Cannabis Use Is Associated With Depression Severity and Suicidality in the National Comorbidity Survey-Adolescent Supplement.

Objective: To investigate the association of cannabis use with major depression and suicidal behavior in adolescence. Method: Data are from the National Comorbidity Survey-Adolescent Supplement N=10,123, a nationally representative survey of adolescents aged 13 to 18 years. Weighted logistic regression and ordinal regression analyses of major depression and suicidal behavior outcomes were conducted on cannabis variables, incorporating sociodemographic characteristics. Results: Adolescents with lifetime cannabis use have 2.07 times higher odds of mild/moderate (adjusted odds ratio [aOR]; 95% CI=1.69, 2.53) and 3.32 times higher odds of severe major depressive disorder (MDD; aOR; 95% CI=2.31, 4.75). Cannabis use (aOR 6.90, 95% CI=4.67,10.19), mild/moderate MDD (aOR 4.10, 95% CI=2.82, 5.98), and severe MDD (aOR 13.97, 95% CI = 7.59, 25.70) were associated with higher odds of suicide attempt. Past 12-month cannabis use (aOR 3.70, 95% CI = 2.16, 6.32), mild/moderate major depressive episodes (MDE) (aOR 7.85, 95% CI=3.59, 17.17), and severe MDE (aOR 36.36, 95% CI=13.68,96.64) were associated with higher odds of suicide attempt. The frequency of past 12-month cannabis use was associated with higher odds of suicide attempt and with MDE severity, with higher odds among individuals who use cannabis 3 or more days than among individuals who use cannabis less frequently, suggesting a dose effect. Among cannabis users, older age of onset of cannabis use was associated with lower odds of suicidal behaviors. Conclusion: Cannabis use is associated with higher odds of depression and depression severity in adolescence. Furthermore, depression and cannabis use are independently associated with higher odds of suicide attempt. Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

Assessing the Validity of the Ask Suicide-Screening Questions in Black Youth.

BACKGROUND: Given the increasing rates of suicide and nonfatal suicide attempts among Black youth in the United States, it is crucial that screening tools are valid in identifying Black youth at risk of suicide. OBJECTIVE: This study assessed the validity of the Ask Suicide-Screening Questions (ASQ) among Black youth. METHODS: This analysis used pooled data from 3 ASQ validation studies of pediatric medical patients aged 10-21 years. All participants completed the ASQ and the gold standard Suicidal Ideation Questionnaire. RESULTS: Of the 1083 participants, 330 (30.5%) were non-Hispanic Black and 753 (69.5%) were non-Hispanic White. ASQ psychometric properties for Black and White participants were equivalent (sensitivity = 94% vs. 90.9%; specificity = 91.4% vs. 91.8%, respectively). CONCLUSIONS: There were no significant differences in ASQ psychometric properties between Black and White youth, indicating that the ASQ is valid for screening Black youth at risk of suicide.

Headache and mental disorders in a nationally representative sample of American youth.

The objective of this study is to examine the association between headache and mental disorders in a nationally representative sample of American youth. We used the National Comorbidity Survey-Adolescent Supplement to assess sex-specific prevalence of lifetime migraine and non-migraine headache using modified International Headache Society criteria and examine associations between headache subtypes and DSM-IV mental disorders. Adolescent report (n = 10,123) was used to identify headache subtypes and anxiety, mood, eating, and substance use disorders. ADHD and behavior disorder were based on parent report (n = 6483). Multivariate logistic regression analyses controlling for key demographic characteristics were used to examine associations between headache and mental disorders. Headache was endorsed by 26.9% (SE = 0.7) of the total sample and was more prevalent among females. Youth with headache were more than twice as likely (OR 2.74, 95% CI 1.94-3.83) to meet criteria for a DSM-IV disorder. Migraine, particularly with aura, was associated with depression and anxiety (adjusted OR 1.90-2.90) and with multiple classes of disorders. Adolescent headache, particularly migraine, is associated with anxiety, mood, and behavior disorders in a nationally representative sample of US youth. Headache is highly prevalent among youth with mental disorders, and youth with headache should be assessed for comorbid depression and anxiety that may influence treatment, severity, and course of both headache and mental disorders.

Associations of Social Capital with Mental Disorder Prevalence, Severity, and Comorbidity among U.S. Adolescents.

OBJECTIVE: To examine cross-sectional associations between social capital constructs and 1) adolescent lifetime mental disorders, 2) severity of functional impairment, and 3) psychiatric comorbidity. METHOD: Data were from the National Comorbidity Survey Adolescent Supplement, a nationally representative mental health survey of 6,483 U.S. adolescents aged 13-18 years. Information from fully-structured diagnostic interviews, including adolescent and caregiver reports, was used to measure seven social capital constructs and lifetime DSM-IV mental disorders (mood, anxiety, behavior, substance use and eating disorder classes). Disorder severity was divided into severe vs. mild/moderate. Comorbidity was measured as the number of different classes of lifetime mental disorders. RESULTS: Adjusted for socio-demographics and caregivers' mental health, the most consistent associations with adolescent mental disorder were for supportive friendships (any disorder OR = 0.95, 95%CI = 0.91-0.99), family cohesion (OR = 0.81, 95%CI = 0.75-0.86), school bonding (OR = 0.76, 95%CI = 0.71-0.81), and extracurricular participation (OR = 0.90, 95%CI = 0.86-0.95), although results differed by disorder class. Caregiver-reported neighborhood trust and reciprocity and caregiver community involvement were less consistently associated with mental disorder. Medium levels of adolescent-reported affiliation with neighbors was associated with lower odds of mood (OR = 0.81, 95%CI = 0.66-0.98) and anxiety (OR = 0.78, 95%CI = 0.64-0.96) disorder, while high levels were associated with higher odds of behavior disorder (OR = 1.47, 95%CI = 1.16-1.87). Several associations were stronger for severe vs. mild/moderate disorder and with increasing comorbidity. CONCLUSION: Although we cannot infer causality, our findings support the notion that improving actual and/or perceived social capital, especially regarding friendships, family, and school, (e.g., through multimodal interventions) could aid in the prevention and treatment of both individual adolescent mental disorders and psychiatric comorbidity.

Mood and anxiety profiles differentially associate with physical conditions in US adolescents.

BACKGROUND: Mood and anxiety are widely associated with physical conditions, but research and treatment are complicated by their overlap, clinical heterogeneity, and manifestation on a spectrum rather than as discrete disorders. In contrast to previous work relying on threshold-level disorders, we examined the association between empirically-derived profiles of mood and anxiety syndromes with physical conditions in a nationally-representative sample of US adolescents. METHODS: Participants were 2,911 adolescents (aged 13-18) from the National Comorbidity Survey-Adolescent Supplement who provided information on physical conditions and reported at least one lifetime mood-anxiety 'syndrome' based on direct interviews with the Composite International Diagnostic Interview Version 3.0. Mood-anxiety syndromes reflected 3-level ratings from subthreshold to severe distress/impairment, and subtyped mood episodes. Stepwise latent profile analysis identified mood-anxiety profiles and tested associations with physical conditions. RESULTS: Three mood-anxiety profiles were identified: "Mood-GAD" (25.6%)-non-atypical depression, mania, generalized anxiety; "Atypical-Panic" (11.3%)-atypical depression, panic; and "Reference" (63.1%)-lower mood and anxiety except specific phobia. Headaches were more prevalent in Mood-GAD and Atypical-Panic than Reference (47.9%, 50.1%, and 37.7%, respectively; p=0.011). Heart problems were more common in Mood-GAD than Atypical-Panic (7.4% v 2.2%, p=0.004) and Reference, with back/neck pain more prevalent in Mood-GAD than Reference (22.5% v 15.3%, p=0.016). LIMITATIONS: Broad categories of physical conditions without information on specific diagnoses; replication regarding specificity is recommended. CONCLUSIONS: Heart problems and pain-related conditions were differentially associated with specific mood-anxiety profiles. Subtyping depression and anxiety-inclusive of subthreshold syndromes-and their patterns of clustering may facilitate etiologic and intervention work in multimorbidity.

Cabbage and Sauerkraut Consumption in Adolescence and Adulthood and Breast Cancer Risk among US-Resident Polish Migrant Women.

BACKGROUND: Breast cancer (BC) incidence and mortality are lower in Poland than in the United States (US). However, Polish-born migrant women to US approach the higher BC mortality rates of US women. We evaluated the association between consumption of cabbage/sauerkraut foods and BC risk in Polish-born migrants to US. METHODS: We conducted a case-control study of BC among Polish-born migrants in Cook County and the Detroit Metropolitan Area. Cases (n = 131) were 20-79 years old with histological/cytological confirmation of invasive BC. Population-based controls (n = 284) were frequency matched to cases on age and residence. Food frequency questionnaires assessed diet during adulthood and age 12-13 years. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated with conditional logistic regression. Consumption of total, raw/short-cooked, and long-cooked cabbage/sauerkraut foods was categorized as low, medium, or high (frequency of servings/week). RESULTS: Higher consumption of total and raw/short-cooked cabbage/sauerkraut foods, during both adolescence and adulthood, was associated with a significantly lower BC risk. Consumption of long-cooked cabbage/sauerkraut foods was low and not significantly associated with risk. The multivariate OR for total cabbage/sauerkraut consumption, high vs. low (>4 vs. ≤2 servings/week) during adolescence was 0.36 (95% CI = 0.18-0.71, ptrend < 0.01) and 0.50 (95% CI = 0.23-1.06, ptrend = 0.08) during adulthood. For raw/short-cooked cabbage/sauerkraut (>3 vs. ≤1.5 servings/week), the ORs were 0.35 (95% CI = 0.16-0.72, ptrend < 0.01) during adolescence and 0.37 (95% CI = 0.17-0.78, ptrend < 0.01) during adulthood. For joint adolescent/adult consumption of raw/short-cooked cabbage/sauerkraut foods, (high, high) vs. (low, low), the OR was 0.23 (95% CI = 0.07-0.65). The significant association for high adolescent consumption of raw/short-cooked cabbage/sauerkraut foods and reduced BC risk was consistent across all levels of consumption in adulthood. CONCLUSION: Greater consumption of total and raw/short-cooked cabbage/sauerkraut foods either during adolescence or adulthood was associated with significantly reduced BC risk among Polish migrant women. These findings contribute to the growing literature suggesting a protective effect of a potentially modifiable factor, cruciferous vegetable intake, on breast cancer risk.

Prenatal diagnosis of Cri-du-Chat syndrome with concomitant distal trisomy 10q syndrome in one fetus with ultrasound anomalies.

OBJECTIVE: The aim of this work was to characterize the genetic abnormalities and prenatal diagnosis indications in one fetus with Cri-du-Chat syndrome with codependent 10q24.2-q26.3 duplication in prenatal screening. MATERIALS AND METHODS: A 31-year-old woman had a second trimester serum screening that indicated the fetus was at low risk. During this pregnancy, the woman underwent amniocentesis at 18+4 weeks' gestation because of adverse fertility history and nuchal fold thickening. Cytogenetic analysis and next-generation sequencing analysis were simultaneously performed to provide genetic analysis of fetal amniotic fluid. According to abnormal results, parental chromosome karyotype of peripheral blood was performed to analysis. RESULTS: CNV-seq detected a 14.00 Mb deletion at 5p15.33-p15.2 and a 34.06 Mb duplication at 10q24.2-q26.3 in the fetus. Cytogenetic analysis of the fetus revealed a karyotype of 46, XY, der(5) t(5;10) (p15.2;q26.3). The karyotype of pregnant women was 46,XX,t(5;10) (p15.2;q24.2). The pregnancy was subsequently terminated after sufficient informed consent. CONCLUSION: This is the first study that reports prenatal diagnosis of a Cri-du-Chat syndrome with concomitant 10 q24.2-q26.3 duplication. Adverse pregnancy history has to be as an important indicator for prenatal diagnosis, and the genetic factors of abnormal pregnancy should be identified before next pregnancy. Nuchal fold thickening is closely related to fetal abnormalities. Combined with ultrasonography, the use of CNV-seq will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies.

Screening Pediatric Medical Patients for Suicide Risk: Is Depression Screening Enough?

PURPOSE: Medically ill youth are at increased risk for suicide. For convenience, hospitals may screen for suicide risk using depression screening instruments, though this practice might not be adequate to detect those at risk for suicide. This study aims to determine whether depression screening can detect suicide risk in pediatric medical inpatients who screen positive on suicide-specific measures. METHODS: A convenience sample of medical inpatients ages 10-21 years were recruited as part of a larger instrument validation study. Participants completed the Ask Suicide-Screening Questions, the Suicidal Ideation Questionnaire/Suicidal Ideation Questionnaire-Junior, and the Patient Health Questionnaire-Adolescent Version (PHQ-A). Univariate and multivariate statistics were calculated to examine the relationship between screening positive for depression and suicide risk. RESULTS: The sample consisted of 600 medical inpatients (59.2% female; 55.2% white; mean age 15.2 ± 2.84 years). Of participants who screened positive for suicide risk (13.5%; 81/600), 39.5% (32/81) did not screen positive for depression, and more than half (45/81) did not endorse PHQ-A item 9, which queries for thoughts of harming oneself or being better off dead. Twenty-six participants (32%) who screened negative for depression and on PHQ-A item nine were at risk for suicide. CONCLUSIONS: In this sample, depression screening alone failed to detect nearly a third of youth at risk for suicide. Although depression and suicide risk are strongly related, a significant portion of pediatric medical inpatients at risk for suicide may pass through the healthcare system unrecognized if depression screening is used as a proxy for identifying suicide risk.

Psychological, physical, and sleep comorbidities and functional impairment in irritable bowel syndrome: Results from a national survey of U.S. adults.

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) in referral practice commonly report mental disorders and functional impairment. Our aim was to determine the prevalence of mental, physical and sleep-related comorbidities in a nationally representative sample of IBS patients and their impact on functional impairment. METHODS: IBS was defined by modified Rome Criteria based on responses to the chronic conditions section of the National Comorbidity Survey-Replication. Associations between IBS and mental, physical and sleep disorders and 30-day functional impairment were examined using logistic regression models. RESULTS: Of 5,650 eligible responders, 186 met criteria for IBS {weighted prevalence 2.5% (SE = 0.3)}. Age >60 years was associated with decreased odds (OR = 0.3; 95% CI:.1-.6); low family income (OR = 2.4; 95% CI:1.2-4.9) and unemployed status (OR = 2.3; 95% CI:1.2-4.2) were associated with increased odds of IBS. IBS was significantly associated with anxiety, behavior, mood disorders (ORs 1.8-2.4), but not eating or substance use disorders. Among physical conditions, IBS was associated with increased odds of headache, chronic pain, diabetes mellitus and both insomnia and hypersomnolence related symptoms (ORs 1.9-4.0). While the association between IBS and patients' role impairment persisted after adjusting for mental disorders (OR = 2.4, 95% CI 1.5-3.7), associations with impairment in self-care, cognition, and social interaction in unadjusted models (ORs 2.5-4.2) were no longer significant after adjustment for mental disorders. CONCLUSION: IBS is associated with socioeconomic disadvantage, comorbidity with mood, anxiety and sleep disorders, and role impairment. Other aspects of functional impairment appear to be moderated by presence of comorbid mental disorders.

Meta-analysis of protein intake on the effect of Crohn's disease and ulcerative colitis.

BACKGROUND AND PURPOSE: published studies have assessed the effect of protein intake on Crohn's disease (CD) and ulcerative colitis (UC). However, the results were inconsistent. To provide a more precise estimation, a meta-analysis was performed to evaluate the association of protein intake in Crohn's disease and ulcerative colitis. METHODS: the PubMed, Chinese National Knowledge Infrastructure databases (CNKI), and Wanfang databases were searched to identify relevant studies. The summarized results of the relative risk (RR) with the corresponding 95 % confidence intervals (CI) were calculated using a random effects model. RESULTS: the final analysis included a total of nine articles. Nine studies reported on protein intake for the risk of UC and five studies reported on protein intake for the risk of CD. Overall, based on current studies, no significant association was found between protein intake and the risk of UC (RR = 1.13, 95 % CI = 0.82-1.55) or CD (RR = 1.18, 95 % CI = 0.51-2.74). A significant change was not found in the stratified analysis by study design and geographic location. CONCLUSIONS: in conclusion, the present meta-analysis suggested that dietary protein intake did not show a significant effect on the risk of UC or CD.

Validation of the ask suicide-screening questions (ASQ) with youth in outpatient specialty and primary care clinics.

OBJECTIVE: Validate the Ask Suicide-Screening Questions (ASQ) with youth in outpatient specialty and primary care clinics. METHOD: This is a cross sectional instrument validation study assessing the validity of the ASQ with respect to the standard criterion, Suicidal Ideation Questionnaire (SIQ/SIQ Jr.). The sample included 515 English speaking youth ages 10-21 years old from outpatient specialty and primary care clinics. ASQ sensitivity, specificity, positive and negative predictive values (PPV/NPV), positive and negative likelihood ratios, c statistic and respective receiver operating characteristic curves were assessed. RESULTS: A total of 335 outpatient specialty and 180 primary care clinic participants completed the study. In outpatient specialty clinics, the ASQ showed a sensitivity of 100.0% (95% CI: 80.5-100.0%), specificity of 91.2% (95% CI: 87.5-94.1%), and NPV of 100.0% (95% CI: 98.7-100.0). In the primary care clinic, the ASQ showed a sensitivity of 100.0% (95% CI: 59.0-100.0%), specificity of 87.9% (95% CI: 82.0-92.3%), and NPV of 100.0% (95% CI: 97.7-100.0). Forty-five (13.4%) outpatient specialty clinic participants and 28 (15.6%) primary care clinic participants screened positive for suicide risk on the ASQ. CONCLUSIONS: The ASQ is a valid screening tool for identifying youth at elevated suicide risk in outpatient clinical settings.

Direct synthesis of 2,3,5-trisubstituted pyrroles via copper-mediated one-pot multicomponent reaction.

We have developed a copper-mediated one-pot synthesis of 2,3,5-trisubstituted pyrroles from 1,3-dicarbonyl compounds and acrylates using ammonium acetate as a nitrogen source. The reaction achieves C-C and C-N bond formation and provides an efficient approach to access highly functionalized pyrroles without further raw material preparation. This method is operationally simple, compatible with a wide range of functional groups, and provides the target products in moderate to good yields.

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.

Validation and Feasibility of the ASQ Among Pediatric Medical and Surgical Inpatients.

OBJECTIVES: To validate the use of a brief suicide risk screening tool, the Ask Suicide-Screening Questions (ASQ) instrument, in pediatric inpatient medical and surgical settings. METHODS: Pediatric patients (10-21 years) hospitalized on inpatient medical and surgical units were recruited through convenience sampling for participation in a cross-sectional instrument validation study. The Suicidal Ideation Questionnaire was used as a standard criterion to validate the ASQ. Patient opinions about screening and parent consent to enroll in a suicide risk screening study were assessed to determine the feasibility of administering the ASQ in this venue. RESULTS: A total of 600 pediatric medical inpatients were screened. Compared with the gold standard, the ASQ had strong psychometric properties, with a sensitivity of 96.67% (95% confidence interval [CI]: 82.78 to 99.92), a specificity of 91.05% (95% CI: 88.40 to 93.27), a negative predictive value of 99.81% (95% CI: 98.93 to 99.99), and an area under curve of 0.94 (95% CI: 0.90 to 0.97). Only 3 participants (0.5%) had acute positive screen results on the ASQ, endorsing current suicidal ideation, whereas 77 participants (12.8%) screened nonacute positive, and 48 participants (8.0%) reported a past suicide attempt. CONCLUSIONS: The brief 4-item ASQ is a valid tool to detect elevated suicide risk in pediatric medical and surgical inpatients. Our findings also reveal that screening is feasible in terms of detection of suicidal thoughts and behaviors and is acceptable to parents and patients.

Validation of the Ask Suicide-Screening Questions for Adult Medical Inpatients: A Brief Tool for All Ages.

BACKGROUND: Few brief suicide risk screening instruments are validated for use in both adult and pediatric medical populations. Using the pediatric Ask Suicide-Screening Questions (ASQ) development study as a model, this study aimed to determine whether the ASQ is a valid suicide risk-screening instrument for use among adults medical patients, as well as to evaluate a set of other potential screening questions for use in adults. METHODS: Adult patients hospitalized on inpatient medical/surgical units from 4 hospitals were recruited to participate in a cross-sectional instrument-validation study. The 4-item ASQ and other candidate items were compared against the 25-item, previously validated Adult Suicidal Ideation Questionnaire as the criterion standard. RESULTS: A total of 727 adult medical inpatients completed the screening process. Compared with the Adult Suicidal Ideation Questionnaire, the ASQ performed best among the full set of candidate items, demonstrating strong psychometric properties, with a sensitivity of 100% (95% confidence interval = 90%-100%), a specificity of 89% (95% confidence interval = 86%-91%), and a negative predictive value of 100% (95% confidence interval = 99%-100%). A total of 4.8% (35/727) of the participants screened positive for suicide risk based on the standard criterion Adult Suicidal Ideation Questionnaire. CONCLUSIONS: The ASQ is a valid and brief suicide risk-screening tool for use among adults. Screening medical/surgical inpatients for suicide risk can be performed effectively for both adult and pediatric patients using this brief, primary screener.

Excessive sleepiness and associated symptoms in the U.S. adult population: prevalence, correlates, and comorbidity.

OBJECTIVE: This study examined the prevalence, sociodemographic features, patterns of comorbidity, and impact on functional impairment of excessive sleepiness (Ex.S) and associated symptoms in a nationally representative sample of adults using the National Comorbidity Survey Replication (NCS-R) dataset. METHODS: Participants ≥18 years (n = 5,962) were queried about their sleep using the Composite International Diagnostic Interview (CIDI). Specifically, respondents were questioned about feeling sleepy during the day and falling asleep in permissive situations, feelings of insufficient sleep despite adequate time in bed, and/or difficulty waking up. Those endorsing daytime sleepiness and at least one additional symptom were considered to have Ex.S plus associated symptoms. Associations between Ex.S plus associated symptoms and sociodemographics, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) mental disorders, chronic physical conditions, and functional impairment were examined. RESULTS: The prevalence of Ex.S plus associated symptoms in U.S. adults was 23.34% (standard error [SE] = 0.88) and significantly co-occurred with insomnia-related symptoms after adjusting for confounders (Odds ratio [OR] = 5.65; 95% confidence interval [CI] = 4.55-7.02). The presence of Ex.S and associated symptoms was more common in women, particularly younger women, those with lower family income, and the unemployed (all P<.001). After controlling for demographic characteristics and other confounders, Ex.S plus associated symptoms was associated with having a DSM-IV mental disorder (OR = 4.25; 95% CI = 3.53-5.10), a chronic physical condition (OR = 2.57; 95% CI = 1.94-3.42) and greater disability (P<.001). CONCLUSION: Ex. S with associated symptoms was common, frequently co-occurred with other mental and physical conditions, and was associated with substantial disability. Dissipation of some associations after controlling for insomnia-related symptoms indicated that physical-mental comorbidity and disability were greater among individuals with more pervasive sleep disturbances.

Prevalence and Correlates of Hypersomnolence Symptoms in US Teens.

OBJECTIVE: Recent attention to pervasive sleep deficits in US adolescents has focused on sleep patterns and insomnia, but there are limited data on the prevalence and correlates of hypersomnolence symptoms. METHOD: The sample included 6,483 adolescents 13 to 18 years of age who were interviewed directly and had parent reports in the National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a nationally representative sample of US youth. Information on sleep patterns/symptoms that were collected in the interview was used to determine the population prevalence of DSM-5 criterion A-defined hypersomnolence and component symptoms. Logistic regression analyses were used to examine associations between sleepiness and sub-symptoms of hypersomnolence with weekday/weekend bedtime, sleep duration, mental disorders, and psychotropic medication use. RESULTS: Of the sample, 41.5% reported feeling sleepy during the daytime and 11.7% met criteria for hypersomnolence. The prevalence of hypersomnolence varied depending on age (p < .001) and was more common in adolescent girls (odds ratio [OR] 1.40, 95% CI 1.09-1.78). Excessive sleepiness and hypersomnolence symptoms were associated with shorter sleep duration and delayed bedtimes on weekdays and weekends Hypersomnolence was significantly associated with insomnia (OR 2.45, 95% CI 1.87-3.21) and mental disorders (OR 1.99, 95% CI 1.42-2.77). After accounting for insomnia, hypersomnolence was no longer associated with use of psychotropic medication (OR 1.61, 95% CI 0.97-2.66). CONCLUSION: Of adolescents with adequate sleep duration, 11.7% still reported symptoms of hypersomnolence. The strong association between hypersomnolence and insomnia suggests that sleep disorders in adolescents can fluctuate between over- and under-sleeping. Potential mechanisms underpinning the strong associations between sleep disturbances and mental disorders should be further pursued and could provide insight into prevention efforts.

Physical-Mental Comorbidity of Pediatric Migraine in the Philadelphia Neurodevelopmental Cohort.

OBJECTIVE: To examine the associations between headaches and migraine with physical and mental disorders in a large pediatric registry. STUDY DESIGN: In total, 9329 youth aged 8-21 years from the Philadelphia Neurodevelopmental Cohort were included. Physical conditions, including headache, were ascertained from electronic medical records and in-person interviews. Modified International Classification of Headache Disorders (ICHD-II) criteria were used to classify migraine symptoms. Forty-two other physical conditions were classified into 14 classes of medical disorders. Mental disorders were assessed using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia. RESULTS: Lifetime prevalence of any headache was 45.5%, and of migraine was 22.6%. Any headache was associated with a broad range of physical disorders, attention-deficit/hyperactivity disorder (OR 1.2 [95% CI 1.1-1.4]), and behavior disorders (1.3 [1.1-1.5]). Youth with migraine had greater odds of specific physical conditions and mental disorders, including respiratory, neurologic/central nervous system, developmental, anxiety, behavior, and mood disorders than those with nonmigraine headache (OR ranged from 1.3 to 1.9). CONCLUSIONS: Comorbidity between headaches with a range of physical conditions that have been associated with adult migraine demonstrates that multimorbidity occurs early in development. Comorbidity may be an important index of heterogeneity of migraine that can guide clinical management, genetic investigation, and future research on shared pathophysiology with other disorders.

Physical Activity and Mental Disorder Among Adolescents in the United States.

OBJECTIVE: To estimate associations between physical activity (PA) and a broad range of lifetime mental disorders among adolescents, and to evaluate whether the context of sports participation impacts these associations. METHODS: The sample included 6,483 13-18 year-olds from the National Comorbidity Survey Adolescent Supplement. Adolescents completed face-to-face psychiatric interviews and a parent provided diagnostic and other family-level information on the participating adolescent by completing a self-administered questionnaire. PA was measured by adolescent self-report and dichotomized to indicate vigorous exercise several times a week. Nineteen psychiatric disorders were assessed using the Diagnostic and Statistical Manual of Mental Disorders criteria. Multiple logistic regression analyses were used to estimate associations of PA with mental disorders, suicidality, and psychological distress. RESULTS: Two thirds of adolescents reported being physically active. Active adolescents had significantly lower odds of mood disorder (Odds ratio[OR] = .74, 95% confidence interval [CI]=.58-.94), bipolar II disorder (OR = .54, 95% CI=.30-.99), and general psychological distress (OR = .71, 95% CI=.52-.96) than less/inactive adolescents. In contrast, adolescents who engaged in PA were more likely to have lifetime alcohol use disorder (OR = 1.78, 95% CI = 1.11-2.85), bulimia (OR = 5.84, 95% CI = 2.48-13.79), generalized anxiety disorder (OR = 2.04, 95% CI = 1.16-3.58), and posttraumatic stress disorder (OR = 1.65, 95% CI = 1.07-2.55). The direct associations between PA and alcohol use disorder and bulimia appeared to be specific to adolescents who participated in organized sports. DISCUSSION: Associations between PA and lifetime mental disorder among adolescents may differ according to both disorder type and the context in which PA occurs. Longitudinal studies that assess the context of PA may be able to explain apparent discrepant associations between PA and mental disorder.

Flightless-I Blocks p62-Mediated Recognition of LC3 to Impede Selective Autophagy and Promote Breast Cancer Progression.

p62 is a receptor that facilitates selective autophagy by interacting simultaneously with cargoes and LC3 protein on the autophagosome to maintain cellular homeostasis. However, the regulatory mechanism(s) behind this process and its association with breast cancer remain to be elucidated. Here, we report that Flightless-I (FliI), a novel p62-interacting protein, promotes breast cancer progression by impeding selective autophagy. FliI was highly expressed in clinical breast cancer samples, and heterozygous deletion of FliI retarded the development of mammary tumors in PyVT mice. FliI induced p62-recruited cargoes into Triton X-100 insoluble fractions (TI) to form aggregates, thereby blocking p62 recognition of LC3 and hindering p62-dependent selective autophagy. This function of Flil was reinforced by Akt-mediated phosphorylation at Ser436 and inhibited by phosphorylation of Ulk1 at Ser64. Obstruction of autophagic clearance of p62-recruited cargoes by FliI was associated with the accumulation of oxidative damage on proteins and DNA, which could contribute to the development of cancer. Heterozygous knockout of FliI facilitated selectively autophagic clearance of aggregates, abatement of ROS levels, and protein oxidative damage, ultimately retarding mammary cancer progression. In clinical breast cancer samples, Akt-mediated phosphorylation of FliI at Ser436 negatively correlated with long-term prognosis, while Ulk1-induced FliI phosphorylation at Ser64 positively correlated with clinical outcome. Together, this work demonstrates that FliI functions as a checkpoint protein for selective autophagy in the crosstalk between FliI and p62-recruited cargoes, and its phosphorylation may serve as a prognostic marker for breast cancer.Significance: Flightless-I functions as a checkpoint protein for selective autophagy by interacting with p62 to block its recognition of LC3, leading to tumorigenesis in breast cancer.Cancer Res; 78(17); 4853-64. ©2018 AACR.