Faculty Bibliography

This study investigates the relationship between childhood attention deficit hyperactivity disorder (ADHD) and later criminality. White boys (n=207, ages 6-12) with ADHD, free of conduct disorder, were assessed at ages 18 and 25 by clinicians who were blind to childhood status. A non-ADHD group served as comparisons. Lifetime arrest records were obtained when subjects were 38 years old for subjects who resided in New York State throughout the follow-up interval (93 probands, 93 comparisons). Significantly more ADHD probands than comparisons had been arrested (47% vs. 24%), convicted (42% vs. 14%), and incarcerated (15% vs. 1%). Rates of felonies and aggressive offenses also were significantly higher among probands. Importantly, the development of an antisocial or substance use disorder in adolescence completely explained the increased risk for subsequent criminality. Results suggest that even in the absence of comorbid conduct disorder in childhood, ADHD increases the risk for developing antisocial and substance use disorders in adolescence, which, in turn, increases the risk for criminal behavior in adolescence and adulthood

Recent efforts to translate basic research to the treatment of clinical disorders have led to a growing interest in exploring mechanisms for diminishing fear. This research has emphasized two approaches: extinction of conditioned fear, examined across species; and cognitive emotion regulation, unique to humans. Here, we sought to examine the similarities and differences in the neural mechanisms underlying these two paradigms for diminishing fear. Using an emotion regulation strategy, we examine the neural mechanisms of regulating conditioned fear using fMRI and compare the resulting activation pattern with that observed during classic extinction. Our results suggest that the lateral PFC regions engaged by cognitive emotion regulation strategies may influence the amygdala, diminishing fear through similar vmPFC connections that are thought to inhibit the amygdala during extinction. These findings further suggest that humans may have developed complex cognition that can aid in regulating emotional responses while utilizing phylogenetically shared mechanisms of extinction

OBJECTIVE: To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70- mg/day groups underwent forced-dose titration. The primary efficacy measure was the clinician-determined ADHD Rating Scale (ADHD-RS) total score. The study was conducted from May 2006 to November 2006. RESULTS: Treatment groups were well matched at baseline, including in ADHD-RS scores. At endpoint, changes in ADHD-RS scores were significantly greater for each lisdexamfetamine dose than for placebo (placebo = -8.2, 30 mg/day lisdexamfetamine = -16.2, 50 mg/day lisdexamfetamine = -17.4, 70 mg/day lisdexamfetamine = -18.6; all p < .0001 vs. placebo), with no differences between doses. Significant differences relative to placebo were observed in each lisdexamfetamine group, beginning at week 1 and for each week throughout. The percentage of subjects who improved (Clinical Global Impressions-Improvement scale rating < or = 2) was significantly greater for each lisdexamfetamine dose than for placebo at each week and at endpoint (placebo = 29%, 30 mg/day lisdexamfetamine = 57%, 50 mg/day lisdexamfetamine = 62%, 70 mg/day lisdexamfetamine = 61%; all p < .01). Adverse events were generally mild and included dry mouth, decreased appetite, and insomnia. CONCLUSION: All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexamfetamine was generally well tolerated by these patients

OBJECTIVE: To examine the association between attention-deficit/hyperactivity disorder symptomatology and parent-reported sleep problems among preschoolers ages 2 to 5 years. METHOD: A total of 1,073 parents of preschoolers ages 2 to 5 years attending a large pediatric clinic completed the Child Behavior Checklist 1(1/2)-5 years. A stratified probability sample of 193 parents of high scorers and 114 parents of low scorers were interviewed with the Preschool Age Psychiatric Assessment. Poisson regression was used to test the association between parent-reported sleep problems and attention-deficit/hyperactivity disorder symptomatology, as well as psychiatric and demographic covariates. RESULTS: When considered without reference to other psychiatric disorders, elevated hyperactive-impulsive symptomatology was positively associated with parent reported problems including sleep assistance, parasomnias, and dyssomnias; however, all of these effects were attenuated to nonsignificance once psychiatric comorbidity was controlled. In contrast, elevated inattentive symptomatology (especially at lower levels of hyperactive-impulsive symptoms) was positively associated with daytime sleepiness even after psychiatric comorbidity was controlled. CONCLUSIONS: Neither hyperactive-impulsive nor inattentive attention-deficit/hyperactivity disorder symptomatology was uniquely related to parent-reported problems involving sleep assistance, parasomnias, or dyssomnias. However, inattentive symptomatology was uniquely related to daytime sleepiness above and beyond commonly occurring patterns of psychiatric comorbidity, sleep duration, and demographic factors.

CONTEXT/BACKGROUND:A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ). OBJECTIVES/OBJECTIVE:To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population. DESIGN/METHODS:Interaction of DISC1, PCM1, and BBS proteins was assessed by immunofluorescent staining and coimmunoprecipitation. Effects of PCM1, DISC1, and BBS on centrosomal functions and corticogenesis in vivo were tested by RNA interference. The PCM1 gene was examined by sequencing 39 exons and flanking splice sites. SETTING/METHODS:Probands and controls were from the collection of one of us (A.E.P.). PATIENTS/METHODS:Thirty-two probands with SZ from families that had excess allele sharing among affected individuals at 8p22 and 219 white controls. MAIN OUTCOME MEASURES/METHODS:Protein interaction and recruitment at the centrosome in cells; neuronal migration in the cerebral cortex; and variant discovery in PCM1 in patients with SZ. RESULTS:PCM1 forms a complex with DISC1 and BBS4 through discrete binding domains in each protein. DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner. In the developing cerebral cortex, suppression of PCM1 leads to neuronal migration defects, which are phenocopied by the suppression of either DISC1 or BBS4 and are exacerbated by the concomitant suppression of both. Furthermore, a nonsense mutation that segregates with SZ spectrum psychosis was found in 1 family. CONCLUSIONS:Our data further support for the role of centrosomal proteins in cortical development and suggest that perturbation of centrosomal function contributes to the development of mental diseases, including SZ.

Several lines of evidence implicate the amygdala in face-emotion processing, particularly for fearful facial expressions. Related findings suggest that face-emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala's response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9-17 years old) and 30 adults (21-40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala-hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions.

BACKGROUND: This study examined neuropsychological functioning in a longitudinal sample of adolescents/young adults with attention deficit/hyperactivity disorder (ADHD) and controls as a function of the persistence of ADHD. We hypothesized that measures of executive processes would parallel adolescent clinical status, with ADHD-persisters, but not remitters, differing significantly from controls. In contrast, persisters and remitters were hypothesized to perform similarly, and different from controls, on tasks requiring less effortful processing. METHODS: Ninety-eight participants diagnosed with ADHD in childhood were reevaluated approximately 10 years later. Eighty-five never-ADHD controls similar in age, IQ, and sex distribution served as a comparison group. Participants were administered a psychiatric interview and neuropsychological test battery. RESULTS: Those with childhood ADHD demonstrated broad neuropsychological deficits relative to controls. When the group with childhood ADHD was subdivided based on adolescent ADHD status, compared to controls, both persisters and remitters showed deficient perceptual sensitivity and response variability, and increased ankle movements recorded by a solid-state actigraph. Only persisters differed from controls on several measures of more effortful executive processes. CONCLUSIONS: Findings provide preliminary support to the hypothesis that ADHD is associated with early-appearing and enduring subcortical dysfunction, while recovery over the course of development is associated with improvements in executive control functions.

The importance of the public hospital system to medical education is often absent from the debate about its value. Best known as a core provider of services to the underserved, the safety net hospital system also plays a critical role in the education of future physicians. Particular strengths include its ability to imbue physicians in training with core professional values, to reveal through the enormous range of clinical experience provided many of the social forces shaping health, and to foster interest in and commitment to advancing population health. Faculty teaching in the public hospital system has unusual opportunities to reveal to learners the broader meanings of their diverse and rich experiences. Now, as an alarming array of pressures bearing down on the safety net system threaten its stability, the potential negative impact on medical education, were it to shrink or be forced to change its essential mission, must be considered. As advocates of the safety net system marshal forces to rationalize its funding and support, its tremendous contribution to the training of physicians and other health care professionals must be clearly set forth to ensure that support for the public hospital system's health is appropriately broad based