Oxytocin and behaviors during a parent-child interaction in children with and without OCD: A statistical analysis plan
Creators: name: Clemmensen, Line
name: Mora-Jensen, Anna-Rosa Cecilie
name: Lønfeldt, Nicole Nadine
name: Pagsberg, Anne Katrine
name: Thoustrup, Christine Lykke
Publisher: name: OSF Registries
Year: 2024
Subjects: subject: Psychiatry and Psychology
subject: Medicine and Health Sciences
subject: behavior
subject: child
subject: obsessive-compulsive disorder
subject: parenting
subject: psychiatry
subject: youth

description: Aim
In this study, we wish to explore if the oxytocin system is connected to parent and child behaviors during parent-child interactions. We will first test specific hypotheses and then perform exploratory analyses.


1) Hypothesis testing
Rationale:
Oxytocin has been suggested to be connected to parenting behaviors in mammals1 and has been associated with parental sensitivity1 and affectionate parenting behaviors in humans2.
Hypotheses:
- Children and parents’ oxytocin concentrations are positively associated with observed parental support sensitivity and dyadic emotional warmth.
- Child oxytocin concentration is negatively associated with child reassurance seeking behavior.


2) Exploratory analyses
We will explore:
- If parent and child behaviors cluster in higher-level constructs that describe the variation in children with and without OCD.
- If any potential higher-level constructs are associated with parent and child oxytocin concentrations.
- Which parent and child behaviors during a parent-child interaction best predict parent and child oxytocin concentrations.


Methods
We will use data from the TECTO trial that consists of 130 children with OCD and their parents and 90 sex- and aged matched controls without current or previous psychiatric disorders and their parents. Our study is a baseline investigation of oxytocin and behavioral data.


Measures:
Oxytocin:
We use information from salivary oxytocin concentrations collected with Salivettes (Sarstedt, Germany) and analyzed with Enzo immunoassay oxytocin kits (NY, USA).


Parent and child behaviors:
Video-recorded parent and child behaviors were coded by investigators with the TEC-M coding scheme3. The TEC-M coding scheme is developed to assess children’s emotion regulation abilities from observations of parent and child behaviors during a frustration task where the child and parent interact. The TEC-M consists of eight codes for parent behaviors, eight codes for child behaviors and one code for dyadic parent-child behavior. Items are scored by a clinician or investigator on frequency (never, rarely, sometimes, often) and intensity (mild, moderate, marked)3. The primary outcome, the EmReg score, is scored by assigning a total score taking all coded behaviors into account. In this study we will use the individual parent and child behavior codes and not the assigned EmReg score.


Diagnostic status:
The diagnostic status of the child is available from screening with the Kiddie-Schedule for Affective Disorders and Schizophrenia – Present and Lifetime Version (K-SADS-PL)4 and the criteria for International Classification of Diseases‑10 (ICD-10)5.


Pubertal stage:
Child pubertal stage was reported by the child after instruction from a clinician using Tanner Stages6,7.


Statistical analyses
1) Hypotheses testing
The association between oxytocin concentrations and behavioral codes will be analyzed with Spearman’s (rank-order) correlations as the behaviors are scored on an ordinal scale. We will use one-sided tests. 
We will include child, mother, and father oxytocin concentrations as outcomes in separate models. Oxytocin concentrations will be included as a continuous variable. We will exclude outliers in oxytocin concentrations (defined as values +/- mean + 3 SD) and separately present the results including outliers in an appendix.
We will include two behavioral codes as possible predictors of parent oxytocin - parental support sensitivity and dyadic emotional warmth. We will include three possible predictors of child oxytocin - parental support sensitivity, dyadic emotional warmth, and child reassurance seeking. The behavioral codes will be included as ordinal variables. In the models analyzing child oxytocin as outcome, we will include child pubertal stage as a possible covariate as this was found associated with child oxytocin in a previous study8. Pubertal stage will be included as a categorical variable. Analyses will be performed with R (R Core Team, Vienna, Austria).
We will perform complete case analyses. Information on 101 mother-child interactions and 63 father-child interactions are available. We will use Benjamin Hoch
bergs method to adjust for multiple testing with a false discovery rate of 5%.


2) Exploratory analyses
We will use different methods to investigate the exploratory aims in this study:
- Decomposition methods like Principle Component Analysis (PCA).
- Cluster analyses such as K-means clustering.
- Machine learning models for predicting like Random Forest.
We will test for multiple comparisons in the exploratory analysis with the Benjamin Hochbergs method with a false discovery rate of 20%.

Results
Participants were included between July 2018 and July 2022. We will start data analysis after pre-registration of the statistical analysis plan and plan to submit the results for publication in August 2024.


TECTO trial Registration: ClinicalTrials.gov NCT03595098; https://clinicaltrials.gov/ct2/show/NCT03595098




References
1. Feldman, R., Gordon, I. &amp; Zagoory-Sharon, O. The cross-generation transmission of oxytocin in humans. Hormones and Behavior 58, 669–676 (2010).
2. Gordon, I., Zagoory-Sharon, O., Leckman, J. F. &amp; Feldman, R. Oxytocin and the Development of Parenting in Humans. Biological Psychiatry 68, 377–382 (2010).
3. Hagstrøm, J. et al. The Puzzle of Emotion Regulation: Development and Evaluation of the Tangram Emotion Coding Manual for Children. Front. Psychiatry 10, 723 (2019).
4. Kaufman, J. et al. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Initial Reliability and Validity Data. Journal of the American Academy of Child &amp; Adolescent Psychiatry 36, 980–988 (1997).
5. World Health Organization. CD-10 - Psykiske Lidelser Og Adfærdsmæssige Forstyr-Relser. Klassifikation Og Diagnostiske Kriterier. 1. Munksgaard. 1994. (1994).
6. Marshall, W. A. &amp; Tanner, J. M. Variations in pattern of pubertal changes in girls. Arch Dis Child 44, 291–303 (1969).
7. Marshall, W. A. &amp; Tanner, J. M. Variations in the Pattern of Pubertal Changes in Boys. Arch Dis Child 45, 13–23 (1970).
8. Mora-Jensen et al. ‘Salivary oxytocin concentrations in children and adolescents with and without OCD’, Unpublished results.