Effects of Environmental Stress and Gender on Associations among Symptoms of Depression and the Serotonin Transporter Gene Linked Polymorphic Region (5-HTTLPR)

Brummett, Beverly H.; Boyle, Stephen H.; Siegler, Ilene C.; Kuhn, Cynthia M.; Ashley-Koch, Allison E.; Jonassaint, Charles R.; Züchner, Stephan; Collins, Andrew; Williams, Redford B.

doi:10.1007/s10519-007-9172-1

Cited by 173 publications

(136 citation statements)

References 71 publications

(86 reference statements)

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“…Comparable findings have been obtained in rhesus macaques carrying a homologue of the s allele and exposed to early life stress (peer rearing) -in which females exhibit enhanced stress hormone responses to stress (Barr et al, 2004). In a somewhat parallel finding in humans, females with the s allele in combination with life stressors (care giver stress or low childhood socioeconomic status) exhibited more severe symptoms of depression than comparable males (Brummett et al, 2008). Finally, and of particular interest to the current discussion, Lee et al recently examined the association between the SERT s allele and PTSD in one hundred PTSD patients and one hundred ninety seven healthy controls using a casecontrol design.…”

Section: Serotonin Transporter (Sert) Dysfunction and Vulnerability Tmentioning

confidence: 77%

Vulnerability to lasting anxiogenic effects of brief exposure to predator stimuli: Sex, serotonin and other factors—Relevance to PTSD

Adamec

Holmes

Blundell

2008

Neuroscience & Biobehavioral Reviews

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Lasting anxiogenic effects of predator stress in rodents may model aspects of post traumatic stress disorder (PTSD). There is a link between genetic variation in the serotonin (5-HT) transporter (SERT) and anxiety in humans, prompting the generation of SERT knockout mice. This review brings together studies of SERT knockout male mice, normal female mice, and different 5-HT receptors in predator stress effects on anxiety. These studies provide for a link between vulnerability to the anxiogenic effects of predator stress and abnormalities of 5-HT transmission induced by a life long reduction in 5-HT reuptake in male mice, which creates a vulnerability like that seen in normal female mice. Data reviewed suggest abnormalities in 5-HT transmission contribute to vulnerability to lasting anxiogenic effects of species relevant stressors. To the extent to which predator stress effects model aspects of PTSD, and in the light of relevant human literature, these considerations implicate abnormalities of 5-HT transmission in vulnerability to PTSD per se, and as a potential contributor to enhanced female vulnerability to PTSD.

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Section: Serotonin Transporter (Sert) Dysfunction and Vulnerability Tmentioning

confidence: 77%

Vulnerability to lasting anxiogenic effects of brief exposure to predator stimuli: Sex, serotonin and other factors—Relevance to PTSD

Adamec

Holmes

Blundell

2008

Neuroscience & Biobehavioral Reviews

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“…However, as this study was not designed to detect gender by risk interactions, this finding will need to be replicated in a more focused design. If sustained, this may reflect gender-specific differences in genetic vulnerability to environmental stress (Barr et al, 2004a;Brummett et al, 2007).…”

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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“…Heim et al (2010) proposed that gene-by-environment interactions might occur in a sex-specific manner as an explanation for the higher prevalence of depression in women. Thus far, only studies using clinical outcome measures support the effect gender has on the association of 5-HTTLPR and stressful life events in the prevalence of depression (Brummett et al, 2008;Sjoberg et al, 2006;Eley et al, 2004), bypassing possible modulating actions of the brain.…”

Section: Introductionmentioning

confidence: 99%

Sex Modulates the Interactive Effect of the Serotonin Transporter Gene Polymorphism and Childhood Adversity on Hippocampal Volume

Everaerd

Gerritsen

Rijpkema

et al. 2012

Neuropsychopharmacol

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The common genetic variation of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been related to depressive symptoms, in particular after stressful life events. Although it has been investigated in the past, results suggesting that the 5-HTTLPR genotype also affects hippocampal volume are often inconsistent and it remains unclear to what extent reduced hippocampal volume is influenced by the effect of stressful life events and 5-HTTLPR genotype. Moreover, sex, which is known to affect the prevalence of depression substantially, has not been taken into account when trying to disentangle the interactive effect of common genetic variation and environmental stressors on the hippocampus. We investigated this potentially relevant three-way interaction using an automatic magnetic resonance imaging (MRI)-based segmentation of the hippocampus in 357 healthy individuals. We determined the 5-HTTLPR genotype as a biallelic locus and childhood adversity (CA) using a standard questionnaire. An interaction for hippocampal volume was found between the factors sex, genotype, and severe CA (p ¼ 0.010) as well as an interaction between genotype and severe CA (p ¼ 0.007) in men only. Post hoc tests revealed that only male S'-allele carriers with severe CA had smaller hippocampi (p ¼ 0.002). Interestingly, there was no main effect of genotype in men, while female S'-allele carriers had smaller hippocampi than L'L' carriers (p ¼ 0.023). Our results indicate that sex modulates the interactive effect of the 5-HTTLPR genotype and CA on hippocampal volume. While the S'-allele is associated with hippocampal volume independent of CA in women, men only have smaller hippocampi if they carry the risk allele and experienced severe CA.

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Effects of Environmental Stress and Gender on Associations among Symptoms of Depression and the Serotonin Transporter Gene Linked Polymorphic Region (5-HTTLPR)

Cited by 173 publications

References 71 publications

Vulnerability to lasting anxiogenic effects of brief exposure to predator stimuli: Sex, serotonin and other factors—Relevance to PTSD

Vulnerability to lasting anxiogenic effects of brief exposure to predator stimuli: Sex, serotonin and other factors—Relevance to PTSD

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

Sex Modulates the Interactive Effect of the Serotonin Transporter Gene Polymorphism and Childhood Adversity on Hippocampal Volume

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