Impact of psychiatric comorbidity,resilience and executive function on childhood and adolescent headaches: A narrative review

Abstract

Background

The impact of psychiatric comorbidities in children and adolescents with headache disorders can be more comprehensively understood through a biopsychosocial perspective, which examines the dynamic interplay of factors beyond headache attacks. Resilience and executive function emerge within this framework, playing a central role in development psychopathology and other critical domains.

Methods

This narrative review aimed to examine the impact of psychiatric comorbidity on migraine and/or high-frequency headaches (HFH) in children and adolescents through a biopsychosocial perspective centered on the role of resilience and executive function (EF), exploring their potential clinical implications. PubMed was searched for English language articles of human participants, from birth to 18 years, published up to 10 April 2025.

Results

Clinical and population-based studies suggest that children and adolescents with migraine and/or HFH are at an increased risk of low resilience and EF impairments. Preliminary interaction and multivariate analyses suggest that high vulnerability (the counterpart to resilience) exerts a moderating role in the psychiatric comorbidity of migraine, as well as a mediating effect in the association of HFH with psychiatric symptoms and disorders. Candidate predictors of psychiatric comorbidity in youths with migraine and/or HFH include EF impairment, high vulnerability, female sex, low socioeconomic status, prenatal exposure to tobacco, poor academic performance and headache attacks accompanied by nausea and vomiting.

Conclusions

The multidimensional impact of psychiatric comorbidities on children and adolescents with headache disorders is clearly demonstrated by consistent evidence of their adverse effects on headache severity and chronification, as well as negative outcomes in quality of life, cognitive performance, academic achievement and overall patient well-being, leading to long-term continuity across childhood, adolescence and adulthood. Most of this impact is probably due to the interactions between reduced resilience, increased vulnerability and EF impairment. This narrative review underscore the relevance of routinely assessing psychiatric symptoms, resilience, executive function skills and school functioning in children and adolescents with headache disorders. Future studies should examine whether early interventions focused on resilience, vulnerability and EF can prevent psychiatric comorbidities and improve headache outcomes in children and adolescents with migraine and/or HFH.

Graphical abstract

This is a visual representation of the abstract.

Keywords

biopsychosocial executive function migraine psychiatric comorbidity resilience vulnerability

Introduction

The multidimensional impact of headache disorders on developmental age has been extensively reported, revealing adverse outcomes extending beyond headache attacks alone, affecting multiple domains. Children and adolescents suffering from migraine and/or high-frequency headache (regardless of the diagnosis) are at an increased risk of having a reduced quality of life (1,2), worse neuropsychological functioning and school achievement (3,4), parenting stress (5), psychosocial adjustment problems (6), and psychiatric comorbidities (7 –10).

Cross-sectional and longitudinal studies have reported the comorbidity of migraine and/or high-frequency headache in children and adolescents with somatic, depressive and anxiety symptoms (11) and disorders (11 –14), suicide ideation (15,16), and attention deficit hyperactivity disorder (ADHD) (17 –19).

Psychiatric comorbidities, particularly ADHD, anxiety and depressive disorders, have a substantial negative impact on the quality of life and daily functioning of children and adolescents with headache disorders (20 –22). Multiple studies have demonstrated that the presence of psychiatric symptoms and/or disorders are associated with greater headache-related disability, poorer overall quality of life and increased impairment in social, academic and family domains (20 –23). Notably, the degree of functional impairment and quality of life reduction are more closely related to the presence and severity of psychiatric symptoms than headache frequency or intensity alone (20,21,24). This suggests that psychiatric comorbidity acts as an independent and additive factor in determining overall impact.

Although the impact of psychiatric comorbidity in children and adolescents with headache disorders is well documented, there remains a paucity of knowledge regarding the underlying neurobiological mechanisms, developmental psychopathology pathways, directionality of comorbidity and potential predictors, mediators or moderator factors (25).

The impact of psychiatric comorbidity on migraine and/or high-frequency headache in children and adolescents can be better understood from a biopsychosocial (BPS) perspective. Unlike the traditional biomedical model, which primarily centers on pathophysiological processes, the BPS model focuses on the dynamic and reciprocal influences of internal (biological and psychological) and external (lifestyle, family and social) factors involved in headache disorders, beyond headache attacks (26). These factors can act as predisposing, precipitating, perpetuating, and/or protective factors, with immediate implications for the treatment decision-making process (27).

Although the BPS model is widely applied in the management of chronic pain syndromes, its clinical application and research in headache disorders remain limited (26).

BPS models have been suggested as a framework for understanding migraine in both children (28,29) and adults (26). The complex pathogenesis of migraine, involving a multitude of internal and external factors characterized by circular causality, may be effectively addressed through the application of BPS models (26). These models encompass a range of factors interacting with the underlying biological mechanisms and categorized as internal (e.g. psychologic features, mood, personality traits, physical and psychiatric comorbidities) and external (e.g. socioeconomic status, lifestyle, habits, family and social support) (26,29).

We take advantage of this narrative review to propose an evidence-based BPS model for migraine and/or high-frequency headache in children and adolescents with the aim of better exploring the impact of psychiatric comorbidities by focusing on self-regulatory skills that play a critical role in the development of psychiatric comorbidities and other BPS factors (Figure 1).

Figure 1.

The biopsychosocial model for migraine and high-frequency headaches in children and adolescents.

Beyond the usual targets of prophylactic and acute treatment of migraine and/or high-frequency headaches, the BPS model proposed here places resilience and executive function at the root of the potential outcomes of internal and external factors that ultimately determine the quality of life. Among the external factors, the model includes socioeconomic status, lifestyle and habits (sleep, exercise, diet and screen time), as well as familial and social support. On the other hand, the internal factors comprise the following outcomes: social competence, cognitive and academic performance, coping skills (pain acceptance and self-efficacy), psychosocial adjustment (behavior and emotions), physical (obesity and rheumatologic diseases), and psychiatric comorbidities (Figure 1).

There is robust and convergent evidence from longitudinal, meta-analytic, and systematic review studies linking self-regulatory skills, particularly resilience and executive functions, to the development and maintenance of psychiatric disorders in childhood and adolescence (30 –32). Executive functions and resilience are also predictors of short- and long-term academic achievement, social competence, mental health and healthier lifestyle behaviors, as well as a reduced risk of physical illness in adolescence and adulthood (33).

A recent meta-analysis and clinical and population-based studies have provided initial evidence that children and adolescents with migraine and/or high-frequency headaches are at increased risk of low resilience and executive function impairment (4,34,35).

Accordingly, this narrative review aimed to examine the impact of psychiatric comorbidity on migraine and/or high-frequency headaches in children and adolescents through a BPS perspective centered in the role of resilience and executive functions exploring their interactions and potential clinical implications.

Methods

PubMed was searched for English language articles of human participants, from birth to 18 years, published up to 10 April 2025, using the following MeSH terms and variations included in the title or abstract of the manuscript: “headache”, “primary headache”, “migraine”, “headache disorder”, “chronic headache”, “tension-type headache”, “mental health”, “comorbidity”, “psychiatric comorbidity”, “psychiatric symptoms”, “psychiatric disorders”, “psychological symptoms”, “behavioral symptoms”, “psychosocial adjustment”, “resilience”, “vulnerability”, “coping”, “executive function”, “self-regulatory skills”, “biopsychosocial”, “neuropsychiatric”, “neuropsychological”, “cognition” and “cognitive”.

The references of the selected studies were screened for additional publications.

Of the 1667 initially identified records, 1282 were excluded due to duplicates and after screening the title. Of the remaining 385 records, 304 were excluded after screening the abstract and full-text review, resulting in 81 studies being included in the narrative review (Figure 2).

Figure 2.

Flow-chart of the literature search.

Psychiatric comorbidity

The association between psychiatric symptoms and primary headaches disorders in children and adolescents is supported by evidence from clinical, population-based, cross-sectional and longitudinal studies. A recent systematic review and meta-analysis specifically focused on internalizing symptoms and disorders in 80 selected clinical, community and population-based studies, and demonstrated that children and adolescents with migraine are at an increased risk of anxiety and depressive symptoms (14). Additionally, these individuals exhibited significantly higher odds of being diagnosed with anxiety and depressive disorders than non-headache controls (14).

A study assessing the data of a nationally representative sample of American youth (The National Comorbidity Survey) found that adolescents with headache and/or migraine, compared to non-headache controls, were more than twice as likely to meet the criteria for a DSM-IV disorder, particularly anxiety and depression in those with migraine (12). Anxiety and depressive disorders were also more prevalent among adolescents with migraine than among those with non-migraine headaches. This study also identified an association between migraine and substance use, eating and disruptive behavior disorders (12).

Clinical and population-based studies have also reported the association of migraine in children and adolescents with somatic symptoms (11,36), social problems (11), oppositional defiant disorder (12) and ADHD (17 –19). Longitudinal population-based studies have also shown the association of psychiatric symptoms and disorders with a higher frequency and severity of headache attacks, worse evolution, earlier onset and chronification of migraine throughout adulthood (37 –40).

Some common predictors of the association between migraine and psychiatric symptoms and disorders in children and adolescents have been identified in a series of cross-sectional population-based studies using a uniform methodology. A higher frequency of migraine attacks (≥10 days per month) predicted an association of migraine with internalizing and externalizing symptoms (11), psychosocial adjustment problems (6) and ADHD diagnosis (17). Interestingly, migraine attacks accompanied by nausea, phonophobia and/or photophobia predicted the association with psychosocial adjustment problems (6). Headache, nausea and vomiting are among the most frequent functional somatic symptoms in children and adolescents associated with young adult psychopathology (41). Prenatal exposure to tobacco was associated with ≥15 days of headache per month (42) and significantly predicted the association between migraine, psychosocial adjustment problems and ADHD diagnosis (6,17).

According to clinical and populational studies, children and adolescents with tension-type headache (TTH) have a higher risk of associated psychiatric symptoms and disorders compared to non-headache controls, even though in a lower magnitude than reported for migraine (6,9,11,43). Other studies have identified distinct patterns of comorbidities, with migraine showing a stronger association with ADHD and depression, whereas TTH appears to be more closely linked to anxiety and a broader spectrum of psychiatric symptoms (44,45).

There is consistent evidence that psychiatric comorbidity, particularly anxiety and depressive symptoms or disorders, negatively affects quality of life in children and adolescents with migraine and/or high-frequency headaches. Multiple cross-sectional and longitudinal studies, as well as systematic reviews, have demonstrated that internalizing symptoms such as anxiety and depression are associated with lower quality of life and greater headache-related disability in this population (14).

Compared to both healthy controls and migraineurs without psychiatric comorbidity, children and adolescents with migraine and comorbid psychiatric disorders exhibit significantly poorer quality of life, with notably lower scores in physical, emotional and social functioning domains (21). Furthermore, the presence of psychiatric comorbidity is associated with greater functional impairment, even when headache frequency, duration and severity are comparable to those without psychiatric comorbidity (24).

School functioning is significantly affected in children and adolescents with migraine and high-frequency headaches. Headache-related school absences are common and correlate with poor school performance and a reduced likelihood of attaining higher educational milestones (46,47). Psychiatric comorbidities, such as anxiety, depression and ADHD, further compounded these difficulties, contributing to increased absenteeism, lower grades and impaired school functioning (3,48,49).

As further discussed in this review, deficits in cognitive performance in children and adolescents with migraine have been reported in the literature and characterized as subtle, although clinically relevant. The presence of psychiatric comorbidities can exacerbate these cognitive vulnerabilities and further impair academic and daily functioning (50).

Social competence was also found to be negatively affected. Children and adolescents with headache, especially those with psychiatric comorbidities, are at increased risk for social isolation, fewer friendships, and reduced participation in extracurricular and social activities (46). The unpredictability of headache attacks, combined with emotional symptoms, can limit engagement with peers and contribute to broader social handicap (46).

The impact of psychiatric comorbidity extends beyond clinical outcomes; children with both headache and psychiatric disorders incur higher healthcare expenditures and are more likely to require more intensive medical interventions, including increased medication use and longer hospitalizations (51).

Although evidence supports the multidimensional impact of psychiatric comorbidities on children and adolescents with migraine and/or high-frequency headaches, the potential cumulative and additive effects of these numerous factors remain poorly understood.

Resilience and vulnerability

Childhood resilience plays a central role in the BPS model and is currently defined as a dynamic developmental process that enables a child to adapt positively when confronted with significant life adversities (52,53). Conversely, vulnerability is defined as increased susceptibility to negative outcomes when an individual is exposed to risk or adversity. Resilience counterbalances vulnerability and a greater resilience is correlated with a lower vulnerability, whereas a reduced resilience is associated with an increased vulnerability (52).

Resilience has been identified as a reliable predictor of better mental health and quality of life in children and adolescents with chronic illnesses, including type 1 diabetes, cancer, inflammatory bowel disease, asthma and chronic pain (54). Despite the scarcity of studies on resilience and vulnerability in children and adolescents with headache disorders, preliminary evidence suggests an association between low resilience and high vulnerability with high-frequency headaches (34) and the possible moderating role of low resilience in headache-related disability (55).

Rather than being a fixed personality trait or solely an individual characteristic, resilience is conceptualized as a two-dimensional construct involving both exposure to adversity and the achievement of positive adjustment outcomes (53). This adaptive process may arise from individual factors (e.g. coping skills and genetic predispositions), environmental influences (e.g. parental and community resources) or the interaction between the two (32).

Positive adaptation refers to a child's ability to achieve healthy psychological, emotional or social functioning even after experiencing significant adversity. In the context of resilience, positive adaptation means not just recovering from difficulties but also maintaining or regaining well-being, normal development, and effective functioning in daily life (52).

According to the literature, high resilience is related to personal traits, such as optimism, sense of trust and self-efficacy, adaptability, perceived support availability, comfort with others and acceptance of differences (52,56). Conversely, high vulnerability is associated with low threshold and intense emotional responses (sensitivity), limited recovery skills and significant challenges in managing strong emotional reactions (56,57). In addition to resilience, various protective factors can mitigate vulnerability including intellectual ability, easy-going temperament, autonomy, self-reliance, communication skills, sociability and effective coping skills (57). Apart from individual factors, resilience and vulnerability are also determined by family dynamics and community support in convergence with the BPS model, moderating the negative effects of psychiatric comorbidities (58).

Children and adolescents with lower resilience and/or higher vulnerability are at an increased risk of internalizing and externalizing symptoms (59), in addition to psychiatric disorders such as depressive and anxiety disorders (60), post-traumatic stress disorder (61), ADHD (62), schizophrenia and bipolar disorders (63).

The pivotal role of resilience in developmental psychopathology has also been recognized in the coping process of children and adolescents with chronic pain (64).

Although resilience and coping are frequently used indistinguishably, they represent distinct conceptual constructs. Resilience pertains to the appraisal of an event and subsequent selection of a positive coping strategy. By contrast, coping specifically refers to strategies or behaviors, whether positive (e.g. pain acceptance, pain self-efficacy) or negative (e.g. pain catastrophizing, fear of pain), which are employed following the appraisal of a stressful situation (65).

Resilience models for pediatric chronic pain have been proposed in the literature and have provided evidence for novel and more effective interventions. According to these resilience models, pain intensity, fear of pain, and pain catastrophizing are the main negative predictors of quality of life and functioning. Conversely, acceptance, optimism, self-efficacy, emotional regulation and cognitive flexibility (the latter two considered core executive functions) are key resilience characteristics and predictors of positive adaptation to chronic pain (64).

Evidence from clinical studies of children and adolescents with headache suggests that pain self-efficacy and pain acceptance are correlated with reduced disability, improved school functioning and fewer depressive symptoms, probably by mitigating the impact of headache-related fear (cephalalgiaphobia) (66,67). Interestingly, a recent clinical study found that adolescents with high-frequency migraine tend to exhibit dysfunctional coping strategies in response to stressful life events compared to low-frequency migraine controls (68).

A clinical cross-sectional study examining the potential factors involved in headache-related disability in adolescents found depression to be the only significant risk factor. It was negatively correlated with resilience, suggesting a possible moderating role of low resilience in headache-related disability in this sample (55).

The scarcity of studies examining the role of resilience and vulnerability in children and adolescents with primary headaches has hampered the development of a comprehensive risk-resilience model for pediatric headache disorders, thereby preventing the emergence and validation of innovative and effective interventions (34).

Given the increased risk of psychiatric comorbidities and maladaptive pain coping strategies reported in children and adolescents with migraine and/or high-frequency headache, we conducted a cross-sectional population-based study with adolescents to examine resilience and vulnerability profiles and explore the extent to which headache frequency and diagnosis are correlated with these outcomes (34). Resilience and vulnerability were assessed using the validated Brazilian version of the Resiliency Scales for Children and Adolescents (RSCA) (69,70).

The RSCA is a functional self-report instrument developed for literate children and adolescents aged 9–18 years to assess three core measurable constructs of resilience: sense of mastery, sense of relatedness, and emotional reactivity. The resilience score is computed as the average of the senses of mastery and relatedness scores, whereas the risk of vulnerability is computed as the difference between the resilience resources and emotional reactivity scores (Table 1) (69).

Table 1.

The core constructs of the Resiliency Scales for Children and Adolescents (RSCA) and their respective domains (69).

Core construct	Domains/subscales	Description
Sense of mastery	Optimism	Consists of positive attitudes about the world/life and one's own life
	Self-efficacy	The development of problem-solving attitudes and strategies
	Adaptability	The ability to be receptive to criticism and to learn from it
Sense of relatedness	Trust	The degree to which individuals perceive each other as reliable
	Support	The individual's belief that he or she can count on others when dealing with adversity
	Comfort	The degree to which an individual can be in the presence of others, without distress or anxiety
	Tolerance	An individual's belief that he or she can safely express differences within a relationship
Emotional reactivity	Sensitivity	The threshold and intensity of an emotional response
	Recovery	The ability to regulate and rebound From negative emotions or stressful experiences
	Impairment	The degree to which emotional responses disrupts everyday life

The main findings of this study can be summarized as follows: (1) compared to non-headache controls, adolescents with high-frequency headaches (≥10 days of headaches per month in the last three months) exhibited a higher risk of having lower sense of mastery and resilience, and increased emotional reactivity and vulnerability; (2) adolescents with intermediate-frequency episodic headaches (5–9 days of headaches per month in the last three months) also showed a higher risk of having lower sense of mastery and higher vulnerability than non-headache controls; (3) headache diagnosis was not significantly associated with a higher risk of having lower resilience or higher vulnerability; (4) interactions analysis revealed that adolescents with psychiatric comorbidity and high vulnerability were more likely to have migraine (odds ratio = 3.60; 95% confidence interval = 1.15–11.24, p = 0.03) than expected from the additive effects of each factor alone, and a high vulnerability partially mediated the association between psychiatric comorbidity and high-frequency headache (indirect effect = 0.224, standard error = 0.106, z = 2.11, p = 0.035); and (5) logistic regression analyses identified female gender and psychiatric comorbidity predicting a low resilience among adolescents with primary headaches, and prenatal tobacco exposure as the only predictor of high vulnerability in this adolescent sample (34).

The preliminary absence of a correlation between resilience, vulnerability and headache diagnosis is noteworthy. One plausible hypothesis is that headache frequency may have a greater impact than other clinical characteristics, such as headache duration and severity and its accompanying symptoms, in the proposed association. Furthermore, the frequency of headache attacks, regardless of etiology, could be the sole mediator between headaches, resilience and vulnerability. In previous population-based studies conducted with children and adolescents, we found that a higher headache frequency, rather than other headache characteristics or headache diagnoses, predicted the association with psychiatric symptoms (11), psychosocial adjustment problems (6), lower school achievement (3) and ADHD (17). However, the interaction analysis added one more piece to the puzzle, showing the simultaneous role of vulnerability as a moderator in the psychiatric comorbidity of migraine and a mediator in the psychiatric comorbidity of high-frequency headache.

Optimism, self-efficacy and adaptability (or flexibility), assessed by the sense of mastery scale, have been recognized as predictors of quality of life in children and adolescents with chronic pain because they aid in reducing the fear and catastrophizing associated with pain (64). The association of lower optimism, self-efficacy and adaptability with high-frequency headache is a new finding that awaits confirmation by other studies with potential therapeutic implications for this group of difficult-to-manage patients.

The association between high-frequency headache, low resilience and high vulnerability is supported by emerging evidence of morphological and functional abnormalities in the cortical and subcortical regions involved in pain modulation, emotional regulation, cognitive reserve, and resilience (71,72). Structural and functional neuroimaging studies have identified key regions within the antinociceptive pathway, such as the rostral and subgenual anterior cingulate cortex and the dorsolateral prefrontal cortex, where greater gray matter volume is positively associated with resilience and inversely associated with pain severity in individuals with chronic pain (72). Changes in these regions may also affect the interactions between cortical and subcortical networks, including the trigeminovascular system and sensory processing networks, contributing to headache chronification (73).

Functional connectivity studies in migraine populations further support the involvement of cognitive and affective brain networks (74). Greater baseline functional connectivity between the right amygdala and frontal regions (including the anterior cingulate cortex and precentral gyrus) predicts greater headache reduction following cognitive behavioral therapy, a resilience-enhancing intervention (75). This suggests that individual differences in the connectivity of these regions may underlie both the resilience processes and headache outcomes. Furthermore, large-scale analyses have linked headache intensity, pain catastrophizing and affective symptoms to connectivity within the frontoparietal and dorsal attention networks, which are major cognitive networks implicated in resilience and pain modulation (74).

Collectively, these findings indicate that the neural substrates most consistently implicated in the relationship between resilience and headache are the anterior cingulate and dorsolateral prefrontal cortex and their functional connectivity with limbic structures, such as the amygdala. These regions are central to both antinociceptive processing and cognitive-affective regulation that underpin resilience, providing a plausible neurobiological basis for the observed correlation between resilience, vulnerability, and headache outcomes (74,75).

Executive function

The close interplay between resilience and executive function and their roles in developmental psychopathology have been extensively reported in the literature, encompassing both clinical and subclinical manifestations (35,63,76,77), in addition to plausible neurobiological substrates (78,79).

Despite somewhat different conceptualizations, executive function can be defined as a set of top-down mental processes that regulate cognition, emotions and behavior with the objective of performing actions in the present or achieving future goals, thus enabling voluntary, independent, organized and targeted actions to reach specific goals (31,57).

Longitudinal and meta-analytic studies have shown that executive function plays a central and transdiagnostic role in developmental psychopathology. Deficits in executive function, including inhibitory control, cognitive flexibility and working memory, are prospectively associated with an increased risk of a broad range of psychiatric symptoms and disorders across childhood, adolescence and adulthood (77,80).

Cognitive dysfunction is part of the complex migraine experience, being largely reported in the different phases of the migraine attack, including interictally (81). A recent meta-analysis concluded that children and adolescents with migraine, assessed by psychometric tests in the interictal phase, exhibited poorer cognitive performance across multiple domains, including motor skills, executive function, learning, memory, language, processing speed, intelligence and visuospatial/construction, compared to non-headache controls (35).

Executive function refers to a set of higher-order cognitive processes that enable the regulation of thoughts, behaviors, and emotions to achieve goal-oriented activities. These processes include core components such as planning, organizing, cognitive flexibility (the capacity to shift perspectives or strategies), inhibitory control (self-control), emotional regulation, working memory (the ability to hold and manipulate information) and voluntary attention, among others (31,57). Executive function skills are essential for problem solving, decision-making and resisting impulsive actions in favor of long-term goals (82). The concept embraces both the unity (shared variance among executive function tasks) and diversity (distinct processes, such as inhibition and shifting) of these cognitive abilities. Therefore, executive functioning is best understood as the capacity for self-directed, goal-oriented control over behavior and cognition, integrating multiple interrelated processes to support adaptive functioning in complex and dynamic environments.

Executive functions are the higher-level cognitive skills applied to control and coordinate other cognitive abilities, such as language, memory, learning and reasoning (83), exhibiting a direct correlation with school achievement in addition to being a more important predictor than intelligence quotient or entry-level reading or math skills (84).

The emergence of executive function deficits in early childhood is commonly reported in a wide range of neurodevelopmental and neuropsychiatric disorders, including learning disabilities, ADHD, autism spectrum disorder, conduct disorder, obsessive–compulsive disorder, depression and anxiety (77).

A comprehensive meta-analysis examining data from over 66,000 children found that stronger executive functions in childhood prospectively predicted fewer future externalizing (such as ADHD symptoms, conduct problems, oppositional defiant disorder and substance use disorder) and internalizing problems (notably depression, but not consistently anxiety) (80). These associations were robust across diverse populations and persisted even after accounting for confounders. Longitudinal studies further confirm that impaired executive function predicts later symptoms of depression, anxiety, ADHD, oppositional defiant disorder and conduct disorder with bidirectional effects because psychiatric symptoms can in turn negatively impact executive functions over time (85).

According to the literature, there is a consistent association between executive functions impairment and chronic pain in children and adolescents. Multiple studies using both neuropsychological testing and behavior rating scales have demonstrated that youth with chronic pain exhibit deficits in several domains of executive functions, particularly working memory, attention, inhibition, flexibility and planning, compared to pain-free controls (86,87). The relationship appears to be bidirectional and potentially cyclical; impaired executive functioning may impair self-management and coping, thereby increasing pain-related disability and perpetuating chronic pain, which in turn may further compromise executive functions (88).

Cognitive complaints are among the most prevalent symptoms in the premonitory and headache phases of migraine attacks and often persist in the postdromal phase (81). During the premonitory phase, cognitive symptoms such as speech and reading difficulties are reliable predictors of incoming migraine attacks (89). A detailed prospective study has shown that 89.7% of patients with migraine experience cognitive symptoms in the headache phase of the attack, and the most commonly reported symptoms are related to attentional or executive dysfunction (90).

Clinical studies comparing cognitive performance in the interictal period between children and adolescents with headache disorders and non-headache controls have shown mixed results, from no significant differences in earlier studies to disparate findings of impairment in short and long-term memories, attention, executive function, and information processing speed in more recent ones (91 –95).

A recent meta-analysis based on clinical studies found a significantly worse overall neuropsychological performance among children and adolescents with primary headache disorders compared to non-headache controls across several domains, including motor skills, executive functioning, learning, memory, language, processing speed, intelligence and visuospatial/construction. Sensitivity analyses revealed that detrimental effects were predominantly associated with migraine diagnosis, whereas no such effects were detected in patients with tension-type headache (4)

Among the limitations of the aforementioned studies, most of them relied on small samples (from 17 to 82 patients), applied different arrays of psychometric tests and statistical analyses, and failed to control for possible moderating effects of preventive medication, proximity of the attack and coexisting psychiatric comorbidities (4,50,91 –95).

Research on neuropsychological performance in individuals with headache disorders based on clinical samples is often limited by a significant selection bias. Factors such as the enrolment of patients who exhibit more severe symptoms and are at a higher risk of psychiatric comorbidities, such as ADHD, depression and anxiety, and consequently, are more likely to use psychoactive medications, may adversely affect cognitive performance.

Evaluating executive function in children is challenging, particularly with regard of psychological instrumentation (96). The available studies examining cognitive performance in youth with primary headache disorders are exclusively based on neuropsychological tests that comprise systematic procedures for the application, scoring and interpretation of structured tasks. The criticism of performance-based tools for assessing executive functions often stems from their limitations in predicting real-world outcomes, as a result of a lack of reliability, predictive value and ecological validity (31,83). This has contributed to the growing interest in functional instruments, based on rating scales fulfilled by parents, caregivers, teachers and/or by the child or adolescent themselves, to evaluate behaviors that mirror their daily executive functioning (31,83,96). According to the literature, the key advantages of using functional instruments for assessing executive functions are their higher ecological validity and predictive value for real-life outcomes, accessibility, simplicity and consideration of context and multiple observer perspectives (31,83,96) (instead of a lack of interobserver and intersetting agreement) (97).

Given the lack of population-based studies using functional assessment of executive function in children and adolescents with headache disorders, we conducted a pilot cross-sectional study to examine potential associations and interactions between factors (98). Executive function was assessed using the Executive Function Inventory for Children and Adolescents, a validated functional rating scale that provides a general index of executive functioning (96). Compared to non-headache controls, adolescents with episodic migraine showed a higher risk of having an abnormal executive function score (relative risk = 3.5; 95% confidence interval = 1.2–10.1). The risk was also significantly increased in adolescents with high-frequency headache (≥10 days of headaches per month in the last three months) (relative risk = 4.9; 95% confidence interval = 1.2–20.6) relative to non-headache controls. In multivariate models, the association between high-frequency headache and an abnormal executive function score was independently predicted by lower socioeconomic status, lower school performance and headache attacks accompanied by vomiting (p < 0.05). These variables did not significantly predict the association of migraine with an abnormal executive functioning score (96).

Resilience, executive function and psychiatric comorbidity from the biopsychosocial perspective

Robust evidence supports the association between executive function and resilience in the context of developmental psychopathology. Cross-sectional and longitudinal studies have demonstrated that executive functions, especially inhibition, working memory, cognitive flexibility and planning, are positively correlated with resilience across childhood, adolescence and early adulthood (99). Longitudinal cohort studies also show that specific executive function skills, such as cognitive flexibility and inhibition, may buffer the impact of adverse childhood experiences on the development of internalizing and externalizing behavior problems, highlighting their moderating role in resilience processes (100,101). Furthermore, executive function and resilience exhibit bidirectional interactions over time; thus, improvements in one domain predict gains in the other, supporting the dynamic and reciprocal interrelationship embedded in the proposed BPS model (Figure 1) (99). In the neurodevelopmental context, executive function is recognized as a set of foundational skills that underpin resilience, enabling adaptive responses to adversity through skills such as impulse inhibition, working memory, cognitive flexibility, planning and problem solving (100). These executive function skills are considered modifiable and targets for interventions aimed at promoting resilience in at-risk populations. Empirical studies also report that executive function and resilience are linearly related, with higher executive functioning scores associated with greater resilience and better academic and social competence, whereas deficits in either domain are linked to an increased risk for internalizing and externalizing psychopathology (102).

Emerging evidence of resilience and executive function impairment among children and adolescents with migraine and/or high-frequency headaches, as well as their influence on psychiatric comorbidities and other key outcomes, highlights the plausibility of the proposed BPS model and provides a comprehensive framework for integrating and understanding these interconnected processes. Furthermore, this framework opens new perspectives for the development of potentially effective interventions tailored to this group of patients.

Conclusions

Growing evidence has indicated the possible role of resilience, vulnerability and executive function in the emergence of psychiatric comorbidities in youth with headache disorders. Population-based studies have provided initial evidence that children and adolescents with migraine and/or high-frequency headache are at an increased risk of having low resilience, high vulnerability and executive function impairment. Therefore, another dimension of psychiatric comorbidity impact refers to the consequences of reduced resilience, increased vulnerability and executive function impairment on child neurodevelopment, expressed by challenges in psychosocial adjustment, mental health, cognitive performance and school achievement.

However, little is known about the possible predictors, mediators and/or moderating factors underlying the psychiatric comorbidities of headache disorders at these ages. Preliminary interaction analyses suggest that high vulnerability may exert a moderating role in the psychiatric comorbidity of migraine, as well as a mediating effect in the association of high-frequency headache with psychiatric symptoms and disorders. Candidate predictors of psychiatric comorbidity in youth with migraine and/or high-frequency headache include executive dysfunction, high vulnerability, female sex, low socioeconomic status, prenatal exposure to tobacco, poor academic performance and headache attacks accompanied by nausea and vomiting.

The identification of predictors would make early interventions feasible for at-risk children with headaches to prevent the development of psychiatric comorbidities. On the other hand, defining the mediators and moderating factors will contribute to clarifying the possible causal pathways and comorbidity directionality, as well as to developing more personalized and evidence-based approaches for headache management in these age groups.

Finally, these findings underscore the relevance of routinely assessing psychiatric symptoms, resilience, executive function skills and school functioning in children and adolescents with headache disorders.

Clinical implications

The multidimensional impact of psychiatric comorbidities on children and adolescents with headache disorders is clearly demonstrated from a biopsychosocial perspective through consistent evidence of their adverse effects on headache severity, chronification and functional impairments in quality of life, cognitive performance, academic achievement and overall patient well-being, leading to long-term continuity across childhood, adolescence and adulthood.

Although the impact of psychiatric comorbidity in children and adolescents with headache disorders is well documented, there remains a paucity of knowledge regarding the underlying neurobiological mechanisms, developmental psychopathology pathways, directionality of comorbidity, and potential predictors, mediators or moderator factors.

Growing evidence has indicated the possible role of resilience, vulnerability, and executive function in developmental psychopathology and, consequently, in the emergence of psychiatric comorbidities in children and adolescents with headache disorders.

Population-based studies have provided initial evidence that children and adolescents with migraine and/or high-frequency headaches are at an increased risk of having low resilience, high vulnerability and executive function impairment.

This narrative review underscore the relevance of routinely assessing psychiatric symptoms, resilience, executive function skills and school functioning in children and adolescents with headache disorders.

Future studies should examine whether early interventions focused on resilience, vulnerability and executive function can prevent psychiatric comorbidities and improve headache outcomes in children and adolescents with migraine and/or high-frequency headache.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.

ORCID iD

Marco Antônio Arruda

Renato Arruda

José Aparecido da Silva

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