ADHD and Depression: the Role of Poor Frustration Tolerance

Abstract

Unipolar depression is a common comorbidity in children with ADHD with rates ranging from 12–50%. Compared to children with ADHD alone, children with comorbid ADHD and depression require more intense interventions since they experience higher levels of stress and more psychosocial and familial problems. One mechanism hypothesized to underlie the relationship between ADHD and depression is emotion dysregulation. Cross-sectional and longitudinal research has shown that emotion dysregulation mediates the relationship between ADHD and depression. However, there are a number of limitations in the extant literature regarding emotion dysregulation as a mechanism underlying the relationship between ADHD and depression. This article aims to review those limitations and propose that by examining a specific type of emotion dysregulation, poor frustration tolerance, we may gain critical insight into the mechanisms underlying ADHD and depression. We discuss the construct of frustration, its neural basis and evidence that poor frustration tolerance is a key impairment in children with ADHD. We conclude by suggesting that poor frustration tolerance may be a key mechanism underlying the relationship between ADHD and depression, and provide recommendations for how future research can utilize affective neuroscience techniques to examine the neural, behavioral and clinical correlates of frustration tolerance in children with ADHD to more comprehensively examine this relationship.

Introduction

Comorbid ADHD and Depression

Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder of childhood affecting 3–10% of children [1–3]. In children with ADHD, comorbidity is the rule more than the exception, as approximately two thirds of children with ADHD are diagnosed with another psychiatric disorder [4–6]. In general, the presence of comorbidity often results in more severe symptoms and a longer duration of illness, as well as greater negative outcomes (e.g., increased social, academic and occupational problems, delinquency, substance use, etc) [7, 8].

Traditionally, ADHD comorbidity research has focused on comorbidity with disruptive behavior disorders, such as oppositional defiant disorder (ODD) or conduct disorder (CD). However, more recently, the comorbidity between ADHD and internalizing disorders has received attention (e.g., Jarrett & Ollendick, 2008; Meinzer et al., 2014), in particular the association between ADHD and unipolar depression [9, 10]. Epidemiological studies show the median odds ratio of cooccurring ADHD and depression is 5.5 (95% CI 3.5–8.4) [11]. Longitudinal research suggests that compared to typically developing (TD) children, children with ADHD are at greater risk for developing sub-threshold and clinical depression [12–14]. Furthermore, a meta-analysis of 29 cross-sectional and longitudinal studies found a medium effect for the association between ADHD and depression, although considerable variability within studies was noted [10]. The impairments and outcomes for children with both ADHD and depressive disorders are worse than those resulting from either disorder alone [5, 12, 15–17]. Compared to children with ADHD alone, children with ADHD and depression require more intense interventions since they experience higher levels of stress and more psychosocial and familial problems. Taken together, this research suggests the critical need to gain a more comprehensive understanding of the mechanisms underlying the relationship between ADHD and depression to target prevention and intervention efforts for those children at greatest risk for negative outcomes.

Emotion Dysregulation as a Mechanism Underlying ADHD and Depression

A number of neurobiological and environmental mechanisms have been posited to underlie the relationship between ADHD and depression. One mechanism, emotion dysregulation (ED), has garnered increased attention as ED is a key impairment for individuals with ADHD [18]. Emotion regulation refers to, “an individual’s ability to modify an emotional state so as to promote adaptive, goal-oriented behaviors”, and is essential to interpersonal, academic, and adaptive functioning [19]. As such, ED is conceptualized as: (1) expressions of emotion that are excessive in relation to societal norms or situational context, (2) rapid and poorly controlled shifts in emotion (i.e., lability), and/or (3) atypical allocation of attention to emotional stimuli [18]. ED is central to etiological theories of both ADHD and depression [20–22]. Moreover, both cross-sectional and longitudinal studies have shown that ED mediates the relationship between ADHD and depression in youth [23–25].

However, there are a number of limitations in the extant literature examining ED as a mechanism underlying ADHD and depression. First, in the existing ADHD literature, ED, a complex neurobiological construct, has been typically measured using parent- or self-report measures which may not adequately assess ED. That is, rating scales rely on subjective descriptions of observable behaviors (e.g., “being upset”) which may be indicative of ED, but do not assess the core underlying neurobiological processes involved in ED (e.g., allocation of attention to emotional stimuli or physiological arousal). Further, as noted in the definition above, ED is a complex construct that can be broken down into many facets (i.e., intensity of emotional response, lability of response, etc) each of which can be individually examined. To date, most research on ED in children with ADHD has examined ED as a unified construct rather than examining its various facets. Finally, it can be argued that ED is too broad a construct to represent an adequate mechanism, and specificity is needed to clarify which component of ED is contributing to the relationship between ADHD and depression. Rating scales that assess ED tend to cover a range of types of emotional responses (e.g., upset, distressed, angry, exuberant) and combine these responses into a broad conceptualization of ED rather than focusing on a specific type of ED.

Therefore, we propose that by examining a specific type of ED that can be operationally defined using affective neuro-science terminology, objectively measured using affective neuroscience techniques and is present across both ADHD and depression, we may be able to clarify the role of ED in the relationship between ADHD and depression. Specifically, we propose that by examining frustration tolerance in children with ADHD, whereby frustration refers to an “affective response to blocked goal attainment” [26, 27], we may be able to elucidate the role of ED in the relationship between ADHD and depression.

Why Frustration Tolerance?

While frustration is a normative affective response to blocked goal attainment, poor frustration tolerance can result in high levels of irritable mood. In fact, irritability is defined as “a mood state characterized by a low threshold for frustration” [26, 27]. Moreover, irritability is common in children with ADHD with rates as high as 72% compared to 3.2% in typically developing (TD) control [28]. Furthermore, irritability is a trans-diagnostic construct that is both a symptom of depression and an associated feature of ADHD [29] suggesting that it may be particularly important in the phenomenology of both disorders. Finally, research shows that compared to TD children, children with ADHD show greater levels of frustration, are more likely to quit a frustrating task, exhibit greater focus on negative aspects of the task, and display less constructive patterns of emotional coping when frustrated [30–33]. In the wake of environmental stressors such as negative parent-child interactions and social and academic difficulties, common impairments for children with ADHD, having poor frustration tolerance may contribute to feelings of demoralization and subsequent symptoms of depression. However, to date, the relationship between poor frustration tolerance and depression in children with ADHD has been unexamined. By examining the neurobiological, behavioral, and clinical correlates of poor frustration tolerance in children with ADHD, we may gain greater insight into why some children with ADHD are at greater risk for developing depression. Therefore, we will review the neurobiological basis of frustration and provide future directions for examining poor frustration tolerance as a mechanism underlying ADHD and depression.

Neural Circuitry of Frustration

By definition, frustration is a complex affective response that involves the interaction of multiple neural circuits involved in emotion regulation, including: (1) core limbic regions (amygdala [AMG], insula, and orbitofrontal cortex [OFC]) in circuit with reward regions (ventral striatum particularly nucleus accumbens [NAcc]) involved in the assessment of emotional/ reward salience and generation of emotion responses; (2) frontal cortical (dorsolateral prefrontal cortex [dlPFC]) regions in circuit with dorsal striatal regions involved in the cognitive control of emotional responses, and (3) regions involved in the interface between emotional and cognitive control circuitry (especially those related to attentional control) including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) [34–38]. Research has shown that deficits within these three circuits are associated with ED in children with ADHD (see Shaw et al., 2014 for a comprehensive review).

In healthy adults, frustration has been associated with increased activation in core limbic regions (e.g., AMG, insula) and regions involved in the interface between emotional and cognitive control circuitry (mPFC; ACC) along with decreased ventral striatal activity [39–41]. The ACC has been hypothesized as a critical point of interaction between the expression of affect and the execution of goal-directed behavior [40, 42]. In TD children, frustration is associated with increased dorsal and ventral mPFC recruitment suggesting the importance of “top-down” engagement of cognitive and attentional resources to assist in the regulation of an emotion. Taken together, research in TD individuals suggests that frustration produces increased activity in both limbic and cognitive control regions, but decreased activity in reward anticipation centers.

Unfortunately in children with ADHD, structural and functional abnormalities in limbic regions, combined with poor “top-down” engagement of cognitive control regions may contribute to poor frustration tolerance. For instance, studies have shown decreased AMG and/or hippocampal volumes in children with ADHD compared to TD controls [43–46]. For example, Posner and colleagues [46] found bilateral hippocampal reductions and reduced hippocampal-OFC resting state connectivity in medication naïve children with ADHD relative to healthy controls. Further, in the ADHD group, reduced volume and connectivity were inversely associated with depression scores. Reduced hippocampal volumes and impaired hippo-campal function have been repeatedly associated with major depressive disorder [47–50], suggesting a possible shared neurobiological abnormality between ADHD and depression. Additionally, functional magnetic resonance imaging (fMRI) studies have revealed that individuals with ADHD have limbic system abnormalities, which contribute to deficits in orienting to emotional stimuli including an over perception of negative stimuli [18]. Over perception of negative stimuli combined with poor frustration tolerance could result in dysregulated emotions and possibly contribute to symptoms of depression.

In concert with limbic system abnormalities, children with ADHD also demonstrate abnormalities in cortical regions critical to the “down-regulation” of emotions. In healthy participants, the addition of emotional stimuli to cognitive tasks results in increased activation in cortical regulatory regions integral to the down-regulation of limbic activity [34]. However, the opposite pattern is seen in individuals with ADHD. When emotional stimuli are added to cognitive tasks, individuals with ADHD show hypoactivation in cortical regions such as the ventrolateral, orbitofrontal, and medial pre-frontal cortices [51, 52]. This literature suggests that children with ADHD may be at increased risk for poor frustration tolerance due to abnormalities in bottom-up limbic regions resulting in overactivation and decreased activation in top-down cortical regulation.

Future Directions

We have provided evidence that poor frustration tolerance is a key impairment in children with ADHD, and that the neuro-biological circuitry involved in frustration tolerance may be altered in individuals with ADHD, thereby placing them at greater risk for poor frustration tolerance. However, to date, no research has comprehensively examined the neural correlates of poor frustration tolerance in children with ADHD or whether poor frustration tolerance underlies the relationship between ADHD and depression. Additional research is needed to examine the longitudinal relationship between poor frustration tolerance and the development of depression in children with ADHD. Critical to these studies will be the examination of the role of environmental stressors, which may interact with poor frustration tolerance to produce symptoms of depression. As frustration is a complex affective response, studies should examine the neural and physiologic correlates of poor frustration tolerance in youth with ADHD to gain a greater understanding of the underlying neurobiology of frustration in youth with ADHD.