Understanding the paradox: anhedonia and the unexpected divergence from reward seeking during adolescence - A commentary on Gupta et al. (2024).

Anhedonia is a symptom encompassing reduced or absence of motivation and pleasure that often emerges in adolescence and conveys risk for different mental illnesses and other difficulties. In their review, Gupta, Eckstrand, and Forbes (Journal of Child Psychology and Psychiatry, 2024) present an empirically-based conceptual neurodevelopmental model of anhedonia whereby brain development and pubertal maturation create openness to vulnerability to anhedonia that is influenced by early life adversity and chronic inflammation. This commentary considers anhedonia as a paradox of adolescence given its juxtaposition to the expected developmental milestones of adolescence. It highlights the need to consider anhedonia in terms of both variability and universality of children's experiences and biological development, missed opportunities for social relationships and experiences, and forms and functions of rewards and anhedonia.

The impact of social disadvantage on autonomic physiology of latinx adolescents: The role of environmental risks.

The experience of poverty embodies complex, multidimensional stressors that may adversely affect physiological and psychological domains of functioning. Compounded by racial/ethnic discrimination, the financial aspect of family poverty typically coincides with additional social and physical environmental risks such as pollution exposure, housing burden, elevated neighborhood unemployment, and lower neighborhood education levels. In this study, we investigated the associations of multidimensional social disadvantage throughout adolescence with autonomic nervous system (ANS) functioning at 17 years. Two hundred and twenty nine low-income Mexican-American adolescents (48.6% female) and their parents were assessed annually between the ages of 10 and 16. Participants' census tracts were matched with corresponding annual administrative data of neighborhood housing burden, education, unemployment, drinking water quality, and fine particulate matter. We combined measures of adolescents' electrodermal response and respiratory sinuses arrhythmia at rest and during a social exclusion challenge (Cyberball) to use as ANS indices of sympathetic and parasympathetic activity, respectively. Controlling for family income-to-needs, youth exposed to greater cumulative water and air pollution from ages 10-16 displayed altered patterns of autonomic functioning at rest and during the social challenge. Conversely, youth living in areas with higher housing burden displayed healthy patterns of autonomic functioning. Altogether, results suggest that toxin exposure in youths' physical environments disrupts the ANS, representing a plausible mechanism by which pollutants and social disadvantage influence later physical and mental health.

Hypothalamic-Pituitary-Adrenal Axis Activity in Childhood Predicts Emotional Memory Effects and Related Neural Circuitry in Adolescent Girls.

Negative emotional experiences can be more difficult to forget than neutral ones, a phenomenon termed the "emotional memory effect." Individual differences in the strength of the emotional memory effect are associated with emotional health. Thus, understanding the neurobiological underpinnings of the emotional memory effect has important implications, especially for individuals at risk for emotional health problems. Although the neural basis of emotional memory effects has been relatively well defined, less is known about how hormonal factors that can modulate emotional memory, such as glucocorticoids, relate to that neural basis. Importantly, probing the role of glucocorticoids in the stress- and emotion-sensitive period of late childhood to adolescence could provide actionable points of intervention. We addressed this gap by testing whether hypothalamic-pituitary-adrenal (HPA) axis activity during a parent-child conflict task at 11 years of age predicted emotional memory and its primary neural circuitry (i.e., amygdala-hippocampus functional connectivity) at 16 years of age in a longitudinal study of 147 girls (104 with complete data). Results showed that lower HPA axis activity predicted stronger emotional memory effects, r(124) = -.236, p < .01, and higher emotional memory-related functional connectivity between the right hippocampus and the right amygdala, ß = -.385, p < .001. These findings suggest that late childhood HPA axis activity may modulate the neural circuitry of emotional memory effects in adolescence, which may confer a potential risk trajectory for emotional health among girls.

The longitudinal stability of fMRI activation during reward processing in adolescents and young adults.

BACKGROUND: The use of functional neuroimaging has been an extremely fruitful avenue for investigating the neural basis of human reward function. This approach has included identification of potential neurobiological mechanisms of psychiatric disease and examination of environmental, experiential, and biological factors that may contribute to disease risk via effects on the reward system. However, a central and largely unexamined assumption of much of this research is that neural reward function is an individual difference characteristic that is relatively stable and trait-like over time. METHODS: In two independent samples of adolescents and young adults studied longitudinally (Ns = 145 & 139, 100% female and 100% male, ages 15-21 and 20-22, 2-4 scans and 2 scans respectively), we tested within-person stability of reward-task BOLD activation, with a median of 1 and 2 years between scans. We examined multiple commonly used contrasts of active states and baseline in both the anticipation and feedback phases of a card-guessing reward task. We examined the effects of cortical parcellation resolution, contrast, network (reward regions and resting-state networks), region-size, and activation strength and variability on the stability of reward-related activation. RESULTS: In both samples, contrasts of an active state relative to a baseline were more stable (ICC: intra-class correlation; e.g., Win>Baseline; mean ICC = 0.13 - 0.33) than contrasts of two active states (e.g., Win>Loss; mean ICC = 0.048 - 0.05). Additionally, activation in reward regions was less stable than in many non-task networks (e.g., dorsal attention), and activation in regions with greater between-subject variability showed higher stability in both samples. CONCLUSIONS: These results show that some contrasts from functional neuroimaging activation during a card guessing reward task have partially trait-like properties in adolescent and young adult samples over 1-2 years. Notably, results suggest that contrasts intended to map cognitive function and show robust group-level effects (i.e. Win > Loss) may be less effective in studies of individual differences and disease risk. The robustness of group-level activation should be weighed against other factors when selecting regions of interest in individual difference fMRI studies.

Neural connectivity biotypes: associations with internalizing problems throughout adolescence.

BACKGROUND: Neurophysiological patterns may distinguish which youth are at risk for the well-documented increase in internalizing symptoms during adolescence. Adolescents with internalizing problems exhibit altered resting-state functional connectivity (RSFC) of brain regions involved in socio-affective processing. Whether connectivity-based biotypes differentiate adolescents' levels of internalizing problems remains unknown. METHOD: Sixty-eight adolescents (37 females) reported on their internalizing problems at ages 14, 16, and 18 years. A resting-state functional neuroimaging scan was collected at age 16. Time-series data of 15 internalizing-relevant brain regions were entered into the Subgroup-Group Iterative Multi-Model Estimation program to identify subgroups based on RSFC maps. Associations between internalizing problems and connectivity-based biotypes were tested with regression analyses. RESULTS: Two connectivity-based biotypes were found: a Diffusely-connected biotype (N = 46), with long-range fronto-parietal paths, and a Hyper-connected biotype (N = 22), with paths between subcortical and medial frontal areas (e.g. affective and default-mode network regions). Higher levels of past (age 14) internalizing problems predicted a greater likelihood of belonging to the Hyper-connected biotype at age 16. The Hyper-connected biotype showed higher levels of concurrent problems (age 16) and future (age 18) internalizing problems. CONCLUSIONS: Differential patterns of RSFC among socio-affective brain regions were predicted by earlier internalizing problems and predicted future internalizing problems in adolescence. Measuring connectivity-based biotypes in adolescence may offer insight into which youth face an elevated risk for internalizing disorders during this critical developmental period.

Direct replication of task-dependent neural activation patterns during sadness introspection in two independent adolescent samples.

Functional neuroimaging results need to replicate to inform sound models of human social cognition and its neural correlates. Introspection, the capacity to reflect on one's thoughts and feelings, is one process required for normative social cognition and emotional functioning. Engaging in introspection draws on a network of brain regions including medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), middle temporal gyri (MTG), and temporoparietal junction (TPJ). Maturation of these regions during adolescence mirrors the behavioral advances seen in adolescent social cognition, but the neural correlates of introspection in adolescence need to replicate to confirm their generalizability and role as a possible mechanism. The current study investigated whether reflecting upon one's own feelings of sadness would activate and replicate similar brain regions in two independent samples of adolescents. Participants included 156 adolescents (50% female) from the California Families Project and 119 adolescent girls from the Pittsburgh Girls Study of Emotion. All participants completed the Emotion Regulation Questionnaire (ERQ) and underwent a functional magnetic resonance imaging scan while completing the same facial emotion-processing task at age 16-17 years. Both samples showed similar whole-brain activation patterns when engaged in sadness introspection and when judging a nonemotional facial feature. Whole-brain activation was unrelated to ERQ scores in both samples. Neural responsivity to task manipulations replicated in regions recruited for socio-emotional (mPFC, PCC, MTG, TPJ) and attention (dorsolateral PFC, precentral gyri, superior occipital gyrus, superior parietal lobule) processing. These findings demonstrate robust replication of neural engagement during sadness introspection in two independent adolescent samples.

Research Review: Brain network connectivity and the heterogeneity of depression in adolescence - a precision mental health perspective.

BACKGROUND: Adolescence is a period of high risk for the onset of depression, characterized by variability in symptoms, severity, and course. During adolescence, the neurocircuitry implicated in depression continues to mature, suggesting that it is an important period for intervention. Reflecting the recent emergence of 'precision mental health' - a person-centered approach to identifying, preventing, and treating psychopathology - researchers have begun to document associations between heterogeneity in features of depression and individual differences in brain circuitry, most frequently in resting-state functional connectivity (RSFC). METHODS: In this review, we present emerging work examining pre- and post-treatment measures of network connectivity in depressed adolescents; these studies reveal potential intervention-specific neural markers of treatment efficacy. We also review findings from studies examining associations between network connectivity and both types of depressive symptoms and response to treatment in adults, and indicate how this work can be extended to depressed adolescents. Finally, we offer recommendations for research that we believe will advance the science of precision mental health of adolescence. RESULTS: Nascent studies suggest that linking RSFC-based pathophysiological variation with effects of different types of treatment and changes in mood following specific interventions will strengthen predictions of prognosis and treatment response. Studies with larger sample sizes and direct comparisons of treatments are required to determine whether RSFC patterns are reliable neuromarkers of treatment response for depressed adolescents. Although we are not yet at the point of using RSFC to guide clinical decision-making, findings from research examining the stability and reliability of RSFC point to a favorable future for network-based clinical phenotyping. CONCLUSIONS: Delineating the correspondence between specific clinical characteristics of depression (e.g., symptoms, severity, and treatment response) and patterns of network-based connectivity will facilitate the development of more tailored and effective approaches to the assessment, prevention, and treatment of depression in adolescents.

Girls' brain structural connectivity in late adolescence relates to history of depression symptoms.

BACKGROUND: Girls' depressive symptoms typically increase in adolescence, with individual differences in course and severity being key risk factors for impaired emotional functioning in young adulthood. Given the continued brain white matter (WM) maturation that occurs in adolescence, the present study tested whether structural connectivity patterns in late adolescence are associated with variation in the course of depression symptom severity throughout adolescence. METHOD: Participants were girls (N = 115) enrolled in a multiyear prospective cohort study of risk for depression. Initial depression severity (intercept) at age 10 and change in severity (linear slope) across ages 10-19 were examined in relation to WM tractography collected at age 19. Network-based statistic analyses were used to identify clusters showing variation in structural connectivity in association with depressive symptom intercept, slope, and their interaction. RESULTS: Higher initial depressive severity and steeper positive slope (separately) were associated with greater structural connectivity between temporal, subcortical socioaffective, and occipital regions. Intercept showed more connectivity associations than slope. The interaction effect indicated that higher initial symptom severity and a steeper negative slope (i.e., alleviating symptoms) were related to greater connectivity between cognitive control regions. Moderately severe symptoms that worsened over time were followed by greater connectivity between self-referential and cognitive regions (e.g., posterior cingulate and frontal gyrus). CONCLUSIONS: Higher depressive symptom severity in early adolescence and increasing symptom severity over time may forecast structural connectivity differences in late adolescence, particularly in pathways involving cognitive and emotion-processing regions. Understanding how clinical course relates to neurobiological correlates may inform new treatment approaches to adolescent depression.

Tuning of brain-autonomic coupling by prior threat exposure: Implications for internalizing problems in Mexican-origin adolescents.

Exposure to threat increases the risk for internalizing problems in adolescence. Deficits in integrating bodily cues into representations of emotion are thought to contribute to internalizing problems. Given the role of the medial prefrontal cortex in regulating bodily responses and integrating them into representations of emotional states, coordination between activity in the medial prefrontal cortex and autonomic nervous system responses may be influenced by past threat exposure with consequences for the emergence of internalizing problems. A sample of 179 Mexican-origin adolescents (88 female) reported on neighborhood and school crime, peer victimization, and discrimination when they were 10-16 years old. At age 17, participants underwent a functional neuroimaging scan during which they viewed pictures of emotional faces while respiratory sinus arrhythmia (RSA) and skin conductance responses were measured. Adolescents also reported symptoms of internalizing problems. Greater exposure to threats across adolescence was associated with more internalizing problems. Threat exposure was also associated with stronger negative coupling between the ventromedial prefrontal cortex and RSA. Stronger negative ventromedial prefrontal cortex-RSA coupling was associated with fewer internalizing problems. These results suggest the degree of coordinated activity between the brain and parasympathetic nervous system is both enhanced by threat experiences and decreased in adolescents with more internalizing problems.

Adolescents' brain-autonomic coupling during emotion processing.

Autonomic nervous system (ANS) activity is a core component of emotion processing. The limbic system and medial prefrontal cortex play important roles in the regulation of ANS activity. However, the integration of brain activity and ANS activity has yet to be investigated in adolescents despite independent evidence of adolescents' heightened neural and physiological sensitivity to emotional stimuli. The present study examined the relations of ANS activity in the parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) with brain activity during emotional face processing in adolescents. 135 adolescents (65 female; M = 17.15 yr, SD = 0.42) completed an emotional faces task during an fMRI scan while electrocardiography and skin conductance were recorded simultaneously. Using linear mixed-effect modelling, we tested the effect of change in respiratory sinus arrhythmia (RSA), a measure of PNS activity, and number of skin conductance responses (SCRs), a measure of SNS activity, on neural activity while adolescents viewed emotional faces. Greater RSA withdrawal, indicating decreased PNS activity, was associated with increased activation in the ventromedial prefrontal cortex (vmPFC). More SCRs, indicating greater SNS activity, were associated with decreased activation in several regions including the dorsomedial prefrontal cortex and increased activation in the left hippocampus. Left hippocampus-SCR coupling and vmPFC-RSA coupling predicted baseline SCR and RSA respectively. These findings implicate the hippocampus for potentiating SNS activity, document that regulation of SNS and PNS activity are coordinated with distinct regions of the medial prefrontal cortex, and suggest potential developmental differences in vmPFC regulation of PNS activity between adolescents and adults.

Girls' pubertal development is associated with white matter microstructure in late adolescence.

Patterns of pubertal maturation have been linked to vulnerability for emotion dysregulation disorders in girls, as well as white matter (WM) development, suggestive of a potential mechanism between pubertal maturation and emotional health. Because pubertal processes begin at varying ages (i.e., status, timing) and proceed at varying rates (i.e., tempo), identifying individual differences in the pubertal course associated with subsequent WM microstructure development may reveal clues about neurobiological mechanisms of girls' emotional well-being. In a prospective cohort study of 107 girls, we examined associations between pubertal status at age 9, pubertal timing and tempo from ages 9-15, and WM microstructure at age 19. Tract-based spatial statistics revealed that girls with more advanced pubertal status at age 9, specific to gonadal-related physical changes, had higher fractional anisotropy, and lower mean diffusivity (MD) and radial diffusivity in tracts relevant to cognitive control and emotion regulation (e.g., the superior longitudinal fasciculus, external capsule, and uncinate fasciculus). Additionally, girls with earlier pubertal timing showed lower MD in the left anterior cingulum bundle. Tempo was unrelated to WM measures. These findings implicate specific aspects of pubertal maturation in subsequent neural signatures, suggesting possible neuroendocrine mechanisms relevant to emotional development. Future work incorporating longitudinal neuroimaging in parallel with pubertal measures may contribute to the understanding of individual variation in pubertal course and WM development.

Neural response to prosocial scenes relates to subsequent giving behavior in adolescents: A pilot study.

Adolescence is characterized by extensive neural development and sensitivity to social context, both of which contribute to engaging in prosocial behaviors. Although it is established that prosocial behaviors are linked to positive outcomes in adulthood, little is known about the neural correlates of adolescents' prosociality. Identifying whether the brain is differentially responsive to varying types of social input may be important for fostering prosocial behavior. We report pilot results using new stimuli and an ecologically valid donation paradigm indicating (1) brain regions typically recruited during socioemotional processing evinced differential activation when adolescents evaluated prosocial compared with social or noninteractive scenes (N = 20, ages 13-17 years, MAge = 15.30 years), and (2) individual differences in temporoparietal junction recruitment when viewing others' prosocial behaviors were related to adolescents' own charitable giving. These novel findings have significant implications for understanding how the adolescent brain processes prosocial acts and for informing ways to support adolescents to engage in prosocial behaviors in their daily lives.

Opportunities for Neurodevelopmental Plasticity From Infancy Through Early Adulthood.

Multiple and rapid changes in brain development occur in infancy and early childhood that undergird behavioral development in core domains. The period of adolescence also carries a second influx of growth and change in the brain to support the unique developmental tasks of adolescence. This special section documents two core conclusions from multiple studies. First, evidence for change in brain-based metrics that underlie cognitive and behavioral functions are not limited to narrow windows in development, but are evident from infancy into early adulthood. Second, the specific evident changes are unique to challenges and goals that are salient for a respective developmental period. These brain-based changes interface with environmental inputs, whether from the child's broader ecology or at an individual level.

Dorsomedial Prefrontal Activity to Sadness Predicts Later Emotion Suppression and Depression Severity in Adolescent Girls.

The present study used cross-lagged panel analyses to test longitudinal associations among emotion regulation, prefrontal cortex (PFC) function, and depression severity in adolescent girls. The ventromedial and dorsomedial PFC (vmPFC and dmPFC) were regions of interest given their roles in depression pathophysiology, self-referential processing, and emotion regulation. At ages 16 and 17, seventy-eight girls completed a neuroimaging scan to assess changes in vmPFC and dmPFC activation to sad faces, and measures of depressive symptom severity and emotion regulation. The 1-year cross-lagged effects of dmPFC activity at age 16 on expressive suppression at age 17 and depressive symptomatology at age 17 were significant, demonstrating a predictive relation between dmPFC activity and both suppression and depressive severity.

Developmental Change in Sibling Support and School Commitment Across Adolescence.

School commitment typically declines across adolescence, but the family-level factors that explain this decline have not been fully characterized. This study investigated sibling support as a family resource in predicting school commitment across 7th-10th grade using a sample of 444 adolescents (Mages  = 12.61, 13.59, 14.59, 15.58 years). Results showed that sibling support linearly increased and school commitment decreased and stabilized, independently, over time. Sibling support positively predicted school commitment in seventh grade and across time, suggesting that having supportive siblings may help to offset adolescents' declines in school commitment. Furthermore, having a brother enhanced this association versus having a sister. These findings provide insight into ways to help youth maintain school commitment across the middle- to high school transition.

Do Hostile School Environments Promote Social Deviance by Shaping Neural Responses to Social Exclusion?

The present study examined adolescents' neural responses to social exclusion as a mediator of past exposure to a hostile school environment (HSE) and later social deviance, and whether family connectedness buffered these associations. Participants (166 Mexican-origin adolescents, 54.4% female) reported on their HSE exposure and family connectedness across Grades 9-11. Six months later, neural responses to social exclusion were measured. Finally, social deviance was self-reported in Grades 9 and 12. The HSE-social deviance link was mediated by greater reactivity to social deviance in subgenual anterior cingulate cortex, a region from the social pain network also implicated in social susceptibility. However, youths with stronger family bonds were protected from this neurobiologically mediated path. These findings suggest a complex interplay of risk and protective factors that impact adolescent behavior through the brain.

Adolescent Externalizing Problems: Contributions of Community Crime Exposure and Neural Function During Emotion Introspection in Mexican-Origin Youth.

Models of the etiology of adolescent antisocial behavior suggest that externalizing problems may reflect a susceptibility to crime exposure and a diminished capacity for emotion introspection. In this study, adolescents of Mexican origin completed a neuroimaging task that involved rating their subjective feelings of sadness in response to emotional facial expressions or a nonemotional aspect of each face. At lower levels of neural activity during sadness introspection in posterior cingulate and left temporoparietal junction, and in left amygdala, brain regions involved in mentalizing and emotion, respectively, a stronger positive association between community crime exposure and externalizing problems was found. The specification of emotion introspection as a psychological process showing neural variation may help inform targeted interventions to positively affect adolescent behavior.

Sleep-amount differentially affects fear-processing neural circuitry in pediatric anxiety: A preliminary fMRI investigation.

Insufficient sleep, as well as the incidence of anxiety disorders, both peak during adolescence. While both conditions present perturbations in fear-processing-related neurocircuitry, it is unknown whether these neurofunctional alterations directly link anxiety and compromised sleep in adolescents. Fourteen anxious adolescents (AAs) and 19 healthy adolescents (HAs) were compared on a measure of sleep amount and neural responses to negatively valenced faces during fMRI. Group differences in neural response to negative faces emerged in the dorsal anterior cingulate cortex (dACC) and the hippocampus. In both regions, correlation of sleep amount with BOLD activation was positive in AAs, but negative in HAs. Follow-up psychophysiological interaction (PPI) analyses indicated positive connectivity between dACC and dorsomedial prefrontal cortex, and between hippocampus and insula. This connectivity was correlated negatively with sleep amount in AAs, but positively in HAs. In conclusion, the presence of clinical anxiety modulated the effects of sleep-amount on neural reactivity to negative faces differently among this group of adolescents, which may contribute to different clinical significance and outcomes of sleep disturbances in healthy adolescents and patients with anxiety disorders.

Role of contingency in striatal response to incentive in adolescents with anxiety.

This study examines the effect of contingency on reward function in anxiety. We define contingency as the aspect of a situation in which the outcome is determined by one's action-that is, when there is a direct link between one's action and the outcome of the action. Past findings in adolescents with anxiety or at risk for anxiety have revealed hypersensitive behavioral and neural responses to higher value rewards with correct performance. This hypersensitivity to highly valued (salient) actions suggests that the value of actions is determined not only by outcome magnitude, but also by the degree to which the outcome is contingent on correct performance. Thus, contingency and incentive value might each modulate reward responses in unique ways in anxiety. Using fMRI with a monetary reward task, striatal response to cue anticipation is compared in 18 clinically anxious and 20 healthy adolescents. This task manipulates orthogonally reward contingency and incentive value. Findings suggest that contingency modulates the neural response to incentive magnitude differently in the two groups. Specifically, during the contingent condition, right-striatal response tracks incentive value in anxious, but not healthy, adolescents. During the noncontingent condition, striatal response is bilaterally stronger to low than to high incentive in anxious adolescents, while healthy adolescents exhibit the expected opposite pattern. Both contingency and reward magnitude differentiate striatal activation in anxious versus healthy adolescents. These findings may reflect exaggerated concern about performance and/or alterations of striatal coding of reward value in anxious adolescents. Abnormalities in reward function in anxiety may have treatment implications.

Adolescent girls' neural response to reward mediates the relation between childhood financial disadvantage and depression.

BACKGROUND: Children who experience socioeconomic disadvantage are at heightened risk for developing depression; however, little is known about neurobiological mechanisms underlying this association. Low socioeconomic status (SES) during childhood may confer risk for depression through its stress-related effects on the neural circuitry associated with processing monetary rewards. METHODS: In a prospective study, we examined the relationships among the number of years of household receipt of public assistance from age 5-16 years, neural activation during monetary reward anticipation and receipt at age 16, and depression symptoms at age 16 in 123 girls. RESULTS: Number of years of household receipt of public assistance was positively associated with heightened response in the medial prefrontal cortex during reward anticipation, and this heightened neural response mediated the relationship between socioeconomic disadvantage and current depression symptoms, controlling for past depression. CONCLUSIONS: Chronic exposure to socioeconomic disadvantage in childhood may alter neural circuitry involved in reward anticipation in adolescence, which in turn may confer risk for depression.