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Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood

Published online by Cambridge University Press:  16 December 2015

G. A. Fonzo ,
H. J. Ramsawh ,
T. M. Flagan ,
A. N. Simmons ,
S. G. Sullivan ,
C. B. Allard ,
M. P. Paulus  and
M. B. Stein
G. A. Fonzo*
Affiliation:
Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA
H. J. Ramsawh
Affiliation:
Department of Clinical Effectiveness Research, Patient-Centered Outcomes Research Institute, Washington, DC, USA
T. M. Flagan
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
A. N. Simmons
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA VA San Diego Healthcare System, San Diego, CA, USA Center of Excellence in Stress and Mental Health, San Diego, CA, USA
S. G. Sullivan
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
C. B. Allard
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA VA San Diego Healthcare System, San Diego, CA, USA Center of Excellence in Stress and Mental Health, San Diego, CA, USA
M. P. Paulus
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA VA San Diego Healthcare System, San Diego, CA, USA Laureate Institute for Brain Research, Tulsa, OK, USA
M. B. Stein
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA VA San Diego Healthcare System, San Diego, CA, USA Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA
*
* Address for correspondence: G. A. Fonzo, Ph.D., Department of Psychiatry & Behavioral Sciences, Stanford University, 401 Quarry Road, MC 4797, Stanford, CA 94305, USA. (Email: gfonzo@stanford.edu)
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Abstract

Background

Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms.

Method

One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood.

Results

During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship.

Conclusions

Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.

Keywords

Amygdalaanxietychildhood maltreatmentearly life stressimaging

Information

Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 5 , April 2016 , pp. 1037 - 1054
Copyright
Copyright © Cambridge University Press 2015 

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References

Amir, N, Klumpp, H, Elias, J, Bedwell, JS, Yanasak, N, Miller, LS (2005). Increased activation of the anterior cingulate cortex during processing of disgust faces in individuals with social phobia. Biological Psychiatry 57, 975–981.CrossRefGoogle ScholarPubMed
Amir, N, Taylor, CT, Bomyea, JA, Badour, CL (2009). Temporal allocation of attention toward threat in individuals with posttraumatic stress symptoms. Journal of Anxiety Disorders 23, 1080–1085.Google Scholar
Amodio, DM, Frith, CD (2006). Meeting of minds: the medial frontal cortex and social cognition. Nature Reviews Neuroscience 7, 268–277.Google Scholar
Asami, T, Yamasue, H, Hayano, F, Nakamura, M, Uehara, K, Otsuka, T, Roppongi, T, Nihashi, N, Inoue, T, Hirayasu, Y (2009). Sexually dimorphic gray matter volume reduction in patients with panic disorder. Psychiatry Research 173, 128–134.Google Scholar
Ashburner, J, Friston, KJ (2000). Voxel-based morphometry – the methods. NeuroImage 11, 805–821.Google Scholar
Bernstein, DP, Stein, JA, Newcomb, MD, Walker, E, Pogge, D, Ahluvalia, T, Stokes, J, Handelsman, L, Medrano, M, Desmond, D, Zule, W (2003). Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse & Neglect 27, 169–190.Google Scholar
Bertolino, A, Arciero, G, Rubino, V, Latorre, V, De Candia, M, Mazzola, V, Blasi, G, Caforio, G, Hariri, A, Kolachana, B, Nardini, M, Weinberger, DR, Scarabino, T (2005). Variation of human amygdala response during threatening stimuli as a function of 5′HTTLPR genotype and personality style. Biological Psychiatry 57, 1517–1525.CrossRefGoogle Scholar
Blake, DD, Weathers, FW, Nagy, LM, Kaloupek, DG (1995). The development of a Clinician-Administered PTSD Scale. Journal of Traumatic Stress 8, 75–90.Google ScholarPubMed
Bonne, O, Vythilingam, M, Inagaki, M, Wood, S, Neumeister, A, Nugent, AC, Snow, J, Luckenbaugh, DA, Bain, EE, Drevets, WC, Charney, DS (2008). Reduced posterior hippocampal volume in posttraumatic stress disorder. Journal of Clinical Psychiatry 69, 1087–1091.Google Scholar
Burghy, CA, Stodola, DE, Ruttle, PL, Molloy, EK, Armstrong, JM, Oler, JA, Fox, ME, Hayes, AS, Kalin, NH, Essex, MJ, Davidson, RJ, Birn, RM (2012). Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nature Neuroscience 15, 1736–1741.CrossRefGoogle ScholarPubMed
Carrion, VG, Weems, CF, Reiss, AL (2007). Stress predicts brain changes in children: a pilot longitudinal study on youth stress, posttraumatic stress disorder, and the hippocampus. Pediatrics 119, 509–516.CrossRefGoogle ScholarPubMed
Casey, BJ, Oliveri, ME, Insel, T (2014). A neurodevelopmental perspective on the research domain criteria (RDoC) framework. Biological Psychiatry 76, 350–353.CrossRefGoogle ScholarPubMed
Comte, M, Schon, D, Coull, JT, Reynaud, E, Khalfa, S, Belzeaux, R, Ibrahim, EC, Guedj, E, Blin, O, Weinberger, DR, Fakra, E (2014). Dissociating bottom-up and top-down mechanisms in the cortico-limbic system during emotion processing. Cerebral Cortex (New York). Published online 27 August 2015. doi:10.1093/cercor/bhu185.Google Scholar
Cox, RW (1996). AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research, an International Journal 29, 162–173.Google Scholar
Cuthbert, BN (2014). The RDoC framework: facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology. World Psychiatry 13, 28–35.CrossRefGoogle ScholarPubMed
Dannlowski, U, Kugel, H, Huber, F, Stuhrmann, A, Redlich, R, Grotegerd, D, Dohm, K, Sehlmeyer, C, Konrad, C, Baune, BT, Arolt, V, Heindel, W, Zwitserlood, P, Suslow, T (2013). Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala. Human Brain Mapping 34, 2899–2909.CrossRefGoogle ScholarPubMed
Dannlowski, U, Stuhrmann, A, Beutelmann, V, Zwanzger, P, Lenzen, T, Grotegerd, D, Domschke, K, Hohoff, C, Ohrmann, P, Bauer, J, Lindner, C, Postert, C, Konrad, C, Arolt, V, Heindel, W, Suslow, T, Kugel, H (2012). Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biological Psychiatry 71, 286–293.CrossRefGoogle ScholarPubMed
Delgado, MR, Nearing, KI, Ledoux, JE, Phelps, EA (2008). Neural circuitry underlying the regulation of conditioned fear and its relation to extinction. Neuron 59, 829–838.CrossRefGoogle ScholarPubMed
Derogatis, LR, Fitzpatrick, M (2004). The SCL-90-R, the Brief Symptom Inventory (BSI), and the BSI-18. In The Use of Psychological Testing for Treatment Panning and Outcomes Assessment: Volume 3: Instruments for Adults, 3rd edn. (ed. Maruish, M. E.), pp. 1–41. Lawrence Erlbaum Associates Publishers: Mahwah, NJ, US.Google Scholar
Dillon, DG, Holmes, AJ, Birk, JL, Brooks, N, Lyons-Ruth, K, Pizzagalli, DA (2009). Childhood adversity is associated with left basal ganglia dysfunction during reward anticipation in adulthood. Biological Psychiatry 66, 206–213.CrossRefGoogle ScholarPubMed
Eckart, C, Stoppel, C, Kaufmann, J, Tempelmann, C, Hinrichs, H, Elbert, T, Heinze, HJ, Kolassa, IT (2010). Structural alterations in lateral prefrontal, parietal and posterior midline regions of men with chronic posttraumatic stress disorder. Journal of Psychiatry & Neuroscience 35, 100010.Google Scholar
Eden, AS, Schreiber, J, Anwander, A, Keuper, K, Laeger, I, Zwanzger, P, Zwitserlood, P, Kugel, H, Dobel, C (2015). Emotion regulation and trait anxiety are predicted by the microstructure of fibers between amygdala and prefrontal cortex. Journal of Neuroscience 35, 6020–6027.CrossRefGoogle ScholarPubMed
Egeland, B (2009). Taking stock: childhood emotional maltreatment and developmental psychopathology. Child Abuse & Neglect 33, 22–26.CrossRefGoogle ScholarPubMed
Etkin, A, Prater, KE, Hoeft, F, Menon, V, Schatzberg, AF (2010). Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. American Journal of Psychiatry 165, 545–554.Google Scholar
Etkin, A, Schatzberg, AF (2011). Common abnormalities and disorder-specific compensation during implicit regulation of emotional processing in generalized anxiety and major depressive disorders. American Journal of Psychiatry 168, 968–978.CrossRefGoogle ScholarPubMed
Etkin, A, Wager, TD (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164, 1476–1488.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1998). Structured Clinical Interview for DSM-IV Axis I Disorders. Biometrics Research, New York State Psychiatric Institute: New York.Google Scholar
Fonzo, GA, Flagan, TM, Sullivan, S, Allard, CB, Grimes, EM, Simmons, AN, Paulus, MP, Stein, MB (2013). Neural functional and structural correlates of childhood maltreatment in women with intimate-partner violence-related posttraumatic stress disorder. Psychiatry Research: Neuroimaging 211, 93–103.Google Scholar
Fonzo, GA, Ramsawh, HJ, Flagan, TM, Sullivan, SG, Letamendi, A, Simmons, AN, Paulus, MP, Stein, MB (2015). Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders. British Journal of Psychiatry 206, 206–215.CrossRefGoogle ScholarPubMed
Fonzo, GA, Simmons, AN, Thorp, SR, Norman, SB, Paulus, MP, Stein, MB (2010). Exaggerated and disconnected insular-amygdalar blood oxygenation level-dependent response to threat-related emotional faces in women with intimate-partner violence posttraumatic stress disorder. Biological Psychiatry 68, 433–441.Google Scholar
Fusar-Poli, P, Placentino, A, Carletti, F, Landi, P, Allen, P, Surguladze, S, Benedetti, F, Abbamonte, M, Gasparotti, R, Barale, F, Perez, J, McGuire, P, Politi, P (2009). Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. Journal of Psychiatry & Neuroscience 34, 418–432.Google ScholarPubMed
Gatt, JM, Williams, LM, Schofield, PR, Dobson-Stone, C, Paul, RH, Grieve, SM, Clark, CR, Gordon, E, Nemeroff, CB (2010). Impact of the HTR3A gene with early life trauma on emotional brain networks and depressed mood. Depression and Anxiety 27, 752–759.Google Scholar
Gibb, BE, Schofield, CA, Coles, ME (2009). Reported history of childhood abuse and young adults’ information-processing biases for facial displays of emotion. Child Maltreatment 14, 148–156.CrossRefGoogle Scholar
Goldin, PR, Manber, T, Hakimi, S, Canli, T, Gross, JJ (2009). Neural bases of social anxiety disorder: emotional reactivity and cognitive regulation during social and physical threat. Archives of General Psychiatry 66, 170–180.Google Scholar
Good, CD, Johnsrude, IS, Ashburner, J, Henson, RN, Friston, KJ, Frackowiak, RS (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage 14, 21–36.Google Scholar
Hamilton, JP, Etkin, A, Furman, DJ, Lemus, MG, Johnson, RF, Gotlib, IH (2012). Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data. The American Journal of Psychiatry 169, 693–703.Google Scholar
Hariri, AR, Drabant, EM, Munoz, KE, Kolachana, BS, Mattay, VS, Egan, MF, Weinberger, DR (2005). A susceptibility gene for affective disorders and the response of the human amygdala. Archives of General Psychiatry 62, 146–152.Google Scholar
Hayes, AF (2013). Introduction to Mediation, Moderation, and Conditional Process Analysis. Guilford Press: New York.Google Scholar
Herringa, RJ, Birn, RM, Ruttle, PL, Burghy, CA, Stodola, DE, Davidson, RJ, Essex, MJ (2013). Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence. Proceedings of the National Academy of Sciences USA 110, 19119–19124.Google Scholar
Hettema, JM, Kettenmann, B, Ahluwalia, V, McCarthy, C, Kates, WR, Schmitt, JE, Silberg, JL, Neale, MC, Kendler, KS, Fatouros, P (2012). Pilot multimodal twin imaging study of generalized anxiety disorder. Depression and Anxiety 29, 202–209.CrossRefGoogle ScholarPubMed
IBM SPSS Inc. (2010). IBM SPSS Statistics for Windows, version 19.0. Released 2010. Armonk, NY: IBM Corp.Google Scholar
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R, Pine, DS, Quinn, K, Sanislow, C, Wang, P (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. American Journal of Psychiatry 167, 748–751.Google Scholar
Insel, TR (2014). The NIMH Research Domain Criteria (RDoC) Project: precision medicine for psychiatry. American Journal of Psychiatry 171, 395–397.CrossRefGoogle ScholarPubMed
Karl, A, Schaefer, M, Malta, LS, Dorfel, D, Rohleder, N, Werner, A (2006). A meta-analysis of structural brain abnormalities in PTSD. Neuroscience and Biobehavioral Reviews 30, 1004–1031.Google Scholar
Kelley, K (2007 a). Methods for the behavioral, educational, and social sciences: an R package. Behavior Research Methods 39, 979–984.Google Scholar
Kelley, K (2007 b). Confidence intervals for standardized effect sizes: theory, application, and implementation. Journal of Statistical Software 20, 1–24.CrossRefGoogle Scholar
Kelley, K, Lai, K (2012). MBESS version 3.3.3 (https://cran.r-project.org/package=MBESS).Google Scholar
Kelly, PA, Viding, E, Wallace, GL, Schaer, M, De Brito, SA, Robustelli, B, McCrory, EJ (2013). Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment: neural markers of vulnerability? Biological Psychiatry 74, 845–852.CrossRefGoogle ScholarPubMed
Kessler, RC, Chiu, WT, Demler, O, Merikangas, KR, Walters, EE (2005). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 617–627.Google Scholar
Klumpp, H, Amir, N (2009). Examination of vigilance and disengagement of threat in social anxiety with a probe detection task. Anxiety, Stress & Coping 22, 283–296.CrossRefGoogle ScholarPubMed
Kremen, WS, O'Brien, RC, Panizzon, MS, Prom-Wormley, E, Eaves, LJ, Eisen, SA, Eyler, LT, Hauger, RL, Fennema-Notestine, C, Fischl, B, Grant, MD, Hellhammer, DH, Jak, AJ, Jacobson, KC, Jernigan, TL, Lupien, SJ, Lyons, MJ, Mendoza, SP, Neale, MC, Seidman, LJ, Thermenos, HW, Tsuang, MT, Dale, AM, Franz, CE (2010). Salivary cortisol and prefrontal cortical thickness in middle-aged men: a twin study. NeuroImage 53, 1093–1102.Google Scholar
Kuo, JR, Goldin, PR, Werner, K, Heimberg, RG, Gross, JJ (2011). Childhood trauma and current psychological functioning in adults with social anxiety disorder. Journal of Anxiety Disorders 25, 467–473.CrossRefGoogle ScholarPubMed
Labuschagne, I, Phan, KL, Wood, A, Angstadt, M, Chua, P, Heinrichs, M, Stout, JC, Nathan, PJ (2012). Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. International Journal of Neuropsychopharmacology 15, 883–896.CrossRefGoogle ScholarPubMed
Liberzon, I, Garfinkel, SN (2009). Functional neuroimaging in post-traumatic stress disorder. In Post-Traumatic Stress Disorder: Basic Science and Clinical Practice (ed. Shiromani, P. J., Keane, T. M. and LeDoux, J. E.), pp. 297–317. Humana Press: Totowa, NJ, US.Google Scholar
MacKinnon, DP, Fairchild, AJ, Fritz, MS (2007). Mediation analysis. Annual Review of Psychology 58, 593–614.Google Scholar
Marsh, AA, Ambady, N, Kleck, RE (2005). The effects of fear and anger facial expressions on approach- and avoidance-related behaviors. Emotion (Washington, D.C) 5, 119–124.Google Scholar
Marusak, HA, Martin, KR, Etkin, A, Thomason, ME (2015). Childhood trauma exposure disrupts the automatic regulation of emotional processing. Neuropsychopharmacology 40, 1250–1258.Google Scholar
Masten, CL, Guyer, AE, Hodgdon, HB, McClure, EB, Charney, DS, Ernst, M, Kaufman, J, Pine, DS, Monk, CS (2008). Recognition of facial emotions among maltreated children with high rates of post-traumatic stress disorder. Child Abuse & Neglect 32, 139–153.Google Scholar
Mehta, MA, Gore-Langton, E, Golembo, N, Colvert, E, Williams, SC, Sonuga-Barke, E (2010). Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life. Journal of Cognitive Neuroscience 22, 2316–2325.Google Scholar
Mendlowicz, MV, Stein, MB (2000). Quality of life in individuals with anxiety disorders. American Journal of Psychiatry 157, 669–682.Google Scholar
Milad, MR, Pitman, RK, Ellis, CB, Gold, AL, Shin, LM, Lasko, NB, Zeidan, MA, Handwerger, K, Orr, SP, Rauch, SL (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biological Psychiatry 66, 1075–1082.Google Scholar
Muthén, LK, Muthén, BO (1998–2012). Mplus User's Guide, 7th edn. Muthén & Muthén: Los Angeles.Google Scholar
Nolte, T, Guiney, J, Fonagy, P, Mayes, LC, Luyten, P (2011). Interpersonal stress regulation and the development of anxiety disorders: an attachment-based developmental framework. Frontiers in Behavioral Neuroscience 5, 55.CrossRefGoogle ScholarPubMed
Ochsner, KN, Gross, JJ (2005). The cognitive control of emotion. Trends in Cognitive Sciences 9, 242–249.Google Scholar
O'Doherty, JP (2004). Reward representations and reward-related learning in the human brain: insights from neuroimaging. Current Opinion in Neurobiology 14, 769–776.Google Scholar
Paulus, MP (2008). The role of neuroimaging for the diagnosis and treatment of anxiety disorders. Depression and Anxiety 25, 348–356.Google Scholar
Paulus, MP, Feinstein, JS, Castillo, G, Simmons, AN, Stein, MB (2005). Dose-Dependent Decrease of Activation in Bilateral Amygdala and Insula by Lorazepam During Emotion Processing. Archives of General Psychiatry 62, 282–288.CrossRefGoogle ScholarPubMed
Pechtel, P, Pizzagalli, DA (2010). Effects of early life stress on cognitive and affective function: an integrated review of human literature. Psychopharmacology 14, 55–70.Google Scholar
Phillips, ML, Ladouceur, CD, Drevets, WC (2008). A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry 13, 829, 833–857.Google Scholar
Pillay, SS, Rogowska, J, Gruber, SA, Simpson, N, Yurgelun-Todd, DA (2007). Recognition of happy facial affect in panic disorder: an fMRI study. Journal of Anxiety Disorders 21, 381–393.Google Scholar
Pizzagalli, DA (2014). Depression, stress, and anhedonia: toward a synthesis and integrated model. Annual Review of Clinical Psychology 10, 393–423.CrossRefGoogle Scholar
Pizzagalli, DA, Holmes, AJ, Dillon, DG, Goetz, EL, Birk, JL, Bogdan, R, Dougherty, DD, Iosifescu, DV, Rauch, SL, Fava, M (2009). Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. American Journal of Psychiatry 166, 702–710.Google Scholar
R Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria (http://www.R-project.org/).Google Scholar
Ray, RD, Zald, DH (2012). Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex. Neuroscience and Biobehavioral Reviews 36, 479–501.CrossRefGoogle ScholarPubMed
Sabatinelli, D, Fortune, EE, Li, Q, Siddiqui, A, Krafft, C, Oliver, WT, Beck, S, Jeffries, J (2011). Emotional perception: meta-analyses of face and natural scene processing. NeuroImage 54, 2524–2533.Google Scholar
Sapolsky, RM (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Archives of General Psychiatry 57, 925–935.Google Scholar
Shaw, P, Kabani, NJ, Lerch, JP, Eckstrand, K, Lenroot, R, Gogtay, N, Greenstein, D, Clasen, L, Evans, A, Rapoport, JL, Giedd, JN, Wise, SP (2008). Neurodevelopmental trajectories of the human cerebral cortex. Journal of Neuroscience 28, 3586–3594.Google Scholar
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 22–33; quiz 34–57.Google Scholar
Simon, NM, Herlands, NN, Marks, EH, Mancini, C, Letamendi, A, Li, Z, Pollack, MH, Van Ameringen, M, Stein, MB (2009). Childhood maltreatment linked to greater symptom severity and poorer quality of life and function in social anxiety disorder. Depression and Anxiety 26, 1027–1032.Google Scholar
Simpson, HB (2012). The rdoc project: a new paradigm for investigating the pathophysiology of anxiety. Depression and Anxiety 29, 251–252.Google Scholar
Smith, KS, Tindell, AJ, Aldridge, JW, Berridge, KC (2009). Ventral pallidum roles in reward and motivation. Behavioural Brain Research 196, 155–167.CrossRefGoogle ScholarPubMed
Smith, SM, Jenkinson, M, Woolrich, MW, Beckmann, CF, Behrens, TE, Johansen-Berg, H, Bannister, PR, De Luca, M, Drobnjak, I, Flitney, DE, Niazy, RK, Saunders, J, Vickers, J, Zhang, Y, De Stefano, N, Brady, JM, Matthews, PM (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23 (Suppl. 1), S208–S219.Google Scholar
Sobanski, T, Wagner, G, Peikert, G, Gruhn, U, Schluttig, K, Sauer, H, Schlosser, R (2010). Temporal and right frontal lobe alterations in panic disorder: a quantitative volumetric and voxel-based morphometric MRI study. Psychological Medicine 40, 1879–1886.Google Scholar
Spinhoven, P, Elzinga, BM, Hovens, JGFM, Roelofs, K, Zitman, FG, van Oppen, P, Penninx, BWJH (2010). The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders. Journal of Affective Disorders 126, 103–112.CrossRefGoogle ScholarPubMed
Stein, MB, Simmons, AN, Feinstein, JS, Paulus, MP (2007). Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. American Journal of Psychiatry 164, 318–327.Google Scholar
Talairach, J, Tournoux, P (1998). Co-planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: an Approach to Cerebral Imaging. Thieme Medical Publishers: New York.Google Scholar
Teicher, MH, Samson, JA (2013). Childhood maltreatment and psychopathology: a case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. The American Journal of Psychiatry 170, 1114–1133.CrossRefGoogle ScholarPubMed
Thomaes, K, Dorrepaal, E, Draijer, N, de Ruiter, MB, van Balkom, AJ, Smit, JH, Veltman, DJ (2010). Reduced anterior cingulate and orbitofrontal volumes in child abuse-related complex PTSD. Journal of Clinical Psychiatry 71, 1636–1644.Google Scholar
Tottenham, N, Hare, TA, Quinn, BT, McCarry, TW, Nurse, M, Gilhooly, T, Millner, A, Galvan, A, Davidson, MC, Eigsti, I, Thomas, KM, Freed, PJ, Booma, ES, Gunnar, MR, Altemus, M, Aronson, J, Casey, BJ (2010). Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Developmental Science 13, 46–61.Google Scholar
Uchida, RR, Del-Ben, CM, Busatto, GF, Duran, FL, Guimaraes, FS, Crippa, JA, Araujo, D, Santos, AC, Graeff, FG (2008). Regional gray matter abnormalities in panic disorder: a voxel-based morphometry study. Psychiatry Research 163, 21–29.Google Scholar
van Harmelen, AL, van Tol, MJ, Dalgleish, T, van der Wee, NJ, Veltman, DJ, Aleman, A, Spinhoven, P, Penninx, BW, Elzinga, BM (2014). Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment. Social Cognitive and Affective Neuroscience 9, 2026–2033.Google Scholar
van Harmelen, AL, van Tol, MJ, Demenescu, LR, van der Wee, NJ, Veltman, DJ, Aleman, A, van Buchem, MA, Spinhoven, P, Penninx, BW, Elzinga, BM (2013). Enhanced amygdala reactivity to emotional faces in adults reporting childhood emotional maltreatment. Social Cognitive and Affective Neuroscience 8, 362–369.Google Scholar
van Harmelen, AL, van Tol, MJ, van der Wee, NJ, Veltman, DJ, Aleman, A, Spinhoven, P, van Buchem, MA, Zitman, FG, Penninx, BW, Elzinga, BM (2010). Reduced medial prefrontal cortex volume in adults reporting childhood emotional maltreatment. Biological Psychiatry 68, 832–838.Google Scholar
Waters, AM, Bradley, BP, Mogg, K (2014). Biased attention to threat in paediatric anxiety disorders (generalized anxiety disorder, social phobia, specific phobia, separation anxiety disorder) as a function of ‘distress’ versus ‘fear’ diagnostic categorization. Psychological Medicine 44, 607–616.Google Scholar
Williams, LM, Gatt, JM, Schofield, PR, Olivieri, G, Peduto, A, Gordon, E (2009). ‘Negativity bias’ in risk for depression and anxiety: brain-body fear circuitry correlates, 5-HTT-LPR and early life stress. NeuroImage 47, 804–814.Google Scholar
Woodward, SH, Schaer, M, Kaloupek, DG, Cediel, L, Eliez, S (2009). Smaller global and regional cortical volume in combat-related posttraumatic stress disorder. Archives of General Psychiatry 66, 1373–1382.Google Scholar
Woon, FL, Hedges, DW (2008). Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis. Hippocampus 18, 729–736.Google Scholar
Wright, MO, Crawford, E, Del Castillo, D (2009). Childhood emotional maltreatment and later psychological distress among college students: the mediating role of maladaptive schemas. Child Abuse & Neglect 33, 59–68.Google Scholar
Yoo, HK, Kim, MJ, Kim, SJ, Sung, YH, Sim, ME, Lee, YS, Song, SY, Kee, BS, Lyoo, IK (2005). Putaminal gray matter volume decrease in panic disorder: an optimized voxel-based morphometry study. European Journal of Neuroscience 22, 2089–2094.CrossRefGoogle ScholarPubMed
Zlotnick, C, Johnson, J, Kohn, R, Vicente, B, Rioseco, P, Saldivia, S (2008). Childhood trauma, trauma in adulthood, and psychiatric diagnoses: results from a community sample. Comprehensive Psychiatry 49, 163–169.Google Scholar
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