Ned H. Kalin, MD
Position title: Hedberg Professor and Chair, Psychiatry
MD, Jefferson Medical College
Contact Information
UW Psychiatric Institute And Clinics
6001 Research Park Blvd
Madison, WI 53719
608.263.6079
nkalin@facstaff.wisc.edu
Lab Website: Kalin Lab
Research Statement
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
-
Moody, J. F., Aggarwal, N., Dean, D. C., 3rd, Tromp, D., Kecskemeti, S. R., Oler, J. A., Kalin, N. H., & Alexander, A. L. (2022). Longitudinal assessment of early-life white matter development with quantitative relaxometry in nonhuman primates. NeuroImage, 251, 118989. https://doi.org/10.1016/j.neuroimage.2022.118989
-
Aggarwal, N., Moody, J. F., Dean, D. C., Tromp, D., Kecskemeti, S. R., Oler, J. A., Alexander, A. L., & Kalin, N. H. (2021). Spatiotemporal dynamics of nonhuman primate white matter development during the first year of life. NeuroImage, 231, 117825. https://doi.org/10.1016/j.neuroimage.2021.117825
-
Dean DC 3rd, Planalp EM, Wooten W, Kecskemeti SR, Adluru N, Schmidt CK, Frye C, Birn RM, Burghy CA, Schmidt NL, Styner MA, Short SJ, Kalin NH, Goldsmith HH, Alexander AL, Davidson RJ. (2019). Association of Prenatal Maternal Depression and Anxiety Symptoms With Infant White Matter Microstructure. JAMA Pediatrics, 172(10):973-981. PMID: 30177999. PMCID: PMC6190835. DOI: 10.1001/jamapediatrics.2018.2132
-
Alisch RS, Van Hulle C, Chopra P, Bhattacharyya A, Zhang SC, Davidson RJ, Kalin NH, Goldsmith HH. (2017). A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals susceptibility loci in humans. Translational Psychiatry, 7(12):1282. PMCID: PMC5802687. DOI: 10.1038/s41398-017-0047-9
-
Shackman AJ, Fox AS, Oler JA, Shelton SE, Oakes TR, Davidson RJ, Kalin NH. (2017). Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Molecular Psychiatry, 22(5):724-732. doi: 10.1038/mp.2016.132.
-
Oler JA, Tromp DP, Fox AS, Kovner R, Davidson RJ, Alexander AL, McFarlin DR, Birn RM, E Berg B, deCampo DM, Kalin NH, Fudge JL. (2017). Connectivity between the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the non-human primate: neuronal tract tracing and developmental neuroimaging studies. Brain Structure & Function, 222(1):21-39. doi: 10.1007/s00429-016-1198-9.
-
Caldwell JZ, Armstrong JM, Hanson JL, Sutterer MJ, Stodola DE, Koenigs M, Kalin NH, Essex MJ, Davidson RJ. (2015) Preschool externalizing behavior predicts gender-specific variation in adolescent neural structure. PLoS One. 6;10(2):e0117453. doi: 10.1371/journal.pone.0117453.
-
Williams LE, Oler JA, Fox AS, McFarlin DR, Rogers GM, Jesson MA, Davidson RJ, Pine DS, Kalin NH. (2015) Fear of the unknown: uncertain anticipation reveals amygdala alterations in childhood anxiety disorders. Neuropsychopharmacology. 40(6):1428-35. doi: 10.1038/npp.2014.328.
-
Fox AS, Oler JA, Shackman AJ, Shelton SE, Raveendran M, McKay DR, Converse AK, Alexander A, Davidson RJ, Blangero J, Rogers J, Kalin NH. (2015) Intergenerational neural mediators of early-life anxious temperament. Proceedings of the National Academy of Sciences USA. 21;112(29):9118-22. doi: 10.1073/pnas.1508593112.
-
Birn RM, Shackman AJ, Oler JA, Williams LE, McFarlin DR, Rogers GM, Shelton SE, Alexander AL, Pine DS, Slattery MJ, Davidson RJ, Fox AS, Kalin NH. (2014) Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety. Molecular Psychiatry. 19(8):915-22.
-
Birn RM, Shackman AJ, Oler JA, Williams LE, McFarlin DR, Rogers GM, Shelton SE, Alexander AL, Pine DS, Slattery MJ, Davidson RJ, Fox AS, Kalin NH. (2014) Extreme early-life anxiety is associated with an evolutionarily conserved reduction in the strength of intrinsic functional connectivity between the dorsolateral prefrontal cortex and the central nucleus of the amygdala. Molecular Psychiatry. 19(8):853.
-
Shackman AJ, Fox AS, Oler JA, Shelton SE, Davidson RJ, Kalin NH. (2013) Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Proceedings of the National Academy of Sciences U S A. 9;110(15):6145-50.
-
Heller AS, Johnstone T, Light SN, Peterson MJ, Kolden GG, Kalin NH, Davidson RJ. (2013) Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment. American Journal of Psychiatry. 1;170(2):197-206.
-
Rosenkranz MA, Davidson RJ, Maccoon DG, Sheridan JF, Kalin NH, Lutz A. (2013) A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation. Brain, Behavior, and Immunity. 27(1):174-84.
-
Christian BT, Wooten DW, Hillmer AT, Tudorascu DL, Converse AK, Moore CF, Ahlers EO, Barnhart TE, Kalin NH, Barr CS, Schneider ML. (2013) Serotonin transporter genotype affects serotonin 5-HT1A binding in primates. Journal of Neuroscience. 6;33(6):2512-6.
-
Oler JA, Birn RM, Patriat R, Fox AS, Shelton SE, Burghy CA, Stodola DE, Essex MJ, Davidson RJ, Kalin NH. (2012) Evidence for coordinated functional activity within the extended amygdala of non-human and human primates. NeuroImage. Jul 16;61(4):1059-66.
-
Burghy CA, Stodola DE, Ruttle PL, Molloy EK, Armstrong JM, Oler JA, Fox ME, Hayes AS, Kalin NH, Essex MJ, Davidson RJ, Birn RM. (2012) Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nature Neuroscience. 15(12):1736-41.
-
Essex MJ, Shirtcliff EA, Burk LR, Ruttle PL, Klein MH, Slattery MJ, Kalin NH, 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. Development and Psychopathology. Nov;23(4):1039-58.
-
Light SN, Heller AS, Johnstone T, Kolden GG, Peterson MJ, Kalin NH, 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. Biological Psychiatry. Nov 15;70(10):962-8.
-
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, & Behavior. Nov;9(8):974-84.
-
Ferrarelli F, Peterson MJ, Sarasso S, Riedner BA, Murphy MJ, Benca RM, Bria P, Kalin NH, Tononi G. (2010) Thalamic dysfunction in schizophrenia suggested by whole-night deficits in slow and fast spindles. American Journal of Psychiatry. Nov;167(11):1339-48.
-
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. Journal of Neuroscience. 30:7023-7027.
-
Oler JA, Fox AS, Shelton SE, Rogers J, Dyer TD, Davidson RJ, Shelledy W, Oakes TR, Blangero J, Kalin NH. (2010) Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Nature. Aug 12;466(7308):864-8.
-
Christian BT, Vandehey NT, Fox AS, Murali D, Oakes TR, Converse AK, Nickles RJ, Shelton SE, Davidson RJ and Kalin NH. (2009) The distribution of D2/D3 receptor binding in the adolescent rhesus monkey using small animal PET imaging. Neuroimage. 44:1334-1344.
-
Whalen PJ, Johnstone T, Somerville LH, Nitschke JB, Polis S, Alexander AL, Davidson RJ, Kalin NH. (2008) A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder. Biological Psychiatry. May 1;63(9):858-63.