Faculty Bibliography

Psychiatric care for children and adolescents is limited in remote and underserved areas because of the shortage of child and adolescent psychiatrists. Telepsychiatry has the potential to alleviate this problem. This article reviews the procedures used to develop telepsychiatry, equipment needed for videoconferencing in telepsychiatry, benefits and limitations of telepsychiatry, and confidentiality issues in telepsychiatry. Many questions regarding confidentiality, legality, reimbursement, cost-effectiveness, and technology still need to be resolved. However, telepsychiatry has the potential to be a useful treatment alternative

Obtaining validation data and comparison metrics for segmentation of magnetic resonance images (MRI) are difficult tasks due to the lack of reliable ground truth. This problem is even more evident for images presenting pathology, which can both alter tissue appearance through infiltration and cause geometric distortions. Systems for generating synthetic images with user-defined degradation by noise and intensity inhomogeneity offer the possibility for testing and comparison of segmentation methods. Such systems do not yet offer simulation of sufficiently realistic looking pathology. This paper presents a system that combines physical and statistical modeling to generate synthetic multi-modal 3D brain MRI with tumor and edema, along with the underlying anatomical ground truth, Main emphasis is placed on simulation of the major effects known for tumor MRI, such as contrast enhancement, local distortion of healthy tissue, infiltrating edema adjacent to tumors, destruction and deformation of fiber tracts, and multi-modal MRI contrast of healthy tissue and pathology. The new method synthesizes pathology in multi-modal MRI and diffusion tensor imaging (DTI) by simulating mass effect, warping and destruction of white matter fibers, and infiltration of brain tissues by tumor cells. We generate synthetic contrast enhanced MR images by simulating the accumulation of contrast agent within the brain. The appearance of the the brain tissue and tumor in MRI is simulated by synthesizing texture images from real MR images. The proposed method is able to generate synthetic ground truth and synthesized MR images with tumor and edema that exhibit comparable segmentation challenges to real tumor MRI. Such image data sets will find use in segmentation reliability studies, comparison and validation of different segmentation methods, training and teaching, or even in evaluating standards for tumor size like the RECIST criteria (response evaluation criteria in solid tumors).

We present a simple computational model of the dentate gyrus to evaluate the hypothesis that pattern separation, defined as the ability to transform a set of similar input patterns into a less-similar set of output patterns, is dynamically regulated by hilar neurons. Prior models of the dentate gyrus have generally fallen into two categories: simplified models that have focused on a single granule cell layer and its ability to perform pattern separation, and large-scale and biophysically realistic models of dentate gyrus, which include hilar cells, but which have not specifically addressed pattern separation. The present model begins to bridge this gap. The model includes two of the major subtypes of hilar cells: excitatory hilar mossy cells and inhibitory hilar interneurons that receive input from and project to the perforant path terminal zone (HIPP cells). In the model, mossy cells and HIPP cells provide a mechanism for dynamic regulation of pattern separation, allowing the system to upregulate and downregulate pattern separation in response to environmental and task demands. Specifically, pattern separation in the model can be strongly decreased by decreasing mossy cell function and/or by increasing HIPP cell function; pattern separation can be increased by the opposite manipulations. We propose that hilar cells may similarly mediate dynamic regulation of pattern separation in the dentate gyrus in vivo, not only because of their connectivity within the dentate gyrus, but also because of their modulation by brainstem inputs and by the axons that 'backproject' from area CA3 pyramidal cells. (c) 2008 Wiley-Liss, Inc

Although antidepressants are moderately effective in treating major depressive disorder (MDD), concerns have arisen that selective serotonin-reuptake inhibitors (SSRIs) are associated with suicidal thinking and behavior, especially in children, adolescents and young adults. Almost no experimental research in model systems has considered the mechanisms by which SSRIs might be associated with this potential side effect in some susceptible individuals. Suicide is a complex behavior and impossible to fully reproduce in an animal model. However, by investigating traits that show strong cross-species parallels in addition to associations with suicide in humans, animal models might elucidate the mechanisms by which SSRIs are associated with suicidal thinking and behavior. Traits linked with suicide in humans that can be successfully modeled in rodents include aggression, impulsivity, irritability and hopelessness/helplessness. Modeling these relevant traits in animals can help to clarify the impact of SSRIs on these traits, suggesting avenues for reducing suicide risk in this vulnerable population.

OBJECTIVE: To report results of the clinical reappraisal study of lifetime DSM-IV diagnoses based on the fully structured lay-administered World Health Organization Composite International Diagnostic Interview (CIDI) Version 3.0 in the U.S. National Comorbidity Survey Replication Adolescent Supplement (NCS-A). METHOD: Blinded clinical reappraisal interviews with a probability subsample of 347 NCS-A respondents were administered using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) as the gold standard. The DSM-IV/CIDI cases were oversampled, and the clinical reappraisal sample was weighted to adjust for this oversampling. RESULTS: Good aggregate consistency was found between CIDI and K-SADS prevalence estimates, although CIDI estimates were meaningfully higher than K-SADS estimates for specific phobia (51.2%) and oppositional defiant disorder (38.7%). Estimated prevalence of any disorder, in comparison, was only slightly higher in the CIDI than K-SADS (8.3%). Strong individual-level CIDI versus K-SADS concordance was found for most diagnoses. Area under the receiver operating characteristic curve, a measure of classification accuracy not influenced by prevalence, was 0.88 for any anxiety disorder, 0.89 for any mood disorder, 0.84 for any disruptive behavior disorder, 0.94 for any substance disorder, and 0.87 for any disorder. Although area under the receiver operating characteristic curve was unacceptably low for alcohol dependence and bipolar I and II disorders, these problems were resolved by aggregation with alcohol abuse and bipolar I disorder, respectively. Logistic regression analysis documented that consideration of CIDI symptom-level data significantly improved prediction of some K-SADS diagnoses. CONCLUSIONS: These results document that the diagnoses made in the NCS-A based on the CIDI have generally good concordance with blinded clinical diagnoses

Although it is known that schizophrenia is associated with social class, controversy exists as to the nature of this association. The authors studied the incidence of schizophrenia in relation to social class at birth in a population-based cohort of 88,829 offspring born in Jerusalem in 1964-1976. They constructed a six-point scale to index social class, based on paternal occupation at the time of birth, with each of 108 occupations being ranked by mean education. Cox proportional hazards methods were used in adjusting for sex, parents' ages, duration of marriage and birth order. Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. There was no gradient of risk for schizophrenia associated with social class at birth; however, offspring of fathers in the lowest social class showed a modest increase in risk (adjusted Relative Risk = 1.4; 95% Confidence interval = 1.1-1.8, P = 0.002). These data suggest that in contrast to many other health outcomes, there is not a continuous gradient for increasing schizophrenia with decreasing social class of origin. Instead, a modest increase in risk for schizophrenia was observed only for those born at the bottom of the social ladder

There has been growing interest in the use of complementary and alternative treatments in pediatric bipolar disorder (BPD). There are limited data, however, regarding the safety and efficacy of these treatments. This article discusses select complementary and alternative treatments that have been considered for use in pediatric BPD and/or depression, including omega-3-fatty acids, inositol, St. John's wort, SAMe, melatonin, lecithin, and acupuncture. Background information, reference to available adult and pediatric data, proposed mechanisms of action, dosing, side effects, and precautions of these treatments are included. Across the board, more research is necessary and warranted regarding the long-term safety and efficacy of available complementary and alternative treatments for the management of pediatric BPD.

OBJECTIVE: The aim of this study was to assess the effectiveness and tolerability of a long-acting methylphenidate (MPH) formulation, beaded MPH (B-MPH), for treatment of attention-deficit/hyperactivity disorder (ADHD) in 4- and 5-year-old children. METHOD: Eleven children (9 boys and 2 girls) with ADHD received 4 weeks of B-MPH treatment in a single-site, open-label pilot study. Medication dosing was flexible, with titration to a maximum of 30 mg/day. A brief education session on behavior management was offered to parents at each treatment visit. RESULTS: Subjects experienced a mean decrease of 1.09 (standard deviation [SD]=0.73, p<0.01) on the Swanson, Nolan, and Pelham Questionnaire (SNAP-IV) ADHD composite score to an end point of 1.18 (SD=0.64). Subjects demonstrated mean decreases in scores of inattention of 1.01 (SD=0.85, p<0.01) and in hyperactivity/impulsivity of 1.17 (SD=0.74, p<0.01), with end point scores of 1.10 (SD=0.61) and 1.26 (SD=0.77), respectively. The Clinical Global Impressions-Severity (CGI-S) scale showed a statistically significant improvement from a baseline mean of 5 to the final visit mean of 3.36 (p<0.01). At the final visit, the mean daily B-MPH dose was 17.73 mg. Subjects did not experience any statistically significant changes in weight, blood pressure, or pulse during the study. The most common adverse event was decreased appetite. CONCLUSION: B-MPH was safe and effective for the treatment of ADHD in the 4- and 5-year-olds participating in this study

Frontolimbic structures involved in fear conditioning have also been associated with hypothalamic-pituitary-adrenal (HPA)-axis modulation, including amygdaloid, hippocampal, and ventromedial prefrontal cortex regions. Although HPA-axis function and endocrine changes have been investigated in the context of stress provocation, much research has not been conducted using functional neuroimaging in the study of the HPA axis and frontolimbic function in response to emotional stimuli. Using functional magnetic resonance imaging, the association of blood-oxygen-level dependent signal with salivary cortisol in response to an emotional visual scene paradigm was investigated, with prescan and postscan salivary cortisol analyzed as a covariate of interest during specific conditions. Cortisol reactivity to the paradigm was positively associated with amygdalar and hippocampal activity and negatively associated with ventromedial prefrontal cortex activity in conditions involving emotional imagery

BACKGROUND: Childhood adversity has been shown to interact with monoamine oxidase-A (MAOA) genotype to confer risk for antisocial behavior. Studies examining this gene-by-environment (G x E) association, however, have produced mixed results. METHODS: Relevant research is reviewed, and results of a study with 114 children (73 maltreated and 41 control subjects) are presented. The maltreated children represent the extreme on a continuum of adversity and were assessed at a time of extreme stress-shortly after removal from their parents' care due to abuse. Measures of aggressive behavior were obtained using standard research instruments, and monoamine oxidase-A MAOA genotypes were obtained from saliva-derived DNA specimens. Population structure was controlled for using ancestral proportion scores computed on the basis of genotypes of ancestry informative markers. RESULTS: Many prior investigations appear to have had reduced power to detect the predicted G x E interaction because of low base rates of maltreatment and antisocial behavior in their samples and failure to use optimal procedures to control for population structure in ethnically diverse cohorts. In this investigation, a significant interaction was detected between exposure to moderate trauma and the 'low-activity' MAOA genotype in conferring risk for aggression. Children with exposure to extreme levels of trauma, however, had high aggression scores regardless of genotype. CONCLUSIONS: Our study suggests that problems in aggressive behavior in maltreated children are moderated by MAOA genotype, but only up to moderate levels of trauma exposure. Extreme levels of trauma appear to overshadow the effect of MAOA genotype, especially in children assessed at time of acute crisis