Abuse in early childhood often leads to depression, although typically not expressed until later in life. How child abuse alters the trajectory of brain development to produce a vulnerability to depression is incompletely understood. We propose to study an experimental model of parental abuse in rats where abuse during a sensitive period in infancy produces disrupted social behavior, increased immobility in a Forced Swim Test (FST) animal model of depression, and amygdala dysfunction. In this proposal we focus on the effects of abuse during infancy and early life on both behavior and brain (amygdala, prefrontal cortex).
In Aim 1 we questions if there is a sensitive period of vulnerability to abuse to cause depressive-like behaviors? Aim 2 we ask if the ontogeny of the amygdala or neural circuits activated during social behavior or FST in developing rats is altered by early life abuse.
In Aim 3 we question if the amygdala or prefrontal cortex or its connectivity to the PFC, which are brain areas strongly impacted by early life trauma, contribute to the behavioral dysfunction following early life abuse. The innovation and significance of our proposed work is that we use a Sensitive Period model that incorporates how the timing of perturbation (abuse) and context of perturbation (presence or absence of mother) interacts with maturational processes to enhance vulnerability to later life depressive-like symptoms. We will question how the infant brain's response to perturbation can differ depending on the time and context of perturbation and question how these experiences alter infant behaviors. This approach will enable us to not only identify infant events that contribute to later life dysfunction but also explore unique behavior and neural changes in the infant to predict later life dysfunction. We will use infants'well-defined sensitive periods for caregiver-attachment learning and infants'unique neurobehavioral response to trauma (maltreatment from mother or more controlled shock) during each period. Furthermore, this work also highlights the strong influence of social interactions and social cues (reared by abusive mother or shock with/without mother) during clearly defined sensitive periods. Indeed, our published data has begun to suggest that the infants'immediate neural response to trauma is dramatically different from the adults'but importantly, that it further differs depending on whether the mother is present.

Public Health Relevance

Adverse experiences during childhood, such as abuse/trauma, increases the incidence of depression in later life. To better understand how this experience alters later life mental health, we use a Sensitive Period model that incorporates how the timing of perturbation (abuse) and context of perturbation (presence or absence of mother) interacts with maturational processes to enhance vulnerability to later life depressive-like symptoms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH091451-04
Application #
8484444
Study Section
Special Emphasis Panel (ZMH1-ERB-L (02))
Program Officer
Zehr, Julia L
Project Start
2010-07-10
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2013
Total Cost
$387,353
Indirect Cost
$74,931
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Debiec, Jacek; Sullivan, Regina M (2016) The neurobiology of safety and threat learning in infancy. Neurobiol Learn Mem :
Tallot, L; Doyère, V; Sullivan, R M (2016) Developmental emergence of fear/threat learning: neurobiology, associations and timing. Genes Brain Behav 15:144-54
Perry, Rosemarie E; Al Aïn, Syrina; Raineki, Charlis et al. (2016) Development of Odor Hedonics: Experience-Dependent Ontogeny of Circuits Supporting Maternal and Predator Odor Responses in Rats. J Neurosci 36:6634-50
Boulanger Bertolus, Julie; Mouly, Anne-Marie; Sullivan, Regina M (2016) Ecologically relevant neurobehavioral assessment of the development of threat learning. Learn Mem 23:556-66
Gunnar, Megan R; Hostinar, Camelia E; Sanchez, Mar M et al. (2015) Parental buffering of fear and stress neurobiology: Reviewing parallels across rodent, monkey, and human models. Soc Neurosci 10:474-8
Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie et al. (2015) Paradoxical neurobehavioral rescue by memories of early-life abuse: the safety signal value of odors learned during abusive attachment. Neuropsychopharmacology 40:906-14
Sullivan, Regina M; Perry, Rosemarie E (2015) Mechanisms and functional implications of social buffering in infants: Lessons from animal models. Soc Neurosci 10:500-11
Debiec, Jacek; Sullivan, Regina Marie (2014) Intergenerational transmission of emotional trauma through amygdala-dependent mother-to-infant transfer of specific fear. Proc Natl Acad Sci U S A 111:12222-7
Perry, Rosemarie; Sullivan, Regina M (2014) Neurobiology of attachment to an abusive caregiver: short-term benefits and long-term costs. Dev Psychobiol 56:1626-34
Hostinar, Camelia E; Sullivan, Regina M; Gunnar, Megan R (2014) Psychobiological mechanisms underlying the social buffering of the hypothalamic-pituitary-adrenocortical axis: a review of animal models and human studies across development. Psychol Bull 140:256-82

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