Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress.

This manuscript reviews recent evidence supporting the utility of telomeres and mitochondrial DNA copy number (mtDNAcn) in detecting the biological impacts of adverse childhood experiences (ACEs) and outlines mechanisms that may mediate the connection between early stress and poor physical and mental health. Critical to interrupting the health sequelae of ACEs such as abuse, neglect, and neighborhood disorder, is the discovery of biomarkers of risk and resilience. The molecular markers of chronic stress exposure, telomere length and mtDNAcn, represent critical biological links between ACEs and poor health outcomes. We examine how telomeres and mtDNAcn may exacerbate health disparities and contribute to the intergenerational transmission of trauma. Finally, we explore how these molecular markers of early stress exposure may help define the role of resilience and develop effective interventions to moderate ACE health risk impact.

A Novel Experiential Quality Improvement Training Program During Residency Improves Quality Improvement Confidence and Knowledge: a Prospective Cohort Study.

OBJECTIVE: The Accreditation Council for Graduate Medical Education (ACGME) mandates resident quality improvement (QI) training to improve patient safety, cost control, and efficiency. Thus, understanding this topic is crucial for early career physicians. This manuscript describes an enhanced, experiential QI curriculum for psychiatry residents and its outcomes. METHODS: Two cohorts of 12 third-year residents completed the curriculum, which included didactics, external resources, and expert guidance through small group project design, implementation, and analysis/presentation. A survey on resident confidence in QI principles and the quality improvement knowledge assessment tool-revised (QIKAT-R) was used before and after curriculum participation. Data were analyzed using parametric descriptive tests and repeated measures general linear models with Benjamini-Hochberg correction for multiple comparisons. RESULTS: Resident confidence in performing seven of the ten steps of QI and QIKAT-R scores significantly improved for both cohorts (p = .011). Eighty-nine percent of residents felt that the curriculum met their goals. CONCLUSIONS: The QI curriculum effectively improved resident QI confidence and knowledge. Residents reported that experiential engagement in the design, implementation, and analysis/presentation of their project was crucial to these achievements. This experiential QI curriculum with resident-generated QI projects addressed ACGME training requirements while integrating QI training directly into the residents' clinical activities, making the QI efforts relevant and meaningful while also achieving ACGME goals.

5-Hz Transcranial Magnetic Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depression.

Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, underscoring the need for new treatments. Repetitive transcranial magnetic stimulation (rTMS) depolarizes neurons in a targeted brain region with magnetic fields typically pulsed at low (1 Hz) or high (10 Hz) frequency to relieve major depressive disorder (MDD). Prior work suggests an intermediate pulse frequency, 5 Hz, is also efficacious for treating comorbid depressive and anxiety symptoms. In this chart review study, we systematically examined the clinical and safety outcomes in 10 patients with comorbid MDD and PTSD syndromes who received 5-Hz rTMS therapy at the Providence VA Medical Center Neuromodulation Clinic. Self-report scales measured illness severity prior to treatment, after every 5 treatments, and upon completion of treatment. Results showed significant reduction in symptoms of PTSD (p = .003, effect size = 1.12, 8/10 with reliable change) and MDD (p = .005, effect size = 1.09, 6/10 with reliable change). Stimulation was well tolerated and there were no serious adverse events. These data indicate 5-Hz rTMS may be a useful option to treat these comorbid disorders. Larger, controlled trials are needed to confirm the benefits of 5-Hz protocols observed in this pilot study.

Telomeres, early-life stress and mental illness.

Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and preserve genomic DNA by serving as a disposable buffer to protect DNA termini during chromosome replication. In this process, the telomere itself shortens with each cell division and can consequently be thought of as a cellular 'clock', reflecting the age of a cell and the time until senescence. Telomere shortening and changes in the levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress) and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying stress-response biomarker that crosses the brain/body distinction that is often made in medicine. Prospective studies will help to clarify whether this biomarker has broad utility in psychiatry and medicine for the evaluation of responses to psychosocial stressors. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches.

Predictors of Long-Acting Injectable Antipsychotic Medication Use in Patients with Schizophrenia Spectrum, Bipolar, and Other Psychotic Disorders in a US Community-based, Integrated Health System.

Background and Hypothesis: Long-acting injectable (LAI) antipsychotics improve patient outcomes and are recommended by treatment guidelines for patients with limited medication adherence in schizophrenia spectrum, bipolar, and other psychotic disorders. Reports of LAI antipsychotic use in these disorders and if use aligns with treatment guidelines are lacking. This study aimed to report patient characteristics associated with LAI antipsychotic use in these disorders. Study Design: Retrospective observational study of patients ≥18-years-old with bipolar or psychotic disorders at a large, integrated, community-based health system. Patient demographic and clinical characteristics served as exposures for the main outcome of adjusted odds ratio (aOR) for LAI versus oral antipsychotic medication use from January 1, 2017 to December 31, 2023. Study Results: There were N = 2685 LAI and N = 31 531 oral antipsychotic users. Being non-white (aOR = 1.3-2.0; P < .0001), non-female (aOR = 1.5; P < .0001), from a high deprivation neighborhood (NDI, aOR = 1.3; P < .0007), having a higher body mass index (BMI, aOR = 1.3-1.7; P < .0009), having a schizophrenia/schizoaffective (aOR = 5.8-6.8; P < .0001), psychotic (aOR = 1.6, P < .0001), or substance use disorder (aOR = 1.4; P < .0001), and outpatient psychiatry (aOR = 2.3-7.5; P < .0001) or inpatient hospitalization (aOR = 2.4; P < .0001) utilization in the prior year with higher odds and age ≥40 (aOR = 0.4-0.7; P < .0001) or bipolar disorder (aOR = 0.9; P < .05) were associated with lower odds of LAI use. Non-white, non-female, age 18-39, and high NDI patients had higher LAI use regardless of treatment adherence markers. Smoking and cardiometabolic markers were also associated with LAI use. Conclusions: Demographic and clinical factors are associated with increased LAI use irrespective of treatment adherence. Research on utilization variation informing equitable formulation use aligned with treatment guideline recommendations is warranted.

Evaluating Implementation and Outcomes of the Achieving Depression and Anxiety Patient-Centered Treatment Collaborative Care Program in a Large, Integrated Health Care System: A Mixed Methods Observational Study Protocol.

Background Collaborative care is an evidence-based multidisciplinary model shown to improve patient depression and anxiety outcomes. Although there is robust literature showing the effectiveness of collaborative care on depression and anxiety symptoms, there is little published on outcomes of collaborative care implementation or the efficacy of collaborative care compared with psychiatric referrals. Reported here is a study protocol examining a novel depression and anxiety collaborative care program in a large, integrated health care system. Methods This is a mixed methods study of the Achieving Depression and Anxiety Patient-Centered Treatment (ADAPT) program as compared to outpatient psychiatric care at Kaiser Permanente Northern California, a large, integrated health care delivery system. The ADAPT program was designed using collaborative care principles, including measurement-based care, accurate diagnosis, and population management. Eligible participants will be ≥ 18 years old with mild to moderate-severe depressive symptoms as measured by the Patient Health Questionnaire-9. Exclusion criteria include acute suicide risk and serious mental health comorbidities. Implementation is examined using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework and interviews with program stakeholders. Results Pending. Conclusion Study data will help inform future collaborative care efforts while expanding the literature base. The Achieving Depression and Anxiety Patient-Centered Treatment program may improve patient outcomes and access to quality depression and/or anxiety care.

Comparison of eating disorder characteristics and depression comorbidity in adolescent males and females: An observational study.

Depression comorbid with eating disorders is common and can worsen the severity of both disorders. Little is published regarding depression and eating disorders in male adolescents. This retrospective observational study compared eating disorder presentation and depression comorbidity between medically-hospitalized male and female adolescents. Standardized chart abstraction was performed for 148 subjects (n=127 females, =21 males). Male adolescents had significantly greater pre-hospitalization weight loss and longer eating disorder duration, and were 1.6 times more likely to have comorbid depression compared to female patients. These findings suggest increased detection and treatment of both disorders in adolescent males is warranted.

Adult Suicide-Related emergency department encounters during the COVID-19 Pandemic: a Cross-Sectional study.

Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in widespread psychosocial disruption, which may impact suicidal thoughts and behaviours. This study characterizes adult suicide-related emergency department (ED) encounters and patient characteristics during the COVID-19 pandemic in 2020 compared to the year prior. Methods: Retrospective cross-sectional study in a large, integrated, community-based health system of adults (≥18-years-old) with suicide-related ED encounters (defined by the Centres for Disease Control-recommended International Statistical Classification of Diseases [ICD-10-CM] codes) during the COVID-19 pandemic compared to the same period in 2019. Population-level incidence rate ratios (IRRs) compared suicide-related ED encounters in 2020 to 2019. Patient characteristics for the first suicide-related ED visit for each period were used to calculate percent relative change comparing 2020 to 2019. Findings: Of 10,651 suicide-related ED encounters in 2020 and 11,476 in 2019, 49.6% and 51.6% were for females and the mean age was 38±17 and 38±16 years-old, respectively. Suicide-related ED encounters significantly declined in each month of 2020 (IRR 0.71-0.91, p<.05), but were equivalent to 2019 levels June-August. Adults in 2020 were more likely to have co-occurring substance use disorders (+15•7%; 95% CI 7•0-24•4%) or have no mental health or suicide diagnosis associated with an outpatient visit in the last year (+21•1%, 95% CI: 12•5-29•6) compared to 2019. Interpretation: Adults with suicidal thoughts and behaviours during the COVID-19 pandemic in 2020 had distinct social and psychiatric characteristics compared to patients in the prior year. These findings can help inform health system responses to mental health needs.

Changes in Diagnostic and Demographic Characteristics of Patients Seeking Mental Health Care During the Early COVID-19 Pandemic in a Large, Community-Based Health Care System.

OBJECTIVE: The early COVID-19 pandemic resulted in great psychosocial disruption and stress, raising speculation that psychiatric disorders may worsen. This study aimed to identify patients vulnerable to worsening mental health during the COVID-19 pandemic. METHODS: This retrospective observational study used electronic health records from March 9 to May 31 in 2019 (n = 94,720) and 2020 (n = 94,589) in a large, community-based health care system. Percent change analysis compared variables standardized to the average patient population for the respective time periods. RESULTS: Compared to 2019, psychiatric visits increased significantly (P < .0001) in 2020, with the majority being telephone/video-based (+264%). Psychiatric care volume increased overall (7%), with the greatest increases in addiction (+42%), behavioral health in primary care (+17%), and adult psychiatry (+5%) clinics. While patients seeking care with preexisting psychiatric diagnoses were mainly stable (−2%), new patients declined (−42%). Visits for substance use (+51%), adjustment (+15%), anxiety (+12%), bipolar (+9%), and psychotic (+6%) disorder diagnoses, and for patients aged 18­25 years (+4%) and 26­39 years (+4%), increased. Child/adolescent and older adult patient visits decreased (−22.7% and −5.5%, respectively), and fewer patients identifying as White (−3.8%) or male (−5.0) or with depression (−3%) or disorders of childhood (−2%) sought care. CONCLUSIONS: The early COVID-19 pandemic was associated with dramatic changes in psychiatric care facilitated by a rapid telehealth care transition. Patient volume, demographic, and diagnostic changes may reflect comfort with telehealth or navigating the psychiatric care system. These data can inform health system resource management and guide future work examining how care delivery changes impact psychiatric care quality and access.

Emergency Department Encounters Among Youth With Suicidal Thoughts or Behaviors During the COVID-19 Pandemic.

Importance: Population-level reports of suicide-related emergency department (ED) encounters among youth during the COVID-19 pandemic are lacking, along with youth characteristics and preexisting psychiatric service use. Objective: To characterize population-level and relative change in suicide-related ED encounters among youth during the COVID-19 pandemic compared with 2019. Design, Setting, and Participants: This cross-sectional study evaluated ED encounters in 2019 and 2020 at Kaiser Permanente Northern California-a large, integrated, community-based health system. Youth aged 5 to 17 years who presented to the ED with suicidal thoughts or behaviors were included. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: Population-level incidence rate ratios (IRRs) and percent relative effects for suicide-related ED encounters as defined by the US Centers for Disease Control and Prevention-recommended International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes in 4 periods in 2020 compared with the same periods in 2019. Results: There were 2123 youth with suicide-related ED encounters in 2020 compared with 2339 in 2019. In the 2020 group, 1483 individuals (69.9%) were female and 1798 (84.7%) were aged 13 to 17 years. In the 2019 group, 1542 (65.9%) were female, and 1998 (85.4%) were aged 13 to 17 years. Suicide-related ED encounter incidence rates were significantly lower in March through May 2020 compared with this period in 2019 (IRR, 0.57; 95% CI, 0.51-0.63; P < .001), then returned to prepandemic levels. However, suicide-related ED visits among female youth from June 1 to August 31, 2020, and September 1 through December 15, 2020, were significantly higher than in the corresponding months in 2019 (IRR, 1.19; 95% CI, 1.04-1.35; P = .04 and IRR, 1.22; 95% CI, 1.11-1.35; P < .001, respectively), while suicide-related ED visits for male youth decreased from September 1 through December 15, 2020 (IRR, 0.81; 95% CI, 0.69 to 0.94). Youth with no history of outpatient mental health or suicide encounters (129.4%; 95% CI, 41.0-217.8) and those with comorbid psychiatric conditions documented at the ED encounter (6.7%; 95% CI, 1.0-12.3) had a higher risk of presenting with suicide-related problems from September to December 2020 vs the same period in 2019. Conclusions and Relevance: In this cross-sectional study of youth experiencing suicidal thoughts and behaviors, suicide-related presentations to the ED initially decreased during the COVID-19 pandemic, likely owing to shelter-in-place orders, then were similar to 2019 levels. However, a greater number of female youth, youth with no psychiatric history, and youth with psychiatric diagnoses at the time of the ED encounter presented for suicide-related concerns during the pandemic, suggesting these may be vulnerable groups in need of further interventions. Adjustments in care may be warranted to accommodate these groups during periods of crisis.

Pharmacist Medication Management of Adults with Attention Deficit: An Alternative Clinical Structure.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric conditions in youth. This disorder can persist into adulthood, with an estimated prevalence of 4.4% to 5.2% in the US. OBJECTIVE: To review adult ADHD diagnostic criteria, adult clinical presentation, and resulting impairments in function and to describe our adult psychiatry clinic's pharmacist-comanaged ADHD medication management program as a model to provide safe and effective care that is accessible, efficient, and well monitored. METHODS: The program consists of 1) screening (urine toxicology, diagnostic evaluation, data collection) by physicians, 2) program participation and treatment agreement with establishment of care goals, and 3) patient maintenance and monitoring. Pharmacists in the Department of Psychiatry manage refills, distributing the clinical caseload among a broader clinician base. RESULTS: This program created a standardized protocol for assessment, referral, and follow-up of adult patients with ADHD, with close monitoring and titration of controlled medications, systematic use of screening measures, and a stimulant treatment contract. DISCUSSION: Development of this program and workflow model could increase care delivery efficiency, potentially improving patient satisfaction and outcomes. There is a great need to use alternative patient management strategies such as this to maintain access to high-quality care while there is a nationwide need for more psychiatric clinicians. CONCLUSION: We believe this program offers a solution to a component of this growing problem, and other clinical sites would benefit from such a program. Next steps include analysis and publication of results of implementation, including patient outcomes, engagement in treatment, and satisfaction.

Femoral shear rate response to knee extensor exercise: an age and sex comparison.

Shear stress is considered an important stimulus for vascular adaptations with exercise training, yet the shear rate response to exercise has not been carefully examined in women or in healthy older adults. Therefore, the purpose of this study was to determine if age or sex differences are present in common femoral artery (CFA) shear rates during leg exercise. Diameter and mean blood velocity were measured in the CFA using Doppler ultrasound in young (20-30 yr) and older (60-79 yr) men and women at rest and during single-leg knee extensor exercise. Shear rate was calculated. Resting shear rate was lower in older compared to young adults (33.9+/-3.7 vs. 58.3+/-3.6 s(-1), respectively; p<0.05) and lower in men than women (36.8+/-3.8 vs. 55.4+/-3.5 s(-1), respectively; p<0.05). During exercise, older adults had overall lower shear rates compared to young adults (within-sex comparison, p<0.05). The rise in shear rate with work rate showed no age difference but was lower in men than women (4.6+/-0.4 vs. 8.6+/-0.4 s(-1) per W, p<0.05). These results suggest that age and sex differences are present in CFA shear rates during exercise which could have implications for vascular adaptability with exercise training.

Physician-Training Stress and Accelerated Cellular Aging.

BACKGROUND: Stress is a key precipitant for many common diseases, but established biological markers to track stress and guide investigations into mechanisms linking stress and disease are lacking. Cross-sectional studies have identified correlations between stress and telomere attrition, but no large, longitudinal studies examining the impacts of chronic stress on telomere length exist. Residency training for physicians is a well-established stressful experience and can be used as a prospective stress model. METHODS: In a longitudinal cohort study of 250 interns (first-year residents) at 55 United States hospital systems serving during the 2015-2016 academic year, we examined associations between measures of the residency experience and saliva-measured telomere attrition. RESULTS: Telomere length shortened significantly over the course of internship year, from mean ± SD of 6465.1 ± 876.8 base pairs before internship to 6321.5 ± 630.6 base pairs at the end of internship (t246 = 2.69; p = .008). Stressful early family environments and neuroticism were significantly associated with shorter preinternship telomere length. Longer work hours were associated with greater telomere intern telomere loss over the year (p = .002). Of note, the mean telomere attrition during internship year was six times greater than the typical annual attrition rate identified in a recent meta-analysis. CONCLUSIONS: This work implicates telomere attrition as a biologically measurable consequence of physician training, with the magnitude of attrition associated with workload. Identification of an objective, biological sequela of residency stress may help to facilitate the development of effective interventions. Further, the findings implicate telomere attrition as an objective biomarker to follow the pathologic effects of stress, in general.

Daily Laboratory Monitoring is of Poor Health Care Value in Adolescents Acutely Hospitalized for Eating Disorders.

PURPOSE: This study investigates how the clinical practice guideline-recommended laboratory monitoring for refeeding syndrome impacts management and outcomes of adolescents with eating disorders hospitalized for acute medical stabilization and examines the value of laboratory monitoring (defined as the patient health outcomes achieved per dollar spent). METHODS: A retrospective chart review of medical admissions in a children's hospital between October 2010 and February 2014 was performed. Encounters were identified using International Classification of Diseases, Ninth Revision codes of eating disorders as primary or secondary diagnoses. Exclusion criteria included systemic diseases associated with significant electrolyte abnormalities. Chart abstraction was performed using a predetermined form. Costs were estimated by converting hospital-fixed Medicaid charges using a statewide cost-to-charge ratio. RESULTS: Of the 196 patient encounters, there were no cases of refeeding syndrome. A total of 3,960 key recommended laboratories were obtained; 1.9% were below normal range and .05% were critical values. Of these, .28% resulted in supplementation; none were associated with a change in inpatient management. Total laboratory costs were $269,250.85; the calculated health care value of this monitoring is 1.04 × 10(-8) differential outcomes per dollar spent. CONCLUSIONS: This study provides evidence to suggest that daily laboratory monitoring for refeeding syndrome is a poor health care value in the management of adolescents hospitalized for acute medical stabilization with eating disorders. This initial analysis suggests that starting at a relatively low caloric level and advancing nutrition slowly may negate the need for daily laboratory assessment, which may have important implications for current guidelines.

Depression and telomere length: A meta-analysis.

BACKGROUND: Several recent studies have investigated the relationship between telomere length and depression with inconsistent results. This meta-analysis examined whether telomere length and depression are associated and explored factors that might affect this association. METHODS: Studies measuring telomere length in subjects with clinically significant unipolar depression were included. A comprehensive search strategy identified studies in PubMed, MEDLINE, PsycINFO, Global Health, The Cochrane Library, and Web of Science. A structured data abstraction form was used and studies were appraised for inclusion or exclusion using a priori conditions. Analyses were conducted using standardized mean differences in a continuous random effects model. RESULTS: Thirty-eight studies (N=34,347) met the inclusion criteria. The association between depression and telomere length was significant, with a Cohen's d effect size of -0.205 (p<0.0001, I(2)=42%). Depression severity significantly associated with telomere length (p=0.03). Trim and fill analysis indicated the presence of publication bias (p=0.003), but that the association remained highly significant after accounting for the bias. Subgroup analysis revealed depression assessment tools, telomere measurement techniques, source tissue and comorbid medical conditions significantly affected the relationship. LIMITATIONS: Other potentially important sub-groups, including antidepressant use, have not been investigated in sufficient detail or number yet and thus were not addressed in this meta-analysis. CONCLUSIONS: There is a negative association between depression and telomere length. Further studies are needed to clarify potential causality underlying this association and to elucidate the biology linking depression and this cellular marker of stress exposure and aging.

Age and regional specificity of peak limb vascular conductance in women.

The influence of age on limb vasodilator capacity in women is unclear. The objectives of this study were to characterize and compare age-associated changes in forearm and calf peak vascular conductance (VC(peak); a functional index of arterial structure) in women and to identify physiological characteristics predictive of variation in limb-specific VC(peak). Peak conductance (plethysmographic flow/mean arterial pressure), VC(peak) of the forearm (forearm VC(peak)), and calf (calf VC(peak)) after 10 min of arterial occlusion were measured in 58 healthy, normally active women aged 21-79 yr. Aerobic capacity (cycle peak oxygen uptake), arterial health (pulse-wave velocity, ankle-brachial index), total cholesterol, limb-specific tissue composition (dual-energy X-ray absorptiometry), and isometric strength (handgrip, plantar flexion) were also assessed. The relative decline in calf VC(peak) with age (-6.8% per decade, P < 0.001) was greater than the forearm (-4.4% per decade, P = 0.004), in contrast to results previously reported for men (forearm decline > calf decline). Limb VC(peak) per kilogram muscle declined with age in the calf (-6.0% per decade; P = 0.002), but not the forearm (P = 0.12). Age, cholesterol, and regional tissue composition were significant predictors of peak conductance in both limbs; however, age was a stronger predictor of peak conductance in the calf. These results suggest that healthy aging is associated with a linear decline in limb vasodilator capacity in women, but the magnitude of this effect is region specific. Further research will be required to determine whether the decline in lower extremity vasodilator capacity with age explains diminished exercising leg vasodilation in older women.

Age and regional specificity of peak limb vascular conductance in men.

Because of methodological variation in previous studies, age-associated changes in peak limb vascular conductance (VC(peak); a functional index of arterial structure) and its determinants remain poorly defined. The objectives of this study were to describe and compare age-associated changes in peak forearm and calf conductance across a broad age range and to identify physiological characteristics that are predictive of variation in limb-specific VC(peak). Peak conductance (plethysmographic flow/brachial mean arterial pressure) of the forearm (forearm VC(peak)) and calf (calf VC(peak)) after 10 min of arterial occlusion was measured twice in 68 healthy, normally active men aged 20-79 yr. Aerobic capacity (cycle peak oxygen consumption), arterial health (ankle-brachial index, pulse wave velocity), and limb-specific measures of muscle mass (dual-energy X-ray absorptiometry) and isometric strength (grip, plantar flexion) were also assessed. The relative decline in forearm VC(peak) with age (-6.6% per decade; P < 0.001) was greater than the decline in calf VC(peak) (-3.4% per decade; P = 0.004). Limb VC(peak) per kilogram of muscle declined with age in the forearm (-3.8% per decade; P = 0.004) but not in the calf (P = 0.35). Age, Vo(2 peak), and regional muscle mass were significant predictors of peak conductance in both limbs; however, these predictors explained considerably less variance in the calf than in the forearm. These results suggest that healthy aging is associated with a linear decline in limb vasodilator capacity in men, but the magnitude of this effect is reduced in the calf relative to the forearm. This could reflect regional differences in habitual muscle use with aging in normally active men.

Association of telomere length and mitochondrial DNA copy number in a community sample of healthy adults.

Cellular aging plays a role in longevity and senescence, and has been implicated in medical and psychiatric conditions, including heart disease, cancer, major depression and posttraumatic stress disorder. Telomere shortening and mitochondrial dysfunction are thought to be central to the cellular aging process. The present study examined the association between mitochondrial DNA (mtDNA) copy number and telomere length in a sample of medically healthy adults. Participants (total n=392) were divided into 4 groups based on the presence or absence of early life adversity and lifetime psychopathology: No Adversity/No Disorder, n=136; Adversity/No Disorder, n=91; No Adversity/Disorder, n=46; Adversity/Disorder, n=119. Telomere length and mtDNA copy number were measured using quantitative polymerase chain reaction. There was a positive correlation between mtDNA and telomere length in the entire sample (r=0.120, p<0.001) and in each of the four groups of participants (No Adversity/No Disorder, r=0.291, p=0.001; Adversity/No Disorder r=0.279, p=0.007; No Adversity/Disorder r=0.449, p=0.002; Adversity/Disorder, r=0.558, p<0.001). These correlations remained significant when controlling for age, smoking, and body mass index and establish an association between mtDNA and telomere length in a large group of women and men both with and without early adversity and psychopathology, suggesting co-regulation of telomeres and mitochondrial function. The mechanisms underlying this association may be important in the pathophysiology of age-related medical conditions, such as heart disease and cancer, as well as for stress-associated psychiatric disorders.

5Hz Repetitive transcranial magnetic stimulation to left prefrontal cortex for major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) to left prefrontal cortex at 10Hz is the most commonly utilized protocol for major depressive disorder (MDD). Published data suggests that left sided 5Hz rTMS may be efficacious and well tolerated. OBJECTIVE: We analyzed outcomes in a naturalistic cohort of MDD patients who could not tolerate 10Hz rTMS and were routinely switched to 5Hz. We hypothesized that the efficacy of 5Hz rTMS would be equivalent to 10Hz. METHODS: Records were reviewed for patients (n=98) who received 15 or more acute rTMS treatments. The sample was split based upon the frequency (10 or 5Hz) at which the majority of treatments were delivered. The Inventory of Depressive Symptoms (IDS-SR) and 9-Item Patient Health Questionnaire (PHQ-9) were used to evaluate outcomes. RESULTS: Baseline IDS-SR was higher in the 5Hz (n=27) than in the 10Hz (n=71) group (p<.05), as was frequency of comorbid anxiety (p=.002). Depression outcomes did not differ between groups, and there were no differences in response or remission rates (all p>.1). Statistical power was sufficient to detect small group differences (d=.26). LIMITATIONS: Open-label data in a naturalistic setting. CONCLUSION: Outcomes associated with 5Hz rTMS did not differ from 10Hz, despite higher baseline depressive symptom severity and anxiety in 5Hz patients. 5Hz stimulation may be an alternative treatment option for patients unable to tolerate 10Hz rTMS.