James Schmitt - Academia.edu (original) (raw)

Papers by James Schmitt

THE QUANTITATIVE GENETICS OF NELRODEVELOPMENT: A MAGNETIC RESONANCE IMAGING STUDY OF CHILDHOOD AN... more THE QUANTITATIVE GENETICS OF NELRODEVELOPMENT: A MAGNETIC RESONANCE IMAGING STUDY OF CHILDHOOD AND ADOLESCENCE By James E. Schmitt A Dissertation submitted in partial filfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2007 Major Directors: Kenneth S. Kendler, M.D. Distinguished Professor, Departments of Psychiatry and Human Genetics and Michael C. Neale, Ph.D. Professor, Departments of Psychiatry and Human Genetics Understanding the causes of individual differences in brain structure may give clues about the etiology of cognition, personality, and psychopathology, and also may identify endophenotypes for molecular genetic studies on brain development. We performed a comprehensive statistical genetic study of anatomic neuroimaging data from a large pediatric sample (N=600+) of twins and family members from the Child Psychiatry Branch at the NINIH. These analyses included variance decomposition ...

NeuroImage, Jan 15, 2010

The impact of genetic and environmental factors on human brain structure is of great importance f... more The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51-59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of glob...

Human Brain Mapping, 2009

In this report, we present the first regional quantitative analysis of age-related differences in... more In this report, we present the first regional quantitative analysis of age-related differences in the heritability of cortical thickness using anatomic MRI with a large pediatric sample of twins, twin siblings, and singletons (n 5 600, mean age 11.1 years, range 5-19). Regions of primary sensory and motor cortex, which develop earlier, both phylogenetically and ontologically, show relatively greater genetic effects earlier in childhood. Later developing regions within the dorsal prefrontal cortex and temporal lobes conversely show increasingly prominent genetic effects with maturation. The observation that regions associated with complex cognitive processes such as language, tool use, and executive function are more heritable in adolescents than children is consistent with previous studies showing that IQ becomes increasingly heritable with maturity(Plomin et al. [1997]: Psychol Sci 8:442-447). These results suggest that both the specific cortical region and the age of the population should be taken into account when using cortical thickness as an intermediate phenotype to link genes, environment, and behavior.

Cerebral Cortex, 2008

Structural magnetic resonance imaging data from 308 twins, 64 singleton siblings of twins, and 22... more Structural magnetic resonance imaging data from 308 twins, 64 singleton siblings of twins, and 228 singletons were analyzed using structural equation modeling and selected multivariate methods to identify genetically mediated intracortical associations. Principal components analyses (PCA) of the genetic correlation matrix indicated a single factor accounting for over 60% of the genetic variability in cortical thickness. When covaried for mean global cortical thickness, PCA, cluster analyses, and graph models identified genetically mediated fronto-parietal and occipital networks. Graph theoretical models suggest that the observed genetically mediated relationships follow small world architectural rules. These findings are largely concordant with other multivariate studies of brain structure and function, the twin literature, and current understanding on the role of genes in cortical neurodevelopment.

Twin Research and Human Genetics, 2007

This article reviews the extant twin studies employing magnetic resonance imaging data (MRI), wit... more This article reviews the extant twin studies employing magnetic resonance imaging data (MRI), with an emphasis on studies of populationbased samples. There have been approximately 75 twin reports using MRI, with somewhat under half focusing on typical brain structure. Of these, most are samples of adults. For large brain regions such as lobar volumes, the heritabilities of large brain volumes are consistently high, with genetic factors accounting for at least half of the phenotypic variance. The role of genetics in generating individual differences in the volumes of small brain regions is less clear, mostly due to a dearth of information, but rarely because of disagreement between studies. Multivariate analyses show strong genetic relationships between brain regions. Cortical regions involved in language, executive function, and emotional regulation appear to be more heritable than other areas. Studies of brain shape also show significant, albeit lower, genetic effects on population...

Journal of NeuroVirology, 2015

Human brain mapping, Jan 24, 2018

Genetic and environmental influences on cortical thickness (CT) and surface area (SA) are thought... more Genetic and environmental influences on cortical thickness (CT) and surface area (SA) are thought to vary in a complex and dynamic way across the lifespan. It has been established that CT and SA are genetically distinct in older children, adolescents, and adults, and that heritability varies across cortical regions. Very little, however, is known about how genetic and environmental factors influence infant CT and SA. Using structural MRI, we performed the first assessment of genetic and environmental influences on normal variation of SA and CT in 360 twin neonates. We observed strong and significant additive genetic influences on total SA (a = 0.78) and small and nonsignificant genetic influences on average CT (a = 0.29). Moreover, we found significant genetic overlap (genetic correlation = 0.65) between these global cortical measures. Regionally, there were minimal genetic influences across the cortex for both CT and SA measures and no distinct patterns of genetic regionalization...

European Neuropsychopharmacology

Academic radiology, Jan 16, 2017

Fluoroscopy-guided lumbar puncture (FGLP) is an operator-dependent procedure that can contribute ... more Fluoroscopy-guided lumbar puncture (FGLP) is an operator-dependent procedure that can contribute to lifetime cumulative radiation dose. Benchmark fluoroscopic times (FTs) have been published for ranges of body mass index (BMI), but trends in FT in FGLPs performed by neuroradiology trainees during their training have not been studied. The purpose of this study was to investigate the trends in FTs in FGLPs performed by neuroradiology fellows in an academic year. We retrospectively reviewed FGLPs performed at our institution from July 2013 to June 2015 and determined the FT average and standard deviation of residents and non-neuroradiology fellows, neuroradiology fellows, and neuroradiology attendings. We used the Kruskal-Wallis test to evaluate group differences in FT in operator groups and academic quarters and by patient age, BMI, and needle length. Linear and Poisson regression analyses were performed to directly examine the relationship between the number of FGLPs performed and FT...

Medecine Et Hygiene, 2001

Biol Psychiat, 2002

This study evaluated differences in caudate volumes in subjects with velo-cardio-facial syndrome ... more This study evaluated differences in caudate volumes in subjects with velo-cardio-facial syndrome due to a 22q11.2 (22qDS) deletion. Because psychosis is observed in 30% of adult subjects with 22qDS, this neurogenetic disorder could represent a putative model for a genetically mediated subtype of schizophrenia. Caudate volumes were measured on high-resolution magnetic resonance images in 30 children and adolescents with 22qDS and 30 gender- and age-matched normal comparison subjects. Caudate head volumes were increased in the 22qDS group independent of neuroleptic medications. Subjects with 22qDS also displayed an abnormal pattern of asymmetry in the anterior caudate, with left side greater than right. Alterations in the basal ganglia circuitry have been implicated in learning, cognitive, and behavioral problems in children and therefore could be involved in the expression of the neurobehavioral phenotype expressed by subjects with 22qDS. Abnormal caudate volume is a neurodevelopmental feature shared with schizophrenia, further establishing 22qDS as a potential neurodevelopmental model for this disorder.

Journal of Psychiatric Research, 2001

Williams syndrome (WMS) is a rare genetic disorder characterized by relative preservations of lan... more Williams syndrome (WMS) is a rare genetic disorder characterized by relative preservations of language ability and facial processing despite deficits in overall intelligence, problem solving, and visuospatial processing. Subjects with WMS also display hypersocial behavior and excessive linguistic affect during conversations and when giving narratives. Neuroimaging studies have shown global reductions in the brain volumes of subjects with WMS compared with normal controls, but with preservations in cerebellar volume. This study examines the neuroanatomic structure of the cerebellar vermis in 20 subjects with WMS and 20 ageand gender-matched controls via high-resolution magnetic resonance imaging. The vermis was divided into lobules I-V, VI-VII, and VIII-X. Lobules VI-VII and VIII-X were both relatively enlarged in the WMS group, and after adjusting for the smaller size of the WMS brain, the posterior vermis was significantly larger in WMS (Mann-Whitney z-value=4.27; P< 0.001). Given that reductions in posterior vermis size have been implicated in flattened affect and autistic features, increased vermis size in subjects with WMS may be related to the hypersociality and heightened affective expression characteristic of individuals with this genetic condition.

European radiology, Jan 11, 2015

To identify features of obstructive airway disease on sagittal reconstruction, compare the accura... more To identify features of obstructive airway disease on sagittal reconstruction, compare the accuracy of findings to traditional imaging characteristics of COPD, and determine the fraction of additional cases identified using new characteristics. The study was approved by the centre's Institutional Review Board and is HIPAA compliant. Two hundred sixteen patients with HRCT and spirometry within a 3-month window were included. Four radiologists evaluated each HRCT for traditional characteristics of COPD and new quantitative and qualitative features of obstruction on axial and sagittal reconstructions. Imaging characteristics were assessed for correlation with the spirometric diagnosis of obstructive airway disease. Quantitative and qualitative findings on sagittal reconstruction are highly specific for COPD (specificity >90 %). Features of hyperinflation on sagittal reconstruction are more accurate predictors of obstruction than traditional axial measures, with greater interobse...

The British journal of radiology, Jan 29, 2015

While hemangiomas are common benign vascular lesions involving the spine, some behave in an aggre... more While hemangiomas are common benign vascular lesions involving the spine, some behave in an aggressive fashion. We investigated the utility of fat suppressed sequences to differentiate between benign and aggressive vertebral hemangiomas. Patients with the diagnosis of aggressive vertebral hemangioma and available STIR or T2 fat saturation sequence were included in the study. Eleven patients with typical asymptomatic vertebral body hemangiomas were selected as the control group. Region of interest signal intensity (SI) analysis of the entire hemangioma as well as the portion of each hemangioma with highest signal on fat saturation sequences was performed and normalized to a reference normal vertebral body. A total of 8 patients with aggressive vertebral hemangioma and 11 patients with asymptomatic typical vertebral hemangioma were included. There was a significant difference between total normalized mean SI ratio (3.14 vs 1.48, p=0.0002), total normalized maximum SI ratio (5.72 vs 2....

Annals of the American Thoracic Society, 2015

To evaluate the rate of agreement of pulmonary embolism in CT-pulmonary angiogram (CTPA) studies ... more To evaluate the rate of agreement of pulmonary embolism in CT-pulmonary angiogram (CTPA) studies and to evaluate the rate of inaccurate interpretations in the community hospital setting. Using the keywords &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;pulmonary embolism/embolus/emboli,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; the radiology information system was searched for CTPA performed over a 3-year period at three US community hospitals. Studies containing probable or definite pulmonary emboli were reviewed independently by four subspecialty thoracic radiologists. Agreement about the presence of PE progressively decreased with decreasing diameter of pulmonary vascular lesions (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). There was a sharp fall in observer agreement for PE of subsegmental lesions (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). The frequency of agreement decreased with decreasing quality of the imaging exam (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Community radiologists were prone to false positive PE diagnosis of small and/or peripheral pulmonary arterial defects. The probability of a false positive diagnosis and indeterminate exams progressively increased with 1) more peripheral location of the lesion, 2) decreased size (short axis diameter) of the lesion and 3) with diminishing quality of the CT examination. 48/177 (27%) of subsegmental vascular defects identified by community radiologists were deemed indeterminate and 27/177 (15%) of subsegmental vascular defects were judged to be false positive for pulmonary embolism by the consensus diagnosis. 54/274 (20%) of vascular defects with short axis less than 6mm were indeterminate for pulmonary embolism and 37/274 (14%) of vascular defects with short axis less than 6mm were false positive for pulmonary embolism. 11/13 (85%) of vascular lesions identified as pulmonary emboli on the lowest quality CT examinations were false positive or indeterminate for pulmonary embolism. False positive examinations were most often due to respiratory motion artifact (19/38, 50%). There is relatively poor interobserver agreement for subsegmental and/or small pulmonary artery defects, especially in CTPA degraded by technical artifacts. These factors can lead to an increased frequency of inaccurate interpretation or indeterminate diagnosis of small or peripheral defects. Caution is indicated in interpreting the significance of small vascular defects in CTPA.

Journal of vascular and interventional radiology : JVIR, 2015

Google Trends was used to characterize the relationship between the interventional radiology (IR)... more Google Trends was used to characterize the relationship between the interventional radiology (IR) applicant pool and related Internet queries for "IR fellowship" from July 2006 to July 2013. Results were compared with National Residency Match Panel data by regression analysis and one-way analysis of variance. Search traffic for IR fellowship demonstrated a statistically significant linear annual increase (R(2) = 0.87; P = .0013). Total IR applicants increased by 184% (R(2) = 0.98; P = .0216). Search traffic was predictive of applicants for each match year (R(2) = 0.92; P = .0004) and programs filled (R(2) = 0.93; P = .0003). Internet queries mirror trainee professional interests, with significant increases in search traffic related to IR fellowship and strong correlation with growth in applicants.

Genetics and Genomics of Neurobehavioral Disorders, 2003

Neuropsychopharmacology, 2014

The advent of magnetic resonance imaging, which safely allows in vivo quantification of anatomica... more The advent of magnetic resonance imaging, which safely allows in vivo quantification of anatomical and physiological features of the brain, has revolutionized pediatric neuroscience. Longitudinal studies are useful for the characterization of developmental trajectories (ie, changes in imaging measures by age). Developmental trajectories (as opposed to static measures) have proven to have greater power in discriminating healthy from clinical groups and in predicting cognitive/behavioral measures, such as IQ. Here we summarize results from an ongoing longitudinal pediatric neuroimaging study that has been conducted at the Child Psychiatry Branch of the National Institute of Mental Health since 1989. Developmental trajectories of structural MRI brain measures from healthy youth are compared and contrasted with trajectories in attention-deficit/hyperactivity disorder (ADHD) and childhood-onset schizophrenia. Across ages 5-25 years, in both healthy and clinical populations, white matter volumes increase and gray matter volumes follow an inverted U trajectory, with peak size occurring at different times in different regions. At a group level, differences related to psychopathology are seen for gray and white matter volumes, rates of change, and for interconnectedness among disparate brain regions.

Psychiatry Research: Neuroimaging, 2006

Velo-cardio-facial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a common genetic ... more Velo-cardio-facial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a common genetic condition associated with increased risk for developing schizophrenia. Given that cortical malformations play an integral role in the pattern of neuroanatomical alterations associated with VCFS, the aim of the present study was to quantify and localize gyral abnormalities. Magnetic resonance images were obtained on a 1.5 T scanner. The gyrification index (GI), a measure of the degree of cortical complexity, was differentially calculated for each lobe using a semi-automated protocol. The GI was calculated for 37 patients affected by VCFS as well as for 36 comparison individuals group-matched for age, handedness, and gender. The subjects affected by VCFS showed a significant decrease in the GI in the frontal and parietal lobes compared with the control group. The pattern of decreased gyrification in the frontal and parietal lobes further defines the structural changes associated with the syndrome and suggests underlying abnormalities in neural connectivity. Aberrant connectivity may be partially responsible for the cognitive and behavioral impairments in the syndrome, as well as the high incidence of schizophrenia among affected individuals.

Twin Research and Human Genetics, 2005

Several large studies have demonstrated that the liability to smoke cigarettes is strongly geneti... more Several large studies have demonstrated that the liability to smoke cigarettes is strongly genetically influenced. However, the role of genetic and environmental risk factors in the use of other common forms of tobacco use has yet to be studied. Data on the regular use of cigarettes, cigars, pipes, dip (moist snuff), and chewing tobacco from 2634 male twins were analyzed with ACE structural equation models. Twin similarity for regular cigarette and dip use was largely genetic in origin. However, twin resemblance for chewing tobacco was just about equally the result of genes and shared environment, and twin similarity for use of pipes and cigars was entirely the result of shared environmental factors. Thus, the genetic influences on the liability for regular tobacco use appear to vary based on tobacco type. The causes for the use of different forms of tobacco are complex and worthy of further study.