The Critical Value of High-Risk Designs and Developmental Psychopathology Frameworks for Understanding Affective Psychopathology: Insights from Research on Anhedonia

Abstract

Developmental psychopathology frameworks view development as a dynamic process that integrates multiple systems, allowing for the ability to understand how psychopathology develops and who develops it. High-risk study designs, such as investigating changes over time in youth with a family history of psychopathology, is one strategy in developmental research. While much of research on psychopathology focus on clinical symptoms after they emerge, this approach hinders the understanding of when and how clinical symptoms and psychopathology develops, and the identification of risk factors, neural mechanisms, and clinical correlates. We review the critical value and advantages of using high-risk designs and developmental psychopathology frameworks for understanding the emergence of affective psychopathology. To make our points, we focus on one example—anhedonia—a transdiagnostic affective symptom that traditionally refers to diminished experiences of pleasure, emerges during adolescence, and occurs prior to the onset of disorders such as depression. We review the phenomenology, behavior, and neural mechanisms of anhedonia, and then approach our discussion of anhedonia from a developmental psychopathology perspective and outline the advantages and disadvantages of using high-risk designs. We synthesize the literature, ending with providing clinical implications and considerations for future directions. We emphasize that these approaches deserve more attention in the field because they are generally critical for understanding mental health such as affective psychopathology.

Introduction

Case example of a 15-year-old Asian American girl with anhedonia.

“I used to enjoy so many things in my life. I really loved spending time with my friends, reading, attending dance classes, and spending time with my family on the weekends. These were the things that brought a lot of joy in my life—these activities were what made me feel excited and I felt like I always had something meaningful to look forward to. But now, I just don’t really feel like making the time and putting effort in to do these activities. I just don’t feel that spark for life and many of these activities feel pointless. I’m just moving through motions not really feeling excited about anything. I feel numb and like I just…exist.”

Adolescence is a period marked by novelty, transformation, and the formation of personal identity; it is also a developmental window in which clinical symptoms such as anhedonia first appear^1,2. In the case example, anhedonia is reflected in the adolescent’s loss of interest and enjoyment in activities that once brought them joy, reduced feelings of excitement or sense of meaning in these activities, and a description of activities feeling “pointless” and feeling “numb”. Anhedonia traditionally refers to a diminished ability to experience or anticipate pleasure and is a devastating and harmful symptom that strongly predicts clinical symptoms and behaviors including psychiatric illnesses such as depression^3,4 and suicidality^5–7. With the rapid changes characteristic of adolescence combined with the inherent vulnerability during this window, this developmental period provides a unique opportunity to investigate the mechanisms underlying clinical symptoms before full-blown psychopathology manifests⁸. Adolescence is also a time when clinical symptoms may be most malleable to intervention, preventing unfavorable short- and long-term outcomes such as the onset of psychiatric illness.

The definitions of anhedonia have undergone significant theoretical expansion in recent years, with contemporary frameworks extending beyond phenomenology to encompass deficits in decision making as well as motivational impairments in both the initiation (drive) and maintenance (persistence) of goal-directed behavior^9,10. Though anhedonia may present as reduced interest or pleasure in activities, individuals can differ along dimensions of consumption, which refers to in-the-moment experiences of pleasure or ‘liking’ (e.g., enjoying the sound of rain or the smell of a candle). Others may also vary on dimensions of anticipation, which refers to pleasure for future rewards, or ‘wanting’ (e.g., looking forward to an upcoming concert). While not a focus of this review, social anhedonia refers to diminished experiences of pleasure in social activities which is associated with social withdrawal and isolation (e.g., not enjoying social activities such as spending time with friends)^11,12.

Developmental psychopathology frameworks offer a valuable perspective for understanding affective symptoms such as anhedonia. Developmental psychopathology has been historically defined as the interplay of typical and atypical functioning across systems over the lifespan¹³. Sroufe and Rutter provided an updated definition of developmental psychopathology, defining it as a “conceptual approach that involves a set of research methods that capitalize on developmental and psychopathological variations to ask questions about mechanisms and processes”¹⁴_. Developmental psychopathology frameworks view development as a dynamic process, integrating multiple systems that can allow for the ability to understand how psychopathology develops and who develops it before symptoms emerge^8,13,15,16. Like research in medicine, which shows that physical health problems (e.g., cardiovascular health) develop over years before reaching a detectable or clinically meaningful state, developmental psychopathology emphasizes the need to examine these processes early in the lifespan. High-risk study designs, such as investigating changes over time in youth with a family history of psychopathology, are strategies used in developmental research¹⁷. These designs offer valuable insights into the factors that shape psychopathology by focusing on people who are at heightened risk and examining how processes unfold across development¹³.

We review the critical value and advantages of using high-risk designs and taking a developmental psychopathology approach for understanding the development of affective psychopathology. To make our points, we focus on one example—anhedonia¹⁸. The goal of this manuscript is to provide a broad overview of how developmental psychopathology topics can be applied to studying anhedonia in order to set the foundation for future research and clinical practice moving forward. Additionally, there are several key concepts of developmental psychopathology but for the purposes of this review, we focus on basic principles in our application of this framework.

It is important to note that using high-risk designs and a developmental psychopathology framework can be applied to any form of psychopathology. We focus on anhedonia because of its prevalence (affecting approximately 70% of patients with depression¹⁹), its role as a predictor of later psychopathology (e.g., approximately 58% of youth with anhedonia develop depression in adulthood⁴), and the fact that it has received limited research attention in the study of affective disorders until the past decade. Additionally, we highlight anhedonia because the emergence of anhedonia during adolescence reflects interacting biological and environmental processes that unfold across time, necessitating a developmental psychopathology approach.

We begin by outlining the phenomenology, behavior, and neural mechanisms of anhedonia, and then approach our discussion of anhedonia from a developmental psychopathology perspective. Additionally, we review the advantages and disadvantages of using high risk designs. We synthesize the literature, ending with providing clinical implications and considerations for future directions. Importantly, conceptualizing anhedonia trandiagnostically—as we do in this review—offers a framework for identifying shared mechanisms and potential treatment targets. At the same time, there are valuable insights to be gained from research on anhedonia across different disorders, particularly given that the transdiagnostic literature on anhedonia is still evolving. Accordingly, while we emphasize anhedonia as a transdiagnostic construct, we also draw on findings from studies of anhedonia in depression and schizophrenia to illustrate our points and highlight areas where diagnosis specific anhedonia patterns may inform broader anhedonia conceptualizations.

Anhedonia Phenomenology and Behavior

While anhedonia is increasingly recognized as a transdiagnostic construct, it remains a central feature of specific adult psychiatric disorders such as depression and schizophrenia^18,20,21. In depression, anhedonia often first appears during adolescence and is associated with greater depression severity, longer time to remission, and increased substance use across adulthood^22,23. In schizophrenia, anhedonia typically precedes the emergence of positive symptoms (e.g., hallucinations) and has traditionally been defined as a diminished capacity for pleasure, based largely on studies using self-report measures²⁴. However, growing research has challenged this definition, showing that responses to laboratory paradigms assessing in-the-moment experiences of pleasure reflect intact levels of positive emotions, with responses on tasks similar to individuals without the disorder^24,25. The presence of anhedonia is more common when individuals with schizophrenia are asked to recall past pleasurable experiences or anticipate future rewards. In contrast, people with depression tend to report reduced in-the-moment experiences of pleasure, a finding supported by both behavioral and fMRI studies²⁰. These differences underscore the complexity of anhedonia, which varies not only across disorders but also across phases of reward processing. Furthermore, anhedonia in schizophrenia, like in depression, is resistant to treatments and first-line, conventional treatments such as psychosocial treatments and psychotropic medications (e.g., SSRIs) tend to be ineffective²⁶.

As demonstrated in the existing literature, research on anhedonia in adults with schizophrenia and depression is currently more comprehensive than in youth. This focus has left significant gaps in our knowledge of how anhedonia unfolds earlier in development, despite evidence that it can emerge across the lifespan and how it functions as a transdiagnostic risk marker for later psychopathology (see Figure 1). For example, although relatively rare in childhood, anhedonia may present itself early in life as a specific symptom of depression for young children. Notably, its presence in young children is almost exclusively associated with depressive disorders, suggesting that the inability to experience pleasure is atypical at this stage and may serve as a clear indicator of early-onset depression^27,28. In adolescence, anhedonia becomes more prevalent and potentially more harmful, often laying the foundation for long-term psychological consequences.

Figure 1. Anhedonia Development Across Time.

Note: Box colors: Grey=early risk factors, blue=anhedonia, orange=new social stressors, white=psychopathology, white (bolded text)=neural reward circuitry; curved line represents changes in the reward system with development/age.

This figure illustrates how anhedonia develops across the lifespan. Although it most commonly emerges during adolescence—a period characterized by heightened neural sensitivity to rewards—it can also arise during childhood and is a common symptom of adult psychiatric disorders such as depression and schizophrenia. This figure highlights several examples of contributing factors to anhedonia, including genetic vulnerability, early life stress, social environment, and altered neural reward circuitry. It also depicts that anhedonia can emerge before the onset of psychopathology. Notably, anhedonia can develop even in the absence of a genetic predisposition to mental illness.

Anhedonia Measurement

The current approaches for assessing anhedonia have largely relied on first- and second-generation self-report measures—such as the Snaith-Hamilton Pleasure Scale (SHAPS)²⁹, although there is increasing work dedicated to expanding the measures and tools for assessing anhedonia (see Rizvi et al., 2016 for a review)^29–32. This includes the development and use of more comprehensive clinical interviews, observation during lab-tasks or naturalistic settings, laboratory-based tasks such as the Effort-Expenditure for Rewards Task, and moment-to-moment assessments such as ecological momentary assessment^32–35. Anhedonia self-report measures also capture the different phases and contexts of anhedonia. For example, the Temporal Experience of Pleasure Scale (TEPS) commonly used in studies of schizophrenia³⁶ includes total scores and anticipatory anhedonia (e.g., diminished anticipation of pleasure) and consummatory anhedonia (diminished in-the-moment experiences of pleasure) subscales, all reported to have good internal consistency (0.79, 0.74, 0.71, respectively) and have been used in studies with adolescents^37,38. However, there is some inconsistent work regarding the two factors structure of the TEPS with different factor structures reported across different cultures³⁹. The Anticipatory and Consummatory Interpersonal Pleasure Scale⁴⁰ measures social anhedonia and includes a modified version for adolescents, with high internal consistency⁴¹. As with most studies involving adolescents, assessing anhedonia benefits from not just reports from adolescents but also reports from multiple informants including family members and teachers to understand behaviors across contexts⁴². Furthermore, it is critical to include multimodal assessments of anhedonia and its mechanisms to capture a more complete picture of this symptom and its complexities.

Neural Reward Systems

A likely underlying mechanism of anhedonia is disruptions in the mesolimbic dopamine (DA) pathway such as decreased DA availability in reward regions including the striatum⁴³. Mesocorticolimbic DA circuitry and related processes such as DA signaling mature in adolescence and into adulthood⁴⁴. The DA system is an essential system in reward processing during adolescence including reward learning, behavioral control, and event salience^45,46. During adolescence, this system promotes flexible self-control well into adulthood⁴⁷. Neural reward sensitivity also changes across development (as shown in Figure 1)^48,49 peaking during adolescence as brain reorganization and maturation occur. For example, dual-systems conceptual models for neural reward mechanisms propose that there is a balance between reward systems and control systems (e.g., fronto-parietal control systems develop into adulthood) with reward-motivated behaviors driven by heightened processing of rewards compared to control systems^50–52. Primary reward regions (see Haber, Knutson, 2010⁵³ for comprehensive description) include the ventral striatum (VS), considered the “hub” of reward responding^54–56, and the medial prefrontal cortex (mPFC), which among many functions is involved in regulating reward responding^57,58.

Interestingly, previous neuroimaging research shows that adolescents with depression tend to exhibit reduced VS activation but heightened activation of the mPFC and stronger VS-mPFC functional connectivity in response to monetary rewards^59,60. This pattern may reflect mPFC overregulation of the VS, attenuating affective responses to reward stimuli⁶¹. Longitudinal studies of adolescents indicate that VS connectivity is linked with anhedonia—but not low mood—2 and 4 years later⁶², and reduced VS activation in response to rewards predicts both subthreshold depression and progression to clinical depression 2 years later⁶³. Additionally, research has begun to differentiate how specific phases and contexts of reward processing relate to anhedonia symptoms in youth. For example, in youth at transdiagnostic risk for serious psychopathology with heightend dmPFC activation in response to rewards, associations are observed between anticipatory, consummatory, and social anhedonia and suicidal ideation⁶⁴. Relatedly, prior work has found that adolescents with higher social anhedonia exhibit greater mPFC activation in response to mutual liking (e.g., being like by someone they also liked) relative to received liking (i.e., being liked by someone whom they did not like), and stronger positive connectivity between the VS and mPFC during mutual vs. received liking⁵⁹.

Social reward systems, while outside the scope of this review, are also associated with anhedonia, and overlap with primary reward and self-related neural systems⁶⁵. Other reward-related regions include the supplementary motor area, and the thalamus, often referred to as a “relay station” transmitting sensory and motor signals to other parts of the brain and regulates information between areas of the brain involved in rewards^66,67. While these regions are not considered primary reward circuitry, they are modulated by dopaminergic signaling and interact with reward regions to support goal-directed, reward-related behavior^68,69. Although understudied, the overlap between motor and reward systems may be particularly relevant in the context of anhedonia in youth, where impairments in motivation and reduced initiation of action toward reward could reflect disruptions in hedonic processing and motor-related circuitry such as those involved in action planning⁷⁰.

The Importance of Examining Anhedonia from a Developmental Psychopathology Framework

Transactional Model

Transactional models of developmental psychopathology recognize that there is a need to consider the intersection of genetic, constitutional, neurobiological, social, and psychological factors when understanding an outcome across time^15,23,71. The premise is that these factors can change through dynamic transactions and there are bidirectional influences at play⁷². For example, an adolescent may experience anhedonia due to adverse childhood experiences such as trauma^73,74, begin to socially withdraw, and experience bullying because they are not participating actively in their social activities. It could also be the case that a person who experiences bullying may experience anhedonia, which may lead to social isolation, and rejection from peers. These noted interacting factors could further exacerbate anhedonia, creating a feedback loop in which anhedonia and social outcomes are reinforcing each other. It is also possible that anhedonia can show persistence and stability, even outside of depressive episodes⁷⁵. These examples highlight the complexity of developmental psychopathology. For some, there may be continuity in symptoms (i.e., stability or slight changes), while for other people, the pathway to psychopathology may not follow a predictable pathway to a disorder (i.e., discontinuity)⁷⁶. By capturing these dynamic processes across time, we can test moderation (i.e., variables which impact the strength or nature of a relationship) and mediation effects (i.e., variables that explain associations between constructs)^77,78 to shed light on the processes and mechanisms through which psychopathology unfolds.

Contextual Factors

It is also essential to view adolescent development within multiple systems and dynamic and ever-changing contexts^79,80. Consistent with Bronfenbrenner’s Ecological Systems Theory⁸¹, contextual factors at many levels of experience are relevant for adolescent development and, relatedly, psychopathology. These vary from established proximal interpersonal factors, such as parenting experiences or trauma within family relationships, to distal, structural factors such as political turmoil and experience of fundamental freedoms. Additionally, contexts can either magnify or buffer against the influence of sensitive developmental periods on behaviors. For example, cumulative stress exposure at the neighborhood level may amplify vulnerability while social support at the family level and adaptive emotion regulation within the adolescent may buffer against anhedonia development^82–84.

To provide a more in-depth example from studies of youth with depression, interpersonal factors such as family and peer environments are central in adolescence⁸⁵. Reviews and meta-analyses report that parenting factors such as low warmth, high parent-child conflict, low autonomy-granting, and harsh psychological control are risk factors for depression⁸⁶, while warmth is protective^87,88. Experiences such as victimization and bullying in peer relationships also influence trajectories of depression in youth^89,90 while support from peers can buffer against depression⁹¹.

Another example of contextual factors to consider in studying anhedonia includes the importance of cultural norms. In the case example above, anhedonia is reported by an Asian American girl. This raises important points related to the differences in cultural norms surrounding positive affect. For example, Japanese Americans tend to report lower positive affect⁹² and Mexican Americans tend to report higher positive affect compared with White Americans⁹³. While there are of course individual differences, culture shapes both the experience and the expression of positive affect⁹⁴, although cultural considerations are not well-documented in the anhedonia literature, and there is more work needed to understand “how” culture matters⁹⁵. Another direction of interest that highlights the importance of contextual factors is the importance of adolescents’ role in the larger social climate. For instance, with the increase in youth involvement in social justice movements (e.g., Black Lives Matter)⁹⁶, the act of joining together may decrease anhedonia through motivation towards social behaviors and an enhanced sense of purpose and meaning.

Together, contextual factors shape adolescents’ affective experiences and contribute to the development of disrupted reward-related processes. Understanding anhedonia during adolescence requires close attention to both the individual and the broader social and environmental contexts in which adolescents are embedded.

Typical Development

Understanding typical adolescent development is essential for identifying when emotional and behavioral changes—such as anhedonia—fall within the range of normal developmental fluctuations, and when they may be a signal of emerging psychopathology. Without this developmental context, we risk mislabeling expected, transient experiences as pathological or, conversely, overlooking early signs of psychopathology.

Adolescence is a time in which youth seek to individuate from family and prepare for more focal work and social activities of adulthood, discovering new passions such as hobbies and interests, and pursuing social connection and romantic interests^1,48,97. There are also substantial changes in the brain including rapid development of neural reward systems and reward-seeking behaviors take an inverted-U shape, peaking at ages 14–15 year of age and then declining^{85(p20),98,99}. While these changes are generally viewed as necessary and adaptive, these dynamic shifts can create a window of vulnerability: the emergence of clinical symptoms such as anhedonia during adolescence can negatively impact the trajectory of some youth.

In the case of anhedonia, this perspective highlights a key paradox of adolescence¹⁰⁰: anhedonia emerges at a time of heightened reward-seeking and sensitivity to rewarding experiences. Yet, adolescent anhedonia also occurs against a backdrop of lower baseline positive affect and even mild-severity depressive symptoms compared with childhood. These contrasting points suggest a complex set of developmental changes in reward systems that could increase vulnerability to pathological-level disruptions. Two pathways from normative adolescent changes to anhedonia have been proposed: one from the disappointment or frustration of not achieving high-valued rewards (e.g., social reward, rejection by a potential romantic partner) ^101–103 and the other from the consequences of persistent risk-taking—common in adolescence⁵²—that alters reward circuitry¹⁰⁴.

Given the wide range of possible developmental trajectories, a clear understanding of what is typical during adolescence provides a critical framework for distinguishing between normative, adaptive changes, and early signs of psychopathology. While we are increasingly understanding processes reflective of typical developmental course, it is still unclear why certain people develop anhedonia during adolescence. Understanding typical and atypical development (e.g., anhedonia development) in parallel can advance this area.

Equifinality and Multifinality

Equifinality and multifinality are foundational theoretical developmental psychopathology concepts that help to explain the complex pathways through which psychological processes like anhedonia develop across time⁷⁶. Equifinality suggests that there are multiple pathways that can lead to the same result or outcome. Possible pathways to anhedonia could include exposure to early life experiences such as trauma, peer victimization, and the stresses of having a family member with psychopathology, as well as disruptions in biological and affective systems, inflammation, early pubertal maturation^{59,74,105–107}. To highlight a specific example of multiple pathways at play, we previously proposed a model that draws on the concept of equifinality to describe one possible pathway to anhedonia in adolescents that considers multiple levels (e.g., environment, biological, neural)¹⁰⁶. Our model highlights that, during pubertal maturation, neural reward systems are especially vulnerable to the negative effects of chronic inflammation resulting from childhood adversity, which could trigger a cascade of negative influences that lead to anhedonia for some youth.

In contrast, multifinality refers to the notion that a symptom can lead to many different outcomes (see Figure 2). Anhedonia may contribute to an exacerbation of symptoms such as anxiety¹⁰⁸ and the emergence of depression and schizophrenia²¹. Importantly, some adolescents who initially experience anhedonia severity may not develop unfavorable outcomes due to less comorbidity and co-occurring symptoms that can exacerbate anhedonia such as depressed mood³⁷, protective factors such as perceived social support¹⁰⁹, and lifestyle factors like diet, exercise, and sleep¹¹⁰. It is important to note that factors that draw from equifinality and multifinality are not acting in isolation: there are mediating and moderating^77,78 influences which are also important to consider when studying anhedonia.

Figure 2. Examples of Equifinality and Multifinality Principles in the Context of Anhedonia.

Note. Equifinality: The principle of equifinality suggests that there are multiple pathways that can lead to the same outcome or endpoint. As illustrated in the figure, various pathways can contribute to the development of anhedonia. These include early life experiences, biological and affective mechanisms (such as disrupted neural reward circuitry), and symptoms and problematic behaviors such as suicidal thoughts. Multifinality: In contrast, the principle of multifinality proposes that a single factor or behavior can result in a range of different outcomes. In the case of anhedonia, for example, it may lead to affective symptoms such as depression, contribute to the onset of disorders like schizophrenia, or, in some individuals, may not result in significant clinical or behavioral problems such as suicidal ideation.

Cross-sectional and Longitudinal Designs

Cross-sectional research has played a critical role in identifying the importance of understanding adolescent anhedonia such as identifying associations between this symptom and its clinical and neural correlates. Cross-sectional designs are often used in psychiatric research and involve collecting data from people (e.g., children, adolescents, adults) at a single timepoint. This research design provides a snapshot of concurrent psychopathological symptoms, behaviors, and processes as well as prevalence rates¹¹¹. Despite clear limitations to cross-sectional designs, including the inability to infer causality nor capture changes in development, it is possible to use this design to identify patterns, generate hypotheses, and provide foundational data for subsequent longitudinal inferences about developmental processes. For example, cross-sectional research has found that adolescent anhedonia is related to suicidal thoughts and behaviors⁵—potentially due to the intolerable nature of anhedonia¹¹²—and can differentiate suicide ideators from attempters¹¹³. These findings highlight the clinical utility of cross-sectional data in pinpointing high-risk symptoms and populations, ultimately informing prevention and early intervention efforts, and clarifying which associations warrant further investigation.

In contrast, longitudinal research designs are uniquely positioned to capture how anhedonia unfolds over time. These designs, which involve gathering data from multiple sources and contexts, allow researchers to observe within person changes, identify distinct developmental trajectories, and clarify how early risk factors predict later outcomes.

Importantly, longitudinal designs support stronger inferences about temporal relationships. For example, studies have shown that anhedonia predicts more severe clinical outcomes, including greater illness severity, longer depressive episode duration, and a higher number of major depressive episodes²². These shifts may, in part, reflect broader biological changes unfolding across adolescence, such as hormonal and neuroinflammatory processes, which longitudinal studies can track in tandem with symptom progression. For example, as discussed, puberty-related neurodevelopmental changes have been postulated to alter sensitivity to positive stimuli¹⁰⁶ and higher baseline levels of inflammation—such as circulating pro-inflammatory proteins including tumor necrosis factor alpha—have been shown to predict increases in anhedonia severity over time¹¹⁴.

Beyond symptom tracking, longitudinal approaches also deepen our understanding of neural mechanisms associated with anhedonia. For instance, building on research indicating disruptions in striatal and mPFC function in response to rewards is associated with anhedonia in youth with depression⁶¹, recent longitudinal work finds that adolescent anhedonia is related to altered function in the striatum following stress¹¹⁵, and functional connectivity between the nucleus accumbens and motor/decision-making regions⁷⁰. Additionally, findings from recent longitudinal designs show that trajectories of anhedonia vary across adolescence—some increasing, decreasing, or remaining stable across adolescence^{23,106,116–118}—and are predicted by specific neurocognitive profiles¹¹⁹. The use of longitudinal designs also offers a valuable approach to better understanding assessment measures. For example, recent evidence in youth suggests that laboratory-based measures of anhedonia translate to real-world contexts while subjective ratings of positive and negative affect are associated with neural responses to rewards and loss³⁵.

High-Risk Designs for Adolescent Anhedonia: A Developmental Strategy

While the utility of high-risk designs is well established, the focus on anhedonia research has been on adults who have already received a diagnosis of a psychiatric illness (e.g., depression, schizophrenia). This focus on clinical samples complicates the differentiation between etiologic factors, correlates, and consequences, but population-level studies addressing these limitations can be expensive, requiring a large sample size and multiple assessment points over time (see Table 1). Examining the development of clinical symptoms and problematic behaviors using high-risk designs before psychopathology emerges can provide critical insights regarding how and when developmental processes go awry and who is most at risk^8,13,120. High-risk designs are powerful approaches to investigate hypotheses by following people prospectively, measuring symptoms and behaviors across sensitive times in development, and can shed light on risk factors and possible causal pathways to psychopathology⁸. Fundamental to developmental psychopathology methods, high-risk designs may clarify points of risk and resilience in the emergence of depression or schizophrenia, improving prevention and intervention during targeted timepoints. Additionally, although high-risk designs have a weaker initial signal due to sample heterogeneity and the low likelihood that individuals considered at risk will develop the disorder, they offer a valuable framework in which the signal-to-noise ratio likely evolves over time. High-risk designs allow for the selection from populations likely to have variability in the characteristic (or likely to experience the characteristic in the near future) and then longitudinal tracking, to detect change in severity and functioning and the onset of syndromes. Previous reviews indicate that the onset of mental disorders often occurs during childhood or adolescence, but there is often a significant delay in treatment¹²¹. Duration of untreated illness is a predictor of clinical outcomes^122,123 and high-risk designs have the potential to increase the likelihood that youth are identified early, underscoring the need to improve early detection in pre-clinical samples.

Table 1.

Pros and Cons of Using High-Risk Designs Compared to Designs After the Onset of Psychopathology

	Pros	Cons
High-Risk Designs	• Retrospective identification of who is most vulnerable • Potential to identify risk factors and clinical correlates • Possible insights on mechanisms • Potential to identify unique trajectories of development, including identifying factors contributing to resiliency • Potential to promote early detection and inform prevention and intervention • Signal-to-noise ratio likely evolves across time and development	• Sample dilution based on < 100% rate of developing the disorder • Symptoms may not be apparent and clear • Cohort effects • Between-person variability in which factors lead to outcome • Ethical concerns about notifying people about risk status • More intensive monitoring longitudinally required to assess change • False positives
After the Onset of Psychopathology	• Observation of clearer symptom presentations unique to a disorder • More directed assessment and treatment and identification of underlying mechanisms tied to the progression of the disorder • Can identify diagnostic subgroups and promote recovery • Can assess long-term outcomes • Can be efficient to detect rare disorders	• Difficulty disentangling etiologic factors, correlates, and consequences • Confounding factors: hospitalization, disrupted educational, vocational, social functioning and medication use • Motivation challenges • Expensive to do population-level study • Difficult to identify and enroll participants due to low base rates

Although high-risk designs have promise, there are of course drawbacks. Symptoms may not yet be apparent and clear, and designs may be convoluted by co-occurring symptoms and comorbid diagnoses. For example, in youth at clinical high-risk for psychosis--adolescents and young adults who are considered at imminent risk for developing a first episode of psychosis¹²⁴--investigating anhedonia as a distinct dimension of psychopathology can be challenging because of comorbid diagnoses such as depression and anxiety¹²⁵. Additionally, with the goal of assessing anhedonia even before it emerges, high-risk designs may involve more resources (e.g., support for time-intensive repeated measures, multiple costly neuroimaging scans) given the need to assess and monitor symptom onset and changes across several years. There are also concerns surrounding the stigma which is important to consider given the possibility of false positives (i.e., indicating a symptom or outcome is present when it is not). Inaccurate findings or misleading interpretations may result in unnecessary concern, stress, and treatments in clinical settings.

High-risk designs can include genetic high-risk designs (i.e., having a family history of psychopathology) and behavioral high-risk designs (see Alloy, Boland, 2015 for more information). Here, we focus on genetic high-risk designs because family history is a robust predictor of affective psychopathology¹⁶. In fact, anhedonia is an early sign of depression in youth¹²⁶ and understanding the development of anhedonia in youth at familial risk for depression can increase early identification of youth who are at risk and provide timely interventions. In our work, we have focused on anhedonia development in a sample of adolescents at varying levels of risk for developing anhedonia. The youth included in these studies are a sample of adolescents with and without a first-degree relative with a depressive disorders, bipolar disorder, and schizophrenia-spectrum disorder. Taking a transdiagnostic approach by recruiting adolescents along a continuum can be useful to capture emerging symptoms. Importantly, extreme cases (very high or very low levels of anhedonia) should be well represented to ensure variability and allow for the potential to examine categorical outcomes or continuous outcomes.

Resilience

In addition to examining risk pathways to anhedonia, it is equally important to consider resilience processes that promote adaptive functioning and buffer against maladjustment. This stance reflects developmental psychopathology’s emphasis on multifinality and a range of trajectories^127,128,129. As demonstrated in reward processing research, resilience often involves compensatory adaptations rather than just the absence of vulnerability markers¹²⁷. For instance, some adolescents maintain motivation and enjoyment in rewarding activities despite exhibiting neural markers of anhedonia (like blunted striatal response to rewards). This resilience emerges through increased activation in brain systems underlying cognitive control and goal-directed behavior¹³⁰. This suggests protection against anhedonia may occur through compensatory systems that help maintain motivated behavior despite altered reward processing. Understanding these neurobiological resilience pathways could inform prevention efforts aimed at strengthening protective regulatory systems in vulnerable youth.

Clinical Implications and Additional Considerations

There are important clinical implications and additional considerations for applying high-risk designs and using a developmental psychopathology framework when investigating affective psychopathology such as anhedonia during adolescence. While a developmental framework for studying anhedonia holds promise for both improving current treatments and potentially preventing the progression to treatment-resistant presentations, current anhedonia-specific treatments are limited. First-line depression treatments (i.e., SSRIs and traditional cognitive behavioral therapy) primarily target negative affect rather than addressing the neural reward mechanisms and positive affect alterations that likely underlie anhedonia¹³¹. While interventions like Positive Affect Treatment show promise in improving both positive and negative affect and enhancing reward responsiveness and hedonic capacity^107,108, these approaches have yet to be evaluated within a developmental framework. Much like evidence-based interventions for anxiety disorders during childhood have shown superior outcomes compared with their use in adults¹³⁴, targeting reward processing alterations during adolescent development may enhance treatment efficacy, positioning people for better trajectories into adulthood and healthy long-term functioning.

Clinical heterogeneity–the variability in symptom presentation or phenotype across people with the same disorder, and also across time within people–has complicated clinical research by creating challenges to understanding mechanistic differences and developing related treatments. For instance, depression varies markedly in its course: some individuals experience only one mild episode in their life, while others exhibit a chronic, relapsing course characterized by early onset, comorbidities, and increased symptom severity¹³⁵. This heterogeneity is highly relevant to anhedonia, a symptom that may or may not be present across different disorders such as depression and schizophrenia, and which itself manifests in internal subtypes (e.g., anticipatory, consummatory)¹³⁶. In depression, for example, anhedonia may not be consistently present throughout clinical course and may occur in some episodes but not others. From a developmental psychopathology perspective, understanding how these heterogenous clinical outcomes emerge and evolve requires attention to early risk factors, trajectories, and developmental timing. This can allow for the identification of pathways and additional factors that differentiate youth who go on to develop chronic, severe anhedonia from those with more transient presentations. Additionally, this approach can help to move past “one-size-fits-all” frameworks used in prevention and intervention of adolescent psychopathology by tailoring interventions to the personalized presentations and needs of an individual.

In one example of clinical heterogeneity in the context of anhedonia⁶⁴, distinct anhedonia profiles were examined cross-sectionally among adolescents at high and low familial risk for developing depression, bipolar disorder or schizophrenia-spectrum disorder. The high-risk group was considered at risk by virtue of a first-degree relative with depression, bipolar disorder, or schizophrenia-spectrum disorders. Subgroups of anhedonia were identified: a subgroup including youth with high levels of anhedonia (e.g., consummatory, anticipatory, and social anhedonia), and a profile of youth with low levels of anhedonia. Interestingly, adolescents in the high anhedonia subgroup reported more suicidal ideation and negative affect, and less positive affect and desire for emotional closeness compared to the low-anhedonia profile. Furthermore, more suicidal ideation, and less positive affect and less desire for emotional closeness differentiated the familial high-risk, high anhedonia profile from the familial high-risk, low anhedonia profile adolescents. These findings highlight the clinical heterogeneity within populations at familial risk for psychopathology, suggesting that distinct anhedonia profiles may reflect distinct pathways of affective disturbances and suicide risk. In a longitudinal example, unique trajectories of anhedonia (high, moderate, low)³⁷were identified across two years in the same adolescent sample. Adolescents with low anhedonia across two years also reported lower depression severity. Additionally, adolescents in this group exhibited lower VS activity in response to rewards (from guessing reward fMRI task) which was linked with lower depression severity—an unexpected pattern given that reduced VS activity is usually associated with higher depression and anhedonia severity in adolescent depression⁶¹. While these unexpected findings may speak to the unique sample of youth at risk, these results also highlight meaningful differences in how brain function relates to symptoms across individuals—some people may show reduced striatal responses to reward but not experience severe depression or anhedonia while others may report more depression or anhedonia severity. These findings highlight the importance of identifying for whom certain brain-depression-anhedonia patterns fit—a key step toward understanding clinical heterogeneity and developing more personalized and effective interventions for adolescent psychopathology.

A potentially fruitful avenue for research on anhedonia that draws on developmental psychopathology concepts is mapping symptoms onto clinical staging models, a framework commonly used in general medicine¹³⁷, with increasing work applying these models to young people with mental health challenges and those with mood disorders and schizophrenia-spectrum disorders^138–142. Clinical staging models could enhance early identification, prevent progression, and provide a treatment roadmap by recognizing that disorders (or transdiagnostic features) develop across the lifespan and progress in definable stages for which treatments can be targeted. Applying clinical staging models to the period of youth, ages 15–25 years, a developmental window of the highest likelihood of the onset of severe psychopathology could be particularly advantages¹³⁷. Generally, Stage 0 includes people who are at-risk for a disorder (e.g., family history of psychopathology) but are relatively asymptomatic. Stage 1a includes the experience of mildly severe nonspecific symptoms like anxiety and depression, while Stage 1b includes more moderate-severity general symptoms or more severe mental health signs (e.g., early signs of psychosis like attenuated positive symptoms the case of schizophrenia). Stages 2–4 include the presence of the full-blown syndrome, from suprathreshold symptoms to chronic illness¹³⁹. Each stage has a set of recommended interventions that are appropriate for the corresponding clinical presentation and developmental period (see Gupta, Mittal, 2019¹⁴⁰ for examples in psychosis). Considering anhedonia in clinical staging frameworks during adolescence, given that this symptom tends to precede the onset of psychopathology, could delay or even prevent the onset of disorders such as depression and schizophrenia in late adolescence and young adulthood. While this would be novel for anhedonia, proposed frameworks for depression¹³⁸ have focused on currently psychiatrically healthy youth with a family history of depression (Stage 0), intervening with psychoeducation, closely monitoring symptoms (Stage 1), and providing cognitive behavior therapy, lifestyle interventions, and antidepressant pharmacotherapy as people progress across stages. Although there are no known effective treatments for adolescent anhedonia, a clinical staging framework could be a promising direction for conceptualizing anhedonia and eventually developing targeted treatments.

Despite the potential for clinical staging models to be of clinical utility for anhedonia, there are, of course, challenges and limitations in applying this framework to anhedonia. Traditionally, this framework has been disorder specific, making the transition to a more transdiagnostic application—such as symptoms like anhedonia—more complex^143,144: the criteria for stage assignment may not be optimal and fine-tuned for symptoms such as anhedonia that span multiple heterogenous disorders¹⁴⁵. Additionally, two individuals in an early stage of anhedonia might present differently—one may exhibit diminished ability to experience pleasure, while another might primarily struggle with motivation deficits—and this heterogeneity could be missed within or between stages. Moreover, anhedonia severity can fluctuate or remain relatively stable (e.g., trait level anhedonia)¹⁴⁶, complicating the identification of transitions between stages and conflicting with the expected trajectory of anhedonia. These challenges are compounded by the fact that clinical staging models tend to be most effective when underlying pathophysiology and interventions are well identified and understood¹⁴⁷; in the case of anhedonia, there is still much to be disentangled about who develops it, how it develops, and when it develops across time.

There are several additional considerations for future research. First, both big-data (e.g., the Adolescent Brain Cognitive Development [ABCD] Study) and smaller-scale, topic-focused datasets provide rich opportunities to utilize a developmental framework in understanding anhedonia development. Together, broad, large-scale studies and high-depth, smaller-scale studies offer the opportunity to investigate how and when anhedonia develops with rigor and reliability. Larger studies provide high generalizability and statistical power, control over confounding variables, and precision, but are limited in the detail with which they measure any single construct. Smaller studies have limited statistical power but are complementary to larger studies in their ability to examine a single construct using multi-modal approaches, apply a more nuanced level of investigation, generate hypotheses, and obtain a comprehensive understanding of the construct.

Research in this area should also consider adopting research strategies that are responsive to the needs of diverse communities and employ culturally sensitive methodologies and health equity-informed frameworks (e.g., community-engaged research). Because adolescent development occurs within varied cultural environments and societal factors that may influence mental health trajectories, it is crucial to include youth from historically marginalized backgrounds in studies with a focus on development. This could enhance the generalizability and impact of research findings, while allowing for more rigorous study of population-specific risk and protective factors. For example, youth from minoritized racial/ethnic and/or sexual/gender groups face unique stressors (e.g., bias and discrimination), in addition to the typical challenges of adolescence, which are hypothesized to contribute to disparities in a broad range of mental health outcomes^148–150. Furthermore, including diverse samples allows examination of the effects of identities that could interact to influence anhedonia trajectories. Incorporating samples from varied backgrounds and groups can strengthen the ecological validity of developmental psychopathology research and contribute to culturally informed interventions¹⁵¹. In addition to elucidating risk factors, greater inclusion can help to uncover mechanisms of resilience that are relevant for marginalized communities (e.g., community connectedness), with implications for informing prevention and intervention efforts.

Conclusions

Taken together, developmental psychopathology and high-risk design approaches generally are critical for a thorough understanding of mental health. Using this framework and approach can allow translation of research findings into improved assessment, intervention, and prevention for symptoms such as anhedonia that are precursors to severe forms of mental illness. Anhedonia is a promising example of how developmental psychopathology frameworks and high-risk designs can be applied, and this approach deserves more attention in the larger field.