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.

[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.

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.

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.

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.

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).

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.

Anxiety or agitation in mood disorder with mixed features: A review with a focus on validity as a dimensional criterion.

BACKGROUND: The diagnostic validity of mixed features, excluding anxiety or psychomotor agitation in mood disorders, has not yet been fully examined. METHOD: PubMed and relevant English-language literature (regardless of year) were searched. Keywords were mixed or mixed state or mixed features or mixed episode and anxious or anxiety or agitation and bipolar disorder or depressive disorder or mood disorder or affective disorder. RESULTS: Most studies on anxiety or psychomotor agitation have included a significant correlation relevant to the "with mixed features" specifier, although it is common in both poles of mood episodes regardless of the predominant polarity. There is some confusion between the characteristic of classical mixed states and the definition of the mixed features specifier with the newly added anxious distress specifier in DSM-5, specifically, whether to include anxiety and agitation as significant characteristics. This change is of concern because a large proportion of patients with mixed features are now unspecified, and this may influence treatment planning and prognosis. CONCLUSIONS: The findings of our review suggest that anxiety and psychomotor agitation can be core symptoms in mood episodes with mixed features and important clinical clues for prediction of treatment effects and disease course.

[Müller-Hegemann's classification of depressions of 1964 as a proposal for a conceptualization of affective disorders: A critical review]. / Müller-Hegemanns Systematik der Depressionen von 1964 als Vorschlag zur Konzeptualisierung der affektiven Störungen. Eine kritische Analyse.

Against the background of current discussions on the classification of psychiatric disorders, this study analyses and discusses the East-German psychiatrist Dietfried Müller-Hegemann's concept of a clinical classification of depressions of 1964.In his paper, Müller-Hegemann differentiated between two main forms of depression, namely the "vitally tinged depression" (= melancholy), found mainly in the depressive phases of the manic-depressive disorder, and the "depressive disgruntlement" (= dysthymia) seen in "reactive and neurotic depression", "involutional depression", and in the depressive states in psychopathic personalities. Due to a lack of sufficient biological evidence, Müller-Hegemann refrained from a purely etiological differentiation.His proposal is significant in so far as it provided a classification that could easily be used in clinical practice, and at the same time, by pointing to the traditional concept of melancholy and by calling for a differentiated psychopathology, anticipated aspects of topical interest.

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.

Unipolar mania: a necessary diagnostic concept.

In the classification of mood disorders, major depressive disorder is separate from bipolar disorders whereas mania is not. Studies on pure mania are therefore rare. Our paper reviews the evidence for distinguishing pure mania (M) and mania with mild depression (Md) from bipolar disorder. Two large epidemiological studies found a prevalence of 1.7-1.8% of M/Md in adolescents and adults. Several clinical follow-up studies demonstrated good stability of the diagnosis after a previous history of three manic episodes. Compared to bipolar disorder, manic disorder is characterised by a weaker family history for depression, an earlier onset, fewer recurrences and better remission, and is less comorbid with anxiety disorders. In addition, mania is strongly associated with a hyperthymic temperament, manifests more psychotic symptoms and is more often treated with antipsychotics. Twin and family studies find mania to be more heritable than depression and show no significant transmission from depression to mania or from mania to depression. Cardiovascular mortality is elevated among patients with mood disorders generally and is highest among those with mania. In non-Western countries, mania and the manic episodes in bipolar disorder are reported to occur more frequently than in Western countries.

Differences in anxiety and depression symptoms: comparison between older and younger clinical samples.

BACKGROUND: Anxiety and depression symptoms change over the lifespan and older adults use different terms to describe their mental health, contributing to under identification of anxiety and depression in older adults. To date, research has not examined these differences in younger and older samples with comorbid anxiety and depression. METHODS: One hundred and seven treatment-seeking participants (47 older, 60% female, and 60 younger, 50% female) with anxiety and mood disorders completed the Anxiety Disorders Interview Schedule and a symptom checklist to examine differences in symptom severity, symptom profiles and terms used to describe anxiety and mood. RESULTS: The findings indicated several key differences between the presentation and description of anxiety and depression in younger and older adults. Older adults with Social Phobia reported fearing a narrower range of social situations and less distress and interference. Older adults with Generalized Anxiety Disorder (GAD) reported less worry about interpersonal relationships and work/school than younger adults, however, there were no differences between age groups for behavioral symptoms endorsed. Further older adults reported phobia of lifts/small spaces more frequently than younger adults. Depressed older depressed adults also reported more anhedonia compared to younger adults, but no differences in terms of reported sadness were found. Finally, older and younger adults differed in their descriptions of symptoms with older adults describing anxiety as feeling stressed and tense, while younger adults described anxiety as feeling anxious, worried or nervous. CONCLUSIONS: Clinicians need to assess symptoms broadly to avoid missing the presence of anxiety and mood disorders especially in older adults.

Is borderline personality disorder a mood disorder?

Borderline personality disorder is by its very naming positioned as an Axis II personality disorder and thus seemingly distinct from an Axis I mood state. Clinical differentiation of those with a borderline condition and those with a bipolar disorder is commonly held to be difficult, so raising the question as to whether they may be independent or interdependent conditions, and allowing several possible answers.

Problems in the boundaries of bipolar disorders.

Classical concepts of bipolarity (bipolar I and bipolar II) have sometimes been extended into a broader spectrum that includes a wide variety of conditions previously diagnosed as separate forms of psychopathology. Differential diagnosis remains important, particularly in personality disorders characterized by affective instability, and in behavior disorders affecting pre-pubertal children. In the absence of biological markers or other external sources of validity, as well as lack of evidence for response to pharmacological treatment when disorders are defined more broadly, the bipolar spectrum remains an unproven hypothesis.

The DSM-5 peripartum specifier: prospects and pitfalls.

The addition of the "with peripartum onset" specifier for mood episodes in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, and broadening the scope of the specifier to include hypomanic episodes, are welcome changes. However, the peripartum onset specifier, by failing to distinguish between "prepartum" onset and "postpartum" onset, obfuscates important differences in mood episodes that might have distinct etiologies, clinical profiles, and responses to treatment. In addition, restricting the specifier to a period of 4 weeks postpartum potentially excludes many mood episodes that are associated with a postpartum onset. We argue that the specifier should be modified to distinguish between episodes with prepartum and postpartum onset, and that the time frame for the specifier should be increased from 4 weeks to 6 months.

[The Temperament Evaluation of Memphis, Pisa and San Diego Autoquestionnaire (TEMPS-A)--an important tool to study affective temperaments]. / Skala TEMPS-A (Temperament Evaluation of Memphis, Pisa and San Diego Autoquestionnaire)--wazne narzedzie do badania temperamentów afektywnych.

The aim of the paper is to describe the Temperament Evaluation of Memphis, Pisa and San Diego Autoquestionnaire (TEMPS-A) constructed by prominent researchers of affective disorders, under the direction of Hagop Akiskal, and functioning in full version since 2005. The article refers to the definitions of temperament, including the concept of affective temperament, related to the area of emotionality and conceptualized as the endophenotype of affective disorders. Based on clinical observations, initially four types of temperament had been delineated: hiperthymic, depressed, irritable and cyclothymic, and, subsequently, the anxious temperament was added. Full version of the scale contains 110 items for the five types of temperament, which were discussed in detail. The TEMPS-A has been translated into 32 languages and its verification was performed in many countries, including Poland. The scale has been widely used in epidemiological and clinical studies in general population, in patients with affective disorders, and in other diseases. In affective disorders, different types of temperament show, among others, a relationship to the type and symptomatology of bipolar disorder as well as to a predisposition to suicidal behavior. In Poznan centre, an association between several dimensions of temperament of the TEMPS-A, and prophylacic efficacy of lithium has been shown. Different types of temperament also play a role in other mental disorders and somatic diseases. In the final section of the article, the studies performed so far on the molecular-genetic determinants of temperament dimensions, measured by the TEMPS-A are presented.

Comorbidity of migraine and mood episodes in a nationally representative population-based sample.

OBJECTIVE: To examine the lifetime comorbidity of migraine with different combinations of mood episodes: (1) manic episodes alone; (2) depressive episodes alone; (3) manic and depressive episodes; (4) controls with no lifetime history of mood episodes, as well as sociodemographic and clinical correlates of migraine for each migraine-mood episode combination. BACKGROUND: Migraine has been found to be comorbid with bipolar disorder and major depressive disorder in clinical and population-based samples. However, variability in findings across studies suggests that examining mood episodes separately may be fruitful in determining which of these mood episodes are specifically associated with migraine. METHODS: Using a cross-sectional, population-based sample from the Canadian Community Health Survey 1.2 (n = 36,984), sociodemographic and clinical correlates of migraine were examined in each combination of mood episodes as well as controls. Logistic regression analyses controlling for age, sex, and education level compared the lifetime prevalence of migraine (1) between controls and each combination of mood episodes, and then (2) among the different combinations of mood episodes. RESULTS: Migraine comorbidity in all combinations of mood episodes was associated with lower socioeconomic status, earlier onset of affective illness, more anxiety, suicidality and use of mental health resources. Compared with controls, the adjusted odds ratio of having migraine was 2.0 (95% confidence interval [CI] 1.4-2.8) for manic episodes alone, 1.9 (95% CI 1.6-2.1) for depressive episodes alone, and 3.0 (95% CI 2.3-3.9) for subjects with both manic and depressive episodes. Compared with those with manic episodes alone and depressive episodes alone, the odds of having migraine were significantly increased in subjects with both manic and depressive episodes (odds ratio 1.5 vs. manic episodes alone; 1.8 vs. depressive episodes alone). In addition, migraine comorbidity was associated with different correlates depending on the specific combination of mood episodes; in subjects with both manic and depressive episodes, migraine comorbidity was associated with an earlier onset of mental illness, while in subjects with either manic or depressive episodes alone, migraine comorbidity was associated with increased suicidality and anxiety. CONCLUSIONS: Migraine comorbidity appears to delineate a subset of individuals with earlier onset of affective illness and more psychiatric complications, suggesting that migraine assessment in mood disorder patients may be useful as an indicator of potential clinical severity. Differences in the prevalence of migraine as well as sociodemographic and clinical correlates associated with specific combinations of mood episodes underscore the importance of examining this comorbidity by specific type of mood episode.