Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether... Show moreOver the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N=272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias. Show less
Over the past three decades, functional MRI (fMRI) has become key to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into... Show moreOver the past three decades, functional MRI (fMRI) has become key to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (n = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (n = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared to full in-person psychiatric screening), recruited at least partly from convenience samples (compared to community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias. Show less
Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture... Show moreMaternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 x 10(-4), R-2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 x 10(-9), R-2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health. Show less
Tollenaar, M.S.; Beijers, R.; Garg, E.; Thao Nguyen, T.T.; Lin, D.T.S.; MacIsaac, J.L.; ... ; Weerth, C. de 2021
Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture... Show moreMaternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 x 10(-4), R-2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 x 10(-9), R-2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health. Show less
In the current study a three-generational design was used to investigate intergenerational transmission of child maltreatment (ITCM) using multiple sources of information on child maltreatment:... Show moreIn the current study a three-generational design was used to investigate intergenerational transmission of child maltreatment (ITCM) using multiple sources of information on child maltreatment: mothers, fathers and children. A total of 395 individuals from 63 families reported on maltreatment. Principal Component Analysis (PCA) was used to combine data from mother, father and child about maltreatment that the child had experienced. This established components reflecting the convergent as well as the unique reports of father, mother and child on the occurrence of maltreatment. Next, we tested ITCM using the multi-informant approach and compared the results to those of two more common approaches: ITCM based on one reporter and ITCM based on different reporters from each generation. Results of our multi-informant approach showed that a component reflecting convergence between mother, father, and child reports explained most of the variance in experienced maltreatment. For abuse, intergenerational transmission was consistently found across approaches. In contrast, intergenerational transmission of neglect was only found using the perspective of a single reporter, indicating that transmission of neglect might be driven by reporter effects. In conclusion, the present results suggest that including multiple informants may be necessary to obtain more valid estimates of ITCM. Show less
Chiu, C.D.; Ng, H.C.; Kwok, W.K.; Tollenaar, M.S. 2020
Child-driven genetic factors can contribute to negative parenting and may increase the risk of being maltreated. Experiencing childhood maltreatment may be partly heritable, but results of twin... Show moreChild-driven genetic factors can contribute to negative parenting and may increase the risk of being maltreated. Experiencing childhood maltreatment may be partly heritable, but results of twin studies are mixed. In the current study, we used a cross-sectional extended family design to estimate genetic and environmental effects on experiencing child maltreatment. The sample consisted of 395 individuals (225 women; M-age = 38.85 years, range(age) = 7-88 years) from 63 families with two or three participating generations. Participants were oversampled for experienced maltreatment. Self-reported experienced child maltreatment was measured using a questionnaire assessing physical and emotional abuse, and physical and emotional neglect. All maltreatment phenotypes were partly heritable with percentages for h(2) ranging from 30% (SE = 13%) for neglect to 62% (SE = 19%) for severe physical abuse. Common environmental effects (c(2)) explained a statistically significant proportion of variance for all phenotypes except for the experience of severe physical abuse (c(2) = 9%, SE = 13%, p = .26). The genetic correlation between abuse and neglect was rho(g) = .73 (p = .02). Common environmental variance increased as socioeconomic status (SES) decreased (p = .05), but additive genetic and unique environmental variances were constant across different levels of SES. Show less
Pittner, K.; Bakermans-Kranenburg, M.J.; Alink, L.R.A.; Buisman, R.S.M.; Berg, L.J.M. van den; Block, L.H.C.G.C.C.; ... ; IJzendoorn, M.H. van 2019
Child-driven genetic factors can contribute to negative parenting and may increase the risk of being maltreated. Experiencing childhood maltreatment may be partly heritable, but results of twin... Show moreChild-driven genetic factors can contribute to negative parenting and may increase the risk of being maltreated. Experiencing childhood maltreatment may be partly heritable, but results of twin studies are mixed. In the current study, we used a cross-sectional extended family design to estimate genetic and environmental effects on experiencing child maltreatment. The sample consisted of 395 individuals (225 women; M-age = 38.85 years, range(age) = 7-88 years) from 63 families with two or three participating generations. Participants were oversampled for experienced maltreatment. Self-reported experienced child maltreatment was measured using a questionnaire assessing physical and emotional abuse, and physical and emotional neglect. All maltreatment phenotypes were partly heritable with percentages for h(2) ranging from 30% (SE = 13%) for neglect to 62% (SE = 19%) for severe physical abuse. Common environmental effects (c(2)) explained a statistically significant proportion of variance for all phenotypes except for the experience of severe physical abuse (c(2) = 9%, SE = 13%, p = .26). The genetic correlation between abuse and neglect was rho(g) = .73 (p = .02). Common environmental variance increased as socioeconomic status (SES) decreased (p = .05), but additive genetic and unique environmental variances were constant across different levels of SES. Show less
