Gestational vitamin D deficiency and autism-related traits: the Generation R Study.

There is intense interest in identifying modifiable risk factors associated with autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in a continuous fashion, share risk factors with ASD, and thus can serve as informative phenotypes in population-based cohort studies. Based on the growing body of research linking gestational vitamin D deficiency with altered brain development, this common exposure is a candidate modifiable risk factor for ASD and autism-related traits. The association between gestational vitamin D deficiency and a continuous measure of autism-related traits at ~6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n=4229). 25-hydroxyvitamin D (25OHD) was assessed from maternal mid-gestation sera and from neonatal sera (collected from cord blood). Vitamin D deficiency was defined as 25OHD concentrations less than 25 nmol l-1. Compared with the 25OHD sufficient group (25OHD>50 nmol l-1), those who were 25OHD deficient had significantly higher (more abnormal) SRS scores (mid-gestation n=2866, ß=0.06, P<0.001; cord blood n=1712, ß=0.03, P=0.01). The findings persisted (a) when we restricted the models to offspring with European ancestry, (b) when we adjusted for sample structure using genetic data, (c) when 25OHD was entered as a continuous measure in the models and (d) when we corrected for the effect of season of blood sampling. Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny.

The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders.

The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30 000). Within the sample of 86 189 individuals, a total of 57 377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information, and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.

The association between adolescent psychopathology and subsequent physical activity in young adulthood: a 21-year birth cohort study.

BACKGROUND: The beneficial effects of physical activity (PA) for both physical and mental wellbeing are well established. Given that adolescence presents a critical developmental period during which life-long patterns of PA become established, the exploration of the longitudinal impact of adolescent psychopathology on adult PA status is of interest. METHODS: We analysed prospective data from 3663 young adults who participated in the Mater-University of Queensland Study of Pregnancy. Psychopathology was measured using the Youth Self-Report (YSR) at age 14. Participants' engagement in three types of PA (vigorous exercise, moderate exercise and walking) at age 21 were dichotomised into either 'none' or 'any'. For our main analysis, we examined the association between the YSR score and subsequent PA engagement using logistic regression. We also conducted sensitivity analyses of longitudinal associations between the YSR internalising and externalising symptoms score at age 14 and PA engagement at age 21. RESULTS: We found no longitudinal association between the total YSR score at age 14 and PA engagement at age 21. In addition, there was no longitudinal association between the YSR internalising or externalising symptoms and PA engagement. CONCLUSION: Our findings suggest that there is no longitudinal association between adolescent psychopathology and PA in young adulthood.

The role of genetic liability in the association of urbanicity at birth and during upbringing with schizophrenia in Denmark.

BACKGROUND: Studies have indicated that the association of urbanicity at birth and during upbringing with schizophrenia may be driven by familial factors such as genetic liability. We used a population-based nested case-control study to assess whether polygenic risk score (PRS) for schizophrenia was associated with urbanicity at birth and at age 15, and to assess whether PRS and parental history of mental disorder together explained the association between urbanicity and schizophrenia. METHODS: Data were drawn from Danish population registries. Cases born since 1981 and diagnosed with schizophrenia between 1994 and 2009 were matched to controls with the same sex and birthdate (1549 pairs). Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of a separate, large meta-analysis. RESULTS: Those with higher PRS were more likely reside in the capital compared with rural areas at age 15 [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01-1.40], but not at birth (OR 1.09, 95% CI 0.95-1.26). Adjustment for PRS produced almost no change in relative risks of schizophrenia associated with urbanicity at birth, but slightly attenuated those for urban residence at age 15. Additional adjustment for parental history led to slight attenuation of relative risks for urbanicity at birth [incidence rate ratio (IRR) for birth in capital = 1.54, 95% CI 1.18-2.02; overall p = 0.016] and further attenuation of relative risks for urbanicity at age 15 (IRR for residence in capital = 1.32, 95% CI 0.97-1.78; overall p = 0.148). CONCLUSIONS: While results regarding urbanicity during upbringing were somewhat equivocal, genetic liability as measured here does not appear to explain the association between urbanicity at birth and schizophrenia.

Smokin' hot: adolescent smoking and the risk of psychosis.

OBJECTIVE: Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective sample (N = 6081) from the Northern Finland Birth Cohort 1986. METHODS: Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. RESULTS: Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87; 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01-1.08). CONCLUSION: Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.

Psychotic experiences and religiosity: data from the WHO World Mental Health Surveys.

OBJECTIVES: Religiosity is often associated with better health outcomes. The aim of the study was to examine associations between psychotic experiences (PEs) and religiosity in a large, cross-national sample. METHODS: A total of 25 542 adult respondents across 18 countries from the WHO World Mental Health Surveys were assessed for PEs, religious affiliation and indices of religiosity, DSM-IV mental disorders and general medical conditions. Logistic regression models were used to estimate the association between PEs and religiosity with various adjustments. RESULTS: Of 25 542 included respondents, 85.6% (SE = 0.3) (n = 21 860) respondents reported having a religious affiliation. Overall, there was no association between religious affiliation status and PEs. Within the subgroup having a religious affiliation, four of five indices of religiosity were significantly associated with increased odds of PEs (odds ratios ranged from 1.3 to 1.9). The findings persisted after adjustments for mental disorders and/or general medical conditions, as well as religious denomination type. There was a significant association between increased religiosity and reporting more types of PEs. CONCLUSIONS: Among individuals with religious affiliations, those who reported more religiosity on four of five indices had increased odds of PEs. Focussed and more qualitative research will be required to unravel the interrelationship between religiosity and PEs.

The association between childhood adversities and subsequent first onset of psychotic experiences: a cross-national analysis of 23 998 respondents from 17 countries.

BACKGROUND: Although there is robust evidence linking childhood adversities (CAs) and an increased risk for psychotic experiences (PEs), little is known about whether these associations vary across the life-course and whether mental disorders that emerge prior to PEs explain these associations. METHOD: We assessed CAs, PEs and DSM-IV mental disorders in 23 998 adults in the WHO World Mental Health Surveys. Discrete-time survival analysis was used to investigate the associations between CAs and PEs, and the influence of mental disorders on these associations using multivariate logistic models. RESULTS: Exposure to CAs was common, and those who experienced any CAs had increased odds of later PEs [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.9-2.6]. CAs reflecting maladaptive family functioning (MFF), including abuse, neglect, and parent maladjustment, exhibited the strongest associations with PE onset in all life-course stages. Sexual abuse exhibited a strong association with PE onset during childhood (OR 8.5, 95% CI 3.6-20.2), whereas Other CA types were associated with PE onset in adolescence. Associations of other CAs with PEs disappeared in adolescence after adjustment for prior-onset mental disorders. The population attributable risk proportion (PARP) for PEs associated with all CAs was 31% (24% for MFF). CONCLUSIONS: Exposure to CAs is associated with PE onset throughout the life-course, although sexual abuse is most strongly associated with childhood-onset PEs. The presence of mental disorders prior to the onset of PEs does not fully explain these associations. The large PARPs suggest that preventing CAs could lead to a meaningful reduction in PEs in the population.

The association between psychotic experiences and disability: results from the WHO World Mental Health Surveys.

OBJECTIVE: While psychotic experiences (PEs) are known to be associated with a range of mental and general medical disorders, little is known about the association between PEs and measures of disability. We aimed to investigate this question using the World Mental Health surveys. METHOD: Lifetime occurrences of six types of PEs were assessed along with 21 mental disorders and 14 general medical conditions. Disability was assessed with a modified version of the WHO Disability Assessment Schedule. Descriptive statistics and logistic regression models were used to investigate the association between PEs and high disability scores (top quartile) with various adjustments. RESULTS: Respondents with PEs were more likely to have top quartile scores on global disability than respondents without PEs (19.1% vs. 7.5%; χ2  = 190.1, P < 0.001) as well as greater likelihood of cognitive, social, and role impairment. Relationships persisted in each adjusted model. A significant dose-response relationship was also found for the PE type measures with most of these outcomes. CONCLUSIONS: Psychotic experiences are associated with disability measures with a dose-response relationship. These results are consistent with the view that PEs are associated with disability regardless of the presence of comorbid mental or general medical disorders.

Associations of maternal and fetal 25-hydroxyvitamin D levels with childhood lung function and asthma: the Generation R Study.

BACKGROUND: Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma. OBJECTIVE: We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school-age children. METHODS: We performed a population-based prospective cohort study among 3130 mothers and their children. Maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels. At age of 6, airway resistance (Rint) was measured by interrupter technique and airway inflammation by fractional exhaled nitric oxide (FENO) using NIOX chemiluminescence analyser. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6. RESULTS: Maternal levels of 25-hydroxyvitamin D in mid-gestation were not associated with Rint, FeNO, wheezing patterns, or asthma. Children in the lowest tertile of 25-hydroxyvitamin D levels at birth had a higher Rint (Z-score (95% confidence interval [95% CI]): -0.42 (-0.84, -0.01), P-value for trend< 0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25-hydroxyvitamin D level was taken into account [Z-score (95% CI): -0.55 (-1.08, 0.01)]. CONCLUSION AND CLINICAL RELEVANCE: Low levels of 25-hydroxyvitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25-hydroxyvitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association and the long-term consequences.

Mental disorders among college students in the World Health Organization World Mental Health Surveys.

BACKGROUND: Although mental disorders are significant predictors of educational attainment throughout the entire educational career, most research on mental disorders among students has focused on the primary and secondary school years. METHOD: The World Health Organization World Mental Health Surveys were used to examine the associations of mental disorders with college entry and attrition by comparing college students (n = 1572) and non-students in the same age range (18-22 years; n = 4178), including non-students who recently left college without graduating (n = 702) based on surveys in 21 countries (four low/lower-middle income, five upper-middle-income, one lower-middle or upper-middle at the times of two different surveys, and 11 high income). Lifetime and 12-month prevalence and age-of-onset of DSM-IV anxiety, mood, behavioral and substance disorders were assessed with the Composite International Diagnostic Interview (CIDI). RESULTS: One-fifth (20.3%) of college students had 12-month DSM-IV/CIDI disorders; 83.1% of these cases had pre-matriculation onsets. Disorders with pre-matriculation onsets were more important than those with post-matriculation onsets in predicting subsequent college attrition, with substance disorders and, among women, major depression the most important such disorders. Only 16.4% of students with 12-month disorders received any 12-month healthcare treatment for their mental disorders. CONCLUSIONS: Mental disorders are common among college students, have onsets that mostly occur prior to college entry, in the case of pre-matriculation disorders are associated with college attrition, and are typically untreated. Detection and effective treatment of these disorders early in the college career might reduce attrition and improve educational and psychosocial functioning.

Towards a classification of biomarkers of neuropsychiatric disease: from encompass to compass.

There is currently considerable imprecision in the nosology of biomarkers used in the study of neuropsychiatric disease. The neuropsychiatric field lags behind others such as oncology, wherein, rather than using 'biomarker' as a blanket term for a diverse range of clinical phenomena, biomarkers have been actively classified into separate categories, including prognostic and predictive tests. A similar taxonomy is proposed for neuropsychiatric diseases in which the core biology remains relatively unknown. This paper divides potential biomarkers into those of (1) risk, (2) diagnosis/trait, (3) state or acuity, (4) stage, (5) treatment response and (6) prognosis, and provides illustrative exemplars. Of course, biomarkers rely on available technology and, as we learn more about the neurobiological correlates of neuropsychiatric disorders, we will realize that the classification of biomarkers across these six categories can change, and some markers may fit into more than one category.

Correlates of physical activity in people living with psychotic illness.

OBJECTIVE: In the light of the high prevalence of physical comorbidities in people with psychotic illness, there is a need to explore modifiable risk factors that may contribute to this disease burden. The benefits of physical activity to both physical and mental health have been well established. We aimed to examine the prevalence and correlates of physical activity in a national sample of adults living with psychotic illness. METHODS: Physical activity was assessed in 1801 people using the International Physical Activity Questionnaire. Participants were dichotomised into low and moderate-high physical activity groups and associations between physical activity and a range of sociodemographic, clinical and physical comorbidity variables were examined using logistic regression. RESULTS: More than half the participants were categorised in the moderate-high physical activity group with nearly half of the sample engaged in physical activity every day. There were significant associations between low physical activity and older age, unemployment, educational non-participation, antipsychotic medication use, social dysfunction, self-reported loneliness and obesity. However, there was no significant association between physical activity and sex, psychosis type, illness duration, physical comorbidity or negative symptoms. CONCLUSION: The findings from this study may inform future interventions designed to increase physical activity in people with psychotic illness.

The onset and offset of psychosis--and what happens in between--a commentary on 'Reappraising the long-term course and outcome of psychotic disorders: the AESOP-10 Study' by Morgan et al. (2014).

As one would expect for a heterogeneous syndrome like schizophrenia, at the individual level the course of symptoms and disability vary widely. Mindful that the definition of recovery/remission varies widely between studies, a recent systematic review and meta-analysis reported that the proportion of those with schizophrenia who recover on both symptom and functional outcome is modest (approximately 14%). A 10-year follow-up of the English multicentre AESOP incidence study provides more 'fine-grained' insights into the time course of symptom fluctuation for schizophrenia and other psychotic disorders. We highlight selected findings from the new study and speculate on the role of different outcome domains for future study (e.g., symptom, occupational/functional, cognition, physical health, patient-nominated outcomes). Because recovery is a multifaceted process, we need to develop a panel of practical and operationalizable criteria for remission and recovery.

Psychosis prevalence and physical, metabolic and cognitive co-morbidity: data from the second Australian national survey of psychosis.

BACKGROUND: There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities. METHOD: The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants. RESULTS: The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18-64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence. CONCLUSIONS: Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness.

Beyond sleep duration: distinct sleep dimensions are associated with obesity in children and adolescents.

OBJECTIVE: Short sleep duration is recognized as a significant risk factor in childhood obesity; however, the question as to how sleep contributes to the development of obesity remains largely unknown. The majority of pediatric studies have relied on sleep duration as the exclusive measure of sleep; this insular approach may be misleading given that sleep is a dynamic multidimensional construct beyond sleep duration, including sleep disturbances and patterns. Although these sleep dimensions partly overlap, it is necessary to determine their independent relation with obesity, which in turn, may inform a more comprehensive understanding of putative pathophysiological mechanisms linking sleep and obesity. The aim of the present study was to investigate whether sleep dimensions including sleep duration, disturbances, and patterns were individually associated with obesity, independent of multiple covariates. The second objective was to examine whether sleep disturbances and patterns were independently associated with obesity, after adjusting for sleep duration. METHODS: Participants included 240 healthy children and adolescents (Mage=12.60, s.d.=1.98; 45.8% females). Anthropometric measures included measured waist and hip circumference, body mass index Z-score, and percent body fat. Subjective sleep measures included sleep duration, sleep disturbances, sleep quality, and sleep patterns from youth- and parental report. RESULTS: Youth with larger adiposity and body composition measures reported poorer sleep quality (ß avg=-0.14, P<0.01), more sleep disturbances (ß avg=0.13, P<0.05), and showed a delayed sleep phase pattern (ß avg=0.15, P<0.05), independent of age, sex, pubertal status, physical activity, screen time, socioeconomic status, and sleep duration. Shorter sleep duration was significantly associated with obesity; however, this link was attenuated after adjustment of covariates. CONCLUSIONS: The results suggest that sleep measures beyond duration may more precisely capture influences that drive the negative association between sleep and obesity, and thus, yield more robust associations. As such, future studies are needed to better understand how distinct sleep dimensions confer risk for childhood obesity.

Changes in the diagnosed incidence of early onset schizophrenia over four decades.

OBJECTIVE: To explore changes in the diagnosed incidence of early onset schizophrenia (EOS) from 1971 to 2010. METHOD: Examination of incidence rates of schizophrenia in patients under 18 years of age, using a nationwide, population-based, mental health register. RESULTS: The age-standardized incidence rate (IR) of EOS in the period 1971-2010 was 3.17 (95% CI: 3.16, 3.18) per 100 000 person years in the age group 0-18 years, and 9.10 (95% CI: 9.00, 9.21) in the age group 12-18 years. In the period 1971-1993, the age-standardized IR of EOS was 1.80 (95% CI: 1.79, 1.82) per 100 000 person years in the age group 0-18 years, and 5.02 (95% CI: 4.92, 5.11) in the age group 12-18 years. In the period 1994-2010, the age-standardized IR of EOS was 5.15 (95% CI: 5.10, 5.20) per 100 000 person years in the age group 0-18 years, and 15.73 (95% CI: 15.22, 16.22) in the age group 12-18 years. The IR was higher for males than females in the periods 1971-1993 and 1971-2010, but in the period 1994-2010 the IR was higher for females than males. CONCLUSION: In recent years, the diagnosed incidence of EOS has increased and the usual male excess has disappeared. The changes in IR could be a result of changes in the diagnostic system, increased awareness of early psychosis or a reflection of actual underlying incidence of the disorder.

The heritability of delusional-like experiences.

OBJECTIVE: Delusional-like experiences (DLE) are common in the general community and are associated with a family history of mental illness. The aim of this study was to estimate the heritability of DLE. METHOD: The Peter's Delusional Inventory (PDI) was administered to a population-based cohort of mothers (n = 2861, aged 35-67 years) and their adult offspring (n = 3079, aged 18-23 years). Heritability of DLE was estimated from the sum scores of the 21 item PDI under the assumption that the covariance between mother-offspring scores is attributable to shared additive genetic factors. RESULTS: The means (medians and standard deviations) for the total PDI scores for the mothers and their offspring were 3.6 (3.0, 3.0) and 5.0 (4.0, 3.5), respectively. The Pearson correlation coefficient between mother and offspring PDI scores was 0.17 (P < 0.001). The heritability was estimated to be 0.35 (standard error 0.04). CONCLUSION: Heritable factors contribute to over a third of the variance of PDI scores in this population. In light of the association between a family history of a wide range of mental disorders and DLE, these experiences may represent a useful quantitative endophenotype for genetic studies of common mental disorders in population settings.