Thomas Hélie

Thomas Hézard

Rémi Mignot

Denis Matignon

One-dimensional acoustic

published or not. The documents may come

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To link to this article: DOI: 10.3813/AAA.918675 URL: http://dx.doi.org/10.3813/AAA.918675 Hélie, Thomas and Hézard, Thomas and Mignot, Rémi and Matignon, Denis One-dimensional acoustic models of horns and comparison with measurements. (2013) Acta Acustica united with Acustica, vol. 99 (n° 6). pp.

960-974. ISSN 1610960-974. ISSN -1928


Jean-Arthur Micoulaud-Franchi

Clélia Quiles

Jean-Marie Batail

Christophe Lancon

Marc Masson

Guillaume Dumas

Michel Cermolacce

Dr Micoulaud Franchi
email: jarthur.micoulaud@gmail.com

Making psychiatric semiology great again: A semiologic, not nosologic challenge

Keywords: Nosology, Semiology, Research Diagnostic Criteria, Diagnostic Statistic Manual, Research 30 Domain Criteria, Latent variable model, Causal network model 31 32

come

Introduction 1

A passionate long-lasting debate in medicine is knowing "what kinds of things are psychiatric 2 disorders?" [1]. This question has engendered complex historical, sociological, 3 epistemological and philosophical concepts with large differences between models and 4 schools of psychiatric thought [1-7]. Such thinking is essential for the development of 5 psychiatric medicine but commonly gives the implicit impression that psychiatric disorders 6 are something different or quite different from non-psychiatric disorders. This purported 7 distinction is particularly evident in the traditional dichotomy between mental and physical 8 disorders. However, psychiatry, like the entire field of medicine, should go beyond this 9 dichotomy [8,[START_REF] Micoulaud-Franchi | Keep calm and carry on: Mental disorder 20 is not more "organic" than any other medical condition[END_REF]. 10

The supposed difference between psychiatric and non-psychiatric disorders also stems from 11 the fact that the individuation of psychiatric disorders seems more complex than for non-12 psychiatric disorders. This individuation process can be related to nosologic and semiologic 13 considerations. Nosologic considerations concern the scheme of classification imposed on 14 clinical and scientific medical information to delineate disorders, thereby increasing its 15 comprehensibility and utility. Semiologic considerations relate to the clinical evaluation and 16 organization of signs and symptoms in order to undertake clinical reasoning leading to the 17 identification of a psychiatric disorder [START_REF] Berrios | What is phenomenology? A review[END_REF][START_REF] Beumont | Phenomenology and the history of psychiatry[END_REF]. 1 This article analyzes whether psychiatric 18 disorders can truly be considered as something different when considered from a clinical 19 nosologic or semiologic point of view. 20 21 22 1 The term semiology is used in this article as a synonym of the term symptomatology, presentation, manifestation or phenomenology of the disorder. In this article, we use the term semiology, in line with the French medical tradition from the early 19th century. In the English tradition, the term semiology has referred since the middle of the 17th century to the science of language. Thus, the English medical tradition is to use "symptomatology", "clinical presentation, manifestation or phenomenology". However, it should also be noted that the term phenomenology used in this sense can be considered as a misuse in clinical psychiatry. Indeed, current usage as a set of signs and symptoms of a patient with a psychiatric disorder is different from the original meaning, which concerned comprehending a patient's subjective self-experience (in line with the continental understanding of phenomenological philosophy).

Are psychiatric disorders different when considered from a nosologic point of view? 1

The long-standing discussion accompanying the construction of contemporary classifications 2 of psychiatric disorders, in particular the Diagnostic and Statistical Manual of Mental 3 Disorders (DSM) [12], demonstrates that unlike in other medical disciplines, it is not easy to 4 classify disorders in psychiatry, thereby reinforcing the impression that psychiatric disorders 5 are something different. Psychiatric disorders might be entities different from non-psychiatric 6 disorders because the ways of establishing the boundaries between the normal and the 7 pathologic, and of classifying the signs and symptoms in different categories of disorder, are 8 not the same. The first part of the article thus analyzes whether the ways of constructing 9 classifications of psychiatric disorders are different than for non-psychiatric disorders. 10 11

Evolution of nosologic issues from the RDC to the RDoC 12

The ways of establishing the boundaries between the normal and the pathologic and the 13 classification of the different disorders have to be evaluated for their reliability and their 14 validity [12]. 15 -Reliability (also called "precision") refers to reducing disagreement among clinicians 16 about whether some phenomena are to be considered as pathologic or not and about 17 the psychiatric diagnosis. 18 -Validity (also called "accuracy") is "the degree to which diagnostic criteria reflect the 19 comprehensive manifestation of an underlying psychopathological disorder" [START_REF]Diagnostic and Statistical Manual of Mental 29 Disorder[END_REF]. [START_REF] Cuthbert | Toward the future of psychiatric diagnosis: the seven pillars 12 of RDoC[END_REF] The early contemporary classification, and in particular the Research Diagnostic Criteria 21 (RDC), sought to establish diagnostic criteria in order to enhance reliability in psychiatry 22 [START_REF] Spitzer | Research diagnostic criteria: rationale and 32 reliability[END_REF]. The RDC project was developed at the Washington University School of Medicine in St 23 Louis. The criteria of the St Louis group are also known as the "Feighner criteria", because 24

Feighner was the author of the seminal article summarizing criteria for 15 psychiatric 25 conditions [15]. The development of the RDC project led to the major revisions in DSM- III 26 [16]. It stated: "Since in DSM-I, DSM-II, and ICD-9 explicit criteria are not provided, the 27 clinician is largely on his or her own in defining the content and boundaries of the diagnostic 28 categories. In contrast, DSM-III provides specific diagnostic criteria as guides for making 29 each diagnosis since such criteria enhance interjudge diagnostic reliability" [17]. The 30 expectation was that each psychiatric disorder would be validated by its separation from other 31 disorders. However, the validity of the RDC and the subsequent DSM has been largely 32 criticized [18,19]. Thus, the Research Domain Criteria (RDoC) was the most important 33 contemporary classification to focus on validity. The aim was to create "new ways of classifying mental disorders based on dimensions of observable behavioral and 1 neurobiological measures" [START_REF] Cuthbert | Toward the future of psychiatric diagnosis: the seven pillars 12 of RDoC[END_REF]. The RDoC, which interestingly used an acronym very close 2 to the RDC project, was developed at the National Institute of Mental Health (NIMH), an 3 agency of the United States Department of Health and Human Services and the largest 4 research organization in the world specializing in mental illness. Thomas Insel, who led the 5 NIMH from 2002 until 2015, largely supported the RDoC project. By proposing a 6 dimensional approach based on brain function, it was thought that the future nosology of 7 psychiatric disorders would be more valid, i.e. closer to underlying physiopathological 8 mechanisms [18]. 9 10

Boundaries between the normal and the pathologic 11

In this section we analyze ways of establishing the boundaries between the normal and the 12 pathologic. The construction of contemporary classifications of psychiatric disorders requires 13 operational criteria to reduce disagreement among clinicians regarding whether a 14 phenomenon are pathologic or not (reliability) and to ensure that it is determined by an 15 underlying impaired physiological mechanism (validity). In this paper, we term "inclusion 16 criteria" the defining criteria used to address reliability and to identify signs and symptoms 17 that may be considered as "clinically significant"; and "exclusion criteria" the defining 18 criteria used to address validity and to identify signs and symptoms that are not to be 19 considered as pathologic. How specific criteria are designed to position the boundaries 20 between two disorders will be analyzed in the following section. 21

In the RDC, these additional criteria were not explicitly defined. However, Feighner et al. 22 stated that "the first step is to describe the clinical picture of the disorder. This may be a 23 single striking clinical feature or a combination of clinical features thought to be associated 24 with one another. Race, sex, age at onset, precipitating factors, and other items may be used 25 to define the clinical picture more precisely. The clinical picture thus does not include only 26

symptoms" [15]. Thus, they clearly indicated that the boundary between the normal and the 27 pathologic should to be determined by features other than only the signs and symptoms. In 28 1978, Spitzer and Endicott proposed a detailed list of operational criteria [21] that are shown 29 in Table 1. They are the most detailed operational criteria known for fixing the boundaries 30 between the normal and the pathologic. These criteria were the bases of the reduced criteria 31 published in the subsequent DSM. The criteria of the different editions of the DSM are shown 32 in Table 2. 33

The "inclusion criteria" to identify signs and symptoms as "clinically significant" are criteria 1 based on the consequence of the disorder: disability. The DSM-5 specifically discussed the 2 consequence of such a position in the field of medical nosology (p 21.) [START_REF]Diagnostic and Statistical Manual of Mental 29 Disorder[END_REF]. Indeed, the 3 classifications developed by the World Health Organization (WHO) have clearly 4 differentiated the concepts of disorder (with the International Classification of Diseases -5 ICD) and disability (with the International Classification of Functioning, Disability and 6

Health -ICF). Disability refers to the consequence of the disorder and not to its definition. In 7 psychiatric classification, disability is part of the boundary of the disorder. This is an 8 important difference between psychiatric and non-psychiatric disorders, and it is widely held 9

that the boundary of a disorder in medicine is based on a biomarker that reflects its 10 pathophysiological mechanism. However, this is to forget, as Claude Bernard pointed out, 11 that boundaries between the normal and the pathologic cannot be defined primarily on the 12 basis of physiology [START_REF] Micoulaud-Franchi | Keep calm and carry on: Mental disorder 20 is not more "organic" than any other medical condition[END_REF]. A boundary is to be set first on clinical and epidemiological factors 13 pertaining to disability or future disability if no therapy is begun [START_REF] Weinberger | RDoCs redux[END_REF]. Biomarkers are the 14 second step and are taken to reflect a disease process explaining the disability or the evolution 15 toward disability. The Spitzer and Endicott 1978 criteria already highlighted this point by 16 using "a condition in the fully developed or extreme form" because "in medicine many 17 conditions are recognizable in an early form, frequently with the aid of laboratory tests, 18 before they have any undesirable consequences" [21]. 19

Interestingly, these two steps are considered in reverse order by many physicians, who 20 consider that the boundaries between the normal and the pathologic are defined primarily 21 from the point of view of the pathophysiology and biomarker. They do not consider disability 22 as being entirely part of the definition of the disorder. The difference between a psychiatric 23 and non-psychiatric disorder is that the consideration of disability remains directly and 24 explicitly within the realm of psychiatry, whereas this notion may be forgotten because 25 biomarkers exist for non-psychiatric disorders. "Unfortunately, in psychiatry we rarely have 26 laboratory procedures which permit us to diagnose mental disorders before they have clinical 27

manifestations" [21]. Fundamentally, however, the process of differentiating the normal and 28 the pathologic remains the same for psychiatric and non-psychiatric disorders. 29 Nevertheless, in line with Claude Bernard who stressed that the physiological mechanisms 30 underlying a pathology should be described in order for medicine to be considered as 31 scientific, a challenge in psychiatry is to identify biomarkers in order to better evaluate 32 disability and future disability, a process also called clinical staging. "To test the concept, 33 there is a clear need to develop illness markers that (…) have the capacity to track the extent of the disease process" [START_REF] Mcgorry | Biomarkers and clinical staging in 18 psychiatry[END_REF]. Biomarkers will also be useful for probing the efficiency of 1 treatments [24] and identifying resilient subjects who could have a biomarker related to a 2 disorder but which does not appear to be affected by the disorder [25]. 3 As biomarkers have not been developed in psychiatry, exclusion criteria have been 4

determined to identify signs and symptoms that are not considered to be due to an underlying 5 physiological deterioration, and thus which are not considered to be pathologic. Table 2. 6 Indeed, "the locus of the disturbance in a medical disorder is at least partly within the 7 organism" [21]. "This does not mean that factors outside of the organism are of no 8 importance" but that "largely within the organism with regard to either initiating or 9 maintaining the condition" [21]. The DSM criteria seem to be rather imprecise and not very 10 operational, because they are based on general sociological considerations about the 11 relationship between the individual and society. On the other hand, the Spitzer and Endicott 12 criteria determined three criteria to establish whether signs and symptoms can be attributed to 13 a supposed mechanism within the organism (criteria B1, B2 and C, in Table 1). [START_REF] Spitzer | Research diagnostic criteria: rationale and 32 reliability[END_REF] The use of such criteria is an important difference between psychiatric and non-psychiatric 15 disorders. In fact, the absence of a biomarker should not mask the fact that the identification 16 of a physiological impairment underlying a disorder is an ideal in medicine that is not 17 absolutely necessary. This ideal was called "the hard medical model" by Kendler, who stated 18 that "the hard medical model, while historically critical in the evolution of disease 19 conceptualization, is in fact an idealization which fully applies to only a small group of 20 Mendelian, nutritional, infectious and parasitic disorders" [START_REF] Kendler | Levels of explanation in psychiatric and substance use disorders: 24 implications for the development of an etiologically based nosology[END_REF]. Moreover, following on from 21

Spitzer and Endicott who stressed that "the nature of what is wrong may be known or 22 unknown, and may or may not be conceptualized in somatic or physiological terms", the 23 MEsH defined disease as "a definite pathologic process with a characteristic set of signs and 24 symptoms" and added that "its etiology, pathology, and prognosis may be known or 25 unknown". The very important point here is that the pathophysiological mechanism may be 26 unknown so it is important to conduct scientific research to identify these mechanisms, not 27 necessarily to have them for conducting clinical medicine [START_REF] Franchi | From clinic to the "foul and exciting 27 field of life": A psychiatric point of view on clinical physiology[END_REF]. Indeed, medicine is also based 28 on clinical science [28,[START_REF] Fava | Road to nowhere[END_REF]. Nevertheless, the wide field of scientific psychiatric research 29 concerning the investigation of what is wrong inside the brain, and more generally the 30 organism, of patients with a psychiatric disorder places psychiatry entirely and rightfully 31 within the realm of scientific medicine. 32 33 34 1

Classification of different disorders: boundaries between disorders 2

In this section we analyze how different disorders are classified. The construction of 3 contemporary classifications of psychiatric disorders has led to operational criteria to reduce 4 disagreement among clinicians about psychiatric diagnosis (reliability) and to ensure that the 5 phenomenon is determined by an underlying impaired physiological mechanism (validity). 6

Reliability has been addressed by defining an appropriate list of criteria to identify signs and 7 symptoms that are easily recognized by a clinician and are clustered together. Validity has 8 been addressed by defining criteria that ensure the possibility of different underlying impaired 9 physiological mechanisms for different disorders. These validity criteria were primarily 10 identified by Robin and Gruze in 1970 [30], then added to by Spitzer and Endicott in 1978 11 [21], by Kendler in 1990 [31] and by the DSM-5 in 2013 [START_REF]Diagnostic and Statistical Manual of Mental 29 Disorder[END_REF]. Table 3. 12 In psychiatric classification, as biomarkers do not exist, a list of validating criteria has been 13

established. This is an important difference between psychiatric and non-psychiatric disorder 14 classifications. Indeed, it is widely considered that the classifications of disorders in medicine 15 are based on biomarkers that reflect pathophysiological mechanisms. However, classifying 16 disorders is a very complex process involving epidemiological, semiologic, prognostic, 17 therapeutic, economic, and genetic factors [START_REF] Franchi | From clinic to the "foul and exciting 27 field of life": A psychiatric point of view on clinical physiology[END_REF]32,33]. interest differ. The more they differ, the more likely it is that the condition represents 21 syndrome or disease and not mere symptoms" [21]. This classification of disorders is in line 22 with the coherence theory of truth that postulates that "the best diagnoses we have are the 23 ones that are heavily intertwined with other things we know about; that is, are 'well 24 validated'. For individuals assigned to that class, we follow the strings and see all the other 25 things that we learn about them" [34]. This paradigm involves the "examination of the entire 26 medical classification system reveals that no single principle accounts for the allocation of 27 disorders to various subgroupings" [21]. Of course, all these relations of validation should be 28 integrated in a unified pathophysiological process in which a biomarker is solely the 29 reflection, but not the primarily cause, of the classification. Moreover, in many cases, such 30 biomarkers are in fact a concept resulting from many causes and mechanisms, i.e. "a 31 therapeutic target rather than an etiological node; that is, not something to find that would 32 explain everything, but something to act upon that would dissolve everything" [START_REF] Belzung | Latent variables and the 11 network perspective[END_REF]. 33

The difference between psychiatric and non-psychiatric disorders is that the validators are by 1 and large explicit in psychiatric classifications and we do not have any reliable simple 2 validator for psychiatric diagnoses, whereas they may be forgotten or considered as 3 biomarkers in non-psychiatric disorders. Fundamentally, however, the process of classifying 4 any type of disorder is the same and has to take into account the multifactorial and 5 etiologically complex nature of the explanatory models in medicine [33]. Biological 6 reductionism is less fruitful than explanatory pluralism in most psychiatric and non-7 psychiatric disorders [32]. One may consider that the DSM-5 implicitly takes explanatory 8 pluralism into account by stating that… "the boundaries between many disorder "categories" 9 are more fluid over the life course than DSM-IV recognized, and many symptoms assigned to 10 a single disorder may occur, at varying levels of severity, in many other disorders. [START_REF] Beumont | Phenomenology and the history of psychiatry[END_REF] findings mean that DSM, like other medical disease classifications, should accommodate 12 ways to introduce dimensional approaches to mental disorders, including dimensions that cut 13 across current categories" [START_REF]Diagnostic and Statistical Manual of Mental 29 Disorder[END_REF]. The question raised by the DSM-5, in line with the RDoC 14 project is whether the actual classification based on categories is the best way to describe the 15 multifactorial and etiologically complex pathophysiological mechanisms implicated in 16 psychiatric disorders. The DSM-5 position underlines the "real paradigm shift" that was 17 proposed by the RDoC project. The RDoC paradigm shifts the heuristic from coherence at the 18 theoretical level to support for experimental observation at the physiological level [36], in line 19 with the traditional translational research approach [START_REF]RDoC is necessary, but very oversold[END_REF]. Indeed, " the RDoC does not take as 20 starting point the traditional view of disorders as symptoms complexes based largely on 21 clinical descriptions" for which validators are required [START_REF] Cuthbert | Toward the future of psychiatric diagnosis: the seven pillars 12 of RDoC[END_REF]. In contrast, the RDoC considered 22 validity from the point of view of physiological and not clinical dysfunction. Thus, it did not 23 categorize clinical signs and symptoms but proposed a dimensional framework in which the 24 different functions of the brain are considered, and supposed that any of these dimensions can 25 be impaired. However, this dimensional approach raises an important question regarding the 26 link between the physiological and medical approach to a disorder, an issue related to the 27 notion of continuity. Indeed, where do we situate the threshold for considering a brain 28 function as pathologic when we also consider each dimension as being continuous? As 29 discussed previously and summarized by Stein in a comment on the RDoC: "we need to 30 accept that diagnosis system cannot "carve nature at her joints". Rather facts and value need 31 to be continually re-assessed, to try optimize classification" [33]. 32

This section has therefore analyzed whether psychiatric disorders differ from non-psychiatric 33 disorders at the nosologic level. We have shown that the lack of biomarkers in psychiatry has 34 led the psychiatric community to clearly and thoughtfully explore the inherent process of 1 establishing the boundaries between the normal and the pathologic and between the different 2 disorders in medicine. This process is as complex in psychiatry as in any other medical field. 3

This does not mean, however, that epistemology of psychiatry ought to be general as part of 4 epistemology in medicine, without the need for regional epistemology [START_REF] Markova | Epistemology of psychiatry[END_REF][START_REF] Markova | Epistemology of mental symptoms[END_REF]. The historical 5

and sociological specificity of psychiatry should not be underestimated. Nevertheless, we 6 believe that the need for a regional epistemology is more semiologic than nosologic. Thus, the 7 question to be asked now is whether psychiatric disorders differ from non-psychiatric 8 disorders at the semiologic level, i.e. with regard to their clinical manifestations. 9 10 11

Are psychiatric disorders different when considered from a semiologic point of view? 1

The discussions concerning the drafting of the DSM-III surprisingly involved little discussion 2 on semiologic issues in psychiatry. Nevertheless, as stated in the DSM-III, the separation 3 between "physical" (non-psychiatric) and "mental" (psychiatric) disorders is not based on 4 pathophysiological mechanisms (organic versus psychologic) but "on the tradition of 5 separating those disorders whose manifestations are primarily behavioral or psychological 6 (i.e., mental disorders) from those whose manifestations are not." Identifying psychiatric 7 manifestations was thus a central issue for the authors of the DSM-III in identifying what kind 8 of entity psychiatric disorders really are. Mental manifestations (symptoms and signs) are 9 considered as the "unit of analysis" that has to be captured in order to make a psychiatric 10 diagnosis [START_REF] Markova | Epistemology of mental symptoms[END_REF]. However, thinking about what a sign or symptom in psychiatry is has not kept 11 in step with reflection on the nosologic aspects of psychiatry [START_REF] Markova | Epistemology of mental symptoms[END_REF]39]. Thus, the second part 12 of this article analyzes whether certain manifestations of psychiatric disorders make them 13 stand apart from non-psychiatric disorders. 14 15

Evolution of semiologic thinking from the RDC to the RDoC 16

Symptoms refer to the subject's that they experience and notice, while signs refer to 17 manifestations that they may experience but which are also externally observable by others 18 [START_REF] Markova | Epistemology of mental symptoms[END_REF]. Whatever the type of psychiatric interview [39], the first essential step when identifying 19 psychiatric symptoms and signs is to conduct a clinical reasoning process about the 20 psychiatric disorder and to take the necessary clinical decisions [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. In line with this medical 21 position, DSM-III discussions focused on operationalizing the criteria in order to enhance the 22 reliability of assessing psychiatric disorders and thus of the diagnosis [START_REF] Spitzer | Psychiatric diagnosis: are clinicians still necessary?[END_REF]. The aim was not 23 to reduce clinical psychiatry to a list of criteria but to consider that: "if the medical 24

practitioner confines himself to diagnosis and to treatment based specifically on [diagnostic 25 tools], the help he can give (…) is in general severely restricted. (…) However, if the doctor 26 cannot make a useful diagnosis, he severely restricts his competence in a different way and 27

becomes immeasurably less useful to his patient" [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. The RDC was developed with this in 28 mind, the first step in scientific medicine being the clinical examination of patients. In the 29 non-psychiatric fields of medicine, the pride of place accorded to non-clinical results obtained 30 from laboratory tests, imaging, etc. can lead the clinician to ignore the importance of the 31 clinical examination in the development of medicine. However, "to neglect this stage would 32 be to misunderstand the nature of scientific enquiry" [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. "Our present sophisticated medical 33 knowledge has accrued because of centuries of observation and description, in which the 34 describers and classifiers have played as dynamic and creative part as those concerned with 1 process" [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. "No disease theory can be elaborated before the clinical syndrome has been 2 recognized and labeled", "the value of those first step should not be underestimated" and 3 "the second step can then be taken, which is to test the validity of various explanatory 4 theories". Figure 2. The RDC project and the resulting DSM criteria were developed in order 5 to enhance the value of the first step. Unfortunately, the list of criteria in the DSM became the 6 reference for semiologic terms in psychiatry, thereby reducing and simplifying the corpus of 7 signs and symptoms [START_REF] Kendler | Explanatory models for psychiatric illness[END_REF][START_REF] Parnas | The Breivik case and "conditio psychiatrica[END_REF]. Moreover, the organization of the corpus of signs and 8 symptoms was based on nosologic categories and not on supposed underlying 9 pathophysiological mechanisms. "In many cases, there are also observable bodily 10

abnormalities [physiological abnormalities]; most evident in the case of anxiety states (…), 11

but nowhere sufficient in themselves for a reliable classification" [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. As a result, it was 12 posited that among the many possible techniques for classifying psychiatric symptoms and 13 signs, the easiest to implement was the clinical diagnosis [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. 14

This subordination of semiology to nosology may be of value given the historical aspects of 15 signs and symptoms in psychiatry. Wakefield has called this the "conceptual validity" of 16 signs and symptoms. Conceptual validity has allowed the psychiatric community to 17 "delineate the domain of psychological condition that fall under the concept of disorder" 18

[44]. Indeed, present-day semiology bears close links to nosographic thinking, which itself 19 can be traced back to historical and "psychosocial" views of the individual. In other words: 20 "Since doctors have been making examinations of 'mental state' from time immemorial, they 21 do not have to start afresh each time but can utilize the experience of their predecessors" 22 [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. Thus, rather than semiologic analysis being used as the first step when testing disease 23 theory, it has come to occupy a subservient role to the categorization of psychiatric disorders. 24

Figure 2. This role of subservience also means that the relationship between semiology and 25 nosography tends to be inversed. In medicine, it is traditionally postulated that signs and 26 symptoms influence which disorder category is to be employed, but not that the disorder 27 category will influence the types of symptoms and signs that are sought in a patient. In 28 psychiatry, symptoms and signs tend to be influenced by the disorder category [START_REF] Fellowes | Symptom modelling can be influenced by psychiatric categories: choices 30 for research domain criteria (RDoC)[END_REF]. This also 29 means that symptoms and signs in psychiatry tend to contain de facto the boundaries between 30 the normal and the pathologic, and the classification of disorder. In some way, the two-step 31 process in which medicine has developed, i.e. clinical description then neurophysiological 32 theory of disorder, is biased on in that clinical descriptions are largely influenced by concepts 33 of disorder category [46]. As Berrios stated "the DSM-III two-stage model, according to 34 which symptom and disease recognition are independent cognitive events, did not work.

(…) 1

The disease hypothesis absolutely controls the way mental symptoms are captured and 2

recognized" [47]. Figure 2. 3

One can even consider that the RDoC project turned the initial project of establishing a 4 classification of psychiatric symptoms upside down [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. It posited that the first step is not to 5 establish clinical descriptions but to gain neurophysiological knowledge about cognitive and 6 brain mechanisms [18]. By doing so, it is propounds the opposite of what Wing, Cooper and 7

Sartorius say [START_REF] Wing | The measurement and classification of psychiatric 20 symptoms[END_REF]. (the individual mental disorders or, as in the DSM-5, the larger grouping of adjacent 14 disorders) will be fully validated when some specific neurobiological factors are "discovered" 15 that confirm that the phenomenal description really corresponds to a neurobiological disease. 16 (…) The RDoC project, which is considered the most promising etiopathogenic approach at 17 play in current debates, shares with the other etiopathogenic approaches a revolutionary 18 shift. While in the neo-Kraepelinian approach validation research is expected to proceed 19 from phenomenally defined disorders back to the discovery of their etiology, in the 20 etiopathogenic approaches the direction is expected to be from "subpersonal" dysfunctions 21 (of genes, brain processes, or cognitive mechanisms) ahead to the resulting phenomenal 22 picture. (…) They all see mental pathologies as biomedical entities resulting form a 23 dysfunction of physiological processes; hence, the difference is just in the direction of the 24 discovery enterprise, i.e., from the syndrome to the underlying pathophysiology in the DSMs, 25 from pathophysiology to the resulting syndromes in the etiopathogenic approaches." [12]. 26

The need for a rethink was also highlighted by Maj's editorial in World Psychiatry [48] in 27 relation with the article by Cuthbert [18]. Maj stated that "the gap between the proposed 28 dimensions and the signs and symptoms that, as Cuthbert acknowledges, are "the actual 29 clinical phenomena that bring patients to the clinic" is sensible in several areas. If the 30 problem with the DSM categories may be that they are too distant from the level of 31 neuroscience, the problem with at least some of the RDoC constructs may be that they are 32 somewhat distant from the level of clinical phenomena" [48]. In fact, Cuthbert in his article 33 did not avoid this issue. He stressed that "Another issue concerns the relationship of the various RDoC measures to presenting signs and symptoms, since of course the latter are the 1 actual clinical phenomena that bring patients to the clinic. Establishing mechanistic 2 relationships by which disruptions in the functioning of one or more constructs (as assessed 3 by various Units of Analysis) result in specified symptoms or impairments is considered as a 4 central task for the RDoC project, and a major component of the grant funding program. 5

Notwithstanding the translational research approach, the RDoC project is very much directed 6 toward an understanding of the impairments that patients experience in their lives, and this 7 desideratum was emphasized by the RDoC workgroup in nominating constructs" [18]. Thus, 8

the RDoC project may be seen more as a semiologic project than a nosologic one. 9

The paradigm shift between the RDC and the RDoC is thus a reversal of the link between 10 clinical descriptions of and scientific knowledge about disorders with a view to driving 11 scientific psychiatric medicine forward. Nevertheless, the problem remains as to what signs 12 and symptoms are in psychiatry, and whether semiologic in psychiatry may be considered as 13 an important difference between psychiatric and non-psychiatric disorders. In fact, the 14 theoretical foundations of how semiology was to be incorporated in the DSM-III received 15 very little attention at the time of its conceptualization, and tended to be discussed only 16 subsequently [START_REF] Kendler | Explanatory models for psychiatric illness[END_REF]49]. 17

The following section thus describes how signs and symptoms are to be considered in 18 psychiatry. It has been stressed that: "What the patient manifests is not an isolated series of 19 independent referring symptoms/signs but rather certain wholes of interpenetrating 20

experiences, feelings, expressions, beliefs, and actions, all permeated by biographical detail. 21

These aspects and these wholes are not constituted by a reference to underlying substrate (…) 22 but by their meaning [50]". Thus, an important question concerning mental manifestations is 23 their coherence. Coherence can be analyzed from an external point of view, which is called 24 explanation or "erklären" by Jaspers. That is: what is the explanation and the mechanism that 25 link together a set of clinical manifestations? The response is here driven by a putative causal 26 substrate. Coherence can also be analyzed from an internal point of view, which is called 27 understanding or "verstehen" by Jaspers [START_REF] Markova | Epistemology of mental symptoms[END_REF]. That is: what is the meaning of a set of 28 symptoms for the subject him/herself? The response is driven here by the comprehensive 29 understanding of the individual rather that the symptoms and signs. Indeed, mental 30 manifestations are clearly part of the entire self-experience of the subject, associated with 31 biographical detail and having a personal meaning. This subjective aspect of signs and 32 symptoms has been largely described by phenomenology, for a review, see: [START_REF] Berrios | What is phenomenology? A review[END_REF][START_REF] Beumont | Phenomenology and the history of psychiatry[END_REF]39,[START_REF] Kendler | Explanatory models for psychiatric illness[END_REF]33 49, 51]. The following section mainly deals with the issue of explanation. Two principal 34 points of view are presented: the so-called latent variable model, i.e. the traditional medical 1 one, which considers them as the manifestation of a given underlying pathophysiological 2 mechanism; and the so-called causal network model, i.e. a more psychiatric-specific point of 3 view in which signs and symptoms have their own causal relationship. 4 5

Psychiatric semiology as seen by the latent variable model 6

Symptoms and signs in non-psychiatric medicine are traditionally considered as an indicator 7 of a latent variable [START_REF] Belzung | Latent variables and the 11 network perspective[END_REF]. A latent variable is a variable that is not directly observed but rather 8 inferred from other variables that are observed. This latent variable is taken to be related to a 9 physiological mechanism and thus to be the cause of the semiologic manifestation. Signs and 10 symptoms are considered as independent things -independent from other signs and symptoms 11 and from the context -but are considered to be dependent with regard to the causal 12 physiological substrate that is to be identified. 13

Two levels of causal physiological substrate and latent variable may be identified, one at the 14 semiologic level and the other at the nosologic level. Signs and symptoms are traditionally 15 considered as manifestations that may be associated with many different disorders. 16

Nevertheless, in non-psychiatric medicine each sign and symptom can be associated with a 17 latent variable that is not a physiological mechanism of the disorder but of the signs and 18 symptoms themselves. We propose to call this latent variable the "distal" latent variable. A 19 distal latent variable may be explained by a different disorder that we propose to refer to as 20 the "proximal" latent variable. The proximal latent variable should explain the occurrence of 21 symptom and signs in a defined disorder, the course of the disorder, its comorbidity, and the 22 treatment response. This distinction between the distal and the proximal is to be found in 23 many fields of medicine. Non-psychiatric semiology has been largely organized until now on 24 the basis of the distal aspects of physiology. The distal is important in any attempt to organize 25 semiologic terminology independently of nosographic issues. To our knowledge, the 26 classification task force of the International League Against Epilepsy (ILAE) is the group that 27 has proposed the best differentiation of the semiologic [52] and the nosographic [53] . 28

The fact that signs and symptoms in psychiatry have not been organized in physiological 29 terms based on the identification of a distal latent variable may be considered as an important 30 difference between psychiatric and non-psychiatric entities. The cause of this putative 31 difference needs to be analyzed thoroughly. 32

First, for non-psychiatric disorders, a semiologic organization based on neurophysiological 33 factors is possible because of the consensus regarding the framework for classifying 34 physiological functions. Although the framework is probably not complete, it is sufficient for 1 organizing signs and symptoms on a practical basis. Despite Cuthbert's statement that "the 2 majors systems of the brain have been delineated and related to their functional outputs" 3

[18], psychiatric semiology may be considered as lacking such a consensual 4 neurophysiological function framework [54]. Thus, symptoms and signs are organized rather 5 according to clinical considerations than physiological ones. 6

Second, the signs and symptoms of non-psychiatric disorders can generally be considered as 7 "objects", i.e. things that are "publicly accessible and involving mutually independent (and 8 typically atomic) entities devoid of subtle or complex forms of meaning, and suitable for 9 context-independent definition and measurement" [39]. In psychiatric semiology, it is more 10 difficult to describe signs and symptoms solely as "objects". As Spitzer and Endicott stated in 11 1978, signs and symptoms are "primarily" psychological in nature [21]. This does not mean 12 that signs and symptoms in non-psychiatric disorders are not subjective. Indeed, these aspects 13 have already been studied in the field of health psychology [START_REF] Franchi | L'inaccessible presque touché. Connaissance 18 minimale en psychologie de la santé à l'usage de l'étudiant en médecine[END_REF]. However, it does mean that 14 signs and symptoms in psychiatry should be considered primarily as the manifestations of the 15 modified cognition, emotion and behavior of the patient, leading to a modified inner 16 experience of self, others or the world, and not as the subjective experience of an altered part 17 of the body. This raises important questions about the means to conduct a reliable and valid 18 psychiatric interview (for a review see [50]), about the relationship between semiologic 19 psychiatry and the underlying neurophysiological distal mechanism [2] and about the 20 formation of mental symptoms [47]. 21

As stated by Kendler: "a more comprehensive explanation of a psychiatric disorder must 22 include an understanding of the production of the key symptoms and signs underlying that 23 disorder (…). As we understand the brain processes, we need to "back-translate" the biology 24 into an understanding -in psychological terms-of the keys psychopathological constructs 25 under investigation" [2]. An optimistic and materialist approach could consider that the 26 development of cognitive science and neuroscience in the domain of self-experience and 27 related physiological mechanisms heralds the possibility of organizing symptoms and signs 28 on the basis of physiology. Chalmers called it a "materialism of type C" [START_REF] Chalmers | The character of consciousness[END_REF]. This 29 materialism posits that if the laws of current physics do not yet allow for the complete 30 exploration of mental symptoms, there is no a priori explanatory gap concerning the two types 31 of data. The belief is strong that, one day, the development of neurosciences will enable us to 32 account entirely for the whole tasting experience strictly in neurophysiological terms. A less 33 materialist approach, close to the neurophenomenological project [57, 58], would involve 34 describing signs and symptoms on the basis of their qualitative/subjective aspects and 1 evaluating their neurophysiological correlates on the basis of reciprocal constraints, in which 2 qualitative/subjective aspects and neurophysiological data mutually inform each other [57]. 3 "An iterative relationship between psychology and biology, where initial psychological 4 constructs are better defined and subdivided by initial biology findings, which in turn help 5 clarify the biology, will needed to reach a more complete understanding. In short biological 6 and psychological perspectives will coevolve" [2]. The first difficulty of this reciprocal 7 constraint approach is the possibility that symptoms form via different pathways [START_REF] Markova | Epistemology of psychiatry[END_REF]47]. 8 "Because of the different ways in which internal changes can be interpreted, one biological 9 signal can give rise to different mental symptoms. Similarly, it can be envisaged that different 10 biological signals might be configured as the same mental symptom" [START_REF] Markova | Epistemology of psychiatry[END_REF]. The second 11 difficulty is that it supposes that we need to refine the semiologic register in psychiatry [START_REF] Markova | Epistemology of psychiatry[END_REF]. 12 As Kendler stressed, "empirical research is crucially dependent on the adequacy of the 13 employed phenotypic distinctions, adequacy that cannot be achieved through a simplistic 14 behaviorist checklist approach" [51]. Berrios also clearly highlighted this issue: "mental 15 symptoms became the "atoms" or "units of analysis" of descriptive psychopathology. This 16 language was calibrated according to the epistemological requirements of contemporary 17 clinical practice and research. Importantly, it has changed little since. (…) Consequently, 18 however, this has resulted in a significant mismatch between the resolution power of the 19 language of psychiatry and that of the instruments devised to capture and measure its proxy 20

variables" [START_REF] Markova | Epistemology of psychiatry[END_REF]. 21

In line with the DSM-III position, psychiatric signs and symptoms are primarily mental and a 22 rigorous methodology is required to organize them in psychiatric semiology and to obtain a 23 reliable neuroscientific explanation for them [START_REF] Kendler | Explanatory models for psychiatric illness[END_REF][START_REF] Parnas | The Breivik case and "conditio psychiatrica[END_REF]49,51]. A challenge in psychiatry is 24 thus to better define and organize a patient's symptoms and signs in terms both of his/her 25 subjacent brain mechanisms and of his/her inner experience of the symptoms and signs 26 (according to a reciprocal constraint approach). 27 28

Psychiatric semiology as seen by the causal network model 29

The previous latent variable model of semiology posited that symptoms and signs are 30 independent things related together by a latent variable [59]. However, it has also been 31

suggested that symptoms and signs have properties with autonomous causal relevance [START_REF] Borsboom | The small world of 29 psychopathology[END_REF]. 32 "Instead of being effect of common cause, psychiatric symptoms have been argued to cause 33 each other" [59]. Thus, symptoms and signs can be related by causal chains that can be better 34 studied by a causal network model. This network approach considers symptoms and signs as 1 "nodes" and causal interactions between symptoms as "connections between nodes". 2

According to this point of view, a psychiatric disorder is to be considered as a set of 3 symptoms and signs that are connected thought a system of causal relations [START_REF] Borsboom | Psychometric perspectives on diagnostic systems[END_REF]. "In such a 4 model, symptoms are not an indicator of an underlying pathological process, rather they are 5 parts of a functionally interconnected causal network" [62]. 6

From a clinical point of view, the causal network model helps the psychiatrist in collecting 7 signs and symptoms. Thus, collection is not solely based on the search for a latent 8 physiological mechanism that might explain the manifestation but also on the understanding 9 of the relationship between the symptoms and signs in the experience of the subject [39, 59]. 10 Indeed, psychiatrists intuitively interpret relations between symptoms as causal networks 11 [START_REF] Aragona | The concept of mental disorder and the DSM-V[END_REF]. For example, the relationship between hallucination, anxiety and insomnia is 12 understandable through their causal relationship without any need for a latent variable. 13

Interestingly, the DSM itself contains criteria with causal relationships, e.g. for the panic 14 disorder: worries about the possible implication of another attack [START_REF] Aragona | The concept of mental disorder and the DSM-V[END_REF], or for the obsessive-15 compulsive disorder: compulsion in response to an obsession [59]. However, a limitation of 16 the causal network model is that it is elusive about what symptoms or signs are to be included 17 in the model. Mental symptoms and signs remain the "units of analysis" but their nature, 18 formation and how they are to be captured are not clearly defined [START_REF] Markova | Epistemology of mental symptoms[END_REF]. Nevertheless, the 19 semiologic register in psychiatry is not a simple and neutral "description" of reality [START_REF] Markova | Epistemology of psychiatry[END_REF]. It 20 construes mental manifestations in particular ways, a point that has received very little 21 attention in the psychiatric literature on the causal network model. Yet this approach could be 22 of interest to better describe the formation of psychiatric manifestations. Indeed, such a 23 network approach model can include social interactions [64] and their impact on the 24 formation of mental symptoms and signs. As Berrios highlighted, "the final description of 25 symptom results from the interaction between a tenuous biological signal (originated in an 26 affected brain site) and the layers of psychosocial codes (noise) partaking in the process of 27 symptom formation. (…) The crucial point here is that clinical 'observation' is never a 28 cognitively innocent activity" [START_REF] Berrios | The History of Mental Symptoms: Descriptive Psychopathology since the 11 Nineteenth Century[END_REF]. This view is known as the Cambridge model of symptom 29 formation [START_REF] Markova | Epistemology of psychiatry[END_REF]47], which is related to the hypothesis that the biological/physiological signal 30 (related to a brain modification) is something pre-linguistic and pre-conceptual (also called 31 the "primordial soup" [47]) that needs to be constructed to be communicated according to 32 social configurators (Figure 1) [65]. Further work could investigate how such configurators 33 could be included in the causal network model. 34

From a physiological point of view, the causal network model is agnostic with regard to how 1 causal relations between symptoms and signs are grounded [59]. However, it involves 2 considering the mechanism underlying the clinical psychiatric manifestation not in terms of a 3 single clear explanation but rather as a multifactorial entity, as with the systemic biological 4 approach to brain functioning [START_REF] Kendler | Levels of explanation in psychiatric and substance use disorders: 24 implications for the development of an etiologically based nosology[END_REF]. Figure 1. The way in which the psychiatric disorder 5 develops into a set of symptoms and signs that are relatively stable may be related to the 6 process regulating homeostatic brain function. They are more or less stable because they 7 reinforce each other mutually and because such a network may be subsumed by brain 8 homeostatic regulation underpinned by complex and mutually reinforcing networks of causal 9 mechanisms. Figure 1. This implies adding a semiologic level to the traditional multilevel 10 analysis in neuroscience. Interestingly, such a semiologic view would involve identifying not 11 only clearly defined signs and symptoms but also "anti-signs" and "anti-symptoms" that 12 "protect against disorder by blocking the spreading of problems through the network" [START_REF] Borsboom | The small world of 29 psychopathology[END_REF]. 13

The fact that signs and symptoms in psychiatry are neither independent nor passive could be 14 considered as an important difference between psychiatric and non-psychiatric entities. 15 Indeed, the model has also been called the "network approach to psychopathology" [59]. 16

However, the causal network model has also been applied to non-psychiatric disorders, in line 17 with the concept of "diseasome" [66] and "network medicine" [64, 67]. However, in such a 18 model, nodes represent "disorders" and not "symptoms and signs". To our knowledge, the 19 causal network model has not been used for the symptoms and signs of non-psychiatric 20 disorders. Nevertheless, the model has been applied to health-related quality of life in healthy 21 adults and patients with cancer [START_REF] Kossakowski | The application of a network approach 14 to Health-Related Quality of Life (HRQoL): introducing a new method for assessing 15 HRQoL in healthy adults and cancer patients[END_REF], which highlight the interest of such an approach in the 22 domain of chronic diseases to better understand the impact and the relationship of cognition, 23 emotion and behavior on patients' health [START_REF] Bragazzi | Rethinking psychiatry with OMICS science in the age of personalized 17 P5 medicine: ready for psychiatome?[END_REF]. 24

The absence of a single latent variable or the absence of a common cause could mean that it is 25 impossible to establish a pragmatic measure of explanation in line with the complexity and 26 the multilevel characteristics of the model. In fact, a "network model load" could be measured 27 and would prove very useful in clinical practice and research. Indeed, multilevel causal chains 28 cutting across levels of organization and timescales can be projected in lower dimensional 29 space. The key challenge is to find the lowest dimensional denominator that explains the 30 behavior of the system and then to extract a metric that is relevant in both nosologic and 31 semiologic terms. Figure 3 provides two examples in which a unidimensional view based on 32 averages does not meaningfully differentiate controls and patients, whereas a 33 multidimensional view allows a problem to be encompassed by a compound metric separating 34 the two populations. Recent development in machine learning has boosted the use of such 1 multivariate metrics but they still need a clear evaluation of their validity in relation to 2 physiological mechanisms. Evaluation of their reliability is more complex and can even 3 question existing boundaries. The recent development of normative modeling, for instance, 4 makes it possible to move away from a traditional case vs. control approach and to consider 5 more complex scenarios with various spectra and comorbidities [START_REF] Marquand | Understanding Heterogeneity in Clinical 19 Cohorts Using Normative Models: Beyond Case-Control Studies[END_REF]. 6

A challenge in psychiatry is thus to incorporate the semiologic more meaningfully into a 7 consensual network model that combines social interaction (including with the medical 8 system), psychological processes, neuronal functioning and even genetic data [71]. As we 9 have underlined, the RDoC is based on an integrative, multilevel, multisystem approach. We 10 think that research in semiology should form part of the RDoC project in order to better 11 understand the link between brain dysfunction and the clinical manifestations of disorders 12 [START_REF] Cuthbert | Toward the future of psychiatric diagnosis: the seven pillars 12 of RDoC[END_REF]. This would link in much better with clinical practice. Nevertheless, two major 13 challenges remaining are: i) to train the new generation of psychiatrists in how such an 14 interdisciplinary perspective may be adopted, and ii) to include digital technology in their 15 training in order to optimize the delivery of psychiatric medicine in the future [71,72]. 16 17

Conclusion 1

This article questions the notion that psychiatric disorders are to be considered differently 2 from non-psychiatric disorders. We have shown that debate until now has focused more on 3 the nosologic than on the semiologic. Rather that highlighting specific features of psychiatric 4 disorders, nosologic point of view reveals factors that co-occur across the entire field of 5 medicine if the objective is to establish the boundaries between the normal and the pathologic 6 and between different disorders. Psychiatry is thus very important in medicine because it 7 exemplifies the inherent problem of the construction of a cognitive framework that has been 8

imposed on clinical and scientific medical information to delineate a classification of 9 disorders and to increase its comprehensibility and utility. In this sense, it can be considered 10 that psychiatric disorders are not different from non-psychiatric disorders, provided that care 11 is taken in how non-psychiatric disorders are defined. This paradigm shift is in line with the 12 position of Spitzer and Endicott in 1978 when they stated that "a mental disorder should be 13 defined as merely a subset of medical disorder, and that our attention should therefore be 14 directed toward defining the broad rubric of medical disorder" [21]. Thinking about 15 psychiatric classification should therefore seek to "clarify the goals of medical classification" 16 and offer "a rationale for decisions as to which consideration should be included or excluded 17 from a medical classification" [21]. 18

In contrast, semiologic point of view has led to the discovery of psychiatric features that 19 underline the great value of psychiatry and the scientific challenges it faces. This position is 20 in line with Berrios who claims that the "primary objects" of psychiatry are mental symptoms 21 and signs, and that mental disorders are "derivative objects", with higher level organizations 22 [47]. This article has focused on the need to better define and classify signs and symptoms in 23 psychiatry based on a dual, mutually interactive biological and psychological perspective and 24 to incorporate semiologic psychiatry into a multilevel multisystem brain/cognitive approach. 25

In such a view, there is an urgent need to "make semiologic psychiatry great again". As for 26 nosologic issues, an international task force should be set up to investigate semiologic 27 psychiatry in the field of medicine. In this task force, historical, societal, epistemological and 28 phenomenological (in it continental philosophical meaning [START_REF] Berrios | What is phenomenology? A review[END_REF]) aspects concerning mental 29 manifestations discussed in this article should be not forgotten. Moreover, as chronic disease 30 becomes an ever greater burden for society [72], such a task force would have a great effect in 31 better understanding the impact of cognition, emotion and behavior on the onset and 32 maintenance of non-psychiatric disorders beyond the dichotomy between mental and physical 33 disorders. 34 1 Table 1: The Spitzer & Endicott 1978 criteria regarding the boundaries between the normal and the pathologic [START_REF] Spitzer | Research diagnostic criteria: rationale and 32 reliability[END_REF].

All four criteria, A through D, must be met for a condition to be designated as a medical disorder.

Criterion A. The condition, in the fully developed or extreme form, in all environments (other than one especially created to compensate for the condition), is directly associated with at least one of the following:

1. distress-acknowledged by the individual or manifested; 2. disability-some impairment in functioning in a wide range of activities; 3. disadvantage (not resulting from the above)-certain forms of disadvantage to the individual in interacting with aspects of the physical or social environment because of an identifiable psychological or physical factor. The following forms of disadvantage, even when not associated with distress or disability, are now considered, in our culture, as suggestive of some type of organismic dysfunction warranting the designation of medical disorder: a. impaired ability to make important environmental discriminations (e.g., color blindness, lack of pain perception).

b. lack of ability to reproduce (e.g., sterility). c. cosmetically unattractive because of a deviation in kind, rather than degree, from physical structure (e.g., fused toes). d. atypical and inflexible sexual or other impulse-driven behavior which often leads to painful consequences (e.g., sexual sadism, kleptomania, pathological gambling). e. impairment in the ability to experience sexual pleasure in an interpersonal context (e.g., fetishism). f. marked impairment in the ability to form relatively lasting and non-conflictual interpersonal relationships (e.g., narcissistic and hysterical personality disorders).

Criterion B.

The controlling variables tend to be attributed to being largely within the organism with regard to either initiating or maintaining the condition. Operationally, this criterion is determined by the following: A condition is included [as a disorder] only if it meets both of the following criteria:

1. Simple informative or standard educational procedures do not lead to a reversal of the condition.

Proposition for framework to better identify nosologic and semiologic issues in psychiatry.

Left part of the figure: delimiting psychiatric disorders (nosologic level) is not only based on brain constraints that reflect pathophysiological mechanisms, but also on the semiologic level and on epidemiological, prognostic, therapeutic and economic factors [START_REF] Franchi | From clinic to the "foul and exciting 27 field of life": A psychiatric point of view on clinical physiology[END_REF].

Figure 3

Sometimes, one need to use multi-dimensional spaces to be able to find a simpler unidimensional metric. A, B) two common cases where two variables can be simplified into one metric: A) interaction between cognitive scores 1 and 2 and B) offset in the cognitive score 1 compared to cognitive score 2. Difference between groups remains hidden when averaging across the age dimension; C) example of a more complex landscape with helicoidal trajectories in three dimensions. The two brain measures can be reduced to a unidimensional composite score by calculating the distance R between each participant and the axis A. D)

The new composite score better explains the separation between the groups.

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Figure 1 .

 1 As posited by Spitzer and 18Endicott in 1978, "the operation by which syndromes and disease are distinguished from each 19 other and from symptoms consist of examining the extent to which the external correlated of 20

Figure 2 .

 2 Thus, by turning the two-step process around, the RDoC may be 8 seen as an attempt to reorganize the classification of psychiatric symptoms and signs on the 9 basis of the underlying physiological mechanisms and not on the basis of the historical 10 classification of disorders. Aragona clearly highlighted the fact that the RDoC turns the 11 original project upside down [12]. "Both the neo-Kraepelinian DSM-III and the DSM-5 are 12 based on the same assumption about validity: i.e., the provisional phenomenal descriptions 13

2.

  Nontechnical interventions do not bring about a quick reversal of the condition. Criterion C. Conditions are not included if the associated distress, disability, or other disadvantage is apparently the necessary price associated with attaining some positive goal. Criterion D. Distinctness from other conditions in one or more of the following features: clinical phenomenology, course, response to treatment, familial incidence, or etiology.

Figure 2 Table 2 :

 22 Figure

  Right part of the figure: adaptation of the Cambridge model of symptom formation [47],which posits that mental manifestations, i.e. the semiologic level, result from interactions between brain constraints and social constraints, which in turn are related to the formation and expression of symptoms and signs within a social network.

Figure 2

 2 Figure 2 Relation between semiologic psychiatry, RDC/DSM project and RDoC project [12].

Table 3 :

 3 Validity criteria to classify different disorders

	References	Validity criteria
	Robin and Gruze criteria 1970	1.	Clinical description
	[30]	2.	Laboratory study
		3.	Delimitation from other disorders
		4.	Follow-up study
		5.	Family study
	Spitzer and Endicott 1978 [14]	1. Clinical phenomenology
		2. Course
		3. Response to treatment
		4. Family incidence
		5. Etiology
	Kendler criteria 1990 [26]	Robin and Gruze criteria
		+
		Differential response to treatment
	DSM-5 criteria 2013 [13]	1.	Shared neural substrates
		2.	Family traits
		3.	Genetic risk factors
		4.	Specific environmental risk factors
		5.	Biomarkers
		6.	Temperamental antecedents
		7.	Abnormalities of emotional or cognitive processing
		8.	Symptom similarity
		9.	Course of illness
		10.	High comorbidity
		11.	Shared treatment response
	RDoC criteria [18]	1.	Inventory of brain functions
		2.	Inventory of brain dysfunction:
			a. the related phenomenological expression
			b. the mechanism of dysfunction (integrative and
			multisystem point of view)

Acknowledgements

1

Many thanks to Ray Cooke for his very careful English editing. 2 3 4

Declaration of interest 5

The authors declare no potential conflicts of interest with respect to the research, authorship 6 and/or publication of this article. 7 8 9

Funding 10

The authors received no financial support for the research, authorship and/or publication of 11 this article. 12 13