HPA Axis Reactivity: A Mechanism Underlying the Associations Among 5-HTTLPR, Stress, and Depression

Gotlib, Ian H.; Joormann, Jutta; Minor, Kelly L.; Hallmayer, Joachim

doi:10.1016/j.biopsych.2007.10.008

Cited by 503 publications

(370 citation statements)

References 35 publications

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“…Moreover, in organotypic hippocampal cultures, chronic exposure (7 days) to corticosterone increased 5-HT 2A protein levels (Trajkovska et al, 2009). Furthermore, several studies suggest a link between increased biological stress reactivity and the serotonergic transmitter system in terms of the low expressing polymorphism of the serotonin transporter promoter gene (Barr et al, 2004b;Gotlib et al, 2008), a gene that is also associated with an increased vulnerability to develop depression in response to life stress (Uher and McGuffin, 2008). Apart from genetic factors, stress reactivity also varies with environmental factors including early life stress (Kajantie, 2006;Talge et al, 2007) and emotional response tendencies (Mormede et al, 2002), for example personality, in human beings (Portella et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Familial Risk for Mood Disorder and the Personality Risk Factor, Neuroticism, Interact in Their Association with Frontolimbic Serotonin 2A Receptor Binding

Frøkjær¹,

Vinberg

Erritzoe³

et al. 2009

Neuropsychopharmacol

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Life stress is a robust risk factor for later development of mood disorders, particularly for individuals at familial risk. Likewise, scoring high on the personality trait neuroticism is associated with an increased risk for mood disorders. Neuroticism partly reflects stress vulnerability and is positively correlated to frontolimbic serotonin 2A (5-HT 2A ) receptor binding. Here, we investigate whether neuroticism interacts with familial risk in relation to frontolimbic 5-HT 2A receptor binding. Twenty-one healthy twins with a co-twin history of mood disorder and 16 healthy twins without a co-twin history of mood disorder were included. They answered self-report personality questionnaires and underwent [ 18 F]altanserin positron emission tomography. We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT 2A receptor binding (p ¼ 0.026) in an analysis adjusting for age and body mass index. Within the high-risk group only, neuroticism and frontolimbic 5-HT 2A receptor binding was positively associated (p ¼ 0.0037). In conclusion, our data indicate that familial risk and neuroticism interact in their relation to frontolimbic 5-HT 2A receptor binding. These findings point at a plausible neurobiological link between genetic and personality risk factors and vulnerability to developing mood disorders. It contributes to our understanding of why some people at high risk develop mood disorders while others do not. We speculate that an increased stress reactivity in individuals at high familial risk for mood disorders might enhance the effect of neuroticism in shaping the impact of potential environmental stress and thereby influence serotonergic neurotransmission.

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Section: Discussionmentioning

confidence: 99%

Familial Risk for Mood Disorder and the Personality Risk Factor, Neuroticism, Interact in Their Association with Frontolimbic Serotonin 2A Receptor Binding

Frøkjær¹,

Vinberg

Erritzoe³

et al. 2009

Neuropsychopharmacol

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“…For example, Jabbi et al (2007) and Gotlib et al (2008) found larger cortisol responses to a stressor in homozygous carriers of the S allele (Gotlib et al, 2008;Jabbi et al, 2007). We recently reported that newborns with two S alleles exhibit the highest cortisol response after a physical stressor (Mueller et al, 2010).…”

Section: -Httlpr Sles and Stressmentioning

confidence: 96%

“…The use of this particular paradigm was motivated by findings that 5-HTTLPR genotype is associated with individual differences in HPA axis activity (Barr et al, 2004;Gotlib et al, 2008). Our primary goal was to assess whether cortisol reactivity would vary as a function of 5-HTTLPR Â SLE interaction.…”

Section: Introductionmentioning

confidence: 99%

Interaction of Serotonin Transporter Gene-Linked Polymorphic Region and Stressful Life Events Predicts Cortisol Stress Response

Mueller

Armbruster

Moser

et al. 2011

Neuropsychopharmacol

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There has been significant controversy whether stressful life events (SLEs) experienced over the lifespan may elevate the risk of depression in individuals who are homozygous for the short (S) allele of the repeat length polymorphism (5-HTTLPR) in the regulatory region of the serotonin transporter gene (SLC6A4), compared with individuals homozygous for the long (L) allele. On the basis of the hypothesis that age may be a critical variable, by which such a gene-by-environment interaction may be present in younger adults, but not in older adults and in children, aim of this study was to investigate the role of 5-HTTLPR and SLEs on the endocrine stress response in multiple age cohorts. A total of 115 children (8-12 years), 106 younger adults (18-31 years), and 99 older adults (54-68 years) were subjected to the Trier Social Stress Test (TSST) and structured interviews on SLEs. The TSST induced significant endocrine stress responses in all groups. There was a main effect of genotype in younger and older adults with individuals homozygous for the more active L allele showing a significantly larger cortisol response to the TSST than individuals carrying at least one of the low-expressing S alleles. As predicted, there was a significant interaction of 5-HTTLPR genotype and SLEs, but this interaction was only significant in younger adults and only when the measured SLEs had occurred during the first 5 years of life, suggesting that both age and the specific type of SLE has a role in whether a significant gene-environment interaction is observed.

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“…These experimental studies provide additional evidence in support of the gene-environment interaction, by finding that the 5-HTTLPR short allele is associated with attentional bias toward threatening stimuli 19,20 and stronger reactivity of cortisol to experimental stressors. 21,22 Examination of published meta-analyses…”

Section: Contribution Of Objective and Experimental Studiesmentioning

confidence: 99%

The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update

2009

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An updated review of 34 human observational studies indicates that the length polymorphism of the serotonin transporter gene moderates the effect of environmental adversity in the development of depression. This finding depends on the use of contextual or objective methods to assess environmental adversity and is attenuated when self-report instruments are used. Inconsistent findings in male adolescents suggest a developmental stage and sex-specific protective mechanism. These systematic relationships between method and results should be followed up to specify causal mechanisms leading to depression.

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HPA Axis Reactivity: A Mechanism Underlying the Associations Among 5-HTTLPR, Stress, and Depression

Cited by 503 publications

References 35 publications

Familial Risk for Mood Disorder and the Personality Risk Factor, Neuroticism, Interact in Their Association with Frontolimbic Serotonin 2A Receptor Binding

Familial Risk for Mood Disorder and the Personality Risk Factor, Neuroticism, Interact in Their Association with Frontolimbic Serotonin 2A Receptor Binding

Interaction of Serotonin Transporter Gene-Linked Polymorphic Region and Stressful Life Events Predicts Cortisol Stress Response

The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update

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