Prader-Willi Syndrome (PWS): Under the direction of Dr. Merlin Butler, the primary focus of this research program is the genetics of obesity, and more recently, autism. This program includes genotype-phenotype correlations in Prader-Willi syndrome (PWS), as the clinical genetic model, and an NIH funded rare disease center for genetics and natural history studies on PWS and early onset morbid obesity. PWS is the most commonly recognized cause of life-threatening obesity in children generally due to a 15q11-q13 deletion of paternal origin. The 15q11-q13 region involves important genes for development of obesity, behavioral problems and autism. Analyzing and comparing the gene expression patterns of individuals with Prader-Willi syndrome and those with simple obesity will allow for the identification of disturbed obesity related gene network pathways leading to a better understanding of factors contributing to obesity and potential treatment modalities applicable to the general population. To date, we have identified two new candidate genes for obesity (e.g., STAR, SAG) in lymphoblasts and brain tissue from PWS subjects through whole genome-wide expression analysis along with confirmation of other genes (e.g., POMC) using a PWS mouse model. This research has led to the discovery of clinical differences in PWS subjects having either the typical type I or type II chromosome 15q11-q13 deletion and identification of four genes (e.g., NIPA1, NIPA2, CYFIP1, CGP5) in the region contributing to greater maladaptive and abnormal behavior in those subjects with the larger type I deletion. Other obesity related measures under study include body composition, energy balance, regional fat distribution and neuropeptides regulating eating behavior and comparison with PWS genetic subtypes. Furthermore, DNA, coding and non-coding RNA (microRNAs) studies are underway with targeted messenger RNAs from structural and regulatory genes involved in the pathogenesis of obesity, autism and neurodevelopment. Additional studies include functional MRI scans of Prader-Willi syndrome and matched obese subjects using a food picture stimulation paradigm during pre- and post-meal assessments to determine activation of specific brain regions involved in eating behavior and satiation by comparing with separate subject groups (PWS and controls), their genotypes, and expression and copy number variants of behavioral related genes (e.g., TPH2, COMT, SERT, MAOA, POMC).
Other projects and research interests include: genomic imprinting, epigenetics, DNA methylation, and nutrient-gene interaction; structural (DNA) and functional (coding and non-coding RNAs) studies in heart disease, alcoholics and rare disorders; bioinflammatory cytokine markers in autism; clinical delineation of rare genetic disorders; and integration of genetic and clinical outcome databases.
Mental Retardation and Autism Spectrum Disorders: Under the direction of Jessica Hellings, several studies in management of behavioral disturbances associated with developmental disability and comorbid psychiatric illness are currently underway. Specifically, the evaluating of risperidone (Risperdal®) in the treatment of aggression and self-injury in children and adults with developmental disabilities as recently been completed. In addition, we are currently evaluating the effects of valproate (Depakote®) in the treatment of aggression in children and adolescents with autism spectrum disorders.
Pain Research: Cutting edge research on pain analgesia is being conducted under the direction of Teresa D. Long, MD. Dr. Long has been funded by the National Institutes of Health to study the effects of Morphine Infused IntraSite Gel for Pressure Ulcer Analgesia. Dr Long’s current research interests include alternative analgesic delivery systems with individual with osteoarthritis and elucidating differences in brain imaging between patients with chronic pain requiring analgesics and those with substance abuse diagnoses
Interactive Media for Remote Psychiatric Care: We have pioneered the use of new PC-based technology for rural psychiatric management and are assessing the efficacy and other features of this intervention. Drs. Liskow and Cain are currently conducting this research.
Alcoholism and Related Psychiatric Disorders: The Department of Psychiatry has a well-established alcoholism research program that includes several large epidemiological studies of risk factors for the development of alcoholism. Recent projects incorporate the use of state-of-the-art microarray technology to investigate genetic influences on alcoholism vulnerability. Research on these projects is under the direction of William Gabrielli, Elizabeth Penick, Ann Manzardo, and Merlin Butler.
Danish Longitudinal Study on Alcoholism: Elizabeth C. Penick, Ph.D., Ann Manzardo, Ph.D. William F. Gabrielli, Jr., M.D., Ph.D., Jeannie Nickel, Wendy Madarsz
The Department of Psychiatry is involved in an international collaborative study of risk factors related to alcoholism using a large Danish birth cohort (born between 1959 and 1961). The database contains extensive, detailed information relating to the pregnancy and birth of 9,125 Danish subjects. This includes specific information relating to the physical condition of subjects at birth, day 5 and 1-yr of age. The Danish Central Psychiatric Register, a national register of all psychiatric diagnosis and admissions, has been the source of psychiatric outcomes for the now adult study subjects. The work has resulted in numerous NIH funded grants, published abstracts and manuscripts spanning a timeframe of more than 20 years.
The Effectiveness of Benfotiamine in Reducing Abusive Drinking among Family History Positive and Negative Alcoholics: Ann Manzardo, Ph.D., Elizabeth C. Penick, Ph.D. , Jan Campbell, M.D, Albert B. Poje, Ph.D., Gregory A. Reed, Ph.D. Merlin Butler, M.D. and Marilyn Logan
We are currently recruiting subjects for a randomized, double-blind, placebo-controlled clinical trial of oral benfotiamine. The study is designed to test the effect of high-dose thiamine replacement on drinking outcomes in chronic, severe alcoholic drinkers. It is hypothesized that improvements in neurocognitive outcomes associated with the restoration of thiamine blood levels in alcoholics will enhance behavioral regulation, reduce alcohol cravings and improve functional outcomes.
Methamphetamine Dependence: Dr. Jan Campbell’s research focus is on psychopharmacologic treatments for methamphetamine dependence. The current studies are part of the Methamphetamine Clinical Trials Group, funded by the National Institute on Drug Abuse and coordinated through the Institute for Substance Abuse Treatment at UCLA. Medication studies are randomized, double-blind, placebo-controlled evaluations of medications to reduce craving; conducted in the setting of manualized psychosocial treatment modeled on the MATRIX program. The treatment program is provided at no charge to subjects enrolled in the studies that take place at the START program. Those interested in the research may contact START at 816-668-9504.
Acoustic Startle Eyeblink Plasticity and Alcoholism: In collaboration with Drs. Manzardo, Penick and Campbell, Dr. Poje is using electromyography (EMG) recordings of long-lead interval startle eyeblink modification in response to emotional and alcohol-related cues to examine early emotional responses to these cues in alcohol dependent individuals. This project is a component of an award from the Hanlon Trust to Dr. Manzardo to investigate the use of benfotiamine in reducing abusive drinking among family history positive and negative individuals with alcohol dependence. The goal of this project is to identify potential biobehavioral markers of alcohol dependence risk, severity, and response to benfotiamine as part of a double-blinded placebo-controlled clinical trial.
Cocaine abuse and treatments: This research related investigations focusing upon the characteristics of cocaine abuse and treatment efforts. The program is starting to generate research under the direction of Jan Campbell, which will have impact on treatment efforts for the addiction.
Psychiatric Co-Morbidities: Elizabeth Penick and Jeannie Nickel are examining combinations of psychiatric illnesses in individuals and in families.
Sensorimotor Gating in Attention-Deficit Hyperactivity Disorder: In collaboration with Drs. Smith, Penick and Hellings, and support from funding from the General Clinical Research Center (GCRC), Dr. Poje is using electromyography (EMG) recordings of short-lead interval startle eyeblink modification to assess automatic and attention-modulated prepulse inhibition (PPI) of the acoustic startle response in children and adolescents diagnosed with Attention-Deficit Hyperactivity Disorder (ADHD). The goal of this project is to examine the contribution of bottom-up and top-down inhibitory and attention systems in ADHD patients to contribute to the understanding of this disorder and potential assessment strategies for ADHD.
A Transition Clinic for Adolescents and Young Adults with Diabetes Mellitus: In collaboration with Drs. Robbins and Casey, and support from the Speas Foundation to Dr. Robbins, Dr. Poje is working with an interdisciplinary team of Diabetes management specialists to help measure and positively impact the psychological and behavioral sequelae of Diabetes in adolescents and young adults. The goal of this project is to reduce negative psychological issues that are barriers to effective care among individuals transitioning from adolescence to adulthood in independent management of this disease.
Diagnosis Specific Therapeutic Modalities: Elizabeth Penick has developed and is testing a protocol for assigning a therapeutic procedure for specific scientific diagnoses. The idea is maximizing therapeutic intervention by targeting the treatment strategy that empirically shows to be the best intervention.