25th Annual Schizophrenia Conference
November 13, 2009
Sheraton Station Square Hotel, Pittsburgh, PA
Course Director:
K.N. Roy Chengappa, MD
The Pittsburgh Schizophrenia Conference is an annual meeting at which the advances in schizophrenia research are reviewed by leading international experts in the field. This year’s meeting will cover a range of topics, including electrical activity and oscillations in the brain and brain imaging research. Furthermore, ways to get back decades of life lost in persons with schizophrenia using approaches to reduce medical co-morbidity such as reducing body weight will also be reviewed. A patient and family perspective regarding patient centered medicine as it applies to people with severe mental illness will be discussed in a panel format. Presentations by the faculty awarded the 2009 Pittsburgh Schizophrenia Conference Award, and the Gerard Hogarty Research Excellence Prize will also take place during the meeting.
Who Should Attend
The conference is designed to disseminate the latest research findings to a wide audience: psychiatrists and other mental health clinicians, including nurses, social workers, psychologists, service coordinators, researchers, patients and their relatives, mental health policy administrators and others who wish to keep abreast of etiologic and treatment research in schizophrenia.
Objectives
At the conclusion of the program, participants should be able to:
- Describe electrical oscillations of the brain and cognitive disturbance in schizophrenia.
- Review brain neuro-receptor imaging research especially as it relates to the dopamine system, and how the neurochemical GABA system may be involved in the clinical symptoms of schizophrenia.
- Consider behavioral strategies aimed at modifying the diet and life-styles of persons with schizophrenia to reduce the incidence of premature heart disease and diabetes.
- Review from a patient and family perspective what it means to have physical illnesses along with mental illness and how best to manage these co-occurring conditions.
- Consider pragmatic psychosocial treatments and how these may be applied in clinical practice.
Presented by:
UPMC Health System Western Psychiatric Institute & Clinic;
Services and Research for Recovery in Serious Mental Illness;
Mental Health Conference Planning;
University of Pittsburgh School of Medicine;
Center for Continuing Education in the Health Sciences
Schizophrenia is a severe disorder that disrupts the function of multiple brain systems, resulting in impaired social and occupational functioning. The etiology and pathogenesis of schizophrenia appear to involve the interplay of a potentially large number of genetic liabilities and adverse environmental events that disrupt brain developmental pathways. In this Review, we discuss strategies for determining how particular common and core clinical features of the illness are associated with pathophysiology in certain circuits of the cerebral cortex. For example, impaired working memory and processing of auditory information in individuals with schizophrenia are attributable, at least in part, to specific pathological alterations in the dorsolateral prefrontal cortex and primary auditory cortex, respectively. These involve, but are not restricted to, disturbances in glutamate, GABA, and dopamine neurotransmission. For example, as illustrated in the figure, auditory cortical processing is initiated by projections from the medial geniculate nucleus of the thalamus. These projections are arranged tonotopically, (i.e., along a frequency gradient that is broadly tuned). The subsequent activation of a reciprocally connected isofrequency network of pyramidal cells (light blue) within layer 3 selectively amplifies a narrower preferred frequency, refining the thalamic tuning curve. Densities of dendritic spines and axonal boutons are reduced in deep layer 3 of subjects with schizophrenia, potentially limiting activation and current flow in the pyramidal cell network. Pyramidal cells are co-tuned (i.e., receive concurrent stimulation from thalamic or cortical projection neurons), with local inhibitory neurons (green), leading to a stereotyped excitatory-inhibitory sequence of post-synaptic potentials, which increases the temporal precision of depolarization and enhances phasic activity of the pyramidal neuron network. The identification of molecular alterations in these circuits is providing critical insights for the rational development of new therapeutic interventions.Lewis DA and Sweet RA: Schizophrenia from a neural circuitry perspective: advancing towards rational pharmacological therapies. J Clin Investigation, in press.
Many human brain diseases are associated with disturbances in the structure and function of cortical synapses. Answering fundamental questions about the synaptic machinery in these disease states requires the ability to image and quantify small synaptic structures in tissue sections and to evaluate protein levels at these major sites of function. We developed a new automated segmentation imaging method specifically to answer such fundamental questions. The method takes advantage of advances in spinning disk confocal microscopy, and combines information from multiple iterations of a fluorescence intensity/morphological segmentation protocol to construct three-dimensional object masks of immunoreactive (IR) puncta. This new methodology is unique in that high- and low-fluorescing IR puncta are equally masked, allowing for quantification of the number of fluorescently-labeled puncta in tissue sections (panel). In addition, the shape of the final object masks highly represents their corresponding original data. Thus, the object masks can be used to extract information about the IR puncta (e.g., average fluorescence intensity of proteins of interest). Importantly, the segmentation method presented can be easily adapted for use with most existing microscopy analysis packages.Fish KN, Sweet RA, Deo AJ, Lewis DA: An automated segmentation methodology for quantifying immunoreactive puncta number and fluorescence intensity in tissue sections. Brain Res, 1240: 62-72, 2008.
Accumulating evidence indicates that synchronization of cortical neuronal activity at gamma-band frequencies is important for various types of perceptual and cognitive processes. Experimental models as well as preclinical studies suggest that GABA-A receptor-mediated transmission is required for the induction of network oscillations. However, to date, there is no evidence linking GABA transmission with gamma-band oscillations in humans. Using a novel positron emission tomography (PET) brain-imaging paradigm, we measured the in vivo binding of the benzodiazepine (BDZ) site specific radiotracer [11C]flumazenil at baseline and in the context of elevated GABA levels induced via blockade of the GABA membrane transporter (GAT1) with tiagabine. Preclinical work suggests that increased GABA levels enhance the affinity of GABA-A receptors for BDZ ligands via a conformational change (termed the ‘GABA-shift’). Theoretically, such an increase in affinity of GABA-A receptors should be detected as an increase in the binding of a GABA-A BDZ-receptor site-specific PET radioligand. In fact, we observed significant increases post-GAT1 blockade in [11C]flumazenil binding over baseline values across all cortical brain regions. This is illustrated in Panel A, showing MRI (top) and coregistered parametric BPND (unitless) maps measured under baseline (middle) and 30 minutes post-tiagabine (bottom) following [11C]flumazenil injection in a healthy female volunteer. Moreover, the ability to increase GABA levels, measured as the change in [11C]flumazenil binding potential, strongly predicted the ability to entrain cortical networks, measured via EEG gamma synchrony in these same subjects (Panel B). These data provide preliminary evidence of the ability to measure acute fluctuations in extracellular GABA levels with PET and provide the first in vivo documentation of the relationship between GABA neurotransmission and gamma-band power in humans.Frankle WG, Cho RY, Narendran R, Mason NS, Vora S, Litschge M, Price JC, Lewis DA, Mathis CA: Tiagabine increases [11C]flumazenil binding in cortical brain regions in healthy control subjects. Neuropsychopharmacology, ePub July 9, 2008.
The Cameos of Caring Program, which includes 55 area healthcare facilities and schools of nursing, recognizes nursing professionals who demonstrate excellence in nursing care, serve as advocates for patients and families, and embody the essence of the nursing profession. This year Kevin Eklund, BSN, was among those recognized for this prestigious award. Kevin serves as project coordinator of the Services for the Treatment of Early Psychoses (STEP) research program at Western Psychiatric Institute and Clinic, and he plays a central role in subject recruitment and diagnostic evaluation for the Clinical Services and Diagnostics Core of the CCNMD. Kevin was selected for the Cameos of Caring award for his consistent excellence and compassion in both clinical care and research. Head nurse in the Diagnostic Evaluation Center, Jennifer Lynn Schneeman says, “Patients and families testify that Kevin’s skills have provided them hope at the commencement and continuum of the recovery process. He is an image and inspiration for staff, patients, and families.” Dr. David Lewis, Director of the CCNMD, has noted that Kevin is “particularly skilled at helping individuals with schizophrenia understand whether a given research project will be a good experience for them, and in supporting them through the process with extraordinary energy and genuine compassion.” CONGRATULATIONS, KEVIN!
25th Annual Schizophrenia Conference
November 21, 2008
Sheraton Station Square Hotel, Pittsburgh, PA
The Pittsburgh Schizophrenia Conference is an annual meeting at which the latest advances in schizophrenia research are reviewed by leading international experts in the field. This year's meeting will cover a diverse range of topics including brain abnormalities and the roles of genes in pathophysiology of schizophrenia. Scientific evidence for the role of cannabis in causing, precipitating, or worsening psychosis will be reviewed. Improving social and vocational function and non-psychiatric medical problems will also be addressed. The family and consumer perspective will also be presented. The presentation of the 2008 Schizophrenia Conference Award and the Gerard E. Hogarty Excellence in Schizophrenia Research Memorial Award will also occur during the meeting.
Who Should Attend
The conference is designed to disseminate the latest research findings to a wide audience: clinicians, researchers, patients and their relatives, and others who wish to keep abreast of etiologic and treatment research in schizophrenia.
Objectives
At the conclusion of the program, participants should be able to:
- Understand the pattern for brain abnormalities commonly associated with schizophrenia.
- Have better understanding of the current knowledge and future directions in research in the genetics of mental illness.
- Understand evidence-based approaches to improving employment outcomes in persons with schizophrenia.
- Understand the increased risk for non-psychiatric medical problems for persons with schizophrenia and proposals for improved integration of mental health and primary care services.
- Understand the ways in which drugs of abuse, like cannabis can induce or precipitate psychotic symptoms and illnesses.
Presented by:
UPMC Health System Western Psychiatric Institute & Clinic;
Schizophrenia Treatment & Research Center;
Mental Health Conference Planning;
University of Pittsburgh School of Medicine;
Center for Continuing Education in the Health Sciences
Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC) result, at least in part, from abnormalities in GABA neurotransmission as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, in this study we sought to determine whether this pattern of altered gene expression is restricted to the DLPFC or could also contribute to the dysfunction of other cortical areas in the illness. Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (DLPFC, anterior cingulate, primary motor and primary visual cortices) from 12 subjects with schizophrenia and matched normal comparison subjects. Expression levels of seven transcripts were lower in the subjects with schizophrenia with the magnitude of the reductions for each transcript indistinguishable across the four areas (Figure). The largest reductions were detected for the mRNAs encoding somatostatin (SST) and parvalbumin (PV), followed by moderate decreases in mRNA expression for the 67 kD isoform of glutamate decarboxylase (GAD67), the GABA membrane transporter 1 (GAT1), and the α1 and δ subunits of GABAA receptors. In contrast, the expression of calretinin (CR) mRNA did not differ between the subject groups in any of the four areas. Because the areas examined represent the major functional domains (e.g., association, limbic, motor and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contributes to the pathophysiology of different clinical features of schizophrenia.Takanori Hashimoto, H Holly Bazmi, Karoly Mirnics, Qiang Wu, Allan R Sampson, and David A Lewis: Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects with Schizophrenia. Am J Psychiatry, 165:479-489, 2008.
Translational Neuroscience Program Seminar Series
Date: Mondays
Time: 12:00-1:00 PM
Location: 16th Floor Conference Room (1695 BST) Biomedical Science Tower
Every Monday from 12:00 – 1:00, the Translational Neuroscience Program and the Department of Psychiatry at the University of Pittsburgh sponsor a lunch-hour seminar dedicated to topics in neuroscience and mental health, with a special emphasis on schizophrenia-relevant research. Scientists from inside and outside the University of Pittsburgh present their work to an audience of faculty, staff, residents and students from various departments.
The TNP Seminar Series represents an excellent forum for the communication of novel research ideas and initiatives. The weekly seminars cultivate an atmosphere of cooperation towards translating basic science and research into a better understanding of brain disorders and clinical practice.
For more information about scheduled lectures, please contact
Robin Klapheke
412-624-3934
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Corrie Long