Neurobiological Bases of Paternal Nurturance

Not Applicable

Completed

Conditions: Healthy

Interventions: Drug: Oxytocin
Drug: Vasopressin
Drug: Placebo

Registration Number: NCT02223429

Lead Sponsor: James K. Rilling, PhD

Brief Summary: The overall goal of this project is to identify the genetic, hormonal, and neurobiological influences on paternal nurturing behavior and to determine if fathers' neural responses to infants can be modulated by neuropeptides known to play a role in parenting in experimental animal models.

The aim is to determine if pharmacological manipulation of central oxytocin (OT) and vasopressin (AVP) levels influences the neural response to viewing pictures of one's own infant or to hearing cry stimuli. In a double-blind procedure, fathers with 1-3 year old children will be scanned on two separate occasions; once under the influence of OT/AVP and once under the influence of placebo. Fathers will be randomized to either OT or AVP, and order of administration of drug and placebo will counterbalanced across subjects. Fathers will be scanned while viewing pictures of their own and an unknown child and while listening to unknown infant cry stimuli.

The investigators hypothesize:

* OT will augment the ventral tegmental area (VTA), ventral striatum and medial orbitofrontal cortex (mOFC) response to viewing pictures of one's own child, and will augment the primary auditory cortex (AI) response of fathers to infant cries.

* AVP will augment the lateral septum response to viewing own child pictures.

Detailed Description: 30 fathers of children aged 1-3 will participate in two functional imaging sequence (fMRI) sessions, once under the influence of OT/AVP, and once under the influence of placebo. Fathers will be restricted to men who are living with their biological child and an adult partner (male or female) that they are in a committed relationship with. All fathers will receive two fMRI scans on two different occasions, separated by 2-10 days. 15 fathers will be randomized to intranasal OT, the other 15 will be randomized to intranasal AVP. Within each drug group, the order of administration of drug and placebo will counterbalanced across subjects, such that 15 will receive OT/AVP first, and 15 will receive OT/AVP second. During the fMRI scans, fathers will view pictures of their own and unknown children, as well as unknown adults. Afterwards, while still in the scanner, they will listen to infant cry and control stimuli. After exiting the scanner, fathers will again listen to the cry stimuli and will rate their emotional reaction to the cry stimuli on the following dimensions using a 7 point likert scale: irritated, sympathetic, alarmed, angry, upset, compassionate, distressed, annoyed, and tender.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

Inclusion Criteria

above 18
biological fathers of 1-3 year old infants who are currently cohabitating with the child's mother
normal or corrected-to-normal vision of 20/40

Exclusion Criteria

current or past history of mental illness
active medical or neurological disorder
current or past history of alcohol or drug dependence
claustrophobic (at the discretion of the PI with subject consultation)
history of seizures or other neurological disorder
history of hypertension, cardiovascular disease, nephritis, diabetes or other endocrine diseases or malignancy
ferrous metal in any part of the body
history of asthma or migraine headaches (can be included at the discretion of the study physician or nurse practitioner if episodes are infrequent and no active problems at time of study, not medicated)
history of head trauma or psychiatric illness, as well as those who are receiving or have received over the past year, medication with known psychoactive effects (included at the discretion of the PI as these are exclusion criteria due to data quality concerns and not safety concerns; head trauma should be minimal enough deemed by the PI)

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
OT + placebo	Placebo	The OT + placebo group will self-administer no more than 1 ml solution of oxytocin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo will counterbalanced across subjects, such that half will receive OT first, and half will receive OT second.
AVP + placebo	Placebo	The AVP + placebo group will self-administer no more than 1 ml solution of vasopressin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo will counterbalanced across subjects, such that half will receive AVP first, and half will receive AVP second.
OT + placebo	Oxytocin	The OT + placebo group will self-administer no more than 1 ml solution of oxytocin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo will counterbalanced across subjects, such that half will receive OT first, and half will receive OT second.
AVP + placebo	Vasopressin	The AVP + placebo group will self-administer no more than 1 ml solution of vasopressin or placebo in each nostril; five (5) sprays per each nostril, for a total of ten (10) sprays. The order of administration of drug and placebo will counterbalanced across subjects, such that half will receive AVP first, and half will receive AVP second.

Primary Outcome Measures

Name	Time	Method
Mean Percent Signal Change in the Anterior Cingulate Cortex	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).
Mean Percent Signal Change in Caudate Nucleus	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).
Mean Percent Signal Change in Ventral Tegmental Area (VTA)	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
Mean Percent Signal Change in Right Ventral Striatum	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
Mean Percent Signal Change in the Visual Cortex	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI).
Mean Percent Signal Change in Right Medial Orbitofrontal Cortex	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.

Secondary Outcome Measures

Name	Time	Method
Difference in Cry Rating Scores Between OT and Placebo	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under OT and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents "not at all" and 7 represents "extremely". Difference is defined as OT minus placebo scores.
Change in Plasma Levels of Vasopressin (AVP)	Baseline, Visit 2 (Up to 10 days)	Peripheral levels of AVP will be assessed via assay of plasma collected.
Change in Plasma Levels of Oxytocin (OT)	Baseline, Visit 2 (Up to 10 days)	Peripheral levels of OT will be assessed via assay of plasma collected.
Mean Percent Signal Change in Primary Auditory Cortex	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between OT treatment and placebo treatments (OT-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the OT group only per protocol.
Difference in Cry Rating Scores Between AVP and Placebo	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by analyzing the differences between ratings of infant cries under AVP and placebo treatment on a 7-point likert scale. Sixteen adjectives will be used to describe two different cries. Participants will rate each cry from 1-7 where one represents "not at all" and 7 represents "extremely". Difference is defined as AVP minus placebo scores.
Mean Percent Signal Change in Right Lateral Septum	Baseline, Visit 2 (Up to 10 days)	The effect of the drug will be assessed by determining changes in brain activation to own child pictures versus adult pictures (O-A) between AVP treatment and placebo treatments (AVP-PL) from functional magnetic resonance imaging (fMRI). Changes will be assessed in the AVP group only per protocol.