Susanna Leivonen

Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders

IMPORTANCE Previous research has focused on examining the familial clustering of schizophrenia, bipolar disorder, and autism spectrum disorders (ASD). Little is known about the clustering of other psychiatric and neurodevelopmental disorders among siblings of persons with ASD. OBJECTIVE To examine the risk for psychiatric and neurodevelopmental disorders among full siblings of probands with ASD. DESIGN, SETTING, AND PARTICIPANTS The Finnish Prenatal Study of Autism and Autism Spectrum Disorders used a population-based cohort that included children born from January 1, 1987, to December 31, 2005, who received a diagnosis of ASD by December 31, 2007. Each case was individually matched to 4 control participants by sex and date and place of birth. The siblings of the cases and controls were born from January 1, 1977, to December 31, 2005, and received a diagnosis from January 1, 1987, to December 31, 2009. This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers. Data were analyzed from March 6, 2014, to February 12, 2016. MAIN OUTCOMES AND MEASURES The adjusted risk ratio (RR) for psychiatric and neurodevelopmental disorders among siblings of probands with ASD vs siblings of matched controls. Additional analyses were conducted separately for ASD subgroups, including childhood autism, Asperger syndrome, and pervasive developmental disorders not otherwise specified. Analyses were further stratified by sex and intellectual disability among the probands. RESULTS Among the 3578 cases with ASD (2841 boys [79.4%]) and 11 775 controls (9345 boys [79.4%]), 1319 cases (36.9%) and 2052 controls (17.4%) had at least 1 sibling diagnosed with any psychiatric or neurodevelopmental disorder (adjusted RR, 2.5; 95% CI, 2.3-2.6). The largest associations were observed for childhood-onset disorders (1061 cases [29.7%] vs 1362 controls [11.6%]; adjusted RR, 3.0; 95% CI, 2.8-3.3), including ASD (374 cases [10.5%] vs 125 controls [1.1%]; adjusted RR, 11.8; 95% CI, 9.4-14.7), tic disorders (28 cases [0.8%] vs 24 controls [0.2%]; adjusted RR, 4.3; 95% CI, 2.3-8.2), attention-deficit/hyperactivity disorder (189 cases [5.3%] vs 180 controls [1.5%]; adjusted RR, 3.7; 95% CI, 2.9-4.7), learning and coordination disorders (563 cases [15.7%] vs 697 controls [5.9%]; adjusted RR, 3.2; 95% CI, 2.8-3.6), intellectual disability (104 cases [2.9%] vs 137 controls [1.2%]; adjusted RR, 3.1; 95% CI, 2.3-4.2), conduct and oppositional disorders (180 cases [5.0%] vs 221 controls [1.9%]; adjusted RR, 2.8; 95% CI, 2.2-3.5), and emotional disorders with onset specific to childhood (126 cases [3.5%] vs 157 controls [1.3%]; adjusted RR, 2.6; 95% CI, 1.9-3.4). Autism spectrum disorders were also associated with schizophrenia spectrum disorders, affective disorders, anxiety disorders, and other neurotic and personality disorders among siblings. CONCLUSIONS AND RELEVANCE Psychiatric and neurodevelopmental disorders cluster among siblings of probands with ASD. For etiologic research, these findings provide further evidence that several psychiatric and neurodevelopmental disorders have common risk factors.

Parental age and the risk of attention-deficit/hyperactivity disorder: a nationwide, population-based cohort study.

OBJECTIVE An increasing number of studies has shown an association between parental age and psychiatric disorders. However, there are inconsistent results regarding whether age at parenthood is associated with attention-deficit/hyperactivity disorder (ADHD). The aim of this study is to examine whether low or advanced parental age is associated with ADHD. METHOD In this nested case-control study, we identified 10,409 individuals with ADHD born in Finland during 1991 to 2005 and diagnosed with ADHD between 1995 and 2011, along with 39,125 controls matched on sex, date, and place of birth, from nationwide population-based registers. Conditional logistic regression was used to examine the association between parental age and ADHD in offspring, adjusting for potential confounding due to parental psychiatric history, maternal socioeconomic status, marital status, maternal smoking during pregnancy, number of previous births, and birth weight for gestational age. RESULTS Fathers younger than 20 years had a 1.5-fold (odds ratio [OR] = 1.55, 95% CI = 1.11-2.18, p = .01) increased risk of having offspring with ADHD as compared to fathers aged 25 to 29 years. Mothers of the same age group had a 1.4-fold (OR = 1.41, 95% CI = 1.15-1.72, p =.0009) increased risk. Advanced maternal age was inversely associated with ADHD (OR = 0.79, 95% CI = 0.64-0.97, p = .02). CONCLUSION ADHD was associated with young fathers or mothers at the time of birth. Health professionals working with young parents should be aware of the increased risk of ADHD in offspring. This will improve early detection; however, for the development of preventive measures and appropriate interventions, more information on the developmental pathways is needed.

A nationwide register study of the characteristics, incidence and validity of diagnosed Tourette syndrome and other tic disorders

The aim of this study was to describe the characteristics and incidence rates of diagnosed tic disorders in the Finnish Hospital Discharge Register, including changing incidence rates between 1991 and 2010. We also aimed to validate the diagnoses of Tourettes syndrome recorded in the register.

The association between congenital anomalies and autism spectrum disorders in a Finnish national birth cohort

The first aim of this study was to evaluate the association between different subgroups of autism spectrum disorders (ASDs) (childhood autism, Asperger syndrome, and pervasive developmental disorder/pervasive developmental disorder – not otherwise specified [PDD/PDD‐NOS]) and congenital anomalies. Second, we assessed the association among intellectually disabled children with ASDs in the subgroups of childhood autism and PDD/PDD‐NOS.

Obstetric and Neonatal Adversities, Parity, and Tourette Syndrome: A Nationwide Registry.

OBJECTIVE To determine the relationships between parity, obstetric adversities, neonatal factors, and Tourette syndrome in a large nationwide cohort. STUDY DESIGN This nationwide, register-based, nested case-control study identified all children diagnosed with Tourette syndrome born between 1991 and 2010 from the Finnish Hospital Discharge Register (n = 767). Each case was matched to 4 controls. Information on parity, obstetric, and neonatal factors was obtained from the Finnish Medical Birth Register. Conditional logistic regression was used to determine the relationship between parity, obstetric, and neonatal factors, and Tourette syndrome. RESULTS Nulliparity was associated with increased odds for Tourette syndrome (OR 1.7, 95% CI 1.4-2.2), and 3 or more previous births was associated with decreased odds for Tourette syndrome (OR 0.5, 95% CI 0.3-0.9) compared with parity 1-2. Birth weight 4000-4499 g was associated with decreased odds for Tourette syndrome (OR 0.7, 95% CI 0.5-0.9). Low birth weight, gestational age, weight for gestational age, Apgar score at 1 minute, induced labor, birth type or presentation, neonatal treatment, or maternal blood pressure were not associated with Tourette syndrome. CONCLUSIONS Increasing parity and high birth weight are associated with decreased odds for Tourette syndrome.

Parental age and the risk of obsessive compulsive disorder and Tourette syndrome / chronic tic disorder in a nationwide population-based sample

OBJECTIVES Advancing paternal age has been associated with several neuropsychiatric disorders in children. However, there is limited understanding of this association with obsessive compulsive disorder (OCD) and Tourette syndrome/chronic tic disorder (TS/CT) with inconsistent findings. We examined the association between parental age and offspring OCD and TS/CT. METHODS This nested case-control study used the Finnish Hospital Discharge Register (FHDR) to identify 1358 individuals with OCD and 1195 with TS/CT, born from 1991 to 2009 and diagnosed by 2010. Each case was matched with four controls from the Finnish Population Register (FPR), without diagnoses of OCD, TS/CT or severe or profound mental retardation. Conditional logistic regression was used to examine the association between parental age and OCD, TS/CT. RESULTS A trend of increasing odds was seen with advancing maternal age. In the final model, offspring of mothers aged 35-39 years had a 1.3-fold increased odd (OR = 1,31, 95% confidence interval (95% CI:1.03-1.66)) of OCD compared with maternal aged 25-29 years. Offspring of fathers younger than 20 years had increased odds of TS/CT in the unadjusted analysis (OR = 2.43, 95% CI: 1.27-4.56). LIMITATIONS The study limitations included using hospital diagnoses to identify cases, with limited diagnostic validity, and the possible over representation of moderate to severe cases. CONCLUSIONS The lack of association between advancing paternal age and OCD is in contrast with schizophrenia, despite sharing demographic characteristics and possible shared neuropathology. Furthermore, these differences suggest different etiological pathways among TS/CT, autism spectrum disorder (ASD) and attention deficit/hyperactive disorder (ADHD), despite their frequently comorbid existence.