTIVE: Few studies have used a combination of objective and self-report measures to examine neuropsychological and behavioral functioning in parents of children with attention-deficit/hyperactivity disorder (ADHD). This study examined attention and inhibitory control in the parents of preschool children who were rated as "at risk" for developing ADHD as compared with parents of controls. METHODS: Preschool children (N=53) were divided into at risk for ADHD and control groups based on parent and teacher ratings of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD symptoms. One parent of each child was administered an identical pairs Continuous Performance Test (CPT-IP), a Go/No-Go task, and the Brown Attention-Deficit Disorder Scale for Adults. RESULTS: Parents of preschoolers at risk for ADHD showed a pattern of responding on measures of vigilance characterized by slower reaction times and increased commission errors as compared with parents of controls. There were no significant group differences on self-report measures on the Brown Attention-Deficit Disorder Scale for Adults. CONCLUSION: Parents of preschoolers at risk for ADHD appear to exhibit cognitive processing deficits that may not be evident using self-report measures. Further research is needed to more clearly identify the specific nature of these neuropsychological deficits and to determine whether they have a negative impact on their children.

OBJECTIVE: This study examines the impact of comorbidity of attention-deficit/hyperactivity disorder (ADHD) with disruptive and anxiety disorders in childhood on clinical course and outcome. We consider the relative contribution of each comorbid symptom constellation, and also their interaction, to assess the following questions: (1) Does early comorbidity with conduct disorder (CD) and anxiety disorders define specific developmental trajectories?; (2) Is comorbid anxiety disorders in childhood continuous with anxiety disorders in adolescence?; (3) Does comorbid anxiety disorders mitigate the negative behavioral outcome of youth with ADHD?; and (4) Is there an interaction between comorbid CD and anxiety disorders, when they occur simultaneously, that predicts a different outcome than either comorbid condition alone? METHOD: Thirty-two 15- to 18-year-old adolescent males, diagnosed with ADHD between 7 and 11 years of age, were re-evaluated for assessment of adolescent outcome 4.3-9.2 years later. Hierarchical regression analyses were run with each of the eight Child Behavior Checklist and Youth Self-Report problem scales, and the four anxiety symptom subscales of the Multidimensional Anxiety Scale for Children serving as outcome variables. RESULTS: Findings indicate that comorbid CD at baseline predicted parent reports of behavior problems in adolescence, while comorbid anxiety disorders in childhood predicted youth reports of anxiety and social problems. Anxiety disorders without CD did not predict poor behavioral outcome. Children with both comorbid CD and anxiety disorder had the highest levels of parent-rated symptoms on follow up. In particular, adolescent social problems were best predicted by the combination of comorbid CD and anxiety disorder in childhood. CONCLUSION: These data provide evidence that children with ADHD plus anxiety disorder do in fact have anxiety disorders, and that the combination of anxiety disorder and CD predicts a more rather than less severe course.

This study evaluated the extent to which first-grade class size predicted child outcomes and observed classroom processes for 651 children (in separate classrooms). Analyses examined observed child-adult ratios and teacher-reported class sizes. Smaller classrooms showed higher quality instructional and emotional support, although children were somewhat less likely to be engaged. Teachers in smaller classes rated typical children in those classes as more socially skilled and as showing less externalizing behavior and reported more closeness toward them. Children in smaller classes performed better on literacy skills. Larger classrooms showed more group activities directed by the teacher, teachers and children interacted more often, and children were more often engaged. Lower class sizes were not of more benefit (or harm) as a function of the child's family income. First-grade class size in the range typical of present-day classrooms in the United States predicts classroom social and instructional processes as well as relative changes in social and literacy outcomes from kindergarten to first grade

Recently, great interest has been shown in understanding the functional roles of specific gap junction proteins (connexins) in brain, lens, retina, and elsewhere. Some progress has been made by studying knockout mice with targeted connexin deletions. For example, such studies have implicated the gap junction protein Cx36 in synchronizing rhythmic activity of neurons in several brain regions. Although knockout strategies are informative, they can be problematic, because compensatory changes sometimes occur during development. Therefore, it would be extremely useful to have pharmacological agents that block specific connexins, without major effects on other gap junctions or membrane channels. We show that mefloquine, an antimalarial drug, is one such agent. It blocked Cx36 channels, expressed in transfected N2A neuroblastoma cells, at low concentrations (IC(50) approximately 300 nM). Mefloquine also blocked channels formed by the lens gap junction protein, Cx50 (IC(50) approximately 1.1 microM). However, other gap junctions (e.g., Cx43, Cx32, and Cx26) were only affected at concentrations 10- to 100-fold higher. To further examine the utility and specificity of this compound, we characterized its effects in acute brain slices. Mefloquine, at 25 microM, blocked gap junctional coupling between interneurons in neocortical slices, with minimal nonspecific actions. At this concentration, the only major side effect was an increase in spontaneous synaptic activity. Mefloquine (25 microM) caused no significant change in evoked excitatory or inhibitory postsynaptic potentials, and intrinsic cellular properties were also mostly unaffected. Thus, mefloquine is expected to be a useful tool to study the functional roles of Cx36 and Cx50

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.

Depression is associated with alterations in hormone and catecholamine circadian rhythms. Analysis of these alterations has the potential to distinguish between three neurobiological models of depression, the catecholamine model, the phase advance model and the dysregulation model. Although a number of studies of 24-h rhythms have been reported, inconsistencies among the findings have complicated efforts to model the chronobiology of depression. The present study takes advantage of frequent plasma sampling over the 24-h period and a multioscillator cosinor model to fit the 24-h rhythms. METHOD: Plasma levels of norepinephrine, cortisol, prolacatin and growth hormone were sampled at 30-min intervals, and MHPG at 60-min intervals, over a 24-h period in 22 patients with major depressive disorder and 20 healthy control volunteers. RESULTS: The depressed patients had phase advanced circadian rhythms for cortisol, norepinephrine and MHPG, phase advanced hemicircadian rhythms for cortisol and prolactin, and a phase advanced ultradian rhythm for prolactin compared to healthy control subjects. In addition, the rhythm-corrected 24-h mean value (mesor) of norepinephrine was lower in the depressed patients compared to the healthy controls. There also was a poorer goodness-of-fit for norepinephrine to the circadian oscillator in the depressed patients relative to the healthy controls. CONCLUSIONS: These findings provide partial support for the dysregulation model of depression and are consistent with those studies that have found phase advances in cortisol, norepinephrine and MHPG rhythms in depression