A precision neuroscience approach to estimating reliability of neural responses during emotion processing: Implications for task-fMRI.

Recent work demonstrating low test-retest reliability of neural activation during fMRI tasks raises questions about the utility of task-based fMRI for the study of individual variation in brain function. Two possible sources of the instability in task-based BOLD signal over time are noise or measurement error in the instrument, and meaningful variation across time within-individuals in the construct itself-brain activation elicited during fMRI tasks. Examining the contribution of these two sources of test-retest unreliability in task-evoked brain activity has far-reaching implications for cognitive neuroscience. If test-retest reliability largely reflects measurement error, it suggests that task-based fMRI has little utility in the study of either inter- or intra-individual differences. On the other hand, if task-evoked BOLD signal varies meaningfully over time, it would suggest that this tool may yet be well suited to studying intraindividual variation. We parse these sources of variance in BOLD signal in response to emotional cues over time and within-individuals in a longitudinal sample with 10 monthly fMRI scans. Test-retest reliability was low, reflecting a lack of stability in between-person differences across scans. In contrast, within-person, within-session internal consistency of the BOLD signal was higher, and within-person fluctuations across sessions explained almost half the variance in voxel-level neural responses. Additionally, monthly fluctuations in neural response to emotional cues were associated with intraindividual variation in mood, sleep, and exposure to stressors. Rather than reflecting trait-like differences across people, neural responses to emotional cues may be more reflective of intraindividual variation over time. These patterns suggest that task-based fMRI may be able to contribute to the study of individual variation in brain function if more attention is given to within-individual variation approaches, psychometrics-beginning with improving reliability beyond the modest estimates observed here, and the validity of task fMRI beyond the suggestive associations reported here.

Examining the Association between Punishment and Reward Sensitivity and Response Inhibition to Previously-Incentivized Cues across Development.

Processing and learning from affective cues to guide goal-directed behavior may be particularly important during adolescence; yet the factors that promote and/or disrupt the ability to integrate value in order to guide decision making across development remain unclear. The present study (N = 1046) assessed individual difference factors (self-reported punishment and reward sensitivity) related to whether previously-rewarded and previously-punished cues differentially impact goal-directed behavior (response inhibition) in a large developmental sample. Participants were between the ages of 8-21 years (Mage = 14.29, SD = 3.97, 50.38% female). Previously-rewarded cues improved response inhibition among participants age 14 and older. Further, punishment sensitivity predicted overall improved response inhibition among participants aged 10 to 18. The results highlight two main factors that are associated with improvements in the ability to integrate value to guide goal-directed behaviour - cues in the environment (e.g., reward-laden cues) and individual differences in punishment sensitivity. These findings have implications for both educational and social policies aimed at characterizing the ways in which youth integrate value to guide decision making.

Graded Variation in T1w/T2w Ratio during Adolescence: Measurement, Caveats, and Implications for Development of Cortical Myelin.

Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (HCP-D; N = 628, ages 8-21). We characterize microstructural changes relevant to myelination by estimating age-related differences in T1w/T2w throughout the cerebral neocortex from childhood to early adulthood. We apply Bayesian spline models and clustering analysis to demonstrate graded variation in age-dependent cortical T1w/T2w differences that are correlated with the sensorimotor-association (S-A) axis of cortical organization reported by others. In sensorimotor areas, T1w/T2w ratio measures start at high levels at early ages, increase at a fast pace, and decelerate at later ages (18-21). In intermediate multimodal areas along the S-A axis, T1w/T2w starts at intermediate levels and increases linearly at an intermediate pace. In transmodal/paralimbic association areas, T1w/T2w starts at low levels and increases linearly at the slowest pace. These data provide evidence for graded variation of the T1w/T2w ratio along the S-A axis that may reflect cortical myelination changes during adolescence underlying the development of complex information processing and psychological functioning. We discuss the implications of these results as well as caveats in interpreting magnetic resonance imaging (MRI)-based estimates of myelination.SIGNIFICANCE STATEMENT Myelin is a lipid membrane that is essential to healthy brain function. Myelin wraps axons to increase neural signaling speed, enabling complex neuronal functioning underlying learning and cognition. Here, we characterize the developmental timing of myelination across the cerebral cortex during adolescence using a noninvasive proxy measure, T1w/T2w mapping. Our results provide new evidence demonstrating graded variation across the cortex in the timing of T1w/T2w changes during adolescence, with rapid T1w/T2w increases in lower-order sensory areas and gradual T1w/T2w increases in higher-order association areas. This spatial pattern of microstructural brain development closely parallels the sensorimotor-to-association axis of cortical organization and plasticity during ontogeny.

Concurrent and prospective associations between fitbit wearable-derived RDoC arousal and regulatory constructs and adolescent internalizing symptoms.

BACKGROUND: Adolescence is characterized by alterations in biobehavioral functioning, during which individuals are at heightened risk for onset of psychopathology, particularly internalizing disorders. Researchers have proposed using digital technologies to index daily biobehavioral functioning, yet there is a dearth of research examining how wearable metrics are associated with mental health. METHODS: We preregistered analyses using the Adolescent Brain Cognitive Development Study dataset using wearable data collection in 5,686 adolescents (123,862 person-days or 2,972,688 person-hours) to determine whether wearable indices of resting heart rate (RHR), step count, and sleep duration and variability in these measures were cross-sectionally associated with internalizing symptomatology. All models were also run controlling for age, sex, body mass index, socioeconomic status, and race. We then performed prospective analyses on a subset of this sample (n = 143) across 25 months that had Fitbit data available at baseline and follow-up in order to explore directionality of effects. RESULTS: Cross-sectional analyses revealed a small, yet significant, effect size (R2 = .053) that higher RHR, lower step count and step count variability, and greater variability in sleep duration were associated with greater internalizing symptoms. Cross-lagged panel model analysis revealed that there were no prospective associations between wearable variables and internalizing symptoms (partial R2 = .026), but greater internalizing symptoms and higher RHR predicted lower step count 25 months later (partial R2 = .010), while higher RHR also predicted lower step count variability 25 months later (partial R2 = .008). CONCLUSIONS: Findings indicate that wearable indices concurrently associate with internalizing symptoms during early adolescence, while a larger sample size is likely required to accurately assess prospective or directional effects between wearable indices and mental health. Future research should capitalize on the temporal resolution provided by wearable devices to determine the intensive longitudinal relations between biobehavioral risk factors and acute changes in mental health.

Language development as a mechanism linking socioeconomic status to executive functioning development in preschool.

Childhood socioeconomic status (SES) is related to disparities in the development of both language and executive functioning (EF) skills. Emerging evidence suggests that language development may precede and provide necessary scaffolding for EF development in early childhood. The present preregistered study investigates how these skills co-develop longitudinally in early childhood and whether language development explains the relationship between SES and EF development. A socioeconomically diverse sample of 305 children completed repeated assessments of language (sentence comprehension) and EF (cognitive flexibility, behavioral inhibition, and cognitive inhibition) at four waves spaced 9 months apart from ages 3 to 5 years. Bivariate latent curve models with structured residuals were estimated to disaggregate between-person and within-person components of stability and change. Results revealed bidirectional relationships between language and EF across all waves. However, at 3 years, language comprehension more strongly predicted EF than the reverse; yet by 5 years, the bidirectional effects across domains did not significantly differ. Children from higher-SES backgrounds exhibited higher initial language and EF skills than children from lower-SES families, though SES was not associated with either rate of growth. Finally, early language-mediated the association between SES and early EF skills, and this model outperformed a reverse direction mediation. Together, results suggest that EF development is driven by early language development, and that SES disparities in EF are explained, at least in part, by early differences in language comprehension. These findings have implications for early interventions to support children's language skills as a potential pathway to improving early EF development.

Brain parcellation selection: An overlooked decision point with meaningful effects on individual differences in resting-state functional connectivity.

Over the past decade extensive research has examined the segregation of the human brain into large-scale functional networks. The resulting network maps, i.e. parcellations, are now commonly used for the a priori identification of functional networks. However, the use of these parcellations, particularly in developmental and clinical samples, hinges on four fundamental assumptions: (1) the various parcellations are equally able to recover the networks of interest; (2) adult-derived parcellations well represent the networks in children's brains; (3) network properties, such as within-network connectivity, are reliably measured across parcellations; and (4) parcellation selection does not impact the results with regard to individual differences in given network properties. In the present study we examined these assumptions using eight common parcellation schemes in two independent developmental samples. We found that the parcellations are equally able to capture networks of interest in both children and adults. However, networks bearing the same name across parcellations (e.g., default network) do not produce reliable within-network measures of functional connectivity. Critically, parcellation selection significantly impacted the magnitude of associations of functional connectivity with age, poverty, and cognitive ability, producing meaningful differences in interpretation of individual differences in functional connectivity based on parcellation choice. Our findings suggest that work employing parcellations may benefit from the use of multiple schemes to confirm the robustness and generalizability of results. Furthermore, researchers looking to gain insight into functional networks may benefit from employing more nuanced network identification approaches such as using densely-sampled data to produce individual-derived network parcellations. A transition towards precision neuroscience will provide new avenues in the characterization of functional brain organization across development and within clinical populations.

Feeling left out or just surprised? Neural correlates of social exclusion and overinclusion in adolescence.

Social belonging is an important human drive that influences mood and behavior. Neural responses to social exclusion are well-characterized, but the specificity of these responses to processing rejection-related affective distress is unknown. The present study compares neural responses to exclusion and overinclusion, a condition that similarly violates fairness expectations but does not involve rejection, with a focus on implications for models of dorsal anterior cingulate cortex (dACC) and anterior insula (AI) function. In an fMRI adaptation of the Cyberball paradigm with adolescents aged 11.1-17.7 years (N = 69), we employed parametric modulators to examine scaling of neural signal with cumulative exclusion and inclusion events, an approach that overcomes arbitrary definitions of condition onsets/offsets imposed on fluid, continuous gameplay. We identified positive scaling of dACC and posterior insula response with cumulative exclusion events, but these same regions exhibited trending signal decreases with cumulative inclusion events. Furthermore, areas within the dACC and insula also responded to context incongruency (throws to the participant in the exclusion run; throws between computer players in the overinclusion run). These findings caution against interpretations that responses in these regions uniquely reflect the affective distress of exclusion within social interaction paradigms. We further identified that the left ventrolateral PFC, rostromedial PFC, and left intraparietal sulcus responded similarly to cumulative exclusion and inclusion. These findings shed light on which neural regions exhibit patterns of differential sensitivity to exclusion or overinclusion, as well as those that are more broadly engaged by both types of social interaction.

Within-person fluctuations in stressful life events, sleep, and anxiety and depression symptoms during adolescence: a multiwave prospective study.

BACKGROUND: Adolescence is characterized by substantial changes in sleep behavior, heightened exposure to stressful life events (SLEs), and elevated risk for internalizing problems like anxiety and depression. Although SLEs are consistently associated with the onset of internalizing psychopathology, the mechanisms underlying this relationship remain poorly understood, especially at the within-person level. Here, we leverage a high-frequency longitudinal design to examine sleep as a potential mechanism linking SLEs to increases in anxiety and depression symptoms over a one-year period. METHODS: Thirty female adolescents aged 15-17 years completed 12 monthly in-laboratory assessments of exposure to SLEs and symptoms of anxiety and depression (n = 355 monthly assessments), and wore an actigraphy wristband for continuous monitoring of sleep for the duration of the study (n = 6,824 sleep days). Multilevel models examined concurrent and lagged within-person associations between SLEs, sleep duration and timing regularity, and anxiety and depression symptoms. RESULTS: Within-person fluctuations in SLEs were associated with variability in sleep duration both concurrently and prospectively, such that when adolescents experienced greater SLEs than was typical for them, they exhibited more variable sleep duration that same month as well as the following month. In turn, within-person increases in sleep duration variability predicted greater anxiety symptoms in the same month and mediated the association between SLEs and anxiety. CONCLUSIONS: These findings highlight sleep disruptions as a mechanism underlying the longitudinal associations between SLEs and anxiety symptoms, and suggest that interventions promoting sleep schedule consistency may help mitigate risk for stress-related psychopathology in adolescence.

Expectations of Social Consequences Impact Anticipated Involvement in Health-Risk Behavior During Adolescence.

This study examined how individual differences in expectations of social consequences relate to individuals' expected involvement in health-risk behaviors (HRBs). A total of 122 adolescents (aged 11-17) reported their expected involvement in a number of risk behaviors and whether or not they expect to be liked more or less by engaging in the behavior: the expected social benefit. Higher perceived social benefit was associated with higher anticipated involvement in said behavior. This relationship was stronger for adolescents who reported a higher degree of peer victimization, supporting the hypothesis that experiencing victimization increases the social value of peer interactions. Findings suggest that adolescents incorporate expectations of social consequences when making decisions regarding their involvement in HRBs.

Ethics-relevant values in adulthood: Longitudinal findings from the life and time study.

OBJECTIVE: This study investigates a set of variables related to the relative valuing of narrow self-interest versus the concerns of a larger community. These values likely capture stable dispositions. Additionally, because ethics-relevant values are associated with ongoing cultural and moral socialization, they may develop over time as in May's theory of "mature" values. METHOD: We administered eight value priority scales (Mature Values, Unmitigated Self-Interest, Materialism, Financial Aspirations, and Horizontal and Vertical Individualism and Collectivism) to a national community sample (N = 864, 66% female, 71% White, mean age 36) on four occasions approximately one year apart (Time 4 N = 570). We examined the mean-level change as cross-sectional age differences and longitudinal change, and rank-order stability. Correlations with Big Five/Big Six personality traits are reported. RESULTS: As people grew older, they increased in Mature Values and Horizontal and Vertical Collectivism, and decreased in Unmitigated Self-Interest, Materialism, and Vertical Individualism. Rank-order stability of the values was nearly as high as personality traits over three years. Stability increased with age for some scales. DISCUSSION: The stability of values scores suggests that they capture dispositional aspects, but age differences and longitudinal trends are also consistent with the hypothesis of socialization toward more inclusive value priorities.

Novel insights from the Yellow Light Game: Safe and risky decisions differentially impact adolescent outcome-related brain function.

Changes across the span of adolescence in the adolescent reward system are thought to increase the tendency to take risks. While developmental differences in decision and outcome-related reward processes have been studied extensively, existing paradigms have largely neglected to measure how different types of decisions modulate reward-related outcome processes. We modified an existing decision-making paradigm (the Stoplight Task; Chein et al., 2011) to create a flexible laboratory measure of decision-making and outcome processing, including the ability to assess modulatory effects of safe versus risky decisions on reward-related outcome processes: the Yellow Light Game (YLG). We administered the YLG in the MRI scanner to 81 adolescents, ages 11-17 years, recruited from the community. Results showed that nucleus accumbens activation was enhanced for (1) risky > safe decisions, (2) positive > negative outcomes, and (3) outcomes following safe decisions compared to outcomes following risky decisions, regardless of whether these outcomes were positive or negative. Outcomes following risky decisions (compared to outcomes following safe decisions) were associated with enhanced activity in cortical midline structures. Furthermore, while there were no developmental differences in risk-taking behavior, more pubertally mature adolescents showed enhanced nucleus accumbens activation during positive > negative outcomes. These findings suggest that outcome processing is modulated by the types of decisions made by adolescents and highlight the importance of investigating processes involved in safe as well as risky decisions to better understand the adolescent tendency to take risks.

The impact of executive function on response to cognitive behavioral therapy in late-life depression.

OBJECTIVE: Late-life depression (LLD) is a common and debilitating condition among older adults. Cognitive behavioral therapy (CBT) has strong empirical support for the treatment of depression in all ages, including in LLD. In teaching patients to identify, monitor, and challenge negative patterns in their thinking, CBT for LLD relies heavily on cognitive processes and, in particular, executive functioning, such as planning, sequencing, organizing, and selectively inhibiting information. It may be that the effectiveness of CBT lies in its ability to train these cognitive areas. METHODS: Participants with LLD completed a comprehensive neuropsychological battery before enrolling in CBT. The current study examined the relationship between neuropsychological function prior to treatment and response to CBT. RESULTS: When using three baseline measures of executive functioning that quantify set shifting, cognitive flexibility, and response inhibition to predict treatment response, only baseline Wisconsin Card Sort Task performance was associated with a significant drop in depression symptoms after CBT. Specifically, worse performance on the Wisconsin Card Sort Task was associated with better treatment response. CONCLUSIONS: These results suggest that CBT, which teaches cognitive techniques for improving psychiatric symptoms, may be especially beneficial in LLD if relative weaknesses in specific areas of executive functioning are present.

Neural Reactivity to Emotional Faces May Mediate the Relationship Between Childhood Empathy and Adolescent Prosocial Behavior.

Reactivity to others' emotions not only can result in empathic concern (EC), an important motivator of prosocial behavior, but can also result in personal distress (PD), which may hinder prosocial behavior. Examining neural substrates of emotional reactivity may elucidate how EC and PD differentially influence prosocial behavior. Participants (N = 57) provided measures of EC, PD, prosocial behavior, and neural responses to emotional expressions at ages 10 and 13. Initial EC predicted subsequent prosocial behavior. Initial EC and PD predicted subsequent reactivity to emotions in the inferior frontal gyrus (IFG) and inferior parietal lobule, respectively. Activity in the IFG, a region linked to mirror neuron processes, as well as cognitive control and language, mediated the relation between initial EC and subsequent prosocial behavior.

Randomized controlled trial of a web-based program for preventing anxiety and depression in university students.

OBJECTIVE: Few online interventions targeting anxiety and depression in university students are designed for universal delivery, and none for group-level delivery. This randomized controlled trial (NCT No. 04361045) examined the effectiveness of such a prevention program. METHOD: StriveWeekly is a web-based intervention designed with weekly self-guided skill modules (e.g., behavioral activation) that are synchronously delivered to all users. Student participants (n = 1,607) were recruited from one large public university, and 65.4% had no prior mental health service use. Participants were randomly assigned to 8 weeks of StriveWeekly (n = 804) or a waitlist condition (n = 803). Participants completed web-based surveys at baseline, posttest, and 3-month follow-up. The primary outcome was the self-reported Depression Anxiety and Stress Scale-21. RESULTS: Piecewise linear mixed-effect models found significant group by time interactions for depression (t = -3.05, p = .002), anxiety (t = -3.01, p = .003), and total symptoms (t = -3.34, p < .001). Relative to the waitlist, students assigned to StriveWeekly improved more from baseline to posttest (between-group d = 0.18-0.21). These small effects were maintained through follow-up, and subsequently replicated by the original waitlist. The intervention was initiated by 73.0% of students in the StriveWeekly condition (modules completed: M = 3.72), and 71.6% of all posttest respondents rated the intervention highly. CONCLUSION: Findings supported StriveWeekly's effectiveness for large scale indicated prevention of anxiety and depression symptoms in university students. However, further development and research are still needed, as not all students used the intervention, reported satisfaction, or experienced improvement. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Challenges with Latent Variable Approaches to Operationalizing Dimensions of Childhood adversity - a Commentary on Sisitsky et al. (2023).

Childhood adversity is a common, powerful risk factor for future mental and physical health problems. Appropriately aggregating and categorizing discrete adverse experiences into cumulative indices remains an active area of research and debate in the field of developmental psychopathology. In a recent article by Sisitsky et al. (2013), they report using confirmatory factor analysis and latent profile analysis to categorize participants into "profiles" of childhood adversity. In this commentary, we argue that categorizing dimensions or profiles of childhood adversity based on the tendency of adversities to co-occur is misaligned with dimensional models of adversity, which derive underlying dimensions from their tendency to cumulatively predict certain outcomes rather than adversity co-occurrence. We summarize the history of theories and methods of operationalizing childhood adversity that led to the development of the dimensional model of adversity and psychopathology. We then explain why latent variable approaches, which simply reflect the tendency of adverse experiences to co-occur, are inappropriate for validating any given approach.

Shifting qualities of negative affective experience through adolescence: Age-related change and associations with functional outcomes.

Research shows negative affect increases in healthy adolescents, and this normative change is paralleled by increasing risk for the onset of psychopathology. However, research is limited in characterizing qualitative differences in the type of negative affect experienced beyond the positive-negative valence dimension. In the current study, we establish the relationship between different forms of negative affect and functioning outcomes (i.e., different facets of social functioning and life satisfaction), and examine whether these forms of negative affect are differentially prevalent across late childhood and adolescence. Seven-hundred and 70 participants aged 8-17 years completed self-report measures that assessed a wide range of negative affective experiences. A factor analysis on the negative affect items revealed a four-factor solution that characterized the dimensions of affective experience, with factors reflecting general anxiety, anger, evaluative anxiety, and sadness. Generalized additive model approaches revealed general anxiety increased nonlinearly with age and was associated with decreased reports of emotional support, a facet of social functioning. Anger was associated with increased perceived hostility, perceived rejection, and decreased life satisfaction, and remained stable across the age range. Evaluative anxiety was associated with greater loneliness and increased linearly with increasing age. Sadness was associated with all outcome measures and showed nonlinear changes with age, with notable increases in midadolescence. These results show that subsuming these subtypes of negative affect under a singular concept may obscure meaningful relationships between affect, age, and functioning. Exploring diverse forms of negative affect may help refine theories of emotional development and ultimately inform windows of risk for psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Hitchhiker's guide to longitudinal models: A primer on model selection for repeated-measures methods.

Longitudinal data are becoming increasingly available in developmental neuroimaging. To maximize the promise of this wealth of information on how biology, behavior, and cognition change over time, there is a need to incorporate broad and rigorous training in longitudinal methods into the repertoire of developmental neuroscientists. Fortunately, these models have an incredibly rich tradition in the broader developmental sciences that we can draw from. Here, we provide a primer on longitudinal models, written in a beginner-friendly (and slightly irreverent) manner, with a particular focus on selecting among different modeling frameworks (e.g., multilevel versus latent curve models) to build the theoretical model of development a researcher wishes to test. Our aims are three-fold: (1) lay out a heuristic framework for longitudinal model selection, (2) build a repository of references that ground each model in its tradition of methodological development and practical implementation with a focus on connecting researchers to resources outside traditional neuroimaging journals, and (3) provide practical resources in the form of a codebook companion demonstrating how to fit these models. These resources together aim to enhance training for the next generation of developmental neuroscientists by providing a solid foundation for future forays into advanced modeling applications.

Multivariate brain-based dimensions of child psychiatric problems: degrees of generalizability.

Multivariate machine learning techniques are a promising set of tools for identifying complex brain-behavior associations. However, failure to replicate results from these methods across samples has hampered their clinical relevance. This study aimed to delineate dimensions of brain functional connectivity that are associated with child psychiatric symptoms in two large and independent cohorts: the Adolescent Brain Cognitive Development (ABCD) Study and the Generation R Study (total n =8,605). Using sparse canonical correlations analysis, we identified three brain-behavior dimensions in ABCD: attention problems, aggression and rule-breaking behaviors, and withdrawn behaviors. Importantly, out-of-sample generalizability of these dimensions was consistently observed in ABCD, suggesting robust multivariate brain-behavior associations. Despite this, out-of-study generalizability in Generation R was limited. These results highlight that the degree of generalizability can vary depending on the external validation methods employed as well as the datasets used, emphasizing that biomarkers will remain elusive until models generalize better in true external settings.

Associations between multi-method latent factors of puberty and brain structure in adolescent girls.

Pubertal processes are associated with structural brain development, but studies have produced inconsistent findings that may relate to different measurements of puberty. Measuring both hormones and physical characteristics is important for capturing variation in neurobiological development. The current study explored associations between cortical thickness and latent factors from multi-method pubertal data in 174 early adolescent girls aged 10-13 years in the Transitions in Adolescent Girls (TAG) Study. Our multi-method approach used self-reported physical characteristics and hormone levels (dehydroepiandrosterone (DHEA), testosterone (T), and estradiol (E2) from saliva) to estimate an overall pubertal factor and for each process of adrenarche and gonadarche. There were negative associations between the overall puberty factor representing later stage and thickness in the posterior cortex, including the occipital cortices and extending laterally to the parietal lobe. However, the multi-method latent factor had weaker cortical associations when examining the adnearcheal process alone, suggesting physical characteristics and hormones capture different aspects of neurobiological development during adrenarche. Controlling for age weakened some of these associations. These findings show that associations between pubertal stage and cortical thickness differ depending on the measurement method and the pubertal process, and both should be considered in future confirmatory studies on the developing brain.

5-HTTLPR short allele, resilience, and successful aging in older adults.

OBJECTIVE: Resilience is proposed as a significant component of successful aging. Young adult carriers of the Serotonin Transporter Polymorphism (5-HTTLPR) short(s) allele appear to have reduced resilience to stress. We examined whether the presence of the short allele was associated with poorer emotional resilience in older adults. METHODS: In a cross-sectional study of 99 healthy, community-dwelling, older adults, we determined 5-HTTLPR genotype status and administered the Connor-Davidson Resilience Scale and self-reported measures of successful aging, cognition, and health. RESULTS: There was no significant association between the 5-HTTLPR s allele and resilience. S allele carriers had worse cognition and self-report ratings of successful aging. CONCLUSION: These findings suggest that the impact of the 5-HTTLPR s allele on stress-related outcomes may attenuate with older age. However, s allele status appears to be a biomarker of poorer self-rated successful aging, and cognitive performance in older adults.