Volunteering for Research Studies |
While it is clear that abnormalities of brain function underlie schizophrenia, the nature and causes of the brain dysfunction remain unknown. The research efforts of the Johns Hopkins Schizophrenia Program are guided by the philosophy that development of rational therapeutics for schizophrenia will depend on discovery of both the factors that cause schizophrenia and the effect of these factors on brain structure and function. This philosophy has led the investigators of the Schizophrenia Program to ask a series of interrelated questions:
- It is possible to distinguish different types of schizophrenia based on
detailed examination of symptoms and cognition? - What genes are involved in schizophrenia?
- What brain processes are altered by mutations or variations in these
genes? - What interventions might help normalize these perturbed brain
processes? - Do genetic factors interact with environmental factors to increase
the risk of developing schizophrenia? - In individuals with schizophrenia, which brain structures are abnormal
in structure or function? - Do certain genetic mutations, or specific brain structural or functionalZ
abnormalities, correlate with different subtypes of schizophrenia? - Do differences in symptoms, genetics, or brain structure or function
predict response to current treatments for schizophrenia? - How can we use information about schizophrenia symptoms, genetic
factors, and brain structure and function to design better treatment
studies?
The clinical manifestations of schizophrenia: defining subtypes of the disease. Dr. Nicola Cascella, Director of Clinical Research for the Schizophrenia Program, and Dr. David Schretlen, Director of Neuropsychology for the Program, have a long-term interest in exploring subtypes of schizophrenia, with the goal of better defining different forms of the illness. This is accomplished by careful clinical examinations, and correlations of clinical symptoms with brain imaging and cognitive profiles. Drs. Cascella and Schretlen are particularly interested in “deficit” schizophrenia, a form of the illness characterized by loss of emotional, cognitive, and functional abilities. This work is critically important in the predication of the long-term prognosis of individuals with schizophrenia, and in properly defining patient groups for genetic and treatment studies. Eventually, this work may help facilitate individualized treatment approaches to schizophrenia.
Genetics: portal into the causes and biology of schizophrenia. The Laboratory of Genetic Neurobiology, directed by Dr. Margolis and a part of the Division of Neurobiology (led by Dr. Christopher A. Ross), is using genetic approaches complementary to traditional linkage and association analyses to find genetic etiologies and risk factors for schizophrenia. Among other projects, the Laboratory is using state of the art “chip” technology to understand the potential contribution of DNA instability (gains and losses of entire sections of the human genome) to the risk of developing schizophrenia. In conjunction with Dr. Ross, the Laboratory is currently characterizing the neurobiological implications of genetic findings on chromosomes 1 and 5.
Neuroimaging: unique views of the living brain to guide diagnosis and treatment. Faculty members of the Schizophrenia Program are using multiple approaches to image brain structure and function in schizophrenia.
Dr. David Schretlen is using magnetic resonance imaging (MRI) to examine quantitative measures of brain volume. His goal is to determine how changes in the structure of specific regions of the cerebral gray matter (a neuron-rich region that performs many of the most complex tasks of the brain) correlate with the clinical and cognitive abnormalities of schizophrenia.
Dr. Sarah Reading, a member of the Division of Neuroimaging of the Department of Psychiatry, is using new methods of brain imaging to determine the structural and functional abnormalities in patients with schizophrenia. One of these methods, Diffusion Tensor Imaging (DTI), enables Dr. Reading to view white matter tracts, the pathways that connect one region of the brain to another. Another method, functional magnetic resonance imaging (MRI), shows the brain regions that are most active during a mental event, such as solving a problem.
Dr. Nicola Cascella, in conjunction with Dr. Dean Wong of the Department of Radiology, is investigating the biology and treatment of schizophrenia using Positron Emission Tomography (PET). PET is a method for assessing the number, location, and functional status of biochemical receptors within the brain. These molecules are critical for the transfer of information among neurons, and serve as important targets for pharmaceutical agents. Drs. Cascella and Wong are currently exploring the role of nicotinic receptors in schizophrenia, and the changes in receptors induced by pharmaceutical agents with potential roles in the treatment of schizophrenia.
Taken together, these methods promise unique insights into the abnormalities of brain structure and circuitry that underlie schizophrenia. The potential impact is great: early and accurate diagnosis, objective data on disease course and the success of treatment, and leads into developing new and better treatments.
Substance abuse and schizophrenia: a neurobiological approach. The research of Dr. Irving Reti is focused on the molecular mechanisms that subserve drug addiction, the most common co-morbid condition confronting patients with schizophrenia. He has identified the protein Narp, a novel mediator of opiate dependence. Dr. Reti is also interested in the clinical application and molecular mechanisms of somatic treatments for psychiatric conditions such as electroconvulsive therapy and transcranial magnetic stimulation.
Neuronal injury and death: new approaches to protecting the brain. Dr. Thomas Sedlak, a new addition to the Johns Hopkins faculty, has recently completed a fellowship with Dr. Solomon Snyder of the Johns Hopkins Department of Neuroscience. Dr. Sedlak’s research interest is in exploring novel pathways that lead to the injury and death of neurons, and potential mechanisms to block this pathogenesis.
Collaborations at Johns Hopkins. The faculty of the Schizophrenia Program work closely with a number of other investigators at Johns Hopkins, helping to recruit patients for studies, collecting and storing clinical samples, and exchanging advice and expertise.
Dr. Christopher Ross, directs the Division of Neurobiology in the Department of Psychiatry and is an expert in the development of biochemical, cell, and animal models for the study of genetic diseases of the brain.
Dr. Mikhail Pletnikov studies the interaction of genetic and infectious factors and the neurobiology of schizophrenia.
Dr. Akira Sawa directs the Program in Molecular Biology in the Department of Psychiatry which works on the translational neuroscience of schizophrenia, studying the neurobiology of genetic and environmental factors for schizophrenia as well as exploring novel biomarkers for the disease by collecting patient tissues of olfactory neurons and peripheral blood cells.
Dr. Robert Yolken, directs the Stanley Division of Developmental Neurovirology in the School of Medicine and studies the role of infection and immune response in psychiatric diseases.
Dr. Ann Pulver directs the Epidemiology-Genetics Program in Schizophrenia and Bipolar Disorders, a multidisciplinary team using large population samples to search for the genetic and non-genetic risk factors underlying severe mental disorders.
Dr. James Potash, directs research for the Mood Disorder Program in the Department of Psychiatry and investigates genetic and epigenetic factors in bipolar disorder and depression.
Dr. Gerald Nestadt, leads a large scale investigation of the genetics of obsessive-compulsive disorder.
Dr. Dean Wong, Vice Chair of the Department of Radiology, is a pioneer in the imaging of brain receptors using PET and other technologies.
Back to top
