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.

  • Review Article
  • Published:

The effects of childhood maltreatment on brain structure, function and connectivity

Key Points

  • Childhood maltreatment (specifically, physical, sexual and emotional abuse, and physical and emotional neglect) exerts a prepotent influence on trajectories of child brain development and constitutes a major risk factor for adult psychopathology.

  • Brain alterations resulting from maltreatment are highly specific, depend on the type and timing of exposure, and probably were once phenotypic adaptations that enhanced species survival and reproductive success but are now associated with substantial medical and psychiatric disadvantages.

  • Maltreatment reduces the volume of the hippocampus (particularly in adults), as well as the volume of anterior cingulate and ventromedial and dorsomedial cortices; affects the development of key fibre tracts (including the corpus callosum, superior longitudinal fasciculus, uncinate fasciculus and cingulum bundle); and appears to alter the development of sensory systems that process and convey stressful experiences.

  • This Review reveals consistent reports of augmented amygdala response to threatening stimuli, diminished ventral striatal response to anticipation or receipt of reward, diminished connectivity between prefrontal regions and the amygdala, and increased volume and network centrality of the precuneus in maltreated individuals.

  • Maltreated and non-maltreated individuals with the same primary psychiatric diagnoses differ clinically, neurobiologically and genetically, such that maltreated individuals seem to represent distinct ecophenotypes of established psychiatric disorders. Thus, maltreatment may be an unrecognized confound in psychiatric neuroimaging studies.

  • Maltreatment-associated brain changes are frequently reported in resilient individuals who show no past or current symptoms of psychopathology. Other neurobiological or molecular alterations are probably present that enable these individuals to effectively compensate for stress-related neurobiological alterations.

Abstract

Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Abuse type-specific effects on the developing brain.
Figure 2: Circuitry underlying threat detection and response.
Figure 3: Maltreatment-associated changes in functional connectivity.
Figure 4: Maltreatment-sensitivity periods for different brain areas.
Figure 5: The dopaminergic reward system.
Figure 6: Network changes associated with childhood maltreatment.

Similar content being viewed by others

References

  1. Takesian, A. E. & Hensch, T. K. Balancing plasticity/stability across brain development. Prog. Brain Res. 207, 3–34 (2013).

    Article  PubMed  Google Scholar 

  2. Teicher, M. H. & Samson, J. A. Childhood maltreatment and psychopathology: a case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. Am. J. Psychiatry 170, 1114–1133 (2013). This article argues that psychiatric disorders need to be subtyped based on maltreatment history.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Dube, S. R., Felitti, V. J., Dong, M., Giles, W. H. & Anda, R. F. The impact of adverse childhood experiences on health problems: evidence from four birth cohorts dating back to 1900. Prev. Med. 37, 268–277 (2003).

    Article  PubMed  Google Scholar 

  4. Dube, S. R. et al. Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study. Pediatrics 111, 564–572 (2003).

    Article  PubMed  Google Scholar 

  5. Anda, R. F. et al. Adverse childhood experiences and prescribed psychotropic medications in adults. Am. J. Prev. Med. 32, 389–394 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Brown, D. W. et al. Adverse childhood experiences and the risk of premature mortality. Am. J. Prev. Med. 37, 389–396 (2009).

    Article  PubMed  Google Scholar 

  7. Price, L. H., Kao, H. T., Burgers, D. E., Carpenter, L. L. & Tyrka, A. R. Telomeres and early-life stress: an overview. Biol. Psychiatry 73, 15–23 (2013).

    Article  CAS  PubMed  Google Scholar 

  8. Ito, Y. et al. Increased prevalence of electrophysiological abnormalities in children with psychological, physical, and sexual abuse. J. Neuropsychiatry Clin. Neurosci. 5, 401–408 (1993).

    Article  CAS  PubMed  Google Scholar 

  9. Schiffer, F., Teicher, M. H. & Papanicolaou, A. C. Evoked potential evidence for right brain activity during the recall of traumatic memories. J. Neuropsychiatry Clin. Neurosci. 7, 169–175 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Teicher, M. H. Wounds that time won't heal: the neurobiology of child abuse. Cerebrum 4, 50–67 (2000).

    Google Scholar 

  11. Teicher, M. H. & Samson, J. A. Annual research review: enduring neurobiological effects of childhood abuse and neglect. J. Child Psychol. Psychiatry 57, 241–266 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Tottenham, N. The importance of early experiences for neuro-affective development. Curr. Top. Behav. Neurosci. 16, 109–129 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  13. McLaughlin, K. A., Sheridan, M. A. & Lambert, H. K. Childhood adversity and neural development: deprivation and threat as distinct dimensions of early experience. Neurosci. Biobehav. Rev. 47, 578–591 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Brewin, C. R., Andrews, B. & Gotlib, I. H. Psychopathology and early experience: a reappraisal of retrospective reports. Psychol. Bull. 113, 82–98 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. De Bellis, M. D. et al. Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study. Biol. Psychiatry 52, 1066–1078 (2002).

    Article  PubMed  Google Scholar 

  16. Teicher, M. H., Tomoda, A. & Andersen, S. L. Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable? Ann. NY Acad. Sci. 1071, 313–323 (2006).

    Article  PubMed  Google Scholar 

  17. National Scientific Council on the Developing Child. Excessive stress disrupts the architecture of the developing brain: working paper #3 (Center on the Developing Child Harvard Univ., 2005).

  18. Lupien, S. J., McEwen, B. S., Gunnar, M. R. & Heim, C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat. Rev. Neurosci. 10, 434–445 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Teicher, M. H. Scars that won't heal: the neurobiology of child abuse. Sci. Am. 286, 68–75 (2002).

    Article  PubMed  Google Scholar 

  20. Teicher, M. H. et al. The neurobiological consequences of early stress and childhood maltreatment. Neurosci. Biobehav. Rev. 27, 33–44 (2003).

    Article  PubMed  Google Scholar 

  21. Gibb, B. E., Schofield, C. A. & Coles, M. E. Reported history of childhood abuse and young adults' information-processing biases for facial displays of emotion. Child Maltreat. 14, 148–156 (2009).

    Article  PubMed  Google Scholar 

  22. Pollak, S. D. Experience-dependent affective learning and risk for psychopathology in children. Ann. NY Acad. Sci. 1008, 102–111 (2003).

    Article  PubMed  Google Scholar 

  23. Rutter, M. Achievements and challenges in the biology of environmental effects. Proc. Natl Acad. Sci. USA 109, 17149–17153 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Belsky, J. & Pluess, M. Beyond risk, resilience, and dysregulation: phenotypic plasticity and human development. Dev. Psychopathol. 25, 1243–1261 (2013).

    Article  PubMed  Google Scholar 

  25. Tomoda, A. et al. Exposure to parental verbal abuse is associated with increased gray matter volume in superior temporal gyrus. Neuroimage 54, S280–S286 (2011).

    Article  PubMed  Google Scholar 

  26. Choi, J., Jeong, B., Rohan, M. L., Polcari, A. M. & Teicher, M. H. Preliminary evidence for white matter tract abnormalities in young adults exposed to parental verbal abuse. Biol. Psychiatry 65, 227–234 (2009).

    Article  PubMed  Google Scholar 

  27. Tomoda, A., Polcari, A., Anderson, C. M. & Teicher, M. H. Reduced visual cortex gray matter volume and thickness in young adults who witnessed domestic violence during childhood. PLoS ONE 7, e52528 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Choi, J., Jeong, B., Polcari, A., Rohan, M. L. & Teicher, M. H. Reduced fractional anisotropy in the visual limbic pathway of young adults witnessing domestic violence in childhood. Neuroimage 59, 1071–1079 (2012).

    Article  PubMed  Google Scholar 

  29. Tomoda, A., Navalta, C. P., Polcari, A., Sadato, N. & Teicher, M. H. Childhood sexual abuse is associated with reduced gray matter volume in visual cortex of young women. Biol. Psychiatry 66, 642–648 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Heim, C. M., Mayberg, H. S., Mletzko, T., Nemeroff, C. B. & Pruessner, J. C. Decreased cortical representation of genital somatosensory field after childhood sexual abuse. Am. J. Psychiatry 170, 616–623 (2013). This study provides evidence for sensory-specific damage after exposure to childhood sexual abuse.

    Article  PubMed  Google Scholar 

  31. Tottenham, N. et al. Elevated amygdala response to faces following early deprivation. Dev. Sci. 14, 190–204 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. McCrory, E. J. et al. Heightened neural reactivity to threat in child victims of family violence. Curr. Biol. 21, R947–R948 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. Garrett, A. S. et al. Brain activation to facial expressions in youth with PTSD symptoms. Depress. Anxiety 29, 449–459 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Grant, M. M., Cannistraci, C., Hollon, S. D., Gore, J. & Shelton, R. Childhood trauma history differentiates amygdala response to sad faces within MDD. J. Psychiatr. Res. 45, 886–895 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bogdan, R., Williamson, D. E. & Hariri, A. R. Mineralocorticoid receptor Iso/Val (rs5522) genotype moderates the association between previous childhood emotional neglect and amygdala reactivity. Am. J. Psychiatry 169, 515–522 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  36. van Harmelen, A. L. et al. Enhanced amygdala reactivity to emotional faces in adults reporting childhood emotional maltreatment. Soc. Cogn. Affect. Neurosci. 8, 362–369 (2013).

    Article  PubMed  Google Scholar 

  37. Dannlowski, U. et al. Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biol. Psychiatry 71, 286–293 (2012). This paper shows evidence of morphometric abnormalities and amygdala hyperreactivity in maltreated subjects without psychopathology.

    Article  PubMed  Google Scholar 

  38. LeDoux, J. Emotional networks and motor control: a fearful view. Prog. Brain Res. 107, 437–446 (1996).

    Article  CAS  PubMed  Google Scholar 

  39. LeDoux, J. Synaptic Self: How Our Brains Become Who We Are (Viking Penguin, 2002).

    Google Scholar 

  40. Herman, J. P. & Mueller, N. K. Role of the ventral subiculum in stress integration. Behav. Brain Res. 174, 215–224 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Maren, S., Phan, K. L. & Liberzon, I. The contextual brain: implications for fear conditioning, extinction and psychopathology. Nat. Rev. Neurosci. 14, 417–428 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Linke, R., Braune, G. & Schwegler, H. Differential projection of the posterior paralaminar thalamic nuclei to the amygdaloid complex in the rat. Exp. Brain Res. 134, 520–532 (2000).

    Article  CAS  PubMed  Google Scholar 

  43. Shang, C. et al. A parvalbumin-positive excitatory visual pathway to trigger fear responses in mice. Science 348, 1472–1477 (2015).

    Article  CAS  PubMed  Google Scholar 

  44. De Bellis, M. D., Keshavan, M. S., Spencer, S. & Hall, J. N-Acetylaspartate concentration in the anterior cingulate of maltreated children and adolescents with PTSD. Am. J. Psychiatry 157, 1175–1177 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Cohen, R. A. et al. Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biol. Psychiatry 59, 975–982 (2006).

    Article  PubMed  Google Scholar 

  46. Kelly, P. A. et al. Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment: neural markers of vulnerability? Biol. Psychiatry 74, 845–852 (2013).

    Article  PubMed  Google Scholar 

  47. Jensen, S. K. et al. Effect of early adversity and childhood internalizing symptoms on brain structure in young men. JAMA Pediatr. 169, 938–946 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Chugani, H. T. et al. Local brain functional activity following early deprivation: a study of postinstitutionalized Romanian orphans. Neuroimage 14, 1290–1301 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Edmiston, E. E. et al. Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment. Arch. Pediatr. Adolesc. Med. 165, 1069–1077 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Andersen, S. L. et al. Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. J. Neuropsychiatry Clin. Neurosci. 20, 292–301 (2008). This study provides the initial evidence for sensitive periods in the hippocampus, corpus callosum and PFC.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Opel, N. et al. Hippocampal atrophy in major depression: a function of childhood maltreatment rather than diagnosis? Neuropsychopharmacology 39, 2723–2731 (2014). This paper shows that hippocampal volume abnormalities are associated more directly with maltreatment than with major depression.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Teicher, M. H., Anderson, C. M. & Polcari, A. Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. Proc. Natl Acad. Sci. USA 109, E563–E572 (2012).

    Article  CAS  PubMed  Google Scholar 

  53. Hanson, J. L. et al. Early stress is associated with alterations in the orbitofrontal cortex: a tensor-based morphometry investigation of brain structure and behavioral risk. J. Neurosci. 30, 7466–7472 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kumari, V. et al. Reduced thalamic volume in men with antisocial personality disorder or schizophrenia and a history of serious violence and childhood abuse. Eur. Psychiatry 28, 225–234 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. Huang, H., Gundapuneedi, T. & Rao, U. White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology. Neuropsychopharmacology 37, 2693–2701 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Benedetti, F. et al. Adverse childhood experiences influence white matter microstructure in patients with bipolar disorder. Psychol. Med. 44, 3069–3082 (2014).

    Article  CAS  PubMed  Google Scholar 

  57. Eluvathingal, T. J. et al. Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study. Pediatrics 117, 2093–2100 (2006).

    Article  PubMed  Google Scholar 

  58. Birn, R. M., Patriat, R., Phillips, M. L., Germain, A. & Herringa, R. J. Childhood maltreatment and combat posttraumatic stress differentially predict fear-related fronto-subcortical connectivity. Depress. Anxiety 31, 880–892 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Cisler, J. M. et al. Differential functional connectivity within an emotion regulation neural network among individuals resilient and susceptible to the depressogenic effects of early life stress. Psychol. Med. 43, 507–518 (2013).

    Article  CAS  PubMed  Google Scholar 

  60. Herringa, R. J. et al. Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence. Proc. Natl Acad. Sci. USA 110, 19119–19124 (2013).

    Article  CAS  PubMed  Google Scholar 

  61. Wang, L. et al. Overlapping and segregated resting-state functional connectivity in patients with major depressive disorder with and without childhood neglect. Hum. Brain Mapp. 35, 1154–1166 (2014). This study demonstrates functional connectivity abnormalities in depressed individuals with and without histories of maltreatment.

    Article  PubMed  Google Scholar 

  62. Morris, J. S., Ohman, A. & Dolan, R. J. A subcortical pathway to the right amygdala mediating “unseen” fear. Proc. Natl Acad. Sci. USA 96, 1680–1685 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Dannlowski, U. et al. Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala. Hum. Brain Mapp. 34, 2899–2909 (2013).

    Article  PubMed  Google Scholar 

  64. Mehta, M. A. et al. Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian Adoptees Study Pilot. J. Child Psychol. Psychiatry 50, 943–951 (2009).

    Article  PubMed  Google Scholar 

  65. Tottenham, N. et al. Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Dev. Sci. 13, 46–61 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Lupien, S. J. et al. Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proc. Natl Acad. Sci. USA 108, 14324–14329 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Pechtel, P., Lyons-Ruth, K., Anderson, C. M. & Teicher, M. H. Sensitive periods of amygdala development: the role of maltreatment in preadolescence. Neuroimage 97, 236–244 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Whittle, S. et al. Childhood maltreatment and psychopathology affect brain development during adolescence. J. Am. Acad. Child Adolesc. Psychiatry 52, 940–952.e1 (2013).

    Article  PubMed  Google Scholar 

  69. Kuo, J. R., Kaloupek, D. G. & Woodward, S. H. Amygdala volume in combat-exposed veterans with and without posttraumatic stress disorder: a cross-sectional study. Arch. Gen. Psychiatry 69, 1080–1086 (2012).

    Article  PubMed  Google Scholar 

  70. Hanson, J. L. et al. Behavioral problems after early life stress: contributions of the hippocampus and amygdala. Biol. Psychiatry 77, 314–323 (2015).

    Article  PubMed  Google Scholar 

  71. Lyons-Ruth, K., Pechtel, P., Yoon, S. A., Anderson, C. M. & Teicher, M. H. Disorganized attachment in infancy predicts greater amygdala volume in adulthood. Behav. Brain Res. 308, 83–93 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Fetterman, A. K., Ode, S. & Robinson, M. D. For which side the bell tolls: the laterality of approach-avoidance associative networks. Motiv. Emot. 37, 33–38 (2013).

    Article  PubMed  Google Scholar 

  73. Kolb, B. & Gibb, R. Searching for the principles of brain plasticity and behavior. Cortex 58, 251–260 (2014).

    Article  PubMed  Google Scholar 

  74. Caldji, C., Diorio, J. & Meaney, M. J. Variations in maternal care alter GABAA receptor subunit expression in brain regions associated with fear. Neuropsychopharmacology 28, 1950–1959 (2003).

    Article  CAS  PubMed  Google Scholar 

  75. Baker, L. M. et al. Impact of early versus late childhood early life stress on brain morphometrics. Brain Imag. Behav. 7, 196–203 (2013).

    Article  Google Scholar 

  76. Hodel, A. S. et al. Duration of early adversity and structural brain development in post-institutionalized adolescents. Neuroimage 105, 112–119 (2015).

    Article  PubMed  Google Scholar 

  77. Riem, M. M., Alink, L. R., Out, D., Van Ijzendoorn, M. H. & Bakermans-Kranenburg, M. J. Beating the brain about abuse: empirical and meta-analytic studies of the association between maltreatment and hippocampal volume across childhood and adolescence. Dev. Psychopathol. 27, 507–520 (2015).

    Article  PubMed  Google Scholar 

  78. Masten, C. L. et al. Recognition of facial emotions among maltreated children with high rates of post-traumatic stress disorder. Child Abuse Negl. 32, 139–153 (2008).

    Article  PubMed  Google Scholar 

  79. Gorka, A. X., Hanson, J. L., Radtke, S. R. & Hariri, A. R. Reduced hippocampal and medial prefrontal gray matter mediate the association between reported childhood maltreatment and trait anxiety in adulthood and predict sensitivity to future life stress. Biol. Mood Anxiety Disord. 4, 12 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Whittle, S. et al. Hippocampal volume and sensitivity to maternal aggressive behavior: a prospective study of adolescent depressive symptoms. Dev. Psychopathol. 23, 115–129 (2011).

    Article  PubMed  Google Scholar 

  81. Morey, R. A., Haswell, C. C., Hooper, S. R. & De Bellis, M. D. Amygdala, hippocampus, and ventral medial prefrontal cortex volumes differ in maltreated youth with and without chronic posttraumatic stress disorder. Neuropsychopharmacology 41, 791–801 (2016).

    Article  PubMed  Google Scholar 

  82. Takiguchi, S. et al. Ventral striatum dysfunction in children and adolescents with reactive attachment disorder: a functional MRI Study. BJPsych Open 1, 121–128 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Hanson, J. L., Hariri, A. R. & Williamson, D. E. Blunted ventral striatum development in adolescence reflects emotional neglect and predicts depressive symptoms. Biol. Psychiatry 78, 598–605 (2015). This study shows an association between childhood emotional neglect, reduced ventral striatal reward activation and depression.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Mehta, M. A. et al. Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life. J. Cogn. Neurosci. 22, 2316–2325 (2010).

    Article  PubMed  Google Scholar 

  85. Boecker, R. et al. Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years. PLoS ONE 9, e104185 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hanson, J. L. et al. Cumulative stress in childhood is associated with blunted reward-related brain activity in adulthood. Soc. Cogn. Affect. Neurosci. 11, 405–412 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Dillon, D. G. et al. Childhood adversity is associated with left basal ganglia dysfunction during reward anticipation in adulthood. Biol. Psychiatry 66, 206–213 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Haber, S. N. & Knutson, B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35, 4–26 (2010).

    Article  PubMed  Google Scholar 

  89. Thomaes, K. et al. Reduced anterior cingulate and orbitofrontal volumes in child abuse-related complex PTSD. J. Clin. Psychiatry 71, 1636–1644 (2010).

    Article  PubMed  Google Scholar 

  90. Teicher, M. H., Anderson, C. M., Ohashi, K. & Polcari, A. Childhood maltreatment: altered network centrality of cingulate, precuneus, temporal pole and insula. Biol. Psychiatry 76, 297–305 (2014). This study shows maltreatment-associated cortical network abnormalities in the cingulate, precuneus and insula.

    Article  PubMed  Google Scholar 

  91. van der Werff, S. J. et al. Resting-state functional connectivity in adults with childhood emotional maltreatment. Psychol. Med. 43, 1825–1836 (2013).

    Article  CAS  PubMed  Google Scholar 

  92. Gerritsen, L. et al. BDNF Val66Met genotype modulates the effect of childhood adversity on subgenual anterior cingulate cortex volume in healthy subjects. Mol. Psychiatry 17, 597–603 (2012).

    Article  CAS  PubMed  Google Scholar 

  93. Balodis, I. M. & Potenza, M. N. Anticipatory reward processing in addicted populations: a focus on the monetary incentive delay task. Biol. Psychiatry 77, 434–444 (2015).

    Article  PubMed  Google Scholar 

  94. De Bellis, M. D. et al. Developmental traumatology part II: brain development. Biol. Psychiatry 45, 1271–1284 (1999). A classic study on childhood trauma, PTSD and altered brain morphology in children.

    Article  CAS  PubMed  Google Scholar 

  95. Teicher, M. H. et al. Childhood neglect is associated with reduced corpus callosum area. Biol. Psychiatry 56, 80–85 (2004).

    Article  PubMed  Google Scholar 

  96. Teicher, M. H., Samson, J. A., Sheu, Y. S., Polcari, A. & McGreenery, C. E. Hurtful words: association of exposure to peer verbal abuse with elevated psychiatric symptom scores and corpus callosum abnormalities. Am. J. Psychiatry 167, 1464–1471 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Bucker, J. et al. Childhood maltreatment and corpus callosum volume in recently diagnosed patients with bipolar I disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM). J. Psychiatr. Res. 48, 65–72 (2014).

    Article  CAS  PubMed  Google Scholar 

  98. Paul, R. et al. The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population. Neuropsychiatr. Dis. Treat. 4, 193–201 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  99. Luders, E., Thompson, P. M. & Toga, A. W. The development of the corpus callosum in the healthy human brain. J. Neurosci. 30, 10985–10990 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Luders, E. et al. Positive correlations between corpus callosum thickness and intelligence. Neuroimage 37, 1457–1464 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Teicher, M. H. et al. Preliminary evidence for abnormal cortical development in physically and sexually abused children using EEG coherence and MRI. Ann. NY Acad. Sci. 821, 160–175 (1997).

    Article  CAS  PubMed  Google Scholar 

  102. De Bellis, M. D. & Keshavan, M. S. Sex differences in brain maturation in maltreatment-related pediatric posttraumatic stress disorder. Neurosci. Biobehav. Rev. 27, 103–117 (2003).

    Article  PubMed  Google Scholar 

  103. Juraska, J. M. & Kopcik, J. R. Sex and environmental influences on the size and ultrastructure of the rat corpus callosum. Brain Res. 450, 1–8 (1988).

    Article  CAS  PubMed  Google Scholar 

  104. Galinowski, A. et al. Resilience and corpus callosum microstructure in adolescence. Psychol. Med. 45, 2285–2294 (2015).

    Article  CAS  PubMed  Google Scholar 

  105. Sheridan, M. A., Fox, N. A., Zeanah, C. H., McLaughlin, K. A. & Nelson, C. A. III. Variation in neural development as a result of exposure to institutionalization early in childhood. Proc. Natl Acad. Sci. USA 109, 12927–12932 (2012).

    Article  CAS  PubMed  Google Scholar 

  106. Rauch, S. L. et al. A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Arch. Gen. Psychiatry 53, 380–387 (1996).

    Article  CAS  PubMed  Google Scholar 

  107. Schutter, D. J. & Harmon-Jones, E. The corpus callosum: a commissural road to anger and aggression. Neurosci. Biobehav. Rev. 37, 2481–2488 (2013).

    Article  PubMed  Google Scholar 

  108. van den Heuvel, M. P. & Hulshoff Pol, H. E. Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur. Neuropsychopharmacol. 20, 519–534 (2010).

    Article  CAS  PubMed  Google Scholar 

  109. He, Y. & Evans, A. Graph theoretical modeling of brain connectivity. Curr. Opin. Neurol. 23, 341–350 (2010).

    PubMed  Google Scholar 

  110. Stevens, F. L., Hurley, R. A. & Taber, K. H. Anterior cingulate cortex: unique role in cognition and emotion. J. Neuropsychiatry Clin. Neurosci. 23, 121–125 (2011).

    Article  PubMed  Google Scholar 

  111. Ross, L. A. & Olson, I. R. Social cognition and the anterior temporal lobes. Neuroimage 49, 3452–3462 (2010).

    Article  PubMed  Google Scholar 

  112. Amodio, D. M. & Frith, C. D. Meeting of minds: the medial frontal cortex and social cognition. Nat. Rev. Neurosci. 7, 268–277 (2006).

    Article  CAS  PubMed  Google Scholar 

  113. Cavanna, A. E. & Trimble, M. R. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129, 564–583 (2006).

    Article  PubMed  Google Scholar 

  114. Li, B. et al. A treatment-resistant default mode subnetwork in major depression. Biol. Psychiatry 74, 48–54 (2013).

    Article  PubMed  Google Scholar 

  115. Craig, A. D. How do you feel — now? The anterior insula and human awareness. Nat. Rev. Neurosci. 10, 59–70 (2009).

    Article  CAS  PubMed  Google Scholar 

  116. Philip, N. S. et al. Early life stress is associated with greater default network deactivation during working memory in healthy controls: a preliminary report. Brain Imag. Behav. 7, 204–212 (2013).

    Article  Google Scholar 

  117. Sripada, R. K., Swain, J. E., Evans, G. W., Welsh, R. C. & Liberzon, I. Childhood poverty and stress reactivity are associated with aberrant functional connectivity in default mode network. Neuropsychopharmacology 39, 2244–2251 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Bluhm, R. L. et al. Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma. J. Psychiatry Neurosci. 34, 187–194 (2009).

    PubMed  PubMed Central  Google Scholar 

  119. Krause-Utz, A. et al. Amygdala and anterior cingulate resting-state functional connectivity in borderline personality disorder patients with a history of interpersonal trauma. Psychol. Med. 44, 2889–2901 (2014).

    Article  CAS  PubMed  Google Scholar 

  120. Marusak, H. A., Etkin, A. & Thomason, M. E. Disrupted insula-based neural circuit organization and conflict interference in trauma-exposed youth. Neuroimage Clin. 8, 516–525 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Philip, N. S. et al. Decreased default network connectivity is associated with early life stress in medication-free healthy adults. Eur. Neuropsychopharmacol. 23, 24–32 (2013).

    Article  CAS  PubMed  Google Scholar 

  122. Graham, A. M., Pfeifer, J. H., Fisher, P. A., Carpenter, S. & Fair, D. A. Early life stress is associated with default system integrity and emotionality during infancy. J. Child Psychol. Psychiatry 56, 1212–1222 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Tursich, M. et al. Distinct intrinsic network connectivity patterns of post-traumatic stress disorder symptom clusters. Acta Psychiatr. Scand. 132, 29–38 (2015).

    Article  CAS  PubMed  Google Scholar 

  124. Cole, J., Costafreda, S. G., McGuffin, P. & Fu, C. H. Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. J. Affect. Disord. 134, 483–487 (2011).

    Article  PubMed  Google Scholar 

  125. Vythilingam, M. et al. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am. J. Psychiatry 159, 2072–2080 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Chaney, A. et al. Effect of childhood maltreatment on brain structure in adult patients with major depressive disorder and healthy participants. J. Psychiatry Neurosci. 39, 50–59 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Gerritsen, L. et al. Childhood maltreatment modifies the relationship of depression with hippocampal volume. Psychol. Med. 45, 3517–3526 (2015).

    Article  CAS  PubMed  Google Scholar 

  128. Samplin, E., Ikuta, T., Malhotra, A. K., Szeszko, P. R. & Derosse, P. Sex differences in resilience to childhood maltreatment: effects of trauma history on hippocampal volume, general cognition and subclinical psychosis in healthy adults. J. Psychiatr. Res. 47, 1174–1179 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Geuze, E., Vermetten, E. & Bremner, J. D. MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol. Psychiatry 10, 160–184 (2005).

    Article  CAS  PubMed  Google Scholar 

  130. Malykhin, N. V., Carter, R., Hegadoren, K. M., Seres, P. & Coupland, N. J. Fronto-limbic volumetric changes in major depressive disorder. J. Affect. Disord. 136, 1104–1113 (2012).

    Article  PubMed  Google Scholar 

  131. Kumari, V. et al. Lower anterior cingulate volume in seriously violent men with antisocial personality disorder or schizophrenia and a history of childhood abuse. Aust. N. Z. J. Psychiatry 48, 153–161 (2014).

    Article  PubMed  Google Scholar 

  132. Sheffield, J. M., Williams, L. E., Woodward, N. D. & Heckers, S. Reduced gray matter volume in psychotic disorder patients with a history of childhood sexual abuse. Schizophr. Res. 143, 185–191 (2013).

    Article  PubMed  Google Scholar 

  133. Bremner, J. D. et al. MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder. Am. J. Psychiatry 160, 924–932 (2003).

    Article  PubMed  Google Scholar 

  134. Shin, L. M. et al. Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: a PET investigation. Am. J. Psychiatry 156, 575–584 (1999).

    CAS  PubMed  Google Scholar 

  135. De Bellis, M. D. et al. Posterior structural brain volumes differ in maltreated youth with and without chronic posttraumatic stress disorder. Dev. Psychopathol. 27, 1555–1576 (2015).

    Article  PubMed  Google Scholar 

  136. van Harmelen, A. L. et al. Reduced medial prefrontal cortex volume in adults reporting childhood emotional maltreatment. Biol. Psychiatry 68, 832–838 (2010).

    Article  PubMed  Google Scholar 

  137. Van Dam, N. T., Rando, K., Potenza, M. N., Tuit, K. & Sinha, R. Childhood maltreatment, altered limbic neurobiology, and substance use relapse severity via trauma-specific reductions in limbic gray matter volume. JAMA Psychiatry 71, 917–925 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  138. van Harmelen, A. L. et al. Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment. Soc. Cogn. Affect. Neurosci. 9, 2026–2033 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Ugwu, I. D., Amico, F., Carballedo, A., Fagan, A. J. & Frodl, T. Childhood adversity, depression, age and gender effects on white matter microstructure: a DTI study. Brain Struct. Funct. 220, 1997–2009 (2015).

    Article  PubMed  Google Scholar 

  140. Seckfort, D. L. et al. Early life stress on brain structure and function across the lifespan: a preliminary study. Brain Imag. Behav. 2, 49–58 (2008).

    Article  Google Scholar 

  141. Carballedo, A. et al. Early life adversity is associated with brain changes in subjects at family risk for depression. World J. Biol. Psychiatry 13, 569–578 (2012).

    Article  PubMed  Google Scholar 

  142. Everaerd, D. et al. Sex modulates the interactive effect of the serotonin transporter gene polymorphism and childhood adversity on hippocampal volume. Neuropsychopharmacology 37, 1848–1855 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Frodl, T. et al. Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression. J. Psychiatry Neurosci. 37, 37–45 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Teicher, M. H., Ohashi, K., Lowen, S. B., Polcari, A. & Fitzmaurice, G. M. Mood dysregulation and affective instability in emerging adults with childhood maltreatment: an ecological momentary assessment study. J. Psychiatr. Res. 70, 1–8 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  145. van der Werff, S. J. et al. Resilience to childhood maltreatment is associated with increased resting-state functional connectivity of the salience network with the lingual gyrus. Child Abuse Negl. 37, 1021–1029 (2013).

    Article  PubMed  Google Scholar 

  146. Pagliaccio, D. et al. Stress-system genes and life stress predict cortisol levels and amygdala and hippocampal volumes in children. Neuropsychopharmacology 39, 1245–1253 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Walsh, N. D. et al. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume. Neuroimage Clin. 4, 308–318 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  148. White, M. G. et al. FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity. Genes Brain Behav. 11, 869–878 (2012).

    Article  CAS  PubMed  Google Scholar 

  149. Hyman, S. E. How adversity gets under the skin. Nat. Neurosci. 12, 241–243 (2009).

    Article  CAS  PubMed  Google Scholar 

  150. Perroud, N. et al. Methylation of serotonin receptor 3A in ADHD, borderline personality, and bipolar disorders: link with severity of the disorders and childhood maltreatment. Depress. Anxiety 33, 45–55 (2016).

    Article  CAS  PubMed  Google Scholar 

  151. Plotsky, P. M. & Meaney, M. J. Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Brain Res. Mol. Brain Res. 18, 195–200 (1993).

    Article  CAS  PubMed  Google Scholar 

  152. Barr, C. S. et al. Serotonin transporter gene variation is associated with alcohol sensitivity in rhesus macaques exposed to early-life stress. Alcohol Clin. Exp. Res. 27, 812–817 (2003).

    Article  CAS  PubMed  Google Scholar 

  153. Jackowski, A. et al. Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates. Psychiatry Res. 192, 37–44 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  154. Weaver, I. C. et al. Epigenetic programming by maternal behavior. Nat. Neurosci. 7, 847–854 (2004).

    Article  CAS  PubMed  Google Scholar 

  155. Maestripieri, D., Lindell, S. G., Ayala, A., Gold, P. W. & Higley, J. D. Neurobiological characteristics of rhesus macaque abusive mothers and their relation to social and maternal behavior. Neurosci. Biobehav. Rev. 29, 51–57 (2005).

    Article  PubMed  Google Scholar 

  156. Meaney, M. J., Brake, W. & Gratton, A. Environmental regulation of the development of mesolimbic dopamine systems: a neurobiological mechanism for vulnerability to drug abuse? Psychoneuroendocrinology 27, 127–138 (2002).

    Article  CAS  PubMed  Google Scholar 

  157. Suderman, M. et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proc. Natl Acad. Sci. USA 109, 17266–17272 (2012).

    Article  CAS  PubMed  Google Scholar 

  158. Berrebi, A. S. et al. Corpus callosum: region-specific effects of sex, early experience and age. Brain Res. 438, 216–224 (1988).

    Article  CAS  PubMed  Google Scholar 

  159. Sapolsky, R. M. Stress, glucocorticoids, and damage to the nervous system: the current state of confusion. Stress 1, 1–19 (1996).

    Article  CAS  PubMed  Google Scholar 

  160. Andersen, S. L. & Teicher, M. H. Delayed effects of early stress on hippocampal development. Neuropsychopharmacology 29, 1988–1993 (2004).

    Article  PubMed  Google Scholar 

  161. Andersen, S. L. & Teicher, M. H. Stress, sensitive periods and maturational events in adolescent depression. Trends Neurosci. 31, 183–191 (2008).

    Article  CAS  PubMed  Google Scholar 

  162. Bock, J., Gruss, M., Becker, S. & Braun, K. Experience-induced changes of dendritic spine densities in the prefrontal and sensory cortex: correlation with developmental time windows. Cereb. Cortex 15, 802–808 (2005).

    Article  PubMed  Google Scholar 

  163. McEwen, B. S. Sex, stress and the hippocampus: allostasis, allostatic load and the aging process. Neurobiol. Aging 23, 921–939 (2002).

    Article  CAS  PubMed  Google Scholar 

  164. Champagne, D. L. et al. Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J. Neurosci. 28, 6037–6045 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Sanchez, M. M., Hearn, E. F., Do, D., Rilling, J. K. & Herndon, J. G. Differential rearing affects corpus callosum size and cognitive function of rhesus monkeys. Brain Res. 812, 38–49 (1998).

    Article  CAS  PubMed  Google Scholar 

  166. Howell, B. R. et al. Early adverse experience increases emotional reactivity in juvenile rhesus macaques: relation to amygdala volume. Dev. Psychobiol. 56, 1735–1746 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Jackowski, A. P. et al. Corpus callosum in maltreated children with posttraumatic stress disorder: a diffusion tensor imaging study. Psychiatry Res. 162, 256–261 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  168. Carrion, V. G. et al. Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric posttraumatic stress disorder: an MRI study. Psychiatry Res. 172, 226–234 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Moutsiana, C. et al. Insecure attachment during infancy predicts greater amygdala volumes in early adulthood. J. Child Psychol. Psychiatry 56, 540–548 (2015).

    Article  PubMed  Google Scholar 

  170. Carrion, V. G., Weems, C. F. & Reiss, A. L. Stress predicts brain changes in children: a pilot longitudinal study on youth stress, posttraumatic stress disorder, and the hippocampus. Pediatrics 119, 509–516 (2007).

    Article  PubMed  Google Scholar 

  171. Thomason, M. E. et al. Altered amygdala connectivity in urban youth exposed to trauma. Soc. Cogn. Affect. Neurosci. 10, 1460–1468 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Sheu, Y. S., Polcari, A., Anderson, C. M. & Teicher, M. H. Harsh corporal punishment is associated with increased T2 relaxation time in dopamine-rich regions. Neuroimage 53, 412–419 (2010).

    Article  PubMed  Google Scholar 

  173. Whittle, S. et al. Observed measures of negative parenting predict brain development during adolescence. PLoS ONE 11, e0147774 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Studies in the authors' laboratory have been supported by RO1 awards (MH-091391, DA-017846 and HD-079484 to M.H.T.) from the US National Institutes of Health (National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA) and National Institute of Child Health and Human Development (NICHD)), the Harvard Clinical and Translational Science Center (UL1 TR001102) and donor support from S. Miller. The authors thank former and present staff members including S. L. Andersen, E. Bolger, J. Choi, C. E. McGreenery, A. Khan, A. Tomoda and G. Vitaliano for their myriad contributions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin H. Teicher.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary Box and tables (PDF 6898 kb)

PowerPoint slides

Glossary

Resilient

Able to withstand stress and trauma so as to maintain or rapidly regain physical and mental well-being.

Ecophenotype

Observable outward characteristics or traits that result from adaptation to environmental agents and that may closely mimic more-intrinsic, genetically determined phenotypes.

Voxel-based morphometry

(VBM). An unbiased technique to identify brain anatomical differences in regional density of grey or white matter between groups.

Tract-based spatial statistics

(TBSS). An unbiased global analysis for assessing group differences in fractional anisotropy and other diffusion measures in white-matter pathways.

Fractional anisotropy

(FA). The degree to which the diffusion of molecules is directionally dependent. Its measures reflect the integrity (involving fibre density, axon diameter and myelination) of white matter.

Sensitive-period analysis

A statistical procedure used to identify time periods when exposure to a particular experience most strongly influences a future outcome.

Negative valence system

A functional construct domain involved in responses to acute threat, potential harm, sustained threat, frustrative non-reward and loss.

Monetary incentive delay task

A task in which individuals respond to target stimuli that are presented after incentive cues to win or avoid losing indicated rewards.

Approach–avoidance situation

A situation in which the same goal has elements that both attract and repel. Behavioural responses depend on the disparity between the drive to approach versus the drive to avoid.

Bucharest Early Intervention Project

A randomized, longitudinal, controlled trial of high-level foster care as an intervention for children placed in one of six institutions in Bucharest, Romania, at birth.

Probe auditory evoked potentials

Electroencephalogram responses to irrelevant auditory probes such as clicks. The degree to which these responses are attenuated reflects the level of brain involvement in a competing cognitive task.

Graph theory

The study and use of graphs — collections of vertices (points or nodes) connected by edges (lines) — to represent, for example, brain regions and their interconnectivity.

Centrality

A graph-theory measure that indicates the importance of nodes in a graph or network.

Theory of mind

The ability to attribute mental states such as beliefs, intentions and desires to ourselves and others, and to recognize that the mental state of others is different from our own.

Default-mode network

(DMN). A network of brain regions that are activated when the brain is resting and not engaged in cognitive or goal-directed tasks.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Teicher, M., Samson, J., Anderson, C. et al. The effects of childhood maltreatment on brain structure, function and connectivity. Nat Rev Neurosci 17, 652–666 (2016). https://doi.org/10.1038/nrn.2016.111

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn.2016.111

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing