The Consortium is a collaborative research enterprise comprised of several leading academic institutions and based on a long-term relationship between the Pritzker family and scientists at the various institutions. The Pritzker Family first established the Pritzker Depression Network (1996) that included Stanford University, the University of Michigan (UM) and The Weill Medical College of Cornell University (Cornell) and was established to study the neurobiological basis of depression. The Consortium was then established (2000) and aims to discover the neurobiological and genetic underpinnings of mood disorders and schizophrenia and to ensure applications of these discoveries are utilized commercially to the fullest extent possible. Groups at UC Davis (UCD), UC Irvine (UCI), Stanford University, UM and Cornell conduct studies on human post-mortem tissue, isolated populations and various animal models to identify altered profiles of gene expression in brain circuits associated with the disorders.

Brain Bank
One of the Consortium's primary strengths is its “brain bank.” Created and maintained through a partnership between UCD and UCI, the brain bank consists of high quality post-mortem brain tissue taken from patients and individually matched controls. A thorough acquisition process, including an investigation of all relevant clinical data, ensures each tissue sample is properly assessed and utilized. Once a sample has been characterized, Consortium scientists employ a special selection methodology to ensure the post-mortem tissue yields high-quality RNA samples for microarray analysis. Dr. William Bunney at UCI has taken the lead in collecting brains, while Dr. Edward Jones has developed storage methods and is an expert neuro-anatomist.

Microarray Studies
Following dissection of the specific brain regions and subregions, microarray technology and other quantitative tools for analyzing mRNA expression are applied to find sets of genes that are consistently differentially expressed between normal and diseased brains. Microarrays, or gene chips, allow scientists to measure the activity of thousands of genes at the same time. These experiments are done in duplicate by scientists at UM, UCI and UCD to provide replication/validation of results.
The Consortium collaborates with Dr. Terry Speed, a biostatistician renowned in the field of microarray analysis, to determine the most appropriate means of analyzing results of the microarray studies.
Dr. Jack Barchas at The Weill Medical College of Cornell University study allele-specific expression (ASE) of genes in human brain tissue. ASE studies identify differences in the level of expression of genes from each of the two parental chromosomes. When differences are seen one of the two chromosomes must contain a regulatory polymorphism that causes the differential expression. These studies interact with other components of the Pritzker consortium to identify genetic risk factors for Psychiatric disorders.

Gene Anatomy and Ontology
Drs. Huda Akil and Stanley Watson at UM study the relationship between genes, behavior and the brain. Drs. Akil and Watson aim to elucidate and validate the function(s) of genes that demonstrate significant differences in expression or structure and to determine their distribution in pathways, circuits and target systems. Several tools are used in these studies. In situ hybridization (ISH) histochemistry is performed at UM and UCD to determine the anatomical and cellular distribution of discovered genes. Selected genes are further characterized by determining the structure and function of translated proteins and their regional and cellular distribution. Finally, laboratory experiments using genetically modified animals and cell cultures are conducted at UM, UCD and Stanford to elucidate the role of certain genes in specific brain circuits involved in psychotic and affective processes.

Novel Gene Detection Technologies
Dr. Richard Myers leads the discovery and validation process at Stanford, where novel gene detection technologies-notably real-time PCR and Serial Analysis of Gene Expression (SAGE)- are used to complement or improve upon microarray results, which can be hampered by poor sensitivity.

Animal Studies
Dr. Alan Schatzberg at Stanford and Dr. Jones study gene expression related to antidepressants and glucocorticoids in non-human primates. Similar experiments in rats at UM and Stanford allow the interspecies comparison of drug effects and may help achieve a better understanding of antidepressants' mechanism of action.

Clinical Research
Candidate genes will be further studied in living patients and in families with a history of mental illness. Geneticists at UCI and at UM lead those studies in human families with a high rate of mental illness. Cornell, UM and Stanford will also be involved in the recruitment and clinical/phenotypic characterization of patient and control subjects, for genetic studies, and for related studies to develop endophenotypes.

Informatics
The Consortium developed a complex informatics system to handle the vast amount of data obtained through analyzing a large number of brain regions and neural cell types. The information management and analysis effort is lead by UM. The system allows improved accuracy of information and deeper analysis as well as real-time sharing of data and analysis results between sites. Results are stored in a secured server and are accessible to all Consortium scientists.

Findings
Sets of genes (some novel, some previously reported) differentially expressed between control subjects and patients suffering from mood disorders or schizophrenia have been discovered in several brain regions. Results are classified according to criteria such as directionality of the changes, pathways, Gene Ontology (GO) terms and drugable targets. Microarray technology was used for initial discovery, but the genes have been validated using RT-PCR, SAGE and/or ISH. Ongoing studies aim to identify the structure and function of particular genes and their products.