Psychiatric Etiology

KEY PUBLICATIONS

• Hammerschlag AR, de Leeuw C, Middeldorp CM, Polderman TJC (2019). Postsynaptic, neuron projection, and brain-expressed gene sets relate to the shared genetic risk across five psychiatric disorders. Psychological Medicine, e-pub JULY 25
• Jansen AG, Dieleman GC, Jansen PR, Verhulst FC, Posthuma D, Polderman TJC (2019). Associating psychiatric polygenic risk scores with neurodevelopmental disorders in a clinical child and adolescent sample. Behavior Genetics, e-pub JULY 11
• Pettersson E, Lichtenstein P, Larsson H, Song J, Attention Deficit/Hyperactivity Disorder Working Group of the iPSYCH-Broad-PGC Consortium, Autism Spectrum Disorder Working Group of the iPSYCH-Broad-PGC Consortium, Bipolar Disorder Working Group of the PGC, Eating Disorder Working Group of the PGC, Major Depressive Disorder Working Group of the PGC, Obsessive Compulsive Disorders and Tourette Syndrome Working Group of the PGC, Schizophrenia Working Group of the PGC + CLOZUK sample, Substance Use Disorder Working Group of the PGC, Argrawal A, Børglum AD, Bulik CM, Daly MJ, Davis LK, Demontis D, Edenberg HJ, Grove J, Gelernter J, Neale BM, Pardinas A, Stahl E, Walters JT, Walters R, Sullivan PF, Posthuma D, Polderman TJC (2018). Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half siblings, and genetic data of 333 748 cases and controls. Psychological Medicine, e-pub
• Jorim Tielbeek, Ada Johansson, Polderman TJC, Raitiainen R, Jansen PR, Taylor M, Burt A, Tiemeier H, Viding E, Plomin R, Martin NG, Beaver KM, Waldman I, Munafo M, Paunio T, Mous SE, Pappa I, De Leeuw C, Hammerschlag AR, Dick D, Faraone SV, Popma A, Medland SE, Posthuma D (2017). Meta-analyses of genome-wide association studies on antisocial behaviour reveal high polygenicity, sex specific effects and pleiotropy with educational attainment. JAMA Psychiatry, 74, 1242-1250
• Polderman TJC, Benyamin B, De Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM & Posthuma D (2015). Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature Genetics, May 2015, doi:10.1038/ng.3285

LINKS
Netherlands Autism Register
Sensory Sensitivity Research
Twin correlations and Heritability estimates of all Traits
Behavior Genetics Association
Minor Brain & Mind

TWEETS: @tincatwin

GENERAL

Nature or Nurture
The ‘Psychiatric Etiology’ group studies the role of nature and nurture, including their interaction, in psychiatric traits. ‘Why do certain individuals develop a disorder, and others not?’ Is it nature or nurture, or a combination of both? My main focus has been on the etiology of neurodevelopmental disorders such as Attention Deficit/Hyperactivity Disorder (ADHD), and Autism Spectrum Disorders (ASD). Based on twin data of the past 50 years, I published a huge heritability study on all human traits in Nature Genetics. This achievement was followed by a recent study in which I tested the homogeneity of heritability estimates of eight common psychiatric disorders based on a Swedish family design and on genetic data of the largest international consortia on psychiatric genetics.

Heterogeneity of psychiatric traits
Like most psychiatric traits, ADHD and ASD are characterized by a heterogeneous manifestation of problems. This heterogeneity is often neglected, blurring the window to causal factors. More homogeneous phenotypes might be obtained by investigating specific symptoms of disorders. Evidence for specific etiological factors comes e.g., from twin studies on ADHD that reported etiological overlap but also specificity for the three core dimensions inattention, hyperactivity and impulsivity. In a new study on ASD we will focus on sensory sensitivity and link these specific behavioral symptoms to neuropsychological and neurophysiological assessments. 

Where are the genes?
Numerous studies have shown that genetic variation (nature) explains a large part of the variation in neurodevelopmental disorders. The identification of genes related to psychiatric traits, and in particular neurodevelopmental disorders, has been proven to be difficult. Apart from a focus on more homogeneous manifestations of problems, new gene finding strategies are crucial as well. One way to elucidate genetic pathways is to focus on functional gene networks, instead of single genes or genetic variants. In addition, the parallel investigation of brain measures and genetic information (‘imaging genetics’) in relation to psychiatric traits is a promising approach.

Gene by environment interaction
Apart from genetic effects alone, the interaction with environmental factors likely plays a role as well. Environmental risk factors that have been suggested for behavioral problems, including ADHD, are in utero exposure to nicotine, alcohol, and medical drugs. We aim to investigate the role of potential environmental risks on ADHD and externalizing problems while controlling for genetic risk, using recently available polygenic risk scores for ADHD and other psychiatric traits. This is in collaboration with two large longitudinal cohorts: the ABCD and Generation R study.