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Risk Factors and Mental Disorders | Research at the EPiCSS group

The etiology of psychiatric disorders remains elusive; however, accumulating evidence suggests causal pathways comprising interaction between genetic vulnerability and key early life environmental exposures.

The research in our group aims to advance current knowledge about key early life risk factors for psychiatric disorders by combining an epidemiological population-based approach with analyses of biological samples.

Research projects

Early life immune environment and risk of psychiatric disorders

Project contact: Renee Gardner, Christina Dalman

It is well known that exposure to certain infectious agents (for example, Toxoplasma gondii or Cytomegalovirus) for the first time during pregnancy can affect the developing brain and nervous system of the fetus, leading to intellectual impairments and learning difficulties later in life.

Our research examines whether more subtle changes in the maternal immune system, such as those associated with infections, and exposure to serious infections during the first years of life can also lead to changes in the developing nervous system, influencing later risk of psychiatric disorders and changes in cognitive abilities.

We use two different types of studies to explore these questions. In the first type of study, we examine whether hospitalization for serious infections during pregnancy or during the early life of the child influences later risk of psychiatric disorders such as autism spectrum disorders (ASD) or schizophrenia and other non-affective psychoses.

For these studies, we use information from our register linkage database, Psychiatry Sweden, that collects data from Swedish regional and national registers regarding health care use and diagnoses. We have shown that infections during early life increase later risk of ASD and non-affective psychoses, as well as impairing later cognitive abilities.

In the second type of study, we take advantage of biological samples collected from pregnant women and newborn babies as part of routine healthcare procedures and stored in national and regional biobanks. Using these samples, we are able to measure specific markers related to maternal and fetal immune function (such as antibodies directed at specific infections and immune signaling molecules) and understand whether changes in these markers are linked to later risk of disorders such as ASD or schizophrenia.

In these studies, we have shown that maternal exposure to certain infections (such as T. gondii and CMV) increases risk of schizophrenia, as does having low levels of markers of innate (or non-specific) immunity at birth.

Association of Childhood Infection With IQ and Adult Nonaffective Psychosis in Swedish Men: A Population-Based Longitudinal Cohort and Co-relative Study.

Publications

Associations Between Maternal Infection During Pregnancy, Childhood Infections, and the Risk of Subsequent Psychotic Disorder--A Swedish Cohort Study of Nearly 2 Million Individuals.
Blomström Å, Karlsson H, Gardner R, Jörgensen L, Magnusson C, Dalman C
Schizophr Bull 2016 Jan;42(1):125-33

Influence of maternal infections on neonatal acute phase proteins and their interaction in the development of non-affective psychosis.
Blomström Å, Gardner RM, Dalman C, Yolken RH, Karlsson H
Transl Psychiatry 2015 Feb;5():e502

Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders.
Lee BK, Magnusson C, Gardner RM, Blomström Å, Newschaffer CJ, Burstyn I, et al
Brain Behav. Immun. 2015 Feb;44():100-5

Maternal nutrition and risk for neurodevelopmental disorders

Project contact: Renee Gardner

Maternal nutrition during pregnancy affects the developing brain. The most well-known example of this is the relationship between low folate and increased risk for neural tube defects.

The goal of this research is to understand if other aspects of nutrition during pregnancy can subtly influence the development of the child’s brain and therefore affect the child’s risk of neurodevelopmental disorders later in life.

We aim to understand whether maternal intake key nutrients and maternal deficiencies in those nutrients influence her child’s risk of developmental disorders. For example, iron is crucial to brain development. Studies in mice, rats, and monkeys have shown that iron deficiency during pregnancy can have lasting impact on the structure and function of the offspring’s brain.

Our ongoing studies explore whether maternal iron status and intake of iron supplements during pregnancy influences children’s risk of neurodevelopmental disorders like autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability.

We also aim to understand how more general measures of maternal nutrition, such as maternal weight at the start of pregnancy and weight gain during pregnancy, influence children’s risk of neurodevelopmental disorder.

We have shown that the total amount of weight a mother gained during pregnancy was associated with her child’s risk for ASD and schizophrenia, with the recommended weight gain of 11.5-16 kilograms during pregnancy offering the greatest protection in terms of preventing neurodevelopmental disorders.

Understanding how maternal nutrition and maternal metabolic disorders, such as gestational diabetes, relate to children’s risk of neurodevelopmental disorders will help us understand whether influencing maternal nutrition may help to prevent such disorders and to eventually inform doctors and midwives working in antenatal clinics regarding the best practice for prevention of neurodevelopmental disorders.

Publications

Association of Gestational Weight Gain and Maternal Body Mass Index in Early Pregnancy With Risk for Nonaffective Psychosis in Offspring.
Mackay E, Dalman C, Karlsson H, Gardner RM
JAMA Psychiatry 2017 04;74(4):339-349

Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study.
DeVilbiss EA, Magnusson C, Gardner RM, Rai D, Newschaffer CJ, Lyall K, et al
BMJ 2017 Oct;359():j4273

Maternal body mass index during early pregnancy, gestational weight gain, and risk of autism spectrum disorders: Results from a Swedish total population and discordant sibling study.
Gardner RM, Lee BK, Magnusson C, Rai D, Frisell T, Karlsson H, et al
Int J Epidemiol 2015 Jun;44(3):870-83

Early life hormonal environment and neurodevelopmental disorders

Project contact: Kyriaki Kosidou

Autism is 2-4 times more prevalent in males than females which implies that factors in sexual differentiation, such as sex hormones during early life, might be important for the development of this disorder. Other neurodevelopmental disorders such as Attention deficit/hyperactivity disorder are also more prevalent in males than females.

This project explores the role of early life hormonal exposure, particularly sex hormones exposure, on the risk of autism and other neurodevelopmental disorders using a combination of register-data and bio-samples.

Publications

Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden.
Kosidou K, Dalman C, Widman L, Arver S, Lee BK, Magnusson C, et al
Mol. Psychiatry 2016 10;21(10):1441-8

Maternal Polycystic Ovary Syndrome and Risk for Attention-Deficit/Hyperactivity Disorder in the Offspring.
Kosidou K, Dalman C, Widman L, Arver S, Lee BK, Magnusson C, et al
Biol. Psychiatry 2017 Nov;82(9):651-659

Brief Report: Sexual Orientation in Individuals with Autistic Traits: Population Based Study of 47,000 Adults in Stockholm County.
Rudolph CES, Lundin A, Åhs JW, Dalman C, Kosidou K
J Autism Dev Disord 2018 02;48(2):619-624