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.

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.

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.

Mood repair via attention refocusing or recall of positive autobiographical memories by adolescents with pediatric-onset major depression.

BACKGROUND: Impaired emotion regulation is increasingly recognized as a core feature of depressive disorders. Indeed, currently and previously depressed adults both report greater problems in attenuating sadness (mood repair) in daily life than healthy controls. In contrast, studies of various strategies to attenuate sad affect have mostly found that currently or previously depressed adults and controls were similarly successful at mood repair in the laboratory. But few studies have examined mood repair among depression-prone youths or the effects of trait characteristics on mood repair outcomes in the laboratory. METHODS: Adolescents, whose first episode of major depressive disorder (MDD) had onset at age 9, on average (probands), and were either in remission or depressed, and control peers, watched a sad film clip. Then, they were instructed to engage in refocusing attention (distraction) or recalling happy memories. Using affect ratings provided by the youths, we tested two developmentally informed hypotheses about whether the subject groups would be similarly able to attenuate sadness via the two mood repair strategies. We also explored if self-reported habitual (trait) mood repair influenced laboratory performance. RESULTS: Contrary to expectations, attention refocusing and recall of happy memories led to comparable mood benefits across subjects. Control adolescents reported significantly greater reductions in sadness than did depressed (Cohen's d = .48) or remitted (Cohen's d = .32) probands, regardless of mood repair strategy, while currently depressed probands remained the saddest after mood repair. Habitual mood repair styles moderated the effects of instructed (state) mood repair in the laboratory. CONCLUSIONS: Whether depressed or in remission, adolescents with MDD histories are not as efficient at mood repair in the laboratory as controls. But proband-control group differences in mood repair outcomes were modest in scope, suggesting that the abilities that subserve affect regulation have been preserved in probands to some degree. Further information about the nature of mood repair problems among youths with depression histories would help to better understand the clinical course of MDD and to design personalized interventions for depression.

The association between major depressive disorder in childhood and risk factors for cardiovascular disease in adolescence.

OBJECTIVE: Depression in adults is associated with risk factors for cardiovascular disease (CVD). It is unclear, however, when the association between clinical depression and cardiac risk factors develops or how early in life this association can be detected. METHODS: In an ongoing study of pediatric depression, we compared CVD risk factors including smoking, obesity, physical activity level, sedentary behavior, and parental history of CVD across three samples of adolescents: probands with established histories of childhood-onset major depressive disorder (n = 210), never-depressed siblings of probands (n = 195), and controls with no history of any major psychiatric disorder (n = 161). RESULTS: When assessed during adolescence, 85% of the probands were not in a major depressive episode. Nevertheless, at that assessment, probands had a higher prevalence of regular smoking (odds ratio [OR] = 12.54, 95% confidence interval [CI] = 4.36-36.12) and were less physically active than controls (OR = 0.59, CI = 0.43-0.81) and siblings (OR = 0.70, CI = 0.52-0.94) and had a higher rate of obesity than did controls (OR = 3.67, CI = 1.42-9.52). Parents of probands reported high rates of CVD (significantly higher than did parents of controls), including myocardial infarction and CVD-related hospitalization (ORs = 1.62-4.36, CIs = 1.03-15.40). Differences in CVD risk factors between probands and controls were independent of parental CVD. CONCLUSIONS: Major depression in childhood is associated with an unfavorable CVD risk profile in adolescence, and risks for pediatric depression and CVD may coincide in families. Effective prevention and treatment of childhood depression may be a means to reduce the incidence of adult CVD.

Using music to maintain the correct rhythm during CPR.

BACKGROUND: Cardiopulmonary resuscitation is a competency required of all health professionals, but they do not always meet chest compression standards. METHOD: Nurses received a traditional chest compression demonstration or one with music. Their compression rates were measured and compared. RESULTS: After instruction, 66% of nurses who had received demonstration with music performed chest compressions within the recommended range, compared with 41% of those receiving traditional demonstration. CONCLUSION: Using music when teaching CPR can improve nurses' performance of chest compressions at the recommended rate.

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.

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.

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.

Association study of early-immediate genes in childhood-onset mood disorders and suicide attempt.

Childhood-onset mood disorders (COMD) are serious affective disorders with deleterious developmental sequelae including interpersonal dysfunction, psychotic symptoms and suicidal behavior. The current study examines 10 markers from two early-immediate genes for association with COMD and suicide attempt (SA) - HOMER1 and human neuronal pentraxin II (NPTX2). We examined individuals diagnosed with COMD versus matched controls, as well as individuals with COMD and a history of at least one lifetime SA versus COMD participants with no history of SA. No significant genotypic association was noted between any of the single nucleotide polymorphisms (SNPs) and COMD. Our sample yielded a nominally significant allelic association between the HOMER1 rs7713917 SNP and COMD. We report significant genotype associations between HOMER1 rs2290639 and SA , and between NPTX2 markers rs705315 and rs1681248 and SA, findings that remained statistically significant after multiple test correction. A three-way interaction was observed among HOMER1 rs4704560, rs2290639 and NPTX2 rs705318. The associations we describe for HOMER1 and NPTX2 with SA should be considered preliminary until replicated.

Atypical development of resting respiratory sinus arrhythmia in children at high risk for depression.

Compromised respiratory sinus arrhythmia (RSA, i.e., low cardiac vagal control) frequently characterizes clinically depressed adults and also has been detected in infants of depressed mothers; however, its existence has not been established in older at-risk offspring. We investigated developmental patterns of RSA in a sample of 163 5- to 14-year-old children, who were either at high risk for depression (due to having a parent with a childhood-onset mood disorder) or low-risk for depression. We hypothesized that high-risk children have lower resting RSA than do low-risk children, which could reflect atypical developmental trajectories. Children's RSA was assessed during resting baseline periods on multiple occasions, typically 1-year apart. Linear growth modeling indicated a group by age interaction. Low-risk children (but not the high-risk children) exhibited a significantly increasing trajectory in resting RSA with age. Mood disorders in offspring did not account for the Group X Age interaction effect. Our study provides new evidence that children at high risk for depression have an atypical developmental trajectory of RSA across late childhood.

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.

Developmental trajectories of positive and negative affect in children at high and low familial risk for depressive disorder.

BACKGROUND: Although low positive affect (PA) and high negative affect (NA) have been posited to predispose to depressive disorders, little is known about the developmental trajectories of these affects in children at familial risk for mood disorders. METHODS: We examined 202 offspring of mothers who had a history of juvenile-onset unipolar depressive disorder (n = 60) or no history of major psychopathology (n = 80). Offspring participated in up to seven annual, structured laboratory tasks that were designed to elicit PA and NA. RESULTS: Growth curve analyses revealed that PA increased linearly and similarly for all children from late infancy through age 9. However, there also were individual differences in early PA. Relative to control peers, offspring of mothers with lifetime unipolar depression had consistently lower levels of PA, and this association remained significant even when controlling for current maternal depression and maternal affect displays. Growth curve analyses also revealed a significant linear decrease in NA in children across time; however, there was no significant inter-individual variation either in early NA or rate of change in NA. CONCLUSION: Attenuated PA (rather than excessive NA) may be an early vulnerability factor for eventual unipolar depressive disorder in at-risk children and may represent one pathway through which depression is transmitted.

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.

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.

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.

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.