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

Biology of Mood & Anxiety Disorders

Adam X Gorka¹  Jamie L Hanson²  Spenser R Radtke¹  Ahmad R Hariri¹ 

[1] Laboratory of NeuroGenetics, Department of Psychology and Neuroscience, Duke University, 417 Chapel Drive, Durham, NC 27708, USA

[2] Center for Developmental Science, University of North Carolina at Chapel Hill, 100 East Franklin Street, Suite 200 CB#8115, Chapel Hill, NC 27599, USA

关键词: Medial prefrontal cortex;    Childhood maltreatment;    MRI;    Anxiety;    Gray matter;    Hippocampus;    Stress;   

Others  :  1084040
DOI  :  10.1186/2045-5380-4-12

 received in 2014-07-24, accepted in 2014-10-30,  发布年份 2014

【 摘 要 】

Background

The experience of early life stress is a consistently identified risk factor for the development of mood and anxiety disorders. Preclinical research employing animal models of early life stress has made inroads in understanding this association and suggests that the negative sequelae of early life stress may be mediated by developmental disruption of corticolimbic structures supporting stress responsiveness. Work in humans has corroborated this idea, as childhood adversity has been associated with alterations in gray matter volumes of the hippocampus, amygdala, and medial prefrontal cortex. Yet, missing from this body of research is a full understanding of how these neurobiological vulnerabilities may mechanistically contribute to the reported link between adverse childhood experiences and later affective psychopathology.

Results

Analyses revealed that self-reported childhood maltreatment was associated with reduced gray matter volumes within the medial prefrontal cortex and left hippocampus. Furthermore, reduced left hippocampal and medial prefrontal gray matter volume mediated the relationship between childhood maltreatment and trait anxiety. Additionally, individual differences in corticolimbic gray matter volume within these same structures predicted the anxious symptoms as a function of life stress 1 year after initial assessment.

Conclusions

Collectively, these findings provide novel evidence that reductions in corticolimbic gray matter, particularly within the hippocampus and medial prefrontal cortex, are associated with reported childhood maltreatment and individual differences in adult trait anxiety. Furthermore, our results suggest that these structural alterations contribute to increased affective sensitivity to stress later in life in those that have experienced early adversity. More broadly, the findings contribute to an emerging literature highlighting the critical importance of early stress on the development of corticolimbic structures supporting adaptive functioning later in life.

【 授权许可】

   
2014 Gorka et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]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.
• [2]Norman RE, Byambaa M, De R, Butchart A, Scott J, Vos T: The long-term health consequences of child physical abuse, emotional abuse, and neglect: a systematic review and meta-analysis. PLoS Med 2012, 9:e1001349.
• [3]Wildeman C, Emanuel N, Leventhal JM, Putnam-Hornstein E, Waldfogel J, Lee H: The prevalence of confirmed maltreatment among US children, 2004 to 2011. JAMA Pediatr 2014, 168(8):706-713.
• [4]Lupien SJ, McEwen BS, Gunnar MR, Heim C: Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 2009, 10:434-445.
• [5]McEwen BS, Eiland L, Hunter RG, Miller MM: Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology 2012, 62:3-12. [Anxiety and Depression]
• [6]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: Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biol Psychiatry 2012, 71:286-293. [Mechanisms of Compromised Stress Resilience During Development and Aging]
• [7]Mehta MA, Golembo NI, Nosarti C, Colvert E, Mota A, Williams SCR, Rutter M, Sonuga-Barke EJS: Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian Adoptees Study Pilot. J Child Psychol Psychiatry 2009, 50:943-951.
• [8]Teicher MH, Anderson CM, Polcari A: Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. Proc Natl Acad Sci 2012, 109:E563-E572.
• [9]Tottenham N, Sheridan MA: A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing. Front Hum Neurosci 2010, 3:68.
• [10]Woon FL, Hedges DW: Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis. Hippocampus 2008, 18:729-736.
• [11]Bremner JD, Vythilingam M, Vermetten E, Nazeer A, Adil J, Khan S, Staib LH, Charney DS: Reduced volume of orbitofrontal cortex in major depression. Biol Psychiatry 2002, 51:273-279.
• [12]Campbell S, Marriott M, Nahmias C, MacQueen GM: Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 2004, 161:598-607.
• [13]DeYoung CG, Hirsh JB, Shane MS, Papademetris X, Rajeevan N, Gray JR: Testing predictions from personality neuroscience brain structure and the big five. Psychol Sci 2010, 21:820-828.
• [14]Gardini S, Cloninger CR, Venneri A: Individual differences in personality traits reflect structural variance in specific brain regions. Brain Res Bull 2009, 79:265-270.
• [15]Karl A, Schaefer M, Malta LS, Dörfel D, Rohleder N, Werner A: A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev 2006, 30:1004-1031.
• [16]Spampinato M, Wood J, De Simone V, Grafman J: Neural correlates of anxiety in healthy volunteers: a voxel-based morphometry study. J Neuropsychiatry Clin Neurosci 2009, 21:199-205.
• [17]Treadway MT, Grant MM, Ding Z, Hollon SD, Gore JC, Shelton RC: Early adverse events, HPA activity and rostral anterior cingulate volume in MDD. PLoS ONE 2009, 4:e4887.
• [18]Rao U, Chen L-A, Bidesi AS, Shad MU, Thomas MA, Hammen CL: Hippocampal changes associated with early-life adversity and vulnerability to depression. Biol Psychiatry 2010, 67:357-364. [Posttraumatic Stress Disorder: Translational Neuroscience Perspectives on Gene-Environment Interactions]
• [19]Finlay-Jones R, Brown GW: Types of stressful life event and the onset of anxiety and depressive disorders. Psychol Med 1981, 11:803-815.
• [20]Kendler KS, Karkowski LM, Prescott CA: Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 1999, 156:837-841.
• [21]Jovanovic T, Blanding NQ, Norrholm SD, Duncan E, Bradley B, Ressler KJ: Childhood abuse is associated with increased startle reactivity in adulthood. Depress Anxiety 2009, 26:1018-1026.
• [22]Pole N, Neylan TC, Otte C, Metzler TJ, Best SR, Henn-Haase C, Marmar CR: Associations between childhood trauma and emotion-modulated psychophysiological responses to startling sounds: a study of police cadets. J Abnorm Psychol 2007, 116:352-361.
• [23]Gross C, Hen R: The developmental origins of anxiety. Nat Rev Neurosci 2004, 5:545-552.
• [24]Kendler KS, Kuhn J, Prescott CA: The interrelationship of neuroticism, sex, and stressful life events in the prediction of episodes of major depression. Am J Psychiatry 2004, 161:631-636.
• [25]Sandi C, Richter-Levin G: From high anxiety trait to depression: a neurocognitive hypothesis. Trends Neurosci 2009, 32:312-320.
• [26]Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC: The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998, 59:22-33.
• [27]Axelrod BN: Validity of the Wechsler abbreviated scale of intelligence and other very short forms of estimating intellectual functioning. Assessment 2002, 9:17-23.
• [28]Spielberger CD, Sydeman SJ, Owen AE, Marsh BJ: Measuring Anxiety and Anger with the State-Trait Anxiety Inventory (STAI) and the State-Trait Anger Expression Inventory (STAXI). In Use Psychol Test Treat Plan Outcomes Assess. 2nd edition. Mahwah, NJ, US: Lawrence Erlbaum Associates Publishers; 1999:993-1021.
• [29]Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W: Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl 2003, 27:169-190.
• [30]Fink LA, Bernstein D, Handelsman L, Foote J, Lovejoy M: Initial reliability and validity of the childhood trauma interview: a new multidimensional measure of childhood interpersonal trauma. Am J Psychiatry 1995, 152:1329-1335.
• [31]McEwen BS: Sex, stress and the hippocampus: allostasis, allostatic load and the aging process. Neurobiol Aging 2002, 23:921-939. [Brain Aging: Identifying the Brakes and Accelerators]
• [32]Clements K, Turpin G: The life events scale for students: validation for use with British samples. Personal Individ Differ 1996, 20:747-751.
• [33]Watson D, Weber K, Assenheimer JS, Clark LA, Strauss ME, McCormick RA: Testing a tripartite model: I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales. J Abnorm Psychol 1995, 104:3-14.
• [34]Reidy J, Keogh E: Testing the discriminant and convergent validity of the mood and anxiety symptoms questionnaire using a British sample. Personal Individ Differ 1997, 23:337-344.
• [35]Ashburner J, Friston KJ: Unified segmentation. NeuroImage 2005, 26:839-851.
• [36]Good CD, Johnsrude I, Ashburner J, Henson RNA, Friston KJ, Frackowiak RSJ: Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. NeuroImage 2001, 14:685-700.
• [37]Hayes AF: PROCESS: a versatile computational tool for observed variable mediation, moderation, and conditional process modeling. [White paper]. Retrieved from http://www.afhayes.com/public/process2012.pdf webcite
• [38]MacKinnon DP, Lockwood CM, Williams J: Confidence limits for the indirect effect: distribution of the product and resampling methods. Multivar Behav Res 2004, 39:99.
• [39]Scher CD, Stein MB, Asmundson GJG, McCreary DR, Forde DR: The childhood trauma questionnaire in a community sample: psychometric properties and normative data. J Trauma Stress 2001, 14:843-857.
• [40]Lightsey OR Jr, Hulsey CD: Impulsivity, coping, stress, and problem gambling among university students. J Couns Psychol 2002, 49:202.
• [41]Knight RG, Waal-Manning HJ, Spears GF: Some norms and reliability data for the state-trait anxiety inventory and the zung self-rating depression scale. Br J Clin Psychol 1983, 22:245-249.
• [42]Bogdan R, Perlis RH, Fagerness J, Pizzagalli DA: The impact of mineralocorticoid receptor ISO/VAL genotype (rs5522) and stress on reward learning. Genes Brain Behav 2010, 9:658-667.
• [43]Cook SC, Wellman CL: Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol 2004, 60:236-248.
• [44]Fabricius K, Wörtwein G, Pakkenberg B: The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus. Brain Struct Funct 2008, 212:403-416.
• [45]Monroy E, Hernández-Torres E, Flores G: Maternal separation disrupts dendritic morphology of neurons in prefrontal cortex, hippocampus, and nucleus accumbens in male rat offspring. J Chem Neuroanat 2010, 40:93-101.
• [46]Sotres-Bayon F, Cain CK, LeDoux JE: Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex. Biol Psychiatry 2006, 60:329-336.
• [47]Maier SF, Ryan SM, Barksdale CM, Kalin NH: Stressor controllability and the pituitary-adrenal system. Behav Neurosci 1986, 100:669-674.
• [48]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.
• [49]Burke K, Burke JD Jr, Regier DA, Rae DS: Age at onset of selected mental disorders in five community populations. Arch Gen Psychiatry 1990, 47:511-518.