Ned H. Kalin

Brain Mechanisms Underlying Fear, Anxiety and Depression

E-mail: nkalin@wisc.edu

Research Strength: Behavior: Cognition and Emotion

My laboratory is investigating the neurobiological basis of fear, anxiety, and depression at preclinical and clinical levels. One of the strengths of our approach is that we are working across a variety of technologies (molecular, preclinical animal models including primates, and human functional brain imaging) to maximize our ability to understand the neural circuitry underlying normal as well as pathological emotional states. At a molecular level, we have cloned key promoter regions of a family of genes (Coricotropin releasing hormone receptors) that are critical in integrating the stress response at behavioral, emotional, autonomic, and endocrine levels. We are in the process of understanding mechanisms that regulate the expression of these genes. In preclinical animal models, we are working with rodents and have recently established that a specific receptor (CRH-R2) located in the lateral septum is critical in mediating behavioral responses induced by stress and associated with fear. In nonhuman primates, we are examining behavioral and physiological correlates of human anxiety. We have identified a fearful endophenotype that is characterized by high levels of trait anxiety, a specific pattern of prefrontal brain electrical activity, and increased levels of stress hormones in the blood and in the brain. We have developed new techniques to selectively lesion the primate amygdala and these studies have provided new insights into the role of the amygdala in mediating acute fearful responses as compared to states of long term anxiety. Finally, we are involved in a series of functional imaging studies examining the neural circuits that are altered in patients with generalized anxiety disorder and depression. Using functional MRI, we are scanning patients prior to, during, and after successful treatment. Taken together, these studies are providing new ideas related to the genesis of psychopathology as well as new insights regarding effective treatments.

Selected Publications:

• Kalin, N.H., S.E. Shelton, R.J. Davidson, and A.E. Kelley. 2001. The primate amygdala mediates acute fear but not the behavioral and physiological components of anxious temperament. J. Neurosci. 21: 2067-2074. [PDF]
• Hsu, D.T., F.L. Chen, L.T. Takahashi, and N.H. Kalin. 1998. Rapid stress-induced elevations in corticotropin-releasing hormone mRNA in rat central amygdala nucleus and hypothalamic paraventricular nucleus: An in situ hybridization analysis. Brain Res. 788: 305-310. [PDF]
• Kalin, N.H. 1993. The neurobiology of fear. Sci. Amer. 268: 94-101.