Taking a look into the future: Do clinical and neurobiological trajectories tell us more than what we already know?

Our understanding of the clinical presentation and the neurobiology of mental illness largely rests on cross-sectional (or repeated cross sectional) assessments due to a paucity of systematic longitudinal phenomenological and biological studies in Psychiatry. As a result, our field lacks in-depth understanding of core phenomenological symptoms and functioning as well as biological changes over time. Typically, our understanding of mental illness is based on studies that investigate symptom reduction during the course of pharmacological or non-pharmacological treatments. While this approach has clinical usefulness, it is at the same time somewhat surprising since the long-term trajectory of the course of the illness may inform on treatment needs as well. In addition, longer term outcomes, such as functionality, may only become apparent to clinicians and patients over time. Of similar importance is the observation that the knowledge about the neurobiology of clinical mental illness as derived from neuroimaging or peripheral biomarkers such as genetics, serum markers, gene expression or from studies of certain pathophysiology (e.g. inflammation) are largely based on cross-sectional designs as if assuming that the neurobiology of mental illness is somewhat static over time, while more and more research indicates that it is highly dynamic depending on the disease stage and the effectiveness of interventions.

While there may be several possible explanations (e.g. funding restrictions, methodological challenges) as to why there is a relative paucity of longitudinal cohort studies, the need for studying both the long-term course of clinical phenomenology and related biology of mental illness has become evident. Studying the long-term patterns of clinical signs and features and the related neurobiology will increase the understanding of course-specific symptom patterns, functionality, relapse patterns and its underlying neurobiology. Such additional knowledge may be very important for diagnostic processes and for novel treatment target development. Specifically, if illness could be predicted early on and patients identified who are more likely to have a severe course of illness, then currently so-called last-resource interventions (e.g. electroconvulsive therapy [ECT], clozapine) could be potentially used more effectively in early detectable stages of detrimental disease progression. On the contrary, patients who are at a low risk of a severe course of illness following a first episode could be prevented from early inappropriate treatments. Studying jointly the biological and clinical course of mental illness may reveal novel trajectories of mental illness that can present as another source of valuable novel scientific information relevant for identifying new treatment targets.

This Special Issue collates high-quality reviews of the existing literature on clinical and neurobiological (with a focus on neuroimaging) trajectories of mental illness with the examples of schizophrenia, bipolar disorder and major depressive disorder across disease stages. The review by Bartholomeusz et al. (this issue) examining structural neuroimaging findings across early stages of psychosis suggests possible specific versus non-specific changes depending on the stage of the illness (e.g. first episode vs ultra-high-risk stage). Grey matter changes appear also to be the predominant structural change in chronic schizophrenia, especially in patients with poor long-term outcome (Dietsche et al., this issue). Interestingly, it appears that the findings on structural neuroimaging research in depression are currently not pointing towards stage-dependent findings, most likely due to a lack of a clear concept and resulting insufficiencies in study design (Dohm et al., this issue). The challenge of heterogeneity in depression becomes also evident when attempting to delineate symptom trajectories over time. However, the review by Schubert et al. (this issue) on studies in young people describes common mood trajectories in young that may help predict illness (or no illness) development into adulthood. Unsurprisingly, searching for clinical symptom–based trajectories in bipolar disorder appears to be even more challenging (Pfennig et al., this issue).

While in these reviews the lack of sufficient longitudinal studies is a common problem, the collection presented in this Special Issue points to important clinical and biological trajectories that can potentially enhance our understanding of the course of mental health and, if utilised properly, they uncover a wealth of scientific information that can be translated into clinical practice. It is hoped that this Special Issue stimulates discussion and prompts future research into the development of targeted interventions based on prospectively valid scientific information. Finally, I wish to thank the authors for contributing their time, effort and thoughts to this important issue.