STRUCTURAL AND FUNCTIONAL BASIS OF PSYCHIATRIC DISEASE
RESEARCH AND TRAINING PROGRAM MENTORS

 

Nancy Andreasen, M.D., Ph.D.
Psychiatry

Dr. Andreasen's research interests include neuroimaging, image analysis techniques & software development, translational integration of systems level and molecular level research in specific diseases, cognitive neuroscience, and schizophrenia. Current projects include the neurobiology of major psychosis, brain imaging in the major psychoses, phenomenology and classification of schizophrenia, neurodevelopment and aging in the normal brain, gender differences in the brain, and mechanisms of creativity in creative persons.

Stephan Arndt, Ph.D.
Psychiatry

Dr. Stephan Arndt is Professor in the Department of Psychiatry and in the Department of Biostatistics. He has specialized in measurement methods, longitudinal, and robust data analyses in biobehavioral clinical research and in epidemiology. He has been involved in several psychiatric clinical trials, multisite investigations, and data safety management boards at local and national levels. Specific areas and populations that Dr. Arndt has researched include patients with schizophrenia and affective disorders, substance abuse in special populations (e.g., elderly), and criminal justice populations. He has authored approximately 200 publications and has been a mentor for several NIH K-awardees. Dr. Arndt is also the Director of the Iowa Consortium for Substance Abuse Research and Evaluation at the University of Iowa.

Gary E. Christensen, D.Sc.
Electrical & Computer Engineering

Gary E. Christensen, D.Sc. has over fourteen years of experience developing and evaluating image high-dimensional nonrigid image registration algorithms including linear elastic, viscous fluid, and inverse consistent image registration algorithms. He has published 22 journal papers and 37 conference papers and has 4 United States patents related to image registration. Over the last five years, he has concentrated on developing image registration methods that reduce correspondence errors based on minimizing the inverse consistency error. More recently, he has developed a large deformation inverse consistent elastic registration algorithm, developed methods for computing average population shape using image registration and developed statistical methods for detecting significant shape differences between populations of images. Dr. Christensen’s image registration research is motivated by and applied to clinically relevant problems. These projects have included studying normal and abnormal craniofacial shape imaged by CT (The Whitaker Foundation, Christensen PI); studying the normal and shape variability of the brain imaged by MRI (NIH NS35368, Vannier PI), tracking shape changes of soft-tissue pelvic structures deformed by intracavitary brachytherapy treatment of cervical cancer imaged by CT (NIH CA75731 Williamson, PI), and modeling the shape of the cochlea to help improve cochlear implants (NIH DC03590, Wang, PI). Dr. Christensen is currently leading the image registration efforts on two NIH grants for modeling the shape and shape variability of normal lungs (HL64368, Hoffman, PI) and for tracking lung motion during radiation treatment of lung cancer tumors (CA096679, Low, PI).

William Coryell, M.D.
Psychiatry

I currently have five areas of research interest. Work for the first three has been underway and large data sets are available for further analyses. The other two areas are the topics of proposals that have been submitted for NIH funding. The most long-standing of these interests concerns the long-term course of the major affective e disorders. I have participated in a multi-center follow-up of a large cohort that began in 1977 and that has recently been renewed for an additional 5 years. The study has provided a unique combination of follow-up duration and surveillance intensity. Over the past 8 years I have explored reactions to CO2 inhalation as a trait marker for panic disorder and now have a large sample of subjects who have a family history, but no personal history, of panic disorder and who have undergone CO2 challenge procedures as well as personality testing. A third area of ongoing data analysis concerns efforts to identify clinical and neuroendocrine predictors of completed suicide. The data describe over 600 individuals evaluated for major depressive disorder 20 years ago and given neuroendocrine challenge tests. Deaths during follow-up have been identified and characterized. Of the 2 proposals under review, one concerns the assessment of omega-3 erythrocyte concentrations as a predictor of response to SSRI antidepressants and the use of omega-3 supplementation in patients who have had inadequate SSRI responses. The other proposes to track volumetric changes in the cingulate gyrus and hippocampus in patients with familial major depressive disorder and to determine correlates with clinical outcome and HPA-axis activity.

Michael Flaum, M.D.
Psychiatry

Michael Flaum, M.D. completed a 2 year post-doctoral fellowship with Dr. Nancy Andreasen in 1990. He then joined the faculty of the University of Iowa and served as Director of the Assessment and Training Core Unit of an NIMH-funded Mental Health Clinical Research Center, and later the Center’s Co-Director until 1999. During that time, the focus of his work was on the assessment and diagnosis of psychotic disorders, as well as structural and functional imaging of psychotic disorders. In 1999, he assumed the Directorship of the Iowa Consortium for Mental Health. With that, his research focus changed to mental health services research in Iowa. This has involved research on telepsychiatry, utilization patterns of psychiatric medications, psychiatric illness in correctional settings, and implementation of evidence-based mental health practices at the community level.

Richard Hichwa, Ph.D.
Radiology

Positron emission tomography (PET) is one of the corner stones of the new molecular imaging approach to investigational research. As part the University of Iowa program, researchers have the opportunity to work on new tracer development (radiopharmaceutical chemistry), clinical imaging protocols (clinical trials), fundamental imaging protocols (biodistribution and pharmacology studies), animal imaging (basic physiology and biochemistry investigation), and analysis of multidimensional data (image processing, blood and tissue analysis, etc). This combination of basic research and translation to clinical utility is key to multidisciplinary research in PET. Candidates for the Multidisciplinary Clinical Research Career Development Program will have full access to the PET facilities which include a medical cyclotron, radiochemistry laboratories, two state-of-the-art PET/CT systems and a dedicated research PET scanner for translational studies. In addition, a complete small animal imaging center is being developed which includes the following imaging systems: microPET, microSPECT, microCT, microMRI, optical imaging and scintigraphy. These provide the initial research capabilities for cancer biology investigation as well as other areas of candidate interest such as cardiac and neurologic research. The research team in PET consists of nuclear medicine physicians, physicists, radiochemists, electrical engineers, software engineers, pharmacokineticists and support staff. PET offers an excellent opportunity for the candidates to participate in a truly multidisciplinary research experience.

Ricardo Jorge, M.D.
Psychiatry

My research interests are centered on the study of behavioral disturbances occurring as a consequence of structural brain damage. Currently, we are studying the effect of antidepressant therapy on recovery from stroke. In the next few years, we will examine the efficacy of serotonin reuptake inhibitors in preventing the onset of post-stroke depression. In addition, we will examine how antidepressants modulate stress responses during the subacute stroke period as well as the effect of antidepressants on the neuroplastic changes that support physical and behavioral recovery from stroke. A related aim is to analyze the effect of s-citalopram on platelet physiology and to assess if the observed changes in platelet function are associated with prevention of cardiovascular complications, including recurrent stroke. A second area of interest concerns the use of Magnetic Stimulation Therapy as a treatment alternative for depressive and apathetic syndromes occurring in patients with neurological illness, particularly refractory depression associated with cerebrovascular disease. We are also using low frequency repetitive Transcranial magnetic Stimulation (rTMS)in combination with Cognitive Behavioral Therapy (CBT) to treat refractory auditory hallucinations in patients with schizophrenia. The physiopathology and treatment of affective disorders occurring after Traumatic Brain Injury constitutes a third but equally important field of future research. Finally, we are also starting preliminary studies on the physiopathology and treatment of depressive and psychotic disorders associated with Parkinson's disease.

Vincent Magnotta, Ph.D.
Radiology

The focus of my research is neuroimaging as related to psychiatric and neurological disorders. The main area of interest is the development of new imaging sequences (e.g. CAIR) and novel image analysis techniques (neural network based segmentation and surface analysis) to study brain morphology and function. This has included high resolution brain morphology and quantitative analysis, diffusion tensor imaging, first pass bolus contrast perfusion imaging, and functional magnetic resonance imaging. Current areas of interest include the development of statistical analysis tools for diffusion tensor data, tract tracing algorithms, study and quantification of scanner geometric distortions for longitudinal studies, and high dimensional inter-subject image registration for group analysis of fMR cognitive paradigms. Finally, I am involved in two multi-center schizophrenia imaging studies (Functional BIRN, MIND). The main effort in these studies is to merge data collected from multiple centers using different scanner platforms, vendors and field strengths. The main challenges in fMR across centers, scanner vendors, and field strengths is the development of a calibration protocol and statistical tools that are able to account for differences in image smoothness, sensitivity and stability across sites.

Del D. Miller, Pharm.D., M.D.
Psychiatry

Dr. Miller’s research has focused primarily on the clinical psychopharmacology of schizophrenia. My research goals have been to improve the clinical treatment of patients with schizophrenia and other psychotic disorders, by undertaking research studies that help inform us about the mechanisms of newer pharmacological treatments, determining useful predictors of maximizing clinical response, comparing the effectiveness of newer medications, and examining the efficacy of new nonpharmacological treatments.

Jeffrey Murray, M.D.
Pediatrics

The focus of our group is to develop an understanding of the genetic and environmental causes of birth defects and to implement programs for their improved treatment and prevention. Our lab uses molecular genetic and epidemiologic approaches to identify genes and their interactions using cleft lip and palate as our primary model system. We collaborate closely with epidemiologists, public health specialists, embryologists, developmental biologists and quantitative geneticists to achieve these goals. Using large populations in multiple sites around the world, including our home state of Iowa, as well as through collaborative interactions with the Centers for Disease Control, the University of Southern Denmark, the University of Rio de Janeiro and Operation Smile in the Philippines. We collect exposure data and utilize DNA from individuals and families with cleft lip and palate to investigate causes. In the last two years our lab has identified three major genes, MSX1, FGFR1, and IRF6 as playing an important role in cleft lip and palate and has also demonstrated the role of folic metabolizing genes and smoking detoxification pathway genes in modifying some of these affects. We have recently initiated two clinical trials, one to decrease mortality and morbidity of children born with clefts and indigent populations in South America and the second to determine whether folic acid supplementation can be used to prevent occurrences of cleft lip and palate and in families in which one child has already been born with the cleft being carried out in Brazil. Our lab works hard to move from the basic science aspects of craniofacial development through epidemiology and clinical trials to implement a comprehensive program related to studying birth defects. Our labs role in the training of clinical scholars would be to provide specific projects that could range from basic science to clinical trials and to demonstrate how a cohesive whole can be developed through strong collaborations and focus on specific environmental and genetic interactions.

Peg Nopoulos, M.D.
Psychiatry

The focus of the research done by Dr. Nopoulos and colleagues is the study of the structure and function of the brain in normal and pathologic conditions. Neuroimaging tools of Magnetic Resonance (MR) and Positron Emission Tomography (PET) are used. In regard to structural imaging, a powerful software package (locally developed) allows for a detailed quantification of brain morphology using MR including tissue volume segmentation (globally and regionally) and fine measures of the cortex including cortical depth, surface area, and sulcal/gyral shape. Functional imaging using fMR and PET allows for functional mapping of the brain. These powerful tools provide images of blood flow (a proxy of metabolism) while a subject is engaged in a task such as attention, memory, or even emotion provocation. The subject population that these tools are used on are varied and include study of the normal brain, schizophrenia, subjects with clefts of the lip/palate, and Huntington's Disease. In regard to the normal brain, focus is on understanding changes during development, especially over the years of puberty and maturation. Another area of study in the normal brain is the differences in structure and function between male and female brains. Studies in schizophrenia are large and ongoing and include topics such as longitudinal change in brain structure over the course of the illness and in regard to treatment. The study of orofacial clefting is focused on children and evaluates the neural underpinnings of abnormal speech and language in this population. These studies also link to molecular genetic studies of orofacial clefting in a powerful research method known as behavioral neurogenetics. Finally, little is known about the early manifestations of Huntington's Disease, another focus of our imaging studies.

Daniel S. O’Leary, Ph.D.
Psychiatry

Daniel S. O’Leary, Ph.D. is a Professor in the Department of Psychiatry at the University of Iowa. His expertise is in cognitive neuroscience, and he conducts research using structural and functional brain imaging and cognitive assessments in several clinical populations including schizophrenia and drug abuse, as well as studying normal brain development. Over the past 15 years Dr. O’Leary has investigated the biological basis of schizophrenia using Positron Emission Tomography (PET), structural and functional magnetic resonance imaging (fMRI), and cognitive tasks. This work is carried out in collaboration with a multi-disciplinary team of researchers in the Department of Psychiatry, which includes graduate students from several programs, and M.D. and Ph.D. post-doctoral fellows. Among other findings, this work has found that the cerebellum has abnormal blood flow during a number of cognitive tasks in schizophrenic subjects. Dr. O’Leary’s current research, funded by NIMH, investigates timing, motor sequencing, and other putative functions of the cerebellum in normal volunteers and schizophrenic subjects. Dr. O’Leary also has an interest in changes in brain function that are caused by acute and chronic use of marijuana. This work has also found that smoking marijuana greatly increases blood flow in the cerebellum and ventral forebrain, and that the cerebellar changes are associated with abnormalities on subjective timing tasks. Current research funded by NIDA uses PET to explore the blood flow changes caused by smoking marijuana in occasional and chronic users of the drug during a number of different tasks that are mediated in part by the cerebellum.

Sergio Paradiso, M.D., Ph.D.
Psychiatry

I conduct research in the emotional consequences of neuropsychiatric disorders and functional neuroimaging using positron emission tomography (PET) and structural magnetic resonance (MR) imaging. We compare the responses of young and older healthy normal volunteers on a series of hierarchically arranged social cognition tests. The neural networks associated with processing social and emotional stimuli will be mapped via fMRI in young and older samples. The long term goals of the research is to longitudinally examine age-related changes in the recognition of affective and social stimuli. We measure social cognitive skills and relate them to emotional experience and psychiatric morbidity, specifically examining the protective versus detrimental nature of reduced perception of affectively unpleasant stimuli. Many conditions such as depression or pain syndromes, rely on self-reported data in determining the diagnosis. These data are influenced by the individual’s perception of his or her “inner and outer world.” Hence a change in emotional and social perception in late life may greatly influence the phenomenology of emotional conditions and how they are detected and treated. The research has a strong neurobiological emphasis, using fMRI to test the applicant’s hypotheses that change in frontal and temporal cortices occurring in late life may influence perception of socially relevant stimuli. These neuroanatomical changes may be detected early with functional imaging techniques.

Jane Paulsen, Ph.D.
Psychiatry

Research Interests: Mental disorders of aging, Huntington’s disease, Alzheimer’s disease, schizophrenia, dementia, psychoses, tardive dyskinesia, neuropsychological features and correlates of the above.

Laura L. Boles Ponto, Ph.D.
Radiology

Dr. Laura L. Boles Ponto, Ph.D., R.Ph., is an associate research scientist in the Positron Emission Tomography (PET) Imaging Center and adjunct assistant professor in the Department of Radiology.  She is an expert in PET data acquisition and analysis for both clinical and research purposes.  As one of the initial faculty instrumental in the establishment of the PET Imaging Center at the University of Iowa, she has been involved in the formulation and implementation of clinical and research protocols for brain, cardiac and whole-body imaging; the education of students, residents, fellows and new investigators in the capabilities and limitations of PET imaging as a tool; and the analysis and interpretation of imaging data.  With the recent acquisition of a small animal PET scanner, she has been involved in the development of methods for imaging small animals (i.e., mice).  Research interests include the use of PET imaging for the monitoring of therapeutic response in oncology, in brain mapping of cognitive processes in normals and diseased individuals, and the relationship between cognition, cerebral blood flow, cerebrovascular reserve and peripheral blood flow in dementia and mild cognitive impairment.

Robert Robinson, M.D.
Psychiatry

Mood disorders associated with brain injury; Animal models of affective disorders; The mechanism and mood manifestations of brain asymmetry; Mechanism of mood regulation in humans; Mood disorders following traumatic brain injury; Use of transcranial magnetic stimulation in the treatment of depression in the elderly.

Susan K. Schultz, M.D.
Psychiatry

Susan K. Schultz, M.D., is an Associate Professor of in the Department of Psychiatry with a joint appointment as Associate Director for Clinical Research for the Center on Aging. Dr. Schultz has board certification in Geriatric Psychiatry and has developed an independent research program focused on impairments in late life related to emotional and cognitive symptoms. Dr. Schultz’ federal grant support has included a National Institutes of Mental Health K08 award to study adverse medication effects in late-life. She also presently directs an NIMH R21 exploratory treatment study to test novel interventions for mild cognitive impairment. This study utilizes positron emission tomography imaging in persons with mild cognitive impairment to longitudinally follow the treatment effects of cholinesterase inhibitors. Dr. Schultz also directs a project in collaboration with the New York State Psychiatric Institute to study the effects of medication discontinuation in elderly adults with dementia. Over the past decade, Dr. Schultz has played a substantial role in the career development of several junior researchers, and she has facilitated the submission of several NIH K-series applications and small grants. Locally, Dr. Schultz conducts a weekly small-group geriatric mentorship meeting within the Department of Psychiatry as well as twice monthly larger seminars with the Center on Aging (i.e., COA Research Seminars for Research Mentorship and Collaboration), which has hosted presentations of grants in development by researchers in Family Medicine, Pharmacy, Public Health and Psychiatry.

Val Sheffield, M.D., Ph.D.
Pediatrics

Our laboratory uses molecular methods to better understand a variety of human genetic diseases including complex disorders. We use positional and candidate approaches to identify disease genes, and use biochemical methods and animal models to help elucidate disease pathophysiology with the goal of improved prevention and treatments. Our laboratory has used genetic mapping methods to map over thirty disease loci and to identify numerous disease genes including genes involved in deafness. Current projects in the lab include the study of inherited blindness, deafness, obesity, hypertension, and autism. In addition, our laboratory has been active in genomic research. We have developed methods for improved detection of DNA mutations, as well as high density maps of the human genome, and transcription maps of the rat genome. We are using expression microarrays to profile gene expression between normal and disease states, and are actively involved in development of bioinformatic methods for the study of human genetic diseases. The laboratory is funded by the Howard Hughes Medical Institute and the National Institutes of Health.

Milan Sonka, Ph.D.
Electrical & Computer Engineering

My research focuses on development and validation of quantitative techniques analyzing human, animal, and cellular biomedical image data. In the last fifteen years, we have developed a number of clinically applicable automated techniques for assessment of cardiac structure and function from X-ray ventriculography, MR, CT, and ultrasound images. Our current focus is on earliest detection of functional changes in congenital heart disease from MR and on quantitative analysis of arterial morphology and plaque composition of coronary arteries. We have introduced and validated automated methods for quantification of endothelial function via flow-mediated dilatation (FMD) from brachial ultrasound image sequences that is widely used worldwide. We are developing a comprehensive tool for quantitative assessment of pulmonary structure and function and tissue characterization from volumetric CT images. We are developing new methods for continuous tracking and shape-change assessment of living cells in microscope images. I am an author of 2 editions of a well-received image processing textbook and an editor of one of three volumes of a comprehensive Handbook of Medical Imaging.

Daniel Tranel, Ph.D.
Neurology

My research deals with the following topics: visual recognition; face recognition; verbal and nonverbal learning and retrieval; nonconscious cognitive processing; acquired disorders of social conduct; emotional processing; psychophysiology. The work is aimed at understanding brain-behavior relationships in humans, at systems level. Two main approaches are used: (1) the lesion method, in which brain-damaged patients are studied with neuropsychological procedures to determine how certain lesion sites are related to certain cognitive and behavioral deficits; and (2) functional imaging, including PET and fMRI, in which the brain activation in normal subjects is measured while the subjects are performing various tasks. My research has been continuously and fully funded for two decades. I have about a thousand square feet of laboratory space in the Department of Neurology in the University of Iowa Hospitals.

Tom Wassink, M.D.
Psychiatry

My laboratory's goal is to identify genes that underlie susceptibility to a variety of psychiatric disorders, with our primary focus being autism. We use a variety of approaches in this endeavor, including positional cloning, sophisticated cytogenetic analyses, and candidate disease gene screening. We perform these studies in DNA obtained from numerous independent samples of families with multiple autistic individuals. We are also equipped to assess the function and expression of identified disease genes using an array of molecular and animal model techniques. Extensive additional resources and expertise are available to us here at Iowa through our collaborations with the Center for Statistical Genetics, the UIHC Cytogenetics laboratory, and the Center for Bioinformatics and Computational Biology. We are also actively investigating the genetics of panic disorder and schizophrenia. The panic disorder work uses traditional positional cloning methods and a sample of moderate to large panic disorder pedigrees. The schizophrenia genetics research is performed in association with the Department of Psychiatry's Mental Health Clinical Research Center. We collect DNA from individuals with schizophrenia, their families, and psychiatrically normal control subjects. All of these individuals participate in protocols that gather data from a wide variety of research domains, including functional and structural brain imaging, cognitive testing, disease phenomenology, longitudinal progression of disease, etc. The goal with the schizophrenia sample, therefore, is to investigate relationships between genetic information and these other types of data.

John Wemmie, M.D., Ph.D.
Psychiatry

Anxiety disorders are a major cause of disability and distress. Understanding the molecular mechanisms of anxiety may lead to improved treatment and prevention of these common illnesses. We recently found that the acid sensing ion channel ASIC1 contributes to Pavlovian fear conditioning, an important animal model of acquired anxiety. We generated knockout mice lacking the ASIC1 gene and produced transgenic mice overexpressing ASIC1. We found that ASIC1 knockout mice had less fear than wild-type littermates, while transgenic mice overexpressing ASIC1 exhibited more fear. Because ASIC1 levels modulated the degree of acquired fear, these data suggest that ASIC1 may contribute to anxiety disorders. Moreover, because disrupting ASIC1 reduced fear without causing any gross physical or behavioral abnormalities, ASIC1 inhibitors might provide a novel and safe approach for treating anxiety in the clinic. ASIC1 is required for neurons to respond normally to a drop in extracellular pH. Therefore ASIC1 activation might be important for sensing brain acidosis, which can be caused by carbon dioxide (CO 2) inhalation, which has long been known to trigger panic attacks in patients with panic disorder. Because ASIC1 can modulate fear and because it is a good candidate for detecting CO 2/acid in the brain, it may contribute to CO 2 sensitivity and perhaps panic disorder. My lab is currently exploring this hypothesis and is beginning to test the potential therapeutic value of ASIC1-inhibitors.