Prenatal maternal depression alters amygdala functional connectivity in 6-month-old infants

Prenatal maternal depression is associated with alterations in the neonatal amygdala microstructure, shedding light on the timing for the influence of prenatal maternal depression on the brain structure of the offspring. This study aimed to examine the association between prenatal maternal depressive symptomatology and infant amygdala functional connectivity and to thus establish the neural functional basis for the transgenerational transmission of vulnerability for affective disorders during prenatal development. Twenty-four infants were included in this study with both structural magnetic resonance imaging (MRI) and resting-state functional MRI (fMRI) at 6 months of age. Maternal depression was assessed at 26 weeks of gestation and 3 months after delivery using the Edinburgh Postnatal Depression Scale. Linear regression was used to identify the amygdala functional networks and to examine the associations between prenatal maternal depressive symptoms and amygdala functional connectivity. Our results showed that at 6 months of age, the amygdala is functionally connected to widespread brain regions, forming the emotional regulation, sensory and perceptual, and emotional memory networks. After controlling for postnatal maternal depressive symptoms, infants born to mothers with higher prenatal maternal depressive symptoms showed greater functional connectivity of the amygdala with the left temporal cortex and insula, as well as the bilateral anterior cingulate, medial orbitofrontal and ventromedial prefrontal cortices, which are largely consistent with patterns of connectivity observed in adolescents and adults with major depressive disorder. Our study provides novel evidence that prenatal maternal depressive symptomatology alters the amygdala's functional connectivity in early postnatal life, which reveals that the neuroimaging correlates of the familial transmission of phenotypes associated with maternal mood are apparent in infants at 6 months of age.

[1]  S. Pawlby,et al.  Antenatal depression predicts depression in adolescent offspring: prospective longitudinal community-based study. , 2008, Journal of affective disorders.

[2]  H. Walter,et al.  Acute and Sustained Effects of Cognitive Emotion Regulation in Major Depression , 2010, The Journal of Neuroscience.

[3]  Bradley Goodyear,et al.  Reduced Intrinsic Connectivity of Amygdala in Adults with Major Depressive Disorder , 2014, Front. Psychiatry.

[4]  Richard J. Davidson,et al.  Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence , 2012, Nature Neuroscience.

[5]  P. Gluckman,et al.  Prenatal Maternal Depression Associates with Microstructure of Right Amygdala in Neonates at Birth , 2013, Biological Psychiatry.

[6]  A. Stein,et al.  Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years. , 2013, JAMA psychiatry.

[7]  D. Hu,et al.  Identifying major depression using whole-brain functional connectivity: a multivariate pattern analysis. , 2012, Brain : a journal of neurology.

[8]  T. Field,et al.  Prenatal depression effects and interventions: a review. , 2010, Infant behavior & development.

[9]  Michael I. Miller,et al.  The emerging discipline of Computational Functional Anatomy , 2009, NeuroImage.

[10]  Daniel S. Margulies,et al.  Functional connectivity of the human amygdala using resting state fMRI , 2009, NeuroImage.

[11]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[12]  Danielle S. Bassett,et al.  A validated network of effective amygdala connectivity , 2007, NeuroImage.

[13]  M. Crommelinck,et al.  Effect of Familiarity on the Processing of Human Faces , 1999, NeuroImage.

[14]  A. Young,et al.  Neural responses to facial and vocal expressions of fear and disgust , 1998, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[15]  D. Weinberger,et al.  Neocortical modulation of the amygdala response to fearful stimuli , 2003, Biological Psychiatry.

[16]  J. Seckl,et al.  Mechanisms of Disease: glucocorticoids, their placental metabolism and fetal 'programming' of adult pathophysiology , 2007, Nature Clinical Practice Endocrinology &Metabolism.

[17]  A. Eskild,et al.  Review of validation studies of the Edinburgh Postnatal Depression Scale. , 2001 .

[18]  A. Eskild,et al.  Review of validation studies of the Edinburgh Postnatal Depression Scale , 2001, Acta psychiatrica Scandinavica.

[19]  D. Nagin,et al.  Depression and anxiety symptoms: onset, developmental course and risk factors during early childhood. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

[20]  A. Young,et al.  A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder , 2005, Biological Psychiatry.

[21]  Colm G. Connolly,et al.  Resting-State Functional Connectivity of Subgenual Anterior Cingulate Cortex in Depressed Adolescents , 2013, Biological Psychiatry.

[22]  M. Furey,et al.  Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression , 2008, Brain Structure and Function.

[23]  J. P. Hamilton,et al.  Neural Substrates of Increased Memory Sensitivity for Negative Stimuli in Major Depression , 2008, Biological Psychiatry.

[24]  K. Braun,et al.  Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy , 2006, The European journal of neuroscience.

[25]  A. Ishai,et al.  Effective connectivity within the distributed cortical network for face perception. , 2007, Cerebral cortex.

[26]  J. Pickens,et al.  Newborns of mothers with depressive symptoms are less expressive , 1996 .

[27]  Peter Seres,et al.  Fronto-limbic volumetric changes in major depressive disorder. , 2012, Journal of affective disorders.

[28]  M. Hoptman,et al.  Functional connectivity in apathy of late-life depression: a preliminary study. , 2013, Journal of affective disorders.

[29]  A. Mian Depression in pregnancy and the postpartum period: balancing adverse effects of untreated illness with treatment risks. , 2005, Journal of psychiatric practice.

[30]  Christina B. Young,et al.  Amygdala Subregional Structure and Intrinsic Functional Connectivity Predicts Individual Differences in Anxiety During Early Childhood , 2014, Biological Psychiatry.

[31]  Jens C. Pruessner,et al.  Deactivation of the Limbic System During Acute Psychosocial Stress: Evidence from Positron Emission Tomography and Functional Magnetic Resonance Imaging Studies , 2008, Biological Psychiatry.

[32]  Alan C. Evans,et al.  Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth , 2011, Proceedings of the National Academy of Sciences.

[33]  A. Salm,et al.  Lateral amygdaloid nucleus expansion in adult rats is associated with exposure to prenatal stress. , 2004, Brain research. Developmental brain research.

[34]  M. Holmes,et al.  Prenatal Excess Glucocorticoid Exposure and Adult Affective Disorders: A Role for Serotonergic and Catecholamine Pathways , 2011, Neuroendocrinology.

[35]  Katiuscia Sacco,et al.  Functional connectivity of the insula in the resting brain , 2011, NeuroImage.

[36]  P. V. Eijndhoven,et al.  Amygdala Volume Marks the Acute State in the Early Course of Depression , 2009, Biological Psychiatry.

[37]  Mario Dzemidzic,et al.  Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression , 2009, Psychiatry Research: Neuroimaging.

[38]  H. Anisman,et al.  Maternal programming of defensive responses through sustained effects on gene expression , 2006, Biological Psychology.

[39]  D. Amaral,et al.  Amygdalo‐cortical projections in the monkey (Macaca fascicularis) , 1984, The Journal of comparative neurology.

[40]  Michael G. Hardin,et al.  Attention alters neural responses to evocative faces in behaviorally inhibited adolescents , 2007, NeuroImage.

[41]  D L Newman,et al.  Behavioral observations at age 3 years predict adult psychiatric disorders. Longitudinal evidence from a birth cohort. , 1996, Archives of general psychiatry.

[42]  A. Campagnoni,et al.  Serum factors and hydrocortisone influence the synthesis of myelin basic proteins in mouse brain primary cultures , 1994, International Journal of Developmental Neuroscience.

[43]  J. Cox,et al.  Screening for depression during pregnancy with the edinburgh depression scale (EDDS) , 1990 .

[44]  Michael S. Gaffrey,et al.  Disrupted amygdala reactivity in depressed 4- to 6-year-old children. , 2013, Journal of the American Academy of Child and Adolescent Psychiatry.

[45]  Junming Shao,et al.  Aberrant Intrinsic Connectivity of Hippocampus and Amygdala Overlap in the Fronto-Insular and Dorsomedial-Prefrontal Cortex in Major Depressive Disorder , 2013, Front. Hum. Neurosci..

[46]  L. Kooistra,et al.  Validation of the Edinburgh Depression Scale during pregnancy. , 2011, Journal of psychosomatic research.

[47]  R. Cabeza,et al.  Interaction between the Amygdala and the Medial Temporal Lobe Memory System Predicts Better Memory for Emotional Events , 2004, Neuron.

[48]  Laura V. Scaramella,et al.  Implications of Timing of Maternal Depressive Symptoms for Early Cognitive and Language Development , 2006, Clinical child and family psychology review.

[49]  Rebecca C. Knickmeyer,et al.  Regional Gray Matter Growth, Sexual Dimorphism, and Cerebral Asymmetry in the Neonatal Brain , 2007, The Journal of Neuroscience.

[50]  Erno J. Hermans,et al.  From Specificity to Sensitivity: How Acute Stress Affects Amygdala Processing of Biologically Salient Stimuli , 2009, Biological Psychiatry.

[51]  James P. Herman,et al.  Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis , 2005, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[52]  J. Pardo,et al.  Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[53]  David L. Shaul,et al.  Postpartum adjustment in first-time mothers: Relations between mood, maternal attitudes, and mother-infant interactions. , 1988 .

[54]  A. Chicz–DeMet,et al.  Prenatal exposure to maternal depression and cortisol influences infant temperament. , 2007, Journal of the American Academy of Child and Adolescent Psychiatry.

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

[56]  J. Buitelaar,et al.  Psychological measures of prenatal stress as predictors of infant temperament. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[57]  J. van os,et al.  Transition from stress sensitivity to a depressive state: longitudinal twin study , 2009, British Journal of Psychiatry.

[58]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[59]  Peter Fransson,et al.  Resting-state networks in the infant brain , 2007, Proceedings of the National Academy of Sciences.

[60]  Randy L. Buckner,et al.  Individual Differences in Amygdala-Medial Prefrontal Anatomy Link Negative Affect, Impaired Social Functioning, and Polygenic Depression Risk , 2012, The Journal of Neuroscience.

[61]  H. Blumberg,et al.  Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder. , 2013, Journal of psychiatry & neuroscience : JPN.

[62]  P A Turski,et al.  Metabolic rate in the right amygdala predicts negative affect in depressed patients , 1998, Neuroreport.

[63]  H. Critchley,et al.  Neural Activity in the Human Brain Relating to Uncertainty and Arousal during Anticipation , 2001, Neuron.

[64]  J. Price,et al.  Neurocircuitry of Mood Disorders , 2010, Neuropsychopharmacology.

[65]  Jr James G. Hazel Atlas of Fetal and Postnatal Brain MR , 2011 .

[66]  Paul Feb. Griffiths,et al.  Atlas of Fetal and Postnatal Brain MR , 2009 .

[67]  K. Dumont,et al.  A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up. , 2007, Archives of general psychiatry.

[68]  Ray Norbury,et al.  Risk for depression and neural responses to fearful facial expressions of emotion. , 2009, The British journal of psychiatry : the journal of mental science.

[69]  B. Shahbaba,et al.  Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems , 2012, Proceedings of the National Academy of Sciences.

[70]  Martin P Paulus,et al.  Amygdala response and functional connectivity during emotion regulation: a study of 14 depressed adolescents. , 2012, Journal of affective disorders.