LAUSR

Neuroimaging has shown promise for diagnosing depression, but these diagnostic systems have not performed as well when tested in large multi-site datasets. Recently, a paper published in Nature Medicine [1] has made major progress and provided good cues about how to understand mental disorders, not limited to depression. It is well known that mental disorders are associated with numerous personal and societal costs. According to the most recent global burden of disease study, mental disorders and substance-use disorders are a leading source of years lived with disability [2]. The World Health Organization estimates that there are [800,000 suicides each year globally, a great many of which are a consequence of a mental disorder. To date, diagnosis in psychiatry, including that of depression, remains restricted to subjective symptoms. Although there is increasing debate about whether to incorporate the concepts of modern biology, especially contemporary genetics and neuroscience, into the diagnosis of mental disorders, current clinical practice is still based on clinical observation, including the identification of symptoms that tend to cluster, the timing of appearance of symptoms, and their tendency to resolve, recur, or become chronic [3]. The regular research paradigm is shown in Fig. 1(A). After all, the differences in genomic variants and brain circuits/networks in studies of people with mental disorders require further validation. One of the critical tests is how well new molecular and neurobiological parameters predict the prognosis or response to treatment. Unfortunately, these parameters, at least for most of the genetic and neuroimaging studies, have fallen short of biomarker standards. Recent studies suggest one important aspect of the reasons for these challenges [4]. Specifically, the diagnostic heterogeneity in psychiatry might emerge as a major obstacle. According to current clinical thinking, a mental disorder is a psychological syndrome. In fact, a cluster of symptoms can result from different biological processes. For example, depression is a heterogeneous clinical syndrome that is diagnosed when a patient reports at least five of nine symptoms. This allows for several hundred unique combinations of changes in mood, appetite, sleep, energy, cognition, and motor activity. The association between clinical symptoms and the underlying biological substrates is inconsistent and variable at the individual level, even when the diagnosis is depression. On the other hand, there are multiple examples of distinct disorders with remarkably similar clinical presentations, but the pathologies and treatments are entirely different. For example, cough and fever can result from bacterial, viral, or fungal infections, or from autoimmunity, with very different treatments and outcomes. Therefore, it is increasingly necessary to deconstruct current psychiatric groups into biologically & Tianzi Jiang [email protected]