Effect of childhood maltreatment on brain structure in adult patients with major depressive disorder and healthy participants.

BACKGROUND Childhood maltreatment has been found to play a crucial role in the development of psychiatric disorders. However, whether childhood maltreatment is associated with structural brain changes described for major depressive disorder (MDD) is still a matter of debate. The aim of this study was to investigate whether patients with MDD and a history of childhood maltreatment display more structural changes than patients without childhood maltreatment or healthy controls. METHODS Patients with MDD and healthy controls with and without childhood maltreatment experience were investigated using high-resolution magnetic resonance imaging (MRI), and data were analyzed using voxel-based morphometry. RESULTS We studied 37 patients with MDD and 46 controls. Grey matter volume was significantly decreased in the hippocampus and significantly increased in the dorsomedial prefrontal cortex (DMPFC) and the orbitofrontal cortex (OFC) in participants who had experienced childhood maltreatment compared with those who had not. Patients displayed smaller left OFC and left DMPFC volumes than controls. No significant difference in hippocampal volume was evident between patients with MDD and healthy controls. In regression analyses, despite effects from depression, age and sex on the DMPFC, OFC and hippocampus, childhood maltreatment was found to independently affect these regions. LIMITATIONS The retrospective assessment of childhood maltreatment; the natural problem that patients experienced more childhood maltreatment than controls; and the restrictions, owing to sample size, to investigating higher order interactions among factors are discussed as limitations. CONCLUSION These results suggest that early childhood maltreatment is associated with brain structural changes irrespective of sex, age and a history of depression.Thus, the study highlights the importance of childhood maltreatment when investigating brain structures.

[1]  Matthew D. Lieberman,et al.  Neural Responses to Emotional Stimuli Are Associated with Childhood Family Stress , 2006, Biological Psychiatry.

[2]  Walter Heindel,et al.  Limbic Scars: Long-Term Consequences of Childhood Maltreatment Revealed by Functional and Structural Magnetic Resonance Imaging , 2012, Biological Psychiatry.

[3]  C. Nemeroff,et al.  The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies , 2001, Biological Psychiatry.

[4]  M. Meaney,et al.  Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. , 1993, Brain research. Molecular brain research.

[5]  G. MacQueen,et al.  The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? , 2011, Molecular Psychiatry.

[6]  M. Angermeyer,et al.  Relationship between parental bonding and mood disorder in six European countries , 2006, Psychiatry Research.

[7]  Hans-Jürgen Möller,et al.  Hippocampal and amygdala changes in patients with major depressive disorder and healthy controls during a 1-year follow-up. , 2004, The Journal of clinical psychiatry.

[8]  R. Kessler,et al.  The effects of stressful life events on depression. , 1997, Annual review of psychology.

[9]  L. Stein,et al.  Psychobiology of childhood maltreatment: effects of allostatic load? , 2008, Revista brasileira de psiquiatria.

[10]  P. Sawchenko,et al.  Noradrenergic Innervation of the Dorsal Medial Prefrontal Cortex Modulates Hypothalamo-Pituitary-Adrenal Responses to Acute Emotional Stress , 2008, The Journal of Neuroscience.

[11]  Martin H. Teicher,et al.  Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum , 2012, Proceedings of the National Academy of Sciences.

[12]  J Foote,et al.  Initial reliability and validity of a new retrospective measure of child abuse and neglect. , 1994, The American journal of psychiatry.

[13]  Hans-Jürgen Möller,et al.  Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. , 2008, Journal of psychiatry & neuroscience : JPN.

[14]  Kevin N. Ochsner,et al.  For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion , 2004, NeuroImage.

[15]  E. Koechlin,et al.  Anterior Prefrontal Function and the Limits of Human Decision-Making , 2007, Science.

[16]  A. Reiss,et al.  Stress Predicts Brain Changes in Children: A Pilot Longitudinal Study on Youth Stress, Posttraumatic Stress Disorder, and the Hippocampus , 2007, Pediatrics.

[17]  G. MacQueen,et al.  A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. , 2009, Journal of psychiatry & neuroscience : JPN.

[18]  T. Egner,et al.  Emotional processing in anterior cingulate and medial prefrontal cortex , 2011, Trends in Cognitive Sciences.

[19]  M. Mintun,et al.  Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus , 2010, Proceedings of the National Academy of Sciences.

[20]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[21]  N. Koutsouleris,et al.  Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression. , 2010, Journal of psychiatric research.

[22]  D. Chapman,et al.  Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study. , 2003, Pediatrics.

[23]  Peter McGuffin,et al.  Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. , 2011, Journal of affective disorders.

[24]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[25]  A. Mechelli,et al.  The University of Birmingham ( Live System ) Reduced orbitofrontal and temporal grey matter in a community sample of maltreated children , 2016 .

[26]  N. McNaughton,et al.  Comparison between the behavioural effects of septal and hippocampal lesions: A review , 1983, Neuroscience & Biobehavioral Reviews.

[27]  D. Yves von Cramon,et al.  Variants of uncertainty in decision-making and their neural correlates , 2005, Brain Research Bulletin.

[28]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[29]  M. Keshavan,et al.  N-Acetylaspartate concentration in the anterior cingulate of maltreated children and adolescents with PTSD. , 2000, The American journal of psychiatry.

[30]  D. Charney,et al.  Effects of early stress on brain structure and function: Implications for understanding the relationship between child maltreatment and depression , 2001, Development and Psychopathology.

[31]  Olga V. Demler,et al.  The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). , 2003, JAMA.

[32]  A. Simmons,et al.  Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. , 2011, Archives of general psychiatry.

[33]  M. Hamilton,et al.  Standardised assessment and recording of depressive symptoms. , 1969, Psychiatria, neurologia, neurochirurgia.

[34]  Liu,et al.  Influence of Neonatal Rearing Conditions on Stress‐Induced Adrenocorticotropin Responses and Norepinepherine Release in the Hypothalamic Paraventricular Nucleus , 2000, Journal of neuroendocrinology.

[35]  Larry A. Tupler,et al.  Segmented Hippocampal Volume in Children and Adolescents with Posttraumatic Stress Disorder , 2006, Biological Psychiatry.

[36]  P. Liddle,et al.  Prefrontal cortex function in remitted major depressive disorder , 2012, Psychological Medicine.

[37]  E. Stein,et al.  Early-life stress induces long-term morphologic changes in primate brain. , 2009, Archives of general psychiatry.

[38]  S. Andersen.  Trajectories of brain development: point of vulnerability or window of opportunity? , 2003, Neuroscience & Biobehavioral Reviews.

[39]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[40]  H. Möller,et al.  Depression-related variation in brain morphology over 3 years: effects of stress? , 2008, Archives of general psychiatry.

[41]  A. Aleman,et al.  Reduced Medial Prefrontal Cortex Volume in Adults Reporting Childhood Emotional Maltreatment , 2010, Biological Psychiatry.

[42]  B. Rothbaum,et al.  Early adversity in chronic depression: clinical correlates and response to pharmacotherapy , 2009, Depression and anxiety.

[43]  Suzanne Wood,et al.  Reduced posterior hippocampal volume in posttraumatic stress disorder. , 2008, The Journal of clinical psychiatry.

[44]  Eric Vermetten,et al.  Childhood trauma associated with smaller hippocampal volume in women with major depression. , 2002, The American journal of psychiatry.

[45]  P. Koolschijn,et al.  Brain volume abnormalities in major depressive disorder: a Meta-analysis of magnetic resonance imaging studies , 2009, NeuroImage.

[46]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[47]  M. Nishi,et al.  Effects of early life stress on brain activity: implications from maternal separation model in rodents. , 2013, General and comparative endocrinology.

[48]  J. Gross,et al.  The cognitive control of emotion , 2005, Trends in Cognitive Sciences.

[49]  Beth E. Molnar,et al.  Child sexual abuse and subsequent psychopathology: results from the National Comorbidity Survey. , 2001, American journal of public health.

[50]  M Davies,et al.  The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability. , 1992 .

[51]  Martin H. Teicher,et al.  The neurobiological consequences of early stress and childhood maltreatment , 2003, Neuroscience & Biobehavioral Reviews.

[52]  M. First,et al.  The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. , 1992, Archives of general psychiatry.

[53]  T. Frodl,et al.  How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans , 2013, Neurobiology of Disease.