Towards a new model and classification of mood disorders based on risk resilience, neuro-affective toxicity, staging, and phenome features using the nomothetic network psychiatry approach.

Current diagnoses of mood disorders are not cross validated. The aim of the current paper is to explain how machine learning techniques can be used to a) construct a model which ensembles risk/resilience (R/R), adverse outcome pathways (AOPs), staging, and the phenome of mood disorders, and b) disclose new classes based on these feature sets. This study was conducted using data of 67 healthy controls and 105 mood disordered patients. The R/R ratio, assessed as a combination of the paraoxonase 1 (PON1) gene, PON1 enzymatic activity, and early life time trauma (ELT), predicted the high-density lipoprotein cholesterol - paraoxonase 1 complex (HDL-PON1), reactive oxygen and nitrogen species (RONS), nitro-oxidative stress toxicity (NOSTOX), staging (number of depression and hypomanic episodes and suicidal attempts), and phenome (the Hamilton Depression and Anxiety scores and the Clinical Global Impression; current suicidal ideation; quality of life and disability measurements) scores. Partial Least Squares pathway analysis showed that 44.2% of the variance in the phenome was explained by ELT, RONS/NOSTOX, and staging scores. Cluster analysis conducted on all those feature sets discovered two distinct patient clusters, namely 69.5% of the patients were allocated to a class with high R/R, RONS/NOSTOX, staging, and phenome scores, and 30.5% to a class with increased staging and phenome scores. This classification cut across the bipolar (BP1/BP2) and major depression disorder classification and was more distinctive than the latter classifications. We constructed a nomothetic network model which reunited all features of mood disorders into a mechanistically transdiagnostic model.

Stress and mood of adults with moyamoya disease: A cross-sectional study.

Moyamoya disease in adults is a chronic, progressive disorder characterized by fine collateral vessel networks in the brain. The disorder can lead to negative mood and stress, which, left unresolved, may increase adverse health outcomes. We conducted a cross-sectional survey to examine stress and mood of adults with moyamoya disease. Participants were recruited at a university hospital in Seoul, Korea. Data were collected through questionnaires and review of participants' electronic medical records. A total of 109 adults participated. Significant correlations were found between perceived stress, anxiety, and depression. Adults with moyamoya disease experience anxiety, depression, and stress related to the risk of cerebral hemorrhage or ischemia, similar to those with other cerebrovascular disease. If negative mood and stress were uncontrolled, those can cuase adverse health outcomes. Health professionals caring for people with moyamoya disease should carefully observe their stress and mood and develop interventions tailored to stages of disease to help them manage. The study results provide baseline information for understanding the level of, and the factors associated with, stress and mood.

The Effects of Casual Videogames on Anxiety, Depression, Stress, and Low Mood: A Systematic Review.

Background: Despite the variety of available treatments for mental health symptoms, many individuals do not engage with treatment and among those who do, dropout rates are often high. Therefore, providing alternative opportunities to access treatment is imperative. Research interest in the therapeutic effects of digital mental health initiatives and serious games has grown in recent years, but the potential of simple, easy-to-use casual videogames (CVGs) that can be played in short bursts of time has seldom been considered. Objective: The objective of the present study is to provide a systematic review of the literature examining the effects of CVGs on treating anxiety, depression, stress, and low mood. Method: A systematic search was conducted, using the terms (casual gam* or casual videogam* or mini gam* or minigam* or mini-gam* or gamif*) and (mental health or anx* or depress* or stress or mood) and (study or trial or treatment or prescribed or prevention) as "Title," "Abstracts," "Keywords," or "Topic" words across all years. A Google search was also completed to check for articles that may have been missed. Results: N = 13 studies met inclusion criteria (no studies were added via the Google search). These studies reported findings for nine different CVGs, with six studies aimed at reducing anxiety, two examining effects for depression, and four investigating the effects of CVGs on treating stress or low mood. Promising effects were identified. Conclusion: CVGs may have promise for treating anxiety, depression, stress, and low mood.

[Attention-deficit/hyperactivity disorder in adults in the clinical description and classification of Emil Kraepelin]. / Die Aufmerksamkeitsdefizit­/Hyperaktivitätsstörung bei Erwachsenen in der klinischen Beschreibung und der Klassifikation von Emil Kraepelin.

This study presents descriptions of symptoms specific to the adult form of attention-deficit/hyperactivity disorder (ADHD) in the 8th edition of the Textbook on Psychiatry by Emil Kraepelin (1856-1926). To identify whether ADHD is a new, fashionable phenomenon in adults or whether early psychiatrists also saw such patients and how they classified them, this textbook is an essential source. Published between 1905 and 1915, it can be perceived as the culmination and at the same time terminal point of Kraepelin's conceptual and nosological work, which in turn marked the beginning of present-day psychiatric classification. Kraepelin did not perceive ADHD as a psychiatric entity of its own, which is either due to the fact that he saw no necessity to do so or that he did not recognize this. If the latter, Kraepelin may have been misled by the manifold psychiatric comorbidities typical for ADHD, which may have masked ADHD. Kraepelin seems to have grouped patients obviously suffering from the adult form of ADHD into two groups: on the one hand into the so-called basic constitution (Grundzustand) of manic-depressive disorder, which he called manic disposition or constitutional excitement (manische Veranlagung oder konstitutionelle Erregung) and on the other hand into the so-called group of anchorless people (Haltlose), which he perceived as a special form of psychopathic personality. It seems that Kraepelin grouped milder grades of ADHD with predominantly ADHD-associated mood swings into the group of manic disposition while grouping more severe forms, which usually occur together with distinct personality disorders and addictive disorders, into that of anchorless people.

Decoding rumination: A machine learning approach to a transdiagnostic sample of outpatients with anxiety, mood and psychotic disorders.

OBJECTIVE: To employ machine learning algorithms to examine patterns of rumination from RDoC perspective and to determine which variables predict high levels of maladaptive rumination across a transdiagnostic sample. METHOD: Sample of 200 consecutive, consenting outpatient referrals with clinical diagnoses of schizophrenia, schizoaffective, bipolar, depression, anxiety disorders, obsessive compulsive and post-traumatic stress. Machine learning algorithms used a range of variables including sociodemographics, serum levels of immune markers (IL-6, IL-1ß, IL-10, TNF-α and CCL11) and BDNF, psychiatric symptoms and disorders, history of suicide and hospitalizations, functionality, medication use and comorbidities. RESULTS: The best model (with recursive feature elimination) included the following variables: socioeconomic status, illness severity, worry, generalized anxiety and depressive symptoms, and current diagnosis of panic disorder. Linear support vector machine learning differentiated individuals with high levels of rumination from those ones with low (AUC = 0.83, sensitivity = 75, specificity = 71). CONCLUSIONS: Rumination is known to be associated with poor prognosis in mental health. This study suggests that rumination is a maladaptive coping style associated not only with worry, distress and illness severity, but also with socioeconomic status. Also, rumination demonstrated a specific association with panic disorder.

Role of personality disorder in randomised controlled trials of pharmacological interventions for adults with mood disorders: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Remission rates for mood disorders, including depressive and bipolar disorders, remain relatively low despite available treatments, and many patients fail to respond adequately to these interventions. Evidence suggests that personality disorder may play a role in poor outcomes. Although personality disorders are common in patients with mood disorders, it remains unknown whether personality disorder affects treatment outcomes in mood disorders. We aim to review currently available evidence regarding the role of personality disorder on pharmacological interventions in randomised controlled trials for adults with mood disorders. METHODS AND ANALYSIS: A systematic search of Cochrane Central Register of Controlled Clinical Trials (CENTRAL) via cochranelibrary.com, PubMed via PubMed, EMBASE via embase.com, PsycINFO via Ebsco and CINAHL Complete via Ebsco databases will be conducted to identify randomised controlled trials that have investigated pharmacological interventions in participants aged 18 years or older for mood disorders (ie, depressive disorders and bipolar spectrum disorders) and have also included assessment of personality disorder. One reviewer will screen studies against the predetermined eligibility criteria, and a second reviewer will confirm eligible studies. Data will be extracted by two independent reviewers. Methodological quality and risk of bias will be assessed using the Cochrane Risk of Bias tool. A systematic review, and if sufficient evidence is identified, a meta-analysis will be completed. Meta-analysis will be conducted using the standardised mean difference approach and reported with 95% CIs. A random effects model will be employed and statistical heterogeneity will be evaluated using the I2 statistic. Prespecified subgroup analyses will be completed. ETHICS AND DISSEMINATION: As this systematic review will use published data, ethics permission will not be required. The outcomes of this systematic review will be published in a relevant scientific journal and presented at a research conference. TRIAL REGISTRATION NUMBER: CRD42018089279.

Normal Versus Pathological Mood: Implications for Diagnosis.

Is there a clear line between normal and abnormal mood? Studies of manifest and latent structure provide strong support for a continuum that extends from asymptomatic to subsyndromal to syndromal cases of increasing severity. Subsyndromal symptoms are impairing, predict syndrome onset and relapse, and account for more doctor's visits and suicide attempts than the full syndromes, yet they are not recognized in the current classification. For most research and some clinical activities, dimensional diagnoses are recommended, and examples are offered for how such diagnoses could be made. For clinical activities requiring decisions, a multithreshold model is proposed in which both lower (e.g., mild depression, capturing subsyndromal cases) and upper (e.g., major depression, capturing clinically significant cases) diagnostic categories are used to inform clinical care. Beyond its implications for diagnosis, the dimensionality of depression and anxiety has implications for etiology and for research aimed at understanding how emotions become disrupted in psychopathology.

The necessity, validity, and clinical utility of a new diagnostic entity: Acute suicidal affective disturbance.

OBJECTIVE: Here we argue for the necessity, validity, and clinical utility of a new diagnostic entity, acute suicidal affective disturbance (ASAD). METHOD: We expand on the conceptual, clinical, and practical rationale for ASAD, propose its defining features, describe research results to date, and suggest avenues for future research. RESULTS: There is accruing evidence for the existence of a previously unclassified, rapid-onset mood disturbance that geometrically escalates and regularly results in life-threatening behavior. CONCLUSIONS: ASAD research may not only improve the field's understanding of suicidal behavior but also enhance clinical effectiveness and save lives.

The Multidimensional Emotional Disorder Inventory (MEDI): Assessing transdiagnostic dimensions to validate a profile approach to emotional disorder classification.

There has been limited progress evaluating the validity of dimensional approaches to emotional disorder classification. This has occurred in part because of a lack of standardized assessment tools developed with the specific intent of studying dimensional classification. The goal of the current study was to develop and validate the Multidimensional Emotional Disorder Inventory (MEDI) to efficiently assess nine empirically supported transdiagnostic dimensions proposed in the Brown and Barlow (2009) profile approach to emotional disorder classification: neurotic temperament, positive temperament, depression, autonomic arousal, somatic anxiety, social anxiety, intrusive cognitions, traumatic reexperiencing, and avoidance. The MEDI factor structure, reliability, and convergent/discriminant validity was evaluated in outpatients with emotional disorders (pilot sample = 227; validation sample = 780). The final 9-factor solution fit the data well. Intercorrelations among MEDI factors were consistent with previous research, and all MEDI dimensions had acceptable reliability. Correlations with common self-report questionnaires and DSM-5 diagnoses supported the convergent/discriminant validity of all nine MEDI dimensions. Collectively, these results support the use of 49-item MEDI in clinical research samples. The MEDI should be used in future research to evaluate the validity of the Brown and Barlow (2009) approach to emotional disorder classification. Because it provides an efficient assessment of several well-established emotional disorder traits and phenotypes, the MEDI also may have utility for general research or clinical purposes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Physicians as second victims after a malpractice claim: An important issue in need of attention.

OBJECTIVE: Being sued for malpractice is extremely stressful and potentially traumatizing. We aim to identify claims' consequences on the physicians' well-being and medical practice. MATERIAL AND METHODS: We administered a confidential telephonic survey to those physicians with a claim closed during 2014, among those insured by the main professional liability insurance company in the region. The questionnaire addressed several topics: symptoms and well-being changes, needs, impairments and practice changes. We used descriptive statistics as well as Chi-square and T-Student tests. RESULTS: A total of 99 physicians responded to the questionnaire (response rate of 64.7%). Most of them (80.8%) acknowledged having suffered a significant emotional distress, no matter the claim's outcome (p=0.958) or the kind of procedure (p=0.928). Anger and mood cluster of symptoms were frequent, and the experience frequently affected their personal, family or social life and professional conduct. Practice changes correlated significantly and positively with the number of symptoms reported (p=0.010), but not with the outcome of the claim (p=0.338) or the kind of procedure (p=0.552). CONCLUSIONS: Most claimed physicians suffer a significant emotional distress after a malpractice claim, which affects their professional performance. According to our results, they should be assessed and assisted in order to minimize the negative consequences on their well-being and their praxis.

Characteristics of depressive and bipolar disorder patients with mixed features.

OBJECTIVE: To assess differences between subjects with vs. without mixed features in major affective disorders. METHODS: In 3099 out-patient subjects with DSM-5 major depressive disorder (MDD, n = 1921) or bipolar disorders (BD, n = 1178), we compared those with (Mx) vs. without (Non-Mx) mixed features (agitated-irritable depression or dysphoric [hypo]mania) in an index episode. RESULTS: Prevalence of Mx averaged 21.9% [CI: 20.5-23.4] overall, ranking: BD-II > BD-I > MDD, and in BD depression ≥ [hypo]mania > MDD. Mx subjects were significantly more likely than Non-Mx cases to (i) have other mixed episodes, (ii) have higher irritable and agitated ratings, (iii) have more substance abuse, (iv) switch into mixed episodes, (v) have more suicide attempts and higher suicidal ratings, (vi) change diagnosis from depression to BD, (vii) have higher hypomania scores when depressed or depression scores when [hypo]manic, (viii) be unmarried or separated with fewer children and siblings, (ix) be diagnosed more with BD than MDD, (x) be unemployed, (xi) have BD, suicide and divorce among first-degree relatives, (xii) be female, (xiii) be younger at illness-onset. Both BD and MDD Mx subjects also received antidepressants less, but antipsychotics and mood-stabilizers more, alone and in combination with antidepressants. CONCLUSIONS: Mood disorder subjects with agitated-irritable depression or dysphoric [hypo]mania differed from those without such mixed features, including having a less favorable clinical course and repeated mixed episodes. They may represent a distinct and prevalent, syndromal clinical subtype with prognostic and therapeutic significance.

A brief history of polarity in mood and its diagnostic evolution.

BACKGROUND: We reviewed the historical development of diagnostic nomenclature and classification systems of mood disorders. METHODS: A literature search in PubMed and Google Scholar was performed using multiple search terms. Also, the criteria and classification of various mood disorders were reviewed and compared across all editions of DSM. We also reviewed several books and the references of the found articles. RESULTS: This review describes the historical development of the concepts and diagnostic nomenclature of mood disorders, including the encompassing of most of the now major depressive disorder under the prior manic-depressive illness. Additionally, we examine how mood disorders have been developed, classified, and split into subcategories historically until the current classification. We observed that the modern nosology (DSM-5) leans a bit more toward a spectrum approach. CONCLUSIONS: The pendulum has swung a bit from splitting toward lumping. The current diagnostic system blurs some of the boundaries between bipolar and unipolar disorders, as in the case of changing nomenclature to "mixed features" in both types of illnesses. This is supported by many experts (and some studies) who advocate for the spectrum concept in mood at the phenotypic level. The spectrum concept is more supported by evidence and further examination driven by both unconfined clinical observations and biological anchor points and markers to scientifically examine the zones of rarity and boundaries between disorders. This would be more fruitful than the arbitrary DSM number of criteria or episode durations and the artificial separation of manic-depressive illness.

Hierarchical structure of emotional disorders: From individual symptoms to the spectrum.

Classification of emotional disorders faces challenges of within-disorder heterogeneity and between-disorder comorbidity. The current study addressed these issues by analyzing all emotional disorder symptoms to identify homogeneous dimensions that characterize this domain. These dimensions were, in turn, used to define coherent syndromes and higher order factors. All of the emotional disorder symptoms specified in diagnostic manuals were assessed by interview in 2 treatment-seeking samples (N = 426 and 305), alongside clinical diagnoses and functioning measures. Exploratory and confirmatory factor analyses were employed to elucidate replicable lower and higher order structures. We found 31 homogenous symptom dimensions that clustered, at different levels of generality, into 8 syndromes (Vegetative Symptoms, Cognitive Depression, Posttraumatic Stress Disorder, Panic, Social Anxiety, Phobia, Obsessive-Compulsive Disorder [OCD], and Mania), 3 subfactors (Distress, Fear, and OCD/Mania), and a single Internalizing spectrum. This structure replicated in both samples. Identified dimensions showed considerable convergence with categorical diagnoses, but provided more information about global functioning than diagnoses. Overall, current results propose a novel comprehensive description of the lower order structure of emotional disorders. The empirical syndromes generally paralleled disorders listed in diagnostic manuals, although several differences were notable. The higher order results also confirmed previously reported Distress, Fear, and Mania subfactors of the Internalizing spectrum using homogeneous dimensional markers. Taken together, results highlight a bottom-up approach to constructing an empirical nosology that does not rely on analysis of diagnostic categories. The resulting hierarchical system can be used clinically and to facilitate research on the pathophysiology of emotional disorders, which, in turn, can inform intervention and prevention. (PsycINFO Database Record

Trauma exposure, incident psychiatric disorders, and disorder transitions in a longitudinal population representative sample.

Heterotypic continuity, whereby individuals transition from one disorder to another, is common; however, longitudinal studies examining transdiagnostic predictors of heterotypic continuity are lacking. The current study examined whether trauma exposure during childhood (maltreatment) and adulthood (interpersonal and non-interpersonal trauma) is associated with heterotypic continuity in a national sample. Men and women (N = 34,653) who participated in Waves 1 (2001-2002) and 2 (2004-2005) of the National Survey of Alcohol and Related Conditions (NESARC) completed face-to-face interviews about trauma exposure and psychopathology. Risk ratios and population attributable risk proportions (PARPs) quantified the effects of childhood maltreatment and interpersonal and non-interpersonal trauma exposure between Waves 1 and 2 on risk for incident disorders and transitions between specific types of disorders. Twenty percent of respondents reported a Wave 2 incident disorder. Those with any Wave 1 disorder were at increased risk of incident mood (RR range = 1.2-2.1) and anxiety (RR = 1.5-2.7) disorders at Wave 2. Child maltreatment and interpersonal trauma exposure since Wave 1 were associated with roughly 50% of the risk for disorder transitions (RR range = 1.2-2.7); non-interpersonal trauma was associated with 30% of the risk for disorder transitions (RR range = 1.0-1.7). Findings suggest that new onset disorders were common in U.S. adults and trauma exposure explained a large proportion of disorder incidence as well as progression from one disorder to another. Universal prevention efforts that begin early in life, rather than those targeted at specific disorders, would be fruitful for reducing the burden of population mental health and preventing a cascade of mental disorders over the life course.

Delineating the joint hierarchical structure of clinical and personality disorders in an outpatient psychiatric sample.

BACKGROUND: A large body of research has focused on identifying the optimal number of dimensions - or spectra - to model individual differences in psychopathology. Recently, it has become increasingly clear that ostensibly competing models with varying numbers of spectra can be synthesized in empirically derived hierarchical structures. METHODS AND MATERIALS: We examined the convergence between top-down (bass-ackwards or sequential principal components analysis) and bottom-up (hierarchical agglomerative cluster analysis) statistical methods for elucidating hierarchies to explicate the joint hierarchical structure of clinical and personality disorders. Analyses examined 24 clinical and personality disorders based on semi-structured clinical interviews in an outpatient psychiatric sample (n=2900). RESULTS: The two methods of hierarchical analysis converged on a three-tier joint hierarchy of psychopathology. At the lowest tier, there were seven spectra - disinhibition, antagonism, core thought disorder, detachment, core internalizing, somatoform, and compulsivity - that emerged in both methods. These spectra were nested under the same three higher-order superspectra in both methods: externalizing, broad thought dysfunction, and broad internalizing. In turn, these three superspectra were nested under a single general psychopathology spectrum, which represented the top tier of the hierarchical structure. CONCLUSIONS: The hierarchical structure mirrors and extends upon past research, with the inclusion of a novel compulsivity spectrum, and the finding that psychopathology is organized in three superordinate domains. This hierarchy can thus be used as a flexible and integrative framework to facilitate psychopathology research with varying levels of specificity (i.e., focusing on the optimal level of detailed information, rather than the optimal number of factors).

Neurocognitive performance as an endophenotype for mood disorder subgroups.

BACKGROUND: There is growing evidence that neurocognitive function may be an endophenotype for mood disorders. The goal of this study is to examine the specificity and familiality of neurocognitive functioning across the full range of mood disorder subgroups, including Bipolar I (BP-I), Bipolar II (BP-II), Major Depressive Disorders (MDD), and controls in a community-based family study. METHODS: A total of 310 participants from 137 families with mood spectrum disorders (n=151) and controls (n=159) completed the University of Pennsylvania's Computerized Neurocognitive Battery (CNB) that assessed the accuracy and speed of task performance across five domains. Mixed effects regression models tested association and familiality. RESULTS: Compared to those without mood disorders, participants with BP-I had increased accuracy in complex cognition, while participants with MDD were more accurate in emotion recognition. There was also a significant familial association for accuracy of complex cognition. Mood disorder subgroups did not differ in performance speed in any of the domains. LIMITATIONS: The small number of BP-I cases, and family size limited the statistical power of these analyses, and the cross-sectional assessment of neurocognitive function precluded our ability to determine whether performance precedes or post dates onset of disorder. CONCLUSIONS: This is one of the few community-based family studies of potential neurocognitive endophenotypes that includes the full range of mood disorder subgroups. There were few differences in neurocognitive function except enhanced accuracy in specific domains among those with BP-I and MDD. The differential findings across specific mood disorder subgroups substantiate their heterogeneity in other biologic and endophenotypic domains.

Disruptive mood dysregulation disorder, severe mood dysregulation and chronic irritability in youth at high familial risk of bipolar disorder.

OBJECTIVE: Disruptive mood dysregulation disorder is a newly proposed childhood disorder included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition to describe children ⩽18 years of age with chronic irritability/temper outbursts. This study aimed to examine the prevalence of disruptive mood dysregulation disorder, severe mood dysregulation and chronic irritability in an Australian study of young people at increased familial risk of developing bipolar disorder ('HR' group) and controls ('CON' group). METHODS: A total of 242 12- to 30-year-old HR or CON subjects were administered the severe mood dysregulation module. Of these, 42 were aged ⩽18 years at the time of assessment, with 29 subjects in the HR group and 13 in the CON group. RESULTS: No subjects ⩽18 years - in either group - fulfilled current or lifetime criteria for disruptive mood dysregulation disorder or severe mood dysregulation, the precursor to disruptive mood dysregulation disorder. Similarly, no subjects in either group endorsed the severe mood dysregulation/disruptive mood dysregulation disorder criteria for irritable mood or marked excessive reactivity. One HR participant endorsed three severe mood dysregulation criteria (distractibility, physical restlessness and intrusiveness), while none of the comparison subjects endorsed any criteria. Exploratory studies of the broader 12- to 30-year-old sample similarly found no subjects with severe mood dysregulation/disruptive mood dysregulation disorder in either the HR or CON group and no increased rates of chronic irritability, although significantly more HR subjects reported at least one severe mood dysregulation/disruptive mood dysregulation disorder criterion (likelihood ratio = 6.17; p = 0.013); most of the reported criteria were severe mood dysregulation 'chronic hyper-arousal' symptoms. CONCLUSION: This study comprises one of the few non-US reports on the prevalence of disruptive mood dysregulation disorder and severe mood dysregulation and is the first non-US study of the prevalence of these conditions in a high-risk bipolar disorder sample. The failure to replicate the finding of higher rates of disruptive mood dysregulation disorder and chronic irritability in high-risk offspring suggests that these are not robust precursors of bipolar disorder.

Marketing Masked Depression: Physicians, Pharmaceutical Firms, and the Redefinition of Mood Disorders in the 1960s and 1970s.

This article investigates the redefinition of depression that took place in the early 1970s. Well before the introduction of the third edition of the Diagnostic and Statistical Manual of Mental Disorders, this rather rare and severe psychiatric disorder hitherto treated in asylums was transformed into a widespread mild mood disorder to be handled by general practitioners. Basing itself on the archives of the Swiss firm Ciba-Geigy, the article investigates the role of the pharmaceutical industry in organizing this shift, with particular attention paid to research and scientific marketing. By analyzing the interplay between the firm, elite psychiatrists specializing in the study of depression, and general practitioners, the article argues that the collective construction of the market for first-generation antidepressants triggered two realignments: first, it bracketed etiological issues with multiple classifications in favor of a unified symptom-oriented approach to diagnosis and treatment; second, it radically weakened the differentiation between antidepressants, neuroleptics, and tranquilizers. The specific construction of masked depression shows how, in the German-speaking context, issues of ambulatory care such as recognition, classification, and treatment of atypical or mild forms of depression were reshaped to meet commercial as well as professional needs.