Factors associated with suicidal ideation among people with HIV engaged in care.

BACKGROUND: People with HIV (PWH) are at elevated risk for suicidal ideation (SI), yet few studies have examined how substance use, clinical and sociodemographic factors are associated with SI among PWH. METHOD: We used substance use (Tobacco, Alcohol, Prescription Medication, and Other Substance Use [TAPS]) and depression (PHQ-9) data from computerized screening of adult PWH in primary care clinics in Northern California, combined with health record data on psychiatric diagnoses, HIV diagnosis, treatment, and control (HIV RNA, CD4), insurance, and neighborhood deprivation index (NDI) to examine factors associated with SI (PHQ-9 item 9 score > 0). Adjusted odds ratios (aOR) for SI were obtained from logistic regression models. RESULTS: Among 2829 PWH screened (92 % male; 56 % white; mean (SD) age of 54 (13) years; 220 (8 %) reported SI. Compared with no problematic use, SI was higher among those reporting one (aOR = 1.65, 95 % CI = 1.17, 2.33), two (aOR = 2.23, 95 % CI = 1.42, 3.49), or ≥ 3 substances (aOR = 4.49, 95 % CI = 2.41, 8.39). SI risk was higher for those with stimulant use (aOR = 3.55, 95 % CI = 2.25, 5.59), depression (aOR = 4.18, 95 % CI = 3.04, 5.74), and anxiety diagnoses (aOR = 1.67, 95 % CI = 1.19, 2.34), or Medicaid (aOR = 2.11, 95%CI = 1.24, 3.60) compared with commercial/other insurance. SI was not associated with HIV-related measures or NDI. LIMITATIONS: SI was assessed with a single PHQ-9 item. Simultaneous SI and exposure data collection restricts the ability to establish substance use as a risk factor. CONCLUSIONS: HIV care providers should consider multiple substance use, stimulant use, depression or anxiety, and public insurance as risk factors for SI and provide interventions when needed.

Association of Adverse Childhood Experiences and Resilience With Depression and Anxiety During Pregnancy.

This was a retrospective cohort study of pregnant individuals in the Kaiser Permanente Northern California system who were screened for adverse childhood experiences and resilience as part of standard prenatal care at about 16 weeks of gestation. Overall, 14,625 pregnancies were included; 17.0% had newly identified depression; 9.8% had newly identified depression symptoms; and 8.9% had newly identified anxiety during the pregnancy with no known preexisting diagnosis. We found that adverse childhood experiences and low resilience were independently associated with newly identified depressive disorders, depression symptoms, and anxiety disorders during pregnancy. When adverse childhood experiences and resilience were modeled in combination, the greatest odds of each outcome occurred in individuals with a combination of four or more adverse childhood experiences and low resilience (vs no adverse childhood experiences and high resilience): depression adjusted odds ratio (aOR) 6.43 (95% CI, 5.23-7.90), depression symptoms aOR 9.49 (95% CI, 7.50-12.0), and anxiety disorder aOR 4.79 (95% CI, 3.81-6.02). Routine screening for adverse childhood experiences and resilience may identify individuals at risk of developing prenatal depression and anxiety, allowing faster resource linkage and potentially improved maternal and child outcomes.

Addiction Medicine Treatment Utilization by Race/Ethnicity Among Adolescents With Substance Use Problems Before Versus During the COVID-19 Pandemic.

PURPOSE: To examine changes in addiction medicine treatment utilization during the COVID-19 pandemic among adolescents (aged 13-17 years) and differences by race/ethnicity. METHODS: We compared treatment initiation (overall and telehealth), engagement, and 12-week retention between insured adolescents with substance use problems during pre-COVID-19 (March to December 2019, n = 1,770) and COVID-19 (March to December 2020, n = 1,177) using electronic health record data from Kaiser Permanente Northern California. RESULTS: Compared to pre-COVID-19, odds of treatment initiation, overall (adjusted odds ratio [95% confidence interval] = 1.42 [1.21-1.67]), and telehealth (5.98 [4.59-7.80]) were higher during COVID-19, but odds of engagement and retention did not significantly change. Depending on the outcome, Asian/Pacific Islander, Black, and Latino/Hispanic (vs. White) adolescents had lower treatment utilization across both periods. Changes in utilization over time did not differ by race/ethnicity. DISCUSSION: Addiction medicine treatment initiation increased among insured adolescents during the pandemic, especially via telehealth. Although racial/ethnic disparities in treatment utilization persisted, they did not worsen.

Associations between Adverse Childhood Experiences (ACEs) and Prenatal Mental Health and Substance Use.

Adverse childhood experiences (ACEs) are common and increase the risk of poor health outcomes. Resilience may offer protection against the impacts of ACEs. This study examined the association between maternal ACEs and mental/behavioral health outcomes during pregnancy overall and by resilience. The sample comprised pregnant patients in two pilot studies screened for eight ACEs and resilience during standard prenatal care in Kaiser Permanente Northern California from 1 March 2016 to 30 July 2016 (Study 1, medical centers A, B) and from 1 April 2018 to 31 March 2019 (Study 2, medical centers A, C). Early pregnancy outcomes included anxiety and depressive disorders, depression symptoms, intimate partner violence (IPV), and substance use. Multivariable logistic regression was used in this cross-sectional study to examine associations between maternal ACEs (0, 1-2, ≥3) and mental/behavioral health outcomes overall and among those with low and high resilience. Patients (n = 1084) averaged 30.8 years (SD 5.1); 41.7% were non-Hispanic White; 41.7% experienced ≥1 ACE, and 40.3% had low resilience. Patients with 1-2 ACEs or ≥3 ACEs (versus 0 ACEs) had higher odds of anxiety and depressive disorders, depressive symptoms, IPV, and any prenatal substance use (OR 1.44-4.40, p < 0.05). Each individual ACE was associated with ≥2 mental/behavioral health outcomes. In stratified analyses, having ≥1 ACE (vs. 0) was associated with a greater number of mental/behavioral health outcomes among patients with low versus high resilience. ACEs were associated with prenatal mental/behavioral health conditions, particularly in the context of low resilience, highlighting the importance of trauma-informed prenatal care and the need to study resilience-building interventions during pregnancy.

Overall and Telehealth Addiction Treatment Utilization by Age, Race, Ethnicity, and Socioeconomic Status in California After COVID-19 Policy Changes.

Importance: Addiction treatment rapidly transitioned to a primarily telehealth modality (telephone and video) during the COVID-19 pandemic, raising concerns about disparities in utilization. Objective: To examine whether there were differences in overall and telehealth addiction treatment utilization after telehealth policy changes during the COVID-19 pandemic by age, race, ethnicity, and socioeconomic status. Design, Setting, and Participants: This cohort study examined electronic health record and claims data from Kaiser Permanente Northern California for adults (age ≥18 years) with drug use problems before the COVID-19 pandemic (from March 1, 2019, to December 31, 2019) and during the early phase of the COVID-19 pandemic (March 1, 2020, to December 31, 2020; hereafter referred to as COVID-19 onset). Analyses were conducted between March 2021 and March 2023. Exposure: The expansion of telehealth services during COVID-19 onset. Main Outcomes and Measures: Generalized estimating equation models were fit to compare addiction treatment utilization during COVID-19 onset with that before the COVID-19 pandemic. Utilization measures included the Healthcare Effectiveness Data and Information Set of treatment initiation and engagement (including inpatient, outpatient, and telehealth encounters or receipt of medication for opioid use disorder [OUD]), 12-week retention (days in treatment), and OUD pharmacotherapy retention. Telehealth treatment initiation and engagement were also examined. Differences in changes in utilization by age group, race, ethnicity, and socioeconomic status (SES) were examined. Results: Among the 19 648 participants in the pre-COVID-19 cohort (58.5% male; mean [SD] age, 41.0 [17.5] years), 1.6% were American Indian or Alaska Native; 7.5%, Asian or Pacific Islander; 14.3%, Black; 20.8%, Latino or Hispanic; 53.4%, White; and 2.5%, unknown race. Among the 16 959 participants in the COVID-19 onset cohort (56.5% male; mean [SD] age, 38.9 [16.3] years), 1.6% were American Indian or Alaska Native; 7.4%, Asian or Pacific Islander; 14.6%, Black; 22.2%, Latino or Hispanic; 51.0%, White; and 3.2%, unknown race. Odds of overall treatment initiation increased from before the COVID-19 pandemic to COVID-19 onset for all age, race, ethnicity, and SES subgroups except for patients aged 50 years or older; patients aged 18 to 34 years had the greatest increases (adjusted odds ratio [aOR], 1.31; 95% CI, 1.22-1.40). Odds of telehealth treatment initiation increased for all patient subgroups without variation by race, ethnicity, or SES, although increases were greater for patients aged 18 to 34 years (aOR, 7.17; 95% CI, 6.24-8.24). Odds of overall treatment engagement increased (aOR, 1.13; 95% CI, 1.03-1.24) without variation by patient subgroups. Retention increased by 1.4 days (95% CI, 0.6-2.2 days), and OUD pharmacotherapy retention did not change (adjusted mean difference, -5.2 days; 95% CI, -12.7 to 2.4 days). Conclusions: In this cohort study of insured adults with drug use problems, there were increases in overall and telehealth addiction treatment utilization after telehealth policies changed during the COVID-19 pandemic. There was no evidence that disparities were exacerbated, and younger adults may have particularly benefited from the transition to telehealth.

Considerations for the Writing of Certification Letters Endorsing Use of Emotional Support Animals.

Emotional support animals (ESAs) are different from service animals, therapy animals, and other disability-related assistance animals. Although pet ownership may confer psychological benefits, limited research has supported the use of ESAs to realize such benefits. If clinicians are asked to write a letter of support for use of an ESA, they need to be familiar with relevant federal, state, and local laws that regulate ESAs and with the essential components of an ESA evaluation. This article provides an overview of terminology; federal, state, and local laws related to ESAs; and clinical and ethical considerations for clinicians who decide to write these letters. The authors also review liability issues related to writing these letters, including those related to ESA aggression.

Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress-Exposed Nonhuman Primates.

Background: Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. Methods: Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD-reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD-reared groups were examined using regression modeling, controlling for sex, weight, and age. Results: VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. Conclusions: Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.

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.

Association Between Prenatal Cannabis Use and Psychotropic Medication Use in Pregnant Patients With Depression and Anxiety.

OBJECTIVES: This cross-sectional study examined associations between prenatal cannabis use and prescribed psychotropic medication use among pregnant patients with depression or anxiety in a large, integrated healthcare system. METHODS: Study patients had a confirmed pregnancy and a depressive or anxiety disorder defined by International Classification of Diseases codes between 2012 and 2018 at Kaiser Permanente Northern California. Patients were screened for prenatal substance use via a self-reported questionnaire and urine toxicology test as part of standard prenatal care. Generalized estimating equation models tested for associations between prenatal cannabis use and any dispensation of antidepressants, benzodiazepines, and hypnotics during gestation. Models were stratified by diagnosis (depression or anxiety) and depression symptom severity. RESULTS: This study included 35,047 pregnancies (32,278 patients; 17.6% aged <25 years, 48.1% non-Hispanic White). Adjusting for patient age, income, race/ethnicity, and depression symptom severity, the 12.6% of patients who screened positive for prenatal cannabis use demonstrated higher odds of prenatal benzodiazepine (adjusted odds ratios [aOR] = 1.40; 95% confidence interval [CI] = 1.20-1.62) and hypnotic (aOR = 1.28; 95% CI = 1.11-1.48), but not antidepressants (aOR = 1.05, 95% CI = 0.96-1.14) use. This pattern persisted when diagnostic groups were examined separately. The odds of prenatal benzodiazepine and hypnotic use associated with prenatal cannabis use were higher among pregnancies with severe depression symptom severity (31.8% of the sample). CONCLUSIONS: Among pregnant patients with depression or anxiety, prenatal cannabis use was associated with higher odds of prenatal benzodiazepine and hypnotic use. As patients may be using cannabis to address depression and anxiety, prescribers should remain vigilant for under- or untreated psychiatric symptoms among pregnant patients and provide evidence-based treatments.

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.

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.

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.

Benefits of Yoga on IL-6: Findings from a Randomized Controlled Trial of Yoga for Depression.

The present research sought to examine whether hatha yoga, implemented as an adjunctive intervention for major depression, influences markers of inflammation. A subset of 84 participants who were enrolled in a randomized controlled trial (RCT) of hatha yoga vs. health education control provided blood samples at baseline (pre-treatment) and at 3-(during treatment) and 10-week (end of treatment) follow-up visits. To be eligible for the RCT, participants met criteria for a current or recent (past two years) major depressive episode, had current elevated depression symptoms, and current antidepressant medication use. Venous blood was drawn between 2 and 6 pm and following at least one hour of fasting, and inflammatory markers (IL-6, CRP, and TNF-α) were assayed. Effects of participation in yoga relative to health education on inflammatory markers over time were examined with latent growth analyses. We observed a significant reduction in IL-6 concentrations in the yoga treatment group relative to the health education control group as demonstrated by a negative interaction between treatment group and slope of IL-6. TNF-α and CRP did not evidence significant interactions of treatment group by mean slope or intercept. In addition to the benefits of hatha yoga as an adjunctive intervention for individuals who have shown inadequate response to antidepressant medications, our findings point to possible benefits of yoga on IL-6 in depressed populations. Further research is needed to explore the effects of hatha yoga on immune function over time.

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.

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.

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.

Associations of maternal diet and placenta leptin methylation.

BACKGROUND: Maternal diet is an important factor in prenatal development that also has implications for disease risk later in life. The adipokine leptin is a key regulator of energy homeostasis and may be involved in the association between maternal nutrition, maternal obesity, and infant outcomes. DNA methylation of placenta genes may occur in response to exposures and may program subsequent infant development. This study examined maternal diet, placenta leptin gene DNA methylation, and neonatal growth in a sample of healthy neonates and their mothers. METHODS: Mothers and their healthy neonates (N = 135) were recruited within 1-2 days following delivery at Women and Infants Hospital in Providence, RI. A structured interview was conducted to assess maternal dietary intake. Maternal pre-pregnancy weight, weight gain during pregnancy, maternal health, medications, and vitamin use were obtained from medical records. Bisulfite pyrosequencing was used to measure methylation of CpG sites in the promoter region of the placenta leptin gene and determine genotype of the leptin single nucleotide polymorphism (SNP) rs2167270, which is known to influence leptin methylation. Bivariate analyses and linear regression models were used to evaluate associations of demographics, diet, and mean leptin methylation. RESULTS: Genotype was a significant predictor of placenta leptin DNA methylation (p < .01), and after controlling for this and other relevant maternal and infant covariates, lower levels of leptin methylation were significantly associated with greater intake of carbohydrates (p < .05), in particular added sugars (p < .05) and white/refined carbohydrates (p < .05). Total caloric intake was also associated with placenta leptin methylation (p < .05), however after controlling for relevant covariates, significance diminished to trend-level. There were no significant associations of placenta leptin methylation and intake of protein (p > .05) or fat (p > .05). CONCLUSION: These findings underline the importance of intake of carbohydrate consumption for methylation of the placenta leptin gene. Because methylation reduces gene transcription, lower methylation may indicate a placenta response to high caloric intake and carbohydrate food that would result in higher levels of this hormone during fetal development. Further investigation of the developmental ramifications of epigenetic changes to placenta leptin methylation should be pursued.

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.