In spite of the proliferation of literature on comorbidity, a number of fundamental issues regarding the meaning of the term persist in recent literature. A key issue pertains to the distinction between disorder concepts as applied to a specific individual and disorder concepts as applied to a sample of individuals. Although this distinction is fundamental, it is a distinction not directly encoded in the term “comorbidity.” Returning to the seminal work of Feinstein (1970)
, he discussed and was concerned about the relevance of comorbidity in studying disease in the population, yet his definition applies to a specific individual patient. This focus is quite sensible from the perspective of the front-line clinician, who deals not with disorder constructs as applied to groups of people, but with those constructs as applied to specific individuals. Consider an example: It is likely that a significant proportion of people who meet criteria for a prevalent mental disorder in clinical settings (e.g., major depression) are also nearsighted. This phenomenon could legitimately be termed comorbidity, following from Feinstein’s (1970)
definition. Moreover, this phenomenon would be of clinical interest and importance with regard to a specific patient. As a clinician, if we encountered a patient who was clearly depressed and also found it difficult to see faraway objects clearly, the responsible course of action would be to treat the depression and to obtain a proper consult for the vision impairment.
Yet the phenomenon that has captured the interest of psychopathology researchers is different from the basic fact that any given person may legitimately qualify for more than one clinical condition. The epidemiological data on comorbidity described above do not refer simply to the fact that any given person with a disorder could also have another disorder. Instead, what is of interest to the field is that a person who meets criteria for a specific mental disorder is much more likely to also meet criteria for other mental disorders than one would expect simply by chance. That is, mental disorder constructs, as applied to groups of people, are correlated. The term comorbidity legitimately encompasses this correlational phenomenon—it allows people to have more than one diagnosis. The problem is that the term also encompasses the simple fact that a person who meets criteria for a specific disorder could meet criteria for another disorder even if no correlation exists between the two disorders. That is, the term comorbidity does not differentiate between the idea that two legitimate diagnoses may be made in a specific individual (a phenomenon that could be described as co-occurrence) and the observation that two diagnoses are correlated or covary in a group of people.
The distinction between co-occurrence and correlation is conceptually important, and a problem noted in recent literature is that the term comorbidity could legitimately refer to either phenomenon. For example, Vella et al. (2000
, p. 25) write that “comorbidity should be defined as two or more diseases, with distinct aetiopathogenesis (or, if the etiology is unknown, with distinct pathophysiology of organ or system), that are present in the same individual in a defined period of time.” This definition is closer to the idea of co-occurrence captured by Feinstein’s (1970)
definition, although it also adds the provision that some evidence of underlying casual distinctiveness is needed for the term “comorbidity” to apply (cf. Lilienfeld et al. 1994
, Meehl 2001
). By way of contrast, in writing on the comorbidity of childhood psychopathologies, Lilienfeld (2003)
restricts his use of the term to “covariation” among diagnoses across individuals rather than co-occurrence among diagnoses within individuals. None of the authors could be said to be wrong in the way they approach working with the term “comorbidity.” The problem is that the term itself is broad enough to encompass too many conceptually distinct phenomena.
For example, how does one compute the comorbidity rate for a specific sample? Working from Feinstein’s (1970)
definition, one could report the percentage of persons with two specific diagnoses. The problem with this approach is that apparently impressive percentages of comorbid cases could, in theory, be compatible with both co-occurrence expected by chance and co-occurrence at rates greater than those expected by chance (i.e., correlation). Co-occurrence expected by chance is the product of the prevalences (also known as base rates) of the two disorders. For example, if the prevalence of Disorder A is 75% and the prevalence of Disorder B is 50%, 38% of the sample would have both disorders, just by chance, because 75% × 50% = 38%. Given that, in clinical settings, the prevalence of many disorders is substantial using both unstructured and structured approaches to interviewing (e.g., major depression; Zimmerman & Mattia 1999
), comorbid cases could be frequently encountered just by chance.
Yet extensive evidence shows that comorbid cases are encountered far more than would be expected by chance. This was noted early on by Boyd et al. (1984)
, who presented a table showing that the number of cases in their sample with two or more coexisting disorders is notably greater than would be expected by chance, whereas the number of cases with only a single disorder is notably less than would be expected by chance. The problem is that this phenomenon is typically termed comorbidity when, in fact, simply observing that some people meet criteria for more than one diagnosis could also legitimately be termed comorbidity.
A related concern emerging in recent literature relates to the prefix “co-” added to the word “morbidity.” That is, Feinstein’s (1970)
definitions pertain to two diagnoses. Yet the general tendency for mental disorders to be correlated means that three or more diagnoses are not uncommon. Should terms such as “trimorbidity” or “quadramorbidity” be used to describe individuals with the requisite number of diagnoses? Inventing more terms for these complex patterns may not be very productive, yet developing a way of conceptualizing persons with complex patterns of more than two diagnoses is crucial for the field. Such persons are more frequent than expected by chance; Boyd et al. (1984)
observed 22.4 times as many cases with three or more diagnoses than would be expected just by chance. These “multimorbid” cases also carry a disproportionate burden of risk for psychopathology. In the National Comorbidity Survey (Kessler et al. 1994
), more than half of mental disorders in the past year occurred in people with a lifetime history of three or more diagnoses. These data are not well captured by the term comorbidity in the sense that the term does not explicitly refer to more than two diagnoses. Interestingly, the conceptual conundrum here is not limited to mental disorders, as the term “multimorbidity” appears to be gaining influence in literature on the epidemiology of more broadly defined medical disease (Van den Akker et al. 1996
) yet appears rarely in literature on mental disorders (Batstra et al. 2002
Other commentators have also expressed concerns about the term and concept of comorbidity, and, at the same time, the importance of understanding the phenomena encompassed by the term. A fascinating interchange is found in the work of Lilienfeld et al. (1994)
and commentaries on that work (Blashfield et al. 1994
, Robins 1994
, Rutter 1994
, Spitzer 1994
, Widiger & Ford-Black 1994
). In addition to discussing the confusion between co-occurrence and covariation, Lilienfeld et al. (1994)
argue that the term comorbidity is not very helpful in psychopathology research because it tends to reify current mental disorder constructs, implying a level of conceptual clarity that is currently lacking (e.g., that disorders are bona fide categories with well-understood and discrete etiologies and pathophysiologies). Lilienfeld et al. (1994)
then suggest that the term “comorbidity” be avoided, and propose the use of the more precise terms “co-occurrence” and “co-variation” as appropriate. A number of commentators on this work were sympathetic with the need for greater precision, but felt that abandoning the term “comorbidity” would be premature and even perhaps counterproductive. Rutter (1994)
, for example, argued that comorbidity should serve as an impetus to research on the validity of current diagnostic constructs, and that abandoning the term could lead to the unintended consequence of stopping such research. Similarly, Spitzer (1994)
regarded comorbidity as a reasonable label for co-occurring entities that may not rise to the conceptual level of bona fide categories with clear-cut etiologies and pathophysiologies—not only in psychiatry, but in medicine more generally—and therefore, that Lilienfeld and colleagues’ concerns were misplaced.
Nevertheless, the issues raised in the Lilienfeld et al. (1994)
exchange, and dissatisfaction with the comorbidity concept, resonate throughout more recent literature. Maj (2005a
suggests that the fact that various mental disorders rarely occur in isolation could be viewed as evidence that comorbidity is an artifact of current diagnostic systems imposing categorical distinctions that do not exist in nature. Along these lines, Meehl (2001)
suggests that the term “comorbidity” would be most meaningfully applied to taxonic categorical conditions, where distinct and discrete latent structures underlie the two comorbid conditions. Bogenschutz & Nurnberg (2000)
emphasize the importance of sorting through these issues to clarify thinking about diagnosis, noting that comorbidity among certain categorical mental disorders (e.g., major depression and posttraumatic stress disorder) may be better understood from a dimensional framework. Batstra et al. (2002)
note that bivariate statistics such as odds ratios tend to be used in studying comorbidity among mental disorders, even though the phenomenon appears to be multivariate in nature and requires a statistical approach capable of mapping the concept of multimorbidity. Van Praag (1996
, p. 132) suggests that the term “comorbidity” “conceals more than it clarifies, if used without further qualification,” noting that the basic data on comorbidity could be compatible with a number of diverse interpretations, a situation indicating a need to build and test more specific models of specific forms of comorbidity.
Concerns have also been raised about comorbidity in everyday clinical practice. Kaplan et al. (2001)
note that few children represent prototypical cases of specific disorders, yet describing a child as “comorbid” may be less helpful in clinical case conceptualization and in parent communication than conceptualizing and communicating about more general mechanisms that may unite putatively distinct disorders (e.g., atypical brain development). In an article on comorbidity among child and adolescent forms of psychopathology, Jensen (2003)
notes that many studies exclude children with comorbid disorders, rendering the relevance of those studies to the typical clinical case unclear.
In sum, the breadth of the phenomena that could be termed “comorbidity” suggests a concept in need of thoughtful refinement. Indeed, Lilienfeld (2003)
describes a personal communication with Feinstein in which he was reported to express dissatisfaction with the overuse of the term. Still, the basic phenomenon that has captured the interest of the field under the comorbidity rubric seems clear and important: Mental disorders are significantly correlated. That is, meeting criteria for one disorder predicts meeting criteria for others. The challenge, then, is to understand why this happens and what it means for how we might best conceptualize and understand psychopathology. This would involve delineating models of the comorbidity among mental disorders (see, e.g., Lilienfeld 2003
, Lyons et al. 1997
, Maser & Cloninger 1990
, Rutter 1997
) and determining which models best capture the empirical data documenting significant correlations among diverse disorders, an endeavor that should help in revealing the meaning of the comorbidity phenomenon.