Childhood Maltreatment Alters the Neural Processing of Chemosensory Stress Signals

Accumulating evidence suggests that childhood maltreatment (CM) confers risk for psychopathology later in life by inducing hypervigilance to social threat cues such as fearful faces. However, it remains unclear whether the modulatory impact of CM extents to the olfactory domain of social communication in humans. To address this question, we examined whether CM modulates the neural processing of chemosensory threat signals in sweat and whether CM affects the stress-reducing effects of oxytocin (OXT) in this context. In a randomized, double-blind within-subject functional MRI study design, 58 healthy participants (30 females) received intranasal OXT (40 IU) or placebo (PLC) and completed a forced-choice emotion recognition task with faces of varying emotion intensities (neutral to fearful) while exposed to sweat stimuli and a non-social control odor. Axillary sweat samples were collected from 30 healthy male donors undergoing an acute psychosocial stressor (stress) and ergometer training (sport) as control in a pre-study. CM was assessed by the 25-item Childhood Trauma Questionnaire (CTQ). The final fMRI analysis included 50 healthy participants (26 females). Regression analysis showed a stress-specific association of CTQ scores with amygdala hyperreactivity, hippocampal deactivation, and increased functional connectivity between the amygdala and the hippocampus, medial orbitofrontal cortex, and the anterior cingulate cortex (ACC) under PLC. Furthermore, we observed a positive association of CTQ scores and the dampening effects of OXT on stress-related amygdala responses. Our findings suggest that CM may induce hypervigilance to chemosensory threat cues in a healthy sample due to inefficient frontolimbic inhibition of amygdala activation. Future studies should investigate whether increased recruitment of the intralimbic amygdala-hippocampus complex reflects a compensatory mechanism that prevents the development of psychopathology in those who have experienced CM. Furthermore, the results reveal that the stress-specific effects of OXT in the olfactory domain are more pronounced in participants with increasing levels of CM exposure.

[1]  K. Roelofs,et al.  Oxytocin Normalizes Approach–Avoidance Behavior in Women With Borderline Personality Disorder , 2020, Frontiers in Psychiatry.

[2]  R. Kievit,et al.  The complex neurobiology of resilient functioning after childhood maltreatment , 2020, BMC Medicine.

[3]  Christina F. Chick,et al.  Identification of Common Neural Circuit Disruptions in Emotional Processing Across Psychiatric Disorders. , 2020, The American journal of psychiatry.

[4]  K. Ioannidis,et al.  The Resilient Emotional Brain: A Scoping Review of the Medial Prefrontal Cortex and Limbic Structure and Function in Resilient Adults With a History of Childhood Maltreatment. , 2019, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[5]  Martin H. Teicher,et al.  Association of Prepubertal and Postpubertal Exposure to Childhood Maltreatment With Adult Amygdala Function. , 2019, JAMA psychiatry.

[6]  L. E. Kunsta,et al.  Intranasal oxytocin enhances stress-protective effects of social support in women with negative childhood experiences during a virtual Trier Social Stress Test , 2019 .

[7]  J. Schultz,et al.  Association of Childhood Maltreatment With Interpersonal Distance and Social Touch Preferences in Adulthood. , 2019, The American journal of psychiatry.

[8]  C. Schmahl,et al.  Adverse Childhood Experiences and the Consequences on Neurobiological, Psychosocial, and Somatic Conditions Across the Lifespan , 2018, Front. Psychiatry.

[9]  T. Uhde,et al.  Paradoxical olfactory function in combat Veterans: The role of PTSD and odor factors , 2018, Military psychology : the official journal of the Division of Military Psychology, American Psychological Association.

[10]  Qing X. Yang,et al.  Preliminary evidence for differential olfactory and trigeminal processing in combat veterans with and without PTSD☆☆☆ , 2017, NeuroImage: Clinical.

[11]  Ruskin H. Hunt,et al.  Separable Effects of Childhood Maltreatment and Adult Adaptive Functioning on Amygdala Connectivity During Emotion Processing. , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[12]  W. Maier,et al.  Oxytocin reduces a chemosensory-induced stress bias in social perception , 2018, Neuropsychopharmacology.

[13]  Sarah K. G. Jensen,et al.  Biological embedding of childhood adversity: from physiological mechanisms to clinical implications , 2017, BMC Medicine.

[14]  Christos Davatzikos,et al.  Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity , 2017, NeuroImage.

[15]  E. Nestler,et al.  Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2 , 2017, Science.

[16]  René Hurlemann,et al.  How the brain codes intimacy: The neurobiological substrates of romantic touch , 2017, Human brain mapping.

[17]  M. Bensafi,et al.  Detection of sickness in conspecifics using olfactory and visual cues , 2017, Proceedings of the National Academy of Sciences.

[18]  M. Wiesmann,et al.  Chemosensory danger detection in the human brain: Body odor communicating aggression modulates limbic system activation , 2017, Neuropsychologia.

[19]  Tobias U. Hauser,et al.  The PhysIO Toolbox for Modeling Physiological Noise in fMRI Data , 2017, Journal of Neuroscience Methods.

[20]  S. W. Rieger,et al.  Fear Spreading Across Senses: Visual Emotional Events Alter Cortical Responses to Touch, Audition, and Vision , 2016, Cerebral cortex.

[21]  Frank Schneider,et al.  Chemosensory anxiety cues enhance the perception of fearful faces – An fMRI study , 2016, NeuroImage.

[22]  Kyoko Ohashi,et al.  The effects of childhood maltreatment on brain structure, function and connectivity , 2016, Nature Reviews Neuroscience.

[23]  C. Nemeroff.  Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse and Neglect , 2016, Neuron.

[24]  Michael L. Thomas,et al.  Minimization of Childhood Maltreatment Is Common and Consequential: Results from a Large, Multinational Sample Using the Childhood Trauma Questionnaire , 2016, PloS one.

[25]  A. Simmons,et al.  Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood , 2015, Psychological Medicine.

[26]  Ruskin H. Hunt,et al.  Long-term consequences of childhood maltreatment: Altered amygdala functional connectivity , 2015, Development and Psychopathology.

[27]  David D Vachon,et al.  Assessment of the Harmful Psychiatric and Behavioral Effects of Different Forms of Child Maltreatment. , 2015, JAMA psychiatry.

[28]  S. Patten,et al.  Consistency in adult reporting of adverse childhood experiences , 2015, Psychological Medicine.

[29]  D. Gitelman,et al.  Olfactory-visual integration facilitates perception of subthreshold negative emotion , 2015, Neuropsychologia.

[30]  T. Fujiwara,et al.  Association of oxytocin level and less severe forms of childhood maltreatment history among healthy Japanese adults involved with child care , 2015, Front. Behav. Neurosci..

[31]  Amit Etkin,et al.  Childhood Trauma Exposure Disrupts the Automatic Regulation of Emotional Processing , 2015, Neuropsychopharmacology.

[32]  Rajendra A. Morey,et al.  Amygdala–Prefrontal Cortex Functional Connectivity During Threat-Induced Anxiety and Goal Distraction , 2015, Biological Psychiatry.

[33]  Katrin T. Lübke,et al.  Always follow your nose: The functional significance of social chemosignals in human reproduction and survival , 2015, Hormones and Behavior.

[34]  J. Pruessner,et al.  Early life stress modulates oxytocin effects on limbic system during acute psychosocial stress. , 2014, Social cognitive and affective neuroscience.

[35]  Jonathan D. Power,et al.  Statistical improvements in functional magnetic resonance imaging analyses produced by censoring high‐motion data points , 2014, Human brain mapping.

[36]  Onur Güntürkün,et al.  An Oxytocin-Induced Facilitation of Neural and Emotional Responses to Social Touch Correlates Inversely with Autism Traits , 2014, Neuropsychopharmacology.

[37]  Cory A. Burghy,et al.  Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence , 2013, Proceedings of the National Academy of Sciences.

[38]  C. Büchel,et al.  Oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder. , 2013, The American journal of psychiatry.

[39]  I. Croy,et al.  Reduced olfactory bulb volume in adults with a history of childhood maltreatment. , 2013, Chemical senses.

[40]  Maarten A. S. Boksem,et al.  Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal , 2013, European Neuropsychopharmacology.

[41]  K. Petrowski,et al.  Altered Olfactory Processing of Stress-Related Body Odors and Artificial Odors in Patients with Panic Disorder , 2013, PloS one.

[42]  Florian Holsboer,et al.  Resting state functional MRI connectivity predicts hypothalamus-pituitary-axis status in healthy males , 2013, Psychoneuroendocrinology.

[43]  K. Luan Phan,et al.  The contextual brain: implications for fear conditioning, extinction and psychopathology , 2013, Nature Reviews Neuroscience.

[44]  A. Hayes.  Introduction to Mediation, Moderation, and Conditional Process Analysis: A Regression-Based Approach , 2013 .

[45]  A. Guastella,et al.  Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research , 2013, Psychoneuroendocrinology.

[46]  M. Bakermans-Kranenburg,et al.  Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy , 2013, Translational Psychiatry.

[47]  A. Simmons,et al.  Neural functional and structural correlates of childhood maltreatment in women with intimate-partner violence-related posttraumatic stress disorder , 2013, Psychiatry Research: Neuroimaging.

[48]  M. Bakermans-Kranenburg,et al.  Oxytocin decreases handgrip force in reaction to infant crying in females without harsh parenting experiences. , 2012, Social cognitive and affective neuroscience.

[49]  Monique A M Smeets,et al.  Chemosignals Communicate Human Emotions , 2012, Psychological science.

[50]  Sterling C. Johnson,et al.  A generalized form of context-dependent psychophysiological interactions (gPPI): A comparison to standard approaches , 2012, NeuroImage.

[51]  G. Demas,et al.  Maternal Contact Differentially Modulates Central and Peripheral Oxytocin in Rat Pups During a Brief Regime of Mother–Pup Interaction that Induces a Filial Huddling Preference , 2012, Journal of neuroendocrinology.

[52]  Asya Karchemskiy,et al.  BRAIN ACTIVATION TO FACIAL EXPRESSIONS IN YOUTH WITH PTSD SYMPTOMS , 2012, Depression and anxiety.

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

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

[55]  C. Mohiyeddini,et al.  Experience of stress in childhood negatively correlates with plasma oxytocin concentration in adult men , 2012, Stress.

[56]  Geoffrey Bird,et al.  Heightened neural reactivity to threat in child victims of family violence , 2011, Current Biology.

[57]  Peter Kirsch,et al.  Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine , 2011, Nature Reviews Neuroscience.

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

[59]  Justin S. Feinstein,et al.  The Human Amygdala and the Induction and Experience of Fear , 2011, Current Biology.

[60]  C. Lemogne,et al.  Olfactory system and emotion: common substrates. , 2011, European annals of otorhinolaryngology, head and neck diseases.

[61]  I. Liberzon,et al.  The Neurocircuitry of Fear, Stress, and Anxiety Disorders , 2011, Neuropsychopharmacology.

[62]  J. Gottfried.  Central mechanisms of odour object perception , 2010, Nature Reviews Neuroscience.

[63]  F. Ansermet,et al.  Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence , 2010, Neuroscience.

[64]  I. Croy,et al.  PTSD, but not childhood maltreatment, modifies responses to unpleasant odors. , 2010, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[65]  Monique Ernst,et al.  A preliminary study of medial temporal lobe function in youths with a history of caregiver deprivation and emotional neglect , 2010, Cognitive, affective & behavioral neuroscience.

[66]  I. Croy,et al.  Women with a History of Childhood Maltreatment Exhibit more Activation in Association Areas Following Non-Traumatic Olfactory Stimuli: A fMRI Study , 2010, PloS one.

[67]  R. Kessler,et al.  Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. , 2010, Archives of general psychiatry.

[68]  K. Felmingham,et al.  Neural responses to masked fear faces: sex differences and trauma exposure in posttraumatic stress disorder. , 2010, Journal of abnormal psychology.

[69]  R. Stevenson.  REVIEW An Initial Evaluation of the Functions of Human Olfaction , 2022 .

[70]  A. Prehn-Kristensen,et al.  Startle response potentiation to chemosensory anxiety signals in socially anxious individuals. , 2009, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[71]  Benoist Schaal,et al.  The Secretion of Areolar (Montgomery's) Glands from Lactating Women Elicits Selective, Unconditional Responses in Neonates , 2009, PloS one.

[72]  C. Nemeroff,et al.  Lower CSF oxytocin concentrations in women with a history of childhood abuse , 2009, Molecular Psychiatry.

[73]  Denis Rubin,et al.  Chemosensory Cues to Conspecific Emotional Stress Activate Amygdala in Humans , 2009, PloS one.

[74]  A. Prehn-Kristensen,et al.  Induction of Empathy by the Smell of Anxiety , 2009, PloS one.

[75]  C. Sarafoleanu,et al.  The importance of the olfactory sense in the human behavior and evolution , 2009, Journal of medicine and life.

[76]  D. Fergusson,et al.  Burden and consequences of child maltreatment in high-income countries , 2008, The Lancet.

[77]  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.

[78]  Kamryn T. Eddy,et al.  Amygdala-frontal connectivity during emotion regulation. , 2007, Social cognitive and affective neuroscience.

[79]  W. Brewer,et al.  Olfactory identification dysfunction, aggression and impulsivity in war veterans with post-traumatic stress disorder , 2007, Psychological Medicine.

[80]  Claus C. Hilgetag,et al.  Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala , 2007, NeuroImage.

[81]  R. Bluhm,et al.  A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation. , 2006, Journal of psychiatric research.

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

[83]  E. Phelps.  Human emotion and memory: interactions of the amygdala and hippocampal complex , 2004, Current Opinion in Neurobiology.

[84]  C. Kirschbaum,et al.  Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress , 2003, Biological Psychiatry.

[85]  E. Rolls,et al.  Different representations of pleasant and unpleasant odours in the human brain , 2003, The European journal of neuroscience.

[86]  M. Newcomb,et al.  Development and validation of a brief screening version of the Childhood Trauma Questionnaire. , 2003, Child abuse & neglect.

[87]  Robert T. Knight,et al.  Orbitofrontal cortex and dynamic filtering of emotional stimuli , 2002, Cognitive, affective & behavioral neuroscience.

[88]  S. Baron-Cohen,et al.  The Autism-Spectrum Quotient (AQ): Evidence from Asperger Syndrome/High-Functioning Autism, Malesand Females, Scientists and Mathematicians , 2001, Journal of autism and developmental disorders.

[89]  M. Meaney,et al.  Variations in Maternal Behaviour are Associated with Differences in Oxytocin Receptor Levels in the Rat , 2000, Journal of neuroendocrinology.

[90]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[91]  T. Hummel,et al.  'Sniffin' sticks': olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. , 1997, Chemical senses.

[92]  Tore Dybå,et al.  : experience in a , 1997 .

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

[94]  C. Kirschbaum,et al.  The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting. , 1993, Neuropsychobiology.

[95]  D. A. Kenny,et al.  The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. , 1986, Journal of personality and social psychology.

[96]  C. Spielberger,et al.  Manual for the State-Trait Anxiety Inventory , 1970 .