Anxiety Disorders, Depression, Postpartum, Stress, Psychological
Conditions
Keywords
Oxytocin, Hypothalamic-pituitary-adrenal axis (HPA)
Brief summary
Mothers who were enrolled in the Mood, Mother and Infant study will be eligible to participate in the 6-year follow-up maternal visit. At the time of this visit, mothers will be randomized to a single 24 IU dose of nasal oxytocin or placebo. Following administration of the study drug, women will participate in the Trier Social Stress Test (TSST), and blood samples will be collected to quantify HPA axis reactivity.
Detailed description
The Mood, Mother and Infant Study is a prospective observational cohort study that began enrollment in May of 2013. Women were recruited in the 3rd trimester of pregnancy and followed prospectively through 12 months postpartum. Mother-infant pairs who completed the 12-month visit will be invited to participate in the current Psychobiology of Resilience in Maternal-Child Pairs follow-up study. The trial described here is a randomized controlled trial embedded within the Psychobiology of Resilience study. Non-pregnant women will be randomized to either 24 IU of nasal oxytocin (OT) or placebo. The Investigational Drug Service (IDS) will use a random number generator to prepare a randomization table. Participants will be block randomized by risk status at enrollment in the Mood, Mother and Infant (MMI) study, as verified by structured clinical diagnostic interview (No history of depression or anxiety, Past depression or anxiety, current depression or anxiety). Both participants and study personnel will be blinded to allocation group. At the end of the protocol, participants will be asked which condition they believed they were in ('oxytocin,' 'control,' 'not sure') to ascertain success of blinding. Forty minutes after treatment, women will undergo the Trier Social Stress Test (TSST), comprised of a speech task and a math task; the TSST reliably induces large and consistent HPA and cardiovascular responses. The TSST is administered as follows: Pre-Task Instructions: (5 minutes) Subjects will be introduced to 3 people (the 'selection committee') and asked to assume the role of a job applicant. Anticipation Period: The subject prepares her speech for 3 minutes in the presence of the committee. Speech: The committee asks the subject to deliver her talk for 5 minutes while being video and audio-recorded. If the subject finishes early, the committee responds with prepared questions to ensure that she speaks for the entire 5 minutes. These questions are designed to be non-harassing but to create a feeling of lack of predictability/controllability (e.g., Do you have any enemies?) Serial Subtraction (PASST): The committee will ask the subject to subtract the number 7 from 2000 as quickly and accurately as possible for 5 minutes. For each mistake, the committee says Stop -- mistake -- start over at 2000. Stress Recovery: The subject sits quietly alone for 20 minutes. Blood will be collected at baseline, during the speech and math tasks, and at 10 and 20 minutes of recovery, as HPA-axis responses are reliably found 10-30 minutes following the TSST. Evidence regarding optimal timing of stress testing is conflicting. Visits will be scheduled for 1 pm to increase likelihood of detecting a stress response unopposed by the circadian influence, based on the experience of investigators in our laboratory and published studies of postpartum women. These investigators have found menstrual cycle phase does not affect TSST results; therefore, the date of last menstrual period and hormone use will be recorded, but visits will not be scheduled based on cycle phase.
Interventions
DRUGIntranasal Oxytocin
Six intranasal sprays of oxytocin. Each insufflation delivers 4 IUs of oxytocin for a total oxytocin dosage of 24 IUs.
DRUGPlacebo
Six intranasal sprays of placebo manufactured to mimic oxytocin nasal spray containing all equivalent ingredients except oxytocin.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants will receive a nasal insufflation bottle of oxytocin intranasal spray or placebo intranasal spray manufactured to mimic oxytocin nasal spray.
Intervention model description
Non-pregnant women will be randomized to either 24 IU of nasal OT or placebo. The Investigational Drug Service will use a random number generator to prepare a randomization table.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
This study will follow-up the existing Mood, Mother and Infant (MMI) prospective longitudinal cohort (R01HD073220), comprised of 222 mother-infant dyads who were recruited between May 2013 and April 2017 and completed the 12-month MMI visit. In the MMI study, 222 mothers ages 18-45 and their infants were enrolled. Participants were recruited from community clinics in the third trimester of pregnancy and continued to participate in the study through 12 months postpartum. At the 12-month visit, mothers were invited to continue to be followed via online surveys at 6-month intervals; more than 80% of women who have completed the MMI study to date have continued to participate. Enrolled participants in the MMI study met the following inclusion and
Exclusion criteria
Inclusion Criteria: 1. Singleton pregnancy; 2. Intention to breastfeed (due to the centrality of breastfeeding to the oxytocin assessment); 3. Intention to remain within 40 miles of the University of North Carolina - Chapel Hill through infant's first birthday; 4. Ability to communicate in English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | The study drug will be administered 40 minutes before the TSST. Serum cortisol will be measured via peripheral IV 40 (-40) and 20 (-20) minutes before the TSST, at the start of the TSST (0 minutes), and at minutes 10 (during the speech task), 15 (during the math task), 28, 38, and 48 (during recovery). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Adrenocorticotropic Hormone (ACTH ) During TSST | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | The study drug will be administered 40 minutes before the TSST. Adrenocorticotropic hormone will be measured via peripheral IV 40 (-40) and 20 (-20) minutes before the TSST, at the start of the TSST (0 minutes), and at minutes 10 (during the speech task), 15 (during the math task), 28, 38, and 48 (during recovery). |
| Lagged Association Between ACTH and CRT During the TSST | ACTH at -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes and Cortisol at -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | Correlations will be quantified between ACTH at time j and CRT at time j+1 to test the extent to which CRT response is blunted by exogenous oxytocin (OT). |
| Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48 | Recording of autonomic activity beginning prior to study drug administration (-40 minutes) until the end of recovery from the TSST (+38 minutes). Mobile Impedance Cardiographs (MindWare Tech Ltd, Gahanna, OH) was used to measure cardiac rate and interbeat interval (IBI). MindWare Heart Rate Variability (HRV) software was used to derive respiration and to calculate high frequency respiratory sinus arrhythmia power from the IBI series as an index of parasympathetic activity. Results are reported as difference from the mean of high frequency respiratory sinus arrhythmia power measured in the first ten minutes of the study visit, prior to administration of OT or placebo. |
| Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48 | Recording of autonomic activity beginning prior to study drug administration (-40 minutes) until the end of recovery from the TSST (+38 minutes). Mobile Impedance Cardiographs (MindWare Tech Ltd, Gahanna, OH) will be used to measure pre-ejection period (PEP). PEP will index sympathetic activation. Results are reported as difference from the mean of pre-ejection period measured in the first ten minutes of the study visit, prior to administration of OT or placebo. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Effect Modification by OXTR Genotype on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST | -30 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on ACTH during the TSST. |
| Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST) | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on CRT during the TSST. |
| Assessment of Effect Modification by OXTR Genotype on Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48 | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on sympathetic activity during the TSST. |
| Assessment of Effect Modification by OXTR Genotype Changes in High Frequency Heart Rate Variability, an Index of Parasympathetic Activity, During the TSST | Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48 | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on parasympathetic activity during the TSST. |
| Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on ACTH during the TSST. |
| Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in High Frequency Heart Rate Variability, an Index of Parasympathetic Activity, During the TSST | Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48 | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on parasympathetic activity during the TSST. |
| Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48 | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on sympathetic activity during the TSST. |
| Assessment of Effect Modification by Oxytocin Receptor (OXTR) Genotype on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST) | -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes | Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on CRT during the TSST. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intranasal Oxytocin Participants block randomized to Oxytocin intranasal spray by risk status at enrollment in the Mood, Mother and Infant (MMI) study and as verified by structured clinical diagnostic interview (no history of depression or anxiety, past depression or anxiety, current depression or anxiety).
Intranasal Oxytocin: Six intranasal sprays of oxytocin. Each insufflation delivers 4 IUs of oxytocin for a total oxytocin dosage of 24 IUs. | 51 |
| Placebo Participants block randomized to placebo Intranasal spray with all equivalent ingredients except oxytocin. Blocks will be stratified by risk status at enrollment in the Mood, Mother and Infant (MMI) study and as verified by structured clinical diagnostic interview (no history of depression or anxiety, past depression or anxiety, current depression or anxiety).
Placebo: Six intranasal sprays of placebo manufactured to mimic oxytocin nasal spray containing all equivalent ingredients except oxytocin. | 54 |
| Total | 105 |
Baseline characteristics
| Characteristic | Intranasal Oxytocin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 37.63 years STANDARD_DEVIATION 4.38 | 37.95 years STANDARD_DEVIATION 4.17 | 38.26 years STANDARD_DEVIATION 3.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 95 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 11 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 84 Participants | 44 Participants |
| Region of Enrollment United States | 51 Participants | 105 Participants | 54 Participants |
| Sex: Female, Male Female | 51 Participants | 105 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 54 |
| other Total, other adverse events | 0 / 51 | 1 / 54 |
| serious Total, serious adverse events | 0 / 51 | 0 / 54 |
Outcome results
Primary
Mean Cortisol (CRT) During Trier Social Stress Test (TSST)
The study drug will be administered 40 minutes before the TSST. Serum cortisol will be measured via peripheral IV 40 (-40) and 20 (-20) minutes before the TSST, at the start of the TSST (0 minutes), and at minutes 10 (during the speech task), 15 (during the math task), 28, 38, and 48 (during recovery).
Time frame: -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes
Population: Samples were collected by IV. In some participants, an IV was not able to be placed and samples could not be collected. In some participants, an IV was successfully placed, but the IV infiltrated before the end of the observation period and not all timepoints were collected. One participant had a vasovagal episode when the IV was placed and samples were not collected. All collected data are reported herein.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intranasal Oxytocin | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +48 minutes | 13.16 pg/mL | Standard Deviation 9.35 |
| Intranasal Oxytocin | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | -40 minutes | 19.17 pg/mL | Standard Deviation 13.46 |
| Intranasal Oxytocin | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | -20 minutes | 15.71 pg/mL | Standard Deviation 10.16 |
| Intranasal Oxytocin | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | 0 minutes | 14.06 pg/mL | Standard Deviation 10.41 |
| Intranasal Oxytocin | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +10 minutes | 14.39 pg/mL | Standard Deviation 10.55 |
| Intranasal Oxytocin | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +15 minutes | 15.27 pg/mL | Standard Deviation 12.56 |
| Intranasal Oxytocin | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +28 minutes | 16.78 pg/mL | Standard Deviation 13.63 |
| Intranasal Oxytocin | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +38 minutes | 14.50 pg/mL | Standard Deviation 12.02 |
| Placebo | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +38 minutes | 15.40 pg/mL | Standard Deviation 9.66 |
| Placebo | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +48 minutes | 14.41 pg/mL | Standard Deviation 9.02 |
| Placebo | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | 0 minutes | 13.03 pg/mL | Standard Deviation 8.99 |
| Placebo | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +10 minutes | 13.60 pg/mL | Standard Deviation 9.45 |
| Placebo | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | -40 minutes | 16.87 pg/mL | Standard Deviation 10.84 |
| Placebo | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +28 minutes | 16.29 pg/mL | Standard Deviation 9.44 |
| Placebo | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | -20 minutes | 13.89 pg/mL | Standard Deviation 9.68 |
| Placebo | Mean Cortisol (CRT) During Trier Social Stress Test (TSST) | +15 minutes | 15.64 pg/mL | Standard Deviation 10.16 |
Comparison: T-test comparing mean cortisol by study arm at 10 minutes.p-value: 0.72t-test, 2 sided
Comparison: T-test comparing mean cortisol by study arm at -40 minutes.p-value: 0.37t-test, 2 sided
Comparison: T-test comparing mean cortisol by study arm at -20 minutes.p-value: 0.4t-test, 2 sided
Comparison: T-test comparing mean cortisol by study arm at 0 minutes.p-value: 0.63t-test, 2 sided
Comparison: T-test comparing mean cortisol by study arm at 15 minutes.p-value: 0.88t-test, 2 sided
Comparison: T-test comparing mean cortisol by study arm at 28 minutes.p-value: 0.85t-test, 2 sided
Comparison: T-test comparing mean cortisol by study arm at 38 minutes.p-value: 0.72t-test, 2 sided
Comparison: T-test comparing mean cortisol by study arm at 48 minutes.p-value: 0.57t-test, 2 sided
Comparison: A mixed effects model with random intercept and slope was used to model cortisol as the outcome variable with time, study arm, and an interaction between time and study arm as the exposure variables. Times are restricted to times 0, +10, +15, and +28, which reflect the measures taken during the Trier Social Stress Test. The p-value presented below is for the interaction term between time and study arm.p-value: 0.96Mixed Models Analysis
Secondary
Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST
Recording of autonomic activity beginning prior to study drug administration (-40 minutes) until the end of recovery from the TSST (+38 minutes). Mobile Impedance Cardiographs (MindWare Tech Ltd, Gahanna, OH) was used to measure cardiac rate and interbeat interval (IBI). MindWare Heart Rate Variability (HRV) software was used to derive respiration and to calculate high frequency respiratory sinus arrhythmia power from the IBI series as an index of parasympathetic activity. Results are reported as difference from the mean of high frequency respiratory sinus arrhythmia power measured in the first ten minutes of the study visit, prior to administration of OT or placebo.
Time frame: Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48
Population: For two participants in each arm, cardiograph recording was unsuccessful. For some time periods for some participants, data quality or quantity (in terms of lacking sufficient numbers of epochs within a period) was insufficient for analysis. All valid, analyzable data are reported herein.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -35 to -30 | -54.8211 ms squared | Standard Deviation 341 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 8 to 13 | -142.7 ms squared | Standard Deviation 729.6 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -15 to -10 | -65.0835 ms squared | Standard Deviation 303.9 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 13 to 18 | -166 ms squared | Standard Deviation 702.4 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -25 to -20 | 8.1879 ms squared | Standard Deviation 412.4 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 18 to 23 | -54.7814 ms squared | Standard Deviation 538.4 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -10 to -5 | -40.6283 ms squared | Standard Deviation 291 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 23 to 28 | -55.4212 ms squared | Standard Deviation 376.5 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -30 to -25 | 25.9791 ms squared | Standard Deviation 520.3 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 28 to 33 | -2.1457 ms squared | Standard Deviation 484.3 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -5 to 0 | -66.7889 ms squared | Standard Deviation 365.5 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 33 to 38 | 10.4342 ms squared | Standard Deviation 551.7 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -20 to -15 | 29.8191 ms squared | Standard Deviation 355.4 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 38 to 43 | -31.2704 ms squared | Standard Deviation 497 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 5 to 8 | -213.8 ms squared | Standard Deviation 577.3 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 43 to 48 | -66.8297 ms squared | Standard Deviation 498.9 |
| Intranasal Oxytocin | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -40 to -35 | 9.4867 ms squared | Standard Deviation 367.6 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 43 to 48 | 82.3593 ms squared | Standard Deviation 289.3 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -40 to -35 | 25.2298 ms squared | Standard Deviation 426.2 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -35 to -30 | -76.7692 ms squared | Standard Deviation 476.9 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -30 to -25 | -34.2107 ms squared | Standard Deviation 513.2 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -25 to -20 | -85.2953 ms squared | Standard Deviation 494 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -20 to -15 | -34.1119 ms squared | Standard Deviation 427.6 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -15 to -10 | -50.8918 ms squared | Standard Deviation 363 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -10 to -5 | -65.8414 ms squared | Standard Deviation 487.4 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | -5 to 0 | -0.2369 ms squared | Standard Deviation 440.3 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 5 to 8 | -60.7299 ms squared | Standard Deviation 424.1 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 8 to 13 | -93.6755 ms squared | Standard Deviation 585.2 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 13 to 18 | 45.2548 ms squared | Standard Deviation 701.9 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 18 to 23 | 140.5 ms squared | Standard Deviation 416 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 23 to 28 | 90.0612 ms squared | Standard Deviation 574.9 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 28 to 33 | 78.347 ms squared | Standard Deviation 480 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 33 to 38 | 94.173 ms squared | Standard Deviation 439.2 |
| Placebo | Changes in High Frequency Respiratory Sinus Arrhythmia Power, an Index of Parasympathetic Activity, During the TSST | 38 to 43 | 74.8732 ms squared | Standard Deviation 390.8 |
Comparison: High frequency heart rate variability at minutes -40 to -35p-value: 0.8441t-test, 2 sided
Comparison: High frequency heart rate variability at minutes -35 to -30p-value: 0.7919t-test, 2 sided
Comparison: High frequency heart rate variability at minutes -30 to -25p-value: 0.5639t-test, 2 sided
Comparison: High frequency heart rate variability at minutes -25 to -20p-value: 0.3139t-test, 2 sided
Comparison: High frequency heart rate variability at minutes -20 to -15p-value: 0.4222t-test, 2 sided
Comparison: High frequency heart rate variability at minutes -15 to -10p-value: 0.834t-test, 2 sided
Comparison: High frequency heart rate variability at minutes -10 to -5p-value: 0.7562t-test, 2 sided
Comparison: High frequency heart rate variability at minutes -5 to 0p-value: 0.4245t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 5 to 8p-value: 0.1425t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 8 to 13p-value: 0.7175t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 13 to 18p-value: 0.1417t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 18 to 23p-value: 0.0514t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 23 to 28p-value: 0.1507t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 8 to 33p-value: 0.4204t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 33 to 38p-value: 0.4209t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 38 to 43p-value: 0.2569t-test, 2 sided
Comparison: High frequency heart rate variability at minutes 43 to 48p-value: 0.0828t-test, 2 sided
Secondary
Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST
Recording of autonomic activity beginning prior to study drug administration (-40 minutes) until the end of recovery from the TSST (+38 minutes). Mobile Impedance Cardiographs (MindWare Tech Ltd, Gahanna, OH) will be used to measure pre-ejection period (PEP). PEP will index sympathetic activation. Results are reported as difference from the mean of pre-ejection period measured in the first ten minutes of the study visit, prior to administration of OT or placebo.
Time frame: Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48
Population: For some participants in each arm, cardiograph recording was unsuccessful. For some time periods for some participants, data quality or quantity (in terms of lacking sufficient numbers of epochs within a period) was insufficient for analysis. All valid, analyzable data are reported herein.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 18 to 23 | 0.3473 milliseconds | Standard Deviation 6.8964 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 23 to 28 | 1.0633 milliseconds | Standard Deviation 5.9026 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -40 to -35 | -0.0133 milliseconds | Standard Deviation 5.0895 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -35 to -30 | -0.4379 milliseconds | Standard Deviation 4.6949 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -30 to -25 | -0.0765 milliseconds | Standard Deviation 4.8828 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -25 to -20 | 0.1364 milliseconds | Standard Deviation 5.4471 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -20 to -15 | 0.4913 milliseconds | Standard Deviation 6.0127 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -15 to -10 | 0.396 milliseconds | Standard Deviation 6.5937 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -10 to -5 | 0.1857 milliseconds | Standard Deviation 5.745 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -5 to 0 | 0.7484 milliseconds | Standard Deviation 5.8793 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 28 to 33 | 1.47 milliseconds | Standard Deviation 5.9291 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 33 to 38 | 1.1908 milliseconds | Standard Deviation 5.6515 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 38 to 43 | 1.3179 milliseconds | Standard Deviation 5.8975 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 43 to 48 | 1.2028 milliseconds | Standard Deviation 5.8875 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 5 to 8 | -4.9659 milliseconds | Standard Deviation 7.7046 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 8 to 13 | -4.9797 milliseconds | Standard Deviation 14.7581 |
| Intranasal Oxytocin | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 13 to 18 | -4.4699 milliseconds | Standard Deviation 14.2813 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 13 to 18 | -7.2932 milliseconds | Standard Deviation 12.2579 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 18 to 23 | -1.7225 milliseconds | Standard Deviation 5.6289 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 23 to 28 | -0.5384 milliseconds | Standard Deviation 5.2814 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -5 to 0 | -2.3991 milliseconds | Standard Deviation 5.8181 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -40 to -35 | -0.5344 milliseconds | Standard Deviation 5.2068 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 43 to 48 | -0.833 milliseconds | Standard Deviation 4.2802 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -35 to -30 | -1.578 milliseconds | Standard Deviation 5.6245 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 28 to 33 | -0.3492 milliseconds | Standard Deviation 4.7881 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -30 to -25 | -1.2421 milliseconds | Standard Deviation 6.3071 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 8 to 13 | -6.7011 milliseconds | Standard Deviation 12.5175 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -25 to -20 | -0.9139 milliseconds | Standard Deviation 6.4616 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 33 to 38 | -0.706 milliseconds | Standard Deviation 4.7005 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -20 to -15 | -0.743 milliseconds | Standard Deviation 5.4354 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 5 to 8 | -6.9426 milliseconds | Standard Deviation 14.7706 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -15 to -10 | -1.2658 milliseconds | Standard Deviation 6.5275 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | 38 to 43 | -0.3979 milliseconds | Standard Deviation 4.7213 |
| Placebo | Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST | -10 to -5 | -1.9649 milliseconds | Standard Deviation 6.0961 |
Comparison: Pre-ejection period at minutes -35 to -30p-value: 0.3228t-test, 2 sided
Comparison: Pre-ejection period at minutes -40 to -35p-value: 0.6452t-test, 2 sided
Comparison: Pre-ejection period at minutes -30 to -25p-value: 0.3541t-test, 2 sided
Comparison: Pre-ejection period at minutes -25 to -20p-value: 0.4311t-test, 2 sided
Comparison: Pre-ejection period at minutes -20 to -15p-value: 0.3349t-test, 2 sided
Comparison: Pre-ejection period at minutes -15 to -10p-value: 0.2646t-test, 2 sided
Comparison: Pre-ejection period at minutes -10 to -5p-value: 0.1095t-test, 2 sided
Comparison: Pre-ejection period at minutes -5 to 0p-value: 0.0194t-test, 2 sided
Comparison: Pre-ejection period at minutes 5 to 8p-value: 0.473t-test, 2 sided
Comparison: Pre-ejection period at minutes 8 to 13p-value: 0.5768t-test, 2 sided
Comparison: Pre-ejection period at minutes 13 to 18p-value: 0.3477t-test, 2 sided
Comparison: Pre-ejection period at minutes 18 to 23p-value: 0.1413t-test, 2 sided
Comparison: Pre-ejection period at minutes 23 to 28p-value: 0.2128t-test, 2 sided
Comparison: Pre-ejection period at minutes 28 to 33p-value: 0.1415t-test, 2 sided
Comparison: Pre-ejection period at minutes 33 to 38p-value: 0.1126t-test, 2 sided
Comparison: Pre-ejection period at minutes 38 to 43p-value: 0.1647t-test, 2 sided
Comparison: Pre-ejection period at minutes 43 to 48p-value: 0.088t-test, 2 sided
Secondary
Lagged Association Between ACTH and CRT During the TSST
Correlations will be quantified between ACTH at time j and CRT at time j+1 to test the extent to which CRT response is blunted by exogenous oxytocin (OT).
Time frame: ACTH at -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes and Cortisol at -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes
Population: Samples were collected by IV. In some participants, an IV was not able to be placed and samples could not be collected. In some participants, an IV was successfully placed, but the IV infiltrated before the end of the observation period and not all timepoints were collected. One participant had a vasovagal episode when the IV was placed and samples were not collected. All collected data are reported herein.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intranasal Oxytocin | Lagged Association Between ACTH and CRT During the TSST | ACTH at +28 minutes with Cortisol at +38 minutes | 0.10 Correlation coefficient |
| Intranasal Oxytocin | Lagged Association Between ACTH and CRT During the TSST | ACTH at +10 minutes with Cortisol at +15 minutes | 0.01 Correlation coefficient |
| Intranasal Oxytocin | Lagged Association Between ACTH and CRT During the TSST | ACTH at -20 minutes with 0 minutes | 0.04 Correlation coefficient |
| Intranasal Oxytocin | Lagged Association Between ACTH and CRT During the TSST | ACTH at +15 minutes with Cortisol at +28 minutes | -0.04 Correlation coefficient |
| Intranasal Oxytocin | Lagged Association Between ACTH and CRT During the TSST | ACTH at -40 minutes with Cortisol at -20 minutes | 0.07 Correlation coefficient |
| Intranasal Oxytocin | Lagged Association Between ACTH and CRT During the TSST | ACTH at +38 minutes with Cortisol at +48 minutes | 0.29 Correlation coefficient |
| Intranasal Oxytocin | Lagged Association Between ACTH and CRT During the TSST | ACTH at 0 minutes with Cortisol at +10 minutes | 0.16 Correlation coefficient |
| Placebo | Lagged Association Between ACTH and CRT During the TSST | ACTH at +38 minutes with Cortisol at +48 minutes | 0.26 Correlation coefficient |
| Placebo | Lagged Association Between ACTH and CRT During the TSST | ACTH at -40 minutes with Cortisol at -20 minutes | 0.44 Correlation coefficient |
| Placebo | Lagged Association Between ACTH and CRT During the TSST | ACTH at -20 minutes with 0 minutes | 0.31 Correlation coefficient |
| Placebo | Lagged Association Between ACTH and CRT During the TSST | ACTH at 0 minutes with Cortisol at +10 minutes | 0.46 Correlation coefficient |
| Placebo | Lagged Association Between ACTH and CRT During the TSST | ACTH at +10 minutes with Cortisol at +15 minutes | 0.34 Correlation coefficient |
| Placebo | Lagged Association Between ACTH and CRT During the TSST | ACTH at +28 minutes with Cortisol at +38 minutes | 0.47 Correlation coefficient |
| Placebo | Lagged Association Between ACTH and CRT During the TSST | ACTH at +15 minutes with Cortisol at +28 minutes | 0.40 Correlation coefficient |
Comparison: Fisher's Z test for correlation between ACTH at -40 minutes and Cortisol at -20 minutes.p-value: 0.07Fisher's Z test
Comparison: Fisher's Z test for correlation between ACTH at -20 minutes and Cortisol at 0 minutes.p-value: 0.22Fisher's Z test
Comparison: Fisher's Z test for correlation between ACTH at 0 minutes and Cortisol at +10 minutes.p-value: 0.14Fisher's Z test
Comparison: Fisher's Z test for correlation between ACTH at +10 minutes and Cortisol at +15 minutes.p-value: 0.14Fisher's Z test
Comparison: Fisher's Z test for correlation between ACTH at +15 minutes and Cortisol at +28 minutes.p-value: 0.05Fisher's Z test
Comparison: Fisher's Z test for correlation between ACTH at +28 minutes and Cortisol at +38 minutes.p-value: 0.1Fisher's Z test
Comparison: Fisher's Z test for correlation between ACTH at +38 minutes and Cortisol at +48 minutes.p-value: 0.9Fisher's Z test
Comparison: A mixed effects model with random intercept and slope was used to model cortisol at time j+1 as the outcome with ACTH at time j, study arm, and an interaction term between ACTH at time j and study arm as the exposure variables. The p-value presented below is for the interaction term between ACTH at time j and study arm.p-value: 0.21Mixed Models Analysis
Secondary
Mean Adrenocorticotropic Hormone (ACTH ) During TSST
The study drug will be administered 40 minutes before the TSST. Adrenocorticotropic hormone will be measured via peripheral IV 40 (-40) and 20 (-20) minutes before the TSST, at the start of the TSST (0 minutes), and at minutes 10 (during the speech task), 15 (during the math task), 28, 38, and 48 (during recovery).
Time frame: -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes
Population: Samples were collected by IV. In some participants, an IV was not able to be placed and samples could not be collected. In some participants, an IV was successfully placed, but the IV infiltrated before the end of the observation period and not all timepoints were collected. One participant had a vasovagal episode when the IV was placed and samples were not collected. All collected data are reported herein.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intranasal Oxytocin | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | -40 minutes | 79.96 pg/mL | Standard Deviation 64.89 |
| Intranasal Oxytocin | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | -20 minutes | 85.73 pg/mL | Standard Deviation 68.28 |
| Intranasal Oxytocin | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | 0 minutes | 84.31 pg/mL | Standard Deviation 54.49 |
| Intranasal Oxytocin | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +10 minutes | 80.31 pg/mL | Standard Deviation 59.49 |
| Intranasal Oxytocin | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +15 minutes | 93.46 pg/mL | Standard Deviation 59.92 |
| Intranasal Oxytocin | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +28 minutes | 84.02 pg/mL | Standard Deviation 64.26 |
| Intranasal Oxytocin | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +38 minutes | 79.38 pg/mL | Standard Deviation 63.01 |
| Intranasal Oxytocin | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +48 minutes | 77.27 pg/mL | Standard Deviation 63.69 |
| Placebo | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +48 minutes | 85.30 pg/mL | Standard Deviation 74.79 |
| Placebo | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | -40 minutes | 86.77 pg/mL | Standard Deviation 103 |
| Placebo | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +15 minutes | 94.21 pg/mL | Standard Deviation 104 |
| Placebo | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | -20 minutes | 87.61 pg/mL | Standard Deviation 92.74 |
| Placebo | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +38 minutes | 84.01 pg/mL | Standard Deviation 81.48 |
| Placebo | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | 0 minutes | 86.10 pg/mL | Standard Deviation 93.42 |
| Placebo | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +28 minutes | 77.48 pg/mL | Standard Deviation 87.08 |
| Placebo | Mean Adrenocorticotropic Hormone (ACTH ) During TSST | +10 minutes | 94.00 pg/mL | Standard Deviation 86.89 |
Comparison: T-test comparing mean ACTH by study arm at -40 minutes.p-value: 0.71t-test, 2 sided
Comparison: T-test comparing mean ACTH by study arm at -20 minutes.p-value: 0.92t-test, 2 sided
Comparison: T-test comparing mean ACTH by study arm at 0 minutes.p-value: 0.92t-test, 2 sided
Comparison: T-test comparing mean ACTH by study arm at 10 minutes.p-value: 0.4t-test, 2 sided
Comparison: T-test comparing mean ACTH by study arm at 15 minutes.p-value: 0.97t-test, 2 sided
Comparison: T-test comparing mean ACTH by study arm at 28 minutes.p-value: 0.71t-test, 2 sided
Comparison: T-test comparing mean ACTH by study arm at 38 minutes.p-value: 0.78t-test, 2 sided
Comparison: T-test comparing mean ACTH by study arm at 48 minutes.p-value: 0.63t-test, 2 sided
Comparison: A mixed effects model with random intercept and slope was used to model cortisol as the outcome variable with time, study arm, and an interaction between time and study arm as the exposure variables. This is the p-value for the interaction term between time and study arm.p-value: 0.11Mixed Models Analysis
Other Pre-specified
Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST
Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on ACTH during the TSST.
Time frame: -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes
Other Pre-specified
Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST)
Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on CRT during the TSST.
Time frame: -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes
Other Pre-specified
Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in High Frequency Heart Rate Variability, an Index of Parasympathetic Activity, During the TSST
Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on parasympathetic activity during the TSST.
Time frame: Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48
Other Pre-specified
Assessment of Effect Modification by Maternal Depression / Anxiety on Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST
Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on sympathetic activity during the TSST.
Time frame: Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48
Other Pre-specified
Assessment of Effect Modification by OXTR Genotype Changes in High Frequency Heart Rate Variability, an Index of Parasympathetic Activity, During the TSST
Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on parasympathetic activity during the TSST.
Time frame: Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48
Other Pre-specified
Assessment of Effect Modification by OXTR Genotype on Changes in Adrenocorticotropic Hormone (ACTH ) During TSST
Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on ACTH during the TSST.
Time frame: -30 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes
Other Pre-specified
Assessment of Effect Modification by OXTR Genotype on Changes in Pre-ejection Period, an Index of Sympathetic Activity, During the TSST
Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on sympathetic activity during the TSST.
Time frame: Minutes -40 to -35, -35 to -30, -30 to -25, -25 to -20, -20 to -15, -15 to -10, -10 to -5, -5 to 0, 0 to 5, 5 to 8, 8 to 13, 13 to 18, 18 to 23, 23 to 28, 28 to 33, 33 to 38, 38 to 43, 43 to 48
Other Pre-specified
Assessment of Effect Modification by Oxytocin Receptor (OXTR) Genotype on Changes in Cortisol (CRT) During Trier Social Stress Test (TSST)
Stratified analyses will be performed to determine the extent to which maternal depression/anxiety modifies the effect of OT/placebo on CRT during the TSST.
Time frame: -40 minutes, -20 minutes, 0 minutes, +10 minutes, +15 minutes, +28 minutes, +38 minutes, +48 minutes