The events of Sept. 11, 2001, have increased both public and professional awareness of PTSD and the widespread need for effective prevention and treatment of the aftereffects of trauma. A considerable body of basic research on the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic/adrenal response to stress is clarifying the physiological mechanisms underlying PTSD. Preclinical studies have shown that memory formation is facilitated by the rise in norepinephrine(Drug information on norepinephrine) following stressful events (McGaugh, 1989), leading to the hypothesis that PTSD may result from excessive noradrenergic stimulation following trauma (Pitman, 1989). Consistent with this, recent findings indicate that the HPA axis is dysregulated in PTSD, resulting in low cortisol levels. Because cortisol normally buffers elevated adrenergic inputs in response to stress, a current prominent theory holds that the abnormal memory formation in PTSD results from low cortisol levels (perhaps resulting from prior traumatic events), which fail to contain the noradrenergic surge (Bremner et al., 1997; Heim et al., 2001; Yehuda et al., 1998). Taken together, these findings suggested that early treatment with behavioral treatments/psychotherapy or with ß-blockers may prevent the development of PTSD (Pitman et al., 2002).
Enhancing Treatment AdherenceToday's psychiatrists have a powerful array of medications to offer patients, but drug treatments are only as powerful as patient adherence permits. In a treatment environment dominated by outpatient care, finding ways to encourage adherence is clearly critical. The NIMH is now stimulating such research, and there are interesting behavioral models to guide these efforts (e.g., the Theory of Reasoned Action [Ajzen and Fishbein, 1980; Fishbein and Ajzen, 1975] and the Health Belief Model [Bebbington, 1995; Becker and Maiman, 1975]). These and other behavioral science theories have successfully informed behavior-change interventions in areas as diverse as AIDS prevention and advertising, and they offer promise for mental health applications. As a very recent case study illustrated (Heinssen 2002), adherence is affected by "the complex interplay of illness features, personal values, interpersonal supports, and environmental conditions," and successful interventions must address these issues in their behavioral complexity.
A review of empirical and clinical findings on medication compliance in schizophrenia (Fenton et al., 1997) suggested that a modified version of the Health Belief Model may be used to guide differential diagnosis of noncompliance and the development of individualized plans to improve adherence. As noted by Fenton et al. (1997), this model posits:
Health behavior is a product of an implicit and subjective assessment of the relative costs and benefits of compliance in relation to personal goals and the constraints of everyday life. Elements of this model include (1) individual goals and priorities; (2) an evaluation of the perceived adverse effects of illness and the personal risk of suffering these effects; (3) the individual's perception of the advocated health behavior's likely effectiveness and feasibility (the patient's subjective assessment of benefits weighed against the costs of treatment, including physical, psychological, and practical disadvantages and barriers to action); and (4) the availability of internal or external cues to action that trigger health behavior.The model suggested a multidimensional perspective that can aid in evaluating and managing medication noncompliance in patients with schizophrenia. It emphasized achieving patients' cooperation through a combined approach: a) understanding the attitudes and behaviors underlying their nonadherence; b) applying individualized behavior-change strategies; and c) using collaborative pharmacotherapy planning that emphasizes how the medications will aid in reaching patients' personal goals. Heinssen's very recent case study (2002) illustrated how a combination of collaborative treatment contracts, analysis of adherence behaviors, and techniques for boosting medication cues and reinforcers transformed a chronically noncompliant middle-aged patient with paranoid schizophrenia and numerous hospitalizations into an adherent outpatient who obtained work and remained adherent throughout a four-year follow-up. Such reports suggest the potential power of this line of study. However, much more research is needed to explore systematically these promising options.
Challenges for Translational ResearchThe potential payoff from translational research for psychiatric clinical care is enormous. But it requires intensive and sustained nurturing to overcome many existing barriers. First, translational research in mental health, an enterprise typically integrating diverse areas such as neuroscience, emotion, cognition and social processes, requires researchers with broad perspectives and skills who are willing to collaborate across disciplinary, departmental and even institutional boundaries. As academic departments are now structured, these collaborations are difficult and often not encouraged. Second, it requires researchers who understand the real needs of patients and those who work with them. But many basic behavioral researchers lack strong clinical training and skills, and many strong clinicians lack research training and acumen. In particular, the need for psychiatrist researchers is particularly acute, but a drought of new psychiatrists has contributed to a dwindling pool. Between 1992 and 2001, there were steep declines in the number of M.D. and M.D./Ph.D. programs in psychiatry (from 143 to 104), and in the number of M.D. and M.D./Ph.D. graduates of these programs (from 342 to 210) (Kupfer, 2002).
The NIMH is addressing both of these issues through new incentives intended to stimulate translational research. For example, a newly issued NIMH program announcement, "Building Translational Research in Behavioral Science," is specifically targeted to support translational mental health research linking behavioral science and clinical science. The NIMH is also sponsoring a number of initiatives designed to bring basic research knowledge to bear on specific aspects of mental disorders. Parallel with efforts to give new impetus to research on cognition in schizophrenia, NIMH is promoting behavioral and clinical research on emotion, emotional regulation and mood in depression. In addition, an upcoming multidisciplinary scientific meeting on borderline personality disorder will focus on behavioral components of the disorder as a basis for developing fresh approaches to diagnosis and treatment. New approaches to fostering treatment adherence in the mental health arena are receiving increased attention through a relatively new NIMH behavioral research program that also sponsors research exploring novel ways to reduce mental illness stigma. New efforts to stimulate clinical research training in psychiatry include a loan repayment program based on research participation, as well as a forthcoming mental health education grant program that offers multiple ways to increase the number of M.D. researchers (e.g., through establishing clinical research residency training programs).
It is still too soon to tell how successful these efforts will be, and how well-established translational research can become within the current structure of academic medicine. However, to date, the research community has responded enthusiastically to these new research directions. And both clinicians and mental health care advocates generally support this new emphasis on making federally sponsored mental health research more relevant to those in the front lines of clinical care.
