Reliability of diurnal salivary cortisol metrics: A meta-analysis and investigation in two independent samples.

Stress-induced dysregulation of diurnal cortisol is a cornerstone of stress-disease theories; however, observed associations between cortisol, stress, and health have been inconsistent. The reliability of diurnal cortisol features may contribute to these equivocal findings. Our meta-analysis (5 diurnal features from 11 studies; total participant n = 3307) and investigation (15 diurnal cortisol features) in 2 independent studies (St. Louis Personality and Aging Network [SPAN] Study, n = 147, ages 61-73; Minnesota Longitudinal Study of Risk and Adaptation [MLSRA] Study, n = 90, age 37) revealed large variability in the day-to-day test-retest reliability of diurnal features derived from salivary cortisol data (i.e., ICC = 0.00-0.75). Collectively, these data indicate that some commonly used diurnal cortisol features have poor reliability that is insufficient for individual differences research (e.g., cortisol awakening response) while others (e.g., area under the curve with respect to ground) have fair-to-good reliability that could support reliable identification of associations in well-powered studies.

Understanding Anhedonia from a Genomic Perspective.

Anhedonia, or the decreased ability to experience pleasure, is a cardinal symptom of major depression that commonly occurs within other forms of psychopathology. Supportive of long-held theory that anhedonia represents a genetically influenced vulnerability marker for depression, evidence from twin studies suggests that it is moderately-largely heritable. However, the genomic sources of this heritability are just beginning to be understood. In this review, we survey what is known about the genomic architecture underlying anhedonia and related constructs. We briefly review twin and initial candidate gene studies before focusing on genome-wide association study (GWAS) and polygenic efforts. As large samples are needed to reliably detect the small effects that typically characterize common genetic variants, the study of anhedonia and related phenotypes conflicts with current genomic research requirements and frameworks that prioritize sample size over precise phenotyping. This has resulted in few and underpowered studies of anhedonia-related constructs that have largely failed to reliably identify individual variants. Nonetheless, the polygenic architecture of anhedonia-related constructs identified in these studies has genetic overlap with depression and schizophrenia as well as related brain structure (e.g., striatal volume), providing important clues to etiology that may usefully guide refinement in nosology. As we await the accumulation of larger samples for more well-powered GWAS of reward-related constructs, novel analytic techniques that leverage GWAS summary statistics (e.g., genomic structural equation modeling) may currently be used to help characterize how the genomic architecture of anhedonia is shared and distinct from that underlying other constructs (e.g., depression, neuroticism, anxiety).

Inflammation is associated with future depressive symptoms among older adults.

Inflammation has been reliably associated with depression. However, the directionality of this association is poorly understood, with evidence that elevated inflammation may promote and precede the development of depression, as well as arise following its expression. Using data from older adults (N â€‹= â€‹1,072, ages 60-73) who participated in the ongoing longitudinal St. Louis Personality and Aging Network (SPAN) study, we examined whether inflammatory markers (interleukin-6: IL-6, C-reactive protein: CRP, and tumor necrosis factor α: TNFα) and depression were prospectively predictive of one another. Fasting serum samples and self-reports of depressive symptoms (Beck Depression Inventory-II) were obtained from participants at 2 sessions approximately 2 years apart. Structural equation models as well as regressions that accounted for a host of potentially confounding covariates and depression at baseline revealed that baseline IL-6 and CRP, but not baseline TNFα were associated with elevated depressive symptoms at the follow-up session (IL-6: ߠ​= â€‹0.080, p â€‹= â€‹0.036; CRP: ߠ​= â€‹0.083, p â€‹= â€‹0.03; TNFα: ߠ​= â€‹0.039, p â€‹= â€‹0.314). However, there was no association between baseline depressive symptoms and follow-up inflammatory markers (ßs â€‹= â€‹-0.12 to -0.006, all ps â€‹> â€‹0.05). Collectively, these data suggest that inflammation prospectively predicts depression, but depression does not predict inflammation in older age. These data add to a growing literature suggesting that inflammatory signaling may plausibly promote the development of depression.

Neuroticism and reward-related ventral striatum activity: Probing vulnerability to stress-related depression.

Elevated neuroticism may confer vulnerability to the depressogenic effects of stressful life events (SLEs). However, the mechanisms underlying this susceptibility remain poorly understood. Accumulating evidence suggests that stress-related disruptions in neural reward processing might undergird links between stress and depression. Using data from the Saint Louis Personality and Aging Network (SPAN) study and Duke Neurogenetics Study (DNS), we examined whether neuroticism moderates links between stressful life events (SLE) and depression as well as SLEs and ventral striatum (VS) response to reward. In the longitudinal SPAN sample (n = 971 older adults), SLEs prospectively predicted future depressive symptoms, especially among those reporting elevated neuroticism, even after accounting for prior depressive symptoms and previous SLE exposure (NxSLE interaction: p = .016, ΔR² = 0.003). Cross-sectional analyses of the DNS, a young adult college sample with neuroimaging data, replicated this interaction (n = 1,343: NxSLE interaction: p = .019, ΔR² = 0.003) and provided evidence that neuroticism moderates the association between SLEs and reward-related VS response (n = 1,195, NxSLE: p = .017, ΔR² = 0.0048). Blunted left VS response to reward was associated with a lifetime depression diagnosis, r = -0.07, p = .02, but not current depressive symptoms, r = -0.003, p = .93. These data suggest that neuroticism may promote vulnerability to stress-related depression and that sensitivity to stress-related reductions in VS response may be a potential neural mechanism underlying vulnerability to clinically significant depression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Associations Between Prenatal Cannabis Exposure and Childhood Outcomes: Results From the ABCD Study.

Importance: In light of increasing cannabis use among pregnant women, the US Surgeon General recently issued an advisory against the use of marijuana during pregnancy. Objective: To evaluate whether cannabis use during pregnancy is associated with adverse outcomes among offspring. Design, Setting, and Participants: In this cross-sectional study, data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development Study, which recruited 11 875 children aged 9 to 11 years, as well as a parent or caregiver, from 22 sites across the United States between June 1, 2016, and October 15, 2018. Exposure: Prenatal cannabis exposure prior to and after maternal knowledge of pregnancy. Main Outcomes and Measures: Symptoms of psychopathology in children (ie, psychotic-like experiences [PLEs] and internalizing, externalizing, attention, thought, and social problems), cognition, sleep, birth weight, gestational age at birth, body mass index, and brain structure (ie, total intracranial volume, white matter volume, and gray matter volume). Covariates included familial (eg, income and familial psychopathology), pregnancy (eg, prenatal exposure to alcohol and tobacco), and child (eg, substance use) variables. Results: Among 11 489 children (5997 boys [52.2%]; mean [SD] age, 9.9 [0.6] years) with nonmissing prenatal cannabis exposure data, 655 (5.7%) were exposed to cannabis prenatally. Relative to no exposure, cannabis exposure only before (413 [3.6%]) and after (242 [2.1%]) maternal knowledge of pregnancy were associated with greater offspring psychopathology characteristics (ie, PLEs and internalizing, externalizing, attention, thought and, social problems), sleep problems, and body mass index, as well as lower cognition and gray matter volume (all |ß| > 0.02; all false discovery rate [FDR]-corrected P < .03). Only exposure after knowledge of pregnancy was associated with lower birth weight as well as total intracranial volume and white matter volumes relative to no exposure and exposure only before knowledge (all |ß| > 0.02; all FDR-corrected P < .04). When including potentially confounding covariates, exposure after maternal knowledge of pregnancy remained associated with greater PLEs and externalizing, attention, thought, and social problems (all ß > 0.02; FDR-corrected P < .02). Exposure only prior to maternal knowledge of pregnancy did not differ from no exposure on any outcomes when considering potentially confounding variables (all |ß| < 0.02; FDR-corrected P > .70). Conclusions and Relevance: This study suggests that prenatal cannabis exposure and its correlated factors are associated with greater risk for psychopathology during middle childhood. Cannabis use during pregnancy should be discouraged.

Reward-Related Neural Predictors and Mechanisms of Symptom Change in Cognitive Behavioral Therapy for Depressed Adolescent Girls.

BACKGROUND: Approximately half of depressed adolescents fail to respond to cognitive behavioral therapy (CBT). Given the variability in response, it is important to identify pretreatment characteristics that predict prognosis. Knowledge of which depressed adolescents are likely to exhibit a positive versus poor outcome to CBT may have important clinical implications (e.g., informing treatment recommendations). Emerging evidence suggests that neural reward responsiveness represents one promising predictor. METHODS: Adolescents with major depressive disorder (n = 36) received CBT and completed a reward task at 3 time points (pretreatment, midtreatment and posttreatment) while 128-channel electroencephalographic data were acquired. Healthy control participants (n = 29) completed the same task at 3 corresponding time points. Analyses focused on event-related potentials linked to 2 stages of neural processing: initial response to rewards (reward positivity) and later, elaborative processing (late positive potential). Moreover, time-frequency analyses decomposed the reward positivity into 2 constituent components: reward-related delta and loss-related theta activity. RESULTS: Multilevel modeling revealed that greater pretreatment reward responsiveness, as measured by the late positive potential to rewards, predicted greater depressive symptom change. In addition, a group × condition × time interaction emerged for theta activity to losses, reflecting normalization of theta power in the group with major depressive disorder from baseline to posttreatment. CONCLUSIONS: An event-related potential measure of sustained (late positive potential)-but not initial (reward positivity)-reward responsiveness predicted symptom improvement, which may help inform which depressed adolescents are most likely to benefit from CBT. In addition to alleviating depression, successful CBT may attenuate underlying neural (theta) hypersensitivity to negative outcomes in depressed youths.

Reward Functioning Abnormalities in Adolescents at High Familial Risk for Depressive Disorders.

BACKGROUND: A parental history of major depressive disorder (MDD) is an established risk factor for MDD in youth, and clarifying the mechanisms related to familial risk transmission is critical. Aberrant reward processing is a promising biomarker of MDD risk; accordingly, the aim of this study was to test behavioral measures of reward responsiveness and underlying frontostriatal resting activity in healthy adolescents both with (high-risk) and without (low-risk) a maternal history of MDD. METHODS: Low-risk and high-risk 12- to 14-year-old adolescents completed a probabilistic reward task (n = 74 low-risk, n = 27 high-risk) and a resting-state functional magnetic resonance imaging scan (n = 61 low-risk, n = 25 high-risk). Group differences in response bias toward reward and resting ventral striatal and medial prefrontal cortex (mPFC) fractional amplitude of low-frequency fluctuations (fALFFs) were examined. Computational modeling was applied to dissociate reward sensitivity from learning rate. RESULTS: High-risk adolescents showed a blunted response bias compared with low-risk adolescents. Computational modeling analyses revealed that relative to low-risk adolescents, high-risk adolescents exhibited reduced reward sensitivity but similar learning rate. Although there were no group differences in ventral striatal and mPFC fALFFs, groups differed in their relationships between mPFC fALFFs and response bias. Specifically, among high-risk adolescents, higher mPFC fALFFs correlated with a blunted response bias, whereas there was no fALFFs-response bias relationship among low-risk youths. CONCLUSIONS: High-risk adolescents exhibit reward functioning impairments, which are associated with mPFC fALFFs. The blunted response bias-mPFC fALFFs association may reflect an excessive mPFC-mediated suppression of reward-driven behavior, which may potentiate MDD risk.

Delineating the social valuation network in adolescents.

Adolescents strive for peer approval, and an increased sensitivity to peers' opinions is normative. However, among vulnerable adolescents, peer evaluation can be detrimental, contributing to affective disorders. It is, therefore, critical to improve our understanding of neural underpinnings of peer evaluation. Prior research has investigated averaged neural responses to peer acceptance or rejection, neglecting to probe trial-by-trial computations that mirror real-time updating of daily activities. In non-social decision-making, a common neural valuation system centered on the medial prefrontal cortex (mPFC) has emerged, which evaluates different reward types on a common scale to guide choices. However, it is unclear whether the mPFC also tracks complex social scenarios involving peer feedback. To address this gap, we acquired fMRI data from 55 healthy adolescents during the Chatroom Task, which probes peer evaluation, and implemented a computational approach to characterize trial-by-trial social value, thereby allowing us to interrogate the neural correlates of social value. Consistent with our hypothesis, social value signals were encoded in the mPFC. Interestingly, analyses also revealed a wider social-specific valuation network including the precuneus and amygdala. Understanding how adolescents make social decisions and neural markers associated with it, may, ultimately, help us clarify promising targets for intervention.

The intergenerational transmission of childhood maltreatment: Nonspecificity of maltreatment type and associations with borderline personality pathology.

One generation's experience of childhood maltreatment is associated with that of the next. However, whether this intergenerational transmission is specific to distinct forms of maltreatment and what factors may contribute to its continuity remains unclear. Borderline personality pathology is predicted by childhood maltreatment and characterized by features (e.g., dysregulated emotion, relationship instability, impulsivity, and inconsistent appraisals of others) that may contribute to its propagation. Among 364 older adults and 573 of their adult children (total n = 937), self-reported exposure to distinct forms of childhood maltreatment (i.e., emotional, physical, and sexual abuse, and emotional and physical neglect as assessed by the Childhood Trauma Questionnaire) showed homotypic and heterotypic associations across generations with little evidence that latent factors unique to specific forms of maltreatment show generational continuity. General nonspecific indices of childhood maltreatment showed evidence of intergenerational transmission after accounting for demographic factors and parent socioeconomic status (b = 0.126, p = 9.21 × 10-4). This continuity was partially mediated by parental borderline personality pathology (assessed longitudinally through a variety of measures and sources, indirect effect: b = 0.031, 95% confidence interval [0.003, 0.060]). The intergenerational continuity of childhood maltreatment may largely represent general risk for nonspecific maltreatment that may, in part, be propagated by borderline personality pathology and/or shared risk factors.

Cognitive versus behavioral skills in CBT for depressed adolescents: Disaggregating within-patient versus between-patient effects on symptom change.

OBJECTIVE: Despite a growing body of research supporting the efficacy of cognitive-behavioral therapy (CBT) for depressed adolescents, few studies have investigated the role of the acquisition and use of CBT skills in accounting for symptom improvement. The present study examined the role of cognitive versus behavioral skills in predicting symptom improvement in depressed youth. Analyses considered different raters of patient skills (patient vs. therapist) as well as disaggregated between-patient versus within-patient effects. METHOD: Data were derived from a 12-week clinical trial of CBT for depressed adolescent females (N = 33; ages 13-18 years; 69.7% White). Both therapist-report and patient-report measures of CBT skills (skills of cognitive therapy) were acquired at 5 time points throughout therapy: Sessions 1, 3, 6, 9, and 12. Depressive symptoms (Beck Depression Inventory-II) were assessed at every session. RESULTS: Therapist and patient ratings of CBT skills showed small to moderate associations (rs = .20-.38). Intraclass correlation coefficients indicated that the majority of the variance in skills scores (61-90%) was attributable to within-patient variance from session to session, rather than due to between-patient differences. When disaggregating within-patient and between-patient effects, and consistent with a causal relationship, within-patient variability in both patient-rated (b = -2.55; p = .025) and therapist-rated (b = -2.41; p = .033) behavioral skills predicted subsequent symptom change. CONCLUSIONS: Analyses highlight the importance of the acquisition and use of behavioral skills in CBT for depressed adolescents. Findings also underscore the importance of disentangling within-patient from between-patient effects in future studies, an approach infrequently used in process-outcome research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Altered reward processing following an acute social stressor in adolescents.

Altered reward processing is a transdiagnostic factor implicated in a wide range of psychiatric disorders. While prior animal and adult research has shown that stress contributes to reward dysfunction, less is known about how stress impacts reward processing in youth. Towards addressing this gap, the present study probed neural activation associated with reward processing following an acute stressor. Healthy adolescents (n = 40) completed a clinical assessment, and fMRI data were acquired while participants completed a monetary guessing task under a no-stress condition and then under a stress condition. Based on prior literature, analyses focused on a priori defined regions-of-interest, specifically the striatum (win trials) and dorsal anterior cingulate cortex [dACC] and insula (loss trials). Two main findings emerged. First, reward-related neural activation (i.e., striatum) was blunted in the stress relative to the no-stress condition. Second, the stress condition also contributed to blunted neural response following reward in loss-related regions (i.e., dACC, anterior insula); however, there were no changes in loss sensitivity. These results highlight the importance of conceptualizing neural vulnerability within the presence of stress, as this may clarify risk for mental disorders during a critical period of development.

Testing neurophysiological markers related to fear-potentiated startle.

Fear-potentiated startle (FPS) paradigms provide insight into fear learning mechanisms that contribute to impairment among individuals with posttraumatic stress symptoms (PTSS). Electrophysiology also has provided insight into these mechanisms through the examination of event-related potentials (ERPs) such as the P100 and LPP. It remains unclear, however, whether the P100 and LPP may be related to fear learning processes within the FPS paradigm. To this end, we tested differences in ERP amplitudes for conditioned stimuli associated (CS+) and not associated (CS-) with an aversive unconditioned stimulus (US) during fear acquisition. Participants included 54 female undergraduate students (mean age = 20.26). The FPS response was measured via electromyography of the orbicularis oculi muscle. EEG data were collected during the FPS paradigm. While the difference between CS+ and CS- P100 amplitude was not significant, LPP amplitudes were significantly enhanced following the CS+ relative to CS-. Furthermore, the LPP difference wave (CS+ minus CS-) was associated with FPS scores for the CS- during the later portion of fear acquisition. These findings suggest that conditioned stimuli may have altered emotional encoding (LPP) during the FPS paradigm. Thus, the LPP may be a promising neurophysiological marker that is related to fear learning processes.

Emotion processing in female youth: Testing the stability of the late positive potential.

The Emotional Interrupt Task (EIT) has been used to probe emotion processing in healthy and clinical samples; however, research exploring the stability and reliability of behavioral measures and ERPs elicited from this task is limited. Establishing the psychometric properties of the EIT is critical, particularly as phenotypes and biological indicators may represent traitlike characteristics that underlie psychiatric illness. To address this gap, test-retest stability and internal consistency of behavioral indices and ERPs resulting from the EIT in healthy, female youth (n = 28) were examined. At baseline, participants were administered the EIT while high-density 128-channel EEG data were recorded to probe the late positive potential (LPP). One month later, participants were readministered the EIT. Four principal findings emerged. First, there is evidence of an interference effect at baseline, as participants showed a slower reaction time for unpleasant and pleasant images relative to neutral images, and test-retest of behavioral measures was relatively stable over time. Second, participants showed a potentiated LPP to unpleasant and pleasant images compared to neutral images, and these effects were stable over time. Moreover, in a test of the difference waves (unpleasant-neutral vs. pleasant-neutral), there was sustained positivity for unpleasant images. Third, behavioral measures and LPP demonstrated excellent internal consistency (odd/even correlations) across conditions. Fourth, highlighting important age-related differences in LPP activity, younger age was associated with larger LPP amplitudes across conditions. Overall, these findings suggest that the LPP following emotional images is a stable and reliable marker of emotion processing in healthy youth.

Neuroanatomical Prediction of Anhedonia in Adolescents.

Anhedonia is a transdiagnostic risk factor implicated in mental illness onset, treatment non-response, and suicidal behaviors. Prior cross-sectional research in adults has shown that anhedonia is associated with reduced dorsal striatal volume, but it is unknown whether this relationship extends to adolescents and whether reduced striatal volume prospectively predicts anhedonia. To address these gaps, the current study investigated whether striatal volume predicted anhedonia severity in adolescents. At baseline, healthy female adolescents aged 12-14 years (n=50) completed a clinical assessment, and structural MRI data were acquired on a 3 Tesla MR scanner. While in the scanner, participants also completed a peer feedback task where subjective ratings following peer 'acceptance' or 'rejection' were obtained. At the three-month follow-up, participants provided self-report assessments of anhedonia, depression, and anxiety symptoms. Three main findings emerged. First, in cross-sectional analyses, right nucleus accumbens volume was inversely related to anhedonia severity. Second, reduced bilateral putamen volume prospectively predicted anhedonia severity while controlling for baseline anhedonia, depression, and anxiety symptoms. Third, a blunted subjective response to peer acceptance (ie, neutral response to positive feedback), but not a more negative subjective response to peer rejection, contributed to anhedonia severity, but only among youth with smaller putamen volume. Collectively, these results suggest that smaller volume in striatal regions critically implicated in reward processing is associated with current and future anhedonic symptoms among healthy female youth. These anatomical features may confer vulnerability to anhedonia and thus, may inform early identification of individuals at high risk for mental illness.

Abnormal neural responses to feedback in depressed adolescents.

Depression rates surge in adolescence, particularly among females. Recent findings suggest that depressed adolescents are characterized by hypersensitivity to negative outcomes and blunted responsiveness to rewards. However, our understanding of the pathophysiology and time course of these abnormalities remains limited. Due to their high temporal resolution, event-related potentials (ERPs) provide an ideal probe to investigate these processes. In the present study, healthy (n = 25) and depressed (n = 26) female adolescents (13-18 years) completed a gambling task during 128-channel ERP recording. Time-domain analyses focused on ERPs linked to initial processing of negative versus rewarding outcomes (feedback-related negativity; FRN), and later, elaborative processing (late positive potential; LPP). Additionally, time-frequency analyses were used to decompose the FRN into its 2 constituent neural signals: loss-related theta and reward-related delta activity, thereby allowing us to separately probe these 2 putative mechanisms underlying FRN abnormalities in depression. Relative to healthy adolescents, depressed youth showed potentiated FRN (loss vs. reward) responses. Time-frequency analyses revealed that this group difference in the FRN was driven by increased loss-related theta activity in depressed youth, and not by reward-related delta activity. For the LPP, healthy adolescents exhibited sustained positivity to rewards versus losses, whereas depressed adolescents showed the opposite pattern. Moreover, an enhanced LPP to losses was associated with rumination. In summary, the LPP may be a sensitive probe of depressive rumination, whereas FRN-linked theta activity may represent a neural marker of hypersensitivity to negative outcomes in depressed youth. Implications for treatment and future ERP research are discussed. (PsycINFO Database Record

Self-referential processing in adolescents: Stability of behavioral and ERP markers.

The self-referential encoding task (SRET)-an implicit measure of self-schema-has been used widely to probe cognitive biases associated with depression, including among adolescents. However, research testing the stability of behavioral and electrocortical effects is sparse. Therefore, the current study sought to evaluate the stability of behavioral markers and ERPs elicited from the SRET over time in healthy, female adolescents (n = 31). At baseline, participants were administered a diagnostic interview and a self-report measure of depression severity. In addition, they completed the SRET while 128-channel ERP data were recorded to examine early (P1) and late (late positive potential [LPP]) ERPs. Three months later, participants were readministered the depression self-report measure and the SRET in conjunction with ERPs. Results revealed that healthy adolescents endorsed, recalled, and recognized more positive and fewer negative words at each assessment, and these effects were stable over time (rs = .44-.83). Similarly, they reported a faster reaction time when endorsing self-relevant positive words, as opposed to negative words, at both the initial and follow-up assessment (r = .82). Second, ERP responses, specifically potentiated P1 and late LPP positivity to positive versus negative words, were consistent over time (rs = .56-.83), and the internal reliability of ERPs were robust at each time point (rs = .52-.80). As a whole, these medium-to-large effects suggest that the SRET is a reliable behavioral and neural probe of self-referential processing.

Electrocortical Reactivity During Self-referential Processing in Female Youth With Borderline Personality Disorder.

BACKGROUND: Borderline personality disorder (BPD) is debilitating, and theoretical models have postulated that cognitive-affective biases contribute to the onset and maintenance of BPD symptoms. Despite advances, our understanding of BPD pathophysiology in youth is limited. The present study used event-related potentials (ERPs) to identify cognitive-affective processes that underlie negative self-referential processing in BPD youth. METHODS: Healthy females (n = 33) and females with BPD (n = 26) 13 to 22 years of age completed a self-referential encoding task while 128-channel electroencephalography data were recorded to examine early (i.e., P1 and P2) and late (late positive potential [LPP]) ERP components. Whole-brain standardized low-resolution electromagnetic tomography explored intracortical sources underlying significant scalp ERP effects. RESULTS: Compared to healthy females, participants with BPD endorsed, recalled, and recognized fewer positive and more negative words. Moreover, unlike the healthy group, females with BPD had faster reaction times to endorse negative versus positive words. In the scalp ERP analyses, the BPD group had greater P2 and late LPP positivity to negative as opposed to positive words. For P2 and late LPP, whole-brain standardized low-resolution electromagnetic tomography analyses suggested that females with BPD overrecruit frontolimbic circuitry in response to negative stimuli. CONCLUSIONS: Collectively, these findings show that females with BPD process negative self-relevant information differently than healthy females. Clinical implications and future directions are discussed.