Circulating Cell-Free Mitochondrial DNA and Depressive Symptoms Among Low-Active Adults Who Smoke.

OBJECTIVES: Mitochondrial dysfunction is implicated in the pathophysiology of psychiatric disorders. Levels of circulating cell-free mitochondrial DNA (cf-mtDNA) are observed to be altered in depression. However, the few studies that have measured cf-mtDNA in depression have reported conflicting findings. This study examined cf-mtDNA and depressive symptoms in low-active adults who smoke. METHODS: Participants were adults 18 to 65 years old ( N = 109; 76% female) with low baseline physical activity and depressive symptoms recruited for a smoking cessation study. Self-report measures assessed depression severity, positive and negative affect, and behavioral activation. Blood was collected and analyzed for cf-mtDNA. Relationships between depressive symptoms and cf-mtDNA were examined with correlations and linear regression. RESULTS: Levels of cf-mtDNA were associated with categorically defined depression (Center for Epidemiologic Studies Depression Scale score >15), lower positive affect, and decreased behavioral activation ( p < .05). Relationships remained significant after adjustment for age, sex, and nicotine dependence. In a linear regression model including all depressive symptom measures as predictors, Center for Epidemiologic Studies Depression Scale group and lower positive affect remained significant. CONCLUSIONS: This work suggests that mitochondrial changes are associated with depressive symptoms in low-active adults who smoke. Higher levels of cf-mtDNA in association with depression and with lower positive affect and decreased behavioral activation are consistent with a possible role for mitochondrial function in depressive symptoms.

Randomized Controlled Trial of Aerobic Exercise for Smoking Cessation among Individuals with Elevated Depressive Symptoms.

INTRODUCTION: Adults with depression have higher rates of cigarette smoking and are more likely to relapse than those without depression. Pharmacological, psychological, and combined interventions have largely yielded small improvements in smoking outcomes for adults with depression. Aerobic exercise (AE) may facilitate smoking cessation in this subpopulation. METHODS: This study was a 12-week two-arm randomized controlled trial that evaluated the effect of a moderate-intensity AE program compared to a health education contact (HEC) control on smoking cessation in adults with elevated depressive symptoms (mild to severe). Participants (n=231) were randomized to AE or HEC and received smoking cessation treatment (telephone counseling and nicotine replacement therapy). Primary (biologically confirmed 7-day point prevalence abstinence) and secondary (depressive symptoms, objective and self-reported physical activity, and cardiorespiratory fitness) outcomes were assessed at baseline, 3-, 6-, and 12-months. Data were analyzed with mixed-effects generalized linear models controlling for age, gender, nicotine dependence, history of major depression disorder, and month of follow-up assessment. RESULTS: There were no significant differences in primary or secondary outcomes between the AE and HEC groups. CONCLUSIONS: The AE program was not superior to HEC in facilitating smoking cessation, increases in physical activity, or improved depressive symptoms. Given evidence for the positive acute effects of exercise on mood and smoking urges, future research should consider testing alternative exercise approaches for aiding smoking cessation beyond structured, aerobic exercise programs. IMPLICATIONS: This study found that an adjunctive aerobic exercise (AE) program was not superior to a health education contact control for adults with elevated depressive symptoms, all of whom also received standard smoking cessation treatment. This finding adds to the growing body of literature that structured aerobic exercise programs for smoking cessation may have limited efficacy for cessation outcomes. Future research is needed to test alternative methods of integrating AE into smoking cessation treatment, such as strategically using exercise to manage cravings and low mood in the moment.

Modeling the antidepressant treatment response to transcranial magnetic stimulation using an exponential decay function.

Recovery from depression often demonstrates a nonlinear pattern of treatment response, where the largest reduction in symptoms is observed early followed by smaller improvements. This study investigated whether this exponential pattern could model the antidepressant response to repetitive transcranial magnetic stimulation (TMS). Symptom ratings from 97 patients treated with TMS for depression were collected at baseline and after every five sessions. A nonlinear mixed-effects model was constructed using an exponential decay function. This model was also applied to group-level data from several published clinical trials of TMS for treatment-resistant depression. These nonlinear models were compared to corresponding linear models. In our clinical sample, response to TMS was well modeled with the exponential decay function, yielding significant estimates for all parameters and demonstrating superior fit compared to a linear model. Similarly, when applied to multiple studies comparing TMS modalities as well as to previously identified treatment response trajectories, the exponential decay models yielded consistently better fits compared to linear models. These results demonstrate that the antidepressant response to TMS follows a nonlinear pattern of improvement that is well modeled with an exponential decay function. This modeling offers a simple and useful framework to inform clinical decisions and future studies.

Corrigendum to "Associations of circulating cell-free DNA, C-reactive protein, and cardiometabolic risk among low-active smokers with elevated depressive symptoms" [Brain Behav. Immun. - Health 25 (2022) 100519].

[This corrects the article DOI: 10.1016/j.bbih.2022.100519.].

An examination of the effects of distress intolerance and rating of perceived exertion on changes in mood and anxiety following aerobic exercise among treatment-seeking smokers.

Aerobic exercise is frequently used as an intervention for depression and smoking cessation because of its antidepressant and anxiolytic effects. Distress intolerance (DI) is a proposed individual difference factor that, coupled with a higher rating of perceived exertion during exercise, may significantly impact the acute mood and anxiolytic effects of exercise. The current study examined the interactive effect of maximum rating of perceived exertion (RPE) and DI on change in mood and anxiety. Treatment-seeking smokers (Mage = 45.32; 72% female) with elevated depressive symptoms completed a 1-mile treadmill walk at their preferred intensity and self-reported their RPE during the test. Analyses were conducted to examine whether there was an interactive effect of maximum RPE and DI on change in self-reported mood and anxiety from before to after the walk test. Findings indicate a significant moderating effect of RPE at lower ratings. Individuals reporting a low maximum RPE and higher DI exhibit a greater change in mood over the course of an exercise session, whereas individuals reporting a low maximum RPE and a lower DI exhibit smaller changes in mood. These results indicate that the subjective effects of exercise within a population of cigarette smokers could be improved by tailoring exercise intensity to individual characteristics. Mild to moderate-intensity exercise, as compared to high-intensity exercise, may result in greater changes in mood for individuals endorsing difficulty tolerating affective and physical distress.

Associations of circulating cell-free DNA, C-reactive protein, and cardiometabolic risk among low-active smokers with elevated depressive symptoms.

Background and aims: Cell-free DNA (cfDNA) is elevated in several disease states. Metabolic syndrome is a constellation of factors associated with poor cardiometabolic outcomes. This study examined associations of cfDNA from the nucleus (cf-nDNA) and mitochondria (cf-mtDNA), C-reactive protein (CRP), and metabolic syndrome risk, in low-active smokers with depressive symptoms. Methods: Participants (N = 109; mean age 47) self-reported medical history. Physical activity was determined by accelerometry and anthropometrics were measured. Blood was collected and analyzed for cf-nDNA, cf-mtDNA, CRP, triglycerides, high-density lipoprotein, hemoglobin A1c. A continuous metabolic syndrome composite risk score was calculated. Relationships of cf-nDNA, cf-mtDNA, CRP, and cardiometabolic risk were examined with correlations and linear regression. Results: CRP and cf-nDNA were significantly associated with metabolic syndrome risk (r = .39 and r = .31, respectively), cf-mtDNA was not (r = .01). In a linear regression, CRP and cf-nDNA significantly predicted the metabolic syndrome risk score, findings that remained significant controlling for age, gender, nicotine dependence, and physical activity. Conclusions: Associations of cf-nDNA with both CRP and metabolic risk suggest a role for cf-nDNA in inflammatory processes associated with metabolic syndrome. The negative findings for cf-mtDNA suggest distinct roles for cf-nDNA and cf-mtDNA in these processes.

Stakeholder perspectives on adjunctive mHealth services during transitions of care for patients with schizophrenia-spectrum disorders.

BACKGROUND: A growing body of research focuses on developing and testing interventions that leverage mental health-related mobile health (mHealth) services for patients with schizophrenia and other schizophrenia-spectrum disorders. Yet, most formative research has focused on patient perspectives, with little attention paid to clinical stakeholders. AIMS: This qualitative study aimed to explore clinical stakeholders' (i.e., administrative supervisors, support staff, and clinicians) perspectives on what might help or hinder the use of mHealth, particularly when patients transition from inpatient to outpatient care. METHODS: In-depth individual qualitative interviews were conducted with 18 stakeholders from inpatient and outpatient psychiatric settings. RESULTS: Four key themes were identified: (a) adherence challenges; (b) role of mobile technology in patient care; (c) clinical professionals' receptiveness to adjunctive mHealth services; and, (d) costs related to implementation of mHealth services. CONCLUSIONS: Overall, stakeholders agree with extant data showing that supportive networks are important in facilitating patients' return to the community following hospitalization. Stakeholders welcome mHealth services but suggest they should be appropriately tailored to the population, both in terms of usability and connection to ongoing traditional treatments. Demonstration of added value will likely facilitate wider implementation of mHealth services in the care of patients with schizophrenia and other schizophrenia-spectrum disorders.

Examining the effect of exercise on the relationship between affect and cravings among smokers engaged in cessation treatment.

Cigarette smoking is associated with multiple adverse health outcomes. When smokers attempt to quit smoking, one of the leading predictors of relapse are cravings. Recent research shows a relationship between positive and negative affect, exercise, and cravings, but the exact nature of this relationship has yet to be understood. This study explored the relationships between positive and negative affect and cravings in a sample of participants with elevated levels of depressive symptoms (N = 202; 68.8% female; mean age = 46.1 years) who were enrolled in a smoking cessation trial to test the efficacy of a 12-week exercise intervention relative to a health education control on smoking outcomes. Data on affect and craving were gathered before weekly study intervention sessions, and data on cravings were gathered again after each session. The results showed that negative affect had a significant and positive association with cravings before an exercise or health education session. After the session, positive and negative affect were not significant predictors of changes in cravings from pre-session. However, regardless of level of positive or negative affect participants in the exercise condition showed greater reductions in craving pre- to post-class than those in the control condition. These findings suggest that negative affect is associated with cravings, but cravings can be mitigated by exercise.

A pilot randomized controlled trial of smartphone-assisted mindfulness-based intervention with contingency management for smokers with mood disorders.

Cigarette smoking disproportionately affects individuals with mood disorders, but smoking cessation interventions have modest effects in this population. Home mindfulness practice during abstinence incentivized via contingency management (CM) may help those in affective distress quit smoking. METHOD: Adult smokers receiving outpatient psychiatric treatment for mood disorders were randomized to receive a smartphone-assisted mindfulness-based smoking cessation intervention with contingency management (SMI-CM, n = 25) or enhanced standard treatment (EST, n = 24) with noncontingent rewards. Participants in SMI-CM were prompted to practice audio-guided mindfulness five times per day for 38 days (vs. no comparison intervention in EST), and received monetary incentives for carbon monoxide (CO) ≤ 6 ppm. The primary outcome was biochemically verified 7-day point prevalence abstinence rates 2, 4, and 13 weeks after a target quit day. RESULTS: Of the 49 participants, 63.3% were Latinx and 30.6% Black; 75.5% reported household incomes < $25,000. Abstinence rates for SMI-CM were 40.0%, 36.0%, and 16.0% versus 4.2%, 8.3%, and 4.2% in EST at weeks 2, 4, and 13. A generalized estimating equations (GEE) model showed significant overall differences in abstinence rates in SMI-CM versus EST (adjusted odds ratio [AOR] = 8.12, 95% CI = 1.42-46.6, p = .019). Those who received SMI-CM reported significantly greater reduction in smoking-specific experiential avoidance from baseline to 3 days prior to quit date (ß = -7.21, 95% CI = -12.1-2.33, p = .006). CONCLUSIONS: SMI-CM may increase cessation rates among smokers with mood disorders, potentially through reduced smoking-specific experiential avoidance. SMI-CM is a promising intervention, and warrants investigation in a fully powered randomized controlled trial (RCT). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Readiness to Quit Smoking among Smokers in Substance Use Treatment: Associations with Stress, Substance Use Severity, Relapse Concerns and Gender.

Smoking prevalence among individuals in substance use treatment remains higher than in the general population. Given that many smokers in substance use treatment are reluctant to quit smoking, it is important to understand the factors that impede smokers' readiness to quit. The current study used baseline data from a randomized controlled trial involving 60 adult smokers receiving substance use treatment to investigate relations between the severity of substance use problems (SSUP), perceived stress (PS), concerns about relapse (i.e., concerns that quitting smoking would hurt one's recovery process (CR)), and readiness to quit smoking. This study also investigated moderating roles of concerns about relapse and gender. Regression analyses showed a significant main effect of concerns about relapse on readiness to quit in the next 30 days, but no effect for either severity of substance use problems, perceived stress, or the SSUPxCR interaction. There were significant interaction effects between PS and both gender and CR. Among men and those with lower concerns about relapse, higher perceived stress was significantly associated with lower readiness to quit. Findings suggest that psychoeducation to alleviate concerns that quitting smoking could limit substance use recovery could be beneficial. Stress management interventions may be especially beneficial to men.

Sustained Care Smoking Cessation Intervention for Individuals Hospitalized for Psychiatric Disorders: The Helping HAND 3 Randomized Clinical Trial.

Importance: Smoking among individuals with serious mental illness (SMI) represents a major public health problem. Intervening during a psychiatric hospital stay may provide an opportunity to aid engagement in smoking cessation treatment and facilitate success in quitting. Objective: To examine the effectiveness of a multicomponent, sustained care (SusC) smoking cessation intervention in adults with SMI receiving inpatient psychiatric care. Design, Setting, and Participants: The Helping HAND 3 randomized clinical trial compared SusC with usual care (UC) among individuals with SMI who smoked daily and were receiving inpatient psychiatric care in Austin, Texas, in a single hospital. The study was conducted from July 2015 through August 2019. Interventions: The UC intervention involved brief smoking cessation information, self-help materials and advice from the admitting nurse, and an offer to provide nicotine replacement therapy during hospitalization. The SusC intervention included 4 main components designed to facilitate patient engagement with postdischarge smoking cessation resources: (1) inpatient motivational counseling; (2) free transdermal nicotine patches on discharge; (3) an offer of free postdischarge telephone quitline, text-based, and/or web-based smoking cessation counseling, and (4) postdischarge automated interactive voice response calls or text messages. Main Outcomes and Measures: The primary outcome was biochemically verified 7-day point-prevalence abstinence at 6-month follow-up. A secondary outcome was self-reported smoking cessation treatment use at 1, 3, and 6 months after discharge. Results: A total of 353 participants were randomized, of whom 342 were included in analyses (mean [SD] age, 35.8 [12.3] years; 268 White individuals [78.4%]; 280 non-Hispanic individuals [81.9%]; 169 women [49.4%]). They reported smoking a mean (SD) of 16.9 (10.4) cigarettes per day. Participants in the SusC group evidenced significantly higher 6-month follow-up point-prevalence abstinence rates than those in the UC group (8.9% vs 3.5%; adjusted odds ratio, 2.95 [95% CI, 1.24-6.99]; P = .01). The number needed to treat was 18.5 (95% CI, 9.6-306.4). A series of sensitivity analyses confirmed effectiveness. Finally, participants in the SusC group were significantly more likely to report using smoking cessation treatment over the 6 months postdischarge compared with participants in the UC group (74.6% vs 40.5%; relative risk, 1.8 [95% CI, 1.51-2.25]; P < .001). Conclusions and Relevance: The findings of this randomized clinical trial provide evidence for the effectiveness of a scalable, multicomponent intervention in promoting smoking cessation treatment use and smoking abstinence in individuals with SMI following hospital discharge. Trial Registration: ClinicalTrials.gov Identifier: NCT02204956.

Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week Randomized Placebo-Controlled Study.

OBJECTIVE: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. METHODS: The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity. RESULTS: The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo. CONCLUSIONS: Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.

Molecular markers of neuroendocrine function and mitochondrial biogenesis associated with early life stress.

OBJECTIVE: Glucocorticoid receptor gene (NR3C1) promoter methylation influences cellular expression of the glucocorticoid receptor and is a proposed mechanism by which early life stress impacts neuroendocrine function. Mitochondria are sensitive and responsive to neuroendocrine stress signaling through the glucocorticoid receptor, and recent evidence with this sample and others shows that mitochondrial DNA copy number (mtDNAcn) is increased in adults with a history of early stress. No prior work has examined the role of NR3C1 methylation in the association between early life stress and mtDNAcn alterations. METHODS: Adult participants (n = 290) completed diagnostic interviews and questionnaires characterizing early stress and lifetime psychiatric symptoms. Medical conditions, active substance abuse, and prescription medications other than oral contraceptives were exclusionary. Subjects with a history of lifetime bipolar, obsessive-compulsive, or psychotic disorders were excluded; individuals with other forms of major psychopathology were included. Whole blood mtDNAcn was measured using qPCR; NR3C1 methylation was measured via pyrosequencing. Multiple regression and bootstrapping procedures tested NR3C1 methylation as a mediator of effects of early stress on mtDNAcn. RESULTS: The positive association between early adversity and mtDNAcn (p = .02) was mediated by negative associations of early adversity with NR3C1 methylation (p = .02) and NR3C1 methylation with mtDNAcn (p < .001). The indirect effect involving early adversity, NR3C1 methylation, and mtDNAcn was significant (95 % CI [.002, .030]). CONCLUSIONS: NR3C1 methylation significantly mediates the association between early stress and mtDNAcn, suggesting that glucocorticoid receptor signaling may be a mechanistic pathway underlying mtDNAcn alterations of interest for future longitudinal work.

Anxiety sensitivity and daily cigarette smoking in relation to sleep disturbances in treatment-seeking smokers.

Although the association between anxiety and sleep disturbance is well-documented, the underlying mechanisms are less clear. Anxiety sensitivity (AS), the fear of physiological arousal and bodily sensations, is a risk factor for anxiety and poor sleep. Smoking also contributes to poor sleep and may compound the effects of AS on sleep quality. This study evaluated the main and interactive effects of AS and cigarettes/day on sleep quality among smokers. Participants (n = 190) were adult treatment-seeking daily smokers who completed a baseline assessment as part of a larger smoking cessation trial. Sleep quality was self-reported. Results indicated that AS was significantly correlated with greater disturbance in sleep duration, subjective sleep quality, sleep onset latency, sleep disturbance, daytime dysfunction, and sleep medication use. There was a significant interaction between AS and cigarettes/day in terms of sleep onset latency, but not other sleep quality indices. AS was associated with significantly longer sleep onset latency minutes among heavier smokers, but not lighter smokers. Specifically, the association between AS and sleep onset latency was significant for those who smoked ≥ 33 cigarettes/day. AS is a psychological factor that may contribute to poor sleep quality, especially in heavy smokers, and thus may be a promising intervention target.

Dose increase of S-Adenosyl-Methionine and escitalopram in a randomized clinical trial for major depressive disorder.

BACKGROUND: The optimal dose of S-adenosyl methionine (SAMe) for major depressive disorder (MDD) remains unclear. The objective of this analysis was to address whether a dose increase provided further improvement in cases of insufficient response using data from an existing randomized clinical trial. METHODS: Sixty-five patients with MDD who failed to respond to SAMe 1,600 mg/day, escitalopram 10 mg/day, or placebo for 6 weeks were treated with doubled doses of the allocated treatments for the following 6 weeks. Changes in 17-item Hamilton Depression Rating Scale, Inventory of Depressive Symptomatology-Self Rated, and Systematic Assessment for Treatment Emergent Events-Specific Inquiry were compared between the lower and higher dose treatments in each treatment group and among the higher dose treatments of SAMe, escitalopram, and placebo. RESULTS: Various depression severity scores decreased significantly for all three treatment arms during the higher dose treatment. No within-group and between-group differences were found in any of the efficacy measures when comparing the doses and treatments. There was a significant difference in reported abdominal discomfort among patients receiving the higher dose of SAMe (31.3%), compared to escitalopram (8.7%) and placebo (3.8%) (χ2=7.32, p = 0.026). LIMITATIONS: The sample size was relatively small. The study duration for dose increase was relatively short. CONCLUSIONS: Patients with MDD failing to respond to 1,600 mg/day of SAMe may improve after increasing the dose to 3,200 mg/day, but we cannot rule out the contribution of a placebo effect and time-related improvement. The risk of abdominal discomfort may be increased with higher doses of SAMe.

Adaptation of a sustained care cessation intervention for smokers hospitalized for psychiatric disorders: Study protocol for a randomized controlled trial.

BACKGROUND: Individuals with serious mental illness (SMI) smoke at disproportionately higher rates than those without SMI, have lifespans 25-32 years shorter, and thus bear an especially large burden of tobacco-related morbidity and mortality. Several recent studies demonstrate that smokers with SMI can successfully quit smoking with adequate support. Further evidence shows that using technology to deliver sustained care interventions to hospitalized smokers can lead to smoking cessation up to 6 months after discharge. The current comparative effectiveness trial adapts a technology-assisted sustained care intervention designed for smokers admitted to a general hospital and tests whether this approach can produce higher cessation rates compared to usual care for smokers admitted to a psychiatric inpatient unit. METHODS: A total of 353 eligible patients hospitalized for psychiatric illness are randomized by cohort into one of two conditions, Sustained Care (SusC) or Usual Care (UC), and are followed for six months after discharge. Participants assigned to UC receive brief tobacco education delivered by a hospital nurse during or soon after admission. Those assigned to SusC receive a 40-min, in-hospital motivational counseling intervention. Upon discharge, they also receive up to 8 weeks of free nicotine patches, automated interactive voice response (IVR) telephone and text messaging, and access to cessation counseling resources lasting 3 months post discharge. Smoking cessation outcomes are measured at 1-, 3- and 6-months post hospital discharge. CONCLUSION: Results from this comparative effectiveness trial will add to our understanding of acceptable and effective smoking cessation approaches for patients hospitalized with SMI.

Childhood maltreatment, behavioral adjustment, and molecular markers of cellular aging in preschool-aged children: A cohort study.

OBJECTIVE: Childhood maltreatment is a major risk factor for the development of behavioral problems and poor physical and mental health. Accelerated cellular aging, through reduced telomere length and mitochondrial dysfunction, may be a mechanism underlying these associations. METHODS: Families with (n = 133) and without (n = 123) child welfare documentation of moderate-severe maltreatment in the past six months participated in this study. Children ranged in age from 3 to 5 years, were racially and ethnically diverse, and 91% qualified for public assistance. Structured record review and interviews were used to assess a history of maltreatment and other adversities. Telomere length and mitochondrial DNA copy number (mtDNAcn) were measured from saliva DNA using real-time PCR. Measures were repeated at a six-month follow-up assessment. Repeated measures general linear models were used to examine the effects of maltreatment and other adversities on telomere length and mtDNAcn over time. RESULTS: Maltreatment and other adverse experiences were significant positive predictors of both telomere length and mtDNAcn over time. Internalizing and externalizing behavior problems were also both significantly associated with telomere length, but only internalizing symptoms were associated with mtDNAcn. CONCLUSIONS: This is the first study to show that mtDNAcn is altered in children with stress and trauma, and the findings are consistent with recent studies of adults. Surprisingly, children who experienced moderate-severe levels of maltreatment in the prior six months had longer telomeres, possibly reflecting compensatory changes in response to recent trauma. Telomere length and mtDNAcn were also associated with behavioral problems, suggesting that these measures of cellular aging may be causally implicated in the pathophysiology of stress-related conditions.