DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences—part 2: bipolar disorders, schizophrenia spectrum disorders, anxiety disorders, obsessive-compulsive disorders, trauma- and stressor-related disorders, personality disorders, substance-related and addictive disorders, neurocognitive disorders.

Eur Arch Psychiatry Clin Neurosci DOI 10.1007/s00406-014-0521-9

ORIGINAL PAPER

DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences—part 2: bipolar disorders, schizophrenia spectrum disorders, anxiety disorders, obsessive–compulsive disorders, trauma- and stressor-related disorders, personality disorders, substance-related and addictive disorders, neurocognitive disorders Hans-Ju¨rgen Mo¨ller • Borwin Bandelow • Michael Bauer • Harald Hampel Sabine C. Herpertz • Michael Soyka • Utako B. Barnikol • Simone Lista • Emanuel Severus • Wolfgang Maier

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Received: 8 May 2014 / Accepted: 1 August 2014 Ó Springer-Verlag Berlin Heidelberg 2014

Abstract Part 1 of this paper discussed several more general aspects of Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and offered a detailed, paradigmatic analysis of changes made to the chapter on depressive disorders. This second part focusses on several other disorders, including bipolar and schizophrenia spectrum disorders. The respective changes and their possible consequences are discussed under consideration of traditional psychiatric classification, particularly from the perspective of European traditions and on the basis of a PubMed search and review papers. The general conclusion is that even seemingly small changes such as the

introduction of the mixed feature specifier can have farreaching consequences. Contrary to the original plans, DSM-5 has not radically changed to become a primarily dimensional diagnostic system but has preserved the categorical system for most disorders. The ambivalence of the respective decision-making becomes apparent from the last minute decision to change the classification of personality disorders from dimensional back to categorical. The advantages and disadvantages of the different approaches are discussed in this context. In DSM-5, only the chapter on addictive disorders has a somewhat dimensional structure. Also in contrast to the original intentions, DSM-5 has

H.-J. Mo¨ller (&) M. Soyka Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany e-mail: [email protected]

M. Soyka Private Hospital Meiringen, Meiringen, Switzerland

B. Bandelow Department of Psychiatry and Psychotherapy, University of Go¨ttingen, Go¨ttingen, Germany M. Bauer E. Severus Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universita¨t Dresden, Dresden, Germany H. Hampel S. Lista Department of Neurology, The Institute of Memory and Alzheimer’s Disease, Pitie´-Salpeˆtrie`re Hospital, Pierre and Marie Curie University, Paris, France

U. B. Barnikol Department of Stereotactic and Functional Neurosurgery, Center for Neurosurgery, Albertus Magnus University of Cologne, Cologne, Germany U. B. Barnikol Department of Child and Adolescent Psychiatry and Psychotherapy, Albertus Magnus University of Cologne, Cologne, Germany W. Maier Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany

S. C. Herpertz Department of General Psychiatry, Center for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany

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not used a more neurobiological approach to disorders by including biological markers to increase the objectivity of psychiatric diagnoses. Even in the most advanced field in terms of biomarkers, the neurocognitive disorders, the primarily symptom-based, descriptive approach has been preserved and the well-known amyloid-related and other biomarkers are not included. This is because, even after so many years of biomarker research, the results are still not considered to be robust enough to use in clinical practice. Keywords DSM-5 Categorical classification Dimensional classification

Introduction While the first part of this review paper was devoted to several general aspects of DSM-5 as well as to a paradigmatic, comprehensive description and discussion of the DSM-5 chapter on depressive disorders, this second part focuses on the description and discussion of some other relevant disorders, i.e. bipolar disorders, schizophrenia spectrum disorders, anxiety disorders, obsessive–compulsive disorders, trauma- and stressor-related disorders, personality disorders, neurocognitive disorders and substance-related and addictive disorders. The changes in the diagnostic criteria are described and discussed under several aspects, including their rationality, evidence base, usefulness and possible consequences. For example, the chapter on personality disorders analyses the advantages and disadvantages of a dimensional or categorical approach. The chapter on addiction follows a similar approach, while the chapter on neurocognitive disorders discusses paradigmatically the question of including biomarkers in DSM-5. For reasons of space, this paper does not present or discuss the DSM-5 system in detail; the interested reader is referred to the DSM-5 manual itself [2] and to detailed publications on individual chapters or disorder groups. Methods DSM-5 was compared with DSM-IV or DSM-IV-TR to identify the important changes to psychiatric diagnosis. Actual changes and their possible consequences as well as unfulfilled expectations are discussed on the basis of the traditional psychiatric classification, especially under the consideration of European traditions [74]. A PubMed search was performed for papers published in the past 20 years on the respective diagnostic categories presented in this manuscript and on the general aspects of psychiatric classification and diagnosis of mental disorders. Research

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results were analysed in detail as they relate to the classification and diagnosis of mental disorders in general and DSM-5 categories in particular. The disorder-related sections of this review were prepared by experts in the respective field. For reasons of space, the review is published in two parts. In this part, Part 2, Michael Bauer and Emanuel Severus discuss bipolar disorders; Hans-Ju¨rgen Mo¨ller, schizophrenia spectrum disorders; Borwin Bandelow, anxiety disorders, obsessive– compulsive disorders and trauma- and stressor-related disorders; Sabine Herpertz, personality disorders; Harald Hampel and Simone Lista, neurocognitive disorders; and Michael Soyka, substance-related and addictive disorders. Hans-Ju¨rgen Mo¨ller provides some concluding remarks to both Part 1 and Part 2.

Bipolar disorders In DSM-IV, mood disorders are divided into depressive disorders (‘‘unipolar depression’’), bipolar disorders and two disorders based on aetiology: mood disorder due to a general medical condition and substance-induced mood disorder. Within mood disorders, the most obvious change in DSM-5 is that bipolar disorders now have a chapter of their own, making it more apparent that bipolar disorders seem to be a separate class of disorders in terms of symptomatology, family history and genetics. Interestingly, DSM-5 places the group of bipolar and related disorders between schizophrenia spectrum and other psychotic disorders and depressive disorders, in recognition of their place as a bridge between the two diagnostic classes. In DSM-5, the group of bipolar and related disorders includes the following seven diagnostic groups: (1) bipolar I disorder, (2) bipolar II disorder, (3) cyclothymic disorder, (4) substance/medication-induced bipolar and related disorder, (5) bipolar and related disorder due to another medical condition, (6) other specified bipolar and related disorder and (7) unspecified bipolar and related disorder. Additionally, a number of specifiers can be added to the diagnosis, such as ‘‘with anxious distress’’ or ‘‘with rapid cycling’’. Overall, the diagnostic criteria for the different groups of bipolar disorders have not undergone many major changes in DSM-5. However, the few major changes may enhance the accuracy of diagnosis and facilitate earlier detection in clinical settings. They may be summarised as follows: 1.

The most fundamental change refers to criterion A for manic and hypomanic episodes. In addition to a distinct period of abnormally and persistently elevated, expansive or irritable mood, criterion A now requires


2.

3.

the simultaneous presence of ‘‘abnormally and persistently increased goal-directed activity or energy’’. In addition, these changes have to be present most of the day, nearly every day. These modifications seem very reasonable and logical specifications of the quality of the change in mood present in (hypo)mania and already described in DSM-IV-TR as ‘‘expansive’’, ‘‘with enthusiasm for interpersonal, sexual, or occupational interactions’’. Furthermore, all of the other symptoms listed under Criterion B manifest themselves with a plus in activity and energy on a behavioural level [e.g. in case of ‘‘inflated self-esteem or grandiosity’’, the individual, ‘‘despite lack of any particular experience or talent’’, ‘‘may embark on complex tasks such as writing a novel or seeking publicity for some impractical invention’’ (DSM–5)]. The fact that these changes have to be present most of the day, nearly every day, seems helpful, particularly for differential diagnosis. Hopefully, taken together, these changes will lead to increased specificity without losing sensitivity. Criterion B now has the additional specification that the respective symptoms listed, such as inflated selfesteem or grandiosity, not only have to be present to a significant degree, but also have to ‘‘represent a noticeable change from usual behaviour’’. This addition nicely emphasises that bipolar disorders are primarily a group of episodic illnesses. The DSM-IV-TR diagnosis of bipolar disorder, mixed episode, requiring that the individual simultaneously meets the full criteria for both mania and major depressive episode has been removed. Instead, a new specifier, ‘‘with mixed features’’, has been added. This specifier should now be applied to episodes of mania or hypomania when at least three depressive symptoms are present and to major depressive episodes when at least three manic or hypomanic symptoms are present but the criteria for (hypo)mania are not fulfilled [111]. This new approach takes into account that patients may present with pure mania, mania with depressive symptoms, depression with manic symptoms or pure depression. The change reflects clinical reality and meets the needs of clinicians. DSM-5 has released a model of bipolar disorders in which symptomatic presentations are seen more in terms of a continuum of a variety of symptoms. The new diagnostic criteria will be helpful because pure mania or pure depression is rarely seen in bipolar patients. As a result of this change, episodes with mixed manic or depressive features can be expected to receive more attention in the future because the mixed specifier makes it much easier than before to label patients as having mixed features. This change is hoped also to stimulate

4.

5.

research on which medication is effective in treating episodes with and without mixed features [69]. Such research is important because episodes with mixed symptoms are among the most difficult to treat (and also dangerous) states in the course of bipolar disorders. In DSM-5, concurrent use of antidepressant medication is no longer an exclusion criterion for a diagnosis of a manic or hypomanic episode [4]. The latter episodes can now also be diagnosed when they evolve during antidepressant treatment, if the episode persists at a fully syndromal level beyond the physiological effect of the antidepressant after cessation of this medication. This change is considered to be an improvement because it solves an old dilemma and a controversy among clinicians: clinicians can now assign a diagnosis of bipolar disorder to those patients who develop manic or hypomanic episodes during antidepressant treatment and who otherwise do not differ phenotypically from other patients with bipolar disorder. Furthermore, it is in line with clinical practice to stop the antidepressant if a patient presents with a hypomanic episode and see whether the symptomatology fades during the next few days or weeks (in case of fluoxetine). The new diagnostic group ‘‘other specified bipolar and related disorder’’ enables the psychiatrist to specify a particular condition, previously summarised under the diagnosis of ‘‘bipolar disorder not otherwise specified’’ (DSM-IV-TR: 296.80). As for bipolar I disorder, bipolar II disorder or cyclothymic disorder, the symptoms required to qualify for this diagnostic group must cause clinically significant distress or impairment in important areas of functioning but not meet the full criteria for any of the above-mentioned other diagnoses. One of these new categories is ‘‘short-duration hypomanic episodes (2–3 days) and major depressive episodes’’ (short-duration hypomania). According to DSM-5, the specific criteria are provided ‘‘in the hope of encouraging further study of this disorder’’. While we in general endorse this undertaking, for several reasons, we remain sceptical whether this approach will truly help to characterise a homogenous new diagnostic class, in particular with regard to response to psychopharmacological treatment. We are aware that patients with established bipolar disorders (bipolar I disorder, bipolar II disorder) will experience shortduration hypomania during the course of their illness that fully meets the symptomatic criteria but falls short of the required four consecutive days period [8]. However, the number of patients with short-duration hypomania who do not fulfil the diagnostic criteria for one of the established bipolar disorders but who will

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eventually develop bipolar I or bipolar II disorder during the course of their illness will, among other factors [117], largely depend on the way we make diagnoses in patients potentially at risk of developing a bipolar disorder. In contrast to major depression (with a major depressive episode as its defining component) or bipolar I disorder (with mania as its defining component), bipolar II disorder is typically diagnosed in the absence of the critical constituent, i.e. the hypomanic episode, at the time of diagnosis [95]. In clinical practice, the diagnosis is most often assigned to young adults presenting with a (first) major depressive episode. In these cases, diagnosis is often exclusively based on the patient’s subjective retrospective recall at a single assessment, not on current psychopathological assessment by the clinician. Unfortunately, this is also true for pivotal research studies relating to this area [5]. However, any retrospective subjective recall of an event, which may have occurred many years ago, is prone to recall bias; such bias may be even more significant during a depressive episode and when the event being recalled happened at a time in which memory problems may have been present (i.e. hypomanic episode) [34] but which quite frequently is experienced by the patient as ego-syntonic. The situation regarding ‘‘short-duration hypomania’’ has become even more complicated with DSM-5, because the requested time period for the hypomanic episode has been shortened to 2–3 days. Within a period as short as 2 days, what exactly constitutes ‘‘nearly every day’’ (the period of time the mood change has to be present, according to the criterion A for hypomania)? Is it 1 day? Or 2 days? Or is this criterion no longer to be applied? Furthermore, it is hard to refer to a 2-day period as an episode—a defining feature for bipolar disorders—in contrast to other potential differential diagnoses that might present with similar symptoms, such as borderline personality disorders [118] or ADHD [57]. Finally, given the short period of time, how can one differentiate hypomania from healthy, normal mood swings occurring in the context of almost inevitable life events such as a first kiss? While there are no easy solutions for this problem, a reasonable first step might be to make a definite diagnosis of past hypomania only if supported by concurrent information provided by significant others (criterion D for [hypo]mania). In addition, prospective, objective, continuous ambulatory monitoring of the behavioural equivalents of the symptoms defining hypomania may be a viable alternative for the future [27]. Finally, until the results of the treatment studies for this condition (i.e. short-duration hypomania) are

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available, we recommend treating this condition according to the guidelines for major depression, while keeping in mind that patients may be at risk of developing bipolar disorders [31, 95, 116].

Schizophrenia spectrum and related disorders Like in DSM-IV, in DSM-5 the chapter on schizophrenia spectrum and related disorders includes schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, delusional disorder, substance-induced psychotic disorder, psychotic disorder secondary to a general medical condition and schizotypal personality disorder. Schizotypal personality disorder does not reach the threshold for psychosis and is therefore included in the section on personality disorders. This chapter underwent several smaller, but nevertheless important changes [48] based on long and intensive discussions about deconstructing psychoses [110]. The titles of the various disorder chapters indicate that the spectrum concept has been formally applied only to schizophrenia and related disorders and not to other disorders like the affective disorders, which—against traditional thinking [65]—have been clearly differentiated into depressive disorders and bipolar disorder, as indicated by their separation into two chapters. The reasons for these differences are not obvious (see the section on depressive disorders in Part 1 of this paper, [29]). Although previous discussions tended towards including schizoaffective disorder in the chapter on affective disorders [55], it has remained in the schizophrenia spectrum chapter. The DSM-5-related publications on schizophrenia viewed it as a conglomerate of distinct diseases [104, 105]. This view is common understanding and probably also applies to most of the other disorders listed in DSM and ICD [73], even Alzheimer dementia. The basic structure of the symptom-related criteria for schizophrenia is similar to that in DSM-IV. However, two changes have been made to criterion A: (1) bizarre delusions and special auditory hallucinations are no longer given special consideration and (2) at least one of two required symptoms to meet criterion A has to be delusions, hallucinations, or disorganised thinking. The two above-mentioned symptom domains are related to Kurt Schneider’s first-rank symptoms [94]. Special auditory hallucinations refer to hallucinations characterised by a running commentary or conversing voices and are typical Schneiderian first-rank symptoms. The term ‘‘bizarre delusion’’ is not well defined. Besides a group of ideas that are clearly implausible, not understandable and not derived from ordinary life experiences, bizarre delusions


involve another group of ideas concerning control or manipulation of a person’s thoughts (thought insertion, thought withdrawal and thought broadcasting) and alien control of activities, also called passivity phenomena [96]. In traditional German/European terminology, the latter group of ideas are called ‘‘ego disturbances’’ and are seen as first-rank symptoms in the sense of Kurt Schneider. Thus, both symptom domains can be related fully or partially to Kurt Schneider’s first-rank symptoms, which play an important role in the ICD-10 criteria for schizophrenia, reflecting a tradition of German/European psychopathology. In DSM-IV, one of these symptoms was sufficient to fulfil criterion A, but this was changed in DSM-5. The subtypes of schizophrenic psychosis have been removed, mainly for the reasons of insufficient course stability. Instead of the catatonic subtype, the catatonic syndrome can be diagnosed indirectly via a respective specifier in terms of a transnosological approach, i.e. it can also be applied to other disorders like major mood disorder and bipolar disorder. In spite of intensive discussions in the forefront of DSM-5, cognitive impairment in the sense of a clearly defined neuropsychological test definition was not included and only the traditional symptom criterion of disorganised speech (e.g. frequent derailment or incoherence) was. A total duration of at least 6 months and social/occupational dysfunction are still required in DSM-5 and differentiate schizophrenia from schizophreniform disorder. In addition to the diagnostic criteria, eight symptom domains that can characterise the clinical manifestation of the disorder in individual patients are suggested for global ratings [7]: delusions, hallucinations, negative symptoms, disorganised speech, cognitive impairment, motor symptoms (e.g. catatonia), depression and mania. A respective 0–4 scale with anchor points for each of the eight items of these dimensions is described in ‘‘Bipolar disorders’’ section of DSM-5. The DSM-5 criteria for a schizophrenic disorder appear to be even shorter than those in DSM-IV, even though schizophrenia is well known to have the richest and most complicated clinical picture, at least of the mental illnesses that used to be considered as ‘‘endogenous’’. This contrasts starkly with the much more detailed description of schizophrenia in ICD-10, where criterion 1 presents a comprehensive description of different positive symptoms in the sense of first-rank symptoms that were traditionally believed to be characteristic (not pathognomonic!) for schizophrenia. DSM-5 does not use the term ‘‘bizarre delusions’’; the term was used in DSM-IV but apparently caused a lot of confusion [15]. The semantic and psychopathological relationship between ‘‘bizarre delusions’’ and ‘‘first-rank symptoms’’ is complex; Nordgaard et al. [81], Shinn et al. [96] and Cermolacce et al. [15] discussed

various conceptual and methodological issues of this relationship in detail. DSM-IV did not provide a much differentiated description of so-called characteristic symptoms of schizophrenia, but even these have been practically abandoned in DSM-5. The less differentiated phenomenological approach that was recognisable in DSM-IV [3] is clearly being continued in DSM-5, with questionable validity arguments. The requirements for specificity have been set very high for this range of symptoms (see below), whereas this does not seem to be the case for the relevant symptoms of other disorders. Not much empirical research has been performed on first-rank symptoms and bizarre delusions and most of the studies are limited in their results by more or less severe methodological problems such as differences in the definition of first-rank symptoms and bizarre delusions, in the definition of the diagnoses and in the general study design [15, 81, 96]. However, two relatively well-performed empirical studies on first-rank symptoms found twice the incidence of these symptoms in patients with schizophrenia than in patients with affective psychoses: 51 % versus 23 % [14] and 43.8 % versus 20.5 % [84]. The review by Nordgaard et al. [81] on studies published in English between 1970 and 2005 came to the general conclusion that first-rank symptoms do not seem to be specific for schizophrenia and, taking into account the variability of the results and all kind of methodological limitations, ‘‘that the reviewed studies do not allow for either a reconfirmation or a rejection of Schneider‘s first-rank symptoms’’ [81]. Consequently, the authors suggest that the concept should be ‘‘de-emphasised in the next revision of our diagnostic system’’. But does this principally reasonable suggestion mean that the concept should be abandoned completely? Why not use it as a comprehensive description without claiming specificity, instead of moving to the simplistic description used in DSM-5? Along similar lines of thinking, even delusions and hallucinations could probably be excluded, because they are also not specific and also occur in affective psychoses, for example. On the basis of a review of studies that investigated the relevance of bizarre delusions, Cermolacce et al. [15] reached a similar conclusion to Nordgaard et al. [81], although the differences in the incidence rates between schizophrenia and major depressive disorder or bipolar disorder were much higher. These authors’ critical conclusion appears rather to be based on other problems like interrater reliability. However, if we put so much emphasis on interrater reliability, should we also abandon the diagnoses of MDD and GAD, because of the extremely low interrater reliability rates in DSM-5 [90]? Or should we omit anxiety disorders and depressive disorders in general, because their symptoms are not at all specific and can be found in all kinds of mental disorders [30]? First-rank symptoms in the sense of

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special auditory hallucinations or psychotic ego disturbances as well as difficult-to-understand delusions seem to have an interesting descriptive value, despite their relatively low discriminative power and focus on phenomena that are somehow characteristic and alert the doctor to the fact that the patient is experiencing something more specific than the common phenomena of reality distortion and hallucinations. From a neurobiological perspective, these symptoms of altered experiences of the ego-environment boundaries or specific acoustic hallucinations (e.g. [20]) might be associated with specific brain localisations and circuits and thus give clues about the neurobiological background [52]. Given the above, why completely neglect first-rank symptoms instead of using them as descriptive criteria? The elimination of the subtypes of schizophrenia is understandable, because of reliability and instability problems as well as a lack of predictive value. However, these prototypes were helpful as a clinical picture and indicated among other things that schizophrenia is a mental disorder not only predominantly characterised by positive symptoms, but sometimes rather by other symptom domains. How can these subtypes now be diagnosed as schizophrenia? At first glance, the proposal to assess several symptom domains by severity ratings, described in ‘‘Bipolar disorders’’ section of the DSM-5 Manual, seems reasonable. The placement in ‘‘Bipolar disorders’’ section, however, indicates that these symptom domains are not yet fully evaluated or that these ratings are not mandatory, or both. Therefore, this approach might not really provide the information traditionally presented by the subtypes, because doctors will probably not perform these ratings. It is also questionable whether global ratings for each syndrome are sophisticated enough to allow sufficiently reliable measurement of these dimensions; for example, one should consider the difficult differentiation between depressive symptoms and negative symptoms. If this is a well-known problem with sophisticated approaches that use rating scales, how much more of a problem might this be with global severity assessments? A better approach, at least for research, would be to use a comprehensive rating scale to ensure adequate psychometric assessment of all these dimensions (for example, see [75]). For pragmatic reasons, DSM-5 did not realise a fully dimensional diagnostic system for schizophrenia in the stricter sense on the basis of differentiated rating scales, although respective suggestions have been made on the basis of a comprehensive psychopathological rating system [53, 75, 108, 109]. Although schizoaffective disorder was discussed in great detail with regard to its validity, reliability, placement in the schizophrenia or bipolar spectrum, clinical

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usefulness and prognostic implications [16, 47, 53–55, 66], it was preserved and placed in the schizophrenia spectrum chapter. Schizoaffective disorder can be seen as the bridge between schizophrenia and bipolar disorder. The primary diagnostic change is the requirement that a major mood episode has to be present for most of the duration of the disorder, making schizoaffective disorder a longitudinal diagnosis rather than a cross-sectional diagnosis, as it was in DSM-IV. This conceptualisation of schizoaffective disorder has a long tradition [55] and has been suggested for a long time by different experts [67, 74]; it appears to have increased the reliability of this diagnosis in DSM-5 [90]. Delusional disorder is clearly demarcated from psychotic variants of obsessive–compulsive disorder and body dysmorphic disorder. Patients with this clinical picture will now receive one single diagnosis, for example obsessive–compulsive disorder (OCD) with psychotic features. In this context, the question arises why there is no transnosological psychosis specifier, similar to the catatonia specifier. Apparently, such a specifier is planned for ICD-11 [32]. The proposed ‘‘attenuated psychosis syndrome’’, which has been well studied in research on the early recognition of schizophrenic psychoses [18, 68, 91, 103], was not included in the main part of DSM-5 but also in ‘‘Bipolar disorders’’ section. The placement of this concept in ‘‘Bipolar disorders’’ section means that it is believed to need further research and validation, despite the empirical evidence for a sufficiently reliable diagnosis—including evidence from the DSM-5 field studies [90]—and its high prognostic value, especially when combined with additional sMRT markers [59]. It is difficult to understand why this syndrome was not included in the chapter on the schizophrenic/psychotic spectrum, given that this syndrome describes part of the spectrum, including some psychotic symptoms (brief transient psychotic symptoms) and that in contrast, the chapter on bipolar disorder includes all kinds of subsyndromal manifestations. The general conclusion is that the schizophrenic disorders are not treated in the same way as the bipolar disorders and that there is a tendency to reduce the possibilities to diagnose a schizophrenic disorder. The bias of the DSM system in favour of the affective disorders, which was already apparent in DSM-III [87], is being continued [73]. This bias may explain why the long-term prognosis for bipolar disorder has become so unfavourable: patients have perhaps been given this diagnosis who would have been diagnosed with schizophrenia according to the more traditional criteria, e.g. patients with ‘‘mood incongruent symptoms’’, which in many studies indicate a poorer outcome [44, 74].


Anxiety disorders, obsessive–compulsive disorders and trauma- and stressor-related disorders Anxiety disorders The DSM-5 no longer requires that individuals with an anxiety disorder have to recognise that their anxiety is excessive or unreasonable. The anxiety must now be ‘‘out of proportion’’ to the actual danger the situation poses, depending on the environment and situation. This change appears to be useful. For example, in contrast to patients with other anxiety disorders who are sometimes afraid of harmless situations or objects (e.g. mice or elevators), patients with generalised anxiety disorder (GAD) often fear ‘‘real’’ dangers (e.g. traffic accidents or plane crashes), but they overestimate the statistical chance of such events happening. Although these individuals recognise that their fears are exaggerated, they would probably not admit that their anxiety is completely unreasonable. Agoraphobia, GAD, separation anxiety disorder, specific phobia and social anxiety disorder now have to be persistent, typically for 6 months or more in adults. On the one hand, this requirement may minimise overdiagnosis of transient fears; however, on the other hand, problems may arise if someone has been experiencing anxiety symptoms for only 5 months. Can such patients receive treatment, even though they do not have a codable disorder? Could health insurance companies refuse to pay for cognitive behaviour therapy for these patients, for example? Only one-month duration is required for panic disorder and selective mutism. Panic disorder DSM-IV differentiated between panic disorder with agoraphobia, panic disorder without agoraphobia and agoraphobia without a history of panic disorder. In DSM-5, panic disorder and agoraphobia are unlinked and form two diagnoses, each with separate criteria. The main reason for the separation was that a larger group of patients has agoraphobia without panic attacks. However, in two-thirds of cases of panic disorder, it co-occurs with agoraphobia; these individuals are now diagnosed as having comorbid panic disorder and agoraphobia. From a clinician’s point of view, disentangling panic and agoraphobia is not useful, because agoraphobia usually develops on average 6 months after a patient has begun experiencing panic attacks [6] as a consequence of the patients’ distorted belief that they need emergency help when having a panic attack; they start to avoid situations in which getting medical help would be impossible or embarrassing. Moreover, most patients suffer more from their panic attacks than from

their agoraphobic avoidance behaviour, with a few exceptions. It is not clear whether this change will affect treatment research, i.e. whether some trials will only include patients with panic disorder, while others will only study individuals with agoraphobia. DSM-5 removes the description of different kinds of panic attacks (limited or full panic attacks) and has just two categories—expected and unexpected. Panic attacks Because panic attacks may not only occur in panic disorder, but also in social anxiety, depressive, bipolar, impulsecontrol and substance use disorders, they can now be used as a specifier that is applicable to all DSM-5 disorders. However, there is one important difference: patients with panic disorder often do not have an explanation for their bodily symptoms and therefore develop a fear of impending death, while patients with social phobia often know why they are so afraid (for example, because they are in an examination situation) and therefore to do not feel they are going to die, which seems to make the situation easier. Agoraphobia In order to distinguish agoraphobia from specific phobias, two of five agoraphobic situations must now be endorsed (formerly only one). Generalised anxiety disorder Only minor changes have been made to the wording for GAD. While DSM-5 was being developed, suggestions were made to include additional items for avoidance behaviour and procrastination of actions (e.g. travel) perceived as potentially dangerous; however, these changes were not implemented. Social anxiety disorder The ‘‘generalised’’ specifier for social anxiety disorder has been deleted, because the requirement ‘‘fears include most social situations’’ was difficult to operationalise. Instead, DSM-5 has a ‘‘performance-only’’ specifier, which applies to individuals who have social fears only in performance situations, e.g. musicians, dancers and athletes, or in work, school and academic settings. Specific phobias Only minor changes have been made to the wording for specific phobias.

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Mixed anxiety depression

Obsessive–compulsive and related disorders

During the development of DSM-5, diagnostic criteria for a category ‘‘mixed anxiety and depression’’ were proposed. However, this category was not adopted in the final version. In ICD-10, the diagnostic category ‘‘mixed anxiety depression’’ defines patients who suffer from both anxiety and depressive symptoms of limited and equal intensity, while neither symptom is present to the extent that justifies a diagnosis if considered separately. Because of the high comorbidity between anxiety disorders and major depression, it seems justified to bring this large group of comorbid patients together under one diagnosis. However, genetic, neurobiological and treatment studies have found more differences than similarities between these diagnostic groups. Still, when both depressive and anxiety symptoms are present and severe enough to justify individual diagnoses, both diagnoses can be used (see also Part 1, subsection (3) New specifier ‘‘with anxious distress’’ in section Depressive Disorders/New diagnostic categories and specifiers [29]).

Obsessive–compulsive disorder (OCD) has been moved from the anxiety disorders to a new chapter, ‘‘Obsessive– Compulsive and Related Disorders’’. Anxiety and OCD experts had advocated this separation for many years, because OCD and the anxiety disorders have more differences than similarities in symptomatology, aetiology, genetics, neurobiology and treatment response [78, 100]. Because it was sometimes difficult to differentiate between insight and poor insight, a distinction can now be made between fair insight, poor insight and absent insight/ delusional. The chapter now also contains body dysmorphic disorder (BDD) [86], hoarding [82], trichotillomania [101] and skin-picking disorder [64]. These disorders have many obsessive–compulsive features. For example, the prevalence of BDD is elevated in first-degree individuals with OCD. Like OCD, BDD can now be diagnosed with the ‘‘absent insight/delusional’’ specifier. In DSM-IV, this condition with delusions had to be coded as ‘‘delusional disorder/somatic type’’. ‘‘Muscle dysmorphia’’ [79] is a new specifier for BDD. This condition is mostly seen in men who are preoccupied with the thought that their body is insufficiently athletic or muscular and pay excessive attention to diet. They tend to exercise and lift weights excessively, sometimes resulting in bodily damage. Hoarding disorder is characterised by difficulty discarding or parting with possessions or items that are discarded by others (e.g. newspapers, leaflets, packaging material and old clothes). A specifier is excessive acquisition of such items (e.g. by buying or stealing).

Separation anxiety disorder Separation anxiety disorder, i.e. the persistent fear that harm could come to one’s parents or other attachment figures (e.g. hijacking) or a fear of events that could lead to separation from attachment figures, has been moved from the ‘‘disorders of infancy, childhood, or adolescence’’ to the anxiety disorders. Consequently, onset no longer has to be before age 18 years. In adults, a duration of around 6 months is required, whereas the duration has to be longer than 4 weeks in children or adolescents. Attachment figures may now include the children of adults with separation anxiety disorder. While children with the disorder often refuse to go to school, adults may avoid their workplace. The extension of separation anxiety disorder to adults carries some risk that every case of marital discord associated with a fear of separation from the partner can now be diagnosed as a pathological phenomenon. Selective mutism Selective mutism has also been moved from the childhood/ adolescence section to the anxiety disorders, because a large majority of children with selective mutism were found to have anxiety. However, selective mutism is a rare disorder that usually occurs before the age of 5 years. In older children, it may be difficult to separate the disorder from ‘‘performance-only’’ social anxiety disorder on the basis of the current description [56].

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Trauma- and stressor-related disorders Post-traumatic stress disorder (PTSD) Post-traumatic stress disorder (PTSD) and acute stress disorder were moved from the anxiety disorders to a new chapter ‘‘trauma- and stressor-related disorders’’, which now contains PTSD, acute stress disorder and adjustment disorders (which had their own chapter in DSM-IV). Post-traumatic stress disorder (PTSD) criteria differ significantly from those in DSM-IV and are now stricter. It is no longer sufficient to be confronted with traumatic events occurring to others who are not family members or close friends. While it was previously possible to diagnose PTSD in persons who were only exposed while watching the news on TV to events involving death or injury of others, this possibility is now explicitly excluded in DSM5. In the case of death of a family member or friend, the


events must have been violent or accidental, i.e. the natural death of a grandmother would not fall into this category. The clearness of the new definition is important. In a large random sample of American adults, 60.7 % had been exposed to traumatic events [58]. The overly liberal definition of PTSD carried the risk of inflationary use of the term PTSD, resulting in the pathologisation of natural events. Many pension claims or actions for damages had been based on the overdiagnosis of PTSD. Acute stress disorder The criteria for acute stress disorder are also stricter in DSM-5. Adjustment disorders Adjustment disorders can be diagnosed immediately after a traumatic event; acute stress disorder can only be diagnosed 3 days to 1 month later and PTSD can be diagnosed once at least 1 month has passed since the occurrence of the event. The criteria for adjustment disorder are still written in vague language and the diagnosis can even be used for the termination of a romantic partnership or an unfulfilling sexual relationship. Adjustment disorder can be diagnosed when bereavement reactions exceed what is normally expected; in even more severe cases, the category ‘‘persistent complex bereavement disorder’’ can be used. Reactive attachment disorder and disinhibited social engagement disorder Two childhood/adolescence disorders are now included in the trauma and stressor-related disorders: ‘‘reactive attachment disorder’’ (children who show minimal social and emotional responsiveness to their caregivers) and ‘‘disinhibited social engagement disorder’’ (lack of reticence when interacting with unfamiliar adults), both of which may occur as a consequence of social neglect or deprivation. The general conclusion is that some moderate changes have been made to the three chapters anxiety disorders, obsessive–compulsive and related disorders and trauma- and stressor-related disorders; however, these changes seem unlikely to lead to relevant changes in clinical practice or research. The rationale behind some changes is not easy to understand, such as the disentangling of agoraphobia and panic disorder, while other changes, e.g. the stricter criteria for PTSD and the separation of OCD and the anxiety disorders, seem to be sensible.

Personality disorders The two approaches of classification of personality disorders in DSM-5 Within DSM-5, there are two fundamentally different approaches to the classification of personality disorders (PDs). A classification approach to PDs that is substantially unmodified from DSM-IV-TR appears in ‘‘Methods’’ section of DSM-5, while an alternative new model developed by the DSM-5 personality and personality disorders work group is presented in ‘‘Bipolar disorders’’ section. The inclusion of both models in DSM-5 reflects the decision of the APA Board of Trustees to preserve continuity with current clinical practice, while also introducing a new approach that aims to address numerous limitations of the current approach. The ‘‘Bipolar disorders’’ section of DSM-5 was integrated to reflect probable advances in the field and to encourage research for new diagnoses. Remarkably, DSM-5 has given up a multiaxial approach to diagnosing mental disorders because the former assumption of a fundamental conceptual difference between axis 1 and axis 2 disorders turned out to be not scientifically reasoned. The current approach in ‘‘Methods’’ section keeps to the categorical classification of ten diagnostic entities based on polythetic criteria lists and subsumes only a limited number of minor changes that grammatically sharpen the formulations of well-known diagnostic criteria. This approach has been criticised for producing extensive co-occurrence, high heterogeneity among patients receiving the same diagnosis, low convergent validity indicating a lack of clarity in operationalising the criteria and temporal instability despite the relative stability of personality traits. Furthermore, the DSM-IV approach is found to be of limited clinical usefulness as the rest category of ‘‘Personality Disorder not otherwise specified’’ is the most frequently diagnosed PD in clinical practice [77].

The alternative DSM-5 model for the classification of personality disorders in DSM-5 The major focus of the ‘‘Alternative DSM-5 Model for Personality Disorders’’ is a categorical-dimensional hybrid model of PDs. It introduces a dimensional model to the assessment and understanding of PDs in addition to preserving a limited number of categories with a sufficient empirical basis, which are thought to be still needed by clinicians educated in the medical diagnostic model. It can be applied not only to patients with pathological personalities but also to all patients beyond a defined diagnostic

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threshold. According to this alternative model, the general criteria of a personality disorder are as follows: (A) (B) (C)

(D)

(E)

(F)

(G)

Moderate impairment or greater in personality (self/ interpersonal) functioning. One or more pathological personality traits. The impairments in personality functioning and personality trait expression are relatively inflexible and pervasive across a broad range of personal and social situations. The impairments in personality functioning and the individual’s personality trait expression are relatively stable across time with onsets that can be traced back to at least adolescence or early adulthood. The impairments in personality functioning and the individual’s personality trait expression are not better explained by another mental disorder. The impairments in personality functioning and the individual’s personality trait expression are not solely attributable to the physiological effects of a substance or another medical condition (e.g. severe head trauma). The impairments in personality functioning and the individual’s personality trait expression are not better understood as normal for an individual’s developmental stage or sociocultural environment.

The number of diagnostic categories has been markedly reduced from ten to six types. Criteria for being preserved as a diagnostic category were as follows: significant prevalence in the general population as well as in clinical settings, high clinical or forensic significance, relationship to other mental disorders, specificity of symptomatology, construct validity, neurobiological correlates, as well as the availability of evidence-based treatments [98]. On the basis of these criteria, the following PDs have been included in the alternative model: antisocial PD, borderline PD, schizotypal PD, anxious/avoidant PD, obsessive–compulsive PD and narcissistic PD. In addition, this approach includes the diagnosis of personality disorder-trait specified (PD-TS), which can be made when a PD is considered present without the patient meeting the diagnostic criteria for a specific disorder. The PD-TS diagnosis is operationalised by the level of personality dysfunction and pathological personality traits on at least one pathological trait domain. The dimensional approach requires two determinations: (1) an assessment of the level of impairment in personality functioning concerning disturbance in self and interpersonal functioning, which should be at least moderate and (2) an assessment of pathological personality trait domains and trait facets. Pathological personality traits are organised into five broad domains: negative affectivity,

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detachment, antagonism, disinhibition and psychoticism as well as 25 specific trait facets (emotional liability, anxiousness, separation insecurity, submissiveness, hostility, perseveration, depressivity, suspiciousness, restricted affectivity, withdrawal, intimacy avoidance, anhedonia, manipulativeness, deceitfulness, grandiosity, attention seeking, callousness, irresponsibility, impulsivity, distractibility, risk taking, rigid perfectionism, unusual beliefs and experiences, eccentricity and cognitive and perceptual dysregulation). The selection of these trait domains and trait facets has been criticised for neglecting accumulated evidence on the structure of normal and disordered personality in the form of the Big Five and Five-Factor models [63, 89]; interestingly, an empirical study supports the hypothesis that the five domains of the DSM-5 dimensional model explain the covariance among the 25 trait facets [107] and demonstrates that they are maladaptive variants of the Big Five, including the domain of psychoticism [35]. The trait domains were intended to be more closely conceptualised according to psychopathology compared to the Big Five, whose factorial structure was studied in the normal population. All trait facets have been chosen with regard to their clinical relevance and exist on a spectrum with two opposing poles. They are operationalised in the Personality Inventory for DSM-5 (PID-5) with a self-report form for patients and an informant-report form [60]. The PID-5 can also be used for a clinical screening option based only on the assessment of domains, while a detailed portrait of a patient’s personality requires the assessment of all 25 facets of the personality trait model based on both self and informant reports. Disturbances in self and interpersonal functioning constitute the core of personality psychopathology [9] and are assessed continuously by means of a five-point global rating (healthy, adaptive functioning [level 0]; some [level 1], moderate [level 2], severe [level 3] and extreme [level 4] impairment) on the Level of Personality Functioning Scale. The Level of Personality Functioning Scale has significant and substantial validity correlations with other measures of personality pathology and with clinical judgments regarding functioning, risk, prognosis and optimal treatment intensity [76, 93]. Self-functioning subsumes identity (does a person experience him- or herself as unique, with distinct boundaries between self and others and the capability to regulate his or her own emotional experiences?) and self-direction (how is a person able to flexibly pursue goals in life and reflect internal standards of behaviour?); interpersonal functioning involves empathy (is a person able to take and appreciate the perspectives of others?) and intimacy (is a person able to form close and stable relationships?). General personality dysfunction and specific personality traits have been shown to be clearly distinct components of personality [10] and the level of


personality functioning is strongly associated with prognosis and outcome of psychiatric patients. The proposed Levels of Personality Functioning are currently being subjected to extensive empirical testing in the DSM-5 field trials. As yet, no interviews are available to reliably assess the levels of personality functioning. Interestingly, the Operationalised Psychodynamic Diagnosis (OPD) system [83] has been recommended as a useful tool for the assessment of the Levels of Personality Functioning [119]. The alternative model demonstrated using the example of borderline personality disorder Patients with borderline personality disorder (BPD) present with at least moderate impairment in personality functioning, manifesting in two out of four areas of functioning (identity, self-direction, empathy and intimacy), and they show at least four out of seven pathological personality traits: emotional lability, anxiousness, separation insecurity, depressivity, impulsivity, risk taking and hostility. Impulsivity, risk taking or hostility should be among the personality traits present in the patient. The selection of these traits is empirically deduced and differs from the DSM-IV criteria in some significant aspects; for example anxiousness, depressivity and fears of rejection. The integration of depressivity into the concept of BPD can be expected to decrease the amount of co-occurrence with mood disorders, with likely implications for treatment strategies. A decrease in comorbid diagnoses of depression may result in a reduction in the prescription of antidepressants, which have frequently been administered to BPD patients without sufficient empirical evidence of efficacy [49, 62]. Comments Despite its limitations, the alternative categorical-dimensional hybrid model could have been the right answer to the current state of research, as it maintains the PD types that represent the evolved knowledge on the clinically most relevant problems and at the same time opens up the opportunity for a new approach that addresses the major shortcomings of this tradition. The alternative model overcomes the scientifically unsubstantiated separation between normal and pathological personalities, eliminates the neither scientifically nor practically reasonable assignment of multiple PD diagnoses to an individual patient and is based on a better empirical foundation of the diagnostic criteria. The dimensional trait concept is likely to provide advantages for neurobiological research, as traits are more likely to be associated with brain dysfunctions than the highly heterogeneous categorical PD entities known to result in inconsistencies of data. The alternative

dimensional approach also holds benefits for clinical practice, as multidimensional configurations allow a detailed profile of traits characteristic of a specific patient to be provided and appears to be less stigmatising and more helpful for explaining diagnosis to patients. Particularly, the assessment of levels of personality functioning could be the right response to longitudinal data indicating high persistence of malfunctioning despite low stability of categorical diagnoses (e.g. [36]), meaning that a trait-based approach may be more helpful to select appropriate treatment interventions and to be a valid indicator of treatment response. The main problem with the new approach lies in the limited empirical basis concerning reliability, as the large field trials on test–retest reliability are still underway. Thus, the question of practicability and feasibility cannot yet be answered. Undoubtedly, dimensional models are unfamiliar to clinicians trained in the medical model of categorical diagnoses, where a single diagnostic entity is used to communicate a large amount of clinical information including not only the patient’s problems but also the related treatment needed [97]. The alternative approach of a dimensional classification in addition to the evaluation of six types is more time-consuming, as a comprehensive PD diagnosis requires clinicians´ ratings on 25 trait dimensions in addition to the ratings of personality dysfunction on a further four dimensions. The hybrid model tries to heighten clinical practicability by allowing clinicians to confine diagnosis to the assessment of five trait domains besides ratings of personality dysfunction depending on limitations on time, information and expertise. Furthermore, we have no sufficient database regarding what may be the clinical implications of a rather low threshold for the diagnosis of a personality disorder, i.e. as defined as the main general criterion (A) ‘‘moderate or greater impairment in personality (self/interpersonal) functioning’’ instead of a higher threshold of ‘‘significant impairment’’ as proposed in an earlier version of DSM-5 (also compare [93]). Further criticisms relate to the criteria applied for the selection of six PD categories, with some doubts about the rationale for reintroducing the narcissistic PD, because of heterogeneous symptomatology and low clinical salience. Livesley [63] has recently questioned the conceptual coherence of the model of juxtaposing six categorical types and five-dimensional domains and rather fears that confusion will arise with regard to how to reconcile typal and dimensional diagnoses applied to the same individual. Although the DSM-5 work group has done a great deal of work over many years, the time did not seem to be ripe for a fundamental change in classifying personality disorders. The time until the publication of DSM 5.1 is needed to enhance empirical evidence for the practicability and feasibility of the alternative model. A pervasive,

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theoretically based and empirically grounded dimensional approach to classifying personality disorders is the more fruitful as it would bring benefit to the classification of mental disorders in general and would thus contribute to facing the major challenge of psychiatry, namely that adhering to the categorical structure of classification in the long run will hinder progress in the investigation of the aetiology of psychiatric disorders.

Neurocognitive disorders The DSM-5 chapter on neurocognitive disorders includes the main groups delirium (the criteria for which have been modified), major neurocognitive disorder (i.e. dementia) and mild neurocognitive disorder (a new category) [33]. The distinction between major and minor neurocognitive disorders is primarily one of severity and may correspond in most progressive disorders with earlier and later stages of the disease [11]. In particular, the DSM-5 proposes a reclassification of dementia and mild cognitive impairment (MCI). The new classification has been introduced to operationalise and distinguish distinct disease aetiologies, such as Alzheimer’s disease (AD), from psychiatric disorders exhibiting cognitive impairment as a symptom or syndrome rather than a defining characteristic hallmark, including schizophrenia or depression. Furthermore, amendments to this section originate from psychiatrists’ aspirations to move from the phenomenological descriptive and categorical paradigm to disease dimensions that better reflect the emerging biological disease concepts and to harmonise the field of cognitive disorders and to integrate with the novel diagnostic guidelines for dementia. In the updated manual, the term ‘‘dementia’’ is redefined as a ‘‘neurocognitive disorder’’ (NCD). This section is mainly characterised by three syndromal diagnoses: ‘‘mild neurocognitive disorder’’ (mild NCD), ‘‘major neurocognitive disorder’’ (major NCD) and ‘‘delirium’’. Since the word dementia derives from the Latin word for ‘‘mad’’ or ‘‘insane’’ (from de‘‘without’’ ? ment, the root of ‘‘mind’’), the introduction of the term neurocognitive disorder is also assumed to help decrease the stigma related to both the word dementia and the conditions that it refers to. However, owing to the term’s long medical history and its familiarity among clinicians and patients, the APA and the new DSM acknowledge the traditional syndromal term dementia as an acceptable alternative to the newly proposed, more descriptive and neutral dimension of (major) neurocognitive disorder [102]. Importantly, besides AD, DSM-5 recognises an array of distinct aetiological subtypes underlying neurocognitive dysfunction, such as vascular disease, Lewy body disease, HIV infection and Parkinson’s

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disease. In addition, each subgroup can be further differentiated dimensionally by the degree of clinical severity, namely into mild or major degrees of cognitive impairment (following the validated research definitions and potential continua of mild cognitive impairment [MCI] and mild-tosevere AD dementia), ‘‘major’’ being especially attributed to the clinically evolving disease impact on the activities of daily living, such as the inability to autonomously perform activities of daily living (ADLs) [102]. Specifically, according to the novel operational criteria proposed in DSM-5, probable vascular NCD is diagnosed if (1) clinical criteria are supported by additional structural neuroimaging evidence of significant parenchymal injury ascribed to cerebrovascular disease or (2) the neurocognitive syndrome is temporally related to one or more documented cerebrovascular events or (3) there is both clinical and genetic evidence of cerebrovascular disease such as, for instance, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Possible vascular NCD is detected if clinical criteria are met but neuroimaging assessment is not obtainable and the temporal link between the neurocognitive syndrome and one or more cerebrovascular events is not documented. DSM-5 emphasises the subdivision of the NCD category into major and mild NCD. Although these novel terms are expected to be employed by central health care professionals and organisations, not all care specialists are likely to make use of them. For instance, the Alzheimer’s Association (AA) presently uses the terms mild cognitive impairment and dementia, the National Institute on Aging– Alzheimer’s Association (NIA-AA guideline) Working Group uses the graded terms of (amnestic or non-amnestic) mild cognitive impairment (due to AD with a graded risk level) and dementia (due to AD with a graded risk level) and the International (AD guideline) Working Group (IWG) uses the terms prodromal AD (of the hippocampal type) and AD dementia. The existing heterogeneity in both clinical as well as research definitions calls for a continued conceptual discussion based on the existing evidence and a global harmonisation effort. The introduction of a clinical syndromal continuum commencing with mild NCD is considered the crucial change in the NCD diagnostic criteria in DSM-5 [11]. There is a coherent explanation from a clinical viewpoint for integrating mild NCD, or what has been described in the literature most frequently as MCI [85], into the diagnostic classifications. Individuals in later life frequently need therapeutic assessment for neurocognitive symptoms that are not developed and severe enough to be categorised as a major NCD or dementia, but are significantly disturbing. Therefore, these subjects are at higher risk to experience progressive cognitive and behavioural problems over time than those without mild NCD [11]. To categorise


patients at milder and earlier clinical stages is relevant. Practically, the awareness of the field is that we need to accurately identify disease-affected patients earlier—particularly, once an effective pharmacological treatment is approved (there is cautious optimism that this will be achieved during the next 10 years, given the large AD drug development pipeline that is marching through clinical trials) that may substantially delay or reverse the development of the NCD (using disease modifiers)—the time for intervention will be as early as possible during the progression of the clinical course (or even before any clinical signs and symptoms appear), whatever the pathophysiology and aetiology [11, 41, 42]. Despite the dimensional approach integrating early clinical stages and operationalising aetiological categories, the neurocognitive disorders section (as most of the DSM-5 sections) still implements no positive diagnostic biological information (biomarkers). It still relies traditionally and exclusively on descriptive phenomenology, clinical signs and symptoms and a diagnosis of exclusion. In view of the large body of evolved evidence since the last revision, this appears to be a key limitation of the new revision. The development of indicative biomarkers for early detection, diagnosis, prediction and prognosis of AD dementia, as well as for mild cognitive impairment, appears to be have substantially matured and provides sufficient evidence of core feasible validated candidates derived from modalities such as structural MRI and positron emission tomography (PET) imaging as well as from cerebrospinal fluid (CSF) analysis. Biomarkers are expected to designate a consistent and objective (measurable) approach to identifying underlying AD and other aetiologies of dementia even before cognitive and/or behavioural symptoms arise. Biomarkers have been validated in large-scale controlled international multicentre clinical trials for their performance at the MCI and AD dementia stages (applicable to the corresponding mild NCD and major NCD stages). This is of paramount importance, because AD could be successfully managed and treated if safe and effective therapies are disclosed that halt the evolution of the disease at the mild NCD, MCI and early dementia phase [11], i.e. before various molecular mechanisms potentially converge downstream into the irreversible neurodegenerative pathway resulting in irreversible morphological, metabolic and functional alterations (such as substantial regional cell death and decompensatory cognitive neural network breakdown), typically characterising the pathophysiology and the biological substrate of cognitive and behavioural symptoms during the late-stage AD dementia syndrome or the major neurocognitive disorder stage [42]. Currently, several promising areas of clinical research are working towards establishing and validating reliable biomarkers for AD with certain strands that are undergoing

transfer into clinical practice through specialised expert centres. The status of the development and validation of multimodal core biomarkers, including neurochemistry [12, 37, 43], neurogenetic [39, 115] and structural/functional/metabolic neuroimaging [26, 106] investigations, has been recently summarised in major invited systematic state of the art and perspective reviews [21, 40–42], also providing the integrating viewpoints of academic, industry stakeholders and regulatory bodies [38] on the AD biomarker discovery and development area. However, more comprehensive biomarker investigations that better explicate the mechanisms of the disease at the early stage are undoubtedly needed. This aspect has been emphasised by the integration of biomarkers, including those from neuroimaging modalities, in the most relevant international guidelines for the diagnostic criteria of AD, such as the European Federation of Neurological Societies (EFNS) guidelines on the diagnosis and management of AD [50, 112], the recent revisions proposed by the IWG for new research criteria for the diagnosis of AD [22, 23] and those from the NIA-AA [1, 70, 99]. As a consequence of the proposals of the IWG and the NIA-AA working groups, two major categories of biomarkers have been delineated with roles in diagnosis and prediction: (I) those indicators of disease state—namely biomarkers of amyloid beta (Ab) accumulation represented by anomalous (i.e. increased) tracer retention on amyloid PET imaging and anomalous (i.e. low) CSF levels of Ab1-42; and (II) those indicators of disease stage—namely biomarkers of neuronal injury represented by grown CSF levels of total tau or phosphorylated-tau, reduced fluorine18 (18F)-2-fluoro-2-deoxy-D-glucose (FDG) uptake on PET in the temporoparietal cortex and atrophy on structural MRI in a well-defined topographical pattern including medial temporal lobes and parietal cortices [19, 92]. Interestingly, the above-reported core feasible biomarkers are reported to appear decades to years before the onset of the clinical signs of an NCD (due to AD). In the light of this, a combination of symptoms of a mild NCD and biomarkers is hypothesised to significantly support the aetiological risk assessment and the increased probability that a mild NCD will in fact advance to a major NCD [11, 85]. Despite accumulating diagnostic or risk-enhancing biomarker evidence and maturity of validation, as integrated in the EFNS 2010 [50] or other clinical guidelines for the diagnosis of dementia and AD and although the conception of a clinically relevant diagnosis and treatment is increasingly moved backwards and upstream in the disease process of NCDs, Blazer notes for the DSM-5 that a reliable sensitive and specific biomarker still needs to be discovered, just as a definitive treatment for most NCDs has not been found [11].

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In summary, while the new DSM-5 section on cognitive disorders significantly differs conceptually from the corresponding DSM-IV section (and after many years of research progress have passed since the last revision), clinicians may practically draw little practical diagnostic innovation from the manual and therefore may barely change how they diagnose AD and other cognitive disorders. Like most of the DSM-5 sections, the NCDs section still requires no biological support criteria for the risk assessment and diagnosis but relies exclusively on descriptive clinical phenomenology, such as signs and symptoms. This is disappointing and appears to be a major practical shortcoming. A future revision should strongly consider that over the years, conditions like mild NCD will greatly benefit from the application of supportive diagnostic and risk biomarkers. Since revisions have taken years to decades to develop into a next evolutionary step, the missing integration of core, feasible validated biomarker candidates, such as fully automated or visual MRIbased hippocampal assessment or analysis of CSF Ab, total tau and phospho-tau measurements and, perhaps, an amyloid PET tracer as supportive tools with a specific evidence-based recommendation grading as in the EFNS guidelines seems to be a missed opportunity. Of note, additional specific markers might be disclosed that can help distinguish between specific subtypes. Moreover, despite considerable progress, neurogenetic markers, particularly the apolipoprotein e4, cannot yet be used as clinically meaningful diagnostic biomarkers because it is considered only a risk factor and, therefore, neither necessary nor sufficient for the occurrence of the underlying disease. The time will come, however, in which genetic and biomarker guidance and screening will be widely introduced into all existing clinical dementia, NCD or AD criteria, even embracing the new era of disease detection in completely asymptomatic or presymptomatic patients suffering from a chronically progressing neurodegenerative disease. This seems more than necessary, since in the upcoming decades, the world is facing the major health care epidemic of agerelated neurodegenerative diseases, primarily with catastrophically increasing numbers of AD patients.

Substance-related and addictive disorders The concepts of addictive disorders as (medical) diseases or disorders have emerged over time. In 1977, an expert work group proposed differentiating between dependence and substance use-related disorders [25, 113] and this notion was later adopted by ICD and DSM. This distinction was clinically relevant and widely accepted by clinicians. DSM-5 now puts forward some important, probably controversial and in part dramatic changes. Some of the most

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relevant changes and aspects will be discussed in brief below. First, 11 substance use categories are now defined and include for the first time a non-substance-related, behavioural disorder, namely gambling disorder. Other so-called behavioural addictions such as pathological Internet use, sex addiction, excessive food consumption or others are not yet included, but DSM-5 has opened the door for these ‘‘novel’’ behavioural addictions. Second and probably even more important, DSM-5 has given up the long-standing categorical distinction between abuse (or harmful use) and dependence and adopted a dimensional concept. Substance use disorders are defined by a problematic pattern of substance use leading to clinically significant impairment in different domains. Modern psychiatric classification systems such as ICD-10 and DSM-IV define substance use disorders as a cluster of physical and psychological symptoms and the social consequences of substance use. DSM-5 specifies 11 symptoms; the presence of 2–3 symptoms indicates a mild disorder, 4–5 a moderate one and six or more a severe disorder. In contrast, the ICD-10 diagnosis criteria for alcohol dependence require three of the following six symptoms: (1) a strong desire or compulsion to drink, (2) tolerance, (3) withdrawal, (4) loss of control, (5) progressive neglect of alternative activities and (6) persistent drinking despite Table 1 Overview of DSM-IV and DSM-5 criteria for ‘‘substance abuse’’, ‘‘dependence’’ and ‘‘substance use disorder’’ using the example of alcohol DSM-IV

DSM-5

Substance abuse

Dependence

Substance use disorder

Neglect of responsibilities Alcohol use despite physical risks

X X

– –

X X

Alcohol use despite psychosocial problems

X

–

X

Alcohol use despite problems with the police or legal problems

X

–

–

Development of tolerance

–

X

X

Withdrawal symptoms

–

X

X

Reduced control

–

X

X

Compulsive drinking

–

X

X

Great deal of time spent in obtaining alcohol

–

X

X

Neglect of other activities

–

X

X

Use despite knowledge about negative consequences

–

X

X

Craving

–

–

X


evidence of harm. For a DSM-IV diagnosis of dependence, three out of seven criteria (rather than six as in ICD-10) had to be present for the past 12 months (see Table 1). Third, valid measurement requires adequate reliability. In DSM-IV, the reliability for alcohol dependence was good to excellent, with kappa values of 0.62–0.82, but lower for abuse [45]. In the DSM-5 field trial, the reliability of alcohol use disorder was much lower (kappa = 0.40 [90]). There may be different explanations for this finding [46], but at present, reliability does not seem very satisfactory. Differences were also found between the DSM-IV and ICD-10 definitions, but the kappa value was 0.67 [13]. Differences between DSM-5 and the forthcoming ICD-11 may be much lower. Various field studies have evaluated congruities and differences for the DSM-IV diagnoses dependence and substance use and the DSM-5 diagnosis substance use disorder. Compton et al. [17] found an optimal agreement between the DSM-IV term dependence and the DSM-5 term substance use disorder for alcohol dependence (n = 23,013), cocaine (n = 271), or opioids (n = 264) when four or more criteria were fulfilled. The highest possible agreement between cocaine dependence (n = 1,622) according to DSM-IV and severe cannabis substance use disorder was achieved when six or more criteria of the substance use disorder for cannabis were fulfilled [17]. Proctor et al. [88] studied the compatibility of cocaine substance use disorder diagnosed according to DSM-IV and DSM-5 in n = 6,871 prisoners. They found a 12-month prevalence rate of 12.7 % according to DSM-IV (substance abuse: 3.8 %; dependence: 8.9 %). A total of 11.0 % of the patients fulfilled the DSM-5 criteria of a cocaine substance use disorder (1.7 % fulfilled the criteria for a moderate substance use disorder, 9.3 % those for a severe substance use disorder). Thus, the prevalence rate and diagnostic classification of the planned DSM-5 criteria for a cocaine substance use disorder agreed very closely with those of the DSM-IV criteria [88]. In a twin study, Edwards et al. [24] found that the prevalence of alcohol use disorder was slightly higher than when diagnosed as alcohol abuse and alcohol dependence according to DSMIV. They also found that individuals who fulfilled either only the DSM-IV criteria or only the DSM-5 criteria had fewer comorbid disorders than those who fulfilled the diagnostic criteria of both systems. People who fulfilled only DSM-5 criteria were less severely ill than those who fulfilled only the DSM-IV criteria [24]. Fourth, what does severity of addiction mean? In DSM5, substance use disorders can be subtyped into mild, moderate, or severe according to the number of symptoms present. Substance research has a long history and extensive research has been performed on treatment outcome

and related predictors. No uniform, generally accepted definition of severity exists. DSM-5 still does not use the amount and dosage of drugs taken, biological parameters, or the individual treatment history to define a certain severity of phenotype. In most studies, prognostic factors are onset and length of substance use, psychiatric comorbidity, history of suicide attempts, previous treatments and related items; these are not reflected by the DSM-5 items. By definition, a long-term, treatment-resistant alcoholic blue collar worker with multiple treatments and a lifethreatening liver cirrhosis who otherwise has a good level of social functioning and experiences little craving and few psychological problems may meet DSM-5 items 1, 2, 9 and 10 while an otherwise physically healthy, treatment-naı¨ve binge-drinking alcoholic worker who has lost his job, wife and driving licence and has financial problems, strong craving and increased alcohol tolerance may meet items 1, 2, 3, 4, 5, 6, 7, 8 and 9 and possibly even 10 and 11—but who is the more severely affected patient? The first patient is facing death in the near future, while the second is experiencing all the psychological and social sequelae of alcoholism but will survive and may be motivated for therapy. The need for classifying the severity of substance use disorders is obvious, but the individual history may be more predictive—and informative—than counting symptoms which, for example craving, may depend greatly on the individual situation. Fifth, emerging conflicts between DSM-5 and ICD-11 are apparent. The 11th version of the International Classification of Diseases (ICD-11) is due to be published in 2017 [114]. According to valid sources, ICD-11 will retain the categorical distinction into harmful use and dependence. This is a nightmare scenario, at least for those active in the substance research arena, because it will become more difficult to compare studies and will be the opposite of the previously hoped for harmonisation between the two systems [28]. Sixth, what does this mean for substance use therapy? While many addiction specialists will probably welcome the inclusion of gambling disorders in the substance use categories, clinicians will wonder about treatment goals. For many decades, abstinence was the primary treatment goal for people dependent on alcohol or other drugs. Harm reduction strategies were second-line options, at least for alcoholism, but are experiencing some revival [80]. What will now be recommended for substance use disorders? Abstinence only for ‘‘severe’’ forms of substance use— whatever this means? Or for all forms? Or ‘‘dimensional’’, stepped care interventions according to the dimensional concept? Clinical research will have to ask these questions—and hopefully find answers to them.

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Conclusion The new edition of the Diagnostic and Statistical Manual of Mental Disorders, DSM-5, brings substantial, if not dramatic changes in the definition of substance-related and addictive disorders. The terms dependence and misuse or abuse have been replaced by the term substance use disorder. Eleven diagnostic criteria are given and only craving is included as a new symptom. The presence of 2–3 symptoms indicates a mild disorder, 4–5 a moderate one and six or more a severe disorder. Pathological gambling is included in DSM-5 as the first behavioural disorder not related to substance use. The imposed changes will have significant consequences for the diagnosis, therapy and research of substance-related and addictive disorders. The leading diagnosis standards DSM and International Classification of Diseases (ICD-10 and its forthcoming revision ICD-11) will probably drift further apart. Emerging problems and possible implications of DSM-5 are discussed are obvious taking alcohol use disorders, the most important substance-related disorder, as an example.

Concluding remarks The final version of DSM-5 is definitely not as bad as a lot of critical comments would like to suggest. Many experts are disappointed that several of the objectives were not achieved, including a change from a categorical system to a dimensional one, increased validity—for example because of a stronger biological foundation—and improved interrater reliability. However, these objectives may have been too far-reaching from the beginning [71] (see also [29]). The apparent abandonment of traditional thinking and several traditional concepts, as was the case also in DSMIII and DSM-IV, seems to be another problem, particularly in the schizophrenia chapter. This development might be seen as painful particularly from the perspective of traditional German-language and European psychiatry and their sophisticated phenomenological approaches [72]. DSM-IV was already criticised for abandoning differentiated psychopathological views [3] and DSM-5 obviously continues to follow this path, at least in some diagnostic entities such as schizophrenia. The question whether this development is always fully evidence-based seems unclear, as mentioned above in the discussion of the schizophrenia chapter. The fact that many other expectations were not fulfilled, including a classification based more on neurobiology or at least including biomarkers as part of the diagnostic criteria [51, 61], gives a realistic picture of the limitations of our current knowledge [74]. However, the respective experts would have appreciated more support for the inclusion of biological markers, especially in the chapter on

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neurocognitive disorders, among other reasons to act as a bridge between psychiatry and neurology. The originally planned, rather radical changes to the diagnosis system, especially in the direction of a primarily dimensional system, were not made because ultimately both the DSM-5 consortium and outside experts considered them to be premature as a general approach. The respective discussion in the chapters on personality and addictive disorders analyses the kind of problems related to this approach. While a dimensional approach has been adopted to a certain degree in the diagnosis of addiction, in the end, the well-prepared dimensional approach to the diagnosis of personality disorders was published only in ‘‘Bipolar disorders’’ section of DSM-5 as a tool for further research. Consequently, the DSM-IV system was largely preserved: the traditional diagnostic framework for psychoses was essentially maintained, while relevant changes were made primarily in the field of affective disorders and other categories. Several examples are described in both parts of this paper. In this context, it must be stressed that even presumably subtle changes can have huge consequences, for example the change to the distinction between unipolar and bipolar depression, which will have strong impact on the psychopharmacological treatment for these disorders. Apart from these differentiations, however, the main categories of medication treatment have been preserved and some new ones have even been added, for example premenstrual dysphoric syndrome. Acknowledgments The authors thank Jacquie Klesing, Board-certified Editor in the Life Sciences (ELS), for editing assistance with the manuscript. Conflict of interest H.H. is supported by the AXA Research Fund (AXA RF) and the Fondation pour la Recherche sur Alzheimer (FRA), Paris, France. All other authors have no conflict of interests to declare.

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