Why Psychological Problems Presage Cardiometabolic Health Problems

The idea that the well-being of mind and body are intimately linked is an ancient one, dating back at least to the observations of Aristotle and Hippocrates. Carefully examining this notion in the age of science is a fundamentally important task for promoting the ability of medicine, psychiatry, and psychology to improve human lives (1). The remarkable article by Chen et al. in this issue (2) adds important new empirical information on the association between psychological problems and a cluster of often co-occurring cardiometabolic conditions—cardiac diseases, type 2 diabetes, hypertension, hyperlipidemia, and obesity. Using Swedish health registries, Chen and colleagues identified a cohort of over 670,000 persons for whom data were available on clinical diagnoses of mental disorders during early adulthood and on cardiometabolic conditions during middle adulthood. After excluding persons in whom cardiometabolic problems were already present during early adulthood, the authors replicated earlier findings of bivariate associations between a range of individual mental disorder diagnoses (depression, anxiety disorders, alcohol abuse, and others) and adjudicated criminal behavior (as an indicator of externalizing problems) at 18–25 years of age, on the one hand, and clinical diagnoses of cardiometabolic conditions during middle adulthood, on the other. These prospective replications are very useful because they are based on the largest sample and the longest follow-up period to date, leaving little doubt that psychological problems temporally precede cardiometabolic conditions that carry high risk of morbidity and mortality (3).

Chen et al. go well beyond the robust replication of bivariate associations, however, and provide new information that should guide future theory and research on mind-health relationships. Using latent factor modeling, they provide novel evidence that the prospective association between mental disorder diagnoses and future cardiometabolic health is highly nonspecific. That is, they found that the variance common to all of the measured mental disorders—the shared variance that defines the general factor of psychological problems (4)—was the best predictor of future cardiometabolic health. Thus, no single kind of psychological problem predicted these health problems; it was (mostly) what all of the measured psychological problems share in common that predicted poor cardiometabolic outcomes. Thus, although focused studies of the health sequelae of single diagnoses may still be useful, our focus should shift to predictive relationships between the nonspecific causes and psychobiological mechanisms shared by all forms of psychological problems and future cardiometabolic health outcomes (5, 6).

These findings from Chen et al. provide a platform for asking the next fundamentally important question. What psychobiological processes do all common forms of psychological problems share that might explain why psychological and cardiometabolic problems are linked? One obvious candidate is neuroticism. This refers to relatively stable individual differences in negative emotional response to threat, frustration, or loss (7, 8). Neuroticism is robustly correlated with essentially all diagnostic categories of mental disorder (9), with their co-occurrence (10), and, indeed, with the general factor of psychological problems (9, 11, 12). Furthermore, neuroticism is a robust prospective predictor of a broad range of physical health conditions, particularly cardiovascular illness, and predicts premature mortality (9, 13, 14). A second (and not mutually exclusive) process linking the general factor of psychological problems to physical health is intelligence. There is clear evidence from several robust studies of an inverse relationship between intelligence and both the general factor of psychological problems (15, 16) and physical health (17).

Thus, growing evidence suggests that the variance shared by essentially all forms of psychological problems that is shared with cardiometabolic health is also shared with neuroticism and intelligence. Put plainly, people who are less intelligent and who experience greater negative emotional reactivity to stress are more likely to develop a broad range of psychological and cardiometabolic problems as they transact with their social and physical environments (1). It is worth noting that the more specific construct of cognitive control may prove to be more informative than general intelligence in understanding psychological and health problems. This highly heritable construct, also known as executive functions, refers to non-automatic processes of behavioral regulation that optimize goal-related behavior. Cognitive control is correlated with, but is separable from, general intelligence (18). Like intelligence, there are replicated findings of associations of measures of cognitive control with the general factor of psychological problems (18–22) and with physical health (23).

What specific mechanisms link cognitive control and neuroticism with cardiometabolic health? Persons with high levels of neuroticism have been found to experience reduced immunity, increased inflammation, and disrupted sleep (24–26). In addition, neuroticism is associated with the generation of interpersonal stress (27) and with reduced social support, which are associated with both psychological and physical health problems (13). Smoking and other substance use also are more common in persons with greater neuroticism (28) and persons with lower intelligence (29). These and other factors, including neuroticism itself, may constitute mechanistic links that are feasible targets for public health interventions (9).

Chen et al. also report findings from sibling analyses (30, 31) that need to be considered as we plan future studies of the casual risk factors underlying the prospective association between the general factor of psychological problems and cardiometabolic health. They estimated the strength of associations between psychological problems and cardiometabolic problems within pairs of full siblings in the same families and compared them to the magnitudes of the same associations across different families. Because all factors shared by siblings are held constant within sibling pairs, they do not contribute to the cross-trait (i.e., psychological and cardiometabolic problems) associations within sibling pairs. Therefore, the finding of attenuated associations within sibling pairs compared with the full sample argues that environmental factors typically shared by siblings, such as family and neighborhood-level poverty during childhood, are not likely to be causes, in any simple way, of the association between psychological and cardiometabolic problems (31, 32).

Thus, the authors accurately conclude that the association between the general factor and the cardiometabolic conditions could either be causal in nature or be attributable to nonshared confounders. That is, it is possible that something about experiencing high general levels of psychopathology could cause an increased risk for cardiometabolic health problems later in adulthood. Nonetheless, the results do not exclude the possibility that the association between the general factor of psychological problems and health is attributable to influences not shared by the siblings (33). Because analyses of full siblings only hold half of their polymorphic genetic variation constant, this means that both genetic influences and environmental factors typically not shared by siblings, such as traumatic events, could explain the association between psychological and cardiometabolic problems. Consistent with this possibility, a considerable amount of evidence from a strong set of studies indicates that essentially all forms of psychological problems substantially share genetic influences with one another (34–36). Furthermore, the genetic influences on cardiometabolic problems (37, 38) appear to be shared with the general factor of psychological problems (39–41). In addition, neuroticism, cognitive control, and intelligence each substantially share genetic influences with both specific diagnosed mental disorders (42) and the general factor of psychological problems—that is, with the variance that psychological problems share in common (11, 12, 16, 19, 43).

Much remains to be learned, of course, but a number of ongoing large population-based studies are likely to move the field forward on these topics. For example, a striking report based on data from the UK Biobank study of >40,000 adults showed that intelligence was genetically correlated with the structure of the right cardiac atrium and neuroticism was genetically correlated with the structure of the right cardiac ventricle, with evidence of direct or indirect pleiotropic genetic causation (44). The most informative future large-scale studies will be ones that not only include strong measures of a broad range of psychological problems and health, but also include measures of the key constructs, like neuroticism and cognitive control, that dispose individuals to develop a diverse range of psychological and health problems. This is because it is feasible to discover the causes and psychobiological mechanisms underlying a few uncorrelated dispositional dimensions, such as cognitive control and neuroticism, but very difficult or impossible to discover those underlying highly correlated forms of psychological and health problems (45).