Children under stress – COMT genotype and stressful life events predict cortisol increase in an acute social stress paradigm

Armbruster, Diana; Mueller, Anett; Strobel, Alexander; Lesch, Klaus‐Peter; Brocke, Burkhard; Kirschbaum, Clemens

doi:10.1017/s1461145711001763

Cited by 71 publications

(47 citation statements)

References 89 publications

(120 reference statements)

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“…However, this benefit comes with a trade-off of disadvantageous emotion-related information processing likely because of increased subcortical tonic and increased cortical phasic dopaminergic signaling (Bilder et al, 2004;Mier et al, 2010). Correspondingly, the Met allele has been associated with stress-related phenotypes, such as exaggerated limbic response to unpleasant stimuli (Smolka et al, 2005(Smolka et al, , 2007, HPA axis hyperreactivity (Armbruster et al, 2012), and increased pain sensitivity (Zubieta et al, 2003). This balance of costs and benefits suggests that each allele can be advantageous depending on the environmental context ("warrior vs worrier" model) in line with our data (Goldman et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The specific mechanisms of how dopamine affects hippocampal volume are still obscure but may involve alterations of the dopamine-modulated stress response that translate to changes of HPA axis function (Armbruster et al, 2012;Hernaus et al, 2013). Moreover, given the high hippocampal COMT expression, also direct effects on local dopamine signaling and hippocampal plasticity may be possible (Matsumoto et al, 2003;Lisman et al, 2011;Laatikainen et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, BDNF Val66Met, a single nucleotide polymorphism (SNP) located in the brain-derived neurotrophic factor gene (BDNF ), has been associated with stress susceptibility (Gatt et al, 2009;. Further, COMT Val158Met, a functional SNP located in the catechol-O-methyltransferase gene (COMT ), has been implicated in HPA axis hyper-reactivity (Armbruster et al, 2012), altered -opioid neurotransmitter responses to pain stressors (Zubieta et al, 2003), and increased limbic reactivity (Smolka et al, 2005). In line with their effects on the stress system and brain function, these variants have repeatedly been shown to directly affect hippocampal volume (Pezawas et al, 2004;Frodl et al, 2008;Honea et al, 2009), although others failed to show these effects (Dutt et al, 2009;Cole et al, 2011;Molendijk et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Additive Gene-Environment Effects on Hippocampal Structure in Healthy Humans

Rabl¹,

Meyer²,

Diers³

et al. 2014

Journal of Neuroscience

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Hippocampal volume loss has been related to chronic stress as well as genetic factors. Although genetic and environmental variables affecting hippocampal volume have extensively been studied and related to mental illness, limited evidence is available with respect to G ϫ E interactions on hippocampal volume. The present MRI study investigated interaction effects on hippocampal volume between three well-studied functional genetic variants (COMT Val158Met, BDNF Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of environmental adversity (life events questionnaire) in a large sample of healthy humans (n ϭ 153). All three variants showed significant interactions with environmental adversity with respect to hippocampal volume. Observed effects were additive by nature and driven by both recent as well as early life events. A consecutive analysis of hippocampal subfields revealed a spatially distinct profile for each genetic variant suggesting a specific role of 5-HTTLPR for the subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3 volume changes. The present study underscores the importance of G ϫ E interactions as determinants of hippocampal volume, which is crucial for the neurobiological understanding of stress-related conditions, such as mood disorders or post-traumatic stress disorder (PTSD).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Additive Gene-Environment Effects on Hippocampal Structure in Healthy Humans

Rabl¹,

Meyer²,

Diers³

et al. 2014

Journal of Neuroscience

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“…Alternatively, another possibility is that Val carriers exhibit abnormal reward processing as found in a neuroimaging study (Camara et al, 2010). COMT is significantly associated with various psychiatric disorders (e.g., Hosak, 2007) as well as levels of cortisol response (e.g., cortisol stress reactivity in Armburster et al, 2012, Jabbi et al, 2007; total morning cortisol output in Walder et al, 2010). …”

Section: Cortisol Reactivity To Stress Stability and Associations Wmentioning

confidence: 99%

Cortisol reactivity to stress among youth: Stability over time and genetic variants for stress sensitivity.

Hankin¹,

Badanes²,

Smolen³

et al. 2015

Journal of Abnormal Psychology

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Stress sensitivity may be one process that can explain why some genetically at-risk individuals are more susceptible to some types of stress-reactive psychopathologies. Dysregulation of the Limbic Hypothalamic Pituitary Adrenal (LHPA) axis, including cortisol reactivity to challenge, represents a key aspect of stress sensitivity. However, the degree of stability over time among youth, especially differential stability as a function of particular genetic variants, has not been investigated. A general community sample of children and adolescents (mean age = 11.4; 56% girls) provided a DNA sample and completed two separate laboratory stress challenges, across an 18-month follow-up (N =224 at Time 1; N = 194 at Time 2), with repeated measures of salivary cortisol. Results showed that test-retest stability for several indices of cortisol reactivity across the laboratory challenge visits were significant and of moderate magnitude for the whole sample. Moreover, gene variants of several biologically plausible systems relevant for stress sensitivity (especially 5-HTTLPR and CRHR1) demonstrated differential stability of cortisol reactivity over 18-months, such that carriers of genotypes conferring enhanced environmental susceptibility exhibited greater stability of cortisol levels over time for some LHPA axis indices. Findings suggest that LHPA axis dysregulation may exhibit some trait-like aspects underlying stress sensitivity in youth, especially for those who carry genes related to greater genetic susceptibility to environmental stress.

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“…Children carrying the Met allele showed a higher cortisol response to stress. However, children who had more stressful life events showed a smaller increase in cortisol, implying that they might be more resilient (Armbruster et al, 2012). This study demonstrated differential effects of genetic and environmental factors on reaction to stress.…”

Section: Noradrenergic and Dopaminergic Systemsmentioning

confidence: 63%

Understanding Resilience

2006

Learning From Resilient People: Lessons We Can Apply to Counseling and Psychotherapy

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Resilience is the ability to adapt successfully in the face of stress and adversity. Stressful life events, trauma, and chronic adversity can have a substantial impact on brain function and structure, and can result in the development of posttraumatic stress disorder (PTSD), depression and other psychiatric disorders. However, most individuals do not develop such illnesses after experiencing stressful life events, and are thus thought to be resilient. Resilience as successful adaptation relies on effective responses to environmental challenges and ultimate resistance to the deleterious effects of stress, therefore a greater understanding of the factors that promote such effects is of great relevance. This review focuses on recent findings regarding genetic, epigenetic, developmental, psychosocial, and neurochemical factors that are considered essential contributors to the development of resilience. Neural circuits and pathways involved in mediating resilience are also discussed. The growing understanding of resilience factors will hopefully lead to the development of new pharmacological and psychological interventions for enhancing resilience and mitigating the untoward consequences.

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Children under stress – COMT genotype and stressful life events predict cortisol increase in an acute social stress paradigm

Cited by 71 publications

References 89 publications

Additive Gene-Environment Effects on Hippocampal Structure in Healthy Humans

Additive Gene-Environment Effects on Hippocampal Structure in Healthy Humans

Cortisol reactivity to stress among youth: Stability over time and genetic variants for stress sensitivity.

Understanding Resilience

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