The aim of the present study was 2-fold: (1) to utilize improved amygdala segmentation and exploratory factor analysis to characterize the latent volumetric structure among amygdala nuclei and (2) to assess the effect of adverse childhood experiences (ACEs) on amygdalar morphometry and current psychiatric symptoms. To investigate these aims, structural (T1) MRI and self-report data were obtained from 119 emerging adults. Regression analysis showed that higher ACE scores were related to reduced volume of the right, but not the left, amygdalar segments. Further, exploratory factor analysis yielded a two-factor structure, basolateral and central-medial nuclei of the right amygdala. Stractual equation modeling analyses revealed that higher ACE scores were significantly related to a reduced volume of the right basolateral and central-medial segments. Furthermore, reduction in the right basolateral amygdala was associated with increased anxiety, depressive symptoms, and alcohol use. This association supports an indirect effect between early adversity and psychiatric problems via reduced right basolateral amygdalar volume. The high-resolution segmentation results reveal a latent structure among amygdalar nuclei, which is consistent with prior work conducted in nonhuman mammals. These findings extend previous reports linking early adversity, right amygdala volume, and psychopathology.
AndaR. F.FelittiV. J.BremnerJ. D.WalkerJ. D.WhitfieldC.PerryB. D.…GilesW. H. (2006). The enduring effects of abuse and related adverse experiences in childhood. European Archives of Psychiatry and Clinical Neuroscience, 256, 174–186.
2.
BaasD.AlemanA.KahnR. S. (2004). Lateralization of amygdala activation: A systematic review of functional neuroimaging studies. Brain Research Reviews, 45, 96–103.
3.
BaborT. F.Higgins-BiddleJ. C.SaundersJ. B.MonteiroM. G. (2001). AUDIT: The Alcohol Use Disorders Identification Test: Guidelines for Use in Pri- mary Health Care. 2nd ed. Geneva, Switzerland: World Health Organization.
4.
BaxterM. G.MurrayE. A. (2002). The amygdala and reward. Nature Reviews Neuroscience, 3, 563.
5.
BrodyG. H.GrayJ. C.YuT.BartonA. W.BeachS. R.GalvánA.…MillerG. E. (2017). Protective prevention effects on the association of poverty with brain development. JAMA Pediatrics, 171, 46–52.
6.
BrownT. A. (2015). Confirmatory factor analysis for applied research. Guilford Publications.
7.
ButtonK. S.IoannidisJ. P.MokryszC.NosekB. A.FlintJ.RobinsonE. S.MunafòM. R. (2013). Power failure: Why small sample size undermines the reliability of neuroscience. Nature Reviews Neuroscience, 14, 365.
8.
CalemM.BromisK.McGuireP.MorganC.KemptonM. J. (2017). Meta-analysis of associations between childhood adversity and hippocampus and amygdala volume in non-clinical and general population samples. NeuroImage: Clinical, 14, 471–479.
9.
CicchettiD. (2016). Socioemotional, personality, and biological development: Illustrations from a multilevel developmental psychopathology perspective on child maltreatment. Annual Review of Psychology, 67, 187–211.
10.
De BellisM. D.ZiskA. (2014). The biological effects of childhood trauma. Child and Adolescent Psychiatric Clinics, 23, 185–222.
11.
DutcherJ. M.CreswellJ. D. (2018). Behavioral interventions in health neuroscience. Annals of the New York Academy of Sciences, 1428, 51–70.
12.
EilandL.RamroopJ.HillM. N.ManleyJ.McEwenB. S. (2012). Chronic juvenile stress produces corticolimbic dendritic architectural remodeling and modulates emotional behavior in male and female rats. Psychoneuroendocrinology, 37, 39–47.
13.
EtkinA.KlemenhagenK. C.DudmanJ. T.RoganM. T.HenR.KandelE. R.HirschJ. (2004). Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Neuron, 44, 1043–1055.
14.
FanselowM. S.LeDouxJ. E. (1999). Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron, 23, 229–232.
15.
FelittiV. J.AndaR. F.NordenbergD.WilliamsonD. F.SpitzA. M.EdwardsV.…MarksJ. S. (1998). Relationship of childhood abuse and household dysfunction too many of the leading causes of death in adults: The adverse childhood experiences (ace) study. American Journal of Preventive Medicine, 14, 245–258.
16.
FischlB.Van Der KouweA.DestrieuxC.HalgrenE.SégonneF.SalatD. H.…KennedyD. (2004). Automatically parcellating the human cerebral cortex. Cerebral Cortex, 14, 11–22.
17.
Fusar-PoliP.PlacentinoA.CarlettiF.AllenP.LandiP.AbbamonteM.…PolitiP. (2009). Laterality effect on emotional faces processing: ALE meta-analysis of evidence. Neuroscience Letters, 452, 262–267.
18.
GattJ.NemeroffC.Dobson-StoneC.PaulR.BryantR.SchofieldP.…WilliamsL. (2009). Interactions between BDNF val66met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molecular Psychiatry, 14, 681.
19.
GlahnD. C.LovalloW. R.FoxP. T. (2007). Reduced amygdala activation in young adults at high risk of alcoholism: Studies from the Oklahoma family health patterns project. Biological Psychiatry, 61, 1306–1309.
20.
GoodkindM.EickhoffS. B.OathesD. J.JiangY.ChangA.Jones-HagataL. B.…KorgaonkarM. S. (2015). Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry, 72, 305–315.
21.
GordonH. (2016). Laterality of brain activation for risk factors of addiction. Current Drug Abuse Reviews, 9, 1–18.
22.
HaasB. W.CanliT. (2008). Emotional memory function, personality structure and psychopathology: A neural system approach to the identification of vulnerability markers. Brain Research Reviews, 58, 71–84.
23.
HackmanD. A.FarahM. J.MeaneyM. J. (2010). Socioeconomic status and the brain: Mechanistic insights from human and animal research. Nature Reviews Neuroscience, 11, 651.
24.
HansonJ. L.NacewiczB. M.SuttererM. J.CayoA. A.SchaeferS. M.RudolphK. D.…DavidsonR. J. (2015). Behavioral problems after early life stress: Contributions of the hippocampus and amygdala. Biological Psychiatry, 77, 314–323.
25.
HarrisonN. A.CritchleyH. D. (2007). Affective neuroscience and psychiatry. British Journal of Psychiatry, 191, 192–194.
26.
HaslerG.DrevetsW. C.ManjiH. K.CharneyD. S. (2004). Discovering endophenotypes for major depression. Neuropsychopharmacology, 29, 1765.
27.
HillS. Y.De BellisM. D.KeshavanM. S.LowersL.ShenS.HallJ.PittsT. (2001). Right amygdala volume in adolescent and young adult offspring from families at high risk for developing alcoholism. Biological Psychiatry, 49, 894–905.
28.
HorwitzB.TagametsM.McIntoshA. R. (1999). Neural modeling, functional brain imaging, and cognition. Trends in Cognitive Sciences, 3, 91–98.
29.
HowellB. R.GrandA. P.McCormackK. M.ShiY.LaPrarieJ. L.MaestripieriD.…SanchezM. M. (2014). Early adverse experience increases emotional reactivity in juvenile rhesus macaques: Relation to amygdala volume. Developmental Psychobiology, 56, 1735–1746. doi:10.1002/dev.21237
30.
HuL. T.BentlerP. M. (1999). Cutoff criteria for fit indexes in covariance structure analysis: Conventional criteria versus new alternatives. Structural Equation Modeling: A Multidisciplinary Journal, 6, 1–55.
31.
KalinN. H.SheltonS. E.DavidsonR. J. (2004). The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. Journal of Neuroscience, 24, 5506–5515.
32.
KoobG.KreekM. J. (2007). Stress, dysregulation of drug reward pathways, and the transition to drug dependence. American Journal of Psychiatry, 164, 1149–1159.
33.
KoobG. F. (2013). Negative reinforcement in drug addiction: The darkness within. Current Opinion in Neurobiology, 23, 559–563. doi:10.1016/j.conb.2013.03.011
34.
LaheyB. B.McNealyK.KnodtA.ZaldD. H.SpornsO.ManuckS. B.…HaririA. R. (2012). Using confirmatory factor analysis to measure contemporaneous activation of defined neuronal networks in functional magnetic resonance imaging. Neuroimage, 60, 1982–1991.
35.
LambertH. K.KingK. M.MonahanK. C.McLaughlinK. A. (2017). Differential associations of threat and deprivation with emotion regulation and cognitive control in adolescence. Development and Psychopathology, 29, 929–940.
36.
LittleR. J.RubinD. B. (2002). Bayes and multiple imputation. In Wiley (ed.) Statistical analysis with missing data (2nd ed., pp. 200–220).
37.
LovalloW. R. (2013). Review: Early life adversity reduces stress reactivity and enhances impulsive behavior: Implications for health behaviors. International Journal of Psychophysiology, 90, 8–16. doi:10.1016/j.ijpsycho.2012.10.006
38.
LupienS. J.ParentS.EvansA. C.TremblayR. E.ZelazoP. D.CorboV.…SéguinJ. R. (2011). Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proceedings of the National Academy of Sciences, 108, 14324–14329.
39.
McEwenB. S.GianarosP. J. (2010). Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease. Annals of the New York Academy of Sciences, 1186, 190–222.
40.
McEwenB. S.NascaC.GrayJ. D. (2016). Stress effects on neuronal structure: Hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology, 41, 3.
41.
MehtaM. A.GolemboN. I.NosartiC.ColvertE.MotaA.WilliamsS. C.…Sonuga-BarkeE. J. (2009). Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: The English and Romanian adoptees study pilot. Journal of Child Psychology and Psychiatry, 50, 943–951.
42.
MerskyJ. P.TopitzesJ.ReynoldsA. J. (2013). Impacts of adverse childhood experiences on health, mental health, and substance use in early adulthood: A cohort study of an urban, minority sample in the US. In (Vol. 37, pp. 917–925).
43.
MerzE. C.TottenhamN.NobleK. G. (2018). Socioeconomic status, amygdala volume, and internalizing symptoms in children and adolescents. Journal of Clinical Child & Adolescent Psychology, 47, 312–323. doi:10.1080/15374416.2017.1326122
44.
MilhamM. P.NugentA. C.DrevetsW. C.DicksteinD. S.LeibenluftE.ErnstM.…PineD. S. (2005). Selective reduction in amygdala volume in pediatric anxiety disorders: A voxel-based morphometry investigation. Biological Psychiatry, 57, 961–966.
45.
MoreyR. A.GoldA. L.LaBarK. S.BeallS. K.BrownV. M.HaswellC. C.…McCarthyG. (2012). Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Archives of General Psychiatry, 69, 1169–1178.
46.
MorrisJ. S.ÖhmanA.DolanR. J. (1999). A subcortical pathway to the right amygdala mediating “unseen” fear. Proceedings of the National Academy of Sciences, 96, 1680–1685.
47.
MuthénL. K.MuthénB. O. (2010). Mplus: Statistical analysis with latent variables: User’s guide. Los Angeles, CA: Muthén & Muthén.
48.
OshriA.RogoschF. A.CicchettiD. (2013). Child maltreatment and mediating influences of childhood personality types on the development of adolescent psychopathology. Journal of Clinical Child and Adolescent Psychology, 42, 287–301.
49.
PardiniD. A.RaineA.EricksonK.LoeberR. (2014). Lower amygdala volume in men is associated with childhood aggression, early psychopathic traits, and future violence. Biological Psychiatry, 75, 73–80.
50.
PhelpsE. A.O’ConnorK. J.GatenbyJ. C.GoreJ. C.GrillonC.DavisM. (2001). Activation of the left amygdala to a cognitive representation of fear. Nature neuroscience, 4, 437.
51.
PhillipsR.LeDouxJ. (1992). Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behavioral Neuroscience, 106, 274.
52.
QinS.YoungC. B.DuanX.ChenT.SupekarK.MenonV. (2014). Amygdala subregional structure and intrinsic functional connectivity predicts individual differences in anxiety during early childhood. Biological Psychiatry, 75, 892–900.
53.
RoozendaalB.McEwenB. S.ChattarjiS. (2009). Stress, memory and the amygdala. Nature Reviews Neuroscience, 10, 423.
54.
SayginZ. M.KliemannD.IglesiasJ.van der KouweA. J.BoydE.ReuterM.…FroschM. P. (2017). High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: Manual segmentation to automatic atlas. Neuroimage, 155, 370–382.
55.
SergerieK.ChocholC.ArmonyJ. L. (2008). The role of the amygdala in emotional processing: A quantitative meta-analysis of functional neuroimaging studies. Neuroscience & Biobehavioral Reviews, 32, 811–830.
56.
ShonkoffJ. P.GarnerA. S.SiegelB. S.DobbinsM. I.EarlsM. F.McGuinnL.…CareD. (2012). The lifelong effects of early childhood adversity and toxic stress. Pediatrics, 129, e232–e246.
57.
SinhaR. (2008). Chronic stress, drug use, and vulnerability to addiction. Annals of the New York Academy of Sciences, 1141, 105–130.
58.
Solano-CastiellaE.AnwanderA.LohmannG.WeissM.DochertyC.GeyerS.…TurnerR. (2010). Diffusion tensor imaging segments the human amygdala in vivo. Neuroimage, 49, 2958–2965.
59.
SpitzerR. L.KroenkeK.WilliamsJ. B., & the Patient Health Questionnaire Primary Care Study Group . (1999). Validation and utility of a self-report version of PRIME-MD: The PHQ primary care study. Journal of the American Medical Association, 282, 1737–1744.
60.
SpitzerR. L.WilliamsJ. B.KroenkeK.HornyakR.McMurrayJ. (2000). Validity and utility of the prime-md patient health questionnaire in assessment of 3000 obstetric-gynecologic patients: The prime-md patient health questionnaire obstetrics-gynecology study. American Journal of Obstetrics & Gynecology, 183, 759–769.
61.
TeicherM. H.SamsonJ. A. (2013). Childhood maltreatment and psychopathology: A case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. American Journal of Psychiatry, 170, 1114–1133.
62.
TofighiD.MacKinnonD. P. (2011). RMediation: An r package for mediation analysis confidence intervals. Behavior Research Methods, 43, 692–700.
63.
WassumK. M.IzquierdoA. (2015). The basolateral amygdala in reward learning and addiction. Neuroscience & Biobehavioral Reviews, 57, 271–283.
64.
WenigerG.LangeC.SachsseU.IrleE. (2009). Reduced amygdala and hippocampus size in trauma-exposed women with borderline personality disorder and without posttraumatic stress disorder. Journal of Psychiatry & Neuroscience, 34, 383.
65.
WilliamsL. M.KempA. H.FelminghamK.BartonM.OlivieriG.PedutoA.…BryantR. A. (2006). Trauma modulates amygdala and medial prefrontal responses to consciously attended fear. Neuroimage, 29, 347–357.
66.
WoonF. L.HedgesD. W. (2008). Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: A meta-analysis. Hippocampus, 18, 729–736.
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