The role impairment associated with mental disorder risk profiles in the WHO World Mental Health International College Student Initiative

OBJECTIVE: The objective of this study is to assess the contribution of mental comorbidity to role impairment among college students. METHODS: Web-based self-report surveys from 14,348 first-year college students (Response Rate [RR] = 45.5%): 19 universities, eight countries of the World Mental Health International College Student Initiative. We assessed impairment (Sheehan Disability Scales and number of days out of role [DOR] in the past 30 days) and seven 12-month DSM-IV disorders. We defined six multivariate mental disorder classes using latent class analysis (LCA). We simulated population attributable risk proportions (PARPs) of impairment. RESULTS: Highest prevalence of role impairment was highest among the 1.9% of students in the LCA class with very high comorbidity and bipolar disorder (C1): 78.3% of them had severe role impairment (vs. 20.8%, total sample). Impairment was lower in two other comorbid classes (C2 and C3) and successively lower in the rest. A similar monotonic pattern was found for DOR. Both LCA classes and some mental disorders (major depression and panic, in particular) were significant predictors of role impairment. PARP analyses suggest that eliminating all mental disorders might reduce severe role impairment by 64.6% and DOR by 44.3%. CONCLUSIONS: Comorbid mental disorders account for a substantial part of role impairment in college students. © 2018 John Wiley & Sons, Ltd

Accuracy of online survey assessment of mental disorders and suicidal thoughts and behaviors in Spanish university students. Results of the WHO World Mental Health- International College Student initiative

Objective To assess the accuracy of WMH-ICS online screening scales for evaluating four common mental disorders (Major Depressive Episode[MDE], Mania/Hypomania[M/H], Panic Disorder[PD], Generalized Anxiety Disorder[GAD]) and suicidal thoughts and behaviors[STB] used in the UNIVERSAL project. Methods Clinical diagnostic reappraisal was carried out on a subsample of the UNIVERSAL project, a longitudinal online survey of first year Spanish students (18-24 years old), part of the WHO World Mental Health-International College Student (WMH-ICS) initiative. Lifetime and 12month prevalence of MDE, M/H, PD, GAD and STB were assessed with the Composite International Diagnostic Interview-Screening Scales [CIDI-SC], the Self-Injurious Thoughts and Behaviors Interview [SITBI] and the Columbia-Suicide Severity Rating Scale [C-SSRS]. Trained clinical psychologists, blinded to responses in the initial survey, administered via telephone the Mini-International Neuropsychiatric Interview [MINI]. Measures of diagnostic accuracy and McNemar chi(2) test were calculated. Sensitivity analyses were conducted to maximize diagnostic capacity. Results A total of 287 students were included in the clinical reappraisal study. For 12-month and lifetime mood disorders, sensitivity/specificity were 67%/88.6% and 65%/73.3%, respectively. For 12-month and lifetime anxiety disorders, these were 76.8%/86.5% and 59.6%/71.1%, and for 12-month and lifetime STB, 75.9%/94.8% and 87.2%/86.3%. For 12-month and lifetime mood disorders, anxiety disorders and STB, positive predictive values were in the range of 18.1-55.1% and negative predictive values 90.2-99.0%; likelihood ratios positive were in the range of 2.1-14.6 and likelihood ratios negative 0.1-0.6. All outcomes showed adequate areas under the curve [AUCs] (AUC> 0.7), except M/H and PD (AUC = 0.6). Post hoc analyses to select optimal diagnostic thresholds led to improved concordance for all diagnoses (AUCs> 0.8). Conclusion The WMS-ICS survey showed reasonable concordance with the MINI telephone interviews performed by mental health professionals, when utilizing optimized cut-off scores. The current study provides initial evidence that the WMS-ICS survey might be useful for screening purposes

Association between maternal depression symptoms across the first eleven years of their child’s life and subsequent offspring suicidal ideation

Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child’s life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population-based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19,4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis

WHO World Mental Health Surveys International College Student Project: Prevalence and Distribution of Mental Disorders

Increasingly, colleges across the world are contending with rising rates of mental disorders, and in many cases, the demand for services on campus far exceeds the available resources. The present study reports initial results from the first stage of the WHO World Mental Health International College Student project, in which a series of surveys in 19 colleges across 8 countries (Australia, Belgium, Germany, Mexico, Northern Ireland, South Africa, Spain, United States) were carried out with the aim of estimating prevalence and basic sociodemographic correlates of common mental disorders among first-year college students. Web-based self-report questionnaires administered to incoming first-year students (45.5% pooled response rate) screened for six common lifetime and 12-month DSM-IV mental disorders: major depression, mania/hypomania, generalized anxiety disorder, panic disorder, alcohol use disorder, and substance use disorder. We focus on the 13,984 respondents who were full-time students: 35% of whom screened positive for at least one of the common lifetime disorders assessed and 31% screened positive for at least one 12-month disorder. Syndromes typically had onsets in early to middle adolescence and persisted into the year of the survey. Although relatively modest, the strongest correlates of screening positive were older age, female sex, unmarried-deceased parents, no religious affiliation, nonheterosexual identification and behavior, low secondary school ranking, and extrinsic motivation for college enrollment. The weakness of these associations means that the syndromes considered are widely distributed with respect to these variables in the student population. Although the extent to which cost-effective treatment would reduce these risks is unclear, the high level of need for mental health services implied by these results represents a major challenge to institutions of higher education and governments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).status: publishe

The descriptive epidemiology of DSM-IV Adult ADHD in the World Health Organization World Mental Health Surveys

We previously reported on the cross-national epidemiology of ADHD from the first 10 countries in the WHO World Mental Health (WMH) Surveys. The current report expands those previous findings to the 20 nationally or regionally representative WMH surveys that have now collected data on adult ADHD. The Composite International Diagnostic Interview (CIDI) was administered to 26,744 respondents in these surveys in high-, upper-middle-, and low-/lower-middle-income countries (68.5% mean response rate). Current DSM-IV/CIDI adult ADHD prevalence averaged 2.8% across surveys and was higher in high (3.6%)- and upper-middle (3.0%)- than low-/lower-middle (1.4%)-income countries. Conditional prevalence of current ADHD averaged 57.0% among childhood cases and 41.1% among childhood subthreshold cases. Adult ADHD was significantly related to being male, previously married, and low education. Adult ADHD was highly comorbid with DSM-IV/CIDI anxiety, mood, behavior, and substance disorders and significantly associated with role impairments (days out of role, impaired cognition, and social interactions) when controlling for comorbidities. Treatment seeking was low in all countries and targeted largely to comorbid conditions rather than to ADHD. These results show that adult ADHD is prevalent, seriously impairing, and highly comorbid but vastly under-recognized and undertreated across countries and cultures

Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells

We thank Anna-Lena Berg (AstraZeneca, Lund) and Cheryl Scudamore (MRC, Harwell, UK) for histological analysis, Julie Foster (Barts Cancer Institute, London) for CT scans, Johan Swinnen and Frank Claessens (Leuven University, Belgium) for discussion and AR-luciferase reporter plasmids, Florian Guillou (INRA, CNRS, Université de Tours, France) for the AMH-Cre mouse line and Laura Milne (MRC Centre for Reproductive Health, The University of Edinburgh) for technical support. We thank the members of the Cell Signalling group for critical input.International audienceThe organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interac

Regulation of p110delta PI 3-kinase gene expression.

BackgroundDespite an intense interest in the biological functions of the phosphoinositide 3-kinase (PI3K) signalling enzymes, little is known about the regulation of PI3K gene expression. This also applies to the leukocyte-enriched p110delta catalytic subunit of PI3K, an enzyme that has attracted widespread interest because of its role in immunity and allergy.Principal findingsWe show that p110delta expression is mainly regulated at the transcriptional level. In fibroblasts, lymphocytes and myeloid cells, p110delta gene transcription appears to be constitutive and not subject to acute stimulation. 5'RACE experiments revealed that p110delta mRNA transcripts contain distinct upstream untranslated exons (named exon -1, -2a, -2b, -2c and -2d), which are located up to 81 kb upstream of the translational start codon in exon 1. The levels of all the different p110delta transcripts are higher in leukocytes compared to non-leukocytes, with the p110delta transcript containing exon -2a most abundantly expressed. We have identified a highly conserved transcription factor (TF) binding cluster in the p110delta gene which has enhanced promoter activity in leukocytes compared to non-leukocytes. In human, this TF cluster is located immediately upstream of exon -2a whilst in mouse, it is located within exon -2a.ConclusionThis study identifies a conserved PIK3CD promoter region that may account for the predominant leukocyte expression of p110delta

Singlet oxygen production by UV and visible photoexcited porphyrins under different states of aggregation

peer reviewedTryptophan photosensitization was used to determine the quantum yield of singlet oxygen production by porphyrins irradiated with ultraviolet or visible light in phosphate buffer at pH 7.0. From a preliminary study of aggregation of these dyes, it was established that uroporphyrin, hematoporphyrin and deuteroporphyrin allowed to investigate the behaviour of monomers, dimers and higher aggregates, respectively. The photosensitization results show that monomers and polymers produce singlet oxygen with very similar yields. Inclusion of Zn2+ and Cu2+ metal ions on deuteroporphyrin inhibits partially (factor 3) and totally the singlet oxygen production

The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock.

Lipopolysaccharide activates plasma-membrane signaling and endosomal signaling by Toll-like receptor 4 (TLR4) through the TIRAP-MyD88 and TRAM-TRIF adaptor complexes, respectively, but it is unclear how the signaling switch between these cell compartments is coordinated. In dendritic cells, we found that the p110δ isoform of phosphatidylinositol-3-OH kinase (PI(3)K) induced internalization of TLR4 and dissociation of TIRAP from the plasma membrane, followed by calpain-mediated degradation of TIRAP. Accordingly, inactivation of p110δ prolonged TIRAP-mediated signaling from the plasma membrane, which augmented proinflammatory cytokine production while decreasing TRAM-dependent endosomal signaling that generated anti-inflammatory cytokines (interleukin 10 and interferon-β). In line with that altered signaling output, p110δ-deficient mice showed enhanced endotoxin-induced death. Thus, by controlling the 'topology' of TLR4 signaling complexes, p110δ balances overall homeostasis in the TLR4 pathway.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe