Oxytocin and Brain Responses in Maternal Addiction

Overview

A prior study by the principal investigator of this project identified dopamine- and oxytocin-related brain pathways that showed a diminished response when addicted mothers viewed the faces of their own vs. unknown infants, compared with non-addicted mothers. These areas include the hypothalamus, striatum and ventromedial prefrontal cortex. Oxytocin, a neuropeptide with decreased blood levels seen in addicted mothers, is integrally involved in maternal brain and behavioral responses. When administered intranasally, the pilot data has shown enhanced activation of the striatum, prefrontal cortex (PFC) and amygdala.

The purpose of this study is to continue and expand upon the previous investigation of maternal addiction, by conducting a randomized, double-blinded, placebo controlled, crossover study of intranasal oxytocin on maternal brain responses. 150 mothers from the University of Iowa and the Yale Child Study Center will be enrolled (75 with a history of drug addiction and 75 matched control mothers), along with their 2 to 12-month-old infants, to participate in four study visits over a two-month period.

Full Title of Study: “Oxytocin and Brain Reward and Stress Responses to Infant Cues in Addicted Mothers”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: January 2021

Detailed Description

Maternal drug addiction constitutes a major public health problem for both women and affected children, with long lasting consequences on children's social, emotional and cognitive development. Current treatment strategies tend to focus on the mother and her current addiction, rather than her relationship with her child, and developmental processes that may perpetuate the addiction problems, such as unresolved childhood attachment trauma, neglect, and chronic stress. Unlike mothers who find engaging with their own infant to be a uniquely rewarding experience, mothers with addictions may be less able to respond appropriately to their infant's cues, finding them less intrinsically rewarding or salient, and more stress provoking.

Aim 1: To examine, in addicted mothers compared to non-addicted control mothers, the effect of intranasal oxytocin (OT) on functional MRI brain responses to reward-related cues: own vs. unknown happy infant faces.

Aim 2: To examine, in addicted mothers compared to non-addicted control mothers, the effect of intranasal OT on brain responses to stress-related cues: own vs. unknown sad infant faces and cries.

Aim 3: To examine the effect of intranasal OT on functional brain connectivity, including the striatum, PFC and amygdala. Specifically, exploring whether, after receiving intranasal OT compared to placebo, addicted mothers show increased functional connectivity between the amygdala and (i) the ventromedial PFC for own-happy infant faces, and (ii) the dorsolateral PFC and striatum for own-sad faces.

Aim 4: To explore how individual differences in adult attachment and mother-infant synchrony, sensation-seeking/risk-taking and stress/trauma exposure are associated with OT brain responses to infant faces.

Interventions

  • Drug: Oxytocin
    • All women in both groups will receive 2 fMRIs according to our research protocol. Fifty minutes before the first fMRI, the women will administer nasal spray which will randomly contain either oxytocin or placebo. A month later the woman will return for the 2nd fMRI and administer nasal spray containing the substance they did not receive at the first scan. The randomization is double blinded with only the pharmacy knowing which nasal spray to provide at which fMRI visit.
  • Drug: Placebos
    • All women in both groups will receive 2 fMRIs according to our research protocol. Fifty minutes before the first fMRI, the women will administer nasal spray which will randomly contain either oxytocin or placebo. A month later the woman will return for the 2nd fMRI and administer nasal spray containing the substance they did not receive at the first scan. The randomization is double blinded with only the pharmacy knowing which nasal spray to provide at which fMRI visit.

Arms, Groups and Cohorts

  • Other: Addicted
    • The addiction group will be scanned twice using functional magnetic resonance imaging (fMRI). Subjects will be randomly assigned to receive either the active comparator (intranasal oxytocin spray) or the placebo comparator before the first scanning session. For the second scan (approximately one month later), the subject will receive the other spray which she did not receive at the time of the first scan.
  • Other: Control
    • The control group will be scanned twice using functional magnetic resonance imaging (fMRI). Subjects will be randomly assigned to receive either the active comparator (intranasal oxytocin spray) or the placebo comparator before the first scanning session. For the second scan (approximately one month later), the subject will receive the other spray which she did not receive at the time of the first scan.

Clinical Trial Outcome Measures

Primary Measures

  • Effect of intranasal oxytocin on brain fMRI activation, independent of addiction status
    • Time Frame: 50 minutes after administration of oxytocin or placebo
    • Specific regions of interests include the striatum and amygdala
  • Effect of intranasal oxytocin on brain fMRI activation in addicted vs controls mothers
    • Time Frame: 50 minutes after administration of oxytocin or placebo
    • Specific region of interest includes the prefrontal cortex

Participating in This Clinical Trial

Inclusion Criteria for addiction sample:

Drug-addicted subjects will be English speaking adult women who:

1. are being evaluated for treatment of their addiction or are currently enrolled in treatment programs;

2. have an infant <12 months;

3. meet criteria for substance abuse or dependence in the past year, as assessed by MINI International Neuropsychiatric Interview (MINI);

4. have a substance abuse history, including use during the most recent pregnancy;

5. are recommended at intake for drug-treatment services for substance abuse;

6. are 18 years and older; and

7. have been speaking English or enrolled in English-speaking school since age 8.

Inclusion Criteria for non-addicted mothers (controls):

Control subjects will be English-speaking adult women who:

1. have an infant <12 months of age;

2. do not meet criteria for past or present drug abuse or dependence;

3. are 18 years and older; and

4. have been speaking English or enrolled in English-speaking school since age 8.

Exclusion Criteria for addiction sample:

Potential drug-addicted subjects will be ineligible if they have:

1. severe psychiatric or substance-related symptoms requiring in-patient psychiatric hospitalization or detoxification for suicidality, homicidality, grave disability, physiological alcohol or drug withdrawal within the last 30 days;

2. past or present diagnosis of schizophrenia or other psychotic disorders;

3. metal implants or other contraindications for MRI scanning;

4. pending legal cases (e.g., outstanding arrest warrants or parental rights hearings) prohibiting them from completing the study;

5. current pregnancy or plans to become pregnant during the course of the study;

6. infants with clinical evidence of in utero drug effects, such as opiate withdrawal symptoms during the neonatal period, facial dysmorphism or intrauterine growth restriction (IUGR) or microcephaly;

7. infants with birth weight less than 3 lb. 5 oz.;

8. infants who have significant vision, hearing or motor problems (such as cerebral palsy) that cannot be corrected;

9. out-of-home placement of infant for the past month or more than 50% of child's life;

10. delivered more than one baby during most recent pregnancy (twins, triplets, etc.).

Exclusion criteria for non-addicted mothers:

Potential control subjects will be ineligible if they have:

1. positive drug toxicology screen at the time of study;

2. drug abuse or dependence based on MINI in the past year or lifetime;

3. use of tobacco products in the past 2 years;

4. current hazardous alcohol use as ascertained by AUDIT score > 8;

5. present or past history of ambulatory detoxification;

6. severe psychiatric symptoms requiring inpatient psychiatric hospitalization for suicidality, homicidality, grave disability, physiological alcohol or drug withdrawal within the past 30 days;

7. past or present diagnosis of schizophrenia or other psychotic disorders;

8. metal implants or other contraindications for MRI scanning;

9. current pregnancy or plans to become pregnant during the course of the study;

10. infants with birth weight less than 3 lb. 5 oz.;

11. infants who have significant vision, hearing or motor problems that cannot be corrected (such as cerebral palsy);

12. out-of-home placement of infant for the past month or more than 50% of child's life; and

13. delivered more than one baby during most recent pregnancy (twins, triplets, etc.).

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Lane Strathearn, MBBS PhD
  • Collaborator
    • Yale University
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Lane Strathearn, MBBS PhD, Professor – University of Iowa
  • Overall Official(s)
    • Lane Strathearn, MBBS PhD, Principal Investigator, University of Iowa
    • Linda Mayes, MD, Principal Investigator, Yale University
    • Helena Rutherford, PhD, Principal Investigator, Yale University
  • Overall Contact(s)
    • Lane Strathearn, MBBS, PhD, 319-356-7044, lane-strathearn@uiowa.edu

References

SAMHSA, "Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings" (Substance Abuse and Mental Health Services Administration, Rockville, MD, 2012).

Chaffin M, Kelleher K, Hollenberg J. Onset of physical abuse and neglect: psychiatric, substance abuse, and social risk factors from prospective community data. Child Abuse Negl. 1996 Mar;20(3):191-203.

Rutherford HJ, Williams SK, Moy S, Mayes LC, Johns JM. Disruption of maternal parenting circuitry by addictive process: rewiring of reward and stress systems. Front Psychiatry. 2011 Jul 6;2:37. doi: 10.3389/fpsyt.2011.00037. eCollection 2011.

Strathearn L, Li J, Fonagy P, Montague PR. What's in a smile? Maternal brain responses to infant facial cues. Pediatrics. 2008 Jul;122(1):40-51. doi: 10.1542/peds.2007-1566. Erratum in: Pediatrics. 2008 Sep;122(3):689.

Kim S, Fonagy P, Allen J, Strathearn L. Mothers' unresolved trauma blunts amygdala response to infant distress. Soc Neurosci. 2014;9(4):352-63. doi: 10.1080/17470919.2014.896287. Epub 2014 Mar 17.

L. C. Mayes, R. Feldman, R. Granger, The effects of polydrug use with and without cocaine on mother infant interaction at 3 and 6 months. Infant behavior & development 20, 489 (1997).

Strathearn L, Mayes LC. Cocaine addiction in mothers: potential effects on maternal care and infant development. Ann N Y Acad Sci. 2010 Feb;1187:172-83. doi: 10.1111/j.1749-6632.2009.05142.x. Review.

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