A Swedish National Twin Study of Lifetime Major Depression

Kendler, Kenneth S.; Gatz, Margaret; Gardner, C. O.; Pedersen, Nancy L.

doi:10.1176/appi.ajp.163.1.109

Cited by 653 publications

(465 citation statements)

References 39 publications

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“…For example, chromosomal loci implicated in the vulnerability to major depression (Holmans et al, 2004;Nash et al, 2004), neuroticism (Fullerton et al, 2003), obsessive-compulsive disorder (OCD; Nestadt et al, 2000), and autism (Stone et al, 2004) differ between men and women. Such differences occur against a background of a sex difference in heritability estimates for some disorders; eg the heritability of major depression is greater in women than in men (Kendler et al, 2006). These indications that there are differences in the genetic factors contributing to psychiatric phenotypes in men and women is consistent with the factFnot always appreciatedFthat the genetic architecture of many, perhaps most, human traits is sexually dimorphic (Weiss et al, 2006).…”

mentioning

confidence: 64%

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Harrison

Tunbridge

2007

Neuropsychopharmacol

269

217

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Sex differences in the genetic epidemiology and clinical features of psychiatric disorders are well recognized, but the individual genes contributing to these effects have rarely been identified. Catechol-O-methyltransferase (COMT), which metabolizes catechol compounds, notably dopamine, is a leading candidate. COMT enzyme activity, and the neurochemistry and behavior of COMT null mice, are both markedly sexually dimorphic. Genetic associations between COMT and various psychiatric phenotypes frequently show differences between men and women. Many of these differences are unconfirmed or minor, but some appear to be of reasonable robustness and magnitude; eg the functional Val 158 Met polymorphism in COMT is associated with obsessive-compulsive disorder in men, with anxiety phenotypes in women, and has a greater impact on cognitive function in boys than girls. Sex-specific effects of COMT are usually attributed to transcriptional regulation by estrogens; however, additional mechanisms are likely to be at least as important. Here we review the evidence for a sexually dimorphic influence of COMT upon psychiatric phenotypes, and discuss its potential basis. We conclude that despite the evidence being incomplete, and lacking a unifying explanation, there are accumulating and in places compelling data showing that COMT differentially impacts on brain function and dysfunction in men and women. Since sex differences in the genetic architecture of quantitative traits are the rule not the exception, we anticipate that additional evidence will emerge for sexual dimorphisms, not only in COMT but also in many other autosomal genes.

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mentioning

confidence: 64%

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Harrison

Tunbridge

2007

Neuropsychopharmacol

269

217

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“…Thus, only women were included. A similar study including men would be of importance as previous research showed that different genetic factors among women and men were influential on depression (Kendler et al, 2006). Further, as this study included twins in the age range between 40 and 65 years, the results cannot be generalized to younger ages.…”

Section: Strengths and Limitationsmentioning

confidence: 91%

“…CIDI-SF criteria for MD were validated against 1-year prevalence data with the full Composite International Diagnostic Interview (Kendler et al, 2006). Twins were considered as positive for a history of MD if they either met the criteria for MD or reported that they used or had used antidepressant medication (Kendler et al, 2006).…”

Section: Major Depression (Md) and Generalized Anxiety Disorder (Gad)mentioning

confidence: 99%

Genetic and Environmental Influences on Disability Pension Due To Mental Diagnoses: Limited Importance of Major Depression, Generalized Anxiety, and Chronic Fatigue

et al. 2015

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Background: Previous research indicates that liability to disability pension (DP) due to mental diagnoses is moderately influenced by genetic factors. This study investigates whether genetic contributions to the liability to DP due to mood and neurotic diagnoses overlap with the genetic influences on major depression (MD), generalized anxiety disorder (GAD), or chronic fatigue (CF). Method: A prospective cohort study including 9,985 female twins born in Sweden 1933Sweden -1958. The presence of MD, GAD, and CF was assessed by computer-assisted telephone interviews conducted in 1998-2002. Data on DP due to mood and neurotic diagnoses were obtained from nationwide registers for the years 1998-2010. Common genetic and environmental influences on the phenotypes were estimated by applying structural equation modeling. Results: The prevalence of MD/GAD was 30%, CF 8%, and DP due to mood and neurotic diagnoses 3% in 2010. Genetic effects on MD/GAD explained 31% of the total genetic variation in DP, whereas genetic contributions in common with CF were small and not significant. The majority of the total non-shared environmental variance in DP (85%) was explained by the factors that were unique to DP. Conclusions: Large proportions of genetic and non-shared environmental influences in DP due to mood and neurotic diagnoses were not explained by the contributions from MD/GAD or CF. The results suggest that the process leading to DP is complex and influenced by factors other than those related to the disorder underlying DP.

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“…Post hoc, the effect of 'gender by risk' interaction was tested, as some genetic-risk factors are likely to be sex specific in their effect (Kendler et al, 2006a).…”

Section: Statisticsmentioning

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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A Swedish National Twin Study of Lifetime Major Depression

Cited by 653 publications

References 39 publications

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Genetic and Environmental Influences on Disability Pension Due To Mental Diagnoses: Limited Importance of Major Depression, Generalized Anxiety, and Chronic Fatigue

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

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