Integrating dynamic psychophysiological indices across time and contexts: Elucidating mechanisms, risk markers, and intervention targets.

Why should researchers measure psychophysiological processes repeatedly over time? The study of psychophysiology inherently involves sampling biological processes as they manifest over time. The most common approach is to use a brief sample to make conclusions about how individuals or groups differ. Although these types of between-subject comparisons have utility for understanding individual and group differences, many of the important conceptual questions in the field involve processes that are dynamic, varying within individuals over time. Using examples from the literature on affect regulation, this conceptual review contrasts three types of study designs: the classic single-observation design and the aggregated and temporally linked repeated observation designs, which have great promise for measuring variables that fluctuate dynamically over time. Importantly, these designs can be integrated to elucidate research questions about risk (when and for whom will the likelihood of an unwanted outcome occurring increase?), mechanisms (how and why does a change in psychophysiology contribute to a change in another process of interest?), and interventions (how and when should interventions take place to modify an outcome?). Researchers are encouraged to implement intensive sampling in their research, which can be conducted in traditional laboratory settings (e.g., fMRI, event-related brain potentials, and heart rate variability) and in ecologically valid contexts in everyday life using ambulatory assessment.

A meta-analysis on the uncinate fasciculus in depression.

Aberrant microstructure of the uncinate fasciculus (UNC), a white matter (WM) tract implicated in emotion regulation, has been hypothesized as a neurobiological mechanism of depression. However, studies testing this hypothesis have yielded inconsistent results. The present meta-analysis consolidates evidence from 44 studies comparing fractional anisotropy (FA) and radial diffusivity (RD), two metrics characterizing WM microstructure, of the UNC in individuals with depression (n = 5016) to healthy individuals (n = 18 425). We conduct meta-regressions to identify demographic and clinical characteristics that contribute to cross-study heterogeneity in UNC findings. UNC FA was reduced in individuals with depression compared to healthy individuals. UNC RD was comparable between individuals with depression and healthy individuals. Comorbid anxiety explained inter-study heterogeneity in UNC findings. Depression is associated with perturbations in UNC microstructure, specifically with respect to UNC FA and not UNC RD. The association between depression and UNC microstructure appears to be moderated by anxiety. Future work should unravel the cellular mechanisms contributing to aberrant UNC microstructure in depression; clarify the relationship between UNC microstructure, depression, and anxiety; and link UNC microstructure to psychological processes, such as emotion regulation.

A Lifespan Model of Interference Resolution and Inhibitory Control: Risk for Depression and Changes with Illness Progression.

The cognitive processes involved in inhibitory control accuracy (IC) and interference resolution speed (IR) or broadly - inhibition - are discussed in this review, and both are described within the context of a lifespan model of mood disorders. Inhibitory control (IC) is a binary outcome (success or no for response selection and inhibition of unwanted responses) for any given event that is influenced to an extent by IR. IR refers to the process of inhibition, which can be manipulated by task design in earlier and later stages through use of distractors and timing, and manipulation of individual differences in response proclivity. We describe the development of these two processes across the lifespan, noting factors that influence this development (e.g., environment, adversity and stress) as well as inherent difficulties in assessing IC/IR prior to adulthood (e.g., cross-informant reports). We use mood disorders as an illustrative example of how this multidimensional construct can be informative to state, trait, vulnerability and neuroprogression of disease. We present aggregated data across numerous studies and methodologies to examine the lifelong development and degradation of this subconstruct of executive function, particularly in mood disorders. We highlight the challenges in identifying and measuring IC/IR in late life, including specificity to complex, comorbid disease processes. Finally, we discuss some potential avenues for treatment and accommodation of these difficulties across the lifespan, including newer treatments using cognitive remediation training and neuromodulation.

Using resting-state intrinsic network connectivity to identify suicide risk in mood disorders.

BACKGROUND: Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), could lead to more targeted treatments to reduce risk. METHODS: Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups. RESULTS: Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1-4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79-88%). CONCLUSIONS: These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.

Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies.

BACKGROUND: Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks. METHOD: The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29 year olds) of typically developing (TD) individuals (n = 97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136). RESULTS: Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood. CONCLUSIONS: The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage.

Self-reported affective biases, but not all affective performance biases, are present in depression remission.

OBJECTIVE: Individuals with active major depressive disorder (MDD) have shown affective biases in cognitive flexibility and memory, particularly for negatively valenced stimuli. We evaluated whether impairments in affective flexibility would remain even during remission (rMDD), potentially representing trait- or scar-like effects of illness. METHOD: Participants completed the Emotion Card Sort Test (ECST), a measure of cognitive flexibility containing emotionally valenced stimuli, and the Emotion Word Stimulus Test (EWST), a measure of affective biases in delayed recall and recognition memory, and several self-report measures. RESULTS: Healthy controls (HCs; n = 35) and individuals with rMDD (n = 93) did not differ on performance for any of the three word types on the ECST or EWT. However, individuals with rMDD demonstrated greater negative bias on EWT recognition trials relative to HCs (d = .36). On self-report measures, individuals with rMDD exhibited greater levels of neuroticism, problems with attentional control, pessimistic attributional style, and negative automatic thoughts compared to HCs. CONCLUSIONS: These results provide initial evidence that some performance, but not self-reported, indices of affective bias may improve during remission from MDD. Results of this study could suggest that some components of affective bias may represent state feature of illness and others trait-like risk or scar features. PRACTITIONER POINTS: This study suggests that self-reported affective biases may persist in remission of major depressive disorder (rMDD). Affective attentional biases and affective memory biases were not demonstrated in individuals with rMDD, with the exception of a bias for recognizing negatively versus neutrally valenced stimuli. CAUTIONS OR LIMITATIONS: A limitation of this study was its cross-sectional design. Under ideal conditions, the same individuals would be studied in both the active and remitted phases of illness. Another limitation of this study was the smaller number of healthy controls relative to individuals with rMDD.

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.

Attenuated intrinsic connectivity within cognitive control network among individuals with remitted depression: Temporal stability and association with negative cognitive styles.

Many individuals with major depressive disorder (MDD) experience cognitive dysfunction including impaired cognitive control and negative cognitive styles. Functional connectivity magnetic resonance imaging studies of individuals with current MDD have documented altered resting-state connectivity within the default-mode network and across networks. However, no studies to date have evaluated the extent to which impaired connectivity within the cognitive control network (CCN) may be present in remitted MDD (rMDD), nor have studies examined the temporal stability of such attenuation over time. This represents a major gap in understanding stable, trait-like depression risk phenotypes. In this study, resting-state functional connectivity data were collected from 52 unmedicated young adults with rMDD and 47 demographically matched healthy controls, using three bilateral seeds in the CCN (dorsolateral prefrontal cortex, inferior parietal lobule, and dorsal anterior cingulate cortex). Mean connectivity within the entire CCN was attenuated among individuals with rMDD, was stable and reliable over time, and was most pronounced with the right dorsolateral prefrontal cortex and right inferior parietal lobule, results that were corroborated by supplemental independent component analysis. Attenuated connectivity in rMDD appeared to be specific to the CCN as opposed to representing attenuated within-network coherence in other networks (e.g., default-mode, salience). In addition, attenuated connectivity within the CCN mediated relationships between rMDD status and cognitive risk factors for depression, including ruminative brooding, pessimistic attributional style, and negative automatic thoughts. Given that these cognitive markers are known predictors of relapse, these results suggest that attenuated connectivity within the CCN could represent a biomarker for trait phenotypes of depression risk. Hum Brain Mapp 38:2939-2954, 2017. © 2017 Wiley Periodicals, Inc.

Integrated cross-network connectivity of amygdala, insula, and subgenual cingulate associated with facial emotion perception in healthy controls and remitted major depressive disorder.

Emotion perception deficits could be due to disrupted connectivity of key nodes in the salience and emotion network (SEN), including the amygdala, subgenual anterior cingulate cortex (sgACC), and insula. We examined SEN resting-state (rs-)fMRI connectivity in rMDD in relation to Facial Emotion Perception Test (FEPT) performance. Fifty-two medication-free people ages 18 to 23 years participated. Twenty-seven had major depressive disorder (MDD) in remission (rMDD, 10 males), as MDD is associated with emotion perception deficits and alterations in rsfMRI. Twenty-five healthy controls (10 males) also participated. Participants completed the FEPT during fMRI, in addition to an 8-minute eyes-open resting-state scan. Seed regions of interest were defined in the amygdala, anterior insula and sgACC. Multiple regression analyses co-varied diagnostic group, sex and movement parameters. Emotion perception accuracy was positively associated with connectivity between amygdala seeds and regions primarily in the SEN and cognitive control network (CCN), and also the default mode network (DMN). Accuracy was also positively associated with connectivity between the sgACC seeds and other SEN regions, and the DMN, particularly for the right sgACC. Connectivity negatively associated with emotion perception was mostly with regions outside of these three networks, other than the left insula and part of the DMN. This study is the first to our knowledge to demonstrate relationships between facial emotion processing and resting-state connectivity with SEN nodes and between SEN nodes and regions located within other neural networks.

Affective instability and the course of bipolar depression: results from the STEP-BD randomised controlled trial of psychosocial treatment.

BACKGROUND: Little is known about predictors of recovery from bipolar depression. AIMS: We investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression. METHOD: A total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n= 141) or a brief psychoeducational intervention (n= 111). All analyses were by intention-to-treat. RESULTS: Degree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression. CONCLUSIONS: Affective instability may be a clinically relevant characteristic that influences the course of bipolar depression.

INFLEXIBLE COGNITION PREDICTS FIRST ONSET OF MAJOR DEPRESSIVE EPISODES IN ADOLESCENCE.

BACKGROUND: Major depressive disorder often is characterized by a lack of cognitive and emotional flexibility, resulting in an impaired ability to adapt to situational demands. Adolescence is an important period of risk for the first onset of depression, yet relatively little is known about whether aspects of inflexibility, such as rumination and deficits in attentional shifting, could confer risk for the development of the disorder during this time. METHOD: In the present study, a sample of 285 never-depressed adolescents completed self-report and behavioral measures of rumination and attentional shifting at a baseline visit, followed by up to 4 years of annual prospective follow-up diagnostic assessments. RESULTS: Survival analyses indicated that adolescents with greater levels of rumination or poorer attentional shifting experienced a shorter time until the first onset of major depressive episodes, even after accounting for baseline symptoms and demographic characteristics. Although girls were twice as likely as boys to experience the first onset of depression, rumination predicted a shorter time until depression onset only for boys. Rumination and attentional shifting were not correlated and predicted time until onset of major depression independently of one another. CONCLUSIONS: These results provide evidence that components of cognition that are characterized by rigidity and perseveration confer risk for the first onset of major depression during adolescence. Evaluating rumination and attentional shifting in adolescence may be useful in identifying individuals who are at risk for depression and who may benefit from interventions that target or alter the development of these characteristics.

SPECIFIC MOOD SYMPTOMS CONFER RISK FOR SUBSEQUENT SUICIDAL IDEATION IN BIPOLAR DISORDER WITH AND WITHOUT SUICIDE ATTEMPT HISTORY: MULTI-WAVE DATA FROM STEP-BD.

BACKGROUND: Little is known about specific mood symptoms that may confer risk for suicidal ideation (SI) among patients with bipolar disorder (BD). We evaluated prospectively whether particular symptoms of depression and mania precede the onset or worsening of SI, among adults with or without a history of a suicide attempt. METHODS: We examined prospective data from a large (N = 2,741) cohort of patients participating in the Systematic Treatment Enhancement Program for BD (STEP-BD). We evaluated history of suicide attempts at baseline, and symptoms of depression and mania at baseline and follow-up visits. Hierarchical linear modeling tested whether specific mood symptoms predicted subsequent levels of SI, and whether the strength of the associations differed based on suicide attempt history, after accounting for the influence of other mood symptoms and current SI. RESULTS: Beyond overall current depression and mania symptom severity, baseline SI, and illness characteristics, several mood symptoms, including guilt, reduced self-esteem, psychomotor retardation and agitation, increases in appetite, and distractibility predicted more severe levels of subsequent SI. Problems with concentration, distraction, sleep loss and decreased need for sleep predicted subsequent SI more strongly among individuals with a suicide attempt history. CONCLUSIONS: Several specific mood symptoms may confer risk for the onset or worsening of SI among treatment-seeking patients with BD. Individuals with a previous suicide attempt may be at greater risk in part due to greater reactivity to certain mood symptoms in the form of SI. However, overall, effect sizes were small, suggesting the need to identify additional proximal predictors of SI.

Identifying a physical indicator of suicide risk: Non-suicidal self-injury scars predict suicidal ideation and suicide attempts.

BACKGROUND: Suicide risk is challenging to quantify due to reliance on self-report, which is limited by individuals' lack of insight and the desire to conceal such intentions. Non-suicidal self-injury (NSSI) is one of the most robust predictors of suicidal ideation (SI) and suicide attempts (SA). Although NSSI often leads to permanent scarring, which can be assessed by objective physical examination, no research has examined whether scarring denotes tangible risk for SI and SA. The present study examined whether NSSI scar presence and number predict current SI and SA history. Further, we examined whether brooding would exacerbate the effects of NSSI scarring on SI or SA. METHODS: Young adults (N=231; M=21.24 years; 78% female) completed self-report questionnaires assessing SA history, frequency of NSSI, presence/number of NSSI scars, brooding, current depressive symptoms, and SI. RESULTS: NSSI scar presence and number predicted current SI and SA history after controlling for current depressive symptoms. Moreover, scar presence and number predicted current SI over and above the effects of SA history and NSSI frequency, method, and medical severity. Further, NSSI scar presence and number predicted SI more strongly among individuals with greater levels of brooding than among individuals with lower levels of brooding. CONCLUSIONS: The presence and number of NSSI scars are objective physical indicators of risk for SI and SAs. Brooding may further heighten the risk of SI for individuals bearing NSSI scars.

A randomized, placebo-controlled proof-of-concept trial of adjunctive topiramate for alcohol use disorders in bipolar disorder.

BACKGROUND AND OBJECTIVES: Topiramate is effective for alcohol use disorders (AUDs) among non-psychiatric patients. We examined topiramate for treating comorbid AUDs in bipolar disorder (BD). METHODS: Twelve participants were randomized to topiramate or placebo for 12 weeks. RESULTS: The topiramate group, with two out of five participants (40%) completing treatment, experienced less improvement in drinking patterns than the placebo group, with five out of seven participants (71%) completing treatment. DISCUSSION AND CONCLUSIONS: Topiramate did not improve drinking behavior and was not well-tolerated. This study failed to recruit adequately. Problems surrounding high attrition, a small study sample, and missing data preclude interpretation of study findings. SCIENTIFIC SIGNIFICANCE: This is the first randomized, placebo-controlled trial of topiramate for AUDs in BD.

Deficits in Emotional Clarity and Vulnerability to Peer Victimization and Internalizing Symptoms Among Early Adolescents.

Peer victimization is a significant risk factor for a range of negative outcomes during adolescence, including depression and anxiety. Recent research has evaluated individual characteristics that heighten the risk of experiencing peer victimization. However, the role of emotional clarity, or the ability to understand one's emotions, in being the target of peer victimization remains unclear. Thus, the present study evaluated whether deficits in emotional clarity increased the risk of experiencing peer victimization, particularly among adolescent girls, which, in turn, contributed to prospective levels of depressive and anxiety symptoms. In the present study, 355 early adolescents (ages 12-13; 53% female; 51% African American) who were part of the Adolescent Cognition and Emotion project completed measures of emotional clarity, depressive symptoms, and anxiety symptoms at baseline, and measures of peer victimization, depressive symptoms, and anxiety symptoms at follow-up. Moderation analyses indicated that deficits in emotional clarity predicted greater peer victimization among adolescent girls, but not adolescent boys. Moderated mediation analyses revealed that deficits in emotional clarity contributed to relational peer victimization, which, in turn, predicted prospective levels of depressive and anxiety symptoms among adolescent girls, but not boys. These findings indicate that deficits in emotional clarity represent a significant risk factor for adolescent girls to experience relational peer victimization, which, in turn, contributed to prospective levels of internalizing symptoms. Thus, prevention programs should target deficits in emotional clarity to prevent peer victimization and subsequent internalizing symptoms among adolescent girls.

The cyclical nature of depressed mood and future risk: Depression, rumination, and deficits in emotional clarity in adolescent girls.

Deficits in emotional clarity, the understanding and awareness of one's own emotions and the ability to label them appropriately, are associated with increased depressive symptoms. Surprisingly, few studies have examined factors associated with reduction in emotional clarity for adolescents, such as depressed mood and ruminative response styles. The present study examined rumination as a potential mediator of the relationship between depressive symptoms and changes in emotional clarity, focusing on sex differences. Participants included 223 adolescents (51.60% female, Mean age = 12.39). Controlling for baseline levels of emotional clarity, initial depressive symptoms predicted decreases in emotional clarity. Further, rumination prospectively mediated the relationship between baseline depressive symptoms and follow-up emotional clarity for girls, but not boys. Findings suggest that depressive symptoms may increase girls' tendencies to engage in repetitive, negative thinking, which may reduce the ability to understand and label emotions, a potentially cyclical process that confers vulnerability to future depression.

The interaction of affective states and cognitive vulnerabilities in the prediction of non-suicidal self-injury.

Non-suicidal self-injury (NSSI) is a serious public health concern and remains poorly understood. This study sought to identify both cognitive and affective vulnerabilities to NSSI and examine their interaction in the prediction of NSSI. A series of regressions indicated that low levels of positive affect (PA) moderated the relationships between self-criticism and brooding and NSSI. The associations of self-criticism and brooding with greater frequency of NSSI were attenuated by higher levels of PA. The interaction of cognitive and affective vulnerabilities is discussed within the context of current NSSI theory.

Rumination and overgeneral autobiographical memory in adolescents: an integration of cognitive vulnerabilities to depression.

During adolescence, rates of depression dramatically increase and girls become twice as likely as boys to develop depression. Research suggests that overgeneral autobiographical memory and rumination are vulnerability factors for depressive symptoms in adolescence that may be triggered by stressful life events. The current longitudinal study included 160 early adolescents (Mage = 12.44 years, 60.0 % African American, 40.0 % Caucasian, and 56.2 % female). At baseline, adolescents completed measures of current depressive symptoms, rumination, and specificity of autobiographical memories. Approximately 9 months later, the adolescents completed measures of current depressive symptoms and stressful life events that had occurred between baseline and follow-up. Analyses indicated that girls with more overgeneral autobiographical memories in combination with higher levels of rumination were most vulnerable to experiencing increases in depressive symptoms following stressful life events. Additionally, retrieving more specific autobiographical memories appeared to buffer against the impact of negative life events on depressive symptoms among both boys and girls. Memory specificity may play a protective role in depression risk, suggesting that memory specificity training interventions may prove beneficial for adolescents.

Pubertal Timing, Peer Victimization, and Body Esteem Differentially Predict Depressive Symptoms in African American and Caucasian Girls.

This study prospectively examined pubertal timing and peer victimization as interactive predictors of depressive symptoms in a racially diverse community sample of adolescents. We also expanded on past research by assessing body esteem as a mechanism by which pubertal timing and peer victimization confer risk for depression. In all, 218 adolescents (53.4% female, 49.3% African American, 50.7% Caucasian) completed both a baseline assessment and a follow-up assessment approximately 8 months later. Early maturing Caucasian girls and late maturing African American girls experienced the greatest increases in depressive symptoms at follow-up if they experienced higher levels of peer victimization between baseline and follow-up. Furthermore, body esteem significantly mediated the relationship between pubertal timing, peer victimization, and depressive symptoms for girls of both races. The interaction of pubertal timing and peer victimization did not predict depressive symptoms for boys of either race. These results support body esteem as a mechanism that contributes to increased depression among girls in adolescence-despite a differential impact of pubertal timing for Caucasian and African American girls.

A vulnerability-stress examination of response styles theory in adolescence: stressors, sex differences, and symptom specificity.

The stress-reactivity extension of the response styles theory of depression suggests that individuals who ruminate (or fail to engage in distraction or problem solving) in response to dysphoric mood are likely to experience higher levels of depression following stress. However, previous studies have not addressed (a) the specificity of these vulnerability-stress relations to symptoms of depression following different types of stressors, and (b) to what extent rumination and stress can account for the sex differences in depression that emerge during early adolescence. A community sample of 256 early adolescents (ages 12-13) completed a baseline visit and a follow-up visit 9 months later. Response styles and symptoms of depression and anxiety were assessed at baseline, and intervening life events, emotional maltreatment, peer relational victimization, and symptoms of depression and anxiety were assessed at follow-up. Higher rumination and lower distraction/problem solving interacted with several types of stressors to predict higher levels of symptoms of depression but not anxiety. Rumination was more strongly associated with elevations in depressive symptoms following the occurrence of relational victimization events in girls than in boys. In addition, dependent interpersonal stress mediated the sex difference in depressive symptoms that emerged at follow-up, and this indirect pathway was stronger among adolescents who tended to ruminate. Rumination may confer vulnerability that is specific to symptoms of depression following recent stressors during early adolescence. Girls who ruminate may be particularly likely to experience depression following relational victimization, and dependent interpersonal stressors may help to account for girls' greater risk for depression during adolescence.