Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

A randomized controlled trial of group cognitive remediation therapy for anorexia nervosa: Effects on set-shifting tasks for inpatient adults and adolescents.

OBJECTIVE: The aim of this randomized controlled trial with a parallel design was to evaluate the effect of brief, cognitive remediation therapy (CRT) for anorexia nervosa (AN) on set-shifting. METHOD: Two hundred seventy-five inpatient adults and adolescents with AN (mean age = 23.1; SD = 12.7) were randomly assigned (using simple randomization procedures) to either a CRT or control condition. All participants received treatment as usual; however, the CRT condition completed five CRT group sessions in lieu of other group therapies provided on the unit. Set-shifting abilities were evaluated by: (a) neuropsychological measures and (b) experimental cognitive behavior therapy thought records. Blinding of group assignment occurred during baseline assessment and ended following group commencement. RESULTS: Data from 135 CRT and 140 control condition participants were analyzed. On all neuropsychological measures, results revealed no between group condition effects, but did show statistically significant time effects, with medium to large effect sizes. Thought record analysis revealed a significant condition by age interaction effect where adults in the CRT condition generated significantly more alternative thoughts and had stronger believability of alternative thoughts than children, a trend that was not found in the control condition. This yielded moderate to large effect sizes of.0.56 and 0.72, respectively. DISCUSSION: Based on traditional neuropsychological measures, these findings do not suggest a differential effect of CRT for AN in the format applied. However, results suggest that CRT may have some increased beneficial cognitive effect for adults, as compared to children, based on thought record analysis.

An investigation of indirect effects of personality features on anorexia nervosa severity through interoceptive dysfunction in individuals with lifetime anorexia nervosa diagnoses.

OBJECTIVE: This study examined a hypothesized pathway by which interoceptive dysfunction accounted for associations between personality features (harm avoidance, self-directedness, and perfectionism) and anorexia nervosa (AN) severity (indicated by drive for thinness, eating disorder-related preoccupations and rituals, and body mass index). METHOD: The study sample (n = 270, mean age = 28.47, 95.2% female, 98% White/Caucasian) consisted of probands and biological relatives who met DSM-IV criteria for lifetime diagnoses of AN (omitting criterion D, amenorrhea) drawn from the Price Foundation Anorexia Nervosa Affected Relative Pairs Study (AN-ARP). Participants completed measures assessing personality, interoceptive dysfunction, and eating pathology. RESULTS: Associations between personality features of low self-directedness and high perfectionism and indicators of AN severity (drive for thinness and eating disorder-related preoccupations and rituals) were significant, as were the hypothesized indirect pathways through interoceptive dysfunction. Neither harm avoidance nor body mass index was significantly related to other study variables, and the proposed indirect pathways involving these variables were not significant. DISCUSSION: Findings suggest that certain personality features may relate to AN severity, in part, through their associations with interoceptive dysfunction. Future research should examine prospective associations and the value of interventions targeting interoceptive dysfunction for interrupting the link between personality and AN severity.

Associations between dimensions of anorexia nervosa and obsessive-compulsive disorder: An examination of personality and psychological factors in patients with anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are highly comorbid. However, the factors that account for this comorbidity are poorly understood. We examined the core dimensions of AN and OCD and psychological and personality factors shared by both disorders. METHOD: In path analyses (N = 732 women with either current AN or recovered from AN), we examined which factors were uniquely and independently associated with the core dimensions of AN and OCD. We also examined recovery from AN as a moderator. RESULTS: When individuals with AN reported greater concern over mistakes, they endorsed more severity in both AN and OCD core dimensions. These unique associations existed above and beyond all other transdiagnostic personality and psychological factors and regardless of AN recovery status. CONCLUSIONS: Concern over mistakes partially accounts for severity in the core dimensions of both AN and OCD. Concern over mistakes may represent an important target in the aetiology of AN and OCD.

The Anorexia Nervosa Genetics Initiative (ANGI): Overview and methods.

BACKGROUND: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. METHODS: ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H. RESULTS: Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable. CONCLUSIONS: Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.govNCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

Disseminating, implementing, and evaluating patient-centered outcomes to improve cardiovascular care using a stepped-wedge design: healthy hearts for Oklahoma.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in the US and incurs high health care costs. While many initiatives promote the implementation of ABCS (aspirin therapy, blood pressure control, cholesterol management, and smoking cessation) measures, most primary care practices (PCPs) lack quality improvement (QI) support and resources to achieve meaningful targets. The Healthy Hearts for Oklahoma (H2O) Study proposes to build a QI infrastructure by (1) constructing a sustainable Oklahoma Primary Healthcare Improvement Collaborative (OPHIC) to support dissemination and implementation (D&I) of QI methods; (2) providing QI support in PCPs to better manage patients at risk for CVD events. Parallel to infrastructure building, H2O aims to conduct a comprehensive evaluation of the QI support D&I in primary care and assess the relationship between QI support uptake and changes in ABCS measures. METHODS: H2O has partnered with public health agencies and communities to build OPHIC and facilitate QI. H2O has 263 small primary care practices across Oklahoma that receive the bundled QI intervention to improve ABCS performance. A stepped-wedge designed is used to evaluate D&I of QI support. Changes in ABCS measures will be estimated as a function of various components of the QI support and capacity and readiness of PCPs to change. Notes from academic detailing and practice facilitation sessions will be analyzed to help interpret findings on ABCS performance. DISCUSSION: H2O program is designed to improve cardiovascular health and outcomes for more than 1.25 million Oklahomans. The infrastructure established as a result of this funding will help reach medically underserved Oklahomans, particularly among rural and tribal populations. Lessons learned from this project will guide future strategies for D&I of evidence-based practices in PCPs. Trained practice facilitators will continue to serve as critical resource to assists small, rural PCPs in adapting to the ever-changing health environment and continue to deliver quality care to their communities.

Do SSRIs and SNRIs reduce the frequency and/or severity of hot flashes in menopausal women.

CLINICAL QUESTION: In menopausal women who experience regular hot flashes, does treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) reduce the frequency and/or severity of hot flashes? ANSWER: Yes. Review of the literature suggests that treatment with SSRIs or SNRIs reduces the frequency and severity of hot flashes in menopausal and post-menopausal women. Studies demonstrated that paroxetine (Paxil), citalopram (Celexa) and escitolapram (Lexapro) were the most effective SSRIs, and venlafaxine (Effexor) was the most effective first line SNRI, with desvenlafaxine as a second option. The most common side effects reported for both SSRIs and SNRIs are nausea and constipation, with most resolving within the first week of treatment. SNRIs have been associated with increased blood pressure in some patients and should be used with caution in women with hypertension. Women with a history of breast cancer and taking tamoxifen should avoid SSRIs, which have been shown to interfere with tamoxifen metabolism. SNRIs are the safest drugs for this population. Treatment choice should be patient-specific and begin with the lowest dose available. LEVEL OF EVIDENCE FOR THE ANSWER: A. SEARCH TERMS: SSRI, SNRI, hot flashes, vasomotor symptoms, menopause. SEARCH CONDUCTED: August 2014, February 2016 and August 2016. INCLUSION CRITERIA: menopausal, perimenopausal or postmenopausal women 18 years of age or older with frequent and/or severe vasomotor symptoms, meta-analyses, systematic reviews, randomized controlled trials, cohort studies. EXCLUSION CRITERIA: pre-menopause, anxiety, depression, panic disorder, bipolar disorder, co-morbid conditions.

A comparison of Tier 1 and Tier 3 medical homes under Oklahoma Medicaid program.

INTRODUCTION: The patient-centered medical home (PCMH) is a team-based model of care that seeks to improve quality of care and control costs. The Oklahoma Health Care Authority (OHCA) directs Oklahoma's Medicaid program and contracts with 861 medical home practices across the state in one of three tiers of operational capacity: Tier 1 (Basic), Tier 2 (Advanced) and Tier 3 (Optimal). Only 13.5% (n = 116) homes are at the optimal level; the majority (59%, n = 508) at the basic level. In this study, we sought to determine the barriers that prevented Tier 1 homes from advancing to Tier 3 level and the incentives that would motivate providers to advance from Tier 1 to 3. Our hypotheses were that Tier 1 medical homes were located in smaller practices with limited resources and the providers are not convinced that the expense of advancing from Tier 1 status to Tier 3 status was worth the added value. METHODS: We analyzed OHCA records to compare the 508 Tier 1 (entry-level) with 116 Tier 3 (optimal) medical homes for demographic differences with regards to location: urban or rural, duration as medical home, percentage of contracts that were group contracts, number of providers per group contract, panel age range, panel size, and member-provider ratio. We surveyed all 508 Tier 1 homes with a mail-in survey, and with focused follow up visits to identify the barriers to, and incentives for, upgrading from Tier 1 to Tier 2 or 3. RESULTS: We found that Tier 1 homes were more likely to be in rural areas, run by solo practitioners, serve exclusively adult panels, have smaller panel sizes, and have higher member-to-provider ratios in comparison with Tier 3 homes. Our survey had a 35% response rate. Results showed that the most difficult changes for Tier 1 homes to implement were providing 4 hours of after-hours care and a dedicated program for mental illness and substance abuse. The results also showed that the most compelling incentives for encouraging Tier 1 homes to upgrade their tier status were less"red tape"with prior authorizations, higher pay, and help with panel member follow-up. DISCUSSION: Multiple interventions may help medical homes in Oklahoma advance from the basic to the optimal level such as sharing of resources among nearby practices, expansion of OHCA online resources to help with preauthorizations and patient follow up, and the generation and transmission of data on the benefits of medical homes.

The role of leptin, melanocortin, and neurotrophin system genes on body weight in anorexia nervosa and bulimia nervosa.

OBJECTIVE: Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to small sample size and clinical heterogeneity. This study: (1) assessed the role of leptin, melanocortin, and neurotrophin genetic variants in conferring risk for AN and BN; and (2) explored the involvement of these genes in body mass index (BMI) variations within AN and BN. METHOD: Our sample consisted of 745 individuals with AN without a history of BN, 245 individuals with BN without a history of AN, and 321 controls. We genotyped 20 markers with known or putative function among genes selected from leptin, melanocortin, and neurotrophin systems. RESULTS: There were no significant differences in allele frequencies among individuals with AN, BN, and controls. AGRP rs13338499 polymorphism was associated with lowest illness-related BMI in those with AN (p = 0.0013), and NTRK2 rs1042571 was associated with highest BMI in those with BN (p = 0.0018). DISCUSSION: To our knowledge, this is the first study to address the issue of clinical heterogeneity in eating disorder genetic research and to explore the role of known or putatively functional markers in genes regulating appetite and weight in individuals with AN and BN. If replicated, our results may serve as an important first step toward gaining a better understanding of weight regulation in eating disorders.

Primary amenorrhea in anorexia nervosa: impact on characteristic masculine and feminine traits.

Animal studies indicate that gonadal hormones at puberty have an effect on the development of masculine and feminine traits. However, it is unknown whether similar processes occur in humans. We examined whether women with anorexia nervosa (AN), who often experience primary amenorrhea, exhibit attenuated feminization in their psychological characteristics in adulthood due to the decrease/absence of gonadal hormones at puberty. Women with AN were compared on a number of psychological characteristics using general linear models on the basis of the presence/absence of primary amenorrhea. Although women with primary amenorrhea exhibited lower anxiety scores than those without primary amenorrhea, in general, results did not provide evidence of attenuated feminization in women with AN with primary amenorrhea. Future research should utilize novel techniques and direct hormone measurement to explore the effects of pubertal gonadal hormones on masculine and feminine traits.

Are at-home sleep studies performed using portable monitors (PMs) as effective at diagnosing obstructive sleep apnea (OSA) in adults as sleep laboratory-based polysomnography (PSG)?

UNLABELLED: RESIDENCY PROGRAM: University of Oklahoma Health Sciences Center, Department of Family and Preventive Medicine, Oklahoma City, OK. ANSWER: In patients with suspected OSA, it is reasonable to use PMs if the patient has a high pretest probability (based on an Epworth Sleepiness Scale (ESS) ≥10 and clinical symptoms*) without significant co-morbid heart disease or other sleep disorders and he/she is able to prove competency in setting up the home equipment properly without assistance. However, if the patient has a negative PM, it is standard to perform PSG as it appears approximately 20% will have a false negative PM. (*Clinical symptoms include snoring, witnessed apneas, obesity, pulmonary hypertension, refractory hypertension, morning headaches, increased neck circumference-->17 inches in men, >16 inches in women--daytime sleepiness.) LEVEL OF EVIDENCE FOR THE ANSWER: A. SEARCH TERMS: obstructive sleep apnea, polysomnography, portable home monitors, efficacy. INCLUSION CRITERIA: polysomnography, ambulatory, adults, humans. ESCLUSION CRITERIA: children.

Factors associated with recovery from anorexia nervosa.

Previous studies of prognostic factors of anorexia nervosa (AN) course and recovery have followed clinical populations after treatment discharge. This retrospective study examined the association between prognostic factors--eating disorder features, personality traits, and psychiatric comorbidity--and likelihood of recovery in a large sample of women with AN participating in a multi-site genetic study. The study included 680 women with AN. Recovery was defined as the offset of AN symptoms if the participant experienced at least one year without any eating disorder symptoms of low weight, dieting, binge eating, and inappropriate compensatory behaviors. Participants completed a structured interview about eating disorders features, psychiatric comorbidity, and self-report measures of personality. Survival analysis was applied to model time to recovery from AN. Cox regression models were used to fit associations between predictors and the probability of recovery. In the final model, likelihood of recovery was significantly predicted by the following prognostic factors: vomiting, impulsivity, and trait anxiety. Self-induced vomiting and greater trait anxiety were negative prognostic factors and predicted lower likelihood of recovery. Greater impulsivity was a positive prognostic factor and predicted greater likelihood of recovery. There was a significant interaction between impulsivity and time; the association between impulsivity and likelihood of recovery decreased as duration of AN increased. The anxiolytic function of some AN behaviors may impede recovery for individuals with greater trait anxiety.

Features associated with diet pill use in individuals with eating disorders.

We investigated the relation between diet pill use and eating disorder subtype, purging and other compensatory behaviors, body mass index (BMI), tobacco and caffeine use, alcohol abuse or dependence, personality characteristics, and Axis I and Axis II disorders in 1,345 participants from the multisite Price Foundation Genetics Studies. Diet pill use was significantly less common in women with restricting type of AN than in women with other eating disorder subtypes. In addition, diet pill use was associated with the use of multiple weight control behaviors, higher BMI, higher novelty seeking, and the presence of anxiety disorders, alcohol abuse or dependence, and borderline personality disorder. Findings suggest that certain clinical and personality variables distinguish individuals with eating disorders who use diet pills from those who do not. In the eating disorder population, vigilant screening for diet pill use should be routine clinical practice.

Temporal patterns of recovery across eating disorder subtypes.

OBJECTIVE: To compare patterns of recovery in individuals with index episodes of anorexia nervosa (AN) and bulimia nervosa (BN). METHOD: Using Kaplan-Meier methods and Cox proportional hazards models, comparisons were conducted that were conditional on duration of eating disorder from onset and included a conservative recovery criterion of 3 asymptomatic years. Data collection was retrospective and from two of the international Price Foundation genetic studies on 901 individuals with eating disorders. RESULTS: Using Kaplan-Meier methods, 11% of those with index AN and 10% of those with index BN met recovery criteria at 10 years. At 15 years, 16% of those with index AN and 25% of those with index BN met recovery criteria. In a Cox proportional hazards model the index BN group had three times the rate of recovery at 10-14 years (p=0.01) than the index AN group. CONCLUSIONS: Initially the probability of recovery was greater for those with index AN, but as the duration of the eating disorder lengthened those with BN had higher probabilities of recovery. Replication of these results with prospective data using similarly stringent recovery criteria and methods is required to confirm trends.

Influence of overanxious disorder of childhood on the expression of anorexia nervosa.

OBJECTIVE: Childhood anxiety often precedes the onset of anorexia nervosa (AN) and may mark a liability to the emergence of an eating disorder for some women. This study investigates the prevalence of overanxious disorder (OAD) among women with AN and explores how OAD impacts AN symptoms and personality traits. METHOD: Participants were 637 women with AN who completed an eating disorders history, the Structured Clinical Interview for DSM-IV Axis I Disorders, and assessments for childhood anxiety, eating disorder attitudes, and associated personality traits. RESULTS: Of 249 women (39.1%) reporting a history of OAD, 235 (94.4%) met criteria for OAD before meeting criteria for AN. In comparison to those without OAD, women with AN and OAD self-reported more extreme personality traits and attitudes and they engaged in more compensatory behaviors. CONCLUSION: Among individuals with AN, those entering AN on a pathway via OAD present with more severe eating disorder pathology.

Patterns of menstrual disturbance in eating disorders.

OBJECTIVE: To describe menstrual disturbance in eating disorders (ED). METHOD: We describe menstrual history in 1,705 women and compare eating, weight, and psychopathological traits across menstrual groups. RESULTS: Menstrual dysfunction occurred across all eating disorder subtypes. Individuals with normal menstrual history and primary amenorrhea reported the highest and lowest lifetime body mass index (BMI), respectively. Normal menstruation and oligomenorrhea groups reported greater binge eating, vomiting, and appetite suppressant use. Amenorrhea was associated with lower caloric intake and higher exercise. Harm avoidance, novelty seeking, perfectionism, and obsessionality discriminated among menstrual status groups. No differences in comorbid Axis I and II disorders were observed. CONCLUSION: Menstrual dysfunction is not limited to any eating disorder subtype. BMI, caloric intake, and exercise were strongly associated with menstrual function. Menstrual status is not associated with comorbidity. Menstrual irregularity is an associated feature of all ED rather than being restricted to AN only.