Comorbidity Research Paper

1. The Causes Of Comorbidity

Some comorbidities occur purely by chance. For example, given that approximately 15 percent of the adult population in the United States suffers from seasonal allergies and that approximately 20 percent suffers from arthritis, one would expect to find 3 percent of adults who suffer from both disorders merely on the basis of chance association (i.e., 15 percent of 20 percent is 3 percent). There are also situations, though, in which certain comorbid disorder clusters occur at higher than chance levels.

Nonrandom comorbidity can be brought about by at least three broad classes of processes. The first is when one disorder directly effects the onset of a second disorder. For example, persistent alcohol abuse can lead to cirrhosis of the liver. A second class of processes involves indirect effects of one disorder on the onset of a second disorder. The stresses associated with the threat and lifestyle changes that follow from receiving a diagnosis of heart disease, for example, can pre-dispose to the onset of an anxiety disorder. A third class of processes that can lead to comorbidity involves common causes. Traumatic life events, for example, can predispose to a wide range of comorbid anxiety and mood disorders. Biological factors can also be common causes. Twin studies, for example, show that there are common genetic factors that play an important part in bringing about the strong comorbidities found among many commonly occurring mental disorders (Kendler et al. 1995).

2. Basic Patterns Of Comorbidity

Three types of comorbidity have been of particular interest to clinical psychologists: comorbidity between different mental disorders; comorbidity between mental disorders and substance use disorders; and co-morbidity between mental disorders and physical disorders. All three types of comorbidity are quite common in the general population. Nearly half of all people with a mental disorder in the general population meet criteria for two or more such disorders, while more than half of people with a substance use disorder and as many as three out of four patients in treatment for substance abuse or dependence also meet criteria for a mental disorder (Kessler et al. 1996). Mental disorders, especially anxiety and depression, are also found in a substantial minority of people in treatment for physical illness and especially among high utilizers of primary care (Miranda et al. 1994).

2.1 Mental–Mental Comorbidities

Bivariate associations between pairs of hierarchy-free DSM-III-R disorders in general population epidemiological surveys reveal three general patterns (Kessler 1997). First, there is a generally positive pattern of associations among the vast majority of commonly occurring anxiety, mood, personality, and substance disorders. Second, associations are generally stronger within than between broad classes of disorders (e.g., anxiety disorders are generally more strongly related to each other than to mood disorders). Third, extremely strong comorbidities are found among dis-orders in clinically recognized syndrome clusters, such as panic and agoraphobia, double depression (major depression and dysthymia), and bipolar disorder (major depression and mania).

Some mental–mental comorbidities appear to be brought about by indirect causal processes, as in the case of panic predisposing to agoraphobia. Others appear to be due to common underlying causes, as in the case of the cycling episodes of depression and mania characteristic of bipolar disorder. Causes are less clear in other types of mental–mental comorbidity. There is currently a great deal of interest in using longitudinal twin and family research designs to investigate some of the more poorly understood of these comorbidities in an effort to refine nosological distinctions.

Many of the strongest comorbidities involve combinations of anxiety and depression—panic, generalized anxiety disorder and social phobia with depression. The anxiety disorder usually starts at an earlier age than the depression in all these cases. Whether this is true because anxiety is the primary disorder or because some types of comorbid anxiety depression are a single disorder in which anxiety is the earliest manifestation is not clear. The fact that certain antidepressant medications have been found to be effective in treating some anxiety disorders but not others, and the fact that the types of anxiety disorders that are affected vary from one antidepressant to another, strongly suggest that complex common neurobiological path-ways are involved in these comorbidities. Although good progress is being made in tracing out these pathways, having enough knowledge to develop pharmacologic agents to treat specific types of comorbid anxiety depression is still a long way in the future (Boyer 2000).

2.2 Mental–Substance Comorbidities

Substance use disorders have strong comorbidities with a number of mental disorders (Kessler et al. 1996). These comorbidities are thought to come about largely because of a combination of indirect effects of mental disorders on substance use disorders (e.g., self-medication) and common causes (e.g., exposure to predisposing environmental experiences). There are also some cases in which substance use disorders bring about mental disorders either directly (e.g., brain kindling caused by heavy use of psychostimulants leading to panic) or indirectly (e.g., alcoholism leading to adverse environmental consequences that predispose to depression). However, these processes are thought to be less common than those involving effects of mental disorders on subsequent substance use disorders.

The patterns and processes involved in mental– substance comorbidity differ by gender. Among women, anxiety and depression are the mental dis-orders most strongly related to substance use disorders (Kessler et al. 1996). These mental disorders typically occur prior to the onset of substance problems among women. Self-medication is thought to be the main process leading to the secondary substance problems. Among men, in comparison, acting out disorders such as oppositional-defiant disorder, conduct disorder, and pathological gambling are the mental disorders most strongly related to substance use disorders. Both sets of disorders are generally thought to be joint consequences of other influences involving such things as impulsivity, risk taking predisposition, and peer influences.

There is a good deal of evidence showing that patients with certain combinations of substance use disorders and comorbid mental disorders are more difficult to treat and have a more severe and chronic course than patients with pure disorders. This is true, in part, because continued use of substances can interfere with psychotherapy for mental disorders as well as because the existence of abuse potential limits the range of pharmacologic therapies available to the clinician to treat the mental disorder. In addition, treatment compliance is often lower and functional impairment is often higher among patients with mental–substance comorbidities than patients with pure disorders. These factors all predispose to a poor prognosis.

There is considerable interest among treatment researchers in using information about these processes to develop targeted interventions for patients with particular types of mental–substance comorbidity (Carroll et al. 1997). These processes are often quite complex. In the case of comorbid substance dependence and antisocial personality disorder, for example, there appear to be reciprocal effects in which antisocial behavior adversely affects the course of substance dependence as well as substance dependence adversely affecting the course of antisocial personality disorder. In addition, people with this type of comorbidity report earlier ages of first use of drugs, more rapid progression from initial drug use to dependence, and greater drug-related problems in daily living than other people with comparable drug problems. This type of comorbidity is also associated with high rates of relapse after treatment.

There has been some success at developing targeted treatment strategies linked to comorbidity. Relapse prevention programs, for example, have had success treating patients with primary anxiety disorders who use drugs to self-medicate their fears by helping these patients recognize that their relapses of substance problems are often triggered by stress reactions. Refinements of this approach have shown that drug abusers who use drugs as a form of self-medication of a mental disorder respond differently to treatment depending on the type of primary mental disorder they have. Large-scale mental–substance patient–program matching efforts that go beyond these cases, though, have had only mixed success so far (Project MATCH Research Group 1998).

Another treatment matching issue of considerable policy importance concerns the distinction between integrated treatment and parallel–sequential treatment. The evidence is clear that both mental and substance use disorders need to be treated in order to successfully reduce the persistence of mental– substance comorbidity. This being the case, integration of the treatment of the two types of disorders in a single setting makes sense both in terms of benefit to the patient and cost-effectiveness. However, integrated treatment remains the exception rather than the rule in the US today due to disciplinary controversies among the professionals who provide treatment for substance disorders and mental disorders. Differences in philosophy of treatment and concerns about control of resources have kept the two systems apart to the detriment of patients.

This is especially true in the public sector, where most states have separate departments of mental health and substance abuse services and where federal block grants to fund the two types of services are often given to separate organizations that refuse to collaborate. This separation has led in many states to a system characterized by parallel and sequential treatment in which the mental health treatment provider refuses to see the patient unless they are free of drugs and the substance abuse counselor ignores mental health treatment issues. Innovative strategies have been developed both to increase integration of these systems and to help patients negotiate these systems with the aid of a single case manager (Miller 1994). These strategies can be effective both in improving the quality of life of patients and in saving money by reducing inefficient duplication of effort across un-coordinated systems of care. However, entrenched systems move slowly and formidable barriers exist to system change.

2.3 Mental–Physical Comorbidities

It has long been known that high utilizers of primary medical care have high rates of anxiety and mood disorders (Katon et al. 1990). Although some of these patients suffer from physical disorders that indirectly predispose to their comorbid mental disorders, others have untreated primary mental disorders that lead to high medical care costs due to unnecessary medical tests and visits (Miranda et al. 1994). Primary care doctors who are aggressive in detecting and treating mental disorders among their patients generate significantly lower overall per panel member health care expenditures than other physicians with comparable case mixes. Furthermore, treatment effectiveness trials designed to help primary care doctors improve their detection and treatment of mental disorders have documented significant reductions both in somatic complaints and in overall treatment costs for somatic complaints (Campbell et al. 2000).

Epidemiological studies have also documented significant comorbidities between particular mental– physical disorder pairs such as panic disorder with asthma and depression with diabetes (Ciechanowski et al. 2000). Prospective epidemiological studies of pre-disposing personality characteristics provide some evidence that early-onset mental disorders might be risk factors for some chronic physical disorders such as cancer and coronary heart disease. In other cases, such as comorbidity between asthma and panic dis-order, the evidence suggests that the physical illness is causally primary.

The evidence is even stronger in showing that comorbid mental disorders, whether causally primary or secondary, adversely affect the course of chronic physical disorders. A variety of reasons have been proposed for this, including effects of mental illness on sensitivity to somatic symptoms, lack of adherence to medical regimens, reduction in immune competence, and increase in sympathetic nervous system reactivity (Rozanski et al. 1999). This evidence is strong enough in the case of some comorbidities to justify experimental trials aimed at evaluating the impact of treating comorbid mental disorders on the course of chronic conditions. For example, the government is currently sponsoring the Recovery in Coronary Heart Disease trial, in which heart patients with comorbid depression are being randomized either to usual care or to an enhanced program of care that includes cognitive-behavioral therapy for their depression.

3. Implications Of Comorbidity For Prevention Of Secondary Disorders

Many strong comorbidities begin with early-onset mental disorders that occur during the school years. One important implication of this fact that has not yet been exploited involves the possibility that temporally secondary disorders could be prevented by aggressive outreach and treatment of these prior mental disorders in school-based screening and intervention programs. This possibility would appear to be especially promising for comorbidities involving early-onset anxiety and mood disorders that predispose to secondary substance use disorders through self-medication. Epidemiological studies show that the time lag be-tween the first onset of these primary mental disorders and subsequent substance abuse averages between six and 10 years (Kessler et al. 1996). This interval of time represents the window of opportunity during which detection and treatment of mental disorders can be used to help prevent or delay the onset of substance use disorders. Little is known about the likely success of these early treatment efforts due to the fact that most people who obtain treatment for anxiety or mood disorders do not receive early intervention. Efforts are currently underway to refine understanding of the transition from primary anxiety and mood disorders to secondary substance use disorders in epidemiological data and to carry out evaluations of early treatment programs in order to determine whether early outreach and treatment of these mental disorders can help prevent later substance abuse. Long-term follow-up of such programs might also provide important insights into the effects of such interventions on the later development of chronic physical disorders.

4. Future Directions

As knowledge about the neurobiology of mental disorders increases, some of the syndrome clusters presently considered mental–mental comorbidities will likely turn out to be single disorders. As this happens, a probable concurrent realization will be that some of the syndromes now considered single disorders are in fact heterogeneous. For example, several different types of depression might be identified, each characterized not only by a somewhat different set of depressive symptoms, but also by a characteristic profile of comorbid anxiety symptoms. The ultimate goal of this subtyping will be to refine treatment. As a result, advances in treatment, especially pharmacologic treatment, will spur on these refinements. Indeed, complex treatment trials evaluating the effects of patient– treatment matching will likely be the core research design used to validate subtypes. Initial trials of this sort already have shown the heterogeneity in newer pharmacologic treatments by their ability to treat various comorbid depression and anxiety disorders. Epidemiological twin and family aggregation studies will be useful to provide hypotheses about potentially important subtypes. Similar refinements will occur in studies of mental–substance comorbidities.

Research on mental–physical comorbidities is likely to proceed in a somewhat different way. Although research eventually may show that there are some common neurobiological pathways that predispose to certain closely related comorbidities of this sort, such as early-onset anxiety and later ulcers, most research on mental–physical comorbidities will probably continue to focus on mental disorders as complicating factors in the course of physical disorders. Chronic disease doctors increasingly are recognizing that anxiety and mood disorders are highly prevalent among their patients and strongly related to illness course. The next logical stage is the development of programs for adjunctive treatment of mental disorders among the physically ill. A great increase in such programs in the future is anticipated. More wide-spread screening for mental disorders in primary care will likely occur in conjunction with these programs. Closer integration of mental health with physical medicine is an inevitable consequence, although the structure of this integration doubtlessly will be shaped by future developments in the organization and financing of services.

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