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. Author manuscript; available in PMC: 2024 Apr 1.
Published in final edited form as: J Adolesc. 2022 Nov 28;95(3):427–436. doi: 10.1002/jad.12125

Genetic influences on the interplay between obsessive-compulsive behavior symptoms and cannabis use during adolescence

Jodi Kutzner 1, Kit K Elam 1, Thao Ha 2
PMCID: PMC10588756  NIHMSID: NIHMS1937211  PMID: 36443914

Abstract

Introduction:

There are overlapping biological origins and behaviors associated with obsessive-compulsive symptoms (OCS) and cannabis use. There is also evidence that OCS and cannabis use are associated over time. Thus, we investigated polygenic predisposition for OCS as predictive of OCS and cannabis use from age 17 to 19. We hypothesized that greater genetic risk for OCS would predict both OCS and cannabis use.

Methods:

The current study used participants from the Project Alliance 1 study, a US-based sample, for whom genomic, OCS, and cannabis use data were available (n = 547). Polygenic risk scores (PRS) were formed via a meta-genome-wide association study on OCS and examined as a predictor of OCS and cannabis use at age 17 and 19. The sample was diverse (52.4% male; 45% European American, 30% African American, 14% multiracial, 5% Hispanic/Latino, 4% Asian American, and 2% other groups). Sensitivity analysis was performed by gender for European American and African American subsamples.

Results:

Across the whole sample, the greater polygenic risk for OCS was negatively associated with cannabis use at age 17 and positively associated with OCS at 19. Cannabis use at age 17 was positively associated with OCS at age 19. The association between polygenic risk for OCS and cannabis use at age 17 was replicated in European American males, whereas the association between cannabis use at age 17 and OCS at age 19 was replicated in African American males.

Conclusions:

Cannabis use may exacerbate OCS through adolescence, and genetic predisposition for OCS may be associated with lower cannabis use in efforts to avoid exacerbation of OCS.

Keywords: adolescence, cannabis, obsessive-compulsive symptoms, polygenic

1 |. INTRODUCTION

There are well-established associations between mental health disorders and substance use, as both exacerbate one another (Flynn & Brown, 2008; Ross & Peselow, 2012), leading to greater functional impairment, higher rates of morbidity and mortality, and worse treatment outcomes (Compton et al., 2007; Han et al., 2017; Kessler, 2004). Previous research indicates that comorbidity in mental health and substance use problems are robust in adolescence, with up to 75% of adolescents with substance use problems also presenting with a co-occurring psychiatric condition (Armstrong & Costello, 2002; Hovens et al., 1994; Lichtenstein et al., 2010). Current best-practice guidelines in adolescent psychiatric care emphasize the importance of integrated treatment of both substance misuse and mental health problems to provide lasting effects and mitigate other issues such as relapse and suicide attempts (Han et al., 2017; A. Hulvershorn et al., 2015; Sacks & Ries, 2005; Shaffer et al., 1996). Therefore, identifying links between early substance use and mental health symptomatology in adolescence is critical for preventing related disorders later in life (Cuzen et al., 2014; Hawke et al., 2020; Hawkins, 2008). In particular, obsessive-compulsive symptoms (OCSs), commonly associated with obsessive-compulsive disorder, frequently emerge with substance use and substance use disorders (SUD). OCS is characterized by symptoms of obsessions such as repetitive thoughts, urges, images, or impulses that produce anxiety and compulsive behaviors consisting of repetitive acts or mental procedures to alleviate anxiety (Richter & Ramos, 2018). OCS often emerges in childhood or adolescence and symptoms fluctuate over time.

Cannabis use also typically begins in adolescence. The National Survey on Drug Use and Health reports increases in cannabis use during adolescence, with accelerated increases in youth with mental health issues (Center for Behavioral Health Statistics, n.d.; Hasin, 2017; Johnson et al., 2020; Pacek et al., 2020). Cannabis use in adolescence is a significant public health issue given these increases which now surpass tobacco use in adolescence (Johnston et al., 2016). Taken together, past research demonstrates that OCS and substance use may develop over time, and some studies support a relationship between OCS and cannabis use (Spradlin et al., 2017; Nicolini et al., 2021). The current study aims to further explore the relationship between OCS and cannabis use across adolescence.

2 |. OCS AND CANNABIS USE

Research demonstrates that individuals with OCS experience greater levels of substance use and addiction compared to the general population (Choi et al., 2012; Figee et al., 2011; Kessler et al., 2005; Mancebo et al., 2009; Ruscio et al., 2010; Torres et al., 2007). However, previous research is mixed with regard to cannabis use. Some studies find a positive relationship between OCS and risky cannabis use (Bakhshaie et al., 2020), whereas others find OCS not related to frequency or quantity of use, but instead cannabis misuse (Spradlin et al., 2017). Conversely, some studies do not report a relationship between greater OCS due to cannabis use but do report individuals with OCS using greater amounts of cannabis and having higher levels of cannabis use compared to controls without OCS (Nicolini et al., 2021). Additional studies suggest that cannabis use may improve OCS (Kayser et al., 2019; Szejko et al., 2020). Finally, individuals with OCS have reported both benefits and harms of cannabis use (Kayser, Raskin, et al., 2020). The relationship between OCS and cannabis use may have biological origins as recent studies have highlighted the endocannabinoid system in the development of compulsive behavior, suggesting cannabis use could preferentially be associated with OCS. To address this gap, the present study investigated genetic predisposition for OCS as predictive of OCS and cannabis use across adolescence.

OCS severity shifts over the life cycle and stressful life events and sensitive developmental periods, such as adolescence, contribute to more drastic symptoms (Imthon et al., 2020). This is accompanied by the typical emergence and increase in substance use during adolescence. In particular, compulsive behavior, repetitive urges, and diminished ability to control these urges, may underlie both OCS and substance use in adolescence. The etiology of compulsive behavior in substance use has been described by Koob and le Moal (2005) as a transition from an impulsive stage via positive reinforcement to the removal of adverse states with negative reinforcement. The combination of both positive and negative reinforcement thus leads to compulsive behavior (Koob & le Moal, 2005). This pattern extends to OCS, as reinforcement implies that compulsions that are caused by anxiety and stress can grow in severity over time with reduced control (Figee et al., 2011, 2016). Positive reinforcement can also occur in early substance use as subjective effects are pleasurable or relaxing but with the escalation in use negative reinforcement can emerge in efforts to avoid withdrawal effects. Moreover, substance use is one mechanism for alleviating obsessive thoughts and compulsive behaviors.

Longitudinal studies show that as OCS severity increases, substance use may escalate in efforts to self-medicate, which, in turn, can exacerbate OCS over time. Previous research has also related negative reinforcement mechanisms within the limbic system with both OCD and addiction (Cuzen et al., 2014; Figee et al., 2011; Koob, 2015; Ruscio et al., 2010), further promoting the idea that compulsive behaviors may help regulate the addiction cycle. This is reinforced by research finding that cannabis use and OCS increase risk for one another. Some studies report that greater severity of OCD diagnosis may predict cannabis use in individuals using cannabis to alleviate symptoms (Kayser, Haney, et al., 2020; Spradlin et al., 2017). Conversely, other studies demonstrate that prolonged cannabis use can trigger or modify OCS by increasing or decreasing obsessive thoughts or repetitive behaviors (Buckner et al., 2007; Spradlin et al., 2017). Yet less is known about specific genetic etiologies underlying both OCS and cannabis use.

Data from family and twin studies suggest a strong genetic component in OCS. In a review of OCS twin studies, van Grootheest et al. (2005), indicated that genetic factors contribute to approximately 45%–65% of the variance in OCS among children and 27%–647% in adults. Other studies have focused on single nucleotide polymorphisms (SNPs), such as Guo et al. (2017); which estimated the heritability of OCD at 42% based on an imputed set of SNPs. Polygenic risk scores (PRS) capture variance in the genome by aggregating across multiple SNPs. PRS have been well utilized in past research studies to find longitudinal associations between substance use and psychopathology in adolescence (Deak et al., 2022; Hicks et al., 2021; Schaefer et al., 2021). In PRS research on OCD, associations have been found between genetic risk for OCD and the development and severity of OCS (Bralten et al., 2020). Findings from studies focused on PRS for OCD and OCS indicate these traits share genetic susceptibility with other mental abnormalities (i.e., harm avoidance, ASD) and substance use (Bey et al., 2020; Guo et al., 2017; Nicolini et al., 2021). One study by Nicolini et al. (2021) explored associations in a Mexican population among a PRS for OCD, cannabis use, and OCS compared to other psychiatric symptoms. Greater cannabis use was found for those with OCS compared with the general population as well as those with other psychiatric symptoms (hypomania, anxiety, depression), except psychosis. No mean differences were found in the PRS for OCD stratified by OCS and cannabis use status. However, this study examined OCS and cannabis use at a single time point in individuals with a very heterogenous age range (12–65). It is important to examine such associations over time as genetic effects on OCS and cannabis use may emerge developmentally as do the phenotypic associations among these behaviors (Hall et al., 2020; Hauser, 2021).

Thus, the current study examines whether genetic risk for OCS predicts cannabis use and OCS from age 17 to 19 while accounting for their relationship over time. We hypothesize that OCS and cannabis use will be positively associated within and across time. We also hypothesize that higher genetic risk for OCS will predict greater cannabis use and OCS. Given the evidence that OCS and cannabis use can vary by gender, we examined these patterns in the whole sample as well as by gender and separately within European Americans and African Americans given known differences in genetic allele frequencies by ancestry. (Chamberlain & Grant, 2020; Cuttler et al., 2016; Keyes et al., 2017; Martins et al., 2021; Mathes et al., 2019).

3 |. METHODS

3.1 |. Participants

Participants were from the Project Alliance 1 study (PAL1), a longitudinal randomized trial of 999 adolescents and their families recruited in Portland, Oregon. Participants were randomized to intervention and control conditions of the family check-up (FCU) (Dishion et al., 2003). The FCU is designed to reduce adolescent problem behaviors by improving parenting and family functioning. The FCU is a brief, three-session intervention based on motivational interviewing which consisted of an initial interview, an assessment session, and a feedback session. All adolescents in sixth grade at three middle schools were invited to participate (of which 90% consented and 50% were randomly assigned to the FCU). Participants were initially assessed at 11–12 years old, followed by four annual assessments. Additional assessments were administered at 16–17, 18–19, 23–24, 24–25, 26–27, and 28–30 years old. The sample was genotyped as part of the age 26–27 assessment. Data from the 16–17 (“age 17” hereafter) and 18–19 (“age 19” hereafter) assessments were used in the present study to capture cannabis use and OCS across adolescence.

The current analyses were for those participants whose genomic, obsessive-compulsive symptomatology, and cannabis use data were available (n = 547). The current sample did not differ from the larger sample based on risk indices or demographic factors for those included in the present sample. Participants were 52.4% male, 45% European American, 30% African American, 14% multiracial, 5% Hispanic/Latino, 4% Asian American, and 2% other groups (Native American, Pacific Islander, “Other”).

3.2 |. Procedures

All study protocols were approved by the Institutional Review Board of the Oregon Research Institute. Parents or guardians provided written informed consent for all minors and adolescents provided assent for participation in the study, while adult participants provided their own written informed consent.

DNA was collected using the Oragene saliva collection kits in young adulthood (Wave 10) and extracted according to Oragene’s recommended procedures. Genotyping was performed at Rutgers University Cell and DNA Repository (RUCDR) using the Affymetrix BioBank Array. Imputation was conducted to the full 1000 Genomes Phase 3 reference panel (1000 Genomes Project Consortium et al., 2015) using SHAPEIT2 (Delaneau et al., 2013) and then IMPUTE2 (Howie et al., 2009). This approach was used to maximize imputation across the diverse sample which included a small number of non-European American ancestry individuals. The initial imputed data included 39,921,474 SNPs excluding those that failed imputation quality. Of these, SNPs were excluded with a genotyping rate of <0.95 (n = 37,90,433), that did not pass Hardy–Weinberg equilibrium (HWE; p < 10−6; n = 165,411), or with a minor allele frequency (MAF) < 0.01 (n = 27,840,960). In total, 8,124,670 SNPs passed these quality control and data cleaning thresholds.

4 |. MEASURES

4.1 |. Polygenic risk for OCS (OCS PRS)

A PRS reflecting OCS was formed leveraging a meta-genome-wide association study on obsessive and compulsion symptoms (Smit et al., 2020). Smit et al. (2020) conducted a meta-analysis of the previous genome-wide association study (GWAS) on obsessive-compulsive disorder (Arnold et al., 2017) in 2688 cases and 7037 controls with a GWAS on compulsion symptoms in 8267 individuals. All samples were of individuals of European Ancestry. Using summary statistics from this meta-GWAS, PRS were created using PRS-CS, Bayesian regression, and continuous shrinkage method (Ge et al., 2019). The PRS-CS method uses linkage disequilibrium (LD) information from 1000 Genomes Project reference panels with the matching ancestry and estimates the posterior effect sizes for SNPs in a given set of GWAS summary statistics. Empirical tests and simulations have shown improved predictive power above traditional methods of polygenic construction. In the current study, PRS-CS was used with ancestry panels aligned with European American and African American groups. Obsessive-compulsive polygenic scores (OCS PRS) based on posterior PRS-CS weights were created using score procedure in PLINK 1.9 (Chang et al., 2015), averaging by the total number of nonmissing SNPs (443407 SNPs).

4.2 |. Population genetic admixture

Principal components (PCs) analysis was conducted to represent population admixture using the snpgdsPCA function from the R SNPRelate package (Zheng et al., 2012) after performing LD pruning and filtering (window size = 1500, step size = 150, R2 = .1) using PLINK. The first 20 PCs were extracted. To account for possible variation the 20 PCs were residualized from the OCS PRS.

4.3 |. Cannabis use

Cannabis use at age 17 and 19 were captured via self-report through a single item “How often did you use cannabis in the last 3 months?.” Responses ranged from 0 = never to 7 = 2–3 times a day or more.

4.4 |. OCS

OCS at age 17 were captured via self-report on the Brief Symptom Inventory (Derogatis & Melisaratos, 1983). Participants were prompted to indicate how much discomfort a list of problems caused during the past week. Six items assessed obsessive and compulsive behaviors (e.g., “Having to check and double-check what you do”). Responses ranged from 1 = not at all to 5 = very. Items were averaged to indicate greater obsessive and compulsive behavior. Internal consistency was good (α = .78)

OCS at age 19 were captured via self-report on the Achenbach System of Empirically Based Assessment, Adult self-report scale (Achenbach, 2003). Eight items assessed obsessive and compulsive behaviors (e.g., “I repeat certain acts over and over”). Responses ranged from 0 = not true to 2 = very true or very often. Items were averaged to indicate greater obsessive and compulsive behavior. Internal consistency was good (α = .69).

4.5 |. Covariates

Participant age, sex, socioeconomic status (SES), intervention condition, and ethnicity were controlled for in the main analyses.

4.5.1 |. Statistical analyses

We examined all relevant statistical assumptions inherent to the application of regression (e.g., multivariate normality) and affirmed a priori. In the whole sample (n = 547), a panel model was tested in which autoregressive and cross-lagged pathways were examined between OCS and cannabis use at age 17 and 19 (see Figure 1). The OCS PRS was included as a predictor of OCS and cannabis use at age 17 and 19. Given that OCS and cannabis use are known to vary by gender and between European Americans and African Americans, (Chamberlain & Grant, 2020; Cuttler et al., 2016; Keyes et al., 2017; Martins et al., 2021; Mathes et al., 2019), sensitivity analyses were tested separately and split by sex; European American males (n = 120), European American females (n = 118), African American males (n = 76), and African American females (n = 96). Full information maximum likelihood was used to handle missing data. Descriptive statistics were conducted in SPSS and all other analyses were conducted in Mplus Version 8.3.

FIGURE 1.

FIGURE 1

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Conceptual model

5 |. RESULTS

Table 1 presents means, standard deviations, and correlations among study variables for the whole sample. Average levels of OCS at age 17 and 19 were low. Cannabis use was low at age 17 and increased slightly at age 19. The OCS PRS was negatively associated with cannabis use at age 17 and 19. OCS and cannabis use at age 17 and 19 were positively associated within time. Cannabis use at age 17 was positively associated with OCS at age 19.

TABLE 1.

Means, standard deviations, and correlations among primary variables

1 2 3 4 5 6 7 8 9 10
1. OCS PRS -
2. OCS age 17 −0.03 -
3. Cannabis age 17 −0.13** 0.18*** -
4. OCS age 19 0.03 0.34*** 0.17*** -
5. Cannabis age 19 −0.10* 0.11 0.51*** 0.10* -
6. Ethnicity 0.02 −0.13 −0.06 −0.08 −0.07 -
7. Gender −0.02 0.10* −0.05 0.08 −0.14** 0.04 -
8. Age −0.05 −0.09* 0.13** 0.06 −0.03 0.04 −0.06 -
9. SES −0.03 0.12** 0.04 0.11* 0.08 −0.49*** −0.04 −0.08 -
10. Intervention 0.00 0.04 0.04 −0.03 −0.03 −0.01 −0.02 0.00 0.04 -
M (SD) 0.00 (1.00) 0.67 (0.63) 0.84 (1.80) 0.37 (0.32) 1.40 (2.34) 1.41 (0.49) 0.48 (0.50) 16.93 (0.75) 0.04 (0.72) 0.49 (0.50)
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Abbreviations: OCS, obsessive-compulsive symptoms; PRS, polygenic risk scores; SD, standard deviation; SES, socioeconomic status.

***

p < .001;

**

p < .01;

*

p < 05.

The model with the full sample showed good fit [χ2 (8) = 5.88, p = .66, RMSEA = 0.00, CFI = 1.00, TLI = 1.93]. Results can be found in Table 2. The OCS PRS was negatively associated with cannabis use at age 17 and positively associated with OCS at age 19. OCS and cannabis use had moderate stability over time and were correlated within time at age 17 but not at age 19. Cannabis use at age 17 was positively associated with OCS at age 19.

TABLE 2.

Model results

OCS age 17 Cannabis age 17 OCS age 19 Cannabis age 19
Overall sample (N = 547)
 OCS PRS −0.02 −0.12** 0.08* −0.04
 OCS age 17 - 0.18*** 0.32*** −0.03
 Cannabis age 17 - - 0.13** 0.53***
 OCS age 19 - - - 0.03
European American males (n = 120)
 OCS PRS 0.01 −0.20* 0.07 −0.15+
 OCS age 17 - 0.20* 0.30** −0.03
 Cannabis age 17 - - 0.15 0.43***
 OCS age 19 - - - −0.03
European American females (n = 118)
 OCS PRS −0.07 −0.16+ 0.12 0.00
 OCS age 17 - 0.32** 0.18+ −0.08
 Cannabis age 17 - - 0.16 0.52***
 OCS age 19 - - - 0.03
African American males (n = 76)
 OCS PRS −0.09 0.10 0.09 0.05
 OCS age 17 - 0.04 0.30** −0.01
 Cannabis age 17 - - 0.26* 0.69***
 OCS age 19 - - - −0.04
African American females (n = 96)
 OCS PRS −0.19+ −0.06 −0.01 0.03
 OCS age 17 - 0.26* 0.43*** 0.05
 Cannabis age 17 - - 0.04 0.57***
 OCS age 19 - - - 0.15
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Abbreviations: OCS, obsessive-compulsive symptoms; PRS, polygenic risk scores.

***

p < .001;

**

p < .01;

*

p < .05.

+

p < .1.

When examining this in European American males, the OCS PRS was negatively associated with cannabis use at age 17. Cannabis use and OCS were positively associated at age 17, and there was moderate stability in the constructs over time. Cannabis use at age 17 was positively associated with OCD symptoms at age 19. In European American females, OCS and cannabis use were positively associated at age 17 and there was moderate stability in cannabis use over time. In African American males, there was moderate stability in OCS and high stability in cannabis use over time. Cannabis use at age 17 was positively associated with OCS at age 19. In African American females, OCS and cannabis use were positively associated at age 17 and there was moderate stability in OCS and cannabis use over time.

6 |. DISCUSSION

Previous research has demonstrated that higher levels of OCS are associated with cannabis use (Nicolini et al., 2021; Spradlin et al., 2017), but less is known about these associations in adolescence or how genetic predisposition for OCS contributes to associations among these constructs over time. The current study examined a PRS for OCS as predictive of OCS and cannabis use across adolescence. In support of our first hypothesis that OCS and cannabis use would be positively associated within and across time, cannabis use and OCS were associated at age 17 in the full sample and all subgroups, except African American males. Over time, cannabis use at age 17 was associated with OCS at age 19, but not vice versa, in both the full sample and African American males. Whereas some research indicates that cannabis use can reduce OCS and anxiety (Kayser, Raskin, et al., 2020; Szejko et al., 2020), several studies indicate the potentially acute, anxiety-inducing impact of cannabis use in controlled settings (Feingold et al., 2016; Fusar-Poli et al., 2009). Other studies note that OCD symptomatology is exacerbated with greater use of cannabis (Buckner et al., 2007; Spradlin et al., 2017). This is further supported in the current study by the present findings, indicating that cannabis use may have exacerbated OCS within and over time.

Our second hypothesis was that higher levels of genetic risk for OCS would be associated with greater levels of cannabis use and OCS over time. Interestingly, in the full sample and European American males, the OCS PRS was negatively associated with cannabis use at age 17. The OCS PRS was positively associated with OCS at age 19 in the full sample. The positive effect of the OCS PRS on OCS at age 19 may be because early adulthood is a stressful transitional period during which a genetic effect emerged (Wheaton & Clarke, 2003). The finding that the OCS PRS was associated with lower levels of cannabis use is contradictory to previous studies examining cannabis misuse and dependence in people with obsessive-compulsive symptomatology (Nicolini et al., 2021), yet another study found no difference between mean levels of a PRS for OCS based on OCS and cannabis use. These divergent findings could be due to differences between existing research and the present study including European Americans and African Americans and different measures of cannabis use across studies. Moreover, Nicolini et al. examined this in a sample ranging from 12 to 65 years old, whereas the current study examined this at age 17–19. It may also be that these associations are developmentally sensitive. The negative association with the OCS PRS was only seen for age 17 cannabis use and not age 19 cannabis use, which may be due to the increased regular use of cannabis in young adulthood compared to adolescents (Coffey & Patton, 2016) who are more likely to experience adverse outcomes by engaging in cannabis use earlier (e.g. difficulties concentrating and learning in school) (Centers for Disease Control and Prevention [CDC], 2021). Whereas the negative association between the OCS PRS and cannabis use appears counterintuitive, this may occur because those with a predisposition for OCS have some underlying symptoms and actively refrain from cannabis use in effort to avoid exacerbating OCS. This trend has been seen with other psychiatric disorders, such as schizophrenia (Rabin et al., 2017, 2018). Thus, the potential benefits of cannabis use to alleviate anxiety or compulsions may not outweigh the risks for these individuals. It may also be that negative genetic associations are specific to adolescence, as this can be a stressful developmental period characterized by new social experiences, increasing independence, and biological changes, all of which may exacerbate underlying OCS, leading adolescents to less cannabis use.

Strengths of this study include the developmental examination of the associations among a PRS for OCS, OCS, and cannabis use in European Americans and African Americans and by gender across adolescence. Limitations include that the measure of OCS was different at age 17 versus 19, but these measures were moderately correlated and are both established measures of OCS. Also, the study population was ethnically diverse, however, the discovery of GWAS was based on European American individuals limiting the portability of the OCS PRS to the diverse sample (Martin et al., 2019). In addition, although we leveraged a meta-GWAS on OCD, the discovery sample size was still small, highlighting the need for future large GWAS, especially in diverse populations. Currently, there is a lack of GWAS on OCS in diverse populations, precluding the formation of aligned PRS. Future research should pursue the examination of the genetic predisposition for substance use and mental health as predictors of these outcomes in more diverse samples.

Despite these limitations, this study identified important etiological factors in OCS and cannabis use in adolescence. Findings have important implications for future prevention and treatment programs among adolescents with OCS and cannabis use. For instance, in complement to substance use education, it may be important to educate youth about OCS, among other psychiatric symptoms, and the risks that substance use may exacerbate symptoms later in life.

ACKNOWLEDGMENTS

We gratefully acknowledge the contribution of the Project Alliance staff, Portland Public Schools, and the participating families. The research reported in this paper was supported by grants from the National Institute of Drug Abuse (TH, DA007031) and (KKE, DA042828, also supported by the Office of the Director and Office of Behavioral and Social Sciences Research). Additional support was given by the National Institute on Alcoholism and Alcohol Abuse (TH, AA022071). The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institute on Drug Abuse, the National Institute on Alcoholism and Alcohol Abuse, or the Office of Behavioral and Social Sciences Research.

Footnotes

CONFLICT OF INTEREST

The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Associated Data

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

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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