Behavioral Problems After Early Life Stress: Contributions of the Hippocampus and Amygdala

doi:10.1016/j.biopsych.2014.04.020

Biological Psychiatry

Volume 77, Issue 4, 15 February 2015, Pages 314-323

https://doi.org/10.1016/j.biopsych.2014.04.020 Get rights and content

Abstract

Background

Early life stress (ELS) can compromise development, with higher amounts of adversity linked to behavioral problems. To understand this linkage, a growing body of research has examined two brain regions involved with socioemotional functioning—amygdala and hippocampus. Yet empirical studies have reported increases, decreases, and no differences within human and nonhuman animal samples exposed to different forms of ELS. This divergence in findings may stem from methodological factors, nonlinear effects of ELS, or both.

Methods

We completed rigorous hand-tracing of the amygdala and hippocampus in three samples of children who experienced different forms of ELS (i.e., physical abuse, early neglect, or low socioeconomic status). Interviews were also conducted with children and their parents or guardians to collect data about cumulative life stress. The same data were also collected in a fourth sample of comparison children who had not experienced any of these forms of ELS.

Results

Smaller amygdala volumes were found for children exposed to these different forms of ELS. Smaller hippocampal volumes were also noted for children who were physically abused or from low socioeconomic status households. Smaller amygdala and hippocampal volumes were also associated with greater cumulative stress exposure and behavioral problems. Hippocampal volumes partially mediated the relationship between ELS and greater behavioral problems.

Conclusions

This study suggests ELS may shape the development of brain areas involved with emotion processing and regulation in similar ways. Differences in the amygdala and hippocampus may be a shared diathesis for later negative outcomes related to ELS.

Section snippets

Subjects

T1-weighted MRI images were collected using a 3T General Electric SIGNA MRI scanner (GE Healthcare, Waukeshau, Wisconsin) (additional information in Supplement 1) for 128 children (61 girls; mean age, 141.9 months; SD ± 20.45; range, 108.23–178.70 months). These children constituted three different ELS risk groups: children who experienced early caregiving neglect while living in institutions for orphaned or abandoned children, children from low SES households, and children who were victims of

Results

To examine whether specific forms of ELS were associated with amygdala or hippocampal differences, three separate linear regression models were used to compare children who experienced different forms of ELS (i.e., physical abuse, early neglect, low SES) with comparison children who had not experienced ELS. Such an approach has been employed and recommended by other research groups (99, 100). Right and left volumes for each structure were entered separately into linear regressions as dependent

Discussion

The goal of this study was to understand if ELS was associated with volumetric differences in the amygdala and hippocampus, two important MTL structures involved with socioemotional functioning. By working with groups of children exposed to different forms of ELS, we additionally sought to overcome limitations of past research studies, such as unobserved or unmeasured characteristics of specific stressful experiences. Rigorous hand-tracing methods revealed that each form of ELS investigated was

Acknowledgments and Disclosures

This work was supported by the National Institute of Mental Health (Grant No. MH61285 and MH68858 to SDP and Grant Nos. P50-MH84051 and MH43454 to RJD), a National Institute of Drug Abuse Fellowship (Grant No. DA028087 to JLH), and a core grant to the Waisman Center Intellectual & Developmental Disabilities Research Center from the National Institute of Child Health and Human Development (Grant No. P30-HD03352). EAS was at the University of Wisconsin-Madison at the time the data were collected,

References (104)

S.H. Ameis et al.
Cortical thickness, cortico-amygdalar networks, and externalizing behaviors in healthy children
Biol Psychiatry
(2014)
S.R. Jaffee et al.
Individual, family, and neighborhood factors distinguish resilient from non-resilient maltreated children: A cumulative stressors model
Child Abuse Neglect
(2007)
W.R. Lovallo et al.
Lifetime adversity leads to blunted stress axis reactivity: Studies from the Oklahoma Family Health Patterns Project
Biol Psychiatry
(2012)
A. Karl et al.
A meta-analysis of structural brain abnormalities in PTSD
Neurosci Biobehav Rev
(2006)
B. Drake et al.
Understanding the relationship between neighborhood poverty and specific types of child maltreatment
Child Abuse Neglect
(1996)
L.E. Jarrard
On the role of the hippocampus in learning and memory in the rat
Behav Neural Biol
(1993)
K.G. Lambert et al.
Activity-stress induces atrophy of apical dendrites of hippocampal pyramidal neurons in male rats
Physiol Behav
(1998)
A.M. Magarinos et al.
Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: Involvement of glucocorticoid secretion and excitatory amino acid receptors
Neuroscience
(1995)
U. Rao et al.
Hippocampal changes associated with early-life adversity and vulnerability to depression
Biol Psychiatry
(2010)
V.G. Carrion et al.
Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder
Biol Psychiatry
(2001)

M.D. De Bellis et al.

A.E. Bennett Research Award. Developmental traumatology. Part II. Brain development

Biol Psychiatry

(1999)

M.D. De Bellis et al.

Brain structures in pediatric maltreatment-related posttraumatic stress disorder: A sociodemographically matched study

Biol Psychiatry

(2002)

M.D. De Bellis et al.

A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder

Biol Psychiatry

(2001)

M.A. Padival et al.

Repeated restraint stress exerts different impact on structure of neurons in the lateral and basal nuclei of the amygdala

Neuroscience

(2013)

A. Vyas et al.

Prolonged behavioral stress enhances synaptic connectivity in the basolateral amygdala

Neuroscience

(2006)

A.L. Goddings et al.

The influence of puberty on subcortical brain development

Neuroimage

(2014)

B. Brierley et al.

The human amygdala: A systematic review and meta-analysis of volumetric magnetic resonance imaging

Brain Res Brain Res Rev

(2002)

S.J. Teipel et al.

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer’s disease

Psychiatry Res Neuroimaging

(2010)

R.A. Morey et al.

A comparison of automated segmentation and manual tracing for quantifying hippocampal and amygdala volumes

Neuroimage

(2009)

J. Dewey et al.

Reliability and validity of MRI-based automated volumetry software relative to auto-assisted manual measurement of subcortical structures in HIV-infected patients from a multisite study

Neuroimage

(2010)

B.S. McEwen

Glucocorticoids, depression, and mood disorders: Structural remodeling in the brain

Metabolism

(2005)

J.A. Rosenkranz et al.

Chronic stress causes amygdala hyperexcitability in rodents

Biol Psychiatry

(2010)

B.S. McEwen

Mood disorders and allostatic load

Biol Psychiatry

(2003)

T. Frodl et al.

Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects

Biol Psychiatry

(2003)

J. Ding et al.

Single-prolonged stress induces apoptosis in the amygdala in a rat model of post-traumatic stress disorder

J Psychiatr Res

(2010)

E.J. McCrory et al.

Heightened neural reactivity to threat in child victims of family violence

Curr Biol

(2011)

A. Vyas et al.

Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior

Neuroscience

(2004)

M.A. Straus et al.

Identification of child maltreatment with the Parent-Child Conflict Tactics Scales: Development and psychometric data for a national sample of American parents

Child Abuse Neglect

(1998)

B.D. Rusch et al.

Hippocampal morphometry in depressed patients and control subjects: Relations to anxiety symptoms

Biol Psychiatry

(2001)

M.L. Belfer

Child and adolescent mental disorders: The magnitude of the problem across the globe

J Child Psychol Psychiatry

(2008)

J. Reef et al.

Developmental trajectories of child to adolescent externalizing behavior and adult DSM-IV disorder: Results of a 24-year longitudinal study

Soc Psychiatry Psychiatr Epidemiol

(2011)

S. Scott et al.

Financial cost of social exclusion: Follow up study of antisocial children into adulthood

BMJ

(2001)

T.P. Beauchaine et al.

Instantiating the multiple levels of analysis perspective in a program of study on externalizing behavior

Dev Psychopathol

(2012)

F. Levy

Internalizing versus externalizing comorbidity: Neural circuit hypothesis

Aust N Z J Psychiatry

(2010)

C.J. Patrick et al.

Reconceptualizing antisocial deviance in neurobehavioral terms

Dev Psychopathol

(2012)

D.M. Fergusson et al.

Resilience to childhood adversity. Results of a 21-year study

B.M. Hicks et al.

Environmental adversity and increasing genetic risk for externalizing disorders

Arch Gen Psychiatry

(2009)

S.R. Jaffee et al.

Physical maltreatment victim to antisocial child: Evidence of an environmentally mediated process

J Abnorm Psychol

(2004)

J.E. Lansford et al.

A 12-year prospective study of the long-term effects of early child physical maltreatment on psychological, behavioral, and academic problems in adolescence

Arch Pediatr Adolesc Med

(2002)

J.E. Lansford et al.

Early physical abuse and later violent delinquency. A prospective longitudinal study

Child Maltreatment

(2007)

B. Hawk et al.

CBCL behavior problems of post-institutionalized international adoptees

Clin Child Fam Psychol Rev

(2010)

E.C. Merz et al.

Behavior problems in children adopted from psychosocially depriving institutions

J Abnorm Child Psychol

(2010)

K.L. Wiik et al.

Behavioral and emotional symptoms of post-institutionalized children in middle childhood

J Child Psychol Psychiatry

(2010)

R.H. Bradley et al.

Socioeconomic status and child development

Annu Rev Psychol

(2002)

J. Brooks-Gunn et al.

The effects of poverty on children

The Future of Children

(1997)

V.C. McLoyd

Socioeconomic disadvantage and child development

Am Psychol

(1998)

S. Barnow et al.

The importance of a positive family history of alcoholism, parental rejection and emotional warmth, behavioral problems and peer substance use for alcohol problems in teenagers: A path analysis

J Stud Alcohol Drugs

(2002)

M.J. Briggs-Gowan et al.

Exposure to potentially traumatic events in early childhood: Differential links to emergent psychopathology

J Child Psychol Psychiatry

(2010)

M.J. Essex et al.

Influence of early life stress on later hypothalamic-pituitary-adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence

Dev Psychopathol

(2011)

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Archival ReportBehavioral Problems After Early Life Stress: Contributions of the Hippocampus and Amygdala

Abstract

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Acknowledgments and Disclosures

Biol Psychiatry

Child Abuse Neglect

Biol Psychiatry

Neurosci Biobehav Rev

Child Abuse Neglect

Behav Neural Biol

Physiol Behav

Neuroscience

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Neuroscience

Neuroscience

Neuroimage

Brain Res Brain Res Rev

Psychiatry Res Neuroimaging

Neuroimage

Neuroimage

Metabolism

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

J Psychiatr Res

Curr Biol

Neuroscience

Child Abuse Neglect

Biol Psychiatry

Child and adolescent mental disorders: The magnitude of the problem across the globe

J Child Psychol Psychiatry

Developmental trajectories of child to adolescent externalizing behavior and adult DSM-IV disorder: Results of a 24-year longitudinal study

Soc Psychiatry Psychiatr Epidemiol

Financial cost of social exclusion: Follow up study of antisocial children into adulthood

BMJ

Instantiating the multiple levels of analysis perspective in a program of study on externalizing behavior

Dev Psychopathol

Internalizing versus externalizing comorbidity: Neural circuit hypothesis

Aust N Z J Psychiatry

Reconceptualizing antisocial deviance in neurobehavioral terms

Dev Psychopathol

Resilience to childhood adversity. Results of a 21-year study

Environmental adversity and increasing genetic risk for externalizing disorders

Arch Gen Psychiatry

Physical maltreatment victim to antisocial child: Evidence of an environmentally mediated process

J Abnorm Psychol

A 12-year prospective study of the long-term effects of early child physical maltreatment on psychological, behavioral, and academic problems in adolescence

Arch Pediatr Adolesc Med

Early physical abuse and later violent delinquency. A prospective longitudinal study

Child Maltreatment

CBCL behavior problems of post-institutionalized international adoptees

Clin Child Fam Psychol Rev

Behavior problems in children adopted from psychosocially depriving institutions

J Abnorm Child Psychol

Behavioral and emotional symptoms of post-institutionalized children in middle childhood

J Child Psychol Psychiatry

Socioeconomic status and child development

Annu Rev Psychol

The effects of poverty on children

The Future of Children

Socioeconomic disadvantage and child development

Am Psychol

The importance of a positive family history of alcoholism, parental rejection and emotional warmth, behavioral problems and peer substance use for alcohol problems in teenagers: A path analysis

J Stud Alcohol Drugs

Exposure to potentially traumatic events in early childhood: Differential links to emergent psychopathology

J Child Psychol Psychiatry

Influence of early life stress on later hypothalamic-pituitary-adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence

Dev Psychopathol

Archival Report
Behavioral Problems After Early Life Stress: Contributions of the Hippocampus and Amygdala