Oxytocin and Brain Responses in Maternal Addiction

Maternal Behavior Clinical Trial

Official title:

Oxytocin and Brain Reward and Stress Responses to Infant Cues in Addicted Mothers

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02979093
• Other study ID #: 201601749
• Status: Terminated
• Phase: Phase 2
• Start date: May 5, 2017
• Est. completion date: May 17, 2021

Study information

• Verified date: November 2022
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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. In addition, the investigators plan to examine activation patterns within the salience network, which includes the anterior cingulate cortex and the anterior insula. 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.

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.

Aim 5: To examine the effect of intranasal OT on activation of the salience network in addicted mothers, as well as connectivity patterns between these regions and the amygdala. We predict that there will be noticeable increase in activity in the salience network (dorsal anterior cingulate and anterior insula) after administering OT. We predict the addiction group will have a greater affect from the OT treatment than the control group.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 73
• Est. completion date: May 17, 2021
• Est. primary completion date: May 17, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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 to 40 years old; 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 to 40 years old; 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. mothers who have significant vision or hearing problems that cannot be corrected;

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

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

12. exclusively breastfeeding

Exclusion criteria for non-addicted mothers:

Potential control subjects will be ineligible if they have:

1. positive drug toxicology screen at any point in the 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. mothers who have significant vision or hearing problems that cannot be corrected;

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

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

15. exclusively breastfeeding

Related Conditions & MeSH terms

• Behavior, Addictive
• Maternal Behavior

Intervention

Drug:
• Oxytocin
All women will receive a nasal spray containing oxytocin.
• Placebos
All women will receive a nasal spray containing a placebo solution.

Procedure:
• Functional MRI scanning
Study participants undergo two functional MRI scans.

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa
United States	Yale Child Study Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Lane Strathearn, MBBS PhD	Yale University

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. doi: 10.1016/s0145-2134(95)00144-1. — View Citation

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. — View Citation

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).

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. — View Citation

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).

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. — View Citation

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. — View Citation

Strathearn L, Mertens CE, Mayes L, Rutherford H, Rajhans P, Xu G, Potenza MN, Kim S. Pathways Relating the Neurobiology of Attachment to Drug Addiction. Front Psychiatry. 2019 Nov 8;10:737. doi: 10.3389/fpsyt.2019.00737. eCollection 2019. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of intranasal oxytocin on brain fMRI activation, independent of addiction status	Specific regions of interests include the striatum and amygdala	50 minutes after administration of oxytocin or placebo
Primary	Effect of intranasal oxytocin on brain fMRI activation in addicted vs controls mothers	Specific region of interest includes the prefrontal cortex	50 minutes after administration of oxytocin or placebo