Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

This is the final version. Available from the publisher via the DOI in this record.UK Biobank Sleep Traits GWAS summary statistics are available at the Sleep Disorder Knowledge Portal (SDKP) website (http://www.sleepdisordergenetics.org). All other data are contained within the article and its supplementary information or available upon request.Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.Medical Research Council (MRC

Partial Support for an Interaction Between a Polygenic Risk Score for Major Depressive Disorder and Prenatal Maternal Depressive Symptoms on Infant Right Amygdalar Volumes

Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother-infant dyads (44 female, 11-54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample

Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

Peer reviewe

J. de Foville. — Les Della Robbia (les grands artistes). — Paris, Laurens

Picavet Camille Georges. J. de Foville. — Les Della Robbia (les grands artistes). — Paris, Laurens. In: Revue internationale de l'enseignement, tome 61, Janvier-Juin 1911. pp. 90-91

Sex-specific predictors of exposure to hospital-treated assaults among former adolescent psychiatric inpatients

Abstract This study examined the associations of psychiatric disorders, suicidal behavior and family-related characteristics during adolescence, to subsequent experiences of hospital-treated physical, or sexual assaults, among 508 young adults with a history of psychiatric inpatient care at adolescence (aged 13–17 years). Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) based adolescent psychiatric disorders were assessed at index hospitalization using Schedule for Affective Disorder and Schizophrenia for School-Age children, Present and Lifetime version (K-SADS-PL). Treatment episodes for assaults were obtained from the health care register, provided by the Finnish National Institute for Health Welfare. About 14.4% of the participants had experienced physical or sexual assault during their lifetime. Results of logistic regression analysis indicated that anxiety disorder (odds ratio [OR] = 9.6) and nonsuicidal self-injury (OR = 3.7) in adolescence for males, and personality disorder (OR = 3.4) for females, were associated with increased likelihood for subsequent assault exposure leading to hospitalization. These findings can be used in targeting vulnerable adolescents and designing primary prevention strategies

Misuse of prescribed psychotropic medication and drug crime offending:a follow-up case-control study of former adolescent psychiatric inpatients

Abstract Background: Various psychotropic prescription drugs are known to have potential for misuse. Among teenagers, non-medical use of prescription drugs may predate illicit drug use or occur concomitantly. Aims: Our aim was to examine prescriptions of psychotropic medications among drug crime offenders and non-criminal controls in a psychiatric inpatient cohort of 13–17-year-olds. Our research question was: were prescribed psychotropic and potentially addictive drugs associated with later drug crime offending. Methods: Our sample was of all 60 adolescents who had been convicted of a drug crime by young adulthood with a twice-sized control group, matched for gender, age and family-type, from a cohort of 508 adolescents consecutively admitted to a psychiatric inpatient care in Finland between April 2001 and March 2006. Adolescence-related information on substance use and psychiatric disorders was obtained by semi-structured interviews. Follow-up information on crimes and medication purchases was obtained from Finnish nationwide registers. The association of studied factors to drug crime offending was examined using stepwise binary logistic regression analysis. Results: 75% of drug crime offenders and 47% of non-criminal controls had used addictive psychotropic medications during the follow-up period (p < 0.001). 74% of all drug crime offenders’ purchases of prescribed addictive drugs occurred within the year preceding drug crimes. Of addictive drugs, the use of clonazepam and gabapentinoids was most likely to associate with drug crime offending (AOR 7.77, p < 0.001). Conduct and substance use disorders diagnosed in adolescence (AOR 3.49, p = 0.010; AOR 2.34, p = 0.050) were predictors for drug crime offending. Conclusions: Our findings suggest that, when treating young adults with conduct disorder and a history of substance use, physicians should prescribe addictive medications with caution, favouring instead non-addictive medications complemented by psychosocial interventions

Moderate associations between BDNF Val66Met gene polymorphism, musical expertise, and mismatch negativity

Auditory predictive processing relies on a complex interaction between environmental, neurophysiological, and genetic factors. In this view, the mismatch negativity (MMN) and intensive training on a musical instrument for several years have been used for studying environment-driven neural adaptations in audition. In addition, brain-derived neurotrophic factor (BDNF) has been shown crucial for both the neurogenesis and the later adaptation of the auditory system. The functional single-nucleotide polymorphism (SNP) Val66Met (rs6265) in the BDNF gene can affect BDNF protein levels, which are involved in neurobiological and neurophysiological processes such as neurogenesis and neuronal plasticity. In this study, we hypothesised that genetic variation within the BDNF gene would be associated with different levels of neuroplasticity of the auditory cortex in 74 musically trained participants. To achieve this goal, musicians and non-musicians were recruited and divided in Val/Val and Met- (Val/Met and Met/Met) carriers and their brain activity was measured with magnetoencephalography (MEG) while they listened to a regular auditory sequence eliciting different types of prediction errors. MMN responses indexing those prediction errors were overall enhanced in Val/Val carriers who underwent intensive musical training, compared to Met-carriers and non-musicians with either genotype. Although this study calls for replications with larger samples, our results provide a first glimpse of the possible role of gene-regulated neurotrophic factors in the neural adaptations of automatic predictive processing in the auditory domain after long-term training

Bullying involvement in relation to personality disorders:a prospective follow-up of 508 inpatient adolescents

Abstract We examined the association of bullying behavior in adolescence to personality disorder (PD) diagnosed in early adulthood. The study sample consisted of 508 adolescents (300 girls, 208 boys) who were admitted to psychiatric inpatient treatment between April 2001 and March 2006. Data were based on semi-structured K-SADSPL-interviews and hospital treatments extracted from the Care Register for Health Care (CRHC). At the end of 2013, details of psychiatric diagnoses recorded on hospital discharges and outpatient visits were extracted from the CRHC. This study showed that female victims of bullying have an almost fourfold likelihood of developing a PD later in life compared to adolescents with no involvement in bullying behavior. Most of the females had Borderline PD. Female adolescents diagnosed with anxiety disorder during adolescence had an over threefold risk of developing a PD during late adolescence or early adulthood. Conversely, we found no associations between bullying involvement among men in adolescence and subsequent PDs. Bullying victimization may influence the development of PDs among females. Adolescent services should pay particular attention to female victims of bullying and those displaying symptoms of anxiety disorders

Somatic morbidity among borderline and other personality disordered young adults:a register-based follow-up study of former adolescent psychiatric inpatients

Abstract Personality disorders (PDs) are related to increased prevalence of somatic diseases. The objective of this follow-up study was to explore somatic morbidity in subjects with PD diagnosed by early adulthood. The initial study population consisted of 508 former adolescent psychiatric inpatients (n=508). Of them, 63 subjects (39 women, 24 men) had a diagnosis of PD, including borderline PD (BPD) (n=38) and other PD (OPD) (n=25). The K-SADS-PL was used to gather information during the adolescent psychiatric hospitalization. The information on in- and outpatient hospital treatments, until the end of 2016, was extracted from the National Care Register for Health Care. 96.8% of subjects with PDs had somatic morbidity during the follow-up period. In comparison of prevalence between BPD and OPD groups, significant differences were found in Infectious and parasitic diseases (BPD vs. OPD, 63.2% vs. 36.0%, p=0.043), Endocrine, nutritional and metabolic diseases (23.7% vs. 0%, p=0.009) and Diseases of the genitourinary system (60.5% vs. 12.0%, <0.001). Symptoms, signs and abnormal findings were more common among BPD than OPD group (89.5% vs. 68.0%, p=0.050). Abdominal pain diagnoses were common among women with PD, especially in those with BPD. Nearly one-fifth of subjects with PD had been diagnosed with acute appendicitis. The findings of this study suggest that subjects with PDs already have high somatic morbidity in young adulthood. This study emphasizes the importance of evaluating the physical health of subjects with PD