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Internalizing and externalizing psychopathology in middle age: genetic and environmental architecture and stability of symptoms over 15 to 20 years

  • Daniel E. Gustavson (a1), Carol E. Franz (a1), Matthew S. Panizzon (a1), Michael J. Lyons (a2) and William S. Kremen (a1) (a3)...



Internalizing and externalizing psychopathology factors explain much of the covariance among psychiatric conditions, especially at the level of genetic risk. However, few studies have examined internalizing and externalizing factors in middle-aged samples, especially their ability to predict later symptoms across midlife. The goals of the current study were (i) to quantify the genetic and environmental influences on internalizing and externalizing psychopathology in individuals in their early 40s, and (ii) examine the extent to which these genetic and environmental influences predict self-reported measures of internalizing and externalizing symptoms 15–20 years later.


1484 male twins completed diagnostic interviews of psychopathology at mean age 41 and self-reported measures of anxiety, depression, substance use, and related variables at up to two time-points in late middle age (mean ages 56 and 62).


Structural equation modeling of the diagnostic interviews confirmed that internalizing and externalizing factors accounted for most of the genetic variance in individual disorders, with substantial genetic (ra = 0.70) and environmental (re = 0.77) correlations between the factors. Internalizing psychopathology at age 41 was correlated with latent factors capturing anxiety, depression, and/or post-traumatic stress symptoms at ages 56 (r = 0.51) and 62 (r = 0.43). Externalizing psychopathology at age 41 was correlated r = 0.67 with a latent factor capturing aggression, tobacco use, and alcohol use at age 56. Stability of both factors was driven by genetic influences.


These findings demonstrate the considerable stability of internalizing and externalizing psychopathology symptoms across middle age, especially their genetic influences. Diagnostic interviews effectively predict self-reported symptoms and behaviors 15–20 years later.


Corresponding author

Author for correspondence: Daniel E. Gustavson, E-mail:


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