Higher inflammatory proteins predict future depressive symptom severity among adolescents with lower emotional clarity.

BACKGROUND: A growing body of work has implicated inflammation in the pathogenesis of depression. As not all individuals with heightened levels of peripheral inflammation develop symptoms of depression, additional work is needed to identify other factors that catalyze the relationship between inflammation and depressive symptoms. Given that elevated levels of inflammatory activity can induce a variety of emotional changes, the present study examined whether emotional clarity, the trait-like ability to identify, discern, and express one's emotions, influences the strength of the association between inflammatory signaling and concurrent and prospective symptoms of depression. METHODS: Community adolescents (N = 225, Mage = 16.63 years), drawn from a larger longitudinal project investigating sex and racial differences in depression onset, provided blood samples to determine peripheral levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) at a baseline visit, along with self-report measures of emotional clarity and depressive symptom severity. Depressive symptom severity was assessed again at a follow-up visit approximately 5-months after baseline. RESULTS: Hierarchical multiple regressions detected a significant interaction between inflammatory markers and emotional clarity on future depression severity, controlling for baseline depressive symptoms. Specifically, among adolescents with low levels of emotional clarity, higher levels of IL-6, CRP, and inflammatory composite scores were significantly associated with greater future depression severity. CONCLUSIONS: These results indicate that low emotional clarity and high inflammatory signaling may jointly confer risk for prospective depressive symptom severity among adolescents. Therapeutic interventions that improve emotional clarity may reduce risk of depressive symptoms among adolescents with low-grade peripheral inflammation.

Concurrent and prospective associations of inflammatory signaling, specific depressive symptoms, and substance use in adolescence.

Substance use and depression frequently co-occur. Adolescence appears to be a vulnerable developmental period for increases in both substance use and depressive symptoms, often attributed to rapid maturation of reward and motivation systems. Another contributing factor could be inflammatory signaling, which has been associated with both substance use disorder and depression. Prior research indicates that an increase in inflammatory activity can cause physical and emotional malaise, which resembles depression, and the anhedonia and somatic symptoms could lead to substance use. This perspective that substance use is a type of self-medication in response to anhedonia and subjective experiencing of increased inflammatory physiology has not been investigated previously. To test these associations, we used path analysis to examine concurrent and prospective associations between three pro-inflammatory markers, specific depressive symptoms, and substance use frequency in a diverse sample of older adolescents. Participants completed repeated self-report measures of specific depressive symptoms (i.e., dysphoria, anhedonia, somatic concerns, negative cognitions, and functional difficulties) and substance use frequency. Blood was collected to quantify circulating levels of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). This analysis showed an indirect effect of IL-6 and TNF-α levels on future substance use, but only via functional difficulties. Substance use also predicted future functional difficulties. Only anhedonia directly predicted future substance use frequency. These findings help to more precisely identify pathways through which inflammatory physiology and specific depressive symptoms synergistically confer risk for substance use.

Linking Maternal Depression to Adolescent Internalizing Symptoms: Transmission of Cognitive Vulnerabilities.

The mechanisms of the well-documented relationship between maternal depression and offspring psychopathology are not yet fully understood. Building upon cognitive theories of depression and the modeling hypothesis, path analyses tested whether maternal depression history predicted adolescent internalizing symptoms via the transmission of cognitive vulnerabilities within a sample of 635 adolescents (Mage = 13.1 years, range = 11.2-17.2 years; 53% female; 48% African American/Black) and their primary female caregivers. Maternal depression history did not directly predict adolescent symptoms. Two significant indirect effects were found; maternal depression history was associated with maternal negative cognitive style, which predicted greater adolescent negative generalization, which, in turn, predicted adolescents' greater depressive and anxiety symptoms. These findings suggest that the transmission of cognitive vulnerabilities may link maternal depression and offspring internalizing psychopathology.

Negative Inferential Style Mediates the Association between Racial Identity and Depressive Symptoms among African American Adolescents.

Negative inferential style is a cognitive vulnerability for depression. Yet, few studies have explored how this risk factor intersects with culturally-specific protective factors, such as racial identity, in a unified cognitive risk-cultural asset model in youth of color. The current study addressed this gap by exploring the interplay between negative inferential style, racial identity, and depressive symptoms in an urban African-American adolescent community sample (N = 233; 51.9% female). Cross-lagged panel analyses estimated concurrent and prospective relationships between study variables. Racial identity dimensions of regard, but not centrality, were significant predictors of inferential style, and buffered against the development of depressive symptoms via the development of a less negative inferential style. Implications for the study of racial identity and cognition, and treatment of African-American adolescents are discussed.

Concurrent and Longitudinal Associations of Sex and Race with Inflammatory Biomarkers during Adolescence.

Chronic, systemic inflammation is implicated in physical and mental health; little is known about whether sex and racial differences detected in adulthood are observed during adolescence or about normative changes occurring during adolescence. This longitudinal, United States-based study examined four biomarkers of systemic inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and IL-8) in 315 adolescents (51% female; 58% black; baseline age = 16.49 years (SD = 1.56; range: 12.14-21.28)] at three timepoints. Notable results included: general decline in inflammatory biomarkers in older adolescents, lower levels of TNF-α/IL-8 in black adolescents, elevated CRP/IL-6 in females, and especially higher levels of IL-6 in black, female adolescents. Implications are discussed, particularly the potential health implications of elevated IL-6 in black females.

Executive dysfunction in depression in adolescence: the role of inflammation and higher body mass.

BACKGROUND: There is substantial evidence that many depressed individuals experience impaired executive functioning. Understanding the causes of executive dysfunction in depression is clinically important because cognitive impairment is a substantial contributor to functional impairment. This study investigated whether elevated levels of an inflammatory cytokine [interleukin-6 (IL-6)] and/or higher body mass index (BMI) concurrently and/or prospectively accounted for the relationship between depressive symptoms and impaired executive functioning in adolescents. METHODS: A diverse, community sample of adolescents (N = 288; mean age = 16.33; 51.4% female; 59.0% African-American) completed assessments of height and weight, IL-6, depressive symptoms, and self-report/behavioral measures of executive functioning (selective attention, switching attention) and future orientation annually over 3 years. Adolescents experiencing acute illness or medical conditions that affect inflammation were excluded from analyses. Path analysis within a structural equation modeling framework simultaneously examined the concurrent and prospective relationships between BMI, IL-6, depressive symptoms, and the measures of cognitive functioning across three timepoints. RESULTS: Across all timepoints, higher BMI was prospectively associated with higher levels of IL-6 and depressive symptoms, while higher levels of IL-6 were associated with worse performance on three behavioral and self-report measures of cognitive functioning. Higher depressive symptoms also were prospectively associated with elevated IL-6 and both higher depressive symptoms and a higher BMI predicted worse future executive functioning via increased IL-6. CONCLUSIONS: More severe depressive symptoms and increased BMI may disrupt executive functioning via elevated IL-6.

Longitudinal changes of inflammatory biomarkers moderate the relationship between recent stressful life events and prospective symptoms of depression in a diverse sample of urban adolescents.

This study investigated whether longitudinal changes in inflammatory physiology moderated the relationship between recent stressful life events and subsequent depressive symptoms in adolescence. A diverse sample of adolescents representative of an urban community (N = 129; Age at baseline = 12.5 years; 48.8% female; 55.0% African American) completed measures of stressful life events, depressive symptoms, and two annual blood draws (BD1 and BD2). Controlling for inflammatory activity at BD1, depression at BD1, demographics and the time between assessments, increases in interleukin-6 (IL-6; b = 0.878, p = .007) and C-reactive protein (CRP; b = 0.252, p = .024) from BD1 to BD2 interacted with recent stressful life events before BD1 to predict severity of depressive symptoms at BD2. Similar associations were evident for IL-6 (b = 2.074, p = .040) and CRP (b = 0.919, p = .050) when considering acute stressful life events that had occurred within the two weeks before the first blood collection. More frequent stressful life events before BD1 predicted significantly more severe depressive symptoms at BD2, but only for adolescents with moderate (50th percentile) and high (84th percentile) levels of IL-6 and CRP at BD2. In conclusion, adolescents who experienced both recent stressful life events and larger increases in inflammatory activity following these stressors were at increased risk for more severe depressive symptoms after approximately one year. The findings indicate that the interaction of stress and larger changes in inflammatory activity following these stressors are prognostic risk factors for depression severity in adolescents.

Early Pubertal Timing Mediates the Association between Low Socioeconomic Status and Poor Attention and Executive Functioning in a Diverse Community Sample of Adolescents.

Low socioeconomic status (SES) may be associated with earlier pubertal timing and impaired attention and executive function (EF) in youth; however, whether pubertal timing mediates the relation between SES and attention or executive functioning remains unclear. Structural equation models tested concurrent and prospective relations between SES, pubertal timing, and attention and executive functioning measures in a gender and racially diverse sample of adolescents (N = 281, 45.6% male, 50.5% White/Caucasian, 46.3% Black/African American, 3.2% Biracial/other, and 44.5% low SES; complete data were not available on some measures). Youth from low SES families experienced earlier pubertal timing, and this accelerated development was associated with worse performance on attention and executive functioning tasks, both concurrently and longitudinally. These findings highlight a pathway by which youth from low socioeconomic backgrounds may develop worse attention and executive functioning abilities during adolescence.

Pubertal Synchrony and Depressive Symptoms: Differences by Race and Sex.

Individual differences in the timing and tempo of pubertal development have been shown to be related to depressive symptoms during adolescence, particularly among girls. Another measure of variability in pubertal development is pubertal synchrony, the degree to which the development of pubertal indicators (e.g., breast growth and ancillary hair growth) are synchronized within the individual. Pubertal synchrony also has been hypothesized to be related to depressive symptoms, but, to date, only one study has tested this hypothesis. However, it remains unclear whether pubertal synchrony confers risk for depressive symptoms more proximally in time or differentially among boys or non-White youth. The current study examined the relation between pubertal synchrony and depressive symptoms concurrently and six months later as a function of race and sex in a community sample of 215 youth (53% female, 44.7% African American; mean age = 12.90 years (SD = 0.86)). Girls with asynchronous development at Time 1 reported significantly higher depressive symptoms at Time 2 than girls with synchronous development and boys with asynchronous development. In addition, boys with asynchronous development at Time 1 had lower depressive symptoms at Time 2 than boys with synchronous development. Race did not moderate pubertal synchrony-depression relations. These results suggest that pubertal asynchrony is a risk factor for girls, but a protective factor for boys, and lend support for pubertal synchrony as a potential contributor to the gender gap in depression that emerges during adolescence.

Pubertal Status and Age are Differentially Associated with Inflammatory Biomarkers in Female and Male Adolescents.

A better understanding of the maturational correlates of inflammatory activity during adolescence is needed to more appropriately study both normal and abnormal development. Inflammation is the immune system's first response to infection, injury, or psychological stress, and it has been shown to be elevated in individuals with both physical and psychological conditions. This study examined unique associations between (1) pubertal status and inflammatory biomarkers, and (2) age and inflammatory biomarkers, and whether these relationships differed by sex in a diverse sample of 155 adolescents (54.2% female, 45.8% male; Mage = 16.22) from a northeastern city in the US. A more advanced pubertal status was uniquely associated with lower levels of tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8). Chronological age was uniquely associated with lower IL-8 levels. The association between pubertal status and C-reactive protein (CRP) levels differed by sex: more mature females had higher CRP, whereas pubertal status and CRP were not significantly associated in males. These findings highlight an important relation between pubertal development and inflammatory activity during adolescence.

Reward Sensitivity, Cognitive Response Style, and Inflammatory Response to an Acute Stressor in Adolescents.

Inflammation is gaining support as a biological mediator between stress and many negative outcomes that have heightened risk during adolescence (e.g., mood disorders). Thus, an important line of inquiry is evaluating whether risk factors for mood psychopathology also are associated with heightened inflammatory responses to stress during this developmental period. Two prominent risk factors that interact to predict mood psychopathology are reward sensitivity and perseverative cognitive response styles, which also have been associated with heightened inflammatory proteins. These factors could influence inflammation by synergistically amplifying stress reactivity. Ninety-nine late adolescents (Mage = 18.3 years, range = 15.6-21.9 years) completed measures of reward sensitivity, cognitive response style, and blood draws before and 60-min after a modified Trier Social Stress Task to determine levels of inflammation. Higher reward drive interacted with more perseverative response style ratios (rumination relative to distraction + problem-solving) to predict larger increases in interleukin-6 (a proinflammatory protein). Follow-up analyses found that reward drive interacted with all three components of the ratio to predict change in interleukin-6. Thus, these results suggest that high reward drive and perseverative cognitive response styles are associated with increased inflammatory response to social stress in adolescents, a potential physiological mechanism linking these risk factors to mood psychopathology during this developmental period.

Unique and predictive relationships between components of cognitive vulnerability and symptoms of depression.

BACKGROUND: Cognitive vulnerability theories of depression outline multiple, distinct inferential biases constitutive of cognitive vulnerability to depression. These include attributing negative events to internal, stable, and global factors, assuming that negative events will lead to further negative consequences, and inferring that negative events reflect negative characteristics about the self. Extant research has insufficiently examined these biases as distinct, limiting our understanding of how the individual cognitive vulnerability components interrelate and confer risk for depression symptoms. Thus, we conducted exploratory network analyses to examine the relationships among the five components of negative cognitive style and explore how components may differentially relate to depressive symptoms in adolescents. METHODS: Participants completed measures of negative cognitive style twice over a two-year period. We estimated Graphical Gaussian Models using contemporaneous data and computed a cross-lagged panel network using temporal data from baseline and 2-year follow-up. RESULTS: Results reveal interesting structural dynamics among facets of negative cognitive style and depressive symptoms. For example, results point to biases towards stable and future-oriented inferences as highly influential among negative cognitive style components. The temporal model revealed the internal attributions component to be heavily influenced by depressive symptoms among adolescents, whereas stable and global attributions most influenced future symptoms. CONCLUSIONS: This study presents novel approaches for investigating cognitive style and depression. From this perspective, perhaps more precise predictions can be made about how cognitive risk factors will lead to the development or worsening of psychopathology.

Cognitive reappraisal attenuates the association between depressive symptoms and emotional response to stress during adolescence.

Depression is associated with increased emotional response to stress. This is especially the case during the developmental period of adolescence. Cognitive reappraisal is an effective emotion regulation strategy that has been shown to reduce the impact of emotional response on psychopathology. However, less is known about whether cognitive reappraisal impacts the relationship between depressive symptoms and emotional responses, and whether its effects are specific to emotional reactivity or emotional recovery. The current study examined whether cognitive reappraisal moderated the relationship between depressive symptoms and trait or state measures of emotional reactivity and recovery. A community sample of 127 adolescents (M-age = 15.28; 49% female, 47% Caucasian), at an age of risk for depression, completed self-report measures of trait emotional responding and depressive symptoms. In addition, they completed an in vivo social stress task and were assessed on state emotional reactivity and recovery from the stressor. Findings suggested that cognitive reappraisal was associated with an attenuated impact of depressive symptoms on trait and state emotional recovery. These results provide evidence that cognitive reappraisal may be an effective strategy for improving some aspects of emotional responding in relation to depressive symptoms among adolescents.

The Combination of Living in High Crime Neighborhoods and High Rumination Predicts Depressive Symptoms among Adolescents.

Living in high crime areas and rumination each have been identified as risk factors for depression among youth, yet it is unclear how crime and rumination may synergistically increase the risk of adolescent depression. Adolescents (N = 309; 51% female, Mage= 12.9, SD = 0.61) completed self-report measures of rumination, depressive symptoms, and provided local addresses, which were used to match police district crime statistics. Approximately one year later, participants again reported depressive symptoms. Moderation analyses indicated that the tendency to ruminate exacerbated the relationship between violent crime rates, but not non-violent crime, and higher prospective levels of depressive symptoms among adolescents. These findings suggest that individual-level interventions that promote more adaptive emotion response styles may lower the risk of depression among adolescents residing in high crime areas.

A Longitudinal Investigation of Cognitive Self-schemas across Adolescent Development.

Research in developmental psychology highlights youth's self-schemas as one possible pathway to improve adolescents' functioning and promote positive developmental outcomes. Despite this, the trajectory of positive and negative self-schemas is relatively understudied. This study addresses this limitation by empirically examining the trajectory of self-schemas in a community sample of 623 youth (M = 13.04 years; 54% female; 49% African American, 4% Biracial, 47% European American) who were followed over a seven-year period. Caregivers completed measures of parenting practices, maternal rumination and negative inferential style, and adolescents completed a computerized behavioral task assessing self-schemas (i.e., mental frameworks that guide attention, interpretation, and memory of one's experiences). Multilevel growth curve modeling results demonstrated a quadratic slope for negative self-schemas and no mean-level change for positive self-schemas. These trajectories did not vary by gender or racial group. However, parenting factors differentially influenced the trajectories. Specifically, higher levels of parental involvement at baseline, or an active interest and engagement in a child's experiences and activities, related to lower levels of negative self-schemas during adolescence. Additionally, higher levels of parental rumination and parental negative control at baseline related to lower levels of youth positive self-schemas at baseline. These findings contribute to models of youth cognitive development.

Immunocognitive Model of Depression Secondary to Anxiety in Adolescents.

There is evidence that anxiety precedes the onset of depression and that rumination contributes to this risk pathway in adolescence. This study examined inflammatory biomarkers as mediators in a risk model of depressive symptoms secondary to anxiety symptoms among adolescents who ruminate. A sample of 140 adolescents (52% female, 54% African American, 40% Caucasian, 6% biracial, mean age at T1 = 16.5 years, SD = 1.2 years) provided blood samples on two visits (T1 and T2; mean time between T1 and T2 = 13.5 months, SD = 5.9 months). Self-report anxiety, depression, and rumination measures were given at T1 and the depression measure was given again at a third visit (T3, mean months since T1 = 26.0 months, SD = 9.0 months). Higher anxiety predicted more interleukin-6, but not more C-reactive protein, for adolescents with high levels of rumination. Moderated mediation analyses (N for analysis after removing cases with missing data and outliers = 86) indicated that interleukin-6, but not C-reactive protein, at T2 mediated the relationship between anxiety symptoms at T1 and depressive symptoms at T3, conditional on rumination. Anxiety and rumination interacted such that, as rumination increased, anxiety predicted greater inflammation and depressive symptoms. These results demonstrate that established cognitive vulnerabilities for the development of depressive symptoms secondary to anxiety symptoms in adolescence might indirectly operate though biological mechanisms such as inflammation. In addition to highlighting risk factors and potential treatment targets for depression, this study suggests a potential biological mechanism underlying the effects of psychotherapies that reduce rumination on negative affect (e.g., cognitive behavioral therapy).

The Development of Future Orientation is Associated with Faster Decline in Hopelessness during Adolescence.

Hopelessness is implicated in multiple psychological disorders. Little is known, however, about the trajectory of hopelessness during adolescence or how emergent future orientation may influence its trajectory. Parallel process latent growth curve modelling tested whether (i) trajectories of future orientation and hopelessness and (ii) within-individual change in future orientation and hopelessness were related. The study was comprised of 472 adolescents [52% female, 47% Caucasian, 47% received free lunch] recruited at ages 12-13 who completed measures of future orientation and hopelessness at five annual assessments. The results indicate that a general decline in hopelessness across adolescence occurs quicker for those experiencing faster development of future orientation, when controlling for age, sex, low socio-economic status in addition to stressful life events in childhood and adolescence. Stressful childhood life events were associated with worse future orientation at baseline and negative life events experienced during adolescence were associated with both an increase in the trajectory of hopelessness as well as a decrease in the trajectory of future orientation. This study provides compelling evidence that the development of future orientation during adolescence is associated with a faster decline in hopelessness.

Laboratory-induced learned helplessness attenuates approach motivation as indexed by posterior versus frontal theta activity.

Research suggests that midline posterior versus frontal electroencephalographic (EEG) theta activity (PFTA) may reflect a novel neurophysiological index of approach motivation. Elevated PFTA has been associated with approach-related tendencies both at rest and during laboratory tasks designed to enhance approach motivation. PFTA is sensitive to changes in dopamine signaling within the fronto-striatal neural circuit, which is centrally involved in approach motivation, reward processing, and goal-directed behavior. To date, however, no studies have examined PFTA during a laboratory task designed to reduce approach motivation or goal-directed behavior. Considerable animal and human research supports the hypothesis put forth by the learned helplessness theory that exposure to uncontrollable aversive stimuli decreases approach motivation by inducing a state of perceived uncontrollability. Accordingly, the present study examined the effect of perceived uncontrollability (i.e., learned helplessness) on PFTA. EEG data were collected from 74 participants (mean age = 19.21 years; 40 females) exposed to either Controllable (n = 26) or Uncontrollable (n = 25) aversive noise bursts, or a No-Noise Condition (n = 23). In line with prediction, individuals exposed to uncontrollable aversive noise bursts displayed a significant decrease in PFTA, reflecting reduced approach motivation, relative to both individuals exposed to controllable noise bursts or the No-Noise Condition. There was no relationship between perceived uncontrollability and frontal EEG alpha asymmetry, another commonly used neurophysiological index of approach motivation. Results have implications for understanding the neurophysiology of approach motivation and establishing PFTA as a neurophysiological index of approach-related tendencies.

Interaction of Biological Stress Recovery and Cognitive Vulnerability for Depression in Adolescence.

Major Depressive Disorder is a common mental illness with rates increasing during adolescence. This has led researchers to examine developmental antecedents of depression. This study examined the association between depressive symptoms and the interaction between two empirically supported risk factors for depression: poor recovery of the biological stress system as measured through heart rate and cortisol, and cognitive vulnerabilities as indexed by rumination and a negative cognitive style. Adolescents (n = 127; 49 % female) completed questionnaires and a social stress task to elicit a stress response measured with neuroendocrine (cortisol) and autonomic nervous system (heart rate) endpoints. The findings indicated that higher depressive symptoms were associated with the combination of higher cognitive vulnerabilities and lower cortisol and heart rate recovery. These findings can enhance our understanding of stress responses, lead to personalized treatment, and provide a nuanced understanding of depression in adolescence.

Cognitive Vulnerabilities to Depression for Adolescents in Single-Mother and Two-Parent Families.

Although research consistently suggests that adolescents in single-mother families are at increased risk for depression, the mechanisms that explain this relationship are unclear. In a community sample of adolescents (N = 368; ages 12-16; 50 % female; 50 % White) and their mothers (42 % single), adolescents completed measures of depressive symptoms, rumination, and depressogenic inferential style at baseline and two yearly follow-ups. Mothers reported on stressful events that occurred in the child's life from birth until baseline. Adolescents raised by single mothers, relative to partnered mothers, experienced more childhood stressors and higher rumination levels at 1-year follow-up. Additionally, higher rumination mediated the relationship between single motherhood and greater youth depressive symptoms at the 2-year follow-up. Clinical implications and developmental considerations are discussed.