Personality as a Vulnerability Factor to Depression

Boyce, Philip; Parker, Gordon; Barnett, Bryanne; Cooney, Margaret; Smith, F. V.

doi:10.1192/bjp.159.1.106

Cited by 324 publications

(209 citation statements)

References 38 publications

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“…Personality traits appear to have a considerable heredity component 68 and it has been suggested that a certain type of personality or temperament represents a risk factor for developing major depression. 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.…”

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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Section: Personalitymentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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“…Its importance as a psychological construct is further enhanced by its well documented correlation with common psychiatric disorders, that is, high levels of neuroticism predict the onset and subsequent episodes of major depression [2][3][4][5] and are associated with symptoms of depression and anxiety in the general population. [6][7][8][9] The correlation between anxiety, major depression and neuroticism is, in part, due to the presence of shared genetic factors, [10][11][12][13] an observation that has spurred attempts to map the genetic basis of neuroticism.…”

Section: Introductionmentioning

confidence: 99%

A whole genome association study of neuroticism using DNA pooling

et al. 2007

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We describe a multistage approach to identify single nucleotide polymorphisms (SNPs) associated with neuroticism, a personality trait that shares genetic determinants with major depression and anxiety disorders. Whole genome association with 452 574 SNPs was performed on DNA pools from B2000 individuals selected on extremes of neuroticism scores from a cohort of 88 142 people from southwest England. The most significant SNPs were then genotyped on independent samples to replicate findings. We were able to replicate association of one SNP within the PDE4D gene in a second sample collected by our laboratory and in a family-based test in an independent sample; however, the SNP was not significantly associated with neuroticism in two other independent samples. We also observed an enrichment of low P-values in known regions of copy number variations. Simulation indicates that our study had B80% power to identify neuroticism loci in the genome with odds ratio (OR) > 2, and B50% power to identify small effects (OR = 1.5). Since we failed to find any loci accounting for more than 1% of the variance, the heritability of neuroticism probably arises from many loci each explaining much less than 1%. Our findings argue the need for much larger samples than anticipated in genetic association studies and that the biological basis of emotional disorders is extremely complex.

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“…Two metaanalyses have concluded that presence of the short variant of this repeat (5-HTT-linked polymorphic region, 5-HTTLPR) is associated with higher levels of neuroticism or harm avoidance (5,6). Although neuroticism itself is a risk factor for depression (7), the link between 5-HTTLPR genotype and depression has been more tenuous, suggesting that 5-HTTLPR genotype does not have a consistent main effect on depression but instead may be moderated through other variables (8).…”

mentioning

confidence: 99%

Neural correlates of epigenesis

Canli

Qiu²,

Omura³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

295

251

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The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging (functional, perfusion, and structural), genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, we found support for a model by which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. These interactions may constitute a neural mechanism for epigenetic vulnerability toward, or protection against, depression.amygdala ͉ emotion ͉ environment ͉ gene ͉ hippocampus A dverse life events can reveal profound interindividual differences, rousing resilience in some and exposing susceptibility to mood disorders, including depression, in others. Diathesis-stress models have sought to explain these individual differences in terms of genetic predispositions interacting with environmental factors (1). Behavioral genetic studies have supported these models (2), with current work focusing on molecular and neural mechanism that may underlie these associations.Dysfunction of the serotonin (5-hydroxytryptophan, 5-HT) system is implicated in mood disorders, and variation within serotonergic genes has been associated with negative emotional traits such as neuroticism and harm avoidance (3). For example, higher scores in these traits are associated with a common short variant of a repetitive sequence in the transcriptional control region of the 5-HT transporter gene (5-HTT, SERT, SLC6A4), which results in low 5-HT uptake function (4). Two metaanalyses have concluded that presence of the short variant of this repeat (5-HTT-linked polymorphic region, 5-HTTLPR) is associated with higher levels of neuroticism or harm avoidance (5, 6). Although neuroticism itself is a risk factor for depression (7), the link between 5-HTTLPR genotype and depression has been more tenuous, suggesting that 5-HTTLPR genotype does not have a consistent main effect on depression but instead may be moderated through other variables (8).Caspi et al. (9) conducted a 23-year longitudinal study in a large sample of individuals who were genotyped for the 5-HTTLPR. They found that carriers of the 5-HTTLPR short variant showed more depressive symptoms, diagnosed depression, and suicidality as a function of stressful life events than individuals homozygous for the 5-HTTLPR long variant, thus demonstrating a significant gene-by-environment (...

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Personality as a Vulnerability Factor to Depression

Cited by 324 publications

References 38 publications

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

A whole genome association study of neuroticism using DNA pooling

Neural correlates of epigenesis

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