Risk and Protective Factors and Etiological Chains

Treatment interventions have been developed from knowledge of risk and protective factors that influence the course and outcome of mental disorders; likewise, preventive interventions have been developed from knowledge based on risk and protective factors that affect the onset of mental disorders. Some of these risk and protective factors are undoubtedly the same for treatment and prevention, and some are undoubtedly different. Research on the factors thought to be associated with onset of disorders—and thus of particular interest in prevention—and on how and where they fit within causal models is still at an early stage (see Chapter 6). Nevertheless, treatment research involving risk and protective factors affecting the course of disorders can provide additional insight. For example, many treatment studies have shown that when language, communication, and social skills are improved—giving individuals more functional control in their environments—disruptive, aggressive, self-injurious, and stigmatizing behaviors can be greatly reduced (Liberman, 1988). This consideration may have utility in prevention of stress-induced onset of disorders whose precursors include information-processing deficits.

As described in Chapter 2, risk factors that function as precursor signs and symptoms of a disorder can be used in indicated preventive interventions to target individuals at high risk for onset. Currently, whether those risk factors were part of the prodrome of the disorder can be known only in retrospect, after onset. Identification of prodromal phases could facilitate use of a treatment intervention to push the boundaries from treatment into an indicated prevention, which, because of its proximity to treatment on the intervention spectrum for mental disorders (see Figure 2.1), is where lessons from treatment are likely to be most applicable.

In the course of schizophrenia, for example, delay in treating the early stages of the disorder leads to maladaptive coping strategies by families and patients, the appearance of negative symptoms, refractoriness to drug therapy, social withdrawal, and greater chronicity. A treatment demonstration project in England by Falloon and colleagues documented a decrease in the prevalence of chronic schizophrenia when early detection and treatment intervention were provided by mental health teams working closely with general practitioners to reduce the duration and intensity of the disorder (Falloon, Shanahan, LaPorta, and Krekorian, 1990). Falloon reported reductions in chronic schizophrenia following an intervention that focused on individuals showing early stages of schizophrenia. Key features of this treatment intervention were (1) the identification of individuals hypothesized to be at risk to move further down the pathway to a chronic schizophrenic disorder, at a point relatively close to the disorder onset; (2) the use of proven, multimodal interventions, including both pharmacological and psychosocial components; and (3) integration of the treatment program within the primary health care and family systems (Falloon, 1992). Thus one prospect for a preventive intervention research program for schizophrenia might be to offer education on the early warning signs of psychosis in middle and high schools and colleges to students, parents, and teachers, as well as through the mass media, so that early identification of precursor signs and symptoms with a high likelihood of leading to the onset of disorder would lead to early indicated prevention, including psychosocial interventions for the individual and his or her family. However, the prevalence of schizophrenia is only 1 percent, and there are considerable dangers in the effects of labeling false positives, so the initiation of such a program would have to be considered very carefully.

Another example of using treatment interventions to push the boundaries from treatment into indicated preventive intervention is in the area of depression. DeRubeis, Hollon, and colleagues have reviewed evidence from studies that have followed up patients who were treated for depression (Hollon, DeRubeis, and Seligman, 1992; DeRubeis, Evans, Hollon, Garvey, Grove, and Tuason, 1990). Overall, the relapse rates for patients who received cognitive therapy were considerably lower than for those who received pharmacotherapy. Thus cognitive preventive interventions might help avert a first episode of depression, especially in individuals with precursor symptoms.

With the development of reliable and sensitive means of detecting prodromal phases of a disorder, the current public education programs on recognition and treatment of depressive and anxiety disorders, sponsored by the National Institute of Mental Health (NIMH) (e.g., NIMH Panic Disorder Campaign (NIMH, 1991)) could be expanded to include identification and preventive intervention of early precursors associated with these and other mental disorders. Information regarding the early precursors of panic and agoraphobia (such as an initial, transient panic experience) could be provided to the public through radio, television, and newspaper “health messages.” Such an educational campaign might result in early identification and indicated preventive interventions, such as cognitive-behavioral approaches for the individual and his or her family, before the full syndrome develops. A research trial could be developed to determine the efficacy of such an approach.

Co-morbidity of Disorders

There is a high rate of co-morbidity in mental disorders. Half of persons with mental disorders have more than one diagnosis (Wolf, Schubert, Patterson, Grande, Brocco, and Pendleton, 1988). Furthermore, three out of four individuals with substance abuse disorders are also diagnosed with another mental disorder (Ross, Glaser, and Germanson, 1988). Data from the Epidemiologic Catchment Area study show that approximately half of mental disorders in the United States occur in persons with a history of some other mental disorder (Robins, Locke, and Regier, 1990).

Treatment research has found that one disorder (the primary disorder) usually occurs at an earlier stage than the other disorder(s) (typically described as secondary). For example, co-morbidity between anxiety disorders and substance use disorders has been found in a number of clinical studies (Roy, DeJong, Lamparski, Adinoff, George, Moore et al., 1991; Chambless, Cherney, Caputo, and Rheinstein, 1987), with phobias almost always preceding substance abuse (Christie, Burke, Regier, Rae, Boyd, and Locke, 1988; Hesselbrock, Meyer, and Keener, 1985; Weiss and Rosenberg, 1985). Klein (1980) suggests that co-morbidity between primary phobia and secondary substance abuse is traditionally attributed to anxiety, which leads to the use of alcohol and drugs as a form of self-medication. This interpretation has been supported by reports that the majority of patients with phobias consciously use drugs and alcohol to manage their fears (Bibb and Chambless, 1986). Other examples of a primary disorder leading to a secondary one include cocaine, marijuana, and amphetamine abuse triggering schizophrenia, panic disorder predating agoraphobia, and dysthymia being followed by major depression.

This evidence on co-morbidity of mental disorders suggests several rationales for preventive intervention research (Kessler and Price, in press). First, when one disorder causes or leads to a second, prevention of the first disorder is a plausible preventive strategy for the second. Preventing the onset of an initial primary disorder could, in principle, reduce the number of lifetime cases of other mental disorders and the substantial impairment, disability, and handicap associated with them. Thus preventive interventions aimed at preventing the initial primary disorder should include outcome measures that assess effects on the incidence of multiple disorders. Second, when precursor signs and symptoms of a primary disorder are identified, preventive interventions should focus not only on the prevention of the primary disorder but also on the other likely co-morbid disorders that could develop. For example, a program to prevent anxiety symptoms from developing into a phobia should be accompanied by preventive strategies to decrease the potential for substance abuse. This might be done by weakening or eliminating causal pathways from the first set of precursor symptoms of the primary disorder to a likely set of precursors for a second disorder that could develop. Third, possible causal mechanisms linking two or more disorders provide a special opportunity for both prevention and etiological research. Interventions aimed at common causes may reduce the incidence of two or more co-morbid states. Finally, individuals who are at high risk for a mental disorder because of their having a primary physical disorder may benefit from preventive interventions. For example, individuals recovering from a myocardial infarction or coronary artery graft surgery—one half of whom can be expected to develop a depressive disorder—would be prime candidates for preventive interventions, especially if they have had precursor symptoms of depression (Brown, Munford, and Munford, 1993).

Progressive Course of Maladaptive Behavior

Treatment research has documented strong associations between children with dysthymic disorder, a persistent depressive condition, and the subsequent development of major depression (Kovacs, Feinberg, Crouse-Novak, Paulauskas, and Finkelstein, 1984a; Kovacs, Feinberg, Crouse-Novak, Paulauskas, Pollock, and Finkelstein, 1984b). Likewise, the early appearance of low levels of disruptive behaviors, such as inattention to classroom or home rules, in young children can progress to full-blown oppositional, conduct, or antisocial disorders that develop at a later age (Koegel, Camarata, and Koegel, 1992; Loeber, Brinhaupt, and Green, 1990). In a similar manner, patterns of seeking attention and social validation and avoiding challenging or anxiety-provoking situations in childhood may establish behavioral trends that can escalate to a mental disorder at a later stage in life. Thus it would appear that preventive intervention research would need to separate normative from abnormal developmental patterns of behavior and focus on eliminating or reducing those elements in the social environment that reinforce abnormal modes of coping and adaptation.

Individual Differences

Treatment in most areas of medicine has been guided by an appreciation of the special needs and responses of the individual patient. In treatment research the focus is often on which type of treatment is best for individual patients with specific mental disorders. Contributing to individual differences are the underlying gene-environment risk patterns and the role they play in etiology and the availability of social and other environmental resources.

One type of treatment intervention design that recognizes the importance of individual differences is the modular approach, which offers discrete elements of the intervention incrementally, in a hierarchy beginning with interventions that are least costly and intrusive to the subject population, depending on each individual's needs and responses (Liberman, Mueser, and Glynn, 1988; Liberman, 1981; Lazarus, 1974). For example, a wide range of modules have been developed for individuals with chronic mental disorders. The modules help teach skills in conversation, money management, home finding and maintenance, and medication self-management. Each identified skill area has specific, targeted behaviors for training (Liberman, 1988).

The modular approach has three primary advantages for treatment. First, it permits considerable latitude in designing a program to fit the specific needs of a given individual, while ensuring that some core elements are consistently applied to all. This approach depends on defining which subgroups will respond to which interventions. An eclectic approach can be developed, using modules that draw from cognitive, social, behavioral, and pharmacological domains.

Second, the modular approach can achieve greater efficiency in cost-effectiveness through providing only as much intervention as is needed and desired. Some targeted individuals may require many months or even years of intervention, whereas others may show the desired change in risk factors with a minimal, brief intervention.

Third, the modular approach fits well with a competence-based approach to intervention. Because many intervention programs aim to enhance skills that confer protection against risk factors—both enduring psychobiological vulnerabilities in the individual and stressful life events—monitoring the acquisition of skills in the targeted population can reveal the point at which incremental, modular intervention has achieved its objective in any one individual. In a like manner, preventive interventions that are flexible and tailored to individual needs may yield better results than a preventive intervention that attempts to change all targeted participants in much the same way with much the same type, intensity, and duration of intervention. Preventive interventions should take cognizance of individual differences in the degree to which participants are “at risk,” possess personal or environmental protective factors, and display readiness for intervention.

Multimodal Interventions

The complexity of mental disorders has led to the use of multimodal treatment interventions including pharmacological and psychosocial-behavioral approaches. These combined approaches have tended to be more effective than either alone (Kaplan and Sadock, 1989; Karasu, 1989). Such combined biopsychosocial interventions also may be more effective than unidimensional interventions in prevention trials.

Before considering the use of pharmacological agents in prevention, the benefit-risk ratio of such a strategy must be carefully weighed. There are several reasons to limit the use of pharmacological agents in prevention programs that have children and adolescents as participants. First, the efficacy of drug therapy for many mental disorders in children is not well documented. Second, the adverse side effects of psychoactive drugs, especially on physical and mental development, may be greater for youths than for adults. Third, the potential for stigmatization may be greater when medications are used.

Some medications have proved effective in alleviating symptoms of some mental disorders and in forestalling relapse. Therefore it may be reasonable—but only with adults, not with children—to study the potential of these psychotropic drugs for preventing or delaying the onset of a disorder if administered to individuals who have precursor signs and symptoms and are at extremely high risk for the disorder. However, this is an extremely controversial issue. Even with adults, benefit-risk ratios for medication strategies must be carefully weighed. Medications with serious and frequent side effects would probably exceed a threshold considered acceptable. In indicated preventive interventions, knowing that an individual is entering a high-risk period for the development of a mental disorder might justify the administration of a psychotropic medication known to be effective with the disorder of concern. The amount of medication could be titrated downward to a subclinical, yet potentially effective, preventive dose in individuals who have shown precursor signs or symptoms of the disorder. Thus judicious administration of antidepressant and antipsychotic medications might find a place in the prevention of depressive and schizophrenic disorders among individuals at extremely high risk for developing these illnesses. This pharmacological preemptive strategy has been used to treat toxic, drug-induced psychoses in individuals thought to be at risk for schizophrenic disorder (Machiyama, 1992). Similarly, rapid treatment of serious panic symptoms with pharmacotherapy and cognitive behavior therapy might prove effective in preempting the development of agoraphobia.

Timing, Duration, and Environment of Interventions

The timing of interventions may be critical to success. For example, parent training with parents of conduct disordered children has been shown to be effective in producing clinically significant behavior changes in children up to age 12½ (Dishion and Patterson, 1992). However, that research has also shown that parents of older children are more likely than parents of younger children to drop out of the intervention before completion. The importance of intervening during sensitive periods, before precursor problem behaviors become rigidly set, is highlighted by the disappointing results of intensive and long-term residential social learning therapy for predelinquent boys. Even though there were efficacious results while the youth were living under close supervision (Phillips, Phillips, and Fixsen, 1971), long-term follow-up studies failed to document a significant effect of the social learning therapy on emergence of delinquency and other antisocial personality traits. It has been suggested that aggression crystallizes around age 8 and that preventive interventions should start before then (McCord and Tremblay, 1992). Both sets of findings suggest that providing parent training in early childhood is likely to be more successful in reducing the prevalence of child conduct problems than is delaying intervention until middle or late childhood, when oppositional and aggressive behavior patterns have stabilized (Loeber and Dishion, 1983).

Duration of interventions may also be critical. The achievement of prevention of mental disorders based on short-term interventions is unlikely to be successful. The literature on treatment intervention research repeatedly shows that the impact of a time-limited treatment tends to be diluted and lost over time because of subsequent intervening biopsychosocial events, natural living environments, and other transactions between individuals and their social settings (Forehand, 1992). Ideally, to sustain the progress derived from the initial intervention, prevention programs need a developmental perspective, with an integrated and comprehensive series of age-specific interventions timed to enhance and sustain healthy adaptation and skills and prevent dysfunction at multiple points over the life course. Successful interventions will need to have a sustained source of funding.

To achieve durable and generalizable effects from preventive interventions, the use of long-term strategies with the continuous or intermittent infusion of elements of the prevention program will need to be carefully considered. These may include the use of “booster” programs or the involvement of natural helpers (such as parents, caregivers, teachers, and peers) to ensure that the individual's social environment will continue to reinforce and strengthen the targeted protective factors. Many effective psychosocial and behavioral treatments have employed natural helpers instead of professional therapists to deliver the interventions (Stein, 1992; Falloon, 1988; Tharp and Wetzel, 1979). Involving natural helpers bearing close relationships with the targeted high-risk individuals may be fruitful in the delivery of preventive interventions as well, especially because these often take place in naturalistic, nonclinical community settings.

With regard to the site of the intervention, Webster-Stratton's (1992) findings from treatment research suggested that low-income, young, single mothers of infants and toddlers were the least likely group to profit from a video-assisted intervention program administered in a clinical setting. These young mothers, constrained by lack of mobility and babysitters, might have responded better to treatment delivered through home visits. In another example of the importance of choice of site, soldiers who have experienced “combat fatigue” or stress syndromes have been treated with combined pharmacological and exposure-in-vivo approaches as close to their front-line positions as possible, rather than in far-off hospitals (Rahe, in press), with the aim of returning the soldiers to duty as quickly as possible. Preventive intervention programs also may have different levels of participation and effectiveness depending on where they are delivered.

Treatment research has illustrated that behaviors and skills transfer to novel environments and demonstrate durability if programming for generalization is a part of the intervention (Liberman, McCann, and Wallace, 1976). Generalization requires specifically linking the intervention in one setting to other situations involving peers, family, school, and work. Generalization techniques include

• gradually “fading” the intervention (such as gradually reducing social reinforcement from the teacher for appropriate social behavior from almost continuous to very intermittent);
• using in vivo interventions (such as teaching the child at risk for conduct disorder to verbally negotiate conflict situations with peers on the playground);
• making the interventions relevant to the participant's natural environment (such as, while coaching unemployed persons at risk for depression on job interviewing skills, making sure that the person role playing the employer accurately represents a coldly rejecting interviewer as well as a congenial interviewer, or having a person at risk for alcoholism use drink-refusal skills in a variety of environments, such as restaurants, bars, and homes, and in response to overtures from bartenders, peers, family members, and strangers);
• overlearning (such as requiring repetition when teaching discriminations or skills); and
• self-instruction and self-management (Eckman, Wirshing, Liberman, Marder, Johnston-Cronk, Mintz, and Zimmerman, 1992; Dobson, 1987).

Other strategies to increase durability include the use of “booster” programs. Pharmacotherapists have documented and accepted the need for “maintenance” drug treatment for chronic and recurrent mental disorders. However, a double standard applies in clinicians' thinking about continuing an indefinite psychosocial treatment for a chronic mental disorder. If the pharmacological treatment is withdrawn and the patient relapses, the treatment is viewed as efficacious; on the other hand, if the psychosocial treatment is withdrawn and the patient relapses, this is considered evidence that the treatment is ineffective. The importance of prolonged, maintenance, and booster treatments for serious and chronic mental disorders has recently received greater recognition, and it is likely that preventive interventions will also increasingly be designed with these attributes.

Intervention Effects on Family Members

Interventions with one family member have been shown to have salutary effects on other family members. For example, treatment delivered to patients with diagnosed mental disorders not only helps to reduce relapse and improve the functional status for the patients directly served, but also reduces the emotional burden, dysphoria, and risks of mental disorder for family members and other caregivers deriving from the untreated mental disorder of the patient (Falloon, 1992; Harris and Bruey, 1988; Zarit, 1988; Falloon, Boyd, McGill, Razani, Moss, Gilderman, and Simpson, 1985). For example, treatment or maintenance interventions for a depressed mother might reduce the emotional risks for her child. Similarly, preventive interventions with a parent, sibling, or child might also reduce risks for other family members, but unless these potential positive “side effects” are anticipated, opportunities to measure them will be lost.

FINDINGS AND LEADS

• When precursor signs and symptoms of an initial primary disorder are identified, preventive interventions should focus not only on the prevention of the primary disorder but also on the other likely co-morbid disorders that could develop. Outcome measures should be used to assess intervention effects on the incidence of multiple disorders.
• With the development of reliable and sensitive means of detecting prodromal phases of a disorder, treatment intervention techniques can be used in indicated preventive interventions for individuals at high risk for developing a disorder.
• Preventive interventions should be tailored to take cognizance of individual differences in the degree to which participants are “at risk,” possess personal or environmental protective factors, and display readiness for intervention.
• Preventive interventions should aim to achieve durable and generalizable effects. Long-term strategies may include the use of “booster” sessions and the involvement of natural helpers from the individual's social environment.
• Preventive interventions with one individual can have salutary effects on other family members. Benefit-cost and cost-effectiveness analyses would do well to consider these other outcomes.
• Preventive intervention programs can have powerful effects. It is imperative, therefore, to be alert to inadvertent adverse outcomes.
• The usefulness of viewing treatment and prevention as part of a spectrum of interventions for mental disorders, instead of in opposition to each other, is apparent. Many principles that have emerged from research in one area can be borrowed, fully formed, for use in the other. Over the next decade, the cutting edge for progress will lie in the development of mutual respect, equal opportunity, and pragmatic collaboration among the scientists and advocates in the prevention and treatment fields.