In his introduction to the first edition of his book entitled Medico-philosophical treatise on mental alienation, 1 Pinel, a visionary French psychiatrist, wrote, as early as 1801:

It is a bad choice to take mental alienation as the specific subject for research, as this opens one up to vague discussions about the seat of the understanding and the nature of its various faults, and nothing is more obscure or more impenetrable than this. But if one confines oneself within sensible limits, keeping to a study of the distinctive varieties of derangement as shown by outward signs, and only adopts the results of enlightened experience as principles of treatment, one then follows the path widely followed in all branches of natural history. Then, by proceeding with reserve in doubtful cases, there is much less fear of going astray.

Then, Esquirol, another French psychiatrist, published in 1838 the results of 40 years of studies and observations of the symptoms of insanity in a book entitled: Mental maladies: a treatise on insanity. 2 In the aftermath of real attempts to classify mental illnesses by French and German psychiatrists during the 19 th century, numerous efforts were made to classify mental disorders in other countries.

Yet, to date, none of these categorical classifications has been the subject of a unanimous consensus among psychiatrists. High rates of comorbidity, nonspecificity of both pharmacological and psychosocial treatments, and lack of support from the current nosology in biomarker research question the specificity of the disorders and their supposed underlying mechanisms. In this issue, Kapadia and colleagues (p 17) have pointed out the inherent Western bias in these classification systems. Methodological flaws have been widely discussed. In particular, the discrepancies between diagnostic systems 3 and the weak stability over the long-term course of symptom-based subtyping 4 were highlighted in schizophrenia as early as in the 1980s. More recently, for DSM-5 , field trials yielded low reliability, with nonexpert clinicians diagnosing patient groups based on checklists rather than standard diagnostic interviews. 5,6 Notable steps in the direction of dimensionality, at least for some diagnoses, were gradually included in the DSM-5 and more recently in the ICD-11 versions. Gaebel et al, in this issue (p 7), have conducted a brief overview of the changes from ICD-10 to ICD-11 .

Nonetheless, amidst this chaos, Research Domain Criteria (RDoC) have been considered as an alternative method of classification with a dimensional approach simultaneously defined by observable behavior (including quantitative measures of cognitive or affective behavior) as well as neurobiological measures. Cuthbert, in this issue, (p 81)will discuss the pros and cons of this classification.

Concurrently, the Hierarchical Taxonomy of Psychopathology (HiTOP) model, which is derived from factor-analytic studies of symptoms, diagnoses, and maladaptive trait data, describes a hierarchy of continuous dimensions accounting for broader spectra as well as symptom-level manifestations of psychopathology. Perkins et al (including the original author of HiTOP) will introduce this approach in this issue (p 51). However, in clinical practice, scores on higher-order psychopathology dimensions are difficult to interpret.

In fact, the connection between neurobiology and psychopathology is not sufficiently understood to establish a diagnostic system based on it. Yet, the genotype-first approach has led to the identification of specific genetic subtypes for autism spectrum disorders and promising pharmacological treatment targets (Morris Rosendhal and Crocq, in this issue, p 65).

Finally, Davidson and Gabos Grecu (in this issue, p 73) will discuss transdiagnostic approaches and advocate for a drug-centered approach with the example of the potential use of similar pharmacological interventions in the case of cognitive disorders associated with schizophrenia or other mental disorders.