Robust is not necessarily reliable: From within-subjects fMRI contrasts to between-subjects comparisons.

Advances in cognitive and affective neuroscience come largely from within-subjects comparisons, in which the functional significance of neural activity is determined by contrasting two or more experimental conditions. Clinical and social neuroscience studies have attempted to leverage between-subject variability in such condition differences to better understand psychopathology and other individual differences. Shifting from within-to between-subjects comparisons requires that measures have adequate internal consistency to function as individual difference variables. This is particularly relevant for difference scores-which have lower reliability. The field has assumed reasonable internal consistency of neural measures based on consistent findings across studies (i.e., if a within-subject difference in neural activity is robust, then it must be reliable). Using one of the most common fMRI paradigms in the clinical neuroscience literature (i.e., a face- and shape-matching task), in a large sample of adolescents (N = 139) we replicate a robust finding: amygdala activation is greater for faces than shapes. Moreover, we demonstrate that the internal consistency of the amygdala in face and shape blocks was excellent (Spearman-Brown corrected reliability [SB] > .94). However, the internal consistency of the activation difference between faces and shapes was nearly zero (SB = -.06). This reflected the fact that the amygdala response to faces and shapes was highly correlated (r = .97) across individuals. Increased neural activation to faces versus shapes could not possibly function as an individual difference measure in these data-illustrating how neural activation can be robust within subjects, but unreliable as an individual difference measure. Strong and reproducible condition differences in neural activity are not necessarily well-suited for individual differences research-and neuroimaging studies should always report the internal consistency of, and correlations between, activations used in individual differences research.

Reduced Hedonic Capacity/Approach Motivation Relates to Blunted Responsivity to Gain and Loss Feedback in Children.

Adolescents and adults with major depressive disorder or elevated depressive symptoms show reduced reward responses and tend to show enhanced responses to negative stimuli. However, reward-related behaviors and adaptive responses to negative feedback undergo dramatic changes across puberty. Thus, key questions remain regarding how altered incentive processing relates to depressive and anhedonic symptoms in prepubertal child populations. Twenty-four nonclinical prepubertal children 7-10 years of age (15 male; 16 Caucasian) completed two signal detection tasks that assessed behavioral responsivity to candy gain and loss feedback, respectively. These tasks were based on Pizzagalli's probabilistic reward task where asymmetric feedback leads to greater bias toward the more frequently rewarded response in more hedonic or nondepressed adults. We further modified the task to create a version where incorrect responses could result in losses from an original allotment of candy. Children and parents/guardians also completed individual difference questionnaires to assess the child's depressive symptoms, general affect, and hedonic capacity/approach motivation. Regressions indicated a relation between hedonic capacity/approach motivation (child self-report) and response bias in both gain and loss tasks. No significant relations were observed between depressive (child self-report), internalizing (parent report), or externalizing symptoms (parent report) and bias in either the gain or loss task in this small sample. These results suggest that reduced hedonic capacity/approach motivation is associated with blunted responses to both gain and loss feedback in prepubertal children.

Brain-behavior relationships in the experience and regulation of negative emotion in healthy children: implications for risk for childhood depression.

Structural and functional alterations in a variety of brain regions have been associated with depression and risk for depression across the life span. A majority of these regions are associated with emotion reactivity and/or regulation. However, it is generally unclear what mechanistic role these alterations play in the etiology of depression. A first step toward understanding this is to characterize the relationships between variation in brain structure/function and individual differences in depression severity and related processes, particularly emotion regulation. To this end, the current study examines how brain structure and function predict concurrent and longitudinal measures of depression symptomology and emotion regulation skills in psychiatrically healthy school-age children (N = 60). Specifically, we found that smaller hippocampus volumes and greater responses to sad faces in emotion reactivity regions predict increased depressive symptoms at the time of scan, whereas larger amygdala volumes, smaller insula volumes, and greater responses in emotion reactivity regions predict decreased emotion regulation skills. In addition, larger insula volumes predict improvements in emotion regulation skills even after accounting for emotion regulation at the time of scan. Understanding brain-behavior relationships in psychiatrically healthy samples, especially early in development, will help inform normative developmental trajectories and neural alterations in depression and other affective pathology.

Candy and the brain: neural response to candy gains and losses.

Incentive processing is a critical component of a host of cognitive processes, including attention, motivation, and learning. Neuroimaging studies have clarified the neural systems underlying processing of primary and secondary rewards in adults. However, current reward paradigms have hindered comparisons across these reward types as well as between age groups. To address methodological issues regarding the timing of incentive delivery (during scan vs. postscan) and the age-appropriateness of the incentive type, we utilized fMRI and a modified version of a card-guessing game (CGG), in which candy pieces delivered postscan served as the reinforcer, to investigate neural responses to incentives. Healthy young adults 22-26 years of age won and lost large and small amounts of candy on the basis of their ability to guess the number on a mystery card. BOLD activity was compared following candy gain (large/small), loss (large/small), and neutral feedback. During candy gains, adults recruited regions typically involved in response to monetary and other rewards, such as the caudate, putamen, and orbitofrontal cortex. During losses, they displayed greater deactivation in the hippocampus than in response to neutral and gain feedback. Additionally, individual-difference analyses suggested a negative relationship between reward sensitivity (assessed by the Behavioral Inhibition/Behavioral Activation Scales) and the difference between high- and low-magnitude losses in the caudate and lateral orbitofrontal cortex. Also within the striatum, greater punishment sensitivity was positively related to the difference in activity following high as compared to low gains. Overall, these results show strong overlap with those from previous monetary versions of the CGG and provide a baseline for future work with developmental populations.

Self-Reported Gonadal Pubertal Timing Predicts Adolescent Borderline Personality Symptoms: Two Extended Replications With Prospective and Cross-Sectional Data.

The current study investigated the understudied relationship between pubertal timing and borderline personality disorder (BPD) symptoms in males and females. We conducted hierarchical linear regressions in a longitudinal Cohort 1 (N = 117) and a cross-sectional Cohort 2 (N = 127). Cohort 1: Pubertal timing was self-reported at age 10; BPD symptoms and covariates were assessed between ages 13 and 19. Cohort 2: All assessments were between ages 8 and 12. Covariates: race, age, internalizing and externalizing symptoms, and income-to-needs ratio. Sex differences were examined post hoc. In Cohort 1, early gonadal timing was associated with more BPD symptoms in females (beta = .46, p = .002), and late gonadal timing was associated with more BPD symptoms in males (beta = -.23, p = .035). In Cohort 2, early gonadal timing was associated with more BPD symptoms (beta = .21, p = .033) without sex moderation. Results indicate that early gonadal development could be a risk indicator for the emergence of BPD in adolescence, particularly in females, which could inform causal mechanisms and intervention targets.

Family income buffers the relationship between childhood adverse experiences and putamen volume.

Adverse experiences and family income in childhood have been associated with altered brain development. While there is a large body of research examining these associations, it has primarily used cross-sectional data sources and studied adverse experiences and family income in isolation. However, it is possible that low family income and adverse experiences represent dissociable and potentially interacting profiles of risk. To address this gap in the literature, we examined brain structure as a function of adverse experiences in childhood and family income in 158 youths with up to five waves of MRI data. Specifically, we assessed the interactive effect of these two risk factors on six regions of interest: hippocampus, putamen, amygdala, nucleus accumbens, caudate, and thalamus. Adverse experiences and family income interacted to predict putamen volume (B = 0.086, p = 0.011) but only in participants with family income one standard deviation below the mean (slope estimate = -0.11, p = 0.03). These results suggest that adverse experiences in childhood result in distinct patterns of brain development across the socioeconomic gradient. Given previous findings implicating the role of the putamen in psychopathology-related behaviors, these results emphasize the importance of considering life events and socioeconomic context when evaluating markers of risk. Future research should include interactive effects of environmental exposures and family income to better characterize risk for psychopathology in diverse samples.

Timing and Type of Early Psychopathology Symptoms Predict Longitudinal Change in Cortical Thickness From Middle Childhood Into Early Adolescence.

BACKGROUND: Early-life experiences have profound effects on functioning in adulthood. Altered cortical development may be one mechanism through which early-life experiences, including poverty and psychopathology symptoms, affect outcomes. However, there is little prospective research beginning early in development that combines clinician-rated psychopathology symptoms and multiwave magnetic resonance imaging to examine when these relationships emerge. METHODS: Children from the Preschool Depression Study who completed diagnostic interviews at three different developmental stages (preschool, school age, early adolescent) and up to three magnetic resonance imaging scans beginning in middle childhood participated in this study (N = 138). Multilevel models were used to calculate intercepts and slopes of cortical thickness within a priori cortical regions of interest. Linear regressions probed how early-life poverty and psychopathology (depression, anxiety, and externalizing symptoms at separate developmental periods) related to intercept/slope. RESULTS: Collectively, experiences during the preschool period predicted reduced cortical thickness, via either reduced intercept or accelerated thinning (slope). Early-life poverty predicted intercepts within sensory and sensory-motor integration regions. Beyond poverty, preschool anxiety symptoms predicted intercepts within the insula, subgenual cingulate, and inferior parietal cortex. Preschool externalizing symptoms predicted accelerated thinning within prefrontal and parietal cortices. Depression and anxiety/externalizing symptoms at later ages were not significant predictors. CONCLUSIONS: Early childhood is a critical period of risk; experiences at this developmental stage specifically have the potential for prolonged influence on brain development. Negative early experiences collectively predicted reduced cortical thickness, but the specific neural systems affected aligned with those typically implicated in these individual disorders/experiences.

Early Childhood Socioeconomic Status and Cognitive and Adaptive Outcomes at the Transition to Adulthood: The Mediating Role of Gray Matter Development Across Five Scan Waves.

BACKGROUND: Early low socioeconomic status (SES) is associated with poor outcomes in childhood, many of which endure into adulthood. It is critical to determine how early low SES relates to trajectories of brain development and whether these mediate relationships to poor outcomes. We use data from a unique 17-year longitudinal study with five waves of structural brain imaging to prospectively examine relationships between preschool SES and cognitive, social, academic, and psychiatric outcomes in early adulthood. METHODS: Children (n = 216, 50% female, 47.2% non-White) were recruited from a study of early onset depression and followed approximately annually. Family income-to-needs ratios (SES) were assessed when children were ages 3 to 5 years. Volumes of cortical gray and white matter and subcortical gray matter collected across five scan waves were processed using the FreeSurfer Longitudinal pipeline. When youth were ages 16+ years, cognitive function was assessed using the NIH Toolbox, and psychiatric diagnoses, high-risk behaviors, educational function, and social function were assessed using clinician administered and parent/youth report measures. RESULTS: Lower preschool SES related to worse cognitive, high-risk, educational, and social outcomes (|standardized B| = 0.20-0.31, p values < .003). Lower SES was associated with overall lower cortical (standardized B = 0.12, p < .0001) and subcortical gray matter (standardized B = 0.17, p < .0001) volumes, as well as a shallower slope of subcortical gray matter growth over time (standardized B = 0.04, p = .012). Subcortical gray matter mediated the relationship of preschool SES to cognition and high-risk behaviors. CONCLUSIONS: These novel longitudinal data underscore the key role of brain development in understanding the long-lasting relations of early low SES to outcomes in children.

The Relationship Between Depression Symptoms and Adolescent Neural Response During Reward Anticipation and Outcome Depends on Developmental Timing: Evidence From a Longitudinal Study.

BACKGROUND: Blunted neural reward responsiveness (RR) is observed in youth depression. However, it is unclear whether symptoms of depression experienced early in development relate to adolescent RR beyond current symptoms and, further, whether such relationships with RR differ during two key components of reward processing: anticipation and outcome. METHODS: Within a prospective longitudinal study oversampled for early depression, children and caregivers completed semiannual diagnostic assessments beginning in preschool. In later adolescence, mean age = 16.49 years (SD = 0.94), youths' (N = 100) neurophysiological responses to cues signaling likely win and loss and these outcomes were assessed. Longitudinally assessed dimensional depression and externalizing symptoms (often comorbid with depression as well as associated with RR) experienced at different developmental periods (preschool [age 3-5.11 years], school age [6-9.11 years], early adolescence [10-14.11 years], current) were used as simultaneous predictors of event-related potentials indexing anticipatory cue processing (cue-P3) and outcome processing (reward positivity/feedback negativity and feedback-P3). RESULTS: Blunted motivated attention to cues signaling likely win (cue-P3) was specifically predicted by early-adolescent depression symptoms. Blunted initial response to win (reward positivity) and loss (feedback negativity) outcomes was specifically predicted by preschool depression symptoms. Blunted motivational salience of win and loss outcomes (feedback-P3) was predicted by cumulative depression, not specific to any developmental stage. CONCLUSIONS: Although blunted anticipation and outcome RR is a common finding in depression, specific deficits related to motivated attention to cues and initial outcome processing may map onto the developmental course of these symptoms.

Age-typical changes in neural reward response are moderated by maternal anhedonia.

Reward response and mood disorders both increase during adolescence. Here, we investigate whether age and gonadal hormone levels relate to neural response to win and loss feedback in 9- to 14-year-old girls and whether such relations are moderated by maternal anhedonia, a factor linked to psychopathology risk and reward response. Psychiatrically healthy daughters of mothers who did not meet criteria for any current DSM-5 disorder or past anxiety/depression diagnosis (N = 69) completed a monetary fMRI guessing task and provided saliva samples for gonadal hormone assay. Voxelwise regressions revealed unique quadratic effects of age and linear effects of gonadal hormones; neither effect was explained by reported puberty. Striatal/insular responses to win/loss feedback peaked between 12 and 13 years, whereas estradiol predicted greater response to wins versus losses within the medial prefrontal cortex, concurrently. Maternal anhedonia specifically moderated the quadratic effect of age within dorsolateral striatum and insula. Daughters of mothers reporting greater anhedonia showed an earlier peak in striatal/insular response to reward and loss feedback. As such, maternal anhedonia predicted blunted striatal/insular response to feedback only in older daughters. A similar pattern was observed for daughters of mothers with lifetime depression in exploratory analyses. These cross-sectional findings suggest that familial anhedonia may relate to altered trajectories of reward responding during adolescence and that these effects are specific to age.

Longitudinal increases in reward-related neural activity in early adolescence: Evidence from event-related potentials (ERPs).

Adolescence is frequently described as a developmental period characterized by increased sensitivity to rewards. However, previous research on age-related changes in the neural response to gains and losses have produced mixed results, with only some studies reporting potentiated neural responses during adolescence. The current study examined the ERP responses to gains and losses during a simple monetary reward (i.e., Doors) task in a large and longitudinal sample of 248 adolescent females assessed at two time points, separated by two years. At baseline, when the sample was 8- to 14-years-old, age related to larger (i.e., more positive) ERP responses to both gains and losses; moreover, age-related effects were stronger in relation to gains than losses. Overall, the amplitude of the ERP response to gains, but not losses, significantly increased from baseline to follow-up; however, this effect was moderated by age, such that reward-related ERPs only increased longitudinally among the younger participants. At the follow-up assessment, ERP responses to gains and losses were equally related to age. Collectively, these within- and between-subjects findings suggest a relatively specific developmental increase in reward-related neural activity during late childhood and early adolescence.

Effects of menstrual cycle phase on electrocortical response to reward and depressive symptoms in women.

The menstrual cycle impacts mood and neural response to reward-phenomena that may be related to natural fluctuations in ovarian hormones. Using a within-subject design, the present study examined ovarian hormones (i.e., estradiol and progesterone) and ERPs in response to feedback indicating gains and losses in both the follicular and luteal phases of the menstrual cycle. We examined whether hormone levels and variation in neural response to reward and loss across menstrual cycle phases were associated with depressive symptoms. Participants high in depressive symptoms showed a reduced reward positivity (RewP) to monetary gains during the luteal phase of the menstrual cycle as compared to the follicular phase, while those low in depressive symptoms showed no change in the RewP to monetary gains between phases. Thus, increased fluctuation in the neural response to gains (but not losses) across menstrual cycle phases was associated with greater depression symptoms. Overall, findings indicate that hormonal fluctuations associated with the menstrual cycle may relate to depressive symptoms by altering reward sensitivity. Furthermore, fluctuation in the neural response to rewards over the menstrual cycle may play an important role in the expression of depressive symptoms.

Ventral Striatal Function Interacts With Positive and Negative Life Events to Predict Concurrent Youth Depressive Symptoms.

BACKGROUND: Life events and reward-system functioning contribute to resilience and risk for depression. However, interactions between life events and neural responses to reward and loss have not been previously investigated in relation to depression symptoms in child and adolescent populations. METHODS: An unselected sample (N = 130) of 8- to 14-year-old girls (mean = 12.6 years) completed the Child Depression Inventory and a functional magnetic resonance imaging guessing task in which they won or lost money on each trial. Parents completed a measure of life events experienced by the child. Life events were separated by positive versus negative and whether they were likely related or unrelated to the daughter's behavior (i.e., dependent vs. independent, respectively). Multiple regressions tested whether the interaction between ventral striatal (VS) response to wins or losses and recent life events were associated with child-reported depressive symptoms. RESULTS: A greater number of dependent positive life events related to decreased total depression symptoms when VS response to wins was robust. Conversely, a greater number of independent negative life events related to increased negative mood depression symptoms when VS response to losses was robust; this relationship was in the opposite direction when VS response to loss was low. CONCLUSIONS: VS response to reward and loss were independent moderators of the relationship between recent life events (positive and negative, respectively) and depressive symptoms. Findings suggest that targeting neural responses (i.e., increasing responses to winning or decreasing responses to losing) may be important for both improving resilience and reducing risk in different environmental contexts.

Individual differences in hedonic capacity, depressed mood, and affective states predict emotional reactivity.

Identifying factors that contribute to inter-individual differences in emotional reactivity is central to understanding the basic mechanisms that give rise to adaptive emotion reactivity and to disruptions that may occur in psychopathology. The current study related emotional reactivity in an unselected young adult sample (N = 101) to individual difference factors relevant to emotional functioning and mood pathology, specifically anhedonia, depressed mood, and current affective state. To assess emotional reactivity, participants rated their emotional responses to 100 pictures from the International Affective Picture System. Increased self-reported anhedonia (i.e. reduced hedonic capacity) predicted blunted emotional reactivity to both positive and negative images, relative to neutral images, while elevated depressed mood predicted potentiated emotional reactivity to negative vs. neutral images. Anhedonia also accounted for far greater variance in emotional reactivity than depressed mood. Further, more positive affective state predicted potentiated reactivity to positive versus neutral images while more negative affective state predicted potentiated reactivity to negative versus neutral images beyond effects of anhedonia and depressed mood. The current study identified separable effects of anhedonia, depressed mood, and current affect on emotional reactivity.

Internal Consistency of Functional Magnetic Resonance Imaging and Electroencephalography Measures of Reward in Late Childhood and Early Adolescence.

BACKGROUND: Abnormal neural response to reward is increasingly thought to function as a biological correlate of emerging psychopathology during adolescence. However, this view assumes such responses have good psychometric properties-especially internal consistency-an assumption that is rarely tested. METHODS: Internal consistency (i.e., spilt-half reliability) was calculated for event-related potentials (ERPs) and Blood Oxygen Level Dependent (BOLD) responses to monetary gain and loss feedback from the same sample of 8-14 year-old females (n=177). Internal consistency for ERPs (i.e. feedback negativity) and BOLD responses within the ventral striatum and medial/lateral prefrontal cortex to gain, loss, difference scores (gain-loss), and residual scores (gain controlling for loss) were compared. Moderation analyses were conducted to investigate whether internal consistency differed by age. RESULTS: ERP and BOLD responses to gain and loss feedback showed high internal consistency in all regions (Spearman Brown Coefficients (SB) ≥ 0.70). When considering difference and residual scores, however, responses showed lower internal consistency (SBs ≤ 0.50), with particularly low internal consistency for subtraction-based scores (SB ≤ 0.36). Age was not a significant moderator of split-half relationships, indicating similar internal consistency across late childhood to early adolescence. CONCLUSIONS: Within the same subjects, high internal consistency was observed for both ERP and fMRI measures of response to gains and losses, which did not vary as a function of age. Moreover, excellent psychometric properties were evident even within the first half of the experiment. Difference scores were characterized by lower internal consistency, although regression-based approaches outperformed subtraction-based difference scores.

Depression Risk Predicts Blunted Neural Responses to Gains and Enhanced Responses to Losses in Healthy Children.

OBJECTIVE: Maternal major depressive disorder (MDD) increases risk for MDD and predicts reduced reward responding in adolescent offspring. However, it is unclear whether alterations in neural response to reward can be detected in school-aged children at high risk before the typical increase in reward response observed in adolescence. METHOD: To assess relationships between neural response to gain/loss feedback, MDD risk, and child depressive symptoms, 47 psychiatrically healthy 7- to 10-year-old children (16 at high risk given maternal MDD) completed questionnaires and a functional magnetic resonance imaging (fMRI) card-guessing game in which candy was gained and lost. RESULTS: High-risk children showed both blunted response to gain and greater deactivation/reduced activation to loss within the ventral striatum and anterior insula. Within the striatum, risk-group differences in response to loss feedback were significantly larger than for gain, with greater deactivation to loss predicting risk-group status above and beyond blunted gain activation. Anhedonia was related to reduced deactivation to loss (i.e., reduced sensitivity to loss), whereas negative mood was related to enhanced deactivation to loss (i.e., enhanced sensitivity to loss) in the ventral striatum. CONCLUSION: High-risk children showed blunted ventral striatal activation to gain feedback, but ventral striatal deactivation to loss was a stronger predictor of MDD risk. Furthermore, relationships between response to loss and elevated depressive symptoms within the ventral striatum and cingulate differed depending on the type of depressive symptom. Together these results highlight the potentially important role of response to loss of reward in childhood risk for depression.

Do losses loom larger for children than adults?

The large impact of loss of reward on behavior has been well documented in adult populations. However, whether responsiveness to loss relative to gain is similarly elevated in child versus adult populations remains unclear. It is also unclear whether relations between incentive behaviors and self-reported reward/punishment sensitivity are similar within different developmental stages. To investigate these questions, 7- to 10-year-old children (N = 70) and young adults (N = 70) completed the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale, along with 2 probabilistic incentive tasks assessing gain approach and loss avoidance behavior. BIS/BAS subscales were calculated per Pagliaccio et al. (2015), which established an age invariant model of the BIS/BAS. Bias toward responses more frequently followed by gain feedback and away from responses more frequently followed by loss feedback, approach, and avoidance behavior, respectively, were quantified via signal detection statistics. Gain approach behavior did not differ across age groups; however, children exhibited significantly elevated loss avoidance relative to adults. Children also showed greater reductions in accuracy and slower RTs specifically following loss feedback relative to adults. Interestingly, despite age group differences in loss avoidance behavior, relations between self-report measures and approach/avoidance behaviors were similar across age groups. Participants reporting elevated motivation (BAS Drive) showed both elevated gain approach and elevated loss avoidance, with both types of behavior predicting unique variance in BAS Drive. Results highlight the often-neglected developmental and motivational roles of responsiveness to loss of reward.

Reward Processing and Risk for Depression Across Development.

Striatal response to reward has been of great interest in the typical development and psychopathology literatures. These parallel lines of inquiry demonstrate that although typically developing adolescents show robust striatal response to reward, adolescents with major depressive disorder (MDD) and those at high risk for MDD show a blunted response to reward. Understanding how these findings intersect is crucial for the development and application of early preventative interventions in at-risk children, ideally before the sharp increase in the rate of MDD onset that occurs in adolescence. Robust findings relating blunted striatal response to reward and MDD risk are reviewed and situated within a normative developmental context. We highlight the need for future studies investigating longitudinal development, specificity to MDD, and roles of potential moderators and mediators.

Revising the BIS/BAS Scale to study development: Measurement invariance and normative effects of age and sex from childhood through adulthood.

Carver and White's (1994) Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales have been useful tools for studying individual differences in reward-punishment sensitivity; however, their factor structure and invariance across development have not been well tested. In the current study, we examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10-year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14- to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N = 844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4-factor model (BIS, Reward Responsivity, Drive, Fun Seeking) in the literature, we conducted exploratory factor analyses in half of the participants and identified problematic items across age groups. The 4-factor model showed poor fit in our sample, whereas removing the BAS Fun Seeking subscale and problematic items from the remaining subscales improved fit in confirmatory factor analyses conducted with the second half of the participants. The revised model showed strict invariance across age groups and by sex, indicating consistent factor structure, item loadings, thresholds, and unique or residual variances. Additionally, in our cross-sectional data, we observed nonlinear relations between age and subscale scores, where scores tended to be higher in young adulthood than in childhood and later adulthood. Furthermore, sex differences emerged across development; adolescent and adult females had higher BIS scores than males in this age range, whereas sex differences were not observed in childhood. These differences may help us to understand the rise in internalizing psychopathology in adolescence, particularly in females. Future developmental studies are warranted to examine the impact of rewording problematic items.