To address this issue, we present here a broad systematic review of transdiagnostic research in psychiatry. We systematically assess the transdiagnostic literature against several empirical variables which index core characteristics as well as potential pitfalls. A bibliometric and conceptual analysis complements the empirical findings, along with practical recommendations to guide future research in this field.

Transdiagnostic research aims at tackling these limitations to introduce a novel approach that could improve the way we classify, formulate, treat, and prevent 15 mental disorders. Moving away from a single‐diagnosis approach towards a transdiagnostic conceptualization and treatment of mental disorders would thus be a significant paradigm shift 15 . Recently, transdiagnostic approaches have been endorsed by other paradigms that cut across different mental disorders, such as the Research Domain Criteria (RDoC) initiative 17 and the clinical staging model 18 . At present, however, it is unclear whether transdiagnostic research meets such high expectations for delivering a radical paradigm shift that impacts classification and clinical care.

The rationale for extending the transdiagnostic paradigm to anxiety and depressive disorders included an additional point that was not originally acknowledged 10 : c) disorder‐specific interventions rely on heterogeneous diagnostic categories and pay relatively limited attention to comorbidity, which is high 15 .

Transdiagnostic approaches originated from cognitive behavioral theories and treatments for eating disorders 9 , 10 , which were then extended to anxiety 11 - 13 and depressive disorders 14 . The initial transdiagnostic rationale leveraged two core points: a) these disorders share common etiological and maintenance processes 9 , 10 , 13 , 15 as well as cognitive‐affective, interpersonal, and behavioral features 9 , 10 , 15 (e.g., the general psychopathology latent factor – p factor 16 ), and b) the ever‐growing number of disorder‐specific treatment manuals is a barrier to the implementation of cognitive behavioral treatments 10 , 13 , 15 .

A promising avenue has been put forward by the so‐called transdiagnostic approach. The prefix “trans” comes from Latin and it can either mean across/through (e.g., transatlantic) or beyond (e.g., transcend) 8 . Therefore, a transdiagnostic approach in psychiatry is expected to cut across existing categorical diagnoses and go beyond them, to produce a better classification system, compared to the existing gold standard.

Since its inception, psychiatric nosology has always been under fire. This is documented by several lines of evidence, including two recent issues of this journal 3 , 5 . Although current diagnostic categories have demonstrated moderate to almost perfect reliability 6 , their usefulness has remained questionable 7 .

Diagnosis, which is the medical application of the process of classification, ubiquitous in science, has been the cornerstone of modern clinical knowledge and practice 1 . Diagnosis in psychiatry started in Europe in the late 17th century, informed by systems that classified animal and plant species as part of other natural sciences 2 . Psychiatric nosology, traditionally represented by the ICD and DSM (gold standard), is based on categorical diagnoses that are intertwined with the key clinical dichotomies that characterize the realm of clinical medicine (e.g., to treat or not to treat) 3 , 4 .

Fourth, we conducted a bibliometric analysis using the list of specific ICD/DSM mental disorders that were analyzed by each study (when available). These data were then loaded into R software and cleaned with the Bibliometrix and TM packages. The processed data were then loaded into Gephi software to generate the network map of the specific ICD/DSM mental disorders investigated by transdiagnostic research. Each node indicated a specific mental disorder, with the node's size reflecting how many different connections (frequency) with other nodes were present. The thickness of the edges reflected the number of connections between a pair of nodes/mental disorders. For graphical purposes, nodes that had frequen‐cy ≤⃒6 and number of co‐occurrent connections ≤⃒3 were filtered out.

Third, the conceptual definition of the transdiagnostic approach was empirically deconstructed. The main aim was to explore the extent to which each transdiagnostic approach related to the existing diagnostic categorical system. As indicated in Figure 1 , the simplest transdiagnostic approach – defined as “across‐diagnoses” – was to compare different ICD/DSM categorical diagnoses against each other, to test their diagnostic boundaries and cross‐cutting features. The across‐diagnoses model could include one diagnostic spectrum, multiple spectra and/or non‐clinical samples, including also healthy individuals. A more elaborated approach involved the definition of new diagnostic‐like constructs, for example based on biotypes or clinical types, and then testing the relatedness of these newly defined constructs against the gold standard. These approaches were termed “beyond‐diagnoses” , because they employed standard ICD/DSM diagnostic information but went beyond it, to test new diagnostic constructs. When studies did not fit within any of the above two categories, the specific approach was described.

Second, each study was assessed against the criteria introduced by Mansell et al 21 to define transdiagnostic approaches in psychiatry: a) presence of a clinical population, b) presence of at least four different mental disorders, c) presence of a non‐clinical sample, and d) demonstration of the transdiagnostic construct in all mental disorders investigated.

Quality assessment was performed by recording if an a priori protocol had been made available, if funding was provided by industry, and if the core findings had been externally replicated in an independent sample.

Variables relating to the transdiagnostic approach included: the exact definition of the transdiagnostic construct as provided by each study; the number of transdiagnostic constructs (single or multiple) 21 ; whether the transdiagnostic construct was descriptive (a construct which is present in multiple disorders, without regard to how or why 22 ) or mechanistic (a construct that may reflect an underlying physiological, neurobiological or functional mechanism 22 ); whether the construct was causally associated with the outcome (to rule out the possibility that a construct may just be epiphenomenal 21 ); whether the transdiagnostic construct was present in all clinical conditions and spectra (universal transdiagnostic process) and in how many of them. We also extracted the type of statistical analysis used to probe the transdiagnostic construct; whether there was a formal statistical assessment of the impact of the transdiagnostic approach compared to the specific‐diagnostic approach; and the results of such a test.

Variables relating to the outcomes included: whether the primary outcome of the study was clearly acknowledged in the manuscript; the specific type of instruments employed to define it; and the total number of primary outcomes.

Variables relating to the definition of the gold standard diag‐nostic criteria included: whether the study explicitly acknowledged the type of gold standard used (DSM or ICD, any version); the specific type of primary diagnoses of mental disorders and their specific ICD or DSM codes; the presence of any other clinical condition as defined by each individual study; the presence of a non‐clinical sample (e.g., healthy controls); the total number of ICD/DSM mental disorders investigated by the study; the total number of diagnostic spectra (defined according to the ICD‐10 diagnostic blocks: organic, including symptomatic mental disorders; mental and behavioral disorders due to psychoactive substance use; schizophrenia, schizotypal and delusional disorders; mood (affective) disorders; neurotic, stress‐related and somatoform disorders; behavioral syndromes associated with physiological disturbances and physical factors; disorders of adult personality and behavior; mental retardation; disorders of psychological development; behavioral and emotional disorders with onset usually occurring in childhood and adolescence; unspecified mental disorders); and the type of psychometric instrument employed to define the gold standard.

The exclusion criteria were: a) reviews, meta‐analyses, study protocols, abstracts and any other non‐original data; b) lacking a clear primary focus on transdiagnostic approaches, defined as above; and c) studies with less than ten participants 20 .

Studies were eligible for inclusion when the following criteria were fulfilled: a) original individual articles, with no restriction on study design (including interventional and observational studies) or topic; b) a clear and primary focus on a transdiagnostic approach, demonstrated by using the word “transdiagnostic” in the title.

The literature search, study selection and data extraction were conducted by two authors (MS, NB) independently. During all stages, in the case of disagreement, consensus was reached through discussion with a third author (PFP).

A multi‐step literature search was performed. First, systematic searches were conducted in the Web of Science (which includes Web of Science Core Collection, BIOSIS Citation Index, KCI ‐ Korean Journal Database, MEDLINE, Russian Science Citation Index, and SciELO Citation Index), until May 5, 2018, with no restrictions on language or publication date. The keyword “transdiagnostic” was used, filtering for the category “psychiatry” through the Web of Science categories function. Second, we searched the reference lists of retrieved articles. Third, abstracts identified by this process were then screened and full‐text articles were inspected against the inclusion and exclusion criteria.

Network map of specific mental disorders analyzed by transdiagnostic research in psychiatry to date. Each node indicates a specific mental disorder, with the node's size reflecting how many different connections with other nodes were present. The thickness of the edges reflects the number of connections between a pair of nodes/mental disorders.

Two further studies used the investigated different subtypes (restricting type and binge eating type) of the same disorder (DSM‐IV anorexia nervosa) 96 or different clinical states of the same disorder (never depressed, past depression, current depression) 109 .

Nine studies (8%) 50 , 59 - 63 , 96 , 109 , 110 were defined as “within the same diagnosis” . Six of them investigated comorbid disorders in addition to a single primary disorder: comorbid depression, generalized anxiety disorder and social anxiety disorder in addition to panic disorder 60 ; comorbid depression, generalized anxiety disorder and panic disorder in addition to social anxiety disorder 61 ; comorbid generalized anxiety disorder, panic disorder and social anxiety disorder in addition to major depressive disorder 62 ; comorbid major depressive disorder, social anxiety disorder and panic disorder in addition to generalized anxiety disorder 63 ; comorbid panic disorder, social anxiety disorder and generalized anxiety disorder in addition to major depression 50 ; and multiple mental disorders in addition to binge eating disorder 59 . Another study investigated comorbid depressive and anxiety symptoms (but not disorders) in patients with post‐traumatic stress disorder 110 .

Five studies (5%) 29 , 86 , 88 , 90 , 91 confounded symptoms and disorders. These studies explored only DSM or ICD‐related symptoms without any clear reference to diagnostic categories of mental disorders, and were therefore defined as “across symptoms” .

Eight studies (7%) 70 , 78 , 82 , 85 , 87 , 92 , 95 , 97 did not consider any ICD/DSM diagnostic information as gold standard nor defined any new diagnostic construct. These were usually population‐based studies which adopted a continuum rather than a categorical measurement of psychopathology, the results of which were completely unrelatable to any existing ICD/DSM category. Therefore, these studies were termed as being “a‐diagnostic” rather than transdiagnostic.

For most of these across/beyond‐diagnoses studies, the transdiagnostic approach was intertwined in the baseline recruitment of participants with different diagnoses. However, two studies (2%) defined their transdiagnostic approach through the inclusion of different diagnostic outcomes, as opposed to different patient groups at baseline (these studies were termed “transdiagnostic outcomes”) 75 , 77 . Two other studies (2%) 24 , 51 defined their transdiagnostic approach as the overlap between physical (gastrointestinal, headache) and mental health (anxiety and depression) symptoms (these studies were termed “across physical and mental health diagnoses”).

The majority of studies (82 out of 111, 74%) (Table 1 ) endorsed an across‐diagnoses approach. Of them, 33 (40%) were conducted within the same diagnostic spectrum (three of which also included a non‐clinical sample) and 49 (60%) were across different diagnostic spectra (22 of which also included a non‐clinical sample) (Table 1 ). Only three studies (3%) 111 , 126 , 130 endorsed a beyond‐diagnoses approach. They were also the most methodologically sophisticated.

Only three studies (3%) 98 , 100 , 117 met Mansell's transdiagnostic criteria. The most frequently unmet requirement was the demonstration of the transdiagnostic construct across all conditions investigated by the study.

Some studies interpreted overfitted and not externally replicated models to favor transdiagnostic over disorder‐specific approaches 76 . Other studies conducted a large number of comparative analyses without controlling for multiple comparisons 106 . One study stated that participants were randomized, but eventually allocated them to a single treatment arm 38 . Another study re‐analyzed data from three previously published interventional studies that adopted different designs, without clarifying how the final database was amalgamated 47 .

A substantial proportion of studies (40%) 23 , 28 - 30 , 37 , 40 , 47 , 67 , 69 - 71 , 73 , 75 , 78 , 80 , 82 - 88 , 93 , 96 - 98 , 100 , 104 - 109 , 113 - 118 , 120 , 124 , 126 , 128 , 130 did not acknowledge an a priori protocol. There were very few studies reporting industry involvement (4%) 52 , 57 , 103 , 110 , 111 . Transdiagnostic findings were hardly ever externally replicated, with the exception of four studies (4%) 73 , 85 , 93 , 111 . Other methodological weaknesses involved the use of clinical prediction methods (i.e., stepwise selection methods) that produce biased models 109 , 82 , in particular in small databases 131 , 120 , 80 . The use of small samples 80 also led to underpowered analyses across diagnostic subgroups 133 .

In general, neuroscientific studies provided better descriptions of these effects. For example, one of them concluded that the transdiagnostic biotypes identified specific, coherent associations between symptoms, behavior, brain function, and real‐world function that cut across DSM‐IV defined diagnoses 111 . Other neuroscientific studies demonstrated shared neurobiological mechanisms across current categories of mental disorders 108 , 112 , 113 , 115 , 117 or both specific and transdiagnostic effects across mental disorders 74 , 116 , 129 .

The qualitative appraisal of the transdiagnostic vs. specific‐diagnostic effects – when available – revealed further inconsistencies. For example, some predictive modelling studies indicated that the transdiagnostic approach was only able to explain an additional 1% of the variance 109 . Other studies acknowledged that the observed transdiagnostic effects were small in magnitude, but at the same time suggested developing transdiagnostic clinical interventions 131 .

Less than half (44%) of the studies 27 , 33 , 38 , 58 , 60 , 61 , 65 , 72 - 75 , 77 , 79 - 81 , 83 , 84 , 89 , 93 , 98 , 100 , 101 , 103 , 105 , 107 - 109 , 111 - 121 , 123 - 133 performed a statistical comparative assessment of the transdiagnostic approach versus a specific‐diagnostic approach. This problem was particularly relevant for interventional studies, half of which lacked a comparative specific‐diagnostic group. Overall, only 16% of them 27 , 33 , 38 , 58 , 60 , 61 , 65 , 83 performed a statistical comparative assessment. Some of these studies acknowledged that reliable conclusions regarding the diagnostic specificity of the findings could not be drawn 34 , 64 . However, other interventional studies lacking both a control group and statistical comparative assessment eventually (over)stated that the transdiagnostic cognitive behavioral treatment was effective in improving outcomes 40 or that it was more effective than the specific‐diagnostic approach 29 . When comparative analyses were available, they generally indicated similar effects of the transdiagnostic vs. the specific‐diagnostic intervention 58 , 60 , 61 , 83 .

The transdiagnostic construct was demonstrated across all clinical conditions investigated only in a minority (34%) of studies 24 , 27 , 30 , 32 , 38 , 42 , 43 , 45 , 47 , 50 , 52 , 53 , 57 , 58 , 60 - 63 , 65 , 71 , 80 , 83 , 89 , 96 , 98 , 109 - 113 , 115 , 117 , 118 , 123 , 128 - 130 , 133 . It was demonstrated in a median of three conditions and one spectrum. Several studies did not clarify at all whether the construct was present in the conditions investigated. Overall, no clear universal transdiagnostic construct that could be valid across all mental disorders and diagnostic spectra was identified.

The exact definition of the transdiagnostic construct per study is provided in Table 1 . Only a minority of constructs (36%) involved multiple processes 28 , 37 , 38 , 48 , 55 , 59 , 70 , 72 , 75 - 77 , 79 , 80 , 85 , 87 , 91 , 92 , 96 , 98 , 100 , 103 , 106 , 110 , 111 , 113 , 114 , 116 , 119 - 121 , 123 - 132 . Most studies (81%) were descriptive in nature. Mechanistic constructs were more infrequent (19%) 28 , 32 , 38 , 48 , 50 - 53 , 58 , 70 , 83 , 103 , 112 - 118 , 131 , 133 , and causal transdiagnostic constructs were hardly ever reported (7%) 24 , 48 , 50 - 53 , 58 , 115 and only during the most recent years (2017‐2018).

Only a minority (35%) 23 - 25 , 32 , 34 - 36 , 40 , 48 , 49 , 51 - 53 , 56 - 62 , 64 , 66 - 68 , 73 , 74 , 83 , 84 , 88 , 100 , 103 , 111 , 112 , 115 , 125 - 128 of studies explicitly acknowledged their primary outcome measure, which may be suggestive of suboptimal study quality. There was also a high variability in the number of primary outcome measures, ranging from one 48 to thirteen 81 (median: two measures) per study.

The number of primary mental disorders investigated by each study was highly variable and overall relatively low, ranging from no evidence of mental disorders at all (13% of studies) 24 , 29 , 70 , 78 , 82 , 85 - 88 , 90 - 92 , 95 , 97 and one mental disorder (8% of studies) 50 , 59 - 63 , 96 , 109 , 110 , up to 353 mental disorders 73 (median: four mental disorders per study). Similarly, the number of ICD‐defined diagnostic spectra was heterogeneous, ranging from zero (12% of studies) 29 , 70 , 78 , 82 , 85 - 88 , 90 - 92 , 95 , 97 to ten 73 (median: one spectrum) per study. The largest transdiagnostic study published to date leveraged an electronic case register to include 353 mental disorders clustered across ten spectra, representing all ICD‐10 mental disorders except organic mental disorders 73 . About one third of the studies (35%) 29 , 40 , 70 , 74 , 76 , 78 , 81 , 82 , 85 - 87 , 90 - 92 , 94 - 98 , 100 , 101 , 103 , 105 - 107 , 111 - 124 included at least one non‐clinical sample.

Frequently, studies did not specify the exact ICD/DSM types of mental disorders that were investigated, but only referred to the general domains of psychotic disorders 34 , 106 , substance induced disorders 28 , 34 , 108 , anxiety disorders 23 , 28 , 54 , 88 , 93 , 104 , mood disorders 23 , 28 , 48 , 49 , 54 , 64 , 88 , 93 , or mood and anxiety disorders 54 , 93 . The specific ICD/DSM diagnostic codes were hardly ever reported.

An interventional study which did not use cut‐offs to define post‐traumatic stress disorder concluded that treating distress was better than treating the categorical disorder 29 . Another interventional study which measured symptoms but not disorders tautologically concluded that the potential advantage of transdiagnostic interventions was a reduced need for disorder‐based assessments 88 . Some studies did apply cut‐offs but eventually did not use them for their main analyses 48 , 94 .

There was also some confusion between the measurement of symptoms as opposed to categorical disorders. This was mainly due to the use of continuous measurements that were not translated into ICD/DSM diagnostic categories through the use of a priori cut‐offs 83 . Three studies measured DSM‐related items in non‐clinical samples without applying cut‐offs to establish the intake of specific diagnostic categories 86 , 90 , 91 . The results were there interpreted in the context of the disorder‐oriented literature 91 , arguing that findings were related to specific categorical diagnoses 86 , 90 . These studies concurrently acknowledged a transdiagnostic approach in their title – as for any other study included in the current review – and “the lack of diagnostic measures” in the study itself 91 .

Some studies used comorbid (as opposed to primary) diagnoses to validate the transdiagnostic construct 50 , 52 , 56 , 59 - 63 , 99 , 103 . In about one third of studies (28%) 34 , 36 , 54 , 69 , 70 , 72 , 74 , 75 , 82 , 85 , 87 , 89 , 104 - 107 , the boundaries between primary and secondary diagnoses were not completely clear.

One interventional study stated that the participants were not diagnosed at all 88 . The study addressed this issue by simply noting that “it would have been informative to know client diagnoses” 88 , raising concerns about unnecessary or excessive treatments in this sample 102 .

Some studies reported non‐existent (e.g., DSM‐IV‐TR bipolar II disorder with psychotic features 84 ) or incorrect diagnoses (e.g., suicidality 34 , marijuana abuse/dependence 76 , 101 , late onset schizophrenia‐like psychosis 100 , social anxiety disorder and social phobia as two distinct DSM‐IV disorders 101 ). Other studies included health anxiety within mental disorders, confusingly defined either as not relating to a specific diagnosis 90 , as hypocondriasis 23 , or as “health‐based anxiety predominant in individuals with illness anxiety disorders and somatic symptom disorders” 90 .

A substantial proportion (27%) of studies 24 , 29 , 36 , 40 , 48 , 49 , 64 , 69 - 71 , 73 , 78 , 80 , 82 - 98 did not acknowledge using any psychometric interview to establish their gold standard diagnoses. Several studies (16%) 29 , 34 , 54 , 70 , 71 , 78 , 82 , 83 , 85 - 88 , 92 , 93 , 95 , 97 , 99 , 100 did not refer to a gold standard diagnostic manual, but speculated on comparative benefits of the transdiagnostic approach over specific diagnoses 29 , 71 .

The vast majority of non‐interventional studies (79%) were cross‐sectional, and only 21% 69 - 81 longitudinal. There was a large variability in study sample size, ranging from 15 participants in the smallest study 42 to 91,199 in the largest 73 (median: 148 participants). The mean age of individuals (when available) ranged from 10 44 to more than 60 23 (median: 33 years).

Cognition and psychological processes was the second most frequent topic (28%), followed by neuroscientific topics (13%). Classification and prediction studies were more infrequent (4% and 10% respectively) (Table 1 ).

Most studies (45%) were investigating interventions (of which 50% were controlled, 48% uncontrolled 23 - 46 , and 2% unclear 47 ). Less than half (46%) 11 , 43 , 48 - 68 of the interventional studies were randomized. All interventional studies focused on neurotic, stress‐related and somatoform disorders or mood (affective) disorders, while other mental disorders were rarely investigated (Table 1 ).

The first study, published in 2004 by Norton et al 11 , addressed the effects of a transdiagnostic psychological intervention for different types of anxiety disorders. Since then, there was one study published in 2006, six in 2008, four in 2009, six in 2012, six in 2013, thirteen in 2014, eleven in 2015, eighteen in 2016, thirty‐four in 2017, and eleven up to May 2018.

The literature search identified 627 potential records that were screened on the basis of title and abstract reading. Of these, 239 were considered eligible for full screening. At this stage, 128 studies were further excluded, leaving a sample of 111 studies, which represented the final database for the current systematic review (Figure 2 ).

DISCUSSION

To the best of our knowledge, this is the most comprehensive review systematically appraising transdiagnostic research in psychiatry. The empirical analysis revealed that the transdiagnostic literature is heterogeneous and intrinsically incoherent. The bibliometric analysis showed that, to date, transdiagnostic research has focused on a limited number of mental disorders. The conceptual analysis leveraged these findings to demonstrate that, at present, transdiagnostic research does not represent a credible paradigm shift that can impact the classification of or clinical care for mental disorders.

This systematic review provides several lines of evidence showing that transdiagnostic approaches in psychiatry are heterogeneous. For example, only three studies out of 111 qualified as being truly transdiagnostic, according to established criteria21. This empirical test demonstrates that the transdiagnostic designation is applied in a loose and unstandardized way, encompassing a number of different and often conflicting conceptualizations.

Paradoxically, some of these approaches were intrinsically incoherent and incompatible with a transdiagnostic framework, because they investigated symptoms and not disorders (across‐symptoms), a single disorder (within‐disorder) or, to the extreme, reported no diagnostic information at all (a‐diagnostic).

Furthermore, transdiagnostic studies were often characterized by methodological weaknesses. For example, the exact ICD/DSM types of mental disorders were frequently poorly defined, raising the question of how the researchers could legitimately challenge the boundaries of mental disorders, if these were not even accurately determined. In addition, the boundaries between primary and comorbid disorders in transdiagnostic literature have often been blurred. Arguably, transdiagnostic approaches have been more heterogeneous, incoherent and paid less attention to the problem of comorbidities than the DSM/ICD diagnoses that were criticized for the very same problems.

The other key methodological caveat was that transdiagnostic studies often tested several outcomes, enhancing the likelihood of type I error from data fishing expeditions. This problem was amplified by the use of arbitrary cut‐offs to measure symptom severity134, a general lack of external replication studies, and by overenthusiastic interpretations of the results. In line with these arguments, there were only a few methodologically sound studies which have been able to identify robust mechanistic transdiagnostic constructs that were causally related with the outcome of interest.

Consistent with the above limitations, most transdiagnostic studies (excluding those not properly transdiagnostic, as noted above) limited their analyses to the search for shared features across a certain set of mental disorders (across‐diagnoses). However, the bibliometric analysis revealed that these studies remained almost entirely confined within the restricted original area of interest of transdiagnostic research: anxiety and depressive disorders.

No universal transdiagnostic process has been identified, and the extent to which transdiagnostic approaches could pragmatically benefit other mental disorders and diagnostic spectra is undetermined. In fact, only a few transdiagnostic studies have eventually tested new classification systems, beyond the existing gold standard (beyond‐diagnoses).

To date, the contribution of transdiagnostic literature to the development and validation of an alternative classification system, which has genuine clinical value – and which is not a “fudge”135 – has been negligible. Notably, transdiagnostic approaches have not replaced classification systems in any other branches of clinical medicine. On the contrary, continuous (transdiagnostic) and categorical (specific‐diagnostic) dimensions frequently co‐exist in organic medicine (e.g., vascular surgery)136, as well as in psychiatry (e.g., the new DSM‐5 dimensional approach to personality disorders137). In reality, transdiagnostic studies have also produced evidence to support the existence of diagnostic categories130, 138.

It is thus apparent that future extensive research in this field is greatly needed, in particular beyond‐diagnoses studies that include several diagnostic spectra. However, a key prerequisite would be to overcome the empirical weaknesses of current transdiagnostic research. To facilitate this outcome, we propose in Table 2 some pragmatic “TRANSD”iagnostic guidelines. We hope these guidelines will improve the consistency and quality of the next generation of transdiagnostic research.

Table 2. “TRANSD”iagnostic research recommendations in psychiatry Transparent definition of the gold standard (ICD, DSM, other), including specific diagnostic types, official codes, primary vs. secondary diagnoses, diagnostic assessment interviews. Report the primary outcome of the study, the study design and the definition of the transdiagnostic construct in the abstract and main text. Appraise the conceptual framework/approach of the transdiagnostic approach: across‐diagnoses, beyond‐diagnoses, other (explain). Numerate the diagnostic categories, spectra and non‐clinical samples in which the transdiagnostic construct is being tested and then validated. Show the degree of improvement of the transdiagnostic approach against the specific diagnostic approach through specific comparative analyses. Demonstrate the generalizability of the transdiagnostic construct through external validation studies.

Transdiagnostic research is also affected by some significant conceptual weaknesses. First, it is less innovative than it often proclaims. The fundamental argument for transdiagnostic approaches is that diagnostic categories (mostly anxiety, depressive and eating disorders) are not discrete entities, because there are shared features cutting across them. However, twenty‐four years ago, when the DSM‐IV was released, an official disclaimer was added to its forefront: “there is no assumption that each category of mental disorder is a completely discrete entity with absolute boundaries dividing it from other mental disorders”139.

It has to be considered that current polythetic (i.e., based on a list of symptoms and signs believed to be characteristic140) diagnostic categories originate in prototypical descriptions containing a core structure (gestalt) of the disorder and its polysymptomatic manifestations. Accordingly, the boundaries of mental disorders, as illustrated in Figure 1, are dotted, not solid. Unfortunately, psychiatric knowledge has overlooked these issues and, over the ensuing two decades, the abstract (rather than physical) nature of DSM‐IV categories141 has been reified to the point that they are often seen as real ontological entities, discrete and demarcated from each other by distinct boundaries.

During this process, the symptoms shared by two or several mental disorders tended to be omitted from the diagnostic lists, in order to strengthen the clinical distinctiveness of the categories140. Therefore, transdiagnostic research represents more of a rediscovery of what has been forgotten from prototypical descriptions as well as the consequence of the diagnostic reification. In fact, it would make no sense to challenge the diagnostic boundaries without assuming that these do exist on some ontological level.

Second, transdiagnostic approaches are largely based on an epistemological error, which triggers an illusion of continuity142. The devaluation143 and simplification of psychopathological phenomena – introduced by recent versions of the DSM and ICD – to brief, ordinary, non‐technical lay language descriptions, has converted complex symptoms and psychic phenomena into phenomenological primitives or homogeneous elementals140. For example, there is only one kind of depressive state, one kind of anxiety, one kind of delusion, and it is assumed that all of these states share the same phenomenological structure when they are observed in different mental disorders140. Consequently, mental disorders, solely constituted by aggregates of such elementals, lose their characteristic salience, and their clinical boundaries become blurred140.

An illustrative example is provided by the use of self‐report psychometric scales that – not surprisingly – are frequently adopted in transdiagnostic research in order to reduce psychopathology to elementals. Some studies measured the severity of “a specific symptom of depression”78 in children through self‐reported lay statements such as “I am sad once in a while” , “I am sad many times” and “I am sad all the time”78. The trivialization of the contextual significance of these statements144 (there are potentially infinite reasons why one could feel sad), is associated with the deprivation of any phenomenological framework (e.g., subjective appraisal of sadness, level of insight, presence of existential despair, perception of time)145, 146. Such a simplification process transforms these statements into self‐contained atomic symptoms147, which become highly blurred and aspecific, in contrast with the claim of the authors that they are specific symptoms. This point is empirically confirmed by the fact that transdiagnostic literature frequently confounded the measurement of psychometric items in non‐clinical samples with clinical symptoms and/or established mental disorders.

Third, the highest interest and biggest clinical contribution of transdiagnostic research has been in the development of emotion‐focused cognitive behavioral therapy (CBT) protocols (e.g., the Unified Protocol58) for anxiety disorders. A recent meta‐analysis indicated that these transdiagnostic treatments lack clinical superiority compared to diagnostic‐specific treatments148.

Although these results and the Unified Protocol are presented as a breakthrough, they are again more like a rediscovery. In fact, psychotherapy was broadly transdiagnostic, driven by a psychoanalytical focus on core emotional issues (termed neurotic conflicts) until 1980, when the DSM‐III initiated a gradual splitting of psychopathology into psychiatric categories149. This led to an outpouring of CBT diagnosis‐specific protocols, which have allowed CBT to balkanize and dominate the psychotherapeutic landscape for over two decades149. In this context, some authors have interpreted the Unified Protocol as the end of the CBT‐centric dominion and as the resurgence of psychodynamic psychotherapies149.

This review has some limitations. Because of the intrinsic heterogeneity in the design, methodology and topic covered, we were unable to perform quantitative analyses. However, our main aim was to provide an extensive, detailed snapshot of transdiagnostic research and not to produce summary estimates. Furthermore, there are most probably other studies that have implicitly employed transdiagnostic approaches which have not been included in this review. However, to deconstruct the core characteristics of transdiagnostic research, we selectively focused on those studies that have explicitly acknowledged transdiagnostic approaches as their core distinctive features in their titles.

In conclusion, transdiagnostic research in psychiatry has, to date, been overenthusiastic and undercritical, heterogeneous, intrinsically incoherent and predominantly focused on a limited subset of mental disorders. It is grounded more in rediscoveries than true innovations, and it is demonstrably affected by conceptual biases. Medicine has always worked by a gradual evolutionary evidence‐based process and, before rejecting time‐tested and progressively refined concepts that are rooted in clinical tradition5, 102, a reliable and valid alternative is needed150.

To date, transdiagnostic approaches have not delivered the substantial empirical clinical “meat”135 required for them to represent a credible paradigm shift5. The risk of an acritical endorsement of transdiagnostic approaches would be to throw the baby out with the bathwater151 and be lost in a controversial102 mare magnum of diagnostic uncertainty that may be deleterious for patients and clinicians5.

Transdiagnostic research has promised (too) much to psychiatry. It is hoped that this review will guide the next generation of transdiagnostic research to complement, refine and improve – less likely to replace5, 136 – the way we currently classify and treat mental disorders.