Clinical Characteristics of Major Depression That Predict Risk of Depression in Relatives

Kendler, Kenneth S.; Gardner, C. O.; Prescott, Carol A.

doi:10.1001/archpsyc.56.4.322

Cited by 117 publications

(78 citation statements)

References 40 publications

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“…Our identified cases reported substantial levels of impairment, distress, and treatment seeking. 59 Our sex-averaged 1-year prevalence estimates of major depression (9.7%) are nearly identical to those reported in the National Comorbidity Survey 18 (10.3%), suggesting that we achieved a considerably lower ratio of last-year to lifetime cases. We may have identified milder cases than some other studies.…”

Section: Limitationssupporting

confidence: 80%

The Structure of Genetic and Environmental Risk Factors for Common Psychiatric and Substance Use Disorders in Men and Women

Kendler

Prescott

Myers

et al. 2003

Arch Gen Psychiatry

Self Cite

1,710

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1,354

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The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors.

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Section: Limitationssupporting

confidence: 80%

The Structure of Genetic and Environmental Risk Factors for Common Psychiatric and Substance Use Disorders in Men and Women

Kendler

Prescott

Myers

et al. 2003

Arch Gen Psychiatry

Self Cite

1,710

136

1,354

View full text Add to dashboard Cite

show abstract

“…Family and twin studies have also examined subtypes of MDD that may confer greater familial risk (Smoller and Perlis, 2004). In particular, increased familial recurrence risk and heritability have been associated with earlier-onset and recurrent depression (Bland et al, 1986;Kendler et al, 1999aKendler et al, , 2005Weissman et al, 1984) as well as greater depression severity or impairment (Klein et al, 2002;Lyons et al, 1998), though these findings have not been universally observed.…”

Section: Family and Twin Studiesmentioning

confidence: 99%

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Smoller

2015

Neuropsychopharmacol

367

243

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Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

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“…Moreover, components of major depression such as altered response to stress (Caspi et al, 2003), impaired cognitive abilities, and dysfunctional reward-related behaviors are easier to model in animals than the depressive syndrome itself (Redei et al, 2001). Finally, intermediate levels of recurrence of depressive episodes have been associated with high genetic liability of MDD (Kendler et al, 1999), while a high temporal stability of the phenotype is favorable for genetic studies. The ensuing discussion dissects MDD into its key components based on biological validity, availability of accurate and quantitative assessment methods, and clinical relevance.…”

Section: Key Components Of Major Depressionmentioning

confidence: 99%

“…Attentional and mnemonic biases in depression have high clinical relevance because they are related to cognitive-behavioral theories of depression, upon which treatment strategies have been based (Beck, 1967). However, there is only preliminary data on the heritability of mood bias: recurrent thoughts of death and suicide appeared to be a specific characteristic of familial MDD (Kendler et al, 1999).…”

Section: Depressed Mood (Mood Bias Toward Negative Emotions)mentioning

confidence: 99%

Discovering Endophenotypes for Major Depression

Hasler

Drevets

Manji

et al. 2004

Neuropsychopharmacol

1,024

739

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The limited success of genetic studies of major depression has raised questions concerning the definition of genetically relevant phenotypes. This paper presents strategies to improve the phenotypic definition of major depression by proposing endophenotypes at two levels: First, dissecting the depressive phenotype into key components results in narrow definitions of putative psychopathological endophenotypes: mood bias toward negative emotions, impaired reward function, impaired learning and memory, neurovegetative signs, impaired diurnal variation, impaired executive cognitive function, psychomotor change, and increased stress sensitivity. A review of the recent literature on neurobiological and genetic findings associated with these components is given. Second, the most consistent heritable biological markers of major depression are proposed as biological endophenotypes for genetic studies: REM sleep abnormalities, functional and structural brain abnormalities, dysfunctions in serotonergic, catecholaminergic, hypothalamic-pituitary-adrenocortical axis, and CRH systems, and intracellular signal transduction endophenotypes. The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiality, and clinical and biological plausibility. Finally, the case is made for the development of a new classification system in order to reduce the heterogeneity of depression representing a major impediment to elucidating the genetic and neurobiological basis of this common, severe, and often life-threatening illness.

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Clinical Characteristics of Major Depression That Predict Risk of Depression in Relatives

Cited by 117 publications

References 40 publications

The Structure of Genetic and Environmental Risk Factors for Common Psychiatric and Substance Use Disorders in Men and Women

The Structure of Genetic and Environmental Risk Factors for Common Psychiatric and Substance Use Disorders in Men and Women

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Discovering Endophenotypes for Major Depression

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