Abstract
Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6–18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS−) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS−, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS− during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat–safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Achenbach TM (1991) Integrative Guide for the 1991 CBCL/4-18, YSR and TRF Profiles. Department of Psychiatry, University of Vermont: Burlington, VT, USA.
Beauchaine TP, Katkin ES, Strassberg Z, Snarr J (2001). Disinhibitory psychopathology in male adolescents: discriminating conduct disorder from attention-deficit/hyperactivity disorder through concurrent assessment of multiple autonomic states. J Abnorm Psychol 110: 610–624.
Bernstein DP, Ahluvalia T, Pogge D, Handelsman L (1997). Validity of the Childhood Trauma Questionnaire in an adolescent psychiatric population. J Am Acad Child Adolesc Psychiatry 36: 340–348.
Bifulco A, Brown GW, Lillie A, Jarvis J (1997). Memories of childhood neglect and abuse: corroboration in a series of sisters. J Child Psychol Psychiatry 38: 365–374.
Birmaher B, Khetarpal S, Brent D, Cully M, Balach L, Kaufman J et al (1997). The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics. J Am Acad Child Adolesc Psychiatry 36: 545–553.
Cacioppa JT, Tassinary LG, Bernston G (2007) Handbook of Psychophysiology. Cambridge University Press: Cambridge, UK.
Craske MG, Waters AM, Bergman RL, Naliboff B, Lipp OV, Negoro H et al (2008). Is aversive learning a marker of risk for anxiety disorders in children? Behav Res Ther 46: 954–967.
Crowell SE, Beauchaine TP, Gatzke-Kopp L, Sylvers P, Mead HK, Chipman-Chacon J (2006). Autonomic correlates of attention-deficit/hyperactivity disorder and oppositional defiant disorder in preschool children. J Abnorm Psychol 115: 174–178.
Dodge KA, Petit GS, Bates JE, Valente E (1995). Social information-processing patterns partially mediate the effect of early physical abuse on later conduct problems. J Abnorm Psychol 104: 632–643.
Fairchild G, van Goozen SHM, Stollery SJ, Goodyer IM (2008). Fear conditioning and affective modulation of the startle reflex in male adolescents with early-onset or adolescence-onset conduct disorder and healthy control subjects. Biol Psychiatry 63: 279–285.
Fischl B, Dale AM (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci 97: 11050–11055.
Glenn CR, Klein DN, Lissek S, Britton JC, Pine DS, Hajcak G (2012). The development of fear learning and generalization in 8-13 year-olds. Dev Psychobiol 54: 675–684.
Grillon C (2002). Associative learning deficits increase symptoms of anxiety in humans. Biol Psychiatry 51: 851–858.
Hanson JL, Chung MK, Avants BB, Shirtcliff EA, Gee JC, Davidson JRT et al (2010). 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.
Hanson JL, Nacewicz BM, Sutterer MJ, Cayo AA, Schaefer SM, Rudolph KD et al (2015). Behavioral problems after early life stress: contributions of the hippocampus and amygdala. Biol Psychiatry 77: 314–323.
Hartley CA, Fischl B, Phelps EA (2011). Brain structure correlates of individual differences in the acquisition and inhibition of conditioned fear. Cereb Cortex 21: 1954–1962.
Hayes AF (2013) Introduction to mediation, Moderation, and Conditional Process Analysis: A Regression-Based Approach. Guilford Press: New York, USA.
Johansen JP, Cain CK, Ostroff LE, LeDoux JE (2011). Molecular mechanisms of fear learning and memory. Cell 147: 509–524.
Jovanovich T, Norrholm SD (2011). Neural mechanisms of impaired fear inhibition in posttraumatic stress disorder. Front Behav Neurosci 5: Article 44.
Jovanovich T, Ressler KJ (2010). How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD. Am J Psychiatry 167: 648–662.
Kilpatrick DG, Ruggiero KJ, Acierno R, Saunders BE, Resnick HS, Best CL (2003). Violence and risk of PTSD, major depression, substance abuse/dependence, and comorbidity: results from the National Survey of Adolescents. J Consult Clin Psychol 71: 692–700.
Kim JH, Richardson R (2010). New findings on extinction of conditioned fear early in development: theoretical and clinical implications. Biol Psychiatry 67: 297–303.
Kim JJ, Jung MW (2006). Neural circuits and mechanisms involved in Pavlovian fear conditioning: a critical review. Neurosci Biobehav Rev 30: 188–202.
Koenen KC, Moffit TE, Caspi A, Taylor A, Purcell S (2003). Domestic violence is associated with environmental suppression of IQ in young children. Dev Psychopathol 15: 297–311.
Kovacs M (1992) Children’s Depression Inventory Manual. Multi-Health Systems: North Tonawanda, NY, USA.
Lau JYF, Lissek S, Nelson EE, Lee Y, Roberson-Nay R, Poeth K et al (2008). Fear conditioning in adolescents with anxiety disorders: results from a novel experimental paradigm. J Am Acad Child Adolesc Psychiatry 47: 94–102.
LeDoux JE, Iwata J, Cicchetti P, Reis DJ (1988). Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear. J Neurosci 8: 2517–2529.
Lissek S, van Meurs B (2015). Learning models of PTSD: theoretical accounts and psychobiological evidence. Int J Psychophysiol 98: 594–605.
Macfie J, Cicchetti D, Toth SL (2001). The development of dissociation in maltreated preschool-aged children. Dev Psychopathol 13: 233–254.
MacMillan HL, Georgiades K, Duku EK, Shea A, Steiner M, Niec A et al (2009). Cortisol response to stress in female youths exposed to childhood maltreatment: results of the Youth Mood Project. Biol Psychiatry 66: 62–68.
Matsumoto M, Togashi H, Konno K, Koseki H, Hirata R, Izumi T et al (2008). Early postnatal stress alters the extinction of context-dependent conditioned fear in adult rats. Pharmacol Biochem Behav 89: 247–252.
McCrory EJ, De Brito SA, Sebastian CL, Mechelli A, Bird G, Kelly PA et al (2011). Heightened neural reactivity to threat in child victims of family violence. Curr Biol 21: R947–R948.
McLaughlin KA, Koenen KC, Hill E, Petukhova M, Sampson NA, Zaslavsky A et al (2013). Trauma exposure and posttraumatic stress disorder in a US national sample of adolescents. J Am Acad Child Adolesc Psychiatry 52: 815–830.
McLaughlin KA, Peverill M, Gold AL, Alves S, Sheridan MA (2015). Child maltreatment and neural systems underlying emotion regulation. J Am Acad Child Adolesc Psychiatry 54: 753–762.
McLaughlin KA, Sheridan MA, Alves S, Mendes WB (2014a). Child maltreatment and autonomic nervous system reactivity: identifying dysregulated stress reactivity patterns using the biopsychosocial model of challenge and threat. Psychosom Med 76: 538–546.
McLaughlin KA, Sheridan MA, Lambert HK (2014b). Childhood adversity and neural development: deprivation and threat as distinct dimensions of early experience. Neurosci Biobehav Rev 47: 578–591.
Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB et al (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry 66: 1075–1082.
Milad MR, Quinn BT, Pitman RK, Orr SP, Fischl B, Rauch SL (2005). Thicnkess of ventromedial prefrontal cortex in humans is correlated with extinction memory. Proc Natl Acad Sci 102: 10706–10711.
Milad MR, Quirk GJ, Pitman RK, Orr SP, Fischl B, Rauch SL (2007). A role for the human dorsal anterior cingulate cortex in fear expression. Biol Psychiatry 62: 1191–1194.
Patwell SS, Duhoux S, Hartley CA, Johnson DC, Jing D, Elliott MD et al (2012). Altered fear learning across development in both mouse and human. Proc Natl Acad Sci 109: 16318–16323.
Phillips RG, LeDoux JE (1992). Differential contributions of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106: 274–285.
Pohlack ST, Nees F, Liebscher C, Cacciaglia R, Diener SJ, Ridder S et al (2012). Hippocampal but not amygdalar volume affects contextual fear conditioning in humans. Hum Brain Mapp 33: 478–488.
Pollak SD, Tolley-Schell SA (2003). Selective attention to facial emotion in physically abused children. J Abnorm Psychol 112 (3): 323–338.
Shechner T, Britton JC, Ronkin E, Jarcho J, Mash J, Michalska KJ et al (2014a). Fear conditioning and extinction in anxious and non-anxious youth and adults: examining a novel developmentally-appropriate fear conditioning task. Depress Anxiety 32: 277–288.
Shechner T, Hong M, Britton JC, Pine DS, Fox NA (2014b). Fear conditioning and extinction across development: evidence from human studies and animal models. Biol Psychol 100: 1–12.
Sheridan MA, McLaughlin KA (2014). Dimensions of early experience and neural development: deprivation and threat. Trends Cogn Sci 18: 580–585.
Steinberg AM, Brymer MJ, Decker KB, Pynoos RS (2004). The University of California at Los Angeles post-traumatic stress disorder reaction index. Curr Psychiatry Rep 6: 96–100.
Steinberg AM, Brymer MJ, Kim S, Briggs EC, Ghosh Ippen C, Ostrowski SA et al (2013). Psychometric properties of the UCLA PTSD Reaction Index: Part 1. J Trauma Stress 26: 1–9.
Toledo-Rodriguez M, Sandi C (2007). Stress before puberty exerts a sex- and age-related impact on auditory and contextual fear conditioning in the rat. Neural Plast 2007: Article ID 71203.
Walker EA, Unutzer J, Rutter C, Gelfand A, Saunders K, VonKorff M et al (1999). Costs of health care use by women HMO members with a history of childhood abuse and neglect. Arch Gen Psychiatry 56: 609–613.
Yang RJ, Mozhui K, Karlsson RM, Cameron HA, Williams RW, Holmes A (2008). Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning. Neuropsychopharmacology 33: 2595–2604.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on the Neuropsychopharmacology website
PowerPoint slides
Rights and permissions
About this article
Cite this article
McLaughlin, K., Sheridan, M., Gold, A. et al. Maltreatment Exposure, Brain Structure, and Fear Conditioning in Children and Adolescents. Neuropsychopharmacol 41, 1956–1964 (2016). https://doi.org/10.1038/npp.2015.365
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/npp.2015.365
This article is cited by
-
Individuals with and without child maltreatment experiences are evaluated similarly and do not differ in facial affect display at zero- and first-acquaintance
Borderline Personality Disorder and Emotion Dysregulation (2023)
-
Can peripheral psychophysiological markers predict response to exposure-based cognitive behavioral therapy in youth with severely impairing irritability? A study protocol
BMC Psychiatry (2023)
-
A proof-of-concept study of vicarious extinction learning and autonomic synchrony in parent–child dyads and posttraumatic stress disorder
Scientific Reports (2023)
-
The influence of being left behind on fear acquisition and academic performance—a study of left-behind children
Current Psychology (2023)
-
Differentiating Between Us & Them: Reduced In-Group Bias as a Novel Mechanism Linking Childhood Violence Exposure with Internalizing Psychopathology
Research on Child and Adolescent Psychopathology (2023)