Longitudinal Development of Symptoms and Staging in Psychiatry and Clinical Psychology: A Tribute to Giovanni Fava

The introduction of diagnostic manuals, such as the first mention of mental disorders in the International Classification of Diseases (ICD-6) in 1948 [1] and the Diagnostic and Statistical Manual of Mental Disorders in 1952 [2], was a big step forward in the fields of psychiatry and clinical psychology. The operationalization of diagnostic criteria for mental disorders such as depression or schizophrenia, which lacked characteristic morphological features or laboratory biomarkers, greatly increased the reliability of clinicians’ diagnoses and their capacity to communicate with one another. However, those classifications were based on a cross-sectional view and informed clinicians, researchers, patients, and their relatives only little about the expected longitudinal course and development of a mental disorder. More specifically, cross-sectional diagnostics did not inform about trajectories of symptom severity over time, individual characteristics and combinations of symptoms, or comorbidities. Such elements are important when it comes to developing a sequential treatment plan and adjusting it as illness characteristics and symptom levels change over time. As early as 1967, Feinstein encouraged clinicians to develop their own “basic science” to use clinical phenomena and data to generate classification systems and to ultimately analyze the clinical process quantitatively [3]. Feinstein appears to have been a lone voice calling in the wilderness at that time though.

Diagnostic Staging in Mood Disorders

In 1991, Fava and Kellner [4] reviewed the literature and found that in affective disorders, a prodromal phase preceding the full syndrome can be observed. They suggested that affective disorders should be studied longitudinally, starting with prodromal symptoms, assessing the fully developed disorder, and also paying attention to residual states following treatment. Two years later, i.e., in 1993, Fava and Kellner [5] were the first to suggest that the concept of staging, which had already been widely used in various disciplines of medicine such as, e.g., oncology, rheumatology, or cardiology, should also be applied to psychiatric classification: “The neglect in psychiatry of staging parallels its reliance on cross-sectional descriptions instead of longitudinal study of prodromes, the fully developed disorder and residual states.” Thus, they proposed, on the basis of the literature, a staging model for unipolar depression, bipolar disorder, panic disorder, and schizophrenia. Staging can be understood within the overarching conceptual framework of clinimetrics, a term that has been introduced in medicine by Feinstein to organize and operationalize signs, symptoms, and other clinical phenomena in a systematic way, using indices, rating scales, and other measures [6, 7]. The concept of clinimetrics was later taken up and further developed for use in psychiatry and clinical psychology by Fava and his group [8-10]. Applying the principles of staging, Fava and Kellner [5] initially suggested classifing unipolar depression into five stages: prodromal phase (stage 1); major depressive episode (stage 2); residual phase (stage 3); dysthymia/recurrent major depression (stage 4); and chronic major depressive episode (stage 5). In 1999, Fava [11] published another, more refined and updated review of the literature, looking into subclinical prodromal as well as residual symptoms in the longitudinal course of mood disorders. It is known that subthreshold depression is a major risk factor for major depressive disorder [12], and that residual subthreshold depressive symptoms predict rapid relapse [13]. Based on this, Fava [14-16] repeatedly emphasized the importance of cognitive-behavioral therapy (CBT) in treating residual symptoms of depression following the discontinuation of antidepressant medication, according to the sequential model.

In 2013, Cosci and Fava [17] published an updated synthesis of the literature on staging in psychiatry and proposed refined staging models for schizophrenia, unipolar depression, bipolar disorder, panic disorder, substance use disorders, and eating disorders. With regard to substance use disorders, particularly alcohol use disorders, they discussed the pros and cons of Prochaska and DiClemente’s [18] transtheoretical model of change, which includes the stages of “pre-contemplation,” “contemplation,” “preparation/determination,” “action,” and “maintenance.” Cosci and Fava [17] pointed out that staging differs from the conventional diagnostic practice in the fields of psychiatry and clinical psychology in “that it not only defines the extent of progression of a disorder at a particular point in time but also where a person is currently located along the continuum of the course of illness.” Thus, in addition to objectively describing a patient’s symptoms, staging may also provide information on how the patient currently relates to his or her psychopathological symptoms.

Staging Treatment Resistance

Since its introduction 30 years ago by Fava and Kellner [5], the concept of staging in psychiatry has been picked up by other researchers and has gained momentum as a more refined form of diagnosis in mental disorders such as, for instance, schizophrenia [19, 20] or substance use disorders [21, 22]. Moreover, in addition to staging the longitudinal course and development of symptoms, several methods of staging treatment resistance in patients with unipolar depression have been put forward and tested [17, 23-30]. Traditionally, treatment resistance was conceived as an insufficient response to antidepressant medication. Again, Cosci and Fava were among the first to emphasize that in addition to focusing on antidepressant medication in staging treatment resistance, a potential lack of response to psychotherapy should be taken into account as well. In mood disorders, medication and psychotherapy need to be combined sequentially, depending on the stage patients are currently in [31-33]. In a seminal article Fava, Cosci, Guidi, and Raffanelli pointed out that “treatment outcome is the cumulative result of the interaction of several classes of variables with a selected treatment: living conditions (e.g., housing, nutrition, work environment, social support), patient characteristics (e.g., age, sex, genetics, general health conditions, personality, well-being), illness features and previous therapeutic experience, self-management, and treatment setting (e.g., physician’s attitude and attention, illness behavior)” [34]. Furthermore, they emphasized that all of these variables, as well as their interactive combinations, can turn out to be either therapeutic or counter-therapeutic. Therefore, it is important to identify counter-therapeutic ingredients when treatment has failed [34].

Finally, only very recently, Cosci and Fava [35] published an updated systematic review of studies concerned with staging models in adult patients with unipolar depression, including an adapted version of their 2013 [17] model of staging unipolar depression: prodromal phase with either nonspecific symptoms or subthreshold depressive symptoms (stage 1); first major depressive episode (stage 2); residual phase, including nonspecific symptoms, residual depressive symptoms, and dysthymia (stage 3); recurrent or double depression (stage 4); and chronic major depressive episode (stage 5). Interestingly, the great majority of studies found in Cosci and Fava’s [35] 2022 review described models of staging treatment resistance, while only a minority dealt with staging models of longitudinal development of symptoms. Also, an additional staging model of tolerance to, and side effects of, antidepressant drugs was proposed by Cosci and Chouinard [36].

Staging in Psychotraumatology?

In the field of psychotraumatology, sequential treatment models have been put forward with respect to trauma-related disorders such as posttraumatic stress disorder (PTSD) and, even more so, complex PTSD [37-39]. However, the concepts of staging the longitudinal development of symptoms as well as staging treatment response and nonresponse have been mentioned only sporadically [40], and have not (yet) been formalized. When developing staging models in psychotraumatology along the lines of Cosci and Fava’s staging of unipolar depression, a number of questions will need to be addressed:

1. According to the vulnerability-stress model [41-43], we can assume that a combination of resilience features and pre-traumatic risk factors [44, 45] will predispose an individual to respond to potentially traumatic events in a certain way. For instance, depending on the number and types of adverse childhood experiences, a person may have developed increased stress reactivity, subthreshold sleep disturbances, and a negative world view, even prior to experiencing their first potentially traumatic event (PTE). How can pre-traumatic symptoms and phenomena be operationalized to meet the criteria of a prodromal phase?

2. Following a PTE, or a series of PTEs, a person may develop acute stress disorder (ASD) [46], and later, i.e., after 1 month, possibly “subsyndromal PTSD,” “subthreshold PTSD,” or “partial PTSD” [47-53]. Such conditions, while not entirely fulfilling the diagnostic criteria for PTSD, are clinically relevant, impact negatively on the quality of life of those affected, and require adequate treatment [54]. Should such disturbances in the acute aftermath of trauma be categorized into a “stage” of their own? Should ASD be separated from subsyndromal PTSD?

3. Once a patient has developed full-blown PTSD, should a distinction be made between “acute PTSD” (one to 3 months post-trauma) and “chronic PTSD” (with symptoms persisting for more than 3 months post-trauma)? What about delayed-onset PTSD where the full diagnostic criteria of PTSD are not met until at least 6 months after the event [46]?

4. There is an extensive literature on the longitudinal development of PTSD symptomatology following a potentially traumatic event, suggesting four patterns or trajectories of posttraumatic symptomatology: resilient (low symptom levels throughout); chronic (high symptom levels early on and throughout); recovery (high symptom levels initially, declining over time); and delayed-onset trajectories (low symptom levels in the immediate aftermath, increasing later on) [55]. Should these trajectories be represented in a staging model?

5. Do we need separate staging systems for PTSD and complex PTSD, with staging of PTSD being similar to staging of depression, and staging of complex PTSD looking more like staging of schizophrenia?

6. The assessment and treatment of residual symptoms following evidence-based trauma-focused treatment has only rarely been mentioned in the literature so far [56, 57]. Is there a relationship between residual and prodromal symptomatology in PTSD and complex PTSD, i.e., a “rollback phenomenon,” as was described by Fava in mood disorders [11]?

In short, the field of psychotraumatology might benefit, in both research and clinical practice, from developing and testing systems of staging in diagnostics (prodromes, the partially and fully developed disorder, and residual states) and therapeutics (treatment response/nonresponse, treatment sequencing).

Fava’s Contributions to the Field

In 2022, Fava [58] has stepped down after 30 years as editor-in-chief of Psychotherapy and Psychosomatics. Over the decades, in his triple role as a clinician, researcher, and editor of a scientific journal, he took up a number of highly clinically relevant concepts that had been suggested by other pioneers in the field early on but had been ignored or forgotten for unknown reasons. Fava not only spotlighted these concepts, drawing clinicians’ and researchers’ attention to their importance, but updated and developed them further. His proposal to introduce a system of staging in psychiatry and clinical psychology is but one out of many examples. It will be interesting to see if and how these concepts will be picked up and developed further in the future.

Twenty years ago, I was fortunate to be invited by Giovanni to join the editorial board of Psychotherapy and Psychosomatics. These were the years of fostering innovations and pluralism (2002–2011), and the decade of developing a “counter-culture” (2012–2021), swimming against the mighty stream of evidence-based medicine, challenging its overly strong focus on drug treatments, which all too often neglected the psychological, behavioral, and social aspects of the field [58]. Maybe one of Giovanni’s most outstanding characteristics was, and still is until today, his capacity to recognize innovative and relevant theoretical concepts and clinical approaches. Once he was “hooked,” Giovanni showed great perseverance, or tenacity, you may even call it stubbornness: he kept deepening his knowledge about the issue, updating the literature repeatedly, conducting his own studies, and refining what he felt was important, thus ultimately advancing our field. I am deeply grateful to have become part of this group of critical thinkers, clinicians, and researchers. This is an ongoing learning experience. Thank you, Giovanni, grazie mille, ragazzo, for all we achieved jointly under your guidance and farsighted leadership! An era comes to an end, and a new era begins. A heartfelt welcome to our new editors-in-chief, Fiammetta Cosci and Jenny Guidi!

Acknowledgments

The author thanks Prof. Monique Pfaltz, Mid Sweden Uni­versity, for critically reviewing and commenting on the draft manuscript.

Conflict of Interest Statement

The author has no conflicts of interest to declare.

Funding Sources

No funding was received.

Author Contributions

Ulrich Schnyder is the sole author of this editorial.

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