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. Author manuscript; available in PMC: 2022 Dec 1.
Published in final edited form as: Depress Anxiety. 2021 Aug 31;38(12):1289–1297. doi: 10.1002/da.23210

Directional Effects of Parent and Child Anxiety One Year Following Treatment of Child Anxiety, and the Mediational Role of Parent Psychological Control

Wendy K Silverman 1, Carla E Marin 1, Yasmin Rey 2, James Jaccard 3, Jeremy W Pettit 2
PMCID: PMC8664994  NIHMSID: NIHMS1731502  PMID: 34464490

Abstract

Background:

We leveraged a recent efficacy trial to investigate directionality between parent anxiety and child anxiety at posttreatment and 12-month follow-up, and the potential role of parent psychological control as a mediator. We also explored child age and sex as moderators.

Method:

Two-hundred and fifty-four children were randomized to individual cognitive behavioral therapy (CBT) or to one of two CBT arms with parent involvement. Parent anxiety was not a treatment target in any of the three arms.

Results:

Child anxiety at posttreatment was associated with parent anxiety and psychological control at 12-month follow-up, providing evidence of child-to-parent directionality. Parent anxiety at posttreatment was associated indirectly with child anxiety at 12-month follow-up through associations with parent psychological control, providing evidence of parent-to-child directionality. At posttreatment, parent psychological control contemporaneously mediated the relation between parent and child anxiety. Neither child age nor sex moderated any association.

Conclusions:

Findings highlight the directional effects between child anxiety, parent anxiety, and psychological control from posttreatment to 12-month follow-up, even when parent anxiety is not a treatment target. Research and clinical implications are discussed, with an emphasis on enhancing durability following treatment effects.

Keywords: anxiety/anxiety disorders, child/adolescent, maternal-child

The theme of this Special Issue, that there are bidirectional or transactional processes from parents to children and back again, is a pervasive concept in psychological models of child development and developmental psychopathology (e.g., Bell, 1968; Sameroff, 2009), as well as models of parent anxiety to child anxiety and back again (e.g., Hudson & Rapee, 2004). (As per the Special Issue, we use “child” to refer to children and adolescents.) Research consistently shows a significant association between parent anxiety and child anxiety (e.g., Blossom et al., 2013; Bögels & van Melick, 2004; Silverman, Cerny, Nelles, & Burke, 1988).

Parent variables are important to consider in models aimed to advance understanding of the linkages between parent and child anxiety. One parent variable emphasized in models is parent psychological control. Psychological control refers to parents’ intrusions into their child’s emotional and behavioral responses through parent expressions of disappointment and shame, and induction of child guilt (e.g., Barber, 1996; Becker, 1964; Schaefer, 1965). Children view parent expressions of psychological control as conveying that the child cannot handle new, challenging, or anxiety-provoking situations, limiting child autonomy in such situations (Hudson & Rapee, 2004). Parents who are anxious may be prone to psychological control to restrain in part their own difficulties in managing uncertainty and anxiety (Woodruff-Borden et al., 2002). However, findings are mixed for a significant association between parent psychological control and parent anxiety (e.g., Bögels & Brechman-Toussaint, 2006; Borelli, Margolin, & Rasmussen, 2015; Turner, Beidel, Roberson-Nay, & Tervo, 2003; Whaley, Pinto, & Sigman, 1999). Findings are consistent , however, in showing that parent psychological control is contemporaneously and prospectively associated with child anxiety (e.g., Bögels & Brechman-Toussaint, 2006; Chorpita & Barlow, 1998; McLeod, Wood, & Weisz, 2007; Wood, McLeod, Sigman, Hwang, & Chu, 2003). Findings from two community studies further demonstrate that parent psychological control mediates the association between parent anxiety and child anxiety (Borelli et al., 2015; Xu, Cui, & Lawrence, 2020).

Understanding of the directional pattern of associations between parent and child anxiety and parent control is limited, largely because most studies used cross-sectional designs (Bögels & Brechman-Touissant, 2006). Cross-sectional, observational studies using experimental designs with mothers of clinically anxious children and mothers of nonclinical children reveal child-to-parent effects; specifically, clinically anxious children compared with nonclinical children elicit more controlling behavior from mothers (e.g., Hudson, Doyle, & Gar, 2009; Hudson & Rapee, 2001).

Treatment studies provide a unique opportunity to develop and test theoretical-mechanistic, directional models while (a) experimentally manipulating (or not) certain parent variables and (b) reducing levels of child anxiety (e.g., Settipani, O’Neil, Podell, Beidas, & Kendall, 2013; Silverman, Kurtines, Jaccard, & Pina, 2009; Silverman, Marin, Rey, Kurtines, Jaccard, & Pettit, 2019). Randomized controlled comparative trials of individual child cognitive behavioral treatment (CBT) versus CBT with parent involvement have targeted not only child anxiety but also parent anxiety when parents reported heightened anxiety symptoms (e.g., Barrett, Dadds, & Rapee, 1996; Bögels & Siqueland, 2006; Cobham, Dadds, & Spence 1998; Creswell, Willets, Murray, Singhal, & Cooper, 2008; Hudson et al., 2014; Kendall, Hudson, Gosch, Flannery-Schroeder, & Suveg, 2008; Silverman et al., 2009; Siqueland, Ryan, & Diamond, 2005).

Findings from the only two individual CBT studies versus parent involvement CBT studies of directionality suggest bidirectional effects (e.g., Settipani et al., 2013; Silverman et al., 2009). Using Kendall and colleagues’ (2008) clinical trial data, Settipani and colleagues (2013) analyzed directionality of change and found two lagged effects: Child anxiety reduction between pre- and posttreatment was associated with parent anxiety reduction between posttreatment and follow-up, and reductions in parent psychological control between pre- and posttreatment were associated with child anxiety reduction between postreatment and follow-up. Silverman and colleagues’ (2009) found a similar directionality pattern with respect to parent anxiety, which was strengthened by finding that parent variables changed even in individual child CBT, with no targeting of any parent variables.

The current study moves beyond evaluation of efficacy outcome (La Greca, Silverman, & Lochman, 2009) and past directionality examinations (Settipani et al., 2013; Silverman et al., 2009; Silverman et al., 2019) by leveraging a recent efficacy trial (Silverman, Rey, Marin, Jaccard & Pettit, 2021) to investigate directionality between parent anxiety and child anxiety at posttreatment and 12-month follow-up, and the potential role of parent psychological control as a mediator. In this trial, parent psychological control was targeted in treatment (as a potential mediator of child anxiety outcome); parent anxiety was not targeted (but it was measured); and child anxiety was the outcome; treatment and follow-up effects on parent psychological control and child anxiety were reported.

Our current focus on the posttreatment to 12-month follow-up interval is a novel and unique contribution in advancing understanding of the patterns of directional associations among these variables (i.e., parent anxiety, parent psychological control as mediator, child anxiety) following treatment. No follow-up study has examined this issue. Follow-up studies have focused exclusively on parent baseline anxiety as a predictor of child anxiety and none found a significant association (e.g., Cobham, Dadds, Spence, & McDermott, 2010; Ginsburg et al., 2014; Nevo et al., 2014). Gibby and colleagues (2017) suggest these null finding may be because, “…parent and child symptomatology changes over time in a bidirectional manner that is not captured by baseline symptoms” (p. 222). Our focus on the posttreatment to 12-month follow-up interval, not pretreatment/baseline, provides a rare glimpse of what may (or may not) occur during this under-studied time interval, and therefore may point to new avenues for mitigating childhood anxiety relapse, resulting in more durable effects. Our examination of this issue has high public health impact given that about 80% of children in the Child/Adolescent Anxiety Multi-Modal Study were classified as chronically ill or relaspers in the six years following treatment (Ginsburg et al., 2018).

In sum, our interest in this study was to examine directionality of parent anxiety and child anxiety following treatment when parent anxiety was not targeted. Also of interest was whether parent psychological control mediated the link between parent and child anxiety, given the important mechanistic role of parent psychological control in past research. Based on the above literature, we made the following hypotheses: (1) parent anxiety would be associated with child anxiety, contemporaneously, at posttreatment and at 12-month follow-up; as well as across posttreatment to follow-up; and (2) parent psychological control would mediate associations between parent anxiety and child anxiety contemporaneously at posttreatment and at 12-month follow-up; as well as across posttreatment to follow-up. Given only two studies have examined the issue (Settipani et al., 2013; Silverman et al., 2009), we did not formulate hypotheses about directionality; instead we tested all directionality patterns: parent-to-child; child-to-parent; and bidirectional. Finally, because child age and sex have been inconsistently found to moderate the association between parent and child anxiety, including in follow-up studies (Gibby et al., 2017; Norris & Kendall, 2020; Ranney, Behar, & Zinsser, 2021), we explored child age and sex as moderators.

Methods

Participants

Data from 254 children and adolescents (7-16 years; M=9.37 years; SD=2.42; 45.3% girls and young women) and their parents (mostly mothers) who completed treatment in Silverman and colleagues (2021) (Trial registration number: NCT00620958) were included in the current analyses. Two hundred eleven youths were Hispanic/Latino (83%), 29 were European American (11.4%), 3 were Asian American (1.2%), 3 were African American (1.2%), 7 reported “other” ethnicity (2.8%), and 1 did not report ethnicity (.4%). Regarding marital status, 83.1% of parents were married, 9.4% were divorced, 3.5% single, 1.6% cohabiting with a partner, .8% separated, .4% widowed, and 1.2% did not report marital status. Regarding annual family income, 14.6% reported incomes less than $20,000, 17.7% between $21,000 and $40,000, 14.6% between $41,000 and $60,000, 16.1% between $61,000 and $80,000, 11% between $81,000 and $100,000, 15.7% between $101,000 and $149,000, 4.7% over $150,000, and 5.6% did not report income. All children met diagnostic criteria for a primary anxiety diagnosis (Diagnostic and Statistical Manual of Mental Disorders-4th Edition; DSM-IV, American Psychiatric Association, 1994) using the Anxiety Disorders Interview Schedule for Children (Parent and Child Versions) (ADIS-IV: P/C; Silverman & Albano, 1996). Primary exclusionary diagnoses were developmental disabilities, psychosis, or current involvement in another psychosocial treatment.

Measures

We report findings from the model that we tested using parent measures. (In Supporting Information, we report findings from the child model.) All measures are widely used and are described in Silverman and colleagues (2021) including psychometric properties. The only measure that was not described in the earlier report is the parent anxiety measure because data from that measure were not examined in that study.

Diagnostic Interview.

The Anxiety Disorders Interview Schedule for DSM-IV: Parent and Child Versions (ADIS-IV: P/C; Silverman & Albano, 1996) was administered by Independent Evaluators (IEs) masked to treatment arm and assessment wave to parents and children, respectively to determine eligibility in the study. Test-retest reliability for diagnoses have been reported to be in the .80 to .92 range (e.g., Silverman, Saavedra, & Pina, 2001) with satisfactory concurrent validity estimates.

Parent Anxiety.

The Symptom Checklist-90-Revised (SCL-90-R; Derogatis, 1977) is a 90-item measure that assesses adult psychopathology symptoms, including anxiety. Respondents rate their symptom experiences along a 5-point scale (0 = not at all, 4 = extremely). We used the 10-item Anxiety subscale in this study; scores range from 0 to 40. One-week retest reliability for the Anxiety Scale has been found to be .80, with satisfactory concurrent validity estimates.

Child Anxiety.

The parent version of the Revised Children's Manifest Anxiety Scale (RCMAS-P; Reynolds & Richmond, 1978) is a 37-item rating scale that assesses parents’ perceptions of child anxiety symptom severity (e.g., Kendall, 1994; Silverman et al., 1999; Silverman et al., 2019). All items are rated either Yes (1) or No (0); scores range from 0 to 28. Among children ages 6-16 years, three-week retest reliability has been found to be .98, with satisfactory concurrent validity estimates (Silverman et al., 2009).

Psychological Control.

The parent version of the Parenting Behavior Inventory (PRPBI-PC; Schludermann & Schludermann, 1970) is a 30-item rating scale that assesses perceived parent behaviors toward their child, including Psychological Control. All items are rated as Not like (0), Somewhat like (1), or A lot like (2). Psychological Control consists of 10 items; scores range from 0 to 20. Retest reliability estimates range from .79 to .89. with satisfactory concurrent validity estimates (Schluderman & Schluderman, 1988).

Procedure

The study was approved by the university’s institutional review board. All parents and youths provided informed consent/assent prior to participation. Study measures were completed at pretreatment, posttreatment, and 12-month follow-up: our research question in this article relates to the variables measured at posttreatment and 12-month follow-up. Participants were randomized using a random numbers table to individual cognitive behavioral therapy (CBT) or to one of two CBT arms with parent involvement, in a dyadic format as in past studies (Silverman et al., 2009; Silverman et al., 2019). All arms targeted youth anxious symptoms with in- and out-of-session exposures and cognitive strategies. Parent anxiety was not a treatment target in any of the three arms. One parent arm emphasized training parents in use of reinforcement strategies; the other emphasized training parents in use of child-parent relationship enhancement strategies. Details appear in Silverman and colleagues (2021).

Results

Preliminary Analyses

We present descriptive statistics and bivariate correlations between measured variables at posttreatment and follow-up in Table 1, given this is the interval of interest in this study. Mean scores on parent anxiety did not significantly differ between posttreatment and follow-up (posttreatment mean = 1.73, SD = 2.73, follow-up mean = 1.83, SD = 2.80; z = 0.27, p = .78), and mean scores on child anxiety and psychological control were significantly lower at follow-up than posttreatment (child anxiety posttreatment mean = 8.34, SD = 5.63, follow-up mean = 7.45, SD = 5.66; z = 2.57, p = .01, d = 0.20; psychological control posttreatment mean = 8.34, SD = 5.63, follow-up mean = 7.45, SD = 5.66; z = 2.57, p = .01, d = 0.20). There were no significant differences between any treatment arms on any variable at posttreatment. At follow-up, there were no significant differences between any treatment arms on parent anxiety and psychological control; child anxiety scores were significantly lower for youth in the parent-involvement CBT arm that targeted parent-child relationships than youth in the individual CBT arm (Mean difference = −2.61; z = −2.98 p = .003, d = 0.37). As noted below, we included treatment arm as a covariate in the statistical model presented below.

Table 1.

Descriptive Statistics and Bivariate Correlations for Study Variables

1 2 3 4 5
M SD
1. SCL-90 Anx Post 1.73 2.73 -
2. SCL-90 Anx 12m FU 1.83 2.81 .42*** -
3. PRPBI – PC Post 3.14 2.76 .18** −.02 -
4. PRPBI – PC 12m FU 2.88 2.56 .12 −.04 .70*** -
5. RCMAS Post 8.35 5.64 .29*** .28** .14* .17* -
6. RCMAS 12m FU 7.26 5.60 .15 .32*** .07 .13 .67***
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Note. SCL-90 Anx = Symptom Checklist – Anxiety; Post = Posttreatment; 12m FU = 12-month follow-up; PRPBI-PC = Parent Report of the Parenting Behavior Inventory – Psychological Control; RCMAS = Revised Children’s Manifest Anxiety Scale

*

= p < .05

**

= p < .01

***

= p < .001.

We ran outlier analyses using the projection-type method (Wilcox, 2017), which revealed 8 outliers. We tested the conceptual model in Figure 1 with and without outliers and findings showed that the statistical significance of most paths remained unchanged (see Table S1 in Supporting Information).

Figure 1.

Figure 1.

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Conceptual Model

Statistical Model

We tested the model in Figure 1 using structural equation modeling in Mplus (Muthén, Muthén, & Asparouhov, 2016), using the robust algorithm (MLR) to accommodate non-normality and full information maximum likelihood to accommodate missing data (Enders, 2010). The model included pretreatment measures of parent anxiety, psychological control, and child anxiety that were assumed to impact corresponding measures at posttreatment and follow-up (serving the role of statistical covariates). Treatment arm was also included in the model as a statistical covariate. We also covaried child sex and ethnicity given their significant bivariate correlations with variables in the model. The model included autoregressive paths to assess the relations between posttreatment and follow-up measures on the same variable (paths j, k, and l). Also included in the model were lagged paths to assess the directionality of temporal relations between parent anxiety and psychological control at posttreatment and child anxiety at follow-up (paths e and g, respectively), between child anxiety at posttreatment and parent anxiety and psychological control at follow-up (paths h and i, respectively), and between parent anxiety at posttreatment and psychological control at follow-up (path d) and psychological control at posttreatment and parent anxiety at follow-up (path f). The model also included contemporaneous paths to assess the effect of parent anxiety on child anxiety (paths c and o), parent anxiety on parent psychological control (paths a and m), and parent psychological control on child anxiety (paths b and n) at posttreatment and follow-up, respectively. We introduced across-time equality constraints between paths b and n. At posttreatment and again at follow-up, we tested for contemporaneous reciprocal causality between parent anxiety and child anxiety, and between psychological control and child anxiety, by including reversed paths between these variables (e.g., path from parent anxiety to child anxiety [path c]; and additional path from child anxiety to parent anxiety at posttreatment). To test for contemporaneous reciprocal causality, we included child ethnicity and child sex as instrumental variables (Bollen, 2012; Jaccard & Bo, 2018).

The tested model and the estimated path coefficients and their associated margins of error (defined as the absolute half widths of 95% confidence intervals) appear in Figure 2. The Figure excludes child sex, ethnicity, treatment arm, and baseline exogenous variables to avoid clutter though these variables were included in the model. Also excluded to avoid clutter are nonsignificant path coefficients. The model provided good fit to the data: chi square = 23.59, df = 26, p = .60; root mean square error of approximation (RMSEA) = .00; p value for close fit (pClose) = .98; CFI = 1.00; standardized root mean residual (SRMR) = .02.

Figure 2.

Figure 2.

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Structural Equation Model with Significant Unstandardized Path Coefficients and Margins of Error. * p < .05; ** p < .01; *** p < .001

Results showed evidence for direct child-to-parent directional effects: Lower child anxiety at posttreatment was significantly associated with lower parent anxiety (path h = 0.11, z = 3.25, p = .001) and psychological control (path i = 0.05, z = 2.10, p = .036) at follow-up. That is, child anxiety was associated with lagged changes in parent anxiety and parent psychological control.

Results also showed evidence for indirect parent-to-child directional effects: Lower parent anxiety at posttreatment was associated with lower child anxiety at follow-up indirectly through lower parent psychological control (path a = 0.15, z = 2.45, p = .014; path k = 0.54, z = 6.81, p = .000; path n = 0.17, z = 11.97, p = .049). That is, parent anxiety was associated with lagged changes in child anxiety through associations with changes in parent psychological control.

Contemporaneous effects also emerged. At posttreatment, lower parent anxiety was significantly associated with lower psychological control (path a = 0.15; z = 2.45, p = .014), which in turn was significantly associated with lower child anxiety (path b = 0.17, z = 1.97, p = .049). There also was an effect of parent anxiety on child anxiety at posttreatment (path c = 0.53, z = 4.21, p = .000): as parent anxiety decreased at posttreatment so did child anxiety, and this effect was partially mediated by decreases in psychological control. There was no evidence of contemporaneous reciprocal causality at posttreatment or follow-up between any of the parent and child variables.

Moderation.

We tested for possible differential effects (path coefficients) of parent anxiety and child anxiety, and parent psychological control and child anxiety, as a function of child age and sex at posttreatment and 12-month follow-up. None of these effects were statistically significant.

Discussion

The current study contributes to the scant literature on bidirectional or transactional processes relating to parent-to-child anxiety and back again, and the role of parent psychological control as a mediator of childhood anxiety at posttreatment and 12 months following treatment. Child anxiety at posttreatment was associated with parent anxiety and psychological control at 12-month follow-up, providing evidence of child-to-parent directionality; parent anxiety was associated with lagged changes in child anxiety through associations with changes in parent psychological control, providing evidence of parent-to-child directionality (albeit indirectly). Parent psychological control contemporaneously mediated the association between parent and child anxiety at posttreatment, but not contemporaneously at 12-month follow-up. Child age and sex did not moderate any associations.

Our findings highlight the knowledge that can be gained by leveraging the longitudinal follow-up design of a clinical trial to advance understanding of the association between parent and child anxiety, and the theoretical-mechanistic role of parent psychological control vis-à-vis this association. Like most past studies (e.g., Bögels & Siqueland, 2006; Creswell et al., 2008; Hudson et al., 2014; Kendall et al., 2008; Silverman et al., 2009), parent anxiety was not an inclusion criterion in our study and mean parent anxiety scores indicated overall low severity; we also did not target parent anxiety in any of the three treatment arms. Still, we found variation in levels of parent anxiety symptoms and importantly this variation was significantly associated in hypothesized ways with variation in child symptoms.

Intriguingly, the direct path coefficient from child-to-parent across time was statistically significant but this was not the case for the parent-to-child direction. Similarly, child anxiety at posttreatment was directly linked to parent psychological control at follow-up. These results are important because the field has viewed the presumed causal dynamic as being from parent to child both in terms of parent anxiety and parent behavior. Our results support the proposition that the associations between these parent constructs and child anxiety can be as much the result of a child’s impact on parents rather than just vice versa (Silverman et al., 2009).

Our findings that parent anxiety at posttreatment was indirectly associated with child anxiety at 12-month follow-up through associations with psychological control requires consideration within the context of past mixed research findings regarding associations between parent psychological control and parent anxiety (e.g., Bogels & Brechman-Toussaint, 2006; Borelli et al., 2014; Turner et al., 2003; Whaley et al., 1999). Findings consistently show that parent psychological control is contemporaneously and prospectively associated with child anxiety (e.g., Bögels & Brechman-Toussaint, 2005; Chorpita & Barlow, 1998; McLeod et al., 2007; Wood et al., 2003). Two community studies showed that parent psychological control mediated the association between parent anxiety and child anxiety (Borelli et al., 2015; Xu et al., 2020). However, these studies measured parent psychological control at a single measurement point only. Our measurement of parent psychological control at posttreatment and follow-up in a sample enrolled in a clinical trial are additional unique features of our study. The current findings further show that parent psychological control operates as a partial mediator contemporaneously at posttreatment, and prospectively over the 12 months following treatment.

Overall, our focus on the posttreatment and 12-month follow-up interval is a novel contribution in advancing understanding of the patterns of directional associations among these variables (i.e., parent anxiety, parent control as mediator of child anxiety outcome at post and following treatment). As the first study to focus on this time interval, our findings may inform efforts to improve durability of childhood anxiety treatment effects. Specifically, the presence of parent anxiety and psychological control at posttreatment are associated with the presence of continued child anxiety at posttreatment, which in turn may elicit parent anxiety and pull parents into further controlling behaviors in the year following treatment, setting up a cycle that maintains child anxiety. Targeting any of these variables might break the mediational chain, including treating child anxiety to remission and/or targeting parent displays of control in response to child anxiety. Research testing these possibilities is important given the scarcity of research on treatment durability, the mechanisms associated with treatment durability, and that the largest childhood anxiety treatment study, the Child/Adolescent Anxiety Multi-Modal Study, classified about 80% of children as chronically ill or relaspers in the six years following treatment (Ginsburg et al., 2018).

Overall, our study’s findings highlight complex causal processes are at work and underscore the need for replication. The study also can serve as a template for future research designs and analyses to advance understanding of directionality in clinial trials. Our finding neither age nor sex to be a significant moderator in any of our analyses is consistent with past general null findings, and findings that have shown inconsistency (Gibby et al., 2017; Norris & Kendall, 2020; Ranney et al., 2021). Further research is clearly needed to understand developmental and sex influences in the broader childhood anxiety literature including the current research questions.

Study Limitations and Future Research

There are several study limitations. Some analyses were correlational in nature and required assumptions about timing of cause and effects and issues of sequential ignorability. It would be helpful for future research to use more intensive and frequent measurement to complete the theoretical tracing of the mediational processes (Gaynor, 2017; Silverman et al., 2019). Reliance on rating scales to measure parent psychological control is another limitation, though this is a reasonable starting point in this underdeveloped area. In addition, having a relatively high proportion of Hispanic/Latino participants is a study strength; we recommend future research be designed though from the onset to advance understanding of the role of ethnicity and related variables (e.g., acculturation).

Despite these limitations, this study is one of the first to focus on (bi)directional patterns and test theoretical-mechanistic models of parent/child variables following treatment of child anxiety. It will be important for future research to continue to develop this line of inquiry and unravel the complex mediational and directional processes between parent anxiety, child anxiety, and parent psychological control, with an eye toward enhancing durability of treatment effects.

Supplementary Material

supinfo

Acknowledgments

This research was supported by the National Institute of Mental Health Grant R01-MH079943. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health.

Data Availability Statement:

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

supinfo
NIHMS1731502-supplement-supinfo.docx (55.2KB, docx)

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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