Temporal changes in the associations between diagnosed psychiatric disorders and dropping out of school early.

Psychiatric problems are risk markers for poor educational attainment. The number of adolescents receiving treatment has increased. We investigated whether the association between psychiatric problems in early adolescence and dropping out of school had changed. We used the register-based 1987 and 1997 Finnish Birth Cohort studies, which include all live births in Finland. Hospital districts with incomplete records were excluded, leaving 25,421 participants born in 1987 and 32,025 born in 1997. The main outcome was not having applied for secondary education by the year the cohort members turned 18. Our main predictors were psychiatric and neurodevelopmental disorders diagnosed by specialized services during 1998-2003 and 2008-2013, when the cohort members were 10-16 years old. We found that 511 (2.0) of subjects born in 1987 and 499 (1.6%) born in 1997 dropped out of school. Having any diagnosis at 10-16 of age was associated with dropping out of school early in both cohorts: 3.9% in 1987 and 4.8% in 1997. The highest proportions were in the subgroup with autism spectrum disorders (ASD), 19.4% in 1987 and 16.2% in 1997. Dropping out early increased among adolescents diagnosed with any psychiatric or neurodevelopmental disorder, from 3.9 to 4.8%, with the clearest increase for learning disabilities, from 3.4 to 9.0%. Dropping out decreased for those with depression, from 4.5 to 2.1%. Adolescents with psychiatric and especially neurodevelopmental disorders, need effective interventions to prevent them dropping out of school early. Increased detection of psychopathology did not result in decreased dropout rates.

Maternal SSRI use during pregnancy and offspring depression or anxiety disorders: A review of the literature and description of a study protocol for a register-based cohort study.

Previous studies examining the relationship between in utero exposure to selective serotonin reuptake inhibitors (SSRI) and long-term offspring depressive or anxiety behaviors are inconclusive. We aimed to critically review the findings of previous studies and describe a new study protocol to investigate the association of prenatal SSRI exposure and offspring depression or anxiety using data from several Finnish national registers. The study includes 1,266,473 mothers and their live-born singleton offspring, born in 1996-2018. The study cohorts include the prenatally SSRI exposed group and three comparison groups: 1) depression exposed/antidepressants unexposed, 2) unexposed to antidepressants or antipsychotics and depression, and 3) discordant siblings. We aim to examine whether depression in prenatally SSRI exposed children is more common or severe than depression in the offspring of mothers with depression but without SSRI exposure. We aim to disambiguate the effects of maternal SSRI from the effects of maternal depression, severity of maternal depression and familial loading history of psychiatric disorders by including data from first-degree relatives of prenatally SSRI exposed and unexposed children. Associations between exposure and outcome are assessed by statistical modeling, accounting for within-family correlation. The study has potential public health significance and in guiding clinicians in considering treatment options for pregnant women.

Comparison of new psychiatric diagnoses among Finnish children and adolescents before and during the COVID-19 pandemic: A nationwide register-based study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) restrictions decreased the use of specialist psychiatric services for children and adolescents in spring 2020. However, little is known about the pattern once restrictions eased. We compared new psychiatric diagnoses by specialist services during pandemic and pre-pandemic periods. METHODS AND FINDINGS: This national register study focused on all Finnish residents aged 0 to 17 years from January 2017 to September 2021 (approximately 1 million a year). The outcomes were new monthly diagnoses for psychiatric or neurodevelopmental disorders in specialist services. These were analyzed by sex, age, home location, and diagnostic groups. The numbers of new diagnoses from March 2020 were compared to predictive models based on previous years. The predicted and observed levels in March to May 2020 showed no significant differences, but the overall difference was 18.5% (95% confidence interval 12.0 to 25.9) higher than predicted in June 2020 to September 2021, with 3,821 more patients diagnosed than anticipated. During this period, the largest increases were among females (33.4%, 23.4 to 45.2), adolescents (34.4%, 25.0 to 45.3), and those living in areas with the highest COVID-19 morbidity (29.9%, 21.2 to 39.8). The largest increases by diagnostic groups were found for eating disorders (27.4%, 8.0 to 55.3), depression and anxiety (21.0%, 12.1 to 51.9), and neurodevelopmental disorders (9.6%, 3.0 to 17.0), but psychotic and bipolar disorders and conduct and oppositional disorders showed no significant differences and self-harm (-28.6, -41.5 to -8.2) and substance use disorders (-15.5, -26.4 to -0.7) decreased in this period. The main limitation is that data from specialist services do not allow to draw conclusions about those not seeking help. CONCLUSIONS: Following the first pandemic phase, new psychiatric diagnoses in children and adolescents increased by nearly a fifth in Finnish specialist services. Possible explanations to our findings include changes in help-seeking, referrals and psychiatric problems, and delayed service access.

Psychotic Disorders in Adolescence and Later Long-term Exclusion From Education and Employment.

BACKGROUND AND HYPOTHESIS: Psychotic disorders have been associated with not being in education, employment, and training (NEET). There is a lack of knowledge on the importance of risk markers for NEET among people with psychotic disorders and what rehabilitation they receive. STUDY DESIGN: We based our research on the register-based 1987 Finnish Birth Cohort study, which included all live births in Finland during that year. The study cohort were 288 people who had been diagnosed with psychotic disorders during 2004-2007, when they were 16-20 year old, and 55 883 who had not. We looked at the national register data for those subjects in 2008-2015, when they were 20-28 year old, and compared any associations between sociodemographic factors and NEET status. STUDY RESULTS: NEET for more than 5 year affected 2.2% of those without psychosis, 35.8% of those with any nonaffective psychotic disorder, and 57.0% of those with schizophrenia or schizoaffective disorders. Family-related risk factors were weaker predictors of long-term NEET in subjects with psychotic disorders than other cohort members. Having a psychotic disorder plus long-term NEET was associated with not applying for upper secondary education, not finishing upper secondary education, parents receiving welfare benefits, being diagnosed with schizophrenia or schizoaffective disorders and being hospitalized for psychosis. Only 24.3% with psychotic disorders had participated in vocational rehabilitation. CONCLUSIONS: A diagnosis of psychosis in adolescence is independently associated with serious long term functional disability. Among those with psychotic disorders, educational problems are markers for adverse labor market outcomes. Despite this, vocational rehabilitation is seldom provided.

A systematic review of the mental health changes of children and young people before and during the COVID-19 pandemic.

There is increasing knowledge that the COVID-19 pandemic has had an impact on mental health of children and young people. However, the global evidence of mental health changes before compared to during the COVID-19 pandemic focusing on children and young people has not been systematically reviewed. This systematic review examined longitudinal and repeated cross-sectional studies comparing before and during COVID-19 pandemic data to determine whether the mental health of children and young people had changed before and during the COVID-19 pandemic. The Web of Science, PubMed, Embase and PsycINFO databases were searched to identify peer-reviewed studies that had been published in English and focused on children and young people between 0 and 24 years of age. This identified 21 studies from 11 countries, covering more than 96,000 subjects from 3 to 24 years of age. Pre-pandemic and pandemic data were compared. Most studies reported longitudinal deterioration in the mental health of adolescents and young people, with increased depression, anxiety and psychological distress after the pandemic started. Other findings included deteriorated negative affect, mental well-being and increased loneliness. Comparing data for pandemic and pre-pandemic periods showed that the COVID-19 pandemic may negatively impact the mental health of children and young people. There is an urgent need for high-quality research to address the impact, risks and protective factors of the pandemic on their mental health, as this will provide a good foundation for dealing with future health emergencies and other crises.

Potential for prediction of psychosis and bipolar disorder in Child and Adolescent Mental Health Services: a longitudinal register study of all people born in Finland in 1987.

Current strategies to predict psychosis identify only a small proportion of individuals at risk. Additional strategies are needed to increase capacity for pre-diction and prevention of serious mental illness, ideally during childhood and adolescence. One possible approach would be to investigate systems in which psychosis risk factors are concentrated during childhood. One notable such system is represented by Child and Adolescent Mental Health Services (CAMHS). Although psychotic disorders are uncommon in CAMHS, many risk factors for psychosis are highly prevalent in young people who enter this system. We hypothesized, therefore, that youth attending CAMHS would be a high-risk group for psychosis if followed into adulthood and, furthermore, that CAMHS systems would capture a substantial proportion of future psychosis cases. We constructed a total population cohort study of all Finns born in 1987 (N=55,875), linking together extensive register data on health care contacts from birth through age 28 years. We identified all individuals diagnosed with a psychotic or bipolar disorder by age 28 (N=1,785). The risk of psychosis/bipolar disorder by age 28 years was 1.8% for individuals who had not attended CAMHS during childhood or adolescence, whereas it was 12.8% for those with a history of any outpatient CAMHS contact (odds ratio, OR=7.9, 95% CI: 7.2-8.7). Furthermore, the risk of psychosis/bipolar disorder by age 28 years was 2.3% for individuals without a history of inpatient CAMHS admission, whereas it was 24.0% for those with a history of inpatient CAMHS admission (OR=13.3, 95% CI: 11.9-14.9), and 36.5% for those with a history of inpatient CAMHS admission in adolescence (age 13-17 years) (OR=24.2, 95% CI: 21.2-27.6). Individuals who attended CAMHS but received no mental disorder diagnosis had an equally high risk of subsequently developing a psychosis/bipolar disorder as individuals who did receive a diagnosis (OR=0.9, 99.5% CI: 0.7-1.1). Compared to other CAMHS attendees, individuals who developed psychosis or bipolar disorder were more likely to have had an initial CAMHS diagnosis of depressive or other mood disorder (OR=2.3, 99.5% CI: 1.6-3.0) and disruptive behaviour disorder (OR=1.7, 99.5% CI: 1.2-2.5). Of all psychosis/bipolar diagnoses by age 28 years, 50.2% occurred in individuals who had, at some point in childhood or adolescence, attended CAMHS, indicating that CAMHS represent not only a high-risk but also a high-capacity system for prediction of psychosis/bipolar disorder. These findings suggest an enormous, untapped potential for large-scale psychosis/bipolar disorder prediction and prevention research within existing specialist CAMHS.

School performance and later diagnoses of nonaffective psychoses, bipolar disorder, and depression.

OBJECTIVE: It is unclear whether there are differences between specific school subject performance and later psychiatric disorders. We examined whether mean grade point average (MGPA) and specific school subjects associated with diagnoses of nonaffective psychoses, bipolar disorder and depression. METHODS: In this register-based study, we studied the Finnish population born in 1987 who had available MGPA and six specific school grades (age = 15.4-16.4 years; n = 50,508). Grades were analyzed with smoothing splines. Covariates included sex, urbanicity, parental education level and parental diagnosed psychiatric disorders. Outcomes were incident nonaffective psychosis, bipolar disorder and depression diagnosed in specialized services until year 2015 (age = 28.0-28.9 years). RESULTS: During the follow-up, 727 individuals were diagnosed with nonaffective psychoses, 489 with bipolar disorder and 3492 with depression. MGPA was inversely associated with all outcomes. In multivariate models including specific school subjects and covariates, the school subject with largest risk ratios (RR) was Physical Education (RR and Bonferroni-corrected confidence interval [CI] at -1.5 SD: nonaffective psychoses 1.63, 1.36-1.95; bipolar disorder 1.64, 1.30-2.05; depression 1.72, 1.53-1.93). Higher grades in Art were associated with nonaffective psychoses and depression (RR and Bonferroni-corrected CI at +1.5 SD: nonaffective psychoses 1.48, 1.11-1.96; depression 1.22, 1.07-1.38). CONCLUSION: There was a robust association between poorer scores on Physical Education and risk for psychosis, bipolar disorder and depression. Higher grades in Art were also associated with risk for later disorders. Subject specific school performance may be more informative about mental disorder risk than overall school performance.

Registered psychiatric service use, self-harm and suicides of children and young people aged 0-24 before and during the COVID-19 pandemic: a systematic review.

BACKGROUND: The COVID-19 pandemic has impacted on psychiatric symptoms of children and young people, but many psychiatric services have been disrupted. It is unclear how service use, self-harm and suicide has changed since the pandemic started. To gain timely information, this systematic review focused on studies based on administrative data that compared psychiatric service use, self-harm and suicide before and during the pandemic among children and young people. METHODS AND FINDING: A systematic review of studies published in English from 1 January 2020 to 22 March 2021 was conducted, using the Web of Science, PubMed, Embase and PsycINFO databases. Increases or reductions in service use were calculated and compared using percentages. Of the 2,676 papers retrieved, 18 were eligible for the review and they provided data from 19 countries and regions. Most studies assessed changes during the early phase of the COVID-19 pandemic, from March to July 2020, and three assessed the changes until October 2020. Fifteen studies reported a total of 21 service use outcomes that were quantitively examined. More than three-quarters of the 21 outcomes (81%) fell by 5-80% (mean reduction = 27.9%, SD = 35%). Ten of the 20 outcomes for psychiatric emergency department (ED) services reduced by 5% to 80% (mean = 40.1%, SD = 34.9%) during the pandemic. Reductions in service use were also recorded for ED visits due to suicide ideation and self-harm, referrals to secondary mental health services, psychiatric inpatient unit admissions and patients receiving treatment for eating disorders. However, there were also some increases. Suicide rate and the number of ED visits due to suicide attempts have increased, and there was an increase in the number of treatment sessions in a service that provided telemedicine. CONCLUSION: Most of the studies showed reductions in the use of psychiatric services by children and young people during the early phase of the pandemic and this highlighted potential delays or unmet needs. Suicide rate has increased during the second wave of the pandemic. Further studies are needed to assess the pattern of service use in the later phases of the COVID-19 pandemic.

Time trends in treated incidence, sociodemographic risk factors and comorbidities: a Finnish nationwide study on anxiety disorders.

BACKGROUND: There has been a lack of research about the time trends and socio-demographic risk factors for children and adolescents who receive treatment for anxiety disorders. This study aimed to fill these gaps in our knowledge by examining a nationwide sample of Finnish children and adolescents diagnosed in specialized healthcare settings. METHODS: This study comprised national register data of all singleton children born in Finland from 1992-2006 who were diagnosed with anxiety disorders from 1998-2012. The changes in time trends in incidence were studied by dividing the study sample into three cohorts by birth years: 1992-1996, 1997-2001 and 2002-2006, who were followed up until the age of 20, 15 and 10 years, respectively. The 22,388 individuals with anxiety disorders were age and gender matched with 76,139 controls from the general population. Logistic regression was used to examine the socio-demographic risk factors and anxiety disorders in the entire sample. Comorbid disorders were examined in the oldest birth cohort (1992-1996 born). RESULTS: Comparing the 1992-1996 and 2002-2006 cohorts showed that the cumulative incidence of treated anxiety disorders at the age of 10 increased from 0.3 to 1.2% among females and 0.46 to 1.9% among males. Subjects had higher likelihood for being diagnosed with an anxiety disorder if their mothers had low maternal socio-economic status class at birth (OR 1.53, 95% CI 1.45-1.61) compared to higher SES class, and marital status was single at the time of birth (OR 2.02, 95% CI 1.87-2.17) compared to married or in a relationship. They had lower risk of anxiety disorders diagnosis if born in rural (OR 0.82, 95% CI 0.79-0.86) or semi-urban areas (OR 0.79, 95% CI 0.76-0.82) when compared to urban residence. There was a wide range of psychiatric comorbidities, and unipolar depression was the most common (31.2%). CONCLUSION: Anxiety disorders diagnosed by specialized Finnish services increased from 1998-2012 in both genders. This could indicate a real increase in overall anxiety disorders or an increase in treatment seeking. The findings on maternal socioeconomic status and single parenting improve the recognition of the environmental risk factors for anxiety disorders among children and adolescents.

Psychiatric disorders diagnosed in adolescence and subsequent long-term exclusion from education, employment or training: longitudinal national birth cohort study.

BACKGROUND: Long-term 'not in education, employment or training' (NEET) status is an important indicator of youth marginalisation. AIMS: To carry out a comprehensive overview of the associations between different psychiatric illnesses and long-term NEET status. METHOD: We used the register-based 1987 Finnish Birth Cohort study, which includes all live births in Finland during that year. The analyses comprised 55 273 individuals after exclusions for intellectual disability, death or emigration. We predicted that psychiatric disorders, diagnosed by specialist services between 1998 and 2007 when the cohort were 10-20 years of age, would be associated with subsequent long-term NEET (defined as NEET for at least 5 years between 2008 and 2015, when they were 20-28 years of age). RESULTS: In total, 1438 individuals (2.6%) were long-term NEET during follow-up and the associations between long-term NEET and the 11 diagnostic categories we studied were statistically significant (P < 0.001). In multivariate models we included sociodemographic characteristics and upper secondary education as covariates, and the highest effect sizes, measured by odds ratios (OR) with 95% confidence intervals (CI), were found for psychosis (OR = 12.0, 95% CI 9.5-15.2) and autism spectrum disorder (OR = 17.3, 95% CI 11.5-26.0). If individuals had not successfully completed this education, 70.6% of those with autism spectrum disorder and 48.4% of those with psychosis were later long-term NEET. CONCLUSIONS: Adolescents who receive treatment for psychiatric disorders, particularly autism spectrum disorder or psychosis, need support to access education and employment. This could help to prevent marginalisation in early adulthood.

The association between treated psychiatric and neurodevelopmental disorders and out-of-home care among Finnish children born in 1997.

Comprehensive overviews of the use of psychiatric services among children and adolescents placed in out-of-home care (OHC) by child welfare authorities are scarce. We examine specialized service use for psychiatric and neurodevelopmental disorders among children and adolescents in a total population involving children in OHC. We used the longitudinal administrative data of a complete Finnish birth cohort 1997 (N = 57,174). We estimated risk ratios (RRs) for a range of diagnosed psychiatric and neurodevelopmental disorders among children in OHC. We also estimated RRs for OHC among those with diagnosed disorders. We used descriptive methods to explore the timing of first entry into OHC relative to the first diagnosis. Among children in OHC, 61.9% were diagnosed with any psychiatric or neurodevelopmental disorder, compared with 18.0% among those never in OHC (RR: 3.7; 95% CI 3.6-3.8). The most common diagnosed disorders among children in OHC were depression and anxiety disorders, neurodevelopmental disorders, and oppositional defiant disorder/conduct disorder (ODD/CD). Among all children with any diagnosis, 18.1% experienced OHC, compared with 2.5% among those without a diagnosis (RR: 7.4; 95% CI 6.9-7.9). Of those diagnosed with self-harm and suicidality, ODD/CD, substance-related disorders, and psychotic and bipolar disorders, 43.5-61.2% experienced OHC. Of the children in OHC receiving psychiatric services, half were diagnosed before first placement in OHC. The majority of children with experience in OHC were diagnosed with psychiatric or neurodevelopmental disorders. They comprised a significant proportion of individuals treated for severe and complex psychiatric disorders and self-harm.

Familial confounding affected the associations between maternal smoking during pregnancy and offspring speech and language, scholastic and coordination disorders.

AIM: This study examined the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders in offspring, using sibling and population controls. METHODS: National Finnish registers were used to identify all 690 654 singletons born between 1996 and 2007 and any cases diagnosed with speech and language, scholastic, coordination and mixed developmental disorders by the end of 2012. Cases were compared to population controls, biological full-siblings and maternal half-siblings born during the same period. Conditional logistic regression was used to assess any associations between smoking during pregnancy and the selected developmental disorders. RESULTS: Prenatal smoking was higher in the mothers of the 27 297 cases (21.7%) than the 99 876 population controls (14.5%). The adjusted odds ratio for smoking throughout pregnancy, and any diagnosis of speech and language, scholastic, coordination or mixed developmental disorders, was 1.29 (95% confidence interval 1.24-1.34). However, when we compared a subsample of 15 406 cases and their 20 657 siblings, the association was no longer statistically significant (odds ratio 1.09, 95% confidence interval 0.98-1.21). CONCLUSION: The sibling comparisons suggested that the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders were confounded by familial factors shared by differentially exposed siblings.

Hospital Presentation for Self-Harm in Youth as a Risk Marker for Later Psychotic and Bipolar Disorders: A Cohort Study of 59 476 Finns.

Expanding clinical strategies to identify high risk groups for psychotic and bipolar disorders is a research priority. Considering that individuals diagnosed with psychotic and bipolar disorder are at high risk of self-harm, we hypothesised the reverse order relationship would also be true (ie, self-harm would predict psychotic/bipolar disorder). Specifically, we hypothesised that hospital presentation for self-harm would be a marker of high risk for subsequent development of psychotic/bipolar disorder and sought to test this hypothesis in a large population sample. This prospective register-based study included everyone born in Finland in 1987, followed until age 28 years (N = 59 476). We identified all hospital records of self-harm presentations, as well as all ICD-10 healthcare registrations of first diagnoses of psychotic and bipolar disorders. Cox proportional hazards models were used to assess the relationship between self-harm and psychotic/bipolar disorders. Of all individuals who presented to hospital with self-harm (n = 481), 12.8% went on to receive a diagnosis of psychosis (hazard ratio [HR] = 6.03, 95% confidence interval [CI] 4.56-7.98) and 9.4% a diagnosis of bipolar disorder (HR = 7.85, 95% CI 5.73-10.76) by age 28 years. Younger age of first self-harm presentation was associated with higher risk-for individuals who presented before age 18 years, 29.1% developed a psychotic or bipolar disorder by age 28 years. Young people who present to hospital with self-harm are at high risk of future psychotic and bipolar disorders. They represent an important cohort for the prevention of serious mental illness.

Incidence and comorbidities of disruptive behavior disorders diagnosed in Finnish specialist psychiatric services.

PURPOSE: Disruptive behavior disorders (DBD), including oppositional defiant disorder (ODD) and conduct disorder (CD), are some of the most common psychiatric conditions in childhood. Despite this, there has been limited research on DBDs. We examined the incidence, comorbidity and gender differences of DBDs diagnosed by specialist services. METHOD: This was a nationwide register study of 570,815 children and adolescents born in 1996-2005. The 7050 individuals diagnosed with DBD by specialist healthcare services were matched to 26,804 controls. RESULTS: By the age of 15, the cumulative incidence of diagnosed DBDs was 3.5% for boys and 1.4% for girls. The yearly incidence rate increased for girls after 13 years of age, while the incidence for boys was relatively stable between 8 and 15 years of age. When we compared subjects born between 1996-1998 and 1999-2001, we found that by the age of 12, the cumulative incidence per 100 people had increased from 0.56 to 0.68 among girls and from 2.3 to 2.6 among boys. This indicated a minor increase in treated incidence. The parents of children diagnosed with DBDs had lower educational levels than the parents of controls. Children with DBD were also more likely to have been diagnosed with other psychiatric disorders. CONCLUSION: Although DBDs were 3.5 times more common among boys during the whole follow-up period, the yearly incidence during adolescence was fairly similar between boys and girls. DBD existed alongside various psychiatric disorders at a relatively young age and only a minor increase in treated incidence was found during childhood.

Cumulative incidences of hospital-treated psychiatric disorders are increasing in five Finnish birth cohorts.

OBJECTIVE: The aim of this study was to explore changes in the incidences of childhood and early adulthood hospital-treated psychiatric disorders in five large Finnish birth cohorts of individuals born between 1966 and 1997. METHODS: The five birth cohorts were as follows: Northern Finland Birth Cohort 1966 (NFBC 1966) and 1986 (NFBC 1986), 1987 Finnish Birth Cohort (FBC 1987) and 1997 (FBC 1997), and Finnish 1981 Birth Cohort Study (FBCS 1981). Incidences of hospital-treated psychiatric disorders in each cohort were calculated separately for males (N = 71,209) and females (N = 65,190). Poisson regression was used to test difference in proportions of psychiatric disorders in wide range of diagnosis classes separately in childhood and adolescence, and early adulthood. RESULTS: The total incidences of psychiatric disorders in childhood and adolescence among males has increased in the birth cohorts over decades (Incidence Rate Ratio, IRR = 1.04 (1.04-1.05); p < 0.001). Similar result was seen among females (IRR = 1.04 (1.03-1.04); p < 0.001). In early adulthood, there was significant increase among females (IRR = 1.04 (1.03-1.05); p < 0.001), but among males, the change was not significant (IRR = 0.99 (0.99-1.00), p = 0.051). CONCLUSIONS: The main finding was that the cumulative incidence of hospital-treated psychiatric disorders increased over the decades in Finland. The increasing trend in hospital-treated psychiatric disorders in early adulthood was detected in females but not in males. In the youngest cohorts, the cumulative incidence of hospital-treated psychiatric disorders was at the same level in males and females, whereas in oldest cohort, males had higher incidence than females.

Risk for Premature Mortality and Intentional Self-harm in Autism Spectrum Disorders.

To examine the risk for premature mortality and intentional self-harm in autism spectrum disorders (ASD). Based on a national birth cohort. Children born in 1987-2005, diagnosed with ASD by 2007 (n = 4695) were matched with four non-ASD subjects (n = 18,450) and followed until 2015 for mortality and intentional self-harm. The risk among ASD subjects was elevated only for natural cause of death. The risk for intentional self-harm was increased in the unadjusted analyses, but decreased to non-significant after adjusting for comorbid psychiatric disorders. ASD subjects are at increased risk for premature mortality due to natural causes of death. While ASD subjects die of suicide and present with more self-harm, the association is explained by comorbid psychiatric disorders.

Maternal Vitamin D Levels and the Risk of Offspring Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Recent evidence has highlighted the importance of vitamin D in the development of the central nervous system. Some studies have shown an association between maternal vitamin D deficiency during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) symptoms based on parent or teacher ratings. There are no previous studies on early pregnancy 25-hydroxyvitamin D [25(OH)D] levels and the risk of diagnosed offspring ADHD. Our aim was to examine maternal 25(OH)D levels in early pregnancy and offspring ADHD. METHOD: In this nationwide population-based case-control study, 1,067 ADHD cases (born between 1998 and 1999 and diagnosed according to the International Classification of Diseases) and 1,067 matched controls were identified from Finnish registers. Maternal 25(OH)D levels were measured using quantitative immunoassay from maternal sera, collected during the first trimester and archived in the national biobank. Conditional logistic regression was used to examine the association between maternal 25(OH)D and offspring ADHD. RESULTS: There was a significant association between decreasing log-transformed maternal 25(OH)D levels and offspring ADHD both in the unadjusted analyses (odds ratio 1.65; 95% CI 1.33-2.05; p < .001) and in the analyses adjusting for maternal socioeconomic status and age (odds ratio 1.45; 95% CI 1.15-1.81; p = .002). Analyses by quintiles of maternal 25(OH)D levels in the lowest versus highest quintile revealed an adjusted odds ratio for offspring ADHD of 1.53 (95% CI 1.11-2.12; p = .010). CONCLUSION: This study demonstrated an association between low maternal 25(OH)D during pregnancy and an elevated risk for offspring ADHD. If replicated in independent samples, this finding may have significant public health implications.

Relative age and specific learning disorder diagnoses: A Finnish population-based cohort study.

Background: Being among the youngest in class has previously been associated with attention-deficit/hyperactivity disorder (ADHD) and academic disadvantage, but the relative age effect on learning disorders is less well understood. This study examined whether relatively young children are more likely to be diagnosed with specific learning disorders than their older peers. Methods: The setting included all 388,650 children born singleton in Finland from 1996 to 2002. Cases diagnosed with specific learning disorders in specialized health care by the age of 10 were identified from national registers. Cumulative incidences of specific learning disorders and the corresponding incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for each birth month compared to January. Results: During follow-up, 3162 (0.8% of 388,650) children were diagnosed with a specific learning disorder. Children born in December displayed higher cumulative incidences for specific learning disorders than children born in January (IRR: 1.77, 95% CI: 1.50-2.11). The findings were similar for girls (IRR: 2.01, 1.44-2.83) and boys (IRR: 1.70, 1.39-2.08). ADHD did not explain the association, as the IRR for the youngest children with specific learning disorders and ADHD was 1.59 (1.13-2.26) compared to those without ADHD (IRR: 1.84, 1.51-2.24). Conclusions: Relatively younger children in Finnish schools were more likely to be diagnosed with a specific learning disorder by the age of 10. Increased awareness of how relative age differences affect the likelihood for children to be diagnosed with specific learning disorders is needed among parents, clinicians, and teachers.

Robust data-driven identification of risk factors and their interactions: A simulation and a study of parental and demographic risk factors for schizophrenia.

OBJECTIVES: Few interactions between risk factors for schizophrenia have been replicated, but fitting all such interactions is difficult due to high-dimensionality. Our aims are to examine significant main and interaction effects for schizophrenia and the performance of our approach using simulated data. METHODS: We apply the machine learning technique elastic net to a high-dimensional logistic regression model to produce a sparse set of predictors, and then assess the significance of odds ratios (OR) with Bonferroni-corrected p-values and confidence intervals (CI). We introduce a simulation model that resembles a Finnish nested case-control study of schizophrenia which uses national registers to identify cases (n = 1,468) and controls (n = 2,975). The predictors include nine sociodemographic factors and all interactions (31 predictors). RESULTS: In the simulation, interactions with OR = 3 and prevalence = 4% were identified with <5% false positive rate and ≥80% power. None of the studied interactions were significantly associated with schizophrenia, but main effects of parental psychosis (OR = 5.2, CI 2.9-9.7; p < .001), urbanicity (1.3, 1.1-1.7; p = .001), and paternal age ≥35 (1.3, 1.004-1.6; p = .04) were significant. CONCLUSIONS: We have provided an analytic pipeline for data-driven identification of main and interaction effects in case-control data. We identified highly replicated main effects for schizophrenia, but no interactions.

Maternal serum C-reactive protein (CRP) and offspring attention deficit hyperactivity disorder (ADHD).

Exposure to infection and inflammation during the fetal period are associated with offspring neuropsychiatric disorders. Few previous studies have examined this association with ADHD with mixed findings. This study aims to examine the association between early gestational maternal C-reactive protein (CRP), prospectively assayed in stored maternal sera and the risk of ADHD in offspring. This study is based on the Finnish Prenatal studies of ADHD (FIPS-ADHD) with a nested case-control design. It includes all singleton-born children in Finland between January 1, 1998 and December 31, 1999 and diagnosed with ADHD. A total of 1079 cases and equal number of controls were matched on date of birth, sex and place of birth. Maternal CRP levels were assessed using a latex immunoassay from archived maternal serum specimens, collected during the first and early second trimester of pregnancy. Elevated maternal CRP when analyzed as a continuous variable was not associated with offspring ADHD (OR 1.05, 95% CI 0.96-1.15). No significant associations were seen in the highest quintile of CRP (OR 1.18, 95% CI 0.88-1.58). The results were similar in both sexes as well as among ADHD cases with or without comorbid ASD or conduct disorder. In this first study examining CRP, a biomarker for inflammation, during early pregnancy in relation to offspring ADHD, we report no significant associations. The lack of any association, when considered with positive findings seen in ASD and schizophrenia, and negative findings in bipolar disorder suggests different pathways linking maternal immune activation and development of various neuropsychiatric disorders.