Epigenetic Changes of FKBP5 as a Link Connecting Genetic and Environmental Risk Factors with Structural and Functional Brain Changes in Major Depression

In both clinical and epidemiological samples, major depression (MD) and generalised anxiety disorder (GAD) display substantial comorbidity. In a prior analysis of lifetime MD and GAD in female twins, the same genetic factors were shown to influence the liability to MD and to GAD. A follow-up interview in the same twin cohort examined one-year prevalence for MD and GAD (diagnosed using a one-month minimum duration of illness). Bivariate twin models were fitted using the program Mx. High levels of comorbidity were observed between MD and GAD. The best-fitting twin models, when GAD was diagnosed with or without a diagnostic hierarchy, found a genetic correlation of unity between the two disorders. The correlation in environmental risk factors was +0.70 when GAD was diagnosed non-hierarchically, but zero when hierarchical diagnoses were used. Our findings provide further support for the hypothesis that in women, MD and GAD are the result of the same genetic factors. Environmental risk factors that predispose to ‘pure’ GAD episodes may be relatively distinct from those that increase risk for MD.

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Major depression and phobias: the genetic and environmental sources of comorbidity

Psychological Medicine ◽

10.1017/s0033291700028464 ◽

1993 ◽

Vol 23 (2) ◽

pp. 361-371 ◽

Cited By ~ 77

Author(s):

Kenneth S. Kendler ◽

Michael C. Neale ◽

Ronald C. Kessler ◽

Andrew C. Heath ◽

Lindon J. Eaves

Keyword(s):

Risk Factors ◽

Major Depression ◽

Social Phobia ◽

Environmental Risk ◽

Population Based ◽

Environmental Risk Factors ◽

The Other ◽

Genetic Vulnerability ◽

Animal Phobias ◽

Shared Genetic

SynopsisIn a population based sample of 2163 personally interviewed female twins, substantial comorbidity was observed between DSM-III-R defined major depression (MD) and 4 subtypes of phobia: agoraphobia, social phobia, animal phobia and situational phobia. However, the level of comorbidity of MD with agoraphobia was much greater than that found with the other phobic subtypes. We conducted bivariate twin analyses to decompose the genetic and environmental sources of comorbidity between MD and the phobias. Our results suggest that a modest proportion of the genetic vulnerability to MD also influences the risk for all phobic subtypes, with the possible exception of situational phobias. Furthermore, the magnitude of comorbidity resulting from this shared genetic vulnerability is similar across the phobic subtypes. By contrast, the non-familial environmental experiences which predispose to depression substantially increase the vulnerability to agoraphobia, have a modest impact on the risk for social and situational phobias and no effect on the risk for animal phobias. The increased comorbidity between MD and agoraphobia results, nearly entirely, from individual-specific environmental risk factors for MD which also increase the risk for agoraphobia but not for other phobias.

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A Review of epigenetics in psychiatry: focus on environmental risk factors

Medizinische Genetik ◽

10.1515/medgen-2020-2004 ◽

2020 ◽

Vol 32 (1) ◽

pp. 57-64

Author(s):

Jessica Keverne ◽

Elisabeth B. Binder

Keyword(s):

Risk Factors ◽

Psychiatric Disorders ◽

Environmental Risk ◽

Cell Function ◽

Epigenetic Modifications ◽

Environmental Risk Factors ◽

Epigenetic Changes ◽

Cell Type Specificity ◽

Environmental Signals ◽

Genetic And Environmental Factors

Abstract Epigenetic modifications play a key role in development and cell type specificity. These modifications seem to be particularly critical for brain development, where mutations in epigenetic enzymes have been associated with neurodevelopmental disorders as well as with the function of post-mitotic neurons. Epigenetic modifications can be influenced by genetic and environmental factors, both known major risk factors for psychiatric disorders. Epigenetic modifications may thus be an important mediator of the effects of genetic and environmental risk factors on cell function. This review summarizes the different types of epigenetic regulation and then focuses on the mechanisms transducing environmental signals, especially adverse life events that are major risk factors for psychiatric disorders, into lasting epigenetic changes. This is followed by examples of how the environment can induce epigenetic changes that relate to the risk of psychiatric disorders.

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Genetic and environmental influences on last-year major depression in adulthood: a highly heritable stable liability but strong environmental effects on 1-year prevalence

Psychological Medicine ◽

10.1017/s0033291717000277 ◽

2017 ◽

Vol 47 (10) ◽

pp. 1816-1824 ◽

Cited By ~ 3

Author(s):

K. S. Kendler ◽

C. O. Gardner

Keyword(s):

Risk Factors ◽

Major Depression ◽

Environmental Effects ◽

Environmental Risk ◽

Structural Equation ◽

Environmental Influences ◽

Diagnostic Error ◽

Environmental Risk Factors ◽

Multiple Time ◽

The Impact

BackgroundThis study seeks to clarify the contribution of temporally stable and occasion-specific genetic and environmental influences on risk for major depression (MD).MethodOur sample was 2153 members of female–female twin pairs from the Virginia Twin Registry. We examined four personal interview waves conducted over an 8-year period with MD in the last year defined by DSM-IV criteria. We fitted a structural equation model to the data using classic Mx. The model included genetic and environmental risk factors for a latent, stable vulnerability to MD and for episodes in each of the four waves.ResultsThe best-fit model was simple and included genetic and unique environmental influences on the latent liability to MD and unique wave-specific environmental effects. The path from latent liability to MD in the last year was constant over time, moderate in magnitude (+0.65) and weaker than the impact of occasion-specific environmental effects (+0.76). Heritability of the latent stable liability to MD was much higher (78%) than that estimated for last-year MD (32%). Of the total unique environmental influences on MD, 13% reflected enduring consequences of earlier environmental insults, 17% diagnostic error and 70% wave-specific short-lived environmental stressors.ConclusionsBoth genetic influences on MD and MD heritability are stable over middle adulthood. However, the largest influence on last-year MD is short-lived environmental effects. As predicted by genetic theory, the heritability of MD is increased substantially by measurement at multiple time points largely through the reduction of the effects of measurement error and short-term environmental risk factors.

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Bulimia nervosa and major depression: a study of common genetic and environmental factors

Psychological Medicine ◽

10.1017/s0033291700038071 ◽

1992 ◽

Vol 22 (3) ◽

pp. 617-622 ◽

Cited By ~ 52

Author(s):

Ellen E. Walters ◽

Michael C. Neale ◽

Lindon J. Eaves ◽

Andrew C. Heath ◽

Ronald C. Kessler ◽

...

Keyword(s):

Risk Factors ◽

Major Depression ◽

Environmental Factors ◽

Family Environment ◽

Environmental Risk ◽

Population Based ◽

Environmental Risk Factors ◽

Future Research ◽

Clinical Diagnoses ◽

Genetic And Environmental Factors

SynopsisA genetic analysis of the co-occurrence of bulimia and major depression (MD) was performed on 1033 female twin pairs obtained from a population based register. Personal interviews were conducted and clinical diagnoses made according to DSM-III-R criteria.Additive genes, but not family environment, are found to play an important aetiological role in both bulimia and MD. The genetic liabilities of the two disorders are correlated 0·456. While unique environmental factors account for around half of the variation in liability to both bulimia and MD, these risk factors appear to be unrelated, i.e., each disorder has its own set of unique environmental risk factors. Thus, the genetic liability of bulimia and MD is neither highly specific nor entirely nonspecific. There is some genetic correlation between the two disorders as well as some genetic and environmental risk factors unique to each disorder. Limitations and directions for future research are discussed.

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