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Faculty: Ned Kalin, MD

Dept: Hedberg Professor and Chairman, Department of Psychiatry
Contact: 6001 Research Park
Training Areas:
  • Molecular and Cellular Pharmacology
  • Neuroscience Training Program
  • Psychology
  • Psychiatric Residency Training
Lab Website: Click Here

Research Interests

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.

Honors & Awards

Other Positions & Affiliations

Selected Publications

(Find recent publications on PubMed)

  • Shackman AJ, Fox AS, Oler JA, Shelton SE, Davidson RJ, and Kalin NH (2013). Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Proc Natl Acad Sci USA. 110:6145-50. Epub 2013 Mar 28. PMID: 23538303 [PubMed - indexed for MEDLINE]
  • Christian BT, Wooten DW, Hillmer AT, Tudorascu DL, Converse AK, Moore CF, Ahlers EO, Barnhart TE, Kalin NH, Barr CS, and Schneider ML (2013). Serotonin Transporter Genotype Affects Serotonin 5-HT1A Binding in Primates. J Neurosci. 33:2512-6. PMID:23392679
  • Heller AS, Johnstone T, Light SN, Peterson MJ, Kolden GG, Kalin NH, and Davidson RJ (2013). Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment. Am J Psychiatry. 170:197-206. PMID: 23223803
  • Burghy CA, Stodola DE, Ruttle PL, Molloy EK, Armstrong JM, Oler JA, Fox ME, Hayes AS, Kalin NH, Essex MJ, Davidson RJ, and Birn RM (2012). Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nat Neurosci. 15:1736-41. Epub 2012 Nov 11. PMID: 23143517
  • Rosenkranz MA, Davidson RJ, Maccoon DG, Sheridan JF, Kalin NH, and Lutz A (2013) . A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation. Brain Behav Immun. 27:174-84. Epub 2012 Oct 22. PMID: 23092711
  • Fox AS, Oler JA, Shelton SE, Nanda SA, Davidson RJ, Roseboom PH, and Kalin NH (2012). Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates. Proc Natl Acad Sci U S A. 109:18108-13. Epub 2012 Oct 15. PMID: 23071305
  • Oler JA, Birn RM, Patriat R, Fox AS, Shelton SE, Burghy CA, Stodola DE, Essex MJ, Davidson RJ, and Kalin NH (2012). Evidence for coordinated functional activity within the extended amygdala of non-human and human primates. Neuroimage. 61:1059-1066. PMID: 22465841
  • Shirtcliff EA, Allison AL, Armstrong JM, Slattery MJ, Kalin NH, and Essex MJ (2012). Longitudinal stability and developmental properties of salivary cortisol levels and circadian rhythms from childhood to adolescence. Dev Psychobiol. 54:493-502. PMID: 21953537
  • Essex MJ, Shirtcliff EA, Burk LR, Ruttle PL, Klein MH, Slattery MJ, Kalin NH, and Armstrong JM (2011). Influence of early life stress on later hypothalamic-pituitary-adrenal axis functioning and its covariation with mental health symptoms: a study of the allostatic process from childhood into adolescence. Dev Psychopathol. 23:1039-1058. PMID: 22018080
  • Light SN, Heller AS, Johnstone T, Kolden GG, Peterson MJ, Kalin NH, and Davidson RJ (2011). Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder. Biol Psychiatry 70:962-968. PMID: 21867991
  • Adluru N, Zhang H, Fox AS, Shelton SE, Ennis CM, Bartosic AM, Oler JA, Tromp do PM, Zakszewski E, Gee JC, Kalin NH, and Alexander AL (2011). A diffusion tensor brain template for rhesus macaques. Neuroimage. 59:306-318. PMID: 21803162
  • Qi C, Roseboom PH, Nanda SA, Lane JC, Speers JM, Kalin NH (2010). Anxiety-related behavioral inhibition in rats: a model to examine mechanisms underlying the risk to develop stress-related psychopathology. Genes Brain Behav. 9:974-984. PMID: 20738409
  • Oler JA, Fox AS, Shelton SE, Rogers J, Dyer TD, Davidson RJ, Shelledy W, Oakes TR, Blangero J, and Kalin NH (2010). Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Nature 466:864-868. PMID: 20703306
  • Fox AS, Shelton SE, Oakes TR, Converse AK, Davidson RJ, and Kalin NH (2010). Orbitofrontal cortex lesions alter anxiety-related activity in the primate bed nucleus of stria terminalis. J Neurosci. 30:7023-7027. PMID: 20484644
  • Jahn AL, Fox AS, Abercrombie HC, Shelton SE, Oakes TR, Davidson RJ, and Kalin NH (2010) Subgenual prefrontal cortex activity predicts individual differences in hypothalamic-pituitary-adrenal activity across different contexts. Biol Psychiatry. 67:175-181. PMID: 19846063