Primary, Secondary and Tertiary Prevention of Pediatric OCD: History
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Xingyu Liu
,
Qing Fan

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by intrusive, repeated and persistent thoughts, desires or images, with subsequent repetitive behaviors or thinking patterns that the individual performs in an attempt to decrease the anxiety or distress or simply according to rigid rules (i.e. compulsions).As a distinctive subtype of OCD, pediatric-onset OCD affects around 2% to 4% of children and adolescents. Considering that children and adolescents are in a critical stage of physical and cognitive development, the onset of OCD during this period may lead to additional developmental disruptions.There is an urgent need for early diagnosis and treatment for OCD, especially the strategies targeting the childhood age group. 

  • pediatric obsessive-compulsive disorder
  • prevention
  • early identification

1. Introduction

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by intrusive, repeated and persistent thoughts, desires or images, with subsequent repetitive behaviors or thinking patterns that the individual performs in an attempt to decrease the anxiety or distress or simply according to rigid rules (i.e. compulsions) [1]. This chronic brain disorder demonstrates a bimodal onset, with one peak at 12–14 years and another at 20–22 years [2]. Studies in adults support the notion that OCD is a lifelong chronic disorder, whereas studies in youth suggest that a high percentage of patients have an episodic course [3]. As a distinctive subtype of OCD [4], pediatric-onset OCD affects around 2% to 4% of children and adolescents [5][6]. Considering that children and adolescents are in a critical stage of physical and cognitive development, the onset of OCD during this period may lead to additional developmental disruptions [7]. Symptoms of pediatric OCD may be less severe, but it can persist throughout the lifespan if left untreated, causing widespread academic, occupational and social damage and reducing the quality of life [8].
Considering that OCD is a debilitating disorder that worsens over time, and symptoms of the disorder can begin very early on—more than half of adult OCD patients have already exhibited subclinical symptoms in childhood [9][10]—there is an urgent need for early diagnosis and treatment [7][11][12][13], especially the strategies targeting the childhood age group [11]. Some studies have found that OCD remission rates in children are much higher and more persistent than in adults [3][8][14]. However, the duration of untreated obsessive-compulsive disorder remains one of the highest of all psychiatric disorders [15], with a gap between onset and diagnosis of approximately 7–10 years in adults and an average of more than two years in children [16][17]. These findings are worrying, especially because a longer disease course predicts a poorer long-term outcome [8]. Meanwhile, research on early identification and interventions for OCD is still in its infancy [7][13]. The OCD treatment guideline in the UK has emphasized the importance of stepped care, which aims to provide the most effective but least intrusive treatments appropriate to a person’s needs, but it did not indicate the concrete interventions that can be taken in the early stages [18]. Fineberg et al. [7] conceptualized the primary, secondary and tertiary prevention of OCD based on the clinical staging model of OCD proposed by Fontenelle and Yücel [19]; however, current research evidence of pediatric OCD is still very limited in constructing a complete prevention framework.

2. Primary, Secondary and Tertiary Prevention of Pediatric OCD

Applying the concept of the three-level prevention to early intervention for OCD has been called for by many scholars [7][11][13]. Primary prevention aims at preventing the development of OCS. Secondary prevention is identifying and treating individuals who develop OCS to prevent progression to full-blown OCD. Finally, tertiary prevention reduces the significant comorbidity and minimizes the impact of OCD once individuals have been diagnosed [7][11]. At present, early interventions for OCD achieved in the clinical field are focused on the stage of secondary prevention. However, in this entry researchers suggest that all three prevention levels should be taken into account. The implementation of each level of prevention in pediatric OCD will be separately discussed.

2.1. Primary Prevention

The achievement of primary prevention requires, at least, the precise identification of at-risk individuals for pediatric OCD and the implementation of a specific approach to improve their resilience and resistance to OCD symptoms developing. However, limitations in understanding the etiology of pediatric OCD have led to very little progress in either aspect. In the following, researchers will review the new approaches that have emerged in recent years that may help advance the identification of at-risk populations and provide an outlook on advisable directions for primary prevention.

2.1.1. Polygenic Risk Scores (PRS)

Although existing genetic studies cannot yet help determine the exact etiology of pediatric OCD, it may be feasible to identify at-risk groups with the help of Polygenic Risk Scores (PRS). Based on GWAS findings, PRS reveals an individual’s genetic risk of developing a disease by detecting all the risk alleles carried by the individual and weighting them according to their effects [20].
It has been found that the OCD PRS can significantly predict an individual’s OCD status, and the personality trait of harm avoidance mediates the association between OCD PRS and OCD diagnosis [21]. Similarly, the potential of the application of PRS in identifying subclinical populations of pediatric OCD was also demonstrated in another study, as it was discovered that polygenic risk for OC traits was associated with OCD case/control status and vice versa [22]. However, the cross-race consistency of PRS results remains to be tested, and the large-scale clinical adoption of PRS for risk assessment and disease diagnosis is still not achievable [13].
One study also investigated whether PRS could be used to predict treatment outcomes in OCD, although the outcome could not demonstrate its practicality [23]. This result needs to be verified by more investigation.

2.1.2. Identifying Endophenotypes

Endophenotypes are inheritable intrinsic traits between the genes and the extrinsic phenotype. They can be found both in patients and their unaffected relatives [24], and need to be measured by neurobiological, biochemical, neuroanatomical, cognitive and neuropsychological laboratory techniques [25]. Because endophenotypes are more closely related to the underlying genetic basis than the behavioral phenotypes and are less influenced by genetic and environmental heterogeneity than the disease itself, they are thought to be more helpful in identifying the genetic variants, etiology and the pathophysiological basis of the disease [24]. By identifying the endophenotypes of pediatric OCD, it can be further precisely located the genes affecting those endophenotypes and thus learn about the biological pathways affecting disease susceptibility, which could help identify populations at high risk for pediatric OCD and inform potential targets for early intervention [24][26][27].
A systematic review focused on the currently proposed neurocognitive endophenotypes of pediatric OCD in 43 studies, finding that abnormal action monitoring is considered a robust endophenotypic feature of pediatric OCD, which has been confirmed by high amplitudes of ERN and abnormal activation in ACC; intolerance of uncertainty, possible impairment of planning ability and the hyperactivity of the frontoparietal regions in working memory tasks are potential endophenotypes, though the results of the available studies are inconsistent [28]. A recent study has provided insights into error-related brain activity in pediatric OCD by time-domain and time-frequency analysis, suggesting that pediatric OCD may be characterized by enhanced error monitoring (i.e., greater theta power) and post-error inhibition (i.e., greater beta power) [29]. However, the participants selected for the study were only pediatric OCD patients, which means the current result has not been validated in their unaffected relatives. Therefore, it remains to be tested whether this can be considered a neurobiological marker for screening at-risk populations.
In addition, deficits in cognitive flexibility and response inhibition, which are commonly found in adult OCD, have not been demonstrated as neurocognitive at-risk markers in pediatric OCD [28][30], suggesting that the cognitive function of the pediatric OCD patients may not be impaired at the onset, but will gradually lead from neurological dysfunction to cognitive impairment during the course of disease progression [31]. Therefore, more attention should be paid to neurological dysfunction rather than abnormalities in cognitive-behavioral performance.
Linking candidate neuropsychological endophenotypes to single nucleotide polymorphisms (SNPs) in genotypes could help confirm whether these intrinsic traits are associated with any candidate genes for OCD and, thus, how endophenotypes interact with genes, environment and disease [28]. A recent study has combined neuroimaging analysis, GWAS and PRS to investigate genetic variants associated with pediatric obsessive-compulsive behaviors (OCB) and imaging endophenotypes, meanwhile determining the relationship between brain activity and pediatric OCB. However, no significant results have been found so far [32]. More research is needed in this field.
Besides, it is now widely recognized that psychiatric disorders are heterogeneous; thus, not everyone with a disorder can be expected to have the same endophenotype, nor are endophenotypes necessarily disorder-specific [24], which is vital for understanding the genetic basis of comorbidities and may contribute to tertiary prevention, yet practice evidence is lacking.

2.1.3. Psychoeducation and Life Style Interventions

Given that the target population for primary prevention has not yet shown typical OCS, the intervention approach for them should be different from that for patients with psychiatric disorders.
The relatively viable natural candidate is psychoeducation. Psychological education in primary interventions is expected to raise people’s awareness of pediatric OCD and help parents identify their children’s risk traits early [11][19][33]. However, these strategies have not been fully evaluated, and there is no idea whether psychoeducation is likely to be effective in protecting against pediatric OCD.
Another helpful attempt is lifestyle intervention. Potential intervention targets supported by current research evidence are developing anti-inflammatory diets and increasing physical activity [34]. Other researchers have suggested that interventions should focus on reducing stress and improving sleep quality [19]. These proposals have also yet to be empirically tested.
Finally, as mentioned before, the difficulty in implementing primary prevention lies not only in researchers' limited knowledge of the etiology of pediatric OCD but also in the fact that at-risk individuals without clinical symptoms are not motivated to seek help. Therefore, the scientific awareness of pediatric OCD should be widespread in the general population, requiring numerous professionals’ involvement.
Overall, psychoeducation is currently the most viable intervention in the primary prevention stage. It is believed that the involvement of schools will contribute to spreading its impact. For example, providing educational lectures and courses at all grade levels in school to enable more students and their parents to tell if they are at high risk (e.g., having a family history of OCD) may help bridge the target population and other prevention strategies that are appropriate for them. Researchers also consider introducing neuropsychological tests that do not require complex equipment into the routine health examination program for all populations as a cost-effective way to help with early identification, which also has great potential for future applications. As for PRS and neuroimaging, which require the support of complex equipment and technical expertise, it is difficult to achieve population-wide application. When they do become available for clinical use, making these techniques available to children and adolescents with a family history of OCD is the primary goal that should strive to achieve, although this process still faces the challenges of ethics, health economics and the availability of resources to action, etc. [35].

2.2. Secondary Prevention

In the secondary prevention phase, it is necessary to identify patients with obsessive-compulsive symptoms early and to enable them to be treated as soon as possible to avoid the development of full-blown OCD. Current identification methods, as well as interventions that contribute to secondary prevention, will be reviewed in this section.

2.2.1. Screening for Early Symptoms

Clinicians should monitor obsessive-compulsive symptoms in children and adolescents, even if they are not currently perceived or complained about by the subject [36]. The school should also be actively involved in this process, considering that students spend so much time on campus. Nevertheless, the efforts of school psychologists in this area have been minimal [37][38]. Several studies have identified potential subthreshold/early symptoms of OCD. For example, symptoms of the symmetry and order dimensions (detected by the Dimensional Yale-Brown Obsessive-Compulsive Scale, DY-BOCS [39]) that have been found to have the earliest onset (13.6 ± 8.6) [40]; “Can’t get mind of certain thoughts” and “Fears might think or do something bad” are the most common symptoms among those who exhibit high OCS in early childhood [41], while “Repeats certain acts over and over” is the most common symptom among those who exhibit high OCS in adolescent periods (detected by the eight-item Obsessive-Compulsive Scale [42]). As mentioned in Section 2.2, a precise distinction needs to be made between normal rituals/routines and maladaptive OCS in the evaluating process, and age is currently the most helpful basis for clinicians to make judgments [43].
Not all early symptoms will turn into full-blown OCD [44]. Based on current knowledge, children and adolescents with OCS are more likely to develop full-blown OCD if they present with other risk factors such as parents with OCD [45][46], maladaptive parenting style [45], attention problems [41], anxiety and depression disorder [47][48] at the same time. Therefore, the abovementioned factors must be carefully investigated while monitoring for OCS.
Long-term follow-up testing is recommended, with immediate intervention if symptoms continue to deteriorate.

2.2.2. Bibliotherapy

Bibliotherapy is the use of books or stories for therapeutic purposes to help an individual gain insight into his or her problems [49]. It not only helps children to understand complex concepts better and cope with frustrating news but also helps clinicians and parents who have difficulty describing the nature of a diagnosis of a disease to their children [49]. All kinds of books can be used for bibliotherapy, including poetry, storytelling, fiction or nonfiction [50]. It can educate readers, provide insights, encourage discussion, provide solutions to problems or new ways of looking at them and make people realize that they are not alone in their situation [51].
Attempts have been made to use bibliotherapy for the secondary prevention of pediatric OCD. Amazing Adam and the Secret Spell is an illustrated book written for children ages 6-10 who are experiencing symptoms of OCD, designed to help readers identify and understand their obsessive-compulsive symptoms, overcome shame and encourage them to seek treatment [49]. So far, readers’ feedback has proven its promising application, yet the large-scale dissemination and output of more language versions of the same type of picture book are still lacking.
Another use of bibliotherapy in pediatric OCD early intervention is showing children how to process self-help cognitive-behavioral therapy (CBT). Cognitive-behavioral therapy is a first-line treatment for OCD in children and adolescents in line with a robust evidence base [36][52]. Some examples of CBT that individuals can implement include activity scheduling, goal setting and cognitive restructuring. Until now, there have been at least three CBT self-help books written specifically for children and adolescents with OCD [53][54][55], but studies of the effectiveness of such books as an intervention in clinical settings are scarce; therefore, their effectiveness and applicability need to be further confirmed [52].

2.2.3. Novel Digital Interventions

The popularity of smartphones and smart electronic wearables provides new opportunities for the early identification of intervention in pediatric OCD.
First, the development of digital phenotypes has led to more observable indicators for the early identification of obsessive-compulsive disorder. For example, some forms of the problematic use of the Internet (PUI) associated with OCD (e.g., repeatedly checking social media, digital hoarding, etc.) can be accurately recorded by digital media. In turn, clinicians can use big data analysis to identify individuals who exhibit digital obsessive-compulsive symptoms [56][57][58].
At the same time, the web-based self-assessment questionnaire also showed good sensitivity and sufficient specificity for detecting OCS when compared with a full-length structured clinical interview. This form of measurement can effectively make it easier for more patients and at-risk individuals to identify and monitor their mental health status [57].
Furthermore, a smartphone app for conducting CBT interventions for OCD has been proven effective, allowing patients to perform relevant CBT exercises at home to recognize and improve their emotions and maladaptive cognitions, helping to reduce OCD-related beliefs and symptoms [59].
Finally, the proactive use of webcams and smartphone cameras gives clinicians the opportunity to monitor individuals’ behavior in the natural environment and the possibility to intervene remotely with CBT, which can significantly reduce the cost of disorder treatment and achieve early detection and intervention for secondary prevention [58].
A professional team has developed an enhanced cognitive behavioral therapy (eCBT) package for pediatric OCD, including a smartphone app with psychoeducational tools, OCD-related symptom assessment tools and ERP training guidance tools for pediatric OCD patients and their parents. It also contains a video conferencing platform that supports face-to-face therapy sessions using a webcam. The effectiveness of this package has been preliminarily proven to have positive treatment outcomes, and it is expected to see more integrated online intervention products promoted in the population in the future [60][61].

2.3. Tertiary Prevention

To date, the duration of illness before treatment was the only stable predictor of long-term course in pediatric OCD [3][62]. Evidence from multiple studies suggests that longer untreated illness duration is associated with many unwanted outcomes, including higher rates of comorbidity and disability, greater family accommodation [63][64], poorer treatment response [65][66][67] and more delayed [68] and less frequent remissions [69]. Therefore, clinicians should provide patients with treatment as early as possible after symptoms have reached the severity of a clinical diagnosis of OCD. According to existing studies, it is not confirmed whether factors such as the severity of symptoms, family accommodation, family history of OCD and comorbidities are associated with a long-term course [3][62], but they are usually related to treatment response and symptom/diagnostic remission [70][71][72]. Improving existing evidence-based treatment protocols to enable patients to receive adequate, specific treatment early is essential to enhance tertiary prevention. Researchers will elaborate on current options for the potentially more effective evidence-based treatment of pediatric OCD in the following.

2.3.1. Pharmacotherapy and Psychotherapy: Alone or in Combination

Effective pharmacological and psychological treatments for pediatric OCD have been established and in clinical use for many years [73]. Among the pharmacological treatments, selective serotonin reuptake inhibitors (SSRIs) are considered the first-line option for pediatric OCD patients [74][75], including fluoxetine, fluvoxamine, sertraline, paroxetine and escitalopram, etc. Patients may respond differently to various medications, and in cases of non-response or inadequate response to one SSRI, another SSRI should be tried [58]. Psychotherapies such as cognitive behavioral therapy (CBT), especially with exposure and response prevention (ERP), are also recommended treatments for children and adolescents with OCD [36][76].
A network meta-analysis showed that the effects of accepting CBT alone and combined with drug therapy were comparable and better than those for youths with mild and severe pediatric OCD [77]. Recently, a retrospective study also showed that one-third of the children and adolescents in the sample did not respond to treatment with SRIs alone, and the existence of symmetry/hoarding symptoms is also associated with poorer response to pharmacological treatments [78]. However, not all patients can benefit from a single CBT treatment in the early treatment phase; for children and adolescents with a family history of OCD, only CBT combined with SSRIs treatment may result in significant improvement [71].
Evidence suggests that medication is not preferred for the early treatment of pediatric OCD compared to CBT. When making specific clinical decisions, information on the patient’s characteristics, such as the family history of OCD and clinical presentation of symptoms, must be considered to optimize treatment planning and provide more accurate prognostic information. More longitudinal studies are required to explore which treatment options are more resistant in reducing relapse and chronic functional disability in the long term.

2.3.2. Family-Based Treatment

Considering that children are deeply embedded in family units, the prospects for intervention in the family environment in tertiary prevention are of great concern.
One of the most well-studied structures of family factors in pediatric OCD is family accommodation (FA), which refers to the act of parents, siblings, or partners accommodating the high-risk individual’s requests to comply with their compulsions in order to avoid or alleviate distress. It is associated with a greater severity of OCD symptoms, more impairment and poorer treatment outcomes [79][80][81]. Reducing FA is considered a promising intervention in all three levels of prevention. However, in this entry researchers only mention it in the third stage because the impact of FA on full-blown OCD has been most intensively studied, while evidence from longitudinal studies that could demonstrate the efficiency of interventions for FA in the primary and secondary prevention stages of pediatric OCD is still lacking [7][11].
Related to the increase in FA are greater parent–child conflict and parental blame. It takes time and effort for parents to adjust to their child’s compulsive behaviors; therefore, a child’s compulsion or avoidance is not tolerated every time. When a parent refuses to accept the behavior of their child with pediatric OCD, the child may show anger or behavioral outbursts [82][83]; in addition, the parent may feel guilty or have more blame expressed toward the patient [84][85]. All of these can affect treatment outcomes [86]. Therefore, the role of family-based intervention approaches for pediatric OCD cannot be underestimated.
There are many ways that parents can be involved in their child’s OCD treatment process. Psychoeducation is one of the available forms; it can be conducted for parents alone or as part of family-based CBT (FCBT) treatment for different purposes, such as increasing parents’ knowledge of mental health, helping create a more supportive family environment, improving their parenting styles and raising parents’ awareness of FA [84]. Furthermore, FCBT interventions include teaching parents to reduce FA, training them to assist their children with homework and ERP therapy and helping parents identify and cope with the pain and anxiety they feel when facing their child’s OCD [87][88][89][90]. Studies have shown that these FCBT techniques have similar effects on parents and OCD children [87]. Parents should also learn to properly communicate with their children about thoughts and emotions [84]. Group FCBT has also provided a new approach to parental involvement, although the current evidence suggests that it is not as effective as individual FCBT [87]. To researchers'  knowledge, no current studies have compared the efficacy of FCBT with conventional CBT for pediatric OCD, but given the high familial heritability of pediatric OCD [91], promoting family-based treatment is a necessary complement to traditional first-line psychotherapy.

2.3.3. Transdiagnostic Treatment

Although the DSM-5 constructed classification system for mental disorders is dominant in clinical practice, which has detailed diagnostic criteria for OCD, it also acknowledges that the symptoms in the current diagnostic criteria are not specific to OCD alone. There are 14 other disorders (or disorder classes) whose symptoms also broadly fit these criteria, and even after a careful differential diagnosis, co-morbidities remain in many cases [92][93]. As a result, there are calls for the creation of new biologically relevant transdiagnostic traits linking genes, molecules, cells, neural circuits and behavioral manifestations across multiple diseases [92]. The therapeutic approaches thus extended will focus on the link between neurocognitive markers and treatment response.
In pharmacotherapy, some studies have begun to investigate whether neurological markers (e.g., OFC gray-matter volume) shared by OCD with other mental disorders can be used as predictors of the treatment response for SSRIs [94] in order to assist in determining the optimal medication dose when coping with co-morbidities in clinical decision making, though current studies have not obtained stable results at present, and study samples in children and adolescent populations are lacking.
As for psychotherapy, principle-driven intervention protocols that target underlying shared mechanisms of comorbidities rather than symptoms complement evidence-based treatment [95]. An emotion-focused transdiagnostic intervention therapy, the Unified Protocols for Transdiagnostic Treatment of Emotional Disorders in Children and Adolescents (UP-C/UP-A) [96], has been shown with significant improvement in obsessive-compulsive symptoms in children and adolescents. However, the samples selected for this study were all patients with anxiety/depression disorders; it is unclear whether equivalent effects would be seen in patients with OCD co-morbidities [97].
In addition, the potential application of a non-invasive neurostimulation technique, transcutaneous auricular vagus nerve stimulation (taVNS), is of interest to treat neurodevelopmental disorders in children and adolescents. It has been shown that by targeting stimulation sites and parameters, taVNS has modulatory effects on cortical and subcortical brain regions associated with the neuropathology of ADHD, DBD, ASD and OCD, etc., further helping regulate some impaired social-emotional functions that are impaired in them [98][99][100][101]. This technique has an extensive potential application for reducing functional impairment in the tertiary prevention phase of pediatric OCD and deserves to be studied on a larger scale in the pediatric population.

This entry is adapted from the peer-reviewed paper 10.3390/brainsci13030399

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