Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety

Molecular Psychiatry volume 19, pages 915–922 (2014)Cite this article

Subjects

Abstract

Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance abuse. These disorders are highly prevalent, debilitating and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and young monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the amygdala is an important substrate. Although it is widely believed that the flow of information across the structural network connecting the Ce nucleus to other brain regions underlies primates’ capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting children with anxiety disorders to identify an evolutionarily conserved pattern of functional connectivity relevant to early-life anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex, a region thought to play a central role in the control of cognition and emotion, and the Ce nucleus was associated with increased anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography imaging provided evidence that elevated Ce nucleus metabolism statistically mediates the association between prefrontal-amygdalar connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Darwin C . The Expression of the Emotions in Man and Animals. 4th edn. Oxford University Press: NY, 1872/2009.

    Book  Google Scholar 

  2. Kagan J, Reznick JS, Snidman N . Biological bases of childhood shyness. Science 1988; 240: 167–171.

    Article  CAS  PubMed  Google Scholar 

  3. Fox NA, Henderson HA, Marshall PJ, Nichols KE, Ghera MM . Behavioral inhibition: linking biology and behavior within a developmental framework. Annu Rev Psychol 2005; 56: 235–262.

    Article  PubMed  Google Scholar 

  4. Blackford JU, Pine DS . Neural substrates of childhood anxiety disorders: a review of neuroimaging findings. Child Adolesc Psychiatr Clin N Am 2012; 21: 501–525.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bystritsky A . Treatment-resistant anxiety disorders. Mol Psychiatry 2006; 11: 805–814.

    Article  CAS  PubMed  Google Scholar 

  6. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU . Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res 2012; 21: 169–184.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cloos JM, Ferreira V . Current use of benzodiazepines in anxiety disorders. Curr Opin Psychiatry 2009; 22: 90–95.

    Article  PubMed  Google Scholar 

  8. Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS et al. Grand challenges in global mental health. Nature 2011; 475: 27–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 2013; 382: 1575–1586.

    Article  PubMed  Google Scholar 

  10. Fox AS, Shelton SE, Oakes TR, Davidson RJ, Kalin NH . Trait-like brain activity during adolescence predicts anxious temperament in primates. PLoS OneNE 2008; 3: e2570.

    Article  Google Scholar 

  11. Shackman AJ, Fox AS, Oler JA, Shelton SE, Davidson RJ, Kalin NH . Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Proc Natl Acad Sci USA 2013; 110: 6145–6150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Oler JA, Fox AS, Shelton SE, Rogers J, Dyer TD, Davidson RJ et al. Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Nature 2010; 466: 864–868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fox AS, Oler JA, Shelton SE, Nanda SA, Davidson RJ, Roseboom PH et al. Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates. Proc Natl Acad Sci USA 2012; 109: 18108–18113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kalin NH, Shelton SE, Turner JG . Effects of alprazolam on fear-related behavioral, hormonal, and catecholamine responses in infant rhesus monkeys. Life Sci 1991; 49: 2031–2044.

    Article  CAS  PubMed  Google Scholar 

  15. Kalin NH, Shelton SE . Defensive behaviors in infant rhesus monkeys: environmental cues and neurochemical regulation. Science 1989; 243: 1718–1721.

    Article  CAS  PubMed  Google Scholar 

  16. Kalin NH, Shelton SE, Davidson RJ . The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. J Neurosci 2004; 24: 5506–5515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Feinstein JS, Adolphs R, Damasio A, Tranel D . The human amygdala and the induction and experience of fear. Curr Biol 2011; 21: 1–5.

    Article  Google Scholar 

  18. Pare D, Duvarci S . Amygdala microcircuits mediating fear expression and extinction. Curr Opin Neurobiol 2012; 22: 717–723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Freese JL, Amaral DG . Neuroanatomy of the primate amygdala. In: Whalen PJ, Phelps EA (eds). The human amygdala. Guilford: NY, 2009, pp 3–42.

    Google Scholar 

  20. Uhlhaas PJ, Singer W . Neuronal dynamics and neuropsychiatric disorders: toward a translational paradigm for dysfunctional large-scale networks. Neuron 2012; 75: 963–980.

    Article  CAS  PubMed  Google Scholar 

  21. Shackman AJ, Salomons TV, Slagter HA, Fox AS, Winter JJ, Davidson RJ . The integration of negative affect, pain and cognitive control in the cingulate cortex. Nat Rev Neurosci 2011; 12: 154–167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Preuss TM . Primate brain evolution in phylogenetic context. In: Kaas JH, Preuss TM (eds). Evolution of Nervous Systems vol. 4. Elsevier: NY, 2007, pp 3–34.

    Google Scholar 

  23. Ongur D, Price JL . The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 2000; 10: 206–219.

    Article  CAS  PubMed  Google Scholar 

  24. Pessoa L . The Cognitive-Emotional Brain: From Interactions to Integration. MIT Press: Cambridge, MA, 2013.

    Book  Google Scholar 

  25. Pessoa L . Beyond brain regions: network perspective of cognition-emotion interactions. Behav Brain Sci 2012; 35: 158–159.

    Article  PubMed  Google Scholar 

  26. Ekstrom LB, Roelfsema PR, Arsenault JT, Bonmassar G, Vanduffel W . Bottom-up dependent gating of frontal signals in early visual cortex. Science 2008; 321: 414–417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Buckner RL, Krienen FM, Yeo BT . Opportunities and limitations of intrinsic functional connectivity MRI. Nat Neurosci 2013; 16: 832–837.

    Article  PubMed  Google Scholar 

  28. Vincent JL, Patel GH, Fox MD, Snyder AZ, Baker JT, Van Essen DC et al. Intrinsic functional architecture in the anaesthetized monkey brain. Nature 2007; 447: 83–86.

    Article  CAS  PubMed  Google Scholar 

  29. Honey CJ, Sporns O, Cammoun L, Gigandet X, Thiran JP, Meuli R et al. Predicting human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci USA 2009; 106: 2035–2040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Dum RP, Levinthal DJ, Strick PL . The spinothalamic system targets motor and sensory areas in the cerebral cortex of monkeys. J Neurosci 2009; 29: 14223–14235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Adachi Y, Osada T, Sporns O, Watanabe T, Matsui T, Miyamoto K et al. Functional connectivity between anatomically unconnected areas is shaped by collective network-level effects in the macaque cortex. Cereb Cortex 2012; 22: 1586–1592.

    Article  PubMed  Google Scholar 

  32. Ghashghaei HT, Barbas H . Pathways for emotion: interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey. Neuroscience 2002; 115: 1261–1279.

    Article  CAS  PubMed  Google Scholar 

  33. Stefanacci L, Amaral DG . Some observations on cortical inputs to the macaque monkey amygdala: an anterograde tracing study. J Comp Neurol 2002; 451: 301–323.

    Article  PubMed  Google Scholar 

  34. Buhle JT, Silvers JA, Wager TD, Lopez R, Onyemekwu C, Kober H et al. Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies. Cereb Cortex 2013 (in press).

  35. Casey BJ, Craddock N, Cuthbert BN, Hyman SE, Lee FS, Ressler KJ . DSM-5 and RDoC: progress in psychiatry research? Nat Rev Neurosci 2013; 14: 810–814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Borsook D, Becerra L, Hargreaves R . A role for fMRI in optimizing CNS drug development. Nat Rev Drug Discov 2006; 5: 411–424.

    Article  CAS  PubMed  Google Scholar 

  37. Oler JA, Birn RM, Patriat R, Fox AS, Shelton SE, Burghy CA et al. Evidence for coordinated functional activity within the extended amygdala of non-human and human primates. Neuroimage 2012; 61: 1059–1066.

    Article  PubMed  Google Scholar 

  38. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P et al. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997; 36: 980–988.

    Article  CAS  PubMed  Google Scholar 

  39. de Bie HM, Boersma M, Wattjes MP, Adriaanse S, Vermeulen RJ, Oostrom KJ et al. Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans. Eur J Pediatr 2010; 169: 1079–1085.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004; 23: S208–S219.

    Article  PubMed  Google Scholar 

  41. Woolrich MW, Jbabdi S, Patenaude B, Chappell M, Makni S, Behrens T et al. Bayesian analysis of neuroimaging data in FSL. Neuroimage 2009; 45: S173–S186.

    Article  PubMed  Google Scholar 

  42. Zhang Y, Brady M, Smith S . Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 2001; 20: 45–57.

    Article  CAS  PubMed  Google Scholar 

  43. Herringa RJ, Birn RM, Ruttle PL, Burghy CA, Stodola DE, Davidson RJ et al. Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence. Proc Natl Acad Sci USA 2013; 110: 19119–19124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Burghy CA, Stodola DE, Ruttle PL, Molloy EK, Armstrong JM, Oler JA et al. Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nat Neurosci 2012; 15: 1736–1741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets V . A comparison of methods to test mediation and other intervening variable effects. Psychol Methods 2002; 7: 83–104.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Baron RM, Kenny DA . The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. J Pers Soc Psychol 1986; 51: 1173–1182.

    Article  CAS  PubMed  Google Scholar 

  47. Lim SL, Padmala S, Pessoa L . Segregating the significant from the mundane on a moment-to-moment basis via direct and indirect amygdala contributions. Proc Natl Acad Sci USA 2009; 106: 16841–16846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wager TD, Davidson ML, Hughes BL, Lindquist MA, Ochsner KN . Prefrontal-subcortical pathways mediating successful emotion regulation. Neuron 2008; 59: 1037–1050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Shackman JE, Shackman AJ, Pollak SD . Physical abuse amplifies attention to threat and increases anxiety in children. Emotion 2007; 7: 838–852.

    Article  PubMed  Google Scholar 

  50. Clogg CC, Petkova E, Shihadeh ES . Statistical methods for analyzing collapsibility in regression models. J Educ Stat 1992; 17: 51–74.

    Article  Google Scholar 

  51. Barbas H, De Olmos J . Projections from the amygdala to basoventral and mediodorsal prefrontal regions in the rhesus monkey. J Comp Neurol 1990; 300: 549–571.

    Article  CAS  PubMed  Google Scholar 

  52. Amaral DG, Insausti R . Retrograde transport of D-[3 H]-aspartate injected into the monkey amygdaloid complex. Exp Brain Res 1992; 88: 375–388.

    Article  CAS  PubMed  Google Scholar 

  53. Amaral DG, Price JL . Amygdalo-cortical projections in the monkey (Macaca fascicularis). J Comp Neurol 1984; 230: 465–496.

    Article  CAS  PubMed  Google Scholar 

  54. Miller EK, Cohen JD . An integrative theory of prefrontal cortex function. Annu Rev Neurosci 2001; 24: 167–202.

    Article  CAS  PubMed  Google Scholar 

  55. Shackman AJ, McMenamin BW, Maxwell JS, Greischar LL, Davidson RJ . Right dorsolateral prefrontal cortical activity and behavioral inhibition. Psychol Sci 2009; 20: 1500–1506.

    Article  PubMed  Google Scholar 

  56. Koenigs M, Huey ED, Calamia M, Raymont V, Tranel D, Grafman J . Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression. J Neurosci 2008; 28: 12341–12348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ekstrom LB, Roelfsema PR, Arsenault JT, Kolster H, Vanduffel W . Modulation of the contrast response function by electrical microstimulation of the macaque frontal eye field. J Neurosci 2009; 29: 10683–10694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Premereur E, Janssen P, Vanduffel W . FEF-microstimulation causes task-dependent modulation of occipital fMRI activity. Neuroimage 2012; 67: 42–50.

    Article  PubMed  Google Scholar 

  59. Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 2005; 8: 828–834.

    Article  CAS  PubMed  Google Scholar 

  60. Kim MJ, Gee DG, Loucks RA, Davis FC, Whalen PJ . Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest. Cereb Cortex 2011; 7: 1667–1673.

    Article  Google Scholar 

  61. Akam T, Kullmann DM . Oscillatory multiplexing of population codes for selective communication in the mammalian brain. Nat Rev Neurosci 2014; 15: 111–122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Cabral J, Kringelbach ML, Deco G . Exploring the network dynamics underlying brain activity during rest. Prog Neurobiol 2014; 114C: 102–131.

    Article  Google Scholar 

  63. Logothetis NK . What we can do and what we cannot do with fMRI. Nature 2008; 453: 869–878.

    Article  CAS  PubMed  Google Scholar 

  64. Arnsten AF . Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci 2009; 10: 410–422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Shackman AJ, Maxwell JS, McMenamin BW, Greischar LL, Davidson RJ . Stress potentiates early and attenuates late stages of visual processing. J Neurosci 2011; 31: 1156–1161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Davis M, Whalen PJ . The amygdala: vigilance and emotion. Mol Psychiatry 2001; 6: 13–34.

    Article  CAS  PubMed  Google Scholar 

  67. Fudge JL, Haber SN . The central nucleus of the amygdala projection to dopamine subpopulations in primates. Neuroscience 2000; 97: 479–494.

    Article  CAS  PubMed  Google Scholar 

  68. Fornito A, Harrison BJ, Goodby E, Dean A, Ooi C, Nathan PJ et al. Functional dysconnectivity of corticostriatal circuitry as a risk phenotype for psychosis. JAMA Psychiatry 2013; 70: 1143–1151.

    Article  PubMed  Google Scholar 

  69. Guller Y, Ferrarelli F, Shackman AJ, Sarasso S, Peterson MJ, Langheim FJ et al. Probing thalamic integrity in schizophrenia using concurrent transcranial magnetic stimulation and functional magnetic resonance imaging. Arch Gen Psychiatry 2012; 69: 662–671.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Chen AC, Oathes DJ, Chang C, Bradley T, Zhou ZW, Williams LM et al. Causal interactions between fronto-parietal central executive and default-mode networks in humans. Proc Natl Acad Sci USA 2013; 110: 19944–19949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bullmore E . The future of functional MRI in clinical medicine. Neuroimage 2012; 62: 1267–1271.

    Article  PubMed  Google Scholar 

  72. Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci 2013; 14: 365–376.

    Article  CAS  PubMed  Google Scholar 

  73. Davidson RJ . Affective style and affective disorders: perspectives from affective neuroscience. Cogn Emot 1998; 12: 307–330.

    Article  Google Scholar 

  74. Badre D, D'Esposito M . Is the rostro-caudal axis of the frontal lobe hierarchical? Nat Rev Neurosci 2009; 10: 659–669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We acknowledge the assistance of E Ahlers, V Balchen, B Christian, A Converse, L Friedman, M Jesson, E Larson, K Mayer, T Oakes, M Riedel, P Roseboom, J Storey, D Tromp, N Vack, H Van Valkenberg and the staffs of the Harlow Center for Biological Psychology, HealthEmotions Research Institute (HERI), Waisman Center, Waisman Laboratory for Brain Imaging and Behavior and Wisconsin National Primate Center. We thank Julie Fudge, Luiz Pessoa, and several anonymous reviewers for critical feedback. This work was supported by the National Institutes of Health (NIH; Intramural Research Program and extramural grants HD003352, HD008352, MH018931, MH046729, MH081884, MH084051, MH090912, MH091550, OD011106 and RR000167), HERI, Meriter Hospital and the University of Maryland.

Author information

Author notes

  1. R M Birn and A J Shackman: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Physics, University of Wisconsin, Madison, WI, USA,

    R M Birn & A L Alexander

  2. Department of Psychiatry, University of Wisconsin, Madison, WI, USA,

    R M Birn, J A Oler, L E Williams, D R McFarlin, G M Rogers, S E Shelton, M J Slattery, R J Davidson, A S Fox & N H Kalin

  3. HealthEmotions Research Institute, Wisconsin Psychiatric Institute and Clinics, University of Wisconsin, Madison, WI, USA,

    R M Birn, J A Oler, L E Williams, D R McFarlin, R J Davidson, A S Fox & N H Kalin

  4. Lane Neuroimaging Laboratory, University of Wisconsin, Madison, WI, USA,

    R M Birn, J A Oler, L E Williams, D R McFarlin, A S Fox & N H Kalin

  5. Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, USA,

    R M Birn, D R McFarlin, A L Alexander, R J Davidson, A S Fox & N H Kalin

  6. Department of Psychology, University of Maryland, College Park, MD, USA

    A J Shackman

  7. Neuroscience and Cognitive Science Program, University of Maryland, College Park, MD, USA

    A J Shackman

  8. Maryland Neuroimaging Center, University of Maryland, College Park, MD, USA

    A J Shackman

  9. Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, MD, USA

    D S Pine

  10. Department of Psychology, University of Wisconsin, Madison, WI, USA,

    R J Davidson, A S Fox & N H Kalin

  11. Center for Investigating Healthy Minds, University of Wisconsin, Madison, WI, USA,

    R J Davidson & A S Fox

Authors
  1. R M Birn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A J Shackman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J A Oler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L E Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D R McFarlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G M Rogers
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S E Shelton
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A L Alexander
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D S Pine
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M J Slattery
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R J Davidson
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A S Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. N H Kalin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N H Kalin.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Author contributions

NHK, JAO, DSP, MJS and SES designed the study. SES collected monkey data. LEW collected human data. ALA optimized imaging methods. DSP, NHK and GMR made childhood psychiatric diagnoses. RMB and ASF developed analytical tools. RMB, JAO, AJS and ASF performed data processing for monkey data. DRM, LEW, JAO, AJS and RMB performed data processing for human data. RMB, AJS, JAO and NHK analyzed monkey data. DRM, LEW, JAO, AJS, RMB and NHK analyzed human data. AJS, NHK, RMB, ASF, JAO, RJD and DSP interpreted data. AJS, ASF, NHK, JAO, LEW and RMB wrote the paper. AJS, ASF and NHK created the figures. AJS, JAO and LEW created the tables. NHK supervised the study. All authors contributed to revising the paper.

Supplementary Information accompanies the paper on the Molecular Psychiatry website

Supplementary information

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Birn, R., Shackman, A., Oler, J. et al. Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety. Mol Psychiatry 19, 915–922 (2014). https://doi.org/10.1038/mp.2014.46

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2014.46

This article is cited by

Search

Advanced search

Quick links