Background
Lack of trust in parental support puts children at risk for the development of psychological problems across the lifespan [
1,
2]. Bowlby [
1] proposed that whether children are able to develop trust in parental support depends for a significant part on children’s experiences of care in response to distress during interactions with their parents. Through repeated interactions with sensitive and responsive parenting, children develop trust in the parent and become securely attached [
3]. Conversely, when children experience recurrent insensitive, unresponsive or inconsistent parenting, they will have difficulty to develop trust in the parent and become insecurely attached [
3]. Research suggests that up to 40% of the children are insecurely attached [
4], and although insecure attachment is neither a necessary nor a sufficient cause for psychopathology development, it is considered an important transdiagnostic risk factor [
5‐
7].
Given the risks associated with insecure attachment, there is need for effective interventions that can promote trust in the context of the parent-child relationship [
8,
9]. The present study aims to investigate the individual and combined effects of a cognitive and a pharmacological intervention, specifically Cognitive Bias Modification (CBM) training and intranasal oxytocin (OT), on trust in maternal support. Although trust is important for psychological wellbeing across the lifespan, in the current study we focus on middle childhood (age range 8–12 years). Middle childhood has been proposed to be an important period for cognitive trust development, during which trust-related expectations can still relatively easily be influenced by new experiences [
10,
11]. This suggests that middle childhood might be a sensitive period for interventions targeting trust in parental support. As a proof-of-principle test of the hypothesis that OT and CBM training can contribute to trust development in middle childhood, the current study aims to explore the effects of the (combination of) interventions within a sample of normally developing middle childhood participants. If the interventions prove effective in increasing trust, they could be a valuable addition to clinical interventions targeting trust in parental support.
Existing early childhood attachment-related interventions mostly focus on enhancing parental sensitivity and parents’ mental representations of the attachment relationships with their own parents [
9,
12]. However, theory and research point to the importance of children’s own cognitive attachment representations and related information processing biases for repairing breaches in trust [
1,
13]. More specifically, it has been shown that information regarding the parent is attended, interpreted and remembered in congruence with children’s attachment-related expectations [
14‐
16]. As a result, interventions focusing solely on improving parenting skills might be less effective when children have insecure expectations. That is, if parents alter their behavior to be more sensitive and responsive, children who lack trust might not be able to adequately encode their parents’ retrained behavior because their insecure expectations were not altered. In support of such claims, research indicates that effect sizes of parenting training are small to moderate [
17]. Moreover, effect sizes decrease when children’s age increases [
18,
19], suggesting that parenting training has less impact when attachment-related information processing becomes increasingly insecure in response to prolonged exposure to insensitive and unresponsive parenting. Therefore, attachment processing biases could be an important additional target for interventions that aim to build or restore trust between parent and child.
A promising paradigm to change the way that information is processed and encoded is that of CBM [
20]. CBM procedures aim to modify information processing styles by systematic practice of a target processing bias [
21]. For anxiety disorders, among others, the CBM method has been shown effective in changing selective information processing biases and reducing disorder symptoms [
22]. Recently, a CBM training paradigm was developed for children aged 8–12 years with the purpose to modify children’s interpretation of attachment-related information [
23]. De Winter et al. [
23] tested the effectiveness of this attachment-related CBM training. In their study, half of the participants received a CBM training, during which children were trained to securely interpret story scenarios that were ambiguous as to whether mother provided support. The other half of the participants received a neutral placebo training in which resolutions of ambiguity were not related to maternal behavior. Results showed that the CBM procedure was effective. That is, children in the CBM training condition showed an increase in secure interpretation bias and a decrease in insecure interpretation bias as compared to children in the neutral training condition. Importantly, trust was causally affected by attachment-related interpretation bias, as indicated by a significant increase in trust in the CBM training condition [
23]. These results suggest that the CBM paradigm has therapeutic potential in the context of insecure attachment and lack of trust, as it could help build or restore children’s trust in their parents’ availability. An important next step towards the implementation of CBM as an intervention procedure is to identify the parameters that can increase the effectiveness of CBM [
22].
A possible candidate for augmentation of the effects of CBM is the neuropeptide OT. Endogenous OT is synthesized in the hypothalamus, while exogenous OT can be noninvasively administrated in humans by means of a nasal spray. Functional brain imaging studies have shown that intranasal OT can modulate activity in, and connectivity between, brain regions involved in social cognition [
24‐
26]. Overall, studies have shown that OT can help form, restore or maintain social relationships. As a result, OT has been proposed as a possible (addition to) treatment of disorders characterized by socioemotional difficulties [
27]. For the current study, we propose that OT could enhance CBM effects on two levels, in accordance with the two-level model of OT effects on social behavior and social cognition as proposed by Quintana et al. [
28]. First, on a behavioral level, OT has been shown to increase trust in social interaction [
29] and improve attachment security [
30,
31]. Therefore, OT could independently have an effect on the trust- and attachment-related outcome measures targeted by the current CBM training. Second, research suggests that OT can increase the salience and reinforcing value of socially relevant stimuli [
32,
33] and enhance the processing of social information (see [
34], and also [
35] for neural evidence in rodents). Since the scenarios in the CBM training all describe social situations in which children might need their mother’s support, we hypothesize that OT might improve the processing of these scenarios. This way, OT could increase learning during CBM training, resulting in an additive effect of OT and CBM training on trust and trust-related outcome measures in the current study.
In pediatric populations, the majority of the limited number of OT studies has targeted children diagnosed with autism spectrum disorder (ASD) and these studies yielded mixed results [
24,
36‐
39]. However, the scope of OT as potential therapeutic intervention reaches beyond the social problems associated with ASD [
40]. Moreover, most OT studies in children were limited in sample size and sample selection. Therefore, researchers generally agree that OT’s precise role and (additive) value need further investigation [
40,
41].
The present study: aims and hypotheses
In the current study, participants administer a nasal spray that either contains OT or a placebo (PL). Additionally, they receive either a CBM training aimed at positively changing trust and related interpretation bias or a neutral training that is conjectured to have no trust-related effects. The aim of the present study is to test the main and interaction effects of CBM training and OT on three levels of trust-related outcome measures in middle childhood: trust-related interpretation bias; self-reported trust; and children’s trust-related behavior towards mother.
At the first level, we investigate the effects of CBM training, OT and both interventions combined on secure attachment interpretation bias and insecure attachment interpretation bias, as compared to no intervention (i.e., neutral training and PL). Based on the study by De Winter et al. [
23], we expect that participants who receive CBM training show an increase in secure interpretation bias and a decrease in insecure interpretation bias as compared to children who receive no intervention. Since this is the first study examining the effects of OT on attachment interpretation bias, it is an empirical question as to what the effect of OT on interpretation bias is. When OT has a positive effect on interpretation bias, this should be reflected in increased secure interpretation bias and decreased insecure interpretation bias for children receiving OT as compared to no intervention. Given the proposed role of OT in improving the salience and processing of social stimuli [
32,
34], intranasal administration of OT could enhance processing of the social stimuli presented in the CBM training and thereby increase its effectiveness. When joint exposure to CBM training and OT is beneficial, children in the combined intervention condition should show increased secure interpretation bias and decreased insecure interpretation bias as compared to participants who receive only one of the interventions.
At the second level, the effects of CBM training, OT, and both interventions combined on change in self-reported trust from pre-intervention to post-intervention are assessed. It is expected that participants who receive any intervention (CBM training, OT, or the two combined) will show an increase in trust as compared to participants receiving no intervention [
23,
29]. If joint exposure to the two interventions is beneficial, this should be reflected in a stronger increase in trust for participants who receive the interventions combined as compared to participants who receive only one of the interventions.
At the third level, intervention-related changes in behavior of children towards mother and mother-child interactional behavior during a distressing task are observed. The main effects of the two interventions as well as the interaction effect of the interventions are assessed. To our knowledge this is the first study examining the effects of CBM training and OT on behavior during mother-child interaction. Nevertheless, previous studies have linked more trust to more positive behavior of child towards mother [
42] and to a more coherent mother-child interactional pattern [
43]. Therefore, if the interventions affect trust and these effects extend to the behavioral level, children who receive any intervention (CBM training, OT, or the two combined) should show an increase in positive approach towards mother as compared to children who receive no intervention. Similarly, mother-child dyads in the intervention groups (CBM training, OT, or the two combined) should show increased interactional coherence compared to mother-child dyads in which children receive neutral training and PL as a control condition.
Although the main goal of the current study is to test the effects of CBM training and OT on the abovementioned trust-related outcome measures, we plan to take the opportunity to carry out some additional explorative analyses. More specifically, we plan to test whether differences in participant characteristics moderate the effects of the interventions in the present study. This is especially relevant for the OT intervention, since accumulating evidence suggests that the effects of intranasally administered OT can be influenced by a variety of factors [
44], including among others caregiving experiences [
26,
45], social functioning [
46], and (early) adverse events [
47]. Since the present study is the first to test the effects of OT, as individual intervention and combined with CBM, on trust-related outcomes in middle childhood, it is an opportunity to explore the effects of participant characteristics to inform future research about possible factors to take into account when administering OT as an (additive) intervention. Importantly, we also closely monitor the side-effects of a single administration of OT in middle childhood to provide further information on the safety of OT administration in this age group.
Discussion
Given the association between lack of trust in the parent and a wide range of psychopathological problems across the lifespan, there is need for interventions that can help build trust in parent-child dyads. The present article describes the protocol for a study that aims to test the individual and combined effects of two interventions – CBM training and intranasal OT – on children’s trust-related information interpretation bias, trust in maternal support, and observed mother-child interactional behavior. To this purpose, children are administered a nasal spray that contains either OT or PL. In addition, they receive either a CBM training aimed at positively changing trust and related interpretation bias or a neutral training that aims to have no trust-related effects. The different outcome measures are administered pre- and post-intervention to allow assessment of change due to the interventions.
The present study is the first study to combine intranasal OT administration with a CBM training procedure. Both individually and combined, the two interventions could exert effects on trust. The current study’s factorial design allows for assessment of these combined and individual effects of CBM training and OT. Other strengths are the double-blind and randomized design of the trial, reducing the risk of bias. Moreover, to our knowledge, the current trial is the first OT study in general-population, middle-childhood children with sufficient power to detect moderate OT effects.
In line with this, an important additional aim of the present study is to increase our knowledge of adverse events or side-effects associated with OT administration in pediatric populations. To date, limited data is available on the side-effects of OT in children, due to a small number of studies performed with limited sample sizes [
40]. In the present study, the side-effects of OT are monitored in a relatively large sample of middle-childhood children, both at the end of the procedure and 24 h after intervention. The current trial can thus provide more insight into any side-effects associated with single-dose OT in middle-childhood children, which is an important step towards the use of OT as an intervention in pediatric populations.
Finally, the study provides the opportunity to explore potential moderators of the effects of the interventions. It must be noted here that the sample size of the current study was budgeted to have adequate power to test the main hypotheses. However, accumulating evidence suggests differential effects of intranasally administered OT depending on a variety of participant characteristics [
26,
44‐
47]. Because this will be the first study with OT in such a large, normal-population, middle-childhood sample, we considered it a missed opportunity not to include potential moderators of OT effects and to perform preliminary exploratory analyses. This might be relevant for future research as it could point to relevant factors to take into account in OT research in this sample. However, lack of power will make it hard to draw conclusions from moderation analyses and, therefore, research in larger samples will be needed to further examine possible moderators. Additionally, although we assess a range of possible moderators in the current study, there are other factors that we did not examine that could affect the working of the OT nasal spray. An interesting question for future research might, for instance, be whether (exclusive) breastfeeding and mode of birth affect children’s responsiveness to intranasal OT even years later [
44,
81].
A limitation regarding the current study design is that effects of the interventions are assessed immediately after intervention. As a result, prolonged long-term effects of the interventions remain unknown. Similarly, since the current study consists of a single session, we cannot assess the impact of multiple sessions of the intervention(s). Without doubt, longer-term effects of OT administration and CBM are important to assess when considering them as clinical interventions to improve or rebuild trust. However, since previous research using the same CBM procedure yielded immediate effects on trust c, the current study was set up to test (1) whether OT can enhance these CBM effects and (2) whether OT as individual intervention has an immediate effect on trust. As the present study is the first to combine these two interventions, it is an important first step to assess the short-term effects and feasibility of a single intervention session. Nonetheless, if the (combined) interventions were to prove effective in the current study, future research will be crucial to explore the long-term effects of the interventions as well as the effect of multiple intervention sessions. Additionally, the effects of the interventions are tested in a normal population sample and, therefore, the effectiveness of the interventions in clinical groups cannot be ascertained from the current study. If the current study were to provide favorable results following the CBM and OT interventions, another important next step is to assess effects of the interventions in clinical samples.
In all, the current paper describes the protocol for a RCT investigating the individual and combined effects of CBM training and OT on trust in mother. Additionally, the current RCT tests the safety of OT administration in 8–12-year-old children. As OT studies in pediatric populations have yielded mixed results, with the current comprehensive protocol description we aim to expedite the clarity and reproducibility of OT research findings. If effective, CBM training and OT could be easily applicable and nonintrusive additions to interventions that target trust in the context of the parent-child relationship.
Trial status
Mother-child dyads began to enter the trial in March 2016. Recruitment is still open.