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

Dr. Kalin’s research combines molecular, preclinical animal models, and human functional imaging studies to elucidate the mechanisms underlying the pathophysiology of anxiety and affective disorders. His work focuses on using translational models in nonhuman primates to elucidate early life mechanisms underlying the development of anxiety and depression. This work combines selective lesion strategies with functional brain imaging to demonstrate the importance of amygdala, bed nucleus of the stria terminalis, and the orbitofrontal cortex in mediating maladaptive responses to stress. Using the nonhuman primate, he has also established early markers of the risk to develop psychopathology, which has proved to be relevant to understanding risk in children. Recent studies in primates demonstrate the molecular underpinnings within the amygdala that underlie early risk. Specifically, RNA sequencing studies demonstrate alterations in the expression of neuroplasticity systems in young primates with high levels of dispositional anxiety. In humans he has performed imaging studies related to understanding mechanisms underlying emotion regulation. He is currently translating findings from his nonhuman primate studies to young children by examining alterations in brain regions underlying emotion regulation in children with high levels of anxious temperament. Taken together, his studies underscore the brain mechanisms underlying adaptive and maladaptive emotion regulation and the importance of emotion regulation in understanding individual differences related to risk for the development of stress-related psychopathology.

Selected Publications

PubMed

Aggarwal, N., Tromp, D. P. M., Blackford, J. U., Pine, D. S., Roseboom, P. H., Williams, L. E., & Kalin, N. H. (2024). Sex-Specific Distributed White Matter Microarchitectural Alterations in Preadolescent Youths With Anxiety Disorders: A Mega-Analytic Study. The American journal of psychiatry, 181(4), 299–309. https://doi.org/10.1176/appi.ajp.20221048
Aggarwal, N., Oler, J. A., Tromp, D. P. M., Roseboom, P. H., Riedel, M. K., Elam, V. R., Brotman, M. A., & Kalin, N. H. (2024). A preliminary study of the effects of an antimuscarinic agent on anxious behaviors and white matter microarchitecture in nonhuman primates. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 49(2), 405–413. https://doi.org/10.1038/s41386-023-01686-1
Kenwood, M. M., Souaiaia, T., Kovner, R., Fox, A. S., French, D. A., Oler, J. A., Roseboom, P. H., Riedel, M. K., Mueller, S. A. L., & Kalin, N. H. (2023). Gene expression in the primate orbitofrontal cortex related to anxious temperament. Proceedings of the National Academy of Sciences of the United States of America, 120(49), e2305775120. https://doi.org/10.1073/pnas.2305775120
Mueller, S. A. L., Oler, J. A., Roseboom, P. H., Aggarwal, N., Kenwood, M. M., Riedel, M. K., Elam, V. R., Olsen, M. E., DiFilippo, A. H., Christian, B. T., Hu, X., Galvan, A., Boehm, M. A., Michaelides, M., & Kalin, N. H. (2023). DREADD-mediated amygdala activation is sufficient to induce anxiety-like responses in young nonhuman primates. Current research in neurobiology, 5, 100111. https://doi.org/10.1016/j.crneur.2023.100111
Kenwood, M. M., Oler, J. A., Tromp, D. P. M., Fox, A. S., Riedel, M. K., Roseboom, P. H., Brunner, K. G., Aggarwal, N., Murray, E. A., & Kalin, N. H. (2023). Prefrontal influences on the function of the neural circuitry underlying anxious temperament in primates. Oxford open neuroscience, 2, kvac016. https://doi.org/10.1093/oons/kvac016
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.