Patient, family caregiver, and economic outcomes of an integrated screening and novel stepped collaborative care intervention in the oncology setting in the USA (CARES): a randomised, parallel, phase 3 trial.

BACKGROUND: The current standard of care of screening and referring patients for treatment for symptoms, such as depression, pain, and fatigue, is not effective. This trial aimed to test the efficacy of an integrated screening and novel stepped collaborative care intervention versus standard of care for patients with cancer and at least one of the following symptoms: depression, pain, or fatigue. METHODS: This randomised, parallel, phase 3 trial was conducted in 29 oncology outpatient clinics associated with the UPMC Hillman Cancer Center in the USA. Patients (aged ≥21 years) with any cancer type and clinical levels of depression, pain, or fatigue (or all of these) were eligible. Eligible family caregivers were aged 21 years or older and providing care to a patient diagnosed with cancer who consented for this study. Patients were randomly assigned (1:1) to stepped collaborative care or standard of care using a central, permuted block design (sizes of 2, 4, and 6) stratified by sex and prognostic status. The biostatistician, oncologists, and outcome assessors were masked to treatment assignment. Stepped collaborative care was once-weekly cognitive behavioural therapy for 50-60 min from a care coordinator via telemedicine (eg, telephone or videoconferencing). Pharmacotherapy for symptoms might be initiated or changed if recommended by the treatment team or preferred by the patient. Standard of care was screening and referral to a health-care provider for treatment of symptoms. The primary outcome was health-related quality of life in patients at 6 months. Maintenance of the treatment benefits was assessed at 12 months. Participants included in the primary analysis were per intention to treat, which included patients missing one or both follow-up assessments. This trial was registered with ClinicalTrials.gov (NCT02939755). FINDINGS: Between Dec 5, 2016, and April 8, 2021, 459 patients and 190 family caregivers were enrolled. 222 patients were assigned to standard of care and 237 to stepped collaborative care. Of 459 patients, 201 (44%) were male and 258 (56%) were female. Patients in the stepped collaborative care group had a greater 0-6-month improvement in health-related quality of life than patients in the standard-of-care group (p=0·013, effect size 0·09). Health-related quality of life was maintained for the stepped collaborative care group (p=0·74, effect size 0·01). Patients in the stepped collaborative care group had greater 0-6-month improvements than the standard-of-care group in emotional (p=0·012), functional (p=0·042), and physical (p=0·033) wellbeing. No adverse events were reported by patients in either group and deaths were considered unrelated to the study. INTERPRETATION: An integrated screening and novel stepped collaborative care intervention, compared with the current standard of care, is recommended to improve health-related quality of life. The findings of this study will advance the implementation of guideline concordant care (screening and treatment) and has the potential to shift the practice of screening and treatment paradigm nationwide, improving outcomes for patients diagnosed with cancer. FUNDING: US National Cancer Institute.

Long-term stability of respiratory sinus arrhythmia among adults with and without a history of depression.

Respiratory sinus arrhythmia (RSA) is an index of parasympathetic nervous system activity reflecting respiratory influences on heart rate. This influence is typically measured as high frequency heart rate variability (HF-HRV) or root mean square of successive differences (RMSSD) of adjacent inter-beat intervals. Examining the long-term stability of its measurement is important as levels of resting RSA have been conceptualized as a marker of individual differences; in particular, of an individual's autonomic regulation and affect-related processes, including emotion regulation. At present, it is not known if resting RSA levels reflect stable differences over a long-term period (i.e., >1 year). Even less is known about how RSA stability differs as a function of depression history and whether it relates to depression risk trajectories. In the present study, we examined the 1.5-year test-retest reliability of resting RSA using the intraclass correlation coefficient (ICC) in 82 adults: n = 41 with a history of depression (ever-depressed); n = 41 controls with no depression history (never-depressed). HF-HRV was fairly stable in both groups (ever-depressed ICC = 0.55, never-depressed ICC = 0.54). RMSSD was also fairly stable in ever-depressed adults (ICC = 0.57) and never-depressed controls (ICC = 0.40). ICC values for both indices did not differ between groups per overlapping 95% confidence intervals. Therefore, RSA stability as assessed by both frequency (HF-HRV) and time domain (RMSSD) measures was not attenuated by a depression history. Implications and the need for future research are discussed.

Effects of current and past depressive episodes on behavioral performance and subjective experience during an N-back task.

BACKGROUND AND OBJECTIVES: Depression impairs working memory (WM). And, while many studies have documented impairment in WM during depression remission, those using the N-back task did not find differences between individuals with remitted depression and healthy controls. One reason for these findings may be that certain depression phenotypes, such as the childhood-onset form, which is likely to be associated with persistent WM problems, are underrepresented or unevenly represented in the studies. Because childhood-onset depression (COD) affects individuals while cognitive development is still ongoing, it is more likely to have lasting detrimental effects, as evidenced in residual memory impairment, than depression that onsets later in life. Further, it is unclear if depression episodes have cumulative effects on WM when measured via the N-back. METHODS: We examined the effects of depression on WM performance (response time, accuracy, signal detection d') and subjective experience (difficulty, mental effort required) during a four-level N-back task among 112 adults with COD (42 currently depressed; 70 remitted depressed) and 80 never-depressed controls. RESULTS: Compared to never-depressed controls, there was minimal evidence of impaired WM performance among participants with remitted or current depression; the groups also reported overall similar subjective experiences during the N-back. Notably, number of lifetime depressive episodes had a detrimental cumulative effect on response accuracy and d'. LIMITATIONS: WM was assessed only in regard to verbal memory. The sample size of currently depressed cases was smaller than that of the other groups. CONCLUSIONS: WM remains largely intact among adults with remitted COD, but increased number of depression episodes worsens WM performance.

History of major depressive disorder is associated with differences in implicit learning of emotional faces.

Major depressive disorder is often associated with worsened reward learning, with blunted reward response persisting after remission. In this study, we developed a probabilistic learning task with social rewards as a learning signal. We examined the impacts of depression on social rewards (facial affect displays) as an implicit learning signal. Fifty-seven participants without a history of depression and sixty-two participants with a history of depression (current or remitted) completed a structured clinical interview and an implicit learning task with social reward. Participants underwent an open-ended interview to evaluate whether they knew the rule consciously. Linear mixed effects models revealed that participants without a history of depression learned faster and showed a stronger preference towards the positive than the negative stimulus when compared to the participants with a history of depression. In contrast, those with a history depression learned slower on average and displayed greater variability in stimulus preference. We did not detect any differences in learning between those with current and remitted depression. The results indicate that on a probabilistic social reward task, people with a history of depression exhibit slower reward learning and greater variability in their learning behavior. Improving our understanding of alterations in social reward learning and their associations with depression and anhedonia may help to develop translatable psychotherapeutic approaches for modification of maladaptive emotion regulation.

Metabolic syndrome among young adults at high and low familial risk for depression.

BACKGROUND: Our study examined whether the early-onset depression phenotype among young adults (probands) is associated with the metabolic syndrome (MetS) and its components, and if MetS characterizes unaffected but high-risk siblings of probands. METHODS: We studied three groups of young adults (Mage = 25 years, s.d. = 3.84 years): probands with histories of childhood onset depression - i.e. early-onset phenotype - (n = 293), their unaffected siblings (high-risk siblings, n = 273), and healthy controls (n = 171). Participants completed a full psychiatric interview, physical and laboratory assessments, and self-rating scales. MetS was defined using the criteria of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (). RESULTS: Early-onset depression phenotype and being a high-risk sibling were associated with higher MetS composite scores relative to that of controls, but did not differ from one another. With regard to MetS components: Probands and siblings had similarly larger waist circumference and lower HDL than did controls, while siblings and controls had lower triglyceride levels than did probands but did not differ from one another. Groups did not differ on glucose levels and SBP. CONCLUSIONS: Our study extends the literature on the association between MetS and depression and underscores the importance of depression phenotypes: failure to account for the clinical heterogeneity of depression may partly underlie the inconsistent findings regarding its relation to MetS. The results also suggest that, in depression-prone populations, MetS may predate and possibly function as a risk factor for eventual depression.

Economic Choice and Heart Rate Fractal Scaling Indicate That Cognitive Effort Is Reduced by Depression and Boosted by Sad Mood.

BACKGROUND: People with depression typically exhibit diminished cognitive control. Control is subjectively costly, prompting speculation that control deficits reflect reduced cognitive effort. Evidence that people with depression exert less cognitive effort is mixed, however, and motivation may depend on state affect. METHODS: We used a cognitive effort discounting task to measure propensity to expend cognitive effort and fractal structure in the temporal dynamics of interbeat intervals to assess on-task effort exertion for 49 healthy control subjects, 36 people with current depression, and 67 people with remitted depression. RESULTS: People with depression discounted more steeply, indicating that they were less willing to exert cognitive effort than people with remitted depression and never-depressed control subjects. Also, steeper discounting predicted worse functioning in daily life. Surprisingly, a sad mood induction selectively boosted motivation among participants with depression, erasing differences between them and control subjects. During task performance, depressed participants with the lowest cognitive motivation showed blunted autonomic reactivity as a function of load. CONCLUSIONS: Discounting patterns supported the hypothesis that people with current depression would be less willing to exert cognitive effort, and steeper discounting predicted lower global functioning in daily life. Heart rate fractal scaling proved to be a highly sensitive index of cognitive load, and data implied that people with lower motivation for cognitive effort had a diminished physiological capacity to respond to rising cognitive demands. State affect appeared to influence motivation among people with current depression given that they were more willing to exert cognitive effort following a sad mood induction.

Ecological momentary assessment of affect in depression-prone and control samples: Survey compliance and affective yield.

BACKGROUND: Ecological momentary assessment (EMA) is a high-frequency ambulatory data collection approach that has come to be widely used in emotion research. It therefore is timely to examine two features of EMA needed for a successful study: compliance with survey prompts and high affective yield (survey prompts that capture affect experience). We posit that compliance may be subject to temporal variation (time-of-day, days in study) and individual differences (depression history), and that affective yield may also differ by social context. METHODS: We examined these issues in a sample of 318 young adults (Mage = 24.7 years, SD = 2.7), including those with current depression (n = 28), remitted depression (n = 168) and never-depressed controls (n = 122) who participated in a 7-day EMA protocol of negative and positive affect (NA and PA, respectively). RESULTS: The overall compliance rate was 91% and remained stable across the survey week. However, subjects were significantly less likely to respond to the first daily prompt compared to those that followed. The likelihood of capturing NA and PA decreased with each EMA protocol day, and affective yield across social contexts differed by participants' depression status. LIMITATIONS: The sample was largely comprised of White young adults. Relative to the remitted and control groups, the sample size for the currently depressed was unbalanced. CONCLUSION: Researchers can optimize compliance and affective yield within EMA by considering depression, time-of-day, study duration, and social context. Clinicians using EMA to monitor affect may benefit from considering these parameters.

Adiposity and Smoking Mediate the Relationship Between Depression History and Inflammation Among Young Adults.

BACKGROUND: Depression is associated with inflammation, but the mechanisms underlying this association are unclear. We examined adiposity and smoking as potential pathways through which childhood depression may lead to an elevated inflammatory status among young adults. METHODS: The sample included 294 subjects with histories of depression (probands), 270 never-depressed siblings of probands (high-risk siblings), and 169 controls. C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) were assessed in serum samples. An adiposity score was computed from body mass index and waist circumference. Smoking behavior was evaluated during an interview. Mixed-effects models were used to test whether adiposity and smoking mediate the relationship between depression and inflammation. RESULTS: Probands (p = .004), but not siblings (p = .071), had higher levels of sICAM-1 compared to controls. However, depression history and risk status had no direct effects on CRP (ps > .13) or IL-6 (ps > .16). Importantly, adiposity indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on all three inflammatory markers. Smoking indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on sICAM-1 only. CONCLUSIONS: Among young adults, the adverse inflammatory consequences of depression history are significant for sICAM-1. Adiposity and smoking are pathways through which depression can indirectly impact several inflammatory markers, suggesting possible preventive interventions to improve the immunologic and cardiovascular health of depression-prone individuals.

Age related sex differences in maladaptive regulatory responses to sadness: A study of youths at high and low familial risk for depression.

Offspring of parents with depression histories are at increased risk of developing depression and also report maladaptive ways of self-regulating sadness. Maladaptive regulation of sadness tends to be more prevalent among females than males and has been proposed as one explanation of sex differences in depression rates that emerge around mid-adolescence. However, there is scant information about the age at which the sex differences in maladaptive regulatory responses become evident and whether such age-related sex differences vary depending on depression risk. The present study examined two samples aged 8-18 years: 86 offspring of emotionally healthy parents and 98 offspring of parents with depression histories. Subjects were clinically assessed and provided self-reports of maladaptive responses to sadness. In the combined samples, sex differences in maladaptive responses were significant at age 12.5 years and older ages (i.e., chronologically earlier than the documented emergence of sex differences in depression). While in the high-risk group, sex differences in maladaptive regulatory responses were significant at 12.11 years of age and older, in the low-risk group there was no age at which sex differences were significant. Our findings support the possible mechanistic role of maladaptive emotion regulation in the emergence of sex disparities in depression rates and have implications for prevention.

Childhood-onset depression and arterial stiffness in young adulthood.

OBJECTIVES: The literature on childhood-onset depression and future compromised vascular function is suggestive but limited. The objective of this study was to determine if arterial stiffness, a predictor of future cardiovascular disease (CVD), measured in young adulthood, is associated with childhood-onset depression. METHODS: Cardiometabolic risk factors and pulse wave velocity (PWV), a measure of arterial stiffness, were cross-sectionally assessed in young adults with a history of childhood-onset depression (clinical diagnosis of major depressive episode or dysthymic disorder; N = 294 probands; initially recruited via child mental health facilities across Hungary; mean age of first depressive episode = 10.4 years), their never-depressed full biological siblings (N = 269), and never-depressed controls (N = 169). The mean ages of probands, siblings, and controls at the PWV visit were 25.6, 25.0, and 21.7 years, respectively, and 8.8% of the probands were in a current depressive episode. RESULTS: Controlling for age, sex, age*sex, education, and family clusters, PWV (m/s) did not statistically differ across the groups (probands = 7.01; siblings = 6.98; controls = 6.81). However, after adjusting for key covariates, there were several across-group differences in CVD risk factors: compared to controls, probands and siblings had higher diastolic blood pressure and lower high-density lipoprotein cholesterol, probands had higher triglycerides, and siblings had higher body mass index (all p < 0.05). CONCLUSION: We found limited evidence of an association between a history of childhood-onset depression and young adulthood arterial stiffness. However, our findings of elevated cardiovascular risk factors in those with childhood-onset depression suggest that pediatric depression may predispose to increased CVD risk later in life and warrants further investigation.

Sympathetic arousal during the processing of dysphoric affect by youths at high and low familial risk for depression.

Youths at high risk for depression have been shown to have problems in repairing their own sad mood. Given that sympathetic arousal has been implicated both in the experience and regulation of affect, an atypical pattern of arousal may be one of the factors that contribute to mood repair problems. In the current study, we measured sympathetic arousal of never-depressed youths at high (n = 56) and low (n = 67) familial risk for depression during sad mood induction and instructed mood repair. Sympathetic arousal was indexed by skin conductance level (SCL) and cardiac pre-ejection period (PEP); mood repair outcome was indexed by self-rated affect. High-risk youths demonstrated increased SCL during sadness induction, which persisted during mood repair; low-risk youths evidenced increased SCL only during mood repair. Shortened PEP was evident only among high-risk youths and only during mood repair. Furthermore, shortened PEP during mood induction predicted less successful mood repair in the low-risk but not in the high-risk group. The findings suggest that: (a) depression-prone youths differ from control peers in patterns of sympathetic responses to emotional stimuli, which may impair their ability to relieve sadness, and (b) activation patterns differ across subsystems (SCL vs. PEP) of sympathetic activity, in conjunction with depression risk status.

Cardiac vagal control mediates the relation between past depression and blood pressure several years later among young adults.

Depression has been associated with high blood pressure (BP). However, the mechanisms of the relation between depression and high BP are unclear. We therefore examined whether impaired cardiac vagal control, indexed as low levels of resting respiratory sinus arrhythmia (RSA), serves as a route from depression to high BP. The sample included 125 subjects with histories of depression (probands), 123 never depressed siblings of probands (high-risk siblings), and 156 controls. Resting RSA was assessed at Time 1 (T1) along with BP when subjects were adolescents (Mage  = 16.3 years); systolic and diastolic BP (SBP and DBP) were measured again at Time 2 (T2) when subjects were young adults (Mage  = 22.3 years). Linear mixed-effects models were used to examine the group differences in resting RSA and T2 BP outcomes and to test for RSA mediation of the relation between depression (history or being at high risk) and BP. Resting RSA was lower among probands than controls but was similar among high-risk siblings and controls, while the subject groups did not differ in T2 SBP or DBP. Controlling for T1 BP, depression history indirectly affected T2 DBP (but not SBP) through resting RSA. The findings suggest that, although the direct detrimental effects of depression on BP are not yet evident in young adulthood, among those with depression histories, impaired cardiac vagal control appears to serve as a mechanism of elevated DBP.

Maladaptive mood repair predicts suicidal behaviors among young adults with depression histories.

BACKGROUND: As the rates of suicidal behaviors continue to rise, research is needed that can facilitate prevention. The present study therefore examined whether a modifiable process, dysfunctional regulation of sadness (maladaptive mood repair), predicts a range of suicidal behaviors and if its impact is affected by risk and protective factors. METHODS: Young adults with histories of childhood-onset mood disorder (COMD) (n = 173) or no histories of major psychiatric illness (controls, n = 96) were followed for approximately 3 years. Self-rated questionnaires and psychiatric evaluations were administered at study entry (T1) and across the follow-up (T2) and clinicians assessed the DSM-range of non-fatal suicidal behaviors. We hypothesized that the impact of depression on suicidal behaviors was mediated by dysfunctional regulation of sadness. RESULTS: At T1, 90% of the COMD group had histories of various suicidal behaviors; 63% had past suicide attempts. During follow-up, 40% exhibited suicidal behaviors; 7% reported suicide attempts. Controlling for prior suicidal behaviors, T1 maladaptive mood repair predicted suicidal behavior during the follow-up and differentiated recurrent thoughts of death from other forms of suicidality. Protective and risk factors lost their predictive power in the presence of maladaptive mood repair. LIMITATIONS: Few control cases exhibited suicidal behavior during the follow-up and the high inter-correlations among several key variables constrained the models that could be fitted. CONCLUSIONS: Programs to prevent suicidal behavior among high-risk individuals should include maladaptive mood repair as an intervention target. Further research is needed on whether recurrent thoughts of death constitute a valid index of suicidality.

Autonomic correlates of lifetime suicidal thoughts and behaviors among adolescents with a history of depression.

Suicidal thoughts and behaviors (STBs) have been associated with emotion dysregulation and atypical responses to affective and stressful stimuli. To investigate the psychophysiology involved, we measured changes in respiratory sinus arrhythmia (RSA) and cardiac pre-ejection period (PEP; indexing parasympathetic and sympathetic functioning, respectively) in response to stressful- and sadness-eliciting laboratory probes. Our sample included adolescents with a history of depression and STBs (n = 177), adolescents with a history of depression but no history of STBs (n = 47), and healthy controls (n = 175). The outcome of interest was the most severe form of clinician-rated STBs across the subject's lifetime. In partial support of our hypotheses, during the stressful task, adolescents with a history of depression and STBs did not evidence the RSA decrease that was exhibited by controls and displayed greater PEP shortening compared to ever-depressed adolescents with no lifetime STBs. No group differences were found in either RSA or PEP reactivity to the sadness-eliciting stimulus. As expected, severity of STBs was positively correlated with the extent of PEP shortening during the stressful task. The results suggest that adolescents with a history of depression and STBs experience blunted parasympathetic responses to stress along with compensatory efforts. Our findings contribute to a better understanding of STBs among youths and underscore that future studies should examine physiological risk factors for these psychopathological outcomes.

Adversity and Depression: The Moderating Role of Stress Reactivity among High and Low Risk Youth.

Adverse life events have been causally linked to depression among youth at high risk for depression. But given that not all high-risk youth develop depression following adversity, individual differences in various processes, including physiological reactivity to stress, are likely to be at play. This longitudinal prospective study tested the hypothesis that, among high-risk youth exposed to adversities, extent of physiological reactivity to laboratory stress (indexed as respiratory sinus arrhythmia; RSA) would predict subsequent depressive symptoms. Subjects were youth at high (n = 80) and low (n = 74) familial risk for depression. At Time 1 (T1), RSA was assessed during a cognitive stress task. At Time 2 (T2) about 2 years later, parents reported on adversities experienced by their offspring during the interim. At T1 and T2, youth received a diagnostic evaluation, which included assessment of their depressive symptoms. The three-way interaction of group-X-adversities-X-RSA predicted T2 depressive symptoms (controlling for T1 depressive symptoms). This interaction was mostly driven by the moderating effect of RSA among high-risk youth, such that adversities predicted higher depressive symptoms for those who displayed greater RSA reactivity to stress. Among low-risk youth, an inverse marginal moderating effect of RSA was found, such that adversities tended to predict depressive symptoms for those who displayed blunted RSA reactivity to stress. Thus, high physiological stress reactivity appears to be an additional risk factor for depressive symptoms only among youth at elevated risk for such outcomes, and should be taken into consideration in efforts to prevent depression in these populations.

Dysregulated behavioral responses to hedonic probes among youth with depression histories and their high-risk siblings.

Affect dysregulation in response to rewarding stimuli has been proposed as a vulnerability factor for major depressive disorder (MDD). However, it remains unclear how affective behavioral dynamics may be altered among individuals who are at high risk for depression but not currently depressed. We examined the dynamics of affective facial behavior during hedonic probes among 3 groups of adolescents: remitted probands who had histories of childhood-onset MDD (n = 187), never-depressed siblings of probands (high familial risk; n = 207), and healthy controls (n = 166). Participants' happy and sad facial expressions were coded during 3 hedonic laboratory tasks: receiving a preferred prize, describing a positive autobiographical memory, and watching a humorous film. Happy and sad behavioral dynamics were indexed by mean level- and time-dependent reactivity, variability (mean of the squared successive differences), and inertia (autocorrelation). Relative to controls, probands and siblings exhibited a more rapid decrease in happy behaviors, and probands exhibited higher inertia of sad behaviors during hedonic probes. Both probands and siblings exhibited lower inertia of sad behaviors while receiving a desired prize, which highlights the importance of context variation in testing hypotheses. Overall, our study provides new evidence that hedonic behavioral dysregulation, as reflected in dynamic facial behavior, may highlight depression vulnerability. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Family functioning as perceived by parents and young offspring at high and low risk for depression.

BACKGROUND: Family dysfunction has been proposed as one of the environmental mechanisms whereby risk of depression is transmitted from mothers to their children. Using our sample of offspring at high and low familial risk for depression, we hypothesized that: a) high-risk offspring (n = 79) and their mothers will report more extensive family dysfunction than low-risk offspring (n = 82) and their mothers, b) family dysfunction will predict the extent of offspring's depressive symptoms, and c) family dysfunction will mediate the impact of mother's depression on offspring's depressive symptoms. METHODS: The study enrolled 161 offspring of parents who, in a previous study, were ascertained to have either childhood onset mood disorder or no history of a major psychiatric disorder. Parents completed questionnaires and a clinical interview about themselves, their offspring, and the family, while offspring also completed questionnaires about themselves and the family. RESULTS: We found support for all three hypotheses. The significant indirect effect between maternal depression and offspring depressive symptoms was driven primarily by offspring's, but not mothers', reports of family dysfunction. LIMITATIONS: Although our assessment of mother's early history of depression was done in a previous study, it is important to note that our results do not inform about causality because of the present study's cross-sectional nature. CONCLUSIONS: The results highlight the importance of detecting and treating family dysfunction, particularly via offspring report, as one way to lower the risk of depression transmission from mothers to their children.

Childhood adversity predicts reduced physiological flexibility during the processing of negative affect among adolescents with major depression histories.

BACKGROUND: Adversity during early development has been shown to have enduring negative physiological consequences. In turn, atypical physiological functioning has been associated with maladaptive processing of negative affect, including its regulation. The present study therefore explored whether exposure to adverse life events in childhood predicted maladaptive (less flexible) parasympathetic nervous system functioning during the processing of negative affect among adolescents with depression histories. METHODS: An initially clinic-referred, pediatric sample (N=189) was assessed at two time points. At Time 1, when subjects were 10.17years old (SD=1.42), on average, and were depressed, parents reported on adverse life events the offspring experienced up to that point. At Time 2, when subjects were 17.18years old (SD=1.28), and were remitted from depression, parents again reported on adverse life events in their offspring's lives for the interim period. At time 2, subjects' parasympathetic nervous system functioning (quantified as respiratory sinus arrhythmia) also was assessed at rest, during sad mood induction, and during instructed mood repair. RESULTS: Extent of adverse life events experienced by T1 (but not events occurring between T1 and T2) predicted less flexible RSA functioning 7years later during the processing of negative affect. Adolescents with more extensive early life adversities exhibited less vagal withdrawal following negative mood induction and tended to show less physiological recovery following mood repair. CONCLUSIONS: Early adversities appear to be associated with less flexible physiological regulatory control during negative affect experience, when measured later in development. Stress-related autonomic dysfunction in vulnerable youths may contribute to the unfavorable clinical prognosis associated with juvenile-onset depression.

Positive Affectivity is Dampened in Youths with Histories of Major Depression and Their Never-Depressed Adolescent Siblings.

While hedonic capacity is diminished during clinical depression, it is unclear whether that deficit constitutes a risk factor and/or persists after depression episodes remit. To examine these issues, adolescents with current/past major depression (probands; n=218), never depressed biological siblings of probands (n=207), and emotionally-well controls (n=183) were exposed to several positively valenced probes. Across baseline and hedonic probe conditions, controls consistently reported higher levels of positive affect than high-risk siblings, and siblings reported higher levels of positive affect than probands (remitted and depressed probands' reports were similar). Extent of positive affect across the protocol predicted adolescents' self-reports of social support network and parental reports of offspring's use of various adaptive mood repair responses in daily life. Attenuated hedonic responding among youths remitted from depression offers partial support for anhedonia as a trait, while its presence among never depressed high-risk siblings argues for anhedonia as a potential diathesis for clinical depression.

Juvenile onset depression alters cardiac autonomic balance in response to psychological and physical challenges.

Cardiac autonomic balance (CAB) indexes the ratio of parasympathetic to sympathetic activation (Berntson, Norman, Hawkley, & Cacioppo, 2008), and is believed to reflect overall autonomic flexibility in the face of environmental challenges. However, CAB has not been examined in depression. We examined changes in CAB and other physiological variables in 179 youth with a history of juvenile onset depression (JOD) and 161 healthy controls, in response to two psychological (unsolvable puzzle, sad film) and two physical (handgrip, and forehead cold pressor) challenges. In repeated measures analyses, controls showed expected reductions in CAB for both the handgrip and unsolvable puzzle, reflecting a shift to sympathetic relative to parasympathetic activation. By contrast, JOD youth showed increased CAB from baseline for both tasks (p's<.05). No effects were found for the forehead cold pressor or sad film tasks, suggesting that CAB differences may arise under conditions requiring greater attentional control or sustained effort.