A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders

Keers, Robert; Coleman, Jonathan R. I.; Lester, Kathryn J.; Roberts, Stephen K.; Breen, Gerome; Thastum, Mikael; Bögels, Susan M.; Schneider, Silvia; Heiervang, Einar; Meiser‐Stedman, Richard; Nauta, Maaike; Creswell, Cathy; Thirlwall, Kerstin; Rapee, Ronald M.; Hudson, Jennifer L.; Lewis, Cathryn M.; Plomin, Robert; Eley, Thalia C.

doi:10.1159/000444023

Cited by 105 publications

(140 citation statements)

References 46 publications

(62 reference statements)

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“…Although a significant association with lower MCS and MH scores was observed, the comparatively large standard error (SE) of the wGRS variable makes any conclusions on its relative importance challenging. The significant interaction term for wGRS-time predicting MH, indicating slower improvements in MH among individuals with high MDD genetic risk, is consistent with previous work indicating that depression genetic risk increases an individual's sensitivity to adverse environmental effects (38,39). Taken together, these findings support the notion that depression is a complex disorder with a modest, albeit important, genetic contribution comprising thousands of alleles of a small effect size.…”

Section: Discussionsupporting

confidence: 88%

The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis

et al. 2017

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Section: Discussionsupporting

confidence: 88%

The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis

et al. 2017

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“…Genetic markers have been found in genes involved in the dopaminergic and serotonergic system. In particular, the carriers of the dopamine receptor D4 7-repeat alleles seem to be open to the environment, for better and for worse, as demonstrated in correlational as well as experimental studies and this genotype might be embedded in larger dopamine-related genetic pathways or polygenetic susceptibility scores (Belsky & van IJzendoorn, 2017;Keers et al, 2016;Lemery-Chalfant et al, 2018). Another marker of differential susceptibility is biological sensitivity to context, involving heightened stress and immune reactivity to negative stimuli in a chaotic and stressful environment, and at the same time elevated processing of positive stimuli in a structured, supportive environment (Boyce, 2019).…”

Section: Figurementioning

confidence: 99%

Annual Research Review: Umbrella synthesis of meta‐analyses on child maltreatment antecedents and interventions: differential susceptibility perspective on risk and resilience

IJzendoorn

Bakermans‐Kranenburg

Coughlan

et al. 2019

Child Psychology Psychiatry

148

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Child maltreatment in the family context is a prevalent and pervasive phenomenon in many modern societies. The global perpetration of child abuse and neglect stands in stark contrast to its almost universal condemnation as exemplified in the United Nation’s Convention on the Rights of the Child. Much work has been devoted to the task of prevention, yet a grand synthesis of the literature is missing. Focusing on two core elements of prevention, that is, antecedents for maltreatment and the effectiveness of (preventative) interventions, we performed an umbrella review of meta‐analyses published between January 1, 2014, and December 17, 2018. Meta‐analyses were systematically collected, assessed, and integrated following a uniform approach to allow their comparison across domains. From this analysis of thousands of studies including almost 1.5 million participants, the following risk factors were derived: parental experience of maltreatment in his or her own childhood (d = .47), low socioeconomic status of the family (d = .34), dependent and aggressive parental personality (d = .45), intimate partner violence (d = .41), and higher baseline autonomic nervous system activity (d = .24). The effect size for autonomic stress reactivity was not significant (d = −.10). The umbrella review of interventions to prevent or reduce child maltreatment showed modest intervention effectiveness (d = .23 for interventions targeting child abuse potential or families with self‐reported maltreatment and d = .27 for officially reported child maltreatment cases). Despite numerous studies on child maltreatment, some large gaps in our knowledge of antecedents exist. Neurobiological antecedents should receive more research investment. Differential susceptibility theory may shed more light on questions aimed at breaking the intergenerational transmission of maltreatment and on the modest (preventive) intervention effects. In combination with family‐based interaction‐focused interventions, large‐scale socioeconomic experiments such as cash transfer trials and experiments with vouchers to move to a lower‐poverty area might be tested to prevent or reduce child maltreatment. Prevalence, antecedents, and preventive interventions of prenatal maltreatment deserve continuing scientific, clinical, and policy attention.

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“…A recent study extended testing the DSH from a candidate gene approach to a GWAS approach36. A polygenic score of environmental sensitivity was derived in a sample of monozygotic twins by a novel method of assessing within-pair emotional problems as a function of genotype.…”

Section: Genetic Variation Influences Differential Sensitivity To Thementioning

confidence: 99%

“…There is also evidence that a small serotonergic PRS is associated with negatively biased attention following a negative mood induction57, while a PRS developed from a GWAS study in major depression disorder (MDD) has been shown to predict reduced cortical thickness in left medial frontal cortex; a region known to be disrupted in MDD58. A recent GWAS study has developed what we might call a PSS (polygenic sensitivity score) and found support for differential susceptibility in terms of heightened emotionality and response to psychological therapy in children with anxiety disorders36.…”

Section: Limitations Of Previous Research and The Way Forwardmentioning

confidence: 99%

Differential sensitivity to the environment: contribution of cognitive biases and genes to psychological wellbeing

Fox

Beevers²

2016

Mol Psychiatry

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Negative cognitive biases and genetic variation have been associated with risk of psychopathology in largely independent lines of research. Here, we discuss ways in which these dynamic fields of research might be fruitfully combined. We propose that gene by environment (G × E) interactions may be mediated by selective cognitive biases and that certain forms of genetic ‘reactivity' or ‘sensitivity' may represent heightened sensitivity to the learning environment in a ‘for better and for worse' manner. To progress knowledge in this field, we recommend including assessments of cognitive processing biases; examining G × E interactions in ‘both' negative and positive environments; experimentally manipulating the environment when possible; and moving beyond single-gene effects to assess polygenic sensitivity scores. We formulate a new methodological framework encapsulating cognitive and genetic factors in the development of both psychopathology and optimal wellbeing that holds long-term promise for the development of new personalized therapies.

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A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders

Cited by 105 publications

References 46 publications

The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis

The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis

Annual Research Review: Umbrella synthesis of meta‐analyses on child maltreatment antecedents and interventions: differential susceptibility perspective on risk and resilience

Differential sensitivity to the environment: contribution of cognitive biases and genes to psychological wellbeing

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