Faculty Bibliography

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).

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 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: The 2003 Medicare Modernization Act shifted medication coverage from Medicaid to Medicare for persons dually eligible for both programs. This study examined the extent to which access to psychiatric and concomitant medications was reduced for dually eligible individuals in New York State. It also examined the extent to which consumer copayments and state costs were changed when the act was implemented in 2006. METHODS: Data were from psychiatric medication Medicaid claims in 2002 for the 36,842 dually eligible adults with severe mental illness and from the 2006 formulary data of New York State's 15 prescription drug plans available after the Medicare Modernization Act was implemented. The study simulated how dually eligible persons in New York State would fare under the plans' random and best-fit enrollment scenarios, taking into account the additional coverage provided by New York State's 2006 safety net policy. RESULTS: Implementation of the Medication Modernization Act reduced drug availability and increased usage restrictions. A study-defined generosity measure estimated a 51%+/-19% reduction in access. Dually eligible individuals with depression experienced the largest treatment gap. Cost changes to the state were essentially budget neutral, primarily because of the required claw-back payment. Consumer copayments increased percentage-wise, but actual dollar amounts remained small; increases were higher under best-fit enrollment compared with random enrollment. CONCLUSIONS: Without a generous safety net policy, dually eligible beneficiaries, especially those with depression, are likely to experience large gaps in their medication coverage and somewhat higher out-of-pocket costs. Treatment gaps were somewhat reduced by placement in best-fit plans, and such placement resulted in no added financial burden to the state. However, this resulted in higher consumer copayments--payments that are small in the actual dollar amount but that might have an impact on spending and on medication access for a largely poor consumer group

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

The authors examined racial/ethnic disparities in mental health service use based on problem type (internalizing/externalizing). A diverse sample of youth in contact with public sectors of care and their families provided reports of youth's symptoms and functional impairment during an initial interview. Specialty and school-based mental health service use during the subsequent 2 years was assessed prospectively. Greater disparities in mental health service receipt were evident for internalizing problems, with non-Hispanic White youth more likely to receive services in response to internalizing symptoms than minority youth. Fewer disparities in rates of unmet need emerged for externalizing problems, but minority youth were more likely to have need for externalizing problems met and African American youth were particularly likely to receive services in response to such problems. Findings highlight the importance of considering problem type when examining racial disparities in mental health services and underscore concerns about the responsiveness of mental health services for minority youth with internalizing disorders.