Faculty Bibliography

BACKGROUND: Methylphenidate (MPH)-related adverse events are well characterized. Their predictors and their relationship with therapeutic effects are less well understood. Here we examine these issues in relation to two long-acting formulations. METHOD: Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. Parents also completed the Barkley Stimulant Side Effect Rating Scale (BSSERS). RESULTS: The BSSERS had six factors: Emotionality, sleep/appetite, disengaged, dizzy, uninterested, and aches. Treatment effects were seen only for emotionality (which improved) and sleep and appetite (which worsened). Adverse events were not predictable from personal and clinical characteristics of patients. Sleep/appetite adverse events were not associated with therapeutic effects. Improvements in attention-deficit/hyperactivity disorder (ADHD) and emotionality were correlated. DISCUSSION: The results support a narrow conceptualization of MPH adverse events with problems restricted to appetite and sleep. These effects were not predictable on the basis of available information and may be due to an underlying mechanism rather distinct from those determining therapeutic effects

BACKGROUND: Methylphenidate (MPH) is an efficacious and normally well-tolerated treatment for attention-deficit/hyperactivity disorder (ADHD). Although treatment effects are usually assessed using parent-rating scales, these can be supplemented by more objective methods. Here we examine the associations between ratings and one such method, assessments made across the day in the laboratory classroom. METHOD: Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. RESULTS: Treatment effects were observed on all measures. Laboratory measures were correlated with each other, most strongly between Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP) inattention and Permanent Product Measure of Performance (PERMP). Parental ratings were correlated with classroom measures during the main morning period (1.5-4.5 hours after dosing) and to a lesser extent in the afternoon (6.0-7.5 hours after dosing), but not, by and large, immediately after dosing or in the evening. The morning correlations seemed stronger for female than for male participants. DISCUSSION: The results suggest that parental ratings and direct observations tap different aspects of MPH response and that both may be required for comprehensive assessment

OBJECTIVE: We sought to examine follow-up service use by students identified at risk for suicidal behavior in a school-based screening program and assess barriers to seeking services as perceived by youths and parents. METHOD: We conducted a longitudinal study of 317 at-risk youths identified by a school-based suicide screening in six high schools in New York State. The at-risk teenagers and their parents were interviewed approximately 2 years after the initial screen to assess service use during the intervening period and identify barriers that may have interfered with seeking treatment. RESULTS: At the time of the screening, 72% of the at-risk students were not receiving any type of mental health service. Of these students, 51% were deemed in need of services and subsequently referred by us to a mental health professional. Nearly 70% followed through with the screening's referral recommendations. The youths and their parents reported perceptions about mental health problems, specifically relating to the need for treatment, as the primary reasons for not seeking service. CONCLUSIONS: Screening seems to be effective in enhancing the likelihood that students at risk for suicidal behavior will get into treatment. Well-developed and systematic planning is needed to ensure that screening and referral services are coordinated so as to facilitate access for youths into timely treatment.

OBJECTIVE: Many children with pervasive developmental disorders (PDDs) have serious, functionally impairing behavioral problems. We tested whether combined treatment (COMB) with risperidone and parent training (PT) in behavior management is superior to medication alone (MED) in improving severe behavioral problems in children with PDDs. METHOD: This 24-week, three-site, randomized, parallel-groups clinical trial enrolled 124 children, aged 4 through 13 years, with PDDs, accompanied by frequent tantrums, self-injury, and aggression. The children were randomized 3:2 to COMB (n = 75) or MED (n = 49). The participants received risperidone monotherapy from 0.5 to 3.5 mg/day (with switch to aripiprazole if risperidone was ineffective). Parents in the COMB group (n = 75; 60.5%) received a mean of 10.9 PT sessions. The primary measure of compliance was the Home Situations Questionnaire (HSQ) score. RESULTS: Primary: intent-to-treat random effects regression showed that COMB was superior to MED on HSQ (p = .006) [effect size at week 24 (d) = 0.34]. The HSQ score declined from 4.31 (+/- 1.67) to 1.23 (+/- 1.36) for COMB compared with 4.16 (+/- 1.47) to 1.68 (+/- 1.36) for MED. Secondary: groups did not differ on Clinical Global Impressions-Improvement scores at endpoint; compared with MED, COMB showed significant reductions on Aberrant Behavior Checklist Irritability (d = 0.48; p = .01), Stereotypic Behavior (d = 0.23; p = .04), and Hyperactivity/Noncompliance subscales (d = 0.55; p = .04). Final risperidone mean dose for MED was 2.26 mg/day (0.071 mg/kg), compared with 1.98 mg/day for COMB (0.066 mg/kg) (p = .04). CONCLUSIONS: Medication plus PT resulted in greater reduction of serious maladaptive behavior than MED in children with PDDs, with a lower risperidone dose

BACKGROUND:Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. METHODS AND FINDINGS/RESULTS:We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data--medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York--were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-9 x lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. CONCLUSIONS:These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.

Atypical features were incorporated into the American Psychiatric Association's Diagnostic and Statistical Manual, Fourth Edition (DSM-IV, 1994) as an illness specifier for major depression and dysthymia. The validity of depression with atypical features was supported by differences relative to depression with melancholic features in syndromal symptoms, course of illness, biology, family history, and treatment response. This paper reviews post-DSM-IV literature relevant to the validity of depression with atypical features. Most studies support the pre-DSM-IV findings. Again, course of illness, biological, family, and treatment differences are shown between melancholia and depression with atypical features. Several biologic studies report nondepressed controls have mean values between depressed subjects having atypical features and other depressed patients. This suggests atypical depression is a distinct depressive group rather than a milder form of melancholia. In addition, some studies show distinctions between depressed subjects with atypical features and those having neither atypical nor melancholic features. As depression with atypical features separates not only from melancholia but also from other depressed groups and controls over a range of meaningful distinctions, we conclude it is a valid clinical syndrome, useful both heuristically and in driving treatment decisions.

REASONS: Schizophrenia is typically an adult neurodevelopmental disorder that has its antecedents in childhood and adolescence. Little is known about disorders 'usually first diagnosed in infancy, childhood and adolescence' (e.g., childhood-onset disorders) in 'prodromal' teens at heightened clinical risk for psychotic disorder. MAIN FINDINGS: Childhood-onset disorders were prevalent in putatively prodromal teens, including anxiety and disruptive disorders, attention-deficit/hyperactivity disorder (ADHD), and, surprisingly, elimination disorders. These may reflect developmental antecedents in psychotic disorders such as schizophrenia. KEY DATA AND STATISTICS: A case series of 9 teens (ages 13-17) identified as prodromal to psychosis were evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). Childhood-onset diagnoses commonly endorsed (threshold or subthreshold) included ADHD (5/9), oppositional defiant disorder (5/9), enuresis or encopresis (4/9), conduct disorder (2/9), separation anxiety (3/9), and transient tic disorder (2/9). Enuresis was identified in 3 of the 4 older teens (ages 15-17). MAJOR CONCLUSIONS: An understanding of the childhood-onset disorders that occur in teens at risk for psychotic illnesses, such as schizophrenia, can shed light on the pathophysiology of schizophrenia and potentially inform early identification and intervention

BACKGROUND: Although schools are often the first institutions to provide recovery efforts for children post-disaster, few studies have involved the school community in research to improve the delivery of these mental health services on campuses. This community-partnered study explores post-disaster counseling services 10 months following Hurricane Katrina. METHODS: In July 2006, nine focus groups, consisting of 39 school-based mental health counselors and six program administrators (10 men, 35 women), were conducted following a 2-day clinical training regarding a youth trauma intervention following Hurricane Katrina. Participants discussed the types of services they had been providing prior to the training and potential barriers to delivering services. RESULTS: Participants identified high mental health needs of students and described populations that did not seem to be adequately supported by current funding sources, including those with pre-existing traumatic experiences and mental health issues, indirect psychological and social consequences of the storms, and those students relocated to communities that were not as affected. Participants also described the need for a centralized information system. CONCLUSIONS: Participants described the need for greater organizational structure that supports school counselors and provides system-level support for services. Implications for next steps of this community-partnered approach are described.

Evidence from macaque monkey tracing studies suggests connectivity-based subdivisions within the precuneus, offering predictions for similar subdivisions in the human. Here we present functional connectivity analyses of this region using resting-state functional MRI data collected from both humans and macaque monkeys. Three distinct patterns of functional connectivity were demonstrated within the precuneus of both species, with each subdivision suggesting a discrete functional role: (i) the anterior precuneus, functionally connected with the superior parietal cortex, paracentral lobule, and motor cortex, suggesting a sensorimotor region; (ii) the central precuneus, functionally connected to the dorsolateral prefrontal, dorsomedial prefrontal, and multimodal lateral inferior parietal cortex, suggesting a cognitive/associative region; and (iii) the posterior precuneus, displaying functional connectivity with adjacent visual cortical regions. These functional connectivity patterns were differentiated from the more ventral networks associated with the posterior cingulate, which connected with limbic structures such as the medial temporal cortex, dorsal and ventromedial prefrontal regions, posterior lateral inferior parietal regions, and the lateral temporal cortex. Our findings are consistent with predictions from anatomical tracer studies in the monkey, and provide support that resting-state functional connectivity (RSFC) may in part reflect underlying anatomy. These subdivisions within the precuneus suggest that neuroimaging studies will benefit from treating this region as anatomically (and thus functionally) heterogeneous. Furthermore, the consistency between functional connectivity networks in monkeys and humans provides support for RSFC as a viable tool for addressing cross-species comparisons of functional neuroanatomy