Alon Chen, Weizmann Institute of Science, Rehovot, Israel
Ned Kalin, University of Wisconsin, Madison, USA
Elisabeth Binder, Max Planck Institute of Psychiatry, Munich, Germany
Alan Schatzberg, Stanford University, USA
Claes Wahlestedt, University of Miami, USA
Clinton Kilts, University of Arkansas for Medical Sciences, USA
Carmine Pariante, King's College London, UK
The preeminent role of stress in the pathogenesis of several of the major psychiatric disorders including major depression, bipolar disorder, and post traumatic stress disorder, as well as drug and alcohol abuse, is well established. In recent years, the importance of early life stress in the form of child abuse and neglect in increasing risk for the aforementioned psychiatry disorders and other disorders, both psychiatric and medical, has been reported with increasing frequency. This course brings together a group of leading investigators from centers throughout the world that have focused their research, educational, and clinical efforts in unraveling the complex interactions between stress and the development of psychiatric disorders. Both basic neurobiological and clinical research will be highlighted.
A major focus of this research has been uncovering the neural systems that mediate the effects of stress resulting in increased disease vulnerability. This involves, by necessity, a comprehensive understanding of the neurotransmitter and endocrine systems that mediate stress responsivity. The discovery by Vale and colleagues of the structure of corticotropin releasing factor (CRF) and the subsequent elucidation of its receptors and binding protein have allowed for elucidation of many of the mechanisms within the CNS and in the periphery by which this neuropeptide "orchestrates" the endocrine, immune, autonomic and behavioral responses to stress. The CRF system will be reviewed in detail, as well as the physiology of the hypothalamic-pituitary-adrenal (HPA) axis, and its role in the pathophysiology of the major psychiatric syndromes. Rodent and non-human primate models of psychopathology will be discussed in detail with a focus on the HPA axis and related systems/circuits. Particular attention will be paid to the role of HPA axis dysfunction in the pathophysiology of psychotic depression and the recent development of novel treatments including glucocorticoid receptor antagonists and other agents that target components of this system.
The emerging importance of inflammatory processes in the stress response and its purported role in the pathogenesis of mood disorders will be reviewed. A major focus of the course will, by necessity, be on genetics, epigenetics, transcriptomics, and proteomics. A primer on psychiatric genetics will be presented and more advanced lectures on gene-environment interactions will follow. Genetic polymorphisms that mediate the depressogenic and anxiogenic mechanisms of child abuse and neglect, including the serotonin transporter, FKBP5, CRF-R1, PAC 1 and others will be described in detail, as will early epigenetic studies. The critical role of non coding regions of the genome and microRNAs in disease vulnerability and etiology will be included. The role of HPA axis genes in cognitive processes and psychosis will be described.
Structural and functional brain imaging studies in laboratory animals, normal volunteers, and psychiatric patients will be reviewed with a focus on both predictors of disease vulnerability, stress responses, disease-mediated effects and predictors of treatment response. Finally, the critical importance of personalized medicine in treatment of these stress related disorders will be highlighted including predictors of treatment response to psychopharmacological agents as well as psychotherapy. The development of novel treatments for these major stress-associated psychiatric disorders based on the emerging neurobiology described above will be critically reviewed.