The Interrelationship of Neuroticism, Sex, and Stressful Life Events in the Prediction of Episodes of Major Depression

Kendler, Kenneth S.; Kuhn, Jonathan W.; Prescott, Carol A.

doi:10.1176/appi.ajp.161.4.631

Cited by 674 publications

(623 citation statements)

References 31 publications

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“…In the current study, the association between neuroticism and cancer survival was stronger among women. Also, the risk of depression is higher among women compared with men (Kendler et al, 2004). A potential explanation for the observed stronger association between neuroticism and cancer survival among women could thus be that high neuroticism involves an increased risk of depression, which may affect the risk of death.…”

Section: Discussionmentioning

confidence: 98%

“…It is also possible that the association is related to depression. In an earlier study using a population-based sample, neuroticism was reported to be a significant risk factor for major depression (Kendler et al, 2004). Furthermore, a number of prospective studies have reported a statistically significant association between depression (higher degree of depressive symptoms or psychiatrically diagnosed depression) and survival in patients with various types of cancer (Hjerl et al, 2003;Goodwin et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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Personality traits and cancer survival: a Danish cohort study

et al. 2006

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We conducted a population-based prospective cohort study in Denmark to investigate associations between the personality traits and cancer survival. Between 1976Between and 1977Between , 1020 residents of the Copenhagen County completed a questionnaire eliciting information on personality traits and various health habits. The personality traits extraversion and neuroticism were measured using the short form of the Eysenck Personality Inventory. Follow-up in the Danish Cancer Registry for 1976 -2002 revealed 189 incidents of primary cancer and follow-up for death from the date of the cancer diagnosis until 2005 revealed 82 deaths from all-cause in this group. A Cox proportional-hazards model was used to estimate the hazard ratios (HRs) of death from all-cause according to extraversion and neuroticism adjusting for potential confounding factors. A significant association was found between neuroticism and risk of death (HR, 2.3 (95% CI ¼ 1.1 -4.7); Linear trend P ¼ 0.04) but not between extraversion and risk of death (HR, 0.9 (0.4 -1.7); Linear trend P ¼ 0.34). Similar results were found when using cancer-related death. Stratification by gender revealed a strong positive association between neuroticism and the risk of death among women (Linear trend P ¼ 0.03). This study showed that neuroticism is positively associated with cancer survival. Further research on neuroticism and cancer survival is needed.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Personality traits and cancer survival: a Danish cohort study

et al. 2006

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“…It has been shown that carriers of the s-allele have an elevated risk of depression in the context of environmental adversity. 73,285,286 Furthermore, in rhesus macaques, which have the same 5-HTTLPR length variations as humans, the s-allele is associated with decreased 5-HTergic function, indicated by lower CSF 5-HIAA concentrations, only in monkeys reared in stressful conditions. 287 In addition, s-allele carriers showed increased activation of the amygdala in response to fearful or threatening stimuli.…”

Section: Biopsychological Interactionsmentioning

confidence: 96%

“…69,70 Depression has been associated with higher scores on neuroticism (N) and the temperament dimension harm avoidance (HA), the tendency to respond to signals of adverse stimuli with behavioral inhibition. [70][71][72][73][74][75][76][77][78] Also, low self-directedness (the ability to regulate one's behavior and commit to chosen goals; SD) and cooperativeness (the ability to identify with and accept other people; C) have been found in depressed patients, 77,79 which may increase after treatment. 80 SD and C have been associated with 5-HTergic activity.…”

Section: Personalitymentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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“…Moreover, particularly in the case of major depression, there is evidence that neuroticism interacts with psychosocial stress to yield psychopathology (Kendler et al, 2003(Kendler et al, , 2004. As such, elucidating the genetics of personality traits such as neuroticism may contribute to a better understanding of the etiology of these disorders (Bienvenu and Stein, 2003;Fullerton et al, 2003;Reif and Lesch, 2003;Van Gestel and Van Broeckhoven, 2003).…”

Section: Introductionmentioning

confidence: 99%

COMT Polymorphisms and Anxiety-Related Personality Traits

Stein

Fallin

Schork

2005

Neuropsychopharmacol

194

126

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High neuroticism and low extraversion are characteristic of anxiety-prone individuals. A functional variant in the catechol-Omethyltransferase (COMT) gene, the Val158Met ('val/met') polymorphism, has been associated in some prior studies with several phenotypes, including neuroticism. We tested the hypothesis that the val158met polymorphism would be associated with both high neuroticism and low extraversion, making it a plausible candidate locus for anxiety susceptibility. To determine whether val158met is responsible for these effects, we also evaluated the association with haplotypes that included two other SNPs within the COMT gene. We collected a sample of 497 undergraduate college students who were phenotyped on a personality inventory (the NEO-Personality Inventory-Raised (NEO-PI-R)). Subjects were genotyped for three COMT polymorphisms: the well-studied nonsynonymous SNP rs4680 that generates a valine-to-methionine substitution (val158met), rs737865 (near exon #1), and rs165599 (also functional, near the 3 0 -UTR). Together, these three SNPs define a haplotype that is associated with reduced COMT expression in human brain. Logistic regression analyses were used to examine the effects of individual SNPs on extraversion and neuroticism scores. Score tests for association between these traits (quantitatively and dichotomously considered) and haplotypes were also conducted. We evaluated potential for population stratification artifact by genotyping a set of 36 unlinked highly polymorphic markers previously demonstrated to distinguish sufficiently ancestry of major American populations. Two of the SNPs (rs4680 ('val/met') and rs737865) were significantly associated with (low) extraversion and, less consistently, with (high) neuroticism, with effects confined to women. A significant association between COMT haplotype and (low) extraversion and (high) neuroticism was also observed. Formal testing showed that population structure did not explain the findings. These data suggest that involvement of the COMT locus in susceptibility to anxiety-related traits (ie low extraversion and high neuroticism) is unlikely to be wholly accounted for by the well-studied rs4680 ('val/met') polymorphism. Other functional variants may exist that contribute to this relationship. Possible sex-specific effects remain to be further studied and explained.

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The Interrelationship of Neuroticism, Sex, and Stressful Life Events in the Prediction of Episodes of Major Depression

Cited by 674 publications

References 31 publications

Personality traits and cancer survival: a Danish cohort study

Personality traits and cancer survival: a Danish cohort study

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

COMT Polymorphisms and Anxiety-Related Personality Traits

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