Faculty Bibliography

We propose a novel method for neurodevelopmental brain mapping that displays how an individual's values for a quantity of interest compare with age-specific norms. By estimating smoothly age-varying distributions at a set of brain regions of interest, we derive age-dependent region-wise quantile ranks for a given individual, which can be presented in the form of a brain map. Such quantile rank maps could potentially be used for clinical screening. Bootstrap-based confidence intervals are proposed for the quantile rank estimates. We also propose a recalibrated Kolmogorov-Smirnov test for detecting group differences in the age-varying distribution. This test is shown to be more robust to model misspecification than a linear regression-based test. The proposed methods are applied to brain imaging data from the Nathan Kline Institute Rockland Sample and from the Autism Brain Imaging Data Exchange (ABIDE) sample.

BACKGROUND: Mixed states have been a fundamental part of Kraepelins conceptualization of the manic-depressive illness. However, after Kraepelin, the study of mixed states was not of great interest, until the publication of the RDC criteria (1978) and then the DSM-III edition (1980), where criteria for mixed manic states were operationalized. The most notable victims of DSM nosology were depressive mixed states, in particular depression with flight of ideas and excited (agitated) depression. METHODS: We briefly review the clinical work of Athanasios Koukopoulos on depressive mixed states (in particular agitated depression) pointing out the diagnostic and therapeutic contributions, especially in the lights of Koukopoulos first description of depressive mixed syndrome in 1992. RESULTS: The mixed depressive syndrome is not a transitory state but a state of long duration, which may last weeks or several months. The clinical picture is characterized by dysphoric mood, emotional lability, psychic and/or motor agitation, talkativeness, crowded and/or racing thoughts, rumination, initial or middle insomnia. Impulsive suicidal attempts may be frequent. The family observes incessant complaints, irritability, occasional verbal outbursts, occasional physical aggression, and occasional hypersexuality. Treatment with antipsychotics and ECT is very effective; antidepressants can worsen the clinical picture. LIMITATIONS: Selective but not systematic review of the literature on depressive mixed states. Relatively little research data is currently available for validation of the criteria proposed by Koukopoulos. CONCLUSIONS: Koukopoulos proposal of mixed depression, besides its diagnostic implications, clearly identifying it as manifestations of bipolar disorder, allows for better clinical characterization of cases and improves treatment decisions.

Without intervention, childhood behavioral problems, including aggression and noncompliance, are likely to continue over the lifespan and adversely affect a child's functioning across several domains. Based on the early emergence of functional impairment and the established negative trajectory of these difficulties, prevention and early intervention programs are critically important. Interventions for disruptive behavior disorders have primarily focused on parent training. However, given the limited access to evidence-based mental health care in many communities and the significant amount of time children spend in school, researchers and clinicians have explored creative ways to provide interventions in the school setting. Increasing attention has been given to prevention efforts. Discussed below are the results of preliminary studies investigating the effectiveness of teacher training in improving behavior management in the classroom. The teacher training is based on the established efficacy of Parent-Child Interaction Therapy (PCIT) for young children with disruptive behavior disorders and their families. This paper reviews the various teacher-child interaction training models that have been used in different settings (e.g., Head Start, general education) and includes discussion of adaptations for the classroom and for consideration in future study.

Primary cutaneous mucoepidermoid carcinoma remains a rare occurrence. This is the first report of a case of primary cutaneous mucoepidermoid carcinoma originating on the scalp and subsequently metastasizing to the parotid gland. The patient was a 53-year-old female who presented with a purple mass on her scalp since 5 months prior to examination. Histopathology revealed nests and islands of atypical epithelioid cells with pleomorphism, medium to prominent nucleoli, and scattered mucin deposition highlighting with a mucicarmine stain. The atypical cells demonstrated intravascular involvement. These findings were compatible with metastatic adenocarcinoma. Later, fine needle aspiration of the patient's parotid lesion revealed malignant cells from a poorly differentiated carcinoma that appeared similar to the patient's previously excised scalp lesion. In addition to summarizing this patient's presentation, clinical course, and management, we discuss the diagnostic challenges posed by this atypical presentation. Primary cutaneous mucoepidermoid carcinoma should be considered in the differential diagnosis of patients presenting with a scalp mass. Moreover, patients with primary cutaneous mucoepidermoid carcinoma originating on the scalp should be evaluated for possible metastases.

Objective: Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). The authors tested interpersonal psychotherapy (IPT), which has demonstrated antidepressant efficacy and shown promise in pilot PTSD research as a non-exposure-based non-cognitive-behavioral PTSD treatment. Method: The authors conducted a randomized 14-week trial comparing IPT, prolonged exposure (an exposure-based exemplar), and relaxation therapy (an active control psychotherapy) in 110 unmedicated patients who had chronic PTSD and a score >50 on the Clinician-Administered PTSD Scale (CAPS). Randomization stratified for comorbid major depression. The authors hypothesized that IPT would be no more than minimally inferior (a difference <12.5 points in CAPS score) to prolonged exposure. Results: All therapies had large within-group effect sizes (d values, 1.32-1.88). Rates of response, defined as an improvement of >30% in CAPS score, were 63% for IPT, 47% for prolonged exposure, and 38% for relaxation therapy (not significantly different between groups). CAPS outcomes for IPT and prolonged exposure differed by 5.5 points (not significant), and the null hypothesis of more than minimal IPT inferiority was rejected (p=0.035). Patients with comorbid major depression were nine times more likely than nondepressed patients to drop out of prolonged exposure therapy. IPT and prolonged exposure improved quality of life and social functioning more than relaxation therapy. Conclusions: This study demonstrated noninferiority of individual IPT for PTSD compared with the gold-standard treatment. IPT had (nonsignificantly) lower attrition and higher response rates than prolonged exposure. Contrary to widespread clinical belief, PTSD treatment may not require cognitive-behavioral exposure to trauma reminders. Moreover, patients with comorbid major depression may fare better with IPT than with prolonged exposure.

BACKGROUND: Antagonists of N-methyl-D-aspartate-type glutamate receptors (NMDAR) induce symptoms that closely resemble those of schizophrenia, including negative symptoms. D-serine is a naturally occurring NMDAR modulator that reverses the effects of NMDAR antagonists in animal models of schizophrenia. D-serine effects have been assessed previously for treatment of established schizophrenia, but not in the early stages of the disorder. We aimed to assess effects of D-serine on negative symptoms in at risk individuals. METHODS: We did a double-blind, placebo-controlled, parallel-group randomised clinical trial at four academic US centres. Individuals were eligible for inclusion in the study if they were at clinical high risk of schizophrenia, aged between 13-35 years, had a total score of more than 20 on the Scale of Prodromal Symptoms (SOPS), and had an interest in participation in the clinical trial. Exclusion criteria included a history of suprathreshold psychosis symptoms (ie, no longer qualifying as prodromal) or clinical judgment that the reported symptoms from the SOPS were accounted for better by another disorder (eg, depression). Randomisation was done using a generated list with block sizes of four. Participants were stratified by site, with participants, investigators, and assessors all masked through use of identical looking placebos and centralised drug dispensation to study assignment. D-serine (60 mg/kg) was given orally in divided daily doses for 16 weeks. The primary endpoint was for negative SOPS, measured weekly for the first 6 weeks, then every 2 weeks. Participants who received at least one post-baseline assessment were included in analysis. Serum cytokine concentrations were collected at baseline, midpoint, and endpoint to assess the mechanism of action. Safety outcomes including laboratory assessments were obtained for all individuals. This trial is registered with ClinicalTrials.gov, number NCT0082620. FINDINGS: We enrolled participants between April 2, 2009, and July 23, 2012. 44 participants were randomly assigned to receive either D-serine (n=20) or placebo (n=24); 35 had assessable data (15 D-serine, 20 placebo). D-serine induced a 35.7% (SD 17.8) improvement in negative symptoms, which was significant compared with placebo (mean final SOPS negative score 7.6 [SEM 1.4] for D-serine group vs 11.3 [1.2] for placebo group; d=0.68, p=0.03). Five participants who received D-serine and nine participants who received placebo discontinued the study early because of withdrawn consent or loss to follow-up (n=8), conversion to psychosis (n=2), laboratory-confirmed adverse events (n=2), or protocol deviations (n=2). INTERPRETATION: This study supports use of NMDAR-based interventions, such as D-serine, for treatment of prodromal symptoms of schizophrenia. On the basis of observed effect sizes, future studies with sample sizes of about 40 per treatment group would be needed for confirmation of beneficial effects on symptoms and NMDAR-related inflammatory changes. Long-term studies are needed to assess effects on psychosis conversion in individuals at clinical high risk of schizophrenia. FUNDING: National Institutes of Health.

PURPOSE: The aim of this study was to examine prevalence and correlates of health-risk behaviors in 12- to 17.5-year-olds investigated by child welfare and compare risk-taking over time and with a national school-based sample. METHODS: Data from the National Survey of Child and Adolescent Well-Being (NSCAW II) were analyzed to examine substance use, sexual activity, conduct behaviors, and suicidality. In a weighted sample of 815 adolescents aged 12-17.5 years, prevalence and correlates for each health-risk behavior were calculated using bivariate analyses. Comparisons to data from NSCAW I and the Youth Risk Behavior Survey were made for each health-risk behavior. RESULTS: Overall, 65.6% of teens reported at least one health-risk behavior with significantly more teens in the 15- to 17.5-year age group reporting such behaviors (81.2% vs. 54.4%; p /=64 reported at least one health-risk behavior. The prevalence of smoking was lower than in NSCAW I (10.5% vs. 23.2%; p