Significance: Crime, substance use problems, suicide, and severe mental illness, such as schizophrenia and bipolar disorder, are associated with enormous personal distress and societal costs. Identifying the causes of these problems, especially very early in life, is a crucial research endeavor. Researchers have identified numerous putative environmental factors that are associated with increased risk for these severe problems, including maternal smoking during pregnancy, maternal stress during pregnancy, maternal age at childbearing, and advancing paternal age at childbearing. We do not know, however, whether these risk factors are casual risk factors for severe forms of psychopathology or are merely indices of family confounding. Our limited understanding of the underlying causal mechanisms is due, in part, to the fact that most existent studies of these risks have failed to use research designs that can test alternative hypotheses, especially the role of environmental and genetic selection factors. Innovation: We propose to utilize powerful quasi-experimental designs, natural experiments that can pull-apart co-occurring risk mechanisms and account for unmeasured genetic and environmental processes, to explore the effects of several putative early risk factors. In particular, we will compare differentially exposed full siblings, an approach that rules out all genetic factors that could account for the statistical association between early putative risks and later outcomes, as well as all environmental factors that siblings share. We will also compare differentially exposed half siblings, offspring of full siblings (full cousins), offspring of half siblings (half cousins), and offspring of twins. These additional comparisons will enable us to provide converging evidence for our findings and identify the source any familial selection factors (genetic and/or environmental). Detailed assessments of offspring, parental, and community- level risks will further enable us to identify the mechanisms through which early risk factors are associated with severe psychopathology. Approach: We propose to analyze a large dataset that includes information on every individual who was born or lived in Sweden from 1940-1995 (NH7,500,000), which includes measures of early environmental risks, correlated familial and community risks, and well-validated indices of severe criminal, substance use, suicide, and mental health problems from Swedish national registries. Because the dataset also includes information on the biological relatedness of each individual with all of their family members, we are able to conduct numerous quasi-experimental studies of the associations by comparing individuals who differ in both their environmental and genetic risk. Environment and Investigators: Our experienced team includes international experts in the risks associated with early prenatal and perinatal factors;the assessment and etiology of severe psychopathology;the use of large, national registries;and the use of quasi-experimental designs to study putative environmental factors. Indiana University and the Karolinska Institutet provide strong environments and relevant resources.

Public Health Relevance

The staggering burden on individuals and society caused by violence, substance use problems, suicide, and severe mental illness has been well documented. Researchers have identified early risk factors that predict these major societal problems, but, it is still unclear whether putative early risks are truly causal or whether part-or most-of the associations with these risks are due to background familial factors. In order to improve prevention programs and our understanding of early risk factors, the current proposal seeks support to analyze a unique resource, a large dataset that includes every individual in Sweden for roughly five decades, relying on natural experiments to rigorously test causal hypotheses.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Social Sciences and Population Studies Study Section (SSPS)
Program Officer
King, Rosalind B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University Bloomington
Schools of Arts and Sciences
United States
Zip Code
Class, Quetzal A; Rickert, Martin E; Oberg, Anna S et al. (2017) Within-Family Analysis of Interpregnancy Interval and Adverse Birth Outcomes. Obstet Gynecol 130:1304-1311
Javaras, K N; Rickert, M E; Thornton, L M et al. (2017) Paternal age at childbirth and eating disorders in offspring. Psychol Med 47:576-584
Sariaslan, A; Fazel, S; D'Onofrio, B M et al. (2016) Schizophrenia and subsequent neighborhood deprivation: revisiting the social drift hypothesis using population, twin and molecular genetic data. Transl Psychiatry 6:e796
Sariaslan, Amir; Lichtenstein, Paul; Larsson, Henrik et al. (2016) Triggers for Violent Criminality in Patients With Psychotic Disorders. JAMA Psychiatry 73:796-803
D'Onofrio, Brian M; Class, Quetzal A; Rickert, Martin E et al. (2016) Translational Epidemiologic Approaches to Understanding the Consequences of Early-Life Exposures. Behav Genet 46:315-28
Sariaslan, A; Larsson, H; Fazel, S (2016) Genetic and environmental determinants of violence risk in psychotic disorders: a multivariate quantitative genetic study of 1.8 million Swedish twins and siblings. Mol Psychiatry 21:1251-6
Bramson, L M; Rickert, M E; Class, Q A et al. (2016) The association between childhood relocations and subsequent risk of suicide attempt, psychiatric problems, and low academic achievement. Psychol Med 46:969-79
Sujan, Ayesha C; Rickert, Martin E; Class, Quetzal A et al. (2016) A Genetically Informed Study of the Associations Between Maternal Age at Childbearing and Adverse Perinatal Outcomes. Behav Genet 46:431-56
Oberg, Anna Sara; D'Onofrio, Brian M; Rickert, Martin E et al. (2016) Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders. JAMA Pediatr 170:e160965
Class, Quetzal A; Mortensen, Preben B; Henriksen, Tine B et al. (2015) Preconception Maternal Bereavement and Infant and Childhood Mortality: A Danish Population-Based Study. Psychosom Med 77:863-9

Showing the most recent 10 out of 65 publications