期刊论文详细信息
Biology of Mood & Anxiety Disorders
Translational neuroscience measures of fear conditioning across development: applications to high-risk children and adolescents
Tanja Jovanovic1  Karin Maria Nylocks1  Kaitlyn L Gamwell1 
[1] Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 49 Jesse Hill Jr Dr, Suite 331, Atlanta, GA 30303, USA
关键词: Extinction;    Fear conditioning;    Adolescence;    Childhood;    Development;    Anxiety disorders;   
Others  :  791862
DOI  :  10.1186/2045-5380-3-17
 received in 2013-02-18, accepted in 2013-06-25,  发布年份 2013
PDF
【 摘 要 】

Several mental illnesses, including anxiety, can manifest during development, with onsets in late childhood. Understanding the neurobiological underpinnings of risk for anxiety is of crucial importance for early prevention and intervention approaches. Translational neuroscience offers tools to investigate such mechanisms in human and animal models. The current review describes paradigms derived from neuroscience, such as fear conditioning and extinction and overviews studies that have used these paradigms in animals and humans across development. The review also briefly discusses developmental trajectories of the relevant neural circuits and the emergence of clinical anxiety. Future studies should focus on developmental changes in these paradigms, paying close attention to neurobiological and hormonal changes associated with childhood and adolescence.

【 授权许可】

   
2013 Jovanovic et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140705022200546.pdf 806KB PDF download
Figure 3. 79KB Image download
Figure 2. 82KB Image download
Figure 1. 59KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】
  • [1]Beesdo K, Knappe S, Pine DS: Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am 2009, 32:483-524.
  • [2]Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE: Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry 2005, 62:593-602.
  • [3]Cohen P, Cohen J, Brook J: An epidemiological study of disorders in late childhood and adolescence–II Persistence of disorders. J Child Psychol Psychiatry 1993, 34:869-877.
  • [4]Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL: Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 1999, 2:861-863.
  • [5]Velez CN, Johnson JIM, Cohen P: A longitudinal analysis of selected risk factors for childhood psychopathology. J Am Acad Child Adolesc Psychiatry 1989, 28:861-864.
  • [6]Pine DS: Integrating research on development and fear learning: a vision for clinical neuroscience? Depress Anxiety 2009, 26:775-779.
  • [7]Jovanovic T, Ressler KJ: How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD. Am J Psychiatry 2010, 167:648-662.
  • [8]Pavlov IP: Conditioned reflexes. Oxford University Press: Oxford University Press; 1927.
  • [9]Fanselow M, LeDoux J: Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron 1999, 23:229-232.
  • [10]Davis M: Animal models of anxiety based on classical conditioning: the conditioned emotional response (CER) and the fear-potentiated startle effect. Pharmacol Ther 1990, 47:147-165.
  • [11]Jovanovic T, Norrholm SD, Keyes M, Fiallos A, Jovanovic S, Myers KM, Davis M, Duncan EJ: Contingency awareness and fear inhibition in a human fear-potentiated startle paradigm. Behav Neurosci 2006, 120:995-1004.
  • [12]LaBar KS, LeDoux JE, Spencer DD, Phelps EA: Impaired fear conditioning following unilateral temporal lobectomy in humans. J Neurosci 1995, 15:6848-6855.
  • [13]Lissek S, Powers AS, McClure EB, Phelps EA, Woldehawariat G, Grillon C, Pine DS: Classical fear conditioning in the anxiety disorders: a meta-analysis. Behav Res Ther 2005, 43:1391-1424.
  • [14]Grillon C, Davis M: Fear-potentiated startle conditioning in humans: explicit and contextual cue conditioning following paired versus unpaired training. Psychophysiology 1997, 34:451-458.
  • [15]Jones SV, Choi DC, Davis M, Ressler KJ: Learning-dependent structural plasticity in the adult olfactory pathway. J Neurosci 2008, 28:13106-13111.
  • [16]Sullivan RM: Unique characteristics of neonatal classical conditioning:the role of the amygdala and locus coeruleus. Integr Physiol Behav Sci 2001, 36:293.
  • [17]Norrholm SD, Anderson KM, Olin IW, Jovanovic T, Kwon C, Warren VT, McCarthy A, Bosshardt L, Sabree J, Duncan EJ, Rothbaum BO, Bradley B: Versatility of fear-potentiated startle paradigms for assessing human conditioned fear extinction and return of fear. Front Behav Neurosci 2011, 5:77.
  • [18]Grillon C, Merikangas KR, Dierker L, Snidman N, Arriaga RI, Kagan J, Donzella B, Dikel T, Nelson C: Startle potentiation by threat of aversive stimuli and darkness in adolescents: a multi-site study. Int J Psychophysiol 1999, 32:63-73.
  • [19]Glenn CR, Lieberman L, Hajcak G: Comparing electric shock and a fearful screaming face as unconditioned stimuli for fear learning. Int J Psychophysiol 2012, 86:214-219.
  • [20]Waters AM, Henry J, Neumann DL: Aversive pavlovian conditioning in childhood anxiety disorders: impaired response inhibition and resistance to extinction. J Abnorm Psychol 2009, 118:311-321.
  • [21]Craske MG, Wolitzky–Taylor KB, Mineka S, Zinbarg R, Waters AM, Vrshek–Schallhorn S, Epstein A, Naliboff B, Ornitz E: Elevated responding to safe conditions as a specific risk factor for anxiety versus depressive disorders: evidence from a longitudinal investigation. J Abnorm Psychol 2012, 121:315-324.
  • [22]Orr SP, Metzger LJ, Lasko NB, Macklin ML, Peri T, Pitman RK: De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. J Abnorm Psychol 2000, 109:290-298.
  • [23]Peri T, Ben-Shakhar G, Orr SP, Shalev AY: Psychophysiologic assessment of aversive conditioning in posttraumatic stress disorder. Biol Psychiatry 2000, 47:512-519.
  • [24]LeDoux J: Fear and the brain: where have we been, and where are we going? Biol Psychiatry 1998, 44:1229-1238.
  • [25]Kazama AM, Schauder KB, McKinnon M, Bachevalier J, Davis M: A novel AX+/BX − paradigm to assess fear learning and safety-signal processing with repeated-measure designs. J Neurosci Methods 2013, 214:177-183.
  • [26]Winslow JT, Parr LA, Davis M: Acoustic startle, prepulse inhibition, and fear-potentiated startle measured in rhesus monkeys. Biol Psychiatry 2002, 51:859-866.
  • [27]LaBar KS, Disterhoft JF: Conditioning, awareness, and the hippocampus. Hippocampus 1998, 8:620-626.
  • [28]Myers KM, Toufexis DJ, Winslow JT, Jovanovic T, Norrholm SD, Duncan E, Davis M: Measurement of fear inhibition in rats, monkeys, and humans with and without posttraumatic stress disorder, using the AX+, BX- paradigm. New York City: The Guilford Press; 2009.
  • [29]LaBar KS, Gatenby JC, Gore JC, LeDoux JE, Phelps EA: Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study. Neuron 1998, 20:937-945.
  • [30]Myers KM, Ressler KJ, Davis M: Different mechanisms of fear extinction dependent on length of time since fear acquisition. Learn Mem 2006, 13:216-223.
  • [31]Norrholm SD, Jovanovic T, Vervliet B, Myers KM, Davis M, Rothbaum BO, Duncan EJ: Conditioned fear extinction and reinstatement in a human fear-potentiated startle paradigm. Learn Mem 2006, 13:681-685.
  • [32]Phelps EA, Delgado MR, Nearing KI, LeDoux JE: Extinction learning in humans: role of the amygdala and vmPFC. Neuron 2004, 43:897-905.
  • [33]Quirk GJ: Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery. Learn Mem 2002, 9:402-407.
  • [34]Kim JH, Richardson R: The effect of temporary amygdala inactivation on extinction and reextinction of fear in the developing Rat: unlearning as a potential mechanism for extinction early in development. J Neurosci 2008, 28:1282-1290.
  • [35]Monfils M-H, Cowansage KK, Klann E, LeDoux JE: Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science 2009, 324:951-955.
  • [36]Norrholm SD, Vervliet B, Jovanovic T, Boshoven W, Myers KM, Davis M, Rothbaum B, Duncan EJ: Timing of extinction relative to acquisition: a parametric analysis of fear extinction in humans. Behav Neurosci 2008, 122:1016-1030.
  • [37]Bouton ME, Bolles RC: Contextual control of the extinction of conditioned fear. Learn Motiv 1979, 10:455-466.
  • [38]Bouton MD, Bolles RC: Role of contextual stimuli in reinstatement of extinguished fear. J Exp Psychol Anim Behav Process 1979, 5:368-378.
  • [39]Quirk GJ: Extinction: new excitement for an old phenomenon. Biol Psychiatry 2006, 60:317-318.
  • [40]Milad MR, Quirk GJ: Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 2002, 420:70-74.
  • [41]Moriceau S, Sullivan RM: Maternal presence serves as a switch between learning fear and attraction in infancy. Nat Neurosci 2006, 9:1004-1006.
  • [42]Rudy JW, Morledge P: Ontogeny of contextual fear conditioning in rats: implications for consolidation, infantile amnesia, and hippocampal system function. Behav Neurosci 1994, 108:227-234.
  • [43]Kim JH, Richardson R: New findings on extinction of conditioned fear early in development: theoretical and clinical implications. Biol Psychiatry 2010, 67:297-303.
  • [44]Li S, Kim JH, Richardson R: Differential involvement of the medial prefrontal cortex in the expression of learned fear across development. Behav Neurosci 2012, 126:217-225.
  • [45]Wilson DA: A comparison of the postnatal development of post-activation potentiation in the neocortex and dentate gyrus of the rat. Brain Res 1984, 318:61-68.
  • [46]Yap CSL, Richardson R: Extinction in the developing rat: an examination of renewal effects. Dev Psychobiol 2007, 49:565-575.
  • [47]Kim JH, Richardson R: A developmental dissociation in reinstatement of an extinguished fear response in rats. Neurobiol Learn Mem 2007, 88:48-57.
  • [48]Pattwell SS, Bath KG, Casey BJ, Ninan I, Lee FS: Selective early-acquired fear memories undergo temporary suppression during adolescence. Proc Natl Acad Sci 2011, 108:1182-1187.
  • [49]Pattwell SS, Duhoux S, Hartley CA, Johnson DC, Jing D, Elliott MD, Ruberry EJ, Powers A, Mehta N, Yang RR, Soliman FG, Charles E, Casey BJ, Ninan I, Lee FS: Altered fear learning across development in both mouse and human. Proc Natl Acad Sci 2012, 109:16318-16323.
  • [50]Kim JH, Li S, Richardson R: Immunohistochemical analyses of long-term extinction of conditioned fear in adolescent rats. Cereb Cortex 2011, 21:530-538.
  • [51]Pan B-X, Ito W, Morozov A: Divergence between thalamic and cortical inputs to lateral amygdala during juvenile–adult transition in mice. Biol Psychiatry 2009, 66:964-971.
  • [52]Mineka S, Davidson M, Cook M, Keir R: Observational conditioning of snake fear in rhesus monkeys. J Abnorm Psychol 1984, 93:355-372.
  • [53]Kalin NH, Shelton SE: Nonhuman primate models to study anxiety, emotion regulation, and psychopathology. Ann NY Acad Sci 2003, 1008:189-200.
  • [54]Nelson EE, Herman KN, Barrett CE, Noble PL, Wojteczko K, Chisholm K, Delaney D, Ernst M, Fox NA, Suomi SJ, Winslow JT, Pine DS: Adverse rearing experiences enhance responding to both aversive and rewarding stimuli in juvenile rhesus monkeys. Biol Psychiatry 2009, 66:702-704.
  • [55]Heim C, Nemeroff CB: The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 2001, 49:1023-1039.
  • [56]Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, Herrera DG, Toth M, Yang C, McEwen BS, Hempstead BL, Lee FS: Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 2006, 314:140-143.
  • [57]Bath KG, Chuang J, Spencer-Segal JL, Amso D, Altemus M, McEwen BS, Lee FS: Variant brain-derived neurotrophic factor (Valine66Methionine) polymorphism contributes to developmental and estrous stage-specific expression of anxiety-like behavior in female mice. Biol Psychiatry 2012, 72:499-504.
  • [58]Soliman F, Glatt CE, Bath KG, Levita L, Jones RM, Pattwell SS, Jing D, Tottenham N, Amso D, Somerville LH, Voss HU, Glover G, Ballon DJ, Liston C, Teslovich T, Van Kempen T, Lee FS, Casey BJ: A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science 2010, 327:863-866.
  • [59]Mahan AL, Ressler KJ: Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder. Trends Neurosci 2012, 35:24-35.
  • [60]Watson JB, Rayner R: Conditioned emotional reactions. J Exp Psychol 1920, 3:1-14.
  • [61]Richards JE: Development of multimodal attention in young infants: modification of the startle reflex by attention. Psychophysiology 2000, 37:65-75.
  • [62]Balaban M: Affective influences on startle in five-month-old infants: reactions to facial expressions of emotion. Child Dev 1995, 66:23-36.
  • [63]Quevedo K, Smith T, Donzella B, Schunk E, Gunnar M: The startle response: developmental effects and a paradigm for children and adults. Dev Psychobiol 2010, 52:78-89.
  • [64]Block JD, Sersen EA, Wortis J: Cardiac classical conditioning and reversal in the mongoloid, encephalopathic, and normal child. Child Dev 1970, 41:771-785.
  • [65]Gao Y, Raine A, Venables PH, Dawson ME, Mednick SA: The development of skin conductance fear conditioning in children from ages 3 to 8 years. Dev Sci 2010, 13:201-212.
  • [66]Glenn CR, Klein DN, Lissek S, Britton JC, Pine DS, Hajcak G: The development of fear learning and generalization in 8–13 year-olds. Dev Psychobiol 2012, 54:675-684.
  • [67]Jovanovic T, Davis T, Smith A, Winkler J, Norrholm SD, Ressler KJ, Bradley B: Anxiety delays the development of fear inhibition in children at high risk for trauma exposure. Hollywood, FL: American College of Neuropsychopharmacology; 2012.
  • [68]Liberman LC, Lipp OV, Spence SH, March S: Evidence for retarded extinction of aversive learning in anxious children. Behav Res Ther 2006, 44:1491-1502.
  • [69]Grillon C, Dierker L, Merikangas KR: Fear-potentiated startle in adolescent offspring of parents with anxiety disorders. Biol Psychiatry 1998, 44:990-997.
  • [70]Reeb-Sutherland BC, Helfinstein SM, Degnan KA, Perez-Edgar K, Henderson HA, Lissek S, Chronis-Tuscano A, Grillon C, Pine DS, Fox NA: Startle response in behaviorally inhibited adolescents with a lifetime occurrence of anxiety disorders. J Am Acad Child Adolesc Psychiatry 2009, 48:610-617.
  • [71]Lau JY, Britton JC, Nelson EE, Angold A, Ernst M, Goldwin M, Grillon C, Leibenluft E, Lissek S, Norcross M, Shiffrin N, Pine DS: Distinct neural signatures of threat learning in adolescents and adults. Proc Natl Acad Sci U S A 2011, 108:4500-4505.
  • [72]Zeidan MA, Igoe SA, Linnman C, Vitalo A, Levine JB, Klibanski A, Goldstein JM, Milad MR: Estradiol modulates medial prefrontal cortex and amygdala activity during fear extinction in women and female rats. Biol Psychiatry 2011, 70:920-927.
  • [73]Glover EM, Jovanovic T, Mercer KB, Kerley K, Bradley B, Ressler KJ, Norrholm SD: Estrogen levels Are associated with extinction deficits in women with posttraumatic stress disorder. Biol Psychiatry 2012, 72:19-24.
  • [74]Borelli JL, Sbarra DA, Crowley MJ, Mayes LC: Mood symptoms and emotional responsiveness to threat in school-aged children. J Clin Child Adolesc Psychol 2011, 40:220-232.
  • [75]Inslicht SS, Metzler TJ, Garcia NM, Pineles SL, Milad MR, Orr SP, Marmar CR, Neylan TC: Sex differences in fear conditioning in posttraumatic stress disorder. J Psychiatr Res 2013, 47:64-71.
  • [76]Walker DL, Davis M: Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in light-enhanced versus fear-potentiated startle. J Neurosci 1997, 17:9375-9383.
  • [77]Allen LS, Gorski RA: Sex difference in the bed nucleus of the stria terminalis of the human brain. J Comp Neurol 1990, 302(4):697-706.
  • [78]Kamkwalala A, Norrholm SD, Poole JM, Brown A, Donely S, Duncan E, Bradley B, Ressler KJ, Jovanovic T: Dark-enhanced startle responses and heart-rate variability in a traumatized civilian sample: putative sex-specific correlates of PTSD. Psychosom Med 2012, 74(2):153-159.
  • [79]Schmitz A, Merikangas K, Swendsen H, Cui L, Heaton L, Grillon C: Measuring anxious responses to predictable and unpredictable threat in children and adolescents. J Exp Child Psychol 2011, 110:159-170.
  • [80]Bremner JD, Vermetten E, Schmahl C, Vaccarino V, Vythilingam M, Afzal N, Grillon C, Charney DS: Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder. Psychol Med 2005, 35:791-806.
  • [81]Knight D: The role of the human amygdala in the production of conditioned fear responses. NeuroImage 2005, 26:1193-1200.
  • [82]Etkin A, Wager TD: Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 2007, 164(10):1476-1488.
  • [83]Schiller D, Levy I, Niv Y, LeDoux JE, Phelps EA: From fear to safety and back: reversal of fear in the human brain. J Neurosci 2008, 28:11517-11525.
  • [84]Milad MR, Wright CI, Orr SP, Pitman RK, Quirk GJ, Rauch SL: Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol Psychiatry 2007, 62:446-454.
  • [85]Jovanovic T, Ely T, Fani N, Glover EM, Gutman D, Tone EB, Norrholm SD, Bradley B, Ressler KJ: Reduced neural activation during an inhibition task is associated with impaired fear inhibition in a traumatized civilian sample. Cortex 2013, 49:1884-1891.
  • [86]Giedd JN, Vaituzis AC, Hamburger SD, Lange N, Rajapakse JC, Kaysen D, Vauss YC, Rapoport JL: Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4–18 years. J Comp Neurol 1996, 366:223-230.
  • [87]Koolschijn PCMP, Crone EA: Sex differences and structural brain maturation from childhood to early adulthood. Dev Cog Neurosci 2013, 5:106-118.
  • [88]Shaw P, Greenstein D, Lerch J, Clasen L, Lenroot R, Gogtay N, Evans A, Rapoport J, Giedd J: Intellectual ability and cortical development in children and adolescents. Nature 2006, 440:676.
  • [89]Mills KL, Lalonde F, Clasen LS, Giedd JN, Blakemore SJ: Developmental changes in the structure of the social brain in late childhood and adolescence. Soc Cogn Affect Neurosci 2012. Epub head of print
  • [90]Lenroot RK, Giedd JN: Sex differences in the adolescent brain. Brain Cogn 2010, 72:46-55.
  • [91]Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF, Herman DH, Clasen LS, Toga AW, Rapoport JL, Thompson PM: Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A 2004, 101:8174-8179.
  • [92]Kolb B, Mychasiuk R, Muhammad A, Li Y, Frost DO, Gibb R: Experience and the developing prefrontal cortex. Proc Natl Acad Sci 2012, 109(Supplement 2):17186-17193.
  • [93]Ladouceur CD, Peper JS, Crone EA, Dahl RE: White matter development in adolescence: the influence of puberty and implications for affective disorders. Developmental Cognitive Neuroscience 2012, 2:36-54.
  • [94]Moore WE, Pfeifer JH, Masten CL, Mazziotta JC, Iacoboni M, Dapretto M: Facing puberty: associations between pubertal development and neural responses to affective facial displays. Soc Cogn Affect Neurosci 2012, 7:35-43.
  • [95]Telzer EH, Humphreys KL, Shapiro M, Tottenham N: Amygdala sensitivity to race is Not present in childhood but emerges over adolescence. J Cogn Neurosci 2013, 25:234-244.
  • [96]Gee DG, Humphreys KL, Flannery J, Goff B, Telzer EH, Shapiro M, Hare TA, Bookheimer SY, Tottenham N: A developmental shift from positive to negative connectivity in human amygdala–prefrontal circuitry. J Neurosci 2013, 33:4584-4593.
  • [97]Guyer AE, Monk CS, McClure-Tone EB, Nelson EE, Roberson-Nay R, Adler AD, Fromm SJ, Leibenluft E, Pine DS, Ernst M: A developmental examination of amygdala response to facial expressions. J Cogn Neurosci 2008, 20:1565-1582.
  • [98]De Bellis MD, Casey BJ, Dahl RE, Birmaher B, Williamson DE, Thomas KM, Axelson DA, Frustaci K, Boring AM, Hall J, Ryan ND: A pilot study of amygdala volumes in pediatric generalized anxiety disorder. Biol Psychiatry 2000, 48:51-57.
  • [99]Tottenham N, Hare TA, Quinn BT, McCarry TW, Nurse M, Gilhooly T, Millner A, Galvan A, Davidson MC, Eigsti IM, Thomas KM, Freed PJ, Booma ES, Gunnar MR, Altemus M, Aronson J, Casey BJ: Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Dev Sci 2010, 13:46-61.
  • [100]Burghy CA, Stodola DE, Ruttle PL, Molloy EK, Armstrong JM, Oler JA, Fox ME, Hayes AS, Kalin NH, Essex MJ, Davidson RJ, Birn RM: Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nat Neurosci 2012, 15:1736-1741.
  • [101]Roy AK, Fudge JL, Kelly C, Perry JSA, Daniele T, Carlisi C, Benson B, Xavier Castellanos F, Milham MP, Pine DS, Ernst M: Intrinsic functional connectivity of amygdala-based networks in adolescent generalized anxiety disorder. J Am Acad Child Adolesc Psychiatry 2013, 52:290-299. e292
  文献评价指标  
  下载次数:37次 浏览次数:25次