Comorbidity from a Categorical to a Transdiagnostic-Dimensional Approach: New Perspectives for Researchers and Clinicians

The categorical, symptom-based psychiatric nosology postulating the formal identification of discrete mental disorders has been adopted by the main international classification systems and formally embraced for clinical aims and for aetiological, pathophysiological, and interventional research purposes (Reed et al., 2019). However, current nosological systems based on the existence of clearly diagnosable, well-defined, discrete categories of mental disorders are persistently challenged by the ubiquitous presence of comorbidity, the coexistence of two or more clinical conditions or disorders. Despite being framed as “pure” cases, individuals with mental disorders often show complex and comorbid conditions, requiring multiple and/or intensive therapeutic interventions. Psychiatric patients are diagnosed with multiple disorders throughout their lives (Plana-Ripoll et al., 2019), at higher rate than that overall rate of any diagnosis; this is considered the “force of comorbidity” in psychiatry (Plana-Ripoll et al., 2020). In addition, clinical symptoms and conditions crossing discrete disorders, such as psychomotor slowing and/or agitation, anhedonia, or delusions, do not support the notion of separate diagnostic classes; rather, they fit with the assumption of the existence of underlying associations among different diagnostic entities (Borsboom & Cramer, 2013). Therefore, to address the unresolved issues of comorbidity and diagnostic stability affecting the traditional nosological system, a transdiagnostic, dimensional framework for describing and explaining psychopathology has become increasingly popular. The dimensional approach moves away from listing symptoms into categories/diagnoses, trying to organize them into a hierarchy of factor-analytically determined psychopathological dimensions. Accordingly, several dimensional structural models of psychopathology have been proposed. The single-factor model postulates the existence of a single higher-order general factor, the p-factor that would represent the propensity towards all psychopathological symptoms, and that might account for a genetic, neuroanatomical, or environmental/traumatic substrate shared by categorically different mental disorders (Caspi & Moffitt, 2018). Caspi and Moffitt (2018) hypothesized that the p-factor runs in families is associated with neurodevelopment in early life, more severe impairment of global functioning later in life, and worse outcomes. Data from the Dunedin Longitudinal Study showed high rates of lifetime psychiatric comorbidity in the examined cohort whose participants, followed from birth to the age of 45 yrs., showed a higher risk of developing a comorbid psychiatric condition when they had already received a first, second, or third lifetime psychiatric diagnosis (Caspi et al., 2020). The bifactor model, including internalizing and externalizing disorders, has subsequently been integrated with a third factor, thought disorders; within this model, the three factors should account for the common variance of closely related symptoms commonly observed in clinical samples (Marshall, 2020).

The Research Domain Criteria (RDoC) initiative attempted at providing a response to the problem of the overwhelming comorbidity rates affecting traditional categorical systems (Cuthbert & Insel, 2010); it is based on brain circuitry activation patterns viewed as dimensional variables related to fundamental psychological adaptive systems and. The RDoC system proposes a matrix of six core domains of human functioning anchored in neural circuits serving biologically designed behaviours: positive and negative valence systems, cognitive systems, arousal and regulatory systems, sensorimotor systems.

Furthermore, clinical staging models, combining categorical and dimensional approaches, are based on the assumption of underlying pathophysiology that may result in persistent or progressive illness; such models have the aim of identifying early (from stage 0, asymptomatic state) and later (stage 4, severe and chronic mental health disorder) stages of mental disorders, for improving more personalized or stratified treatment selection and timing of interventions in psychiatry (McGorry et al., 2007; Hartmann et al., 2021). Clinical stage transition studies showed differential rates of progression from an “at-risk” albeit asymptomatic state, through an initial stage of mild, undifferentiated anxiety, somatic, and depressive symptoms, followed by a worsening of the existing symptoms, the acquisition of new ones, the progressive development of a certain syndromal specificity, personality changes and impaired functioning, until the occurrence of a first episode of a full-threshold syndrome, corresponding to stage 2; further progression includes the presence of persistent symptoms, recurrent relapses and stable functional impairment (McGorry et al., 2014). The transdiagnostic approach suggests that staging can be applied to clinical presentations both within and across traditional diagnostic categories, and capturing both homotypic and heterotypic progression. Moreover, progressive stages could differentiate “sub-threshold” from “threshold-level” disorders providing a more useful diagnostic tool in detecting latent mental illnesses (Shah et al., 2020). Therefore, this concept highlights the importance of the early onset of mental disorders and underlines the diagnostic transition from childhood to adulthood, as longitudinal studies in psychiatry have focused on childhood-adulthood continuity (Caron & Rutter, 1991).

Together, the single-factor (p-factor) model, the internalizing/externalizing approach, the RDoC six spectra construct, and the staging model provide a transnosological effort challenging the categorical classification of mental disorders, and aimed at understanding the full spectrum of mental health and illness through integrating existing neurobiological, behavioral, and psychological knowledge. At the same time, all the above cited models seek to overcome existing problems of comorbidity, symptom-based heterogeneity, and research limitations induced by current diagnostic categories.

From this perspective, the concept of comorbidity in psychiatry loses its absolute value, since the possibility of an "index" disease, to which other clinical pictures are progressively added, would be excluded. Therefore, the comorbidity becomes the expression of symptomatologic clusters of different psychopathological domains based on a lifetime transdiagnostic-dimensional model.

Conclusion

We propose that conceptualizing the question of comorbidity within a transdiagnostic-dimensional framework may be potentially useful to bring new knowledge in the diagnostic processes and to establish more effective preventive and treatment strategies.

The existence of a general psychopathological factor, together with the transdiagnostic staging model, could partly explain the observed variance among psychiatric symptoms and be predictive of different outcomes, including impaired functioning, an important measure of the severity/grade of psychiatric disorders strongly related to lifetime comorbidity rates.

Finally, there is a critical need for biology-grounded, longitudinal studies on developmental trajectories and psychopathological transitions from childhood to adulthood, aimed at increasing our current knowledge on the lifetime evolution of the clinical signs and symptoms of mental disorders, and at constructing valid diagnostic categories in psychiatry.