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To establish an overarching definition of what constitutes a sleep disorder, it is essential to know which health conditions should be included in the classifications of sleep disorders and to better distinguish the normal from the pathological in sleep medicine. This would bring together several professional organizations in their understanding of this hitherto heterogeneous concept. However, no consensus regarding a general definition of a sleep disorder currently exists. We explore two of the main frameworks used in medical epistemology that could be used to define sleep disorders rigorously: harmful dysfunction analysis (HDA) and symptom network theory. For each framework, we detail the conceptual background, the method for applying it to the establishment of a general definition of a sleep disorder, the application to main sleep disorders of the ICSD-3-TR (with an emphasis on insomnia disorder) and a discussion of the main aspects of these two general definitions in the context of sleep medicine. The complementarity between the two definitions could then be considered as an "epistemic hub" which could serve to clarify the debate about what sleep disorders are, so that our understanding of them and their clinical management improve., Competing Interests: Declaration of competing interest All the authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this review., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In 1978, G. Klerman published an essay in which he named the then-nascent "neo-Kraepelinian" movement and formulated a "credo" of nine propositions expressing the movement's essential claims and aspirations. Klerman's essay appeared on the eve of the triumph of neo-Kraepelinian ideas in the DSM-III. However, this diagnostic system has subsequently come under attack, opening the way for competing proposals for the future of psychiatric nosology. To better understand what is at stake, in this paper I provide a close reading and consideration of Klerman's credo in light of the past forty years of research and reflection. The credo is placed in the context of two equally seminal publications in the same year, one by S. Guze, the leading neo-Kraepelinian theorist, and the other by R. Spitzer and J. Endicott, defining mental disorder. The divergences between Spitzer and standard neo-Kraepelinianism are highlighted and argued to be much more important than is generally realized. The analysis of Klerman's credo is also argued to have implications for how to satisfactorily resolve the current nosological ferment in psychiatry. In addition to issues such as creating descriptive syndromal diagnostic criteria, overthrowing psychoanalytic dominance of psychiatry, and making psychiatry more scientific, neo-Kraepelinians were deeply concerned with the conceptual issue of the nature of mental disorder and the defense of psychiatry's medical legitimacy in response to antipsychiatric criticisms. These issues cannot be ignored, and I argue that proposals currently on offer to replace the neo-Kraepelinian system, especially popular proposals to replace it with dimensional measures, fail to adequately address them., (© 2022 World Psychiatric Association.)

Background: Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC)., Methods: Participants with newly diagnosed EOC due for platinum-based chemotherapy and interval debulking surgery were recruited prospectively in a multicentre study (n = 47 participants). Apparent diffusion coefficient (ADC) and solid tumour volume (up to 10 lesions per participant) were obtained from DW-MRI before and after NAC (including double-baseline for repeatability assessment in n = 19). Anatomically matched lesions were analysed after surgical excision (65 lesions obtained from 25 participants). A trained algorithm determined tumour cell fraction, percentage tumour and percentage necrosis on histology. Whole-lesion post-NAC ADC and pre/post-NAC ADC changes were compared with histological metrics (residual tumour/necrosis) for each tumour site (ovarian, omental, peritoneal, lymph node)., Results: Tumour volume reduced at all sites after NAC. ADC increased between pre- and post-NAC measurements. Post-NAC ADC correlated negatively with tumour cell fraction. Pre/post-NAC changes in ADC correlated positively with percentage necrosis. Significant correlations were driven by peritoneal lesions., Conclusions: Following NAC in EOC, the ADC (measured using DW-MRI) increases differentially at disease sites despite similar tumour shrinkage, making its utility site-specific. After NAC, ADC correlates negatively with tumour cell fraction; change in ADC correlates positively with percentage necrosis., Clinical Trial Registration: ClinicalTrials.gov NCT01505829.

Is addiction a medical disorder, and if so, what kind of disorder is it? Addiction is considered a brain disease by NIDA, based on observed brain changes in addicts that are interpreted as brain damage. Critics argue that the brain changes result instead from normal neuroplasticity and learning in response to the intense rewards provided by addictive substances, thus addiction is not a disorder but rather a series of normal-range if problematic choices. Relying on the harmful dysfunction analysis of medical disorder to evaluate disorder versus nondisorder status, I argue that even if one accepts the critics' reinterpretation of NIDA's brain evidence and rejects the brain disease account, the critics' conclusion that addiction is not a medical disorder but is rather a matter of problematic nondisordered choice does not follow. This is because there is a further possible account of addiction, the evolutionary "hijack" view, that holds that addiction is due to the availability of substances and stimuli that were unavailable during human species evolution and that coopt certain brain areas concerned with human motivation, creating biologically undesigned peremptory desires. I argue that if the hijack theory is correct, then it opens up the possibility that addiction could be a true motivational medical disorder for which there is no underlying neurological-level dysfunction. Finally, I explore the implications of this account for how we see the social responsibility for addiction and how we attempt to control it., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Wakefield's harmful dysfunction analysis asserts that the concept of medical disorder includes a naturalistic component of dysfunction (failure of biologically designed functioning) and a value (harm) component, both of which are required for disorder attributions. Muckler and Taylor, defending a purely naturalist, value-free understanding of disorder, argue that harm is not necessary for disorder. They provide three examples of dysfunctions that, they claim, are considered disorders but are entirely harmless: mild mononucleosis, cowpox that prevents smallpox, and minor perceptual deficits. They also reject the proposal that dysfunctions need only be typically harmful to qualify as disorders. We argue that the proposed counterexamples are, in fact, considered harmful; thus, they fail to disconfirm the harm requirement: incapacity for exertion is inherently harmful, whether or not exertion occurs, cowpox is directly harmful irrespective of indirect benefits, and colorblindness and anosmia are considered harmful by those who consider them disorders. We also defend the typicality qualifier as viably addressing some apparently harmless disorders and argue that a dysfunction's harmfulness is best understood in dispositional terms., (© The Author(s) 2020. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Treatment of advanced epithelial ovarian cancer results in a relapse rate of 75%. Early markers of response would enable optimization of management and improved outcome in both primary and recurrent disease. Purpose To assess the apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI, as an indicator of response, progression-free survival (PFS), and overall survival. Materials and Methods This prospective multicenter trial (from 2012-2016) recruited participants with stage III or IV ovarian, primary peritoneal, or fallopian tube cancer (newly diagnosed, cohort one; relapsed, cohort two) scheduled for platinum-based chemotherapy, with interval debulking surgery in cohort one. Cohort one underwent two baseline MRI examinations separated by 0-7 days to assess ADC repeatability; an additional MRI was performed after three treatment cycles. Cohort two underwent imaging at baseline and after one and three treatment cycles. ADC changes in responders and nonresponders were compared (Wilcoxon rank sum tests). PFS and overall survival were assessed by using a multivariable Cox model. Results A total of 125 participants (median age, 63.3 years [interquartile range, 57.0-70.7 years]; 125 women; cohort one, n = 47; cohort two, n = 78) were included. Baseline ADC (range, 77-258 × 10 -5 mm 2 s -1 ) was repeatable (upper and lower 95% limits of agreement of 12 × 10 -5 mm 2 s -1 [95% confidence interval {CI}: 6 × 10 -5 mm 2 s -1 to 18 × 10 -5 mm 2 s -1 ] and -15 × 10 -5 mm 2 s -1 [95% CI: -21 × 10 -5 mm 2 s -1 to -9 × 10 -5 mm 2 s -1 ]). ADC increased in 47% of cohort two after one treatment cycle, and in 58% and 53% of cohorts one and two, respectively, after three cycles. Percentage change from baseline differed between responders and nonresponders after three cycles (16.6% vs 3.9%; P = .02 [biochemical response definition]; 19.0% vs 6.2%; P = .04 [radiologic definition]). ADC increase after one cycle was associated with longer PFS in cohort two (adjusted hazard ratio, 0.86; 95% CI: 0.75, 0.98; P = .03). ADC change was not indicative of overall survival for either cohort. Conclusion After three cycles of platinum-based chemotherapy, apparent diffusion coefficient (ADC) changes are indicative of response. After one treatment cycle, increased ADC is indicative of improved progression-free survival in relapsed disease. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Competing Interests: Competing interests: None declared.

Background: "Complicated" subthreshold depression (CsD) includes at least one of six pathosuggestive "complicated" symptoms: >6 months duration, marked role impairment, sense of worthlessness, suicidal ideation, psychotic ideation, and psychomotor retardation. "Uncomplicated" subthreshold depression (UsD) has no complicated features. Whereas studies show that complicated (CMDD) versus uncomplicated (UMDD) major depression differ substantially in severity and prognosis, UsD and CsD severity has not been previously compared. This study evaluates UsD and CsD pathology validator levels and examines whether the complicated/uncomplicated distinction offers incremental concurrent validity over the standard number-of-symptoms dimension as a depression severity measure., Methods: Using nationally representative community data from the National Comorbidity Survey, seven depression lifetime history subgroups were identified: one MDD screener symptom (n=1432); UsD (n=430); CsD (n=611); UMDD (n=182); and CMDD with 5-6 symptoms (n=518), 7 symptoms (n=217), and 8-9 symptoms (n=291). Severity was evaluated using five concurrent pathology validators: suicide attempt, interference with life, help seeking, hospitalization, and generalized anxiety disorder., Results: CsD validator levels are substantially higher than both UsD and UMDD levels, and similar to mild CMDD, disconfirming the "monotonicity thesis" that severity increase with symptom number. Complicated/uncomplicated status predicts severity, and when complicatedness is controlled, number of symptoms no longer predicts validator levels., Limitations: Diagnoses were based on respondents' fallible retrospective symptom reports during a lay-administered structured interview, which may not yield diagnoses comparable to clinicians' assessments., Conclusion: CsD is more severe than UsD and comparable to mild MDD. Complicated status more validly indicates depression severity than the standard number-of-symptoms measure., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Uncomplicated major depressive disorder (UMDD) is defined as MDD that does not include any of six pathosuggestive features: more than six months duration, marked functional impairment, sense of worthlessness, suicidal ideation, psychotic ideation, and psychomotor retardation. Complicated MDD (CMDD) includes all episodes containing one or more of these features. UMDD has been shown to be lower than CMDD and indistinguishable from no-MDD-history on predictive pathology validators. This study's purpose is to establish where on the number-of-symptoms depressive continuum UMDD is located, using the criterion of predictive validity., Methods: Using two-wave longitudinal community data, seven baseline depression history subgroups were identified: no MDD symptoms (n=23,214), one MDD screener symptom (n=609), subthreshold or "minor" depression (mD; 2-4 MDD symptoms; n=2,623), UMDD (n=505), and complicated MDD with 5-6 symptoms (n=1,106), 7 symptoms (n=1,200), and 8-9 symptoms (n=2,408). Predictive validity was evaluated by four follow-up variables: major depressive episode; generalized anxiety disorder; suicide attempt; and manic/hypomanic episode., Results: UMDD predictive pathology validator rates are not significantly different from rates for subthreshold mD but significantly different from those for all other depression categories; UMDD is higher in symptoms but lower in validator levels than 5-6 symptom CMDD., Limitations: Baseline and follow-up diagnoses were based on respondents' fallible retrospective symptom reports in response to a lay-administered structured questionnaire, which may not yield diagnoses comparable to clinicians' assessments., Conclusion: Uncomplicated MDD's follow-up outcomes resemble subthreshold depression, not CMDD, even when CMDD has less symptoms. Clinical decisions should reflect the relatively benign prognosis of uncomplicated MDD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To establish which symptoms of major depressive episode (MDE) predict postremission suicide attempts in complicated single-episode cases., Method: Using the nationally representative two-wave National Epidemiologic Survey on Alcohol and Related Conditions data set, we identified wave 1 lifetime single-episode MDE cases in which the episode remitted by the beginning of the wave 2 three-year follow-up period (N = 2791). The analytic sample was further limited to 'complicated' cases (N = 1872) known to have elevated suicide attempt rates, defined as having two or more of the following: suicidal ideation, marked role impairment, feeling worthless, psychomotor retardation, and prolonged (>6 months) duration., Results: Logistic regression analyses showed that, after controlling for wave 1 suicide attempt which significantly predicted postremission suicide attempt (OR = 10.0), the additional complicated symptom 'feelings of worthlessness' during the wave 1 index episode significantly and very substantially predicted postremission suicide attempt (OR = 6.96). Neither wave 1 psychomotor retardation nor wave 1 suicidal ideation nor any of the other wave 1 depressive symptoms were significant predictors of wave 2 suicide attempt., Conclusion: Among depressive symptoms during an MDE, feelings of worthlessness is the only significant indicator of elevated risk of suicide attempt after the episode has remitted, beyond previous suicide attempts., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was the most controversial in the manual's history. This review selectively surveys some of the most important changes in DSM-5, including structural/organizational changes, modifications of diagnostic criteria, and newly introduced categories. It analyzes why these changes led to such heated controversies, which included objections to the revision's process, its goals, and the content of altered criteria and new categories. The central focus is on disputes concerning the false positives problem of setting a valid boundary between disorder and normal variation. Finally, this review highlights key problems and issues that currently remain unresolved and need to be addressed in the future, including systematically identifying false positive weaknesses in criteria, distinguishing risk from disorder, including context in diagnostic criteria, clarifying how to handle fuzzy boundaries, and improving the guidelines for "other specified" diagnosis.

Objectives: To assess goodness-of-fit and repeatability of mono-exponential, stretched exponential and bi-exponential models of diffusion-weighted MRI (DW-MRI) data in primary and metastatic ovarian cancer., Methods: Thirty-nine primary and metastatic lesions from thirty-one patients with stage III or IV ovarian cancer were examined before and after chemotherapy using DW-MRI with ten diffusion-weightings. The data were fitted with (a) a mono-exponential model to give the apparent diffusion coefficient (ADC), (b) a stretched exponential model to give the distributed diffusion coefficient (DDC) and stretching parameter (α), and (c) a bi-exponential model to give the diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*)., Results: Coefficients of variation, established from repeated baseline measurements, were: ADC 3.1%, DDC 4.3%, α 7.0%, D 13.2%, f 44.0%, D* 165.1%. The bi-exponential model was unsuitable in these data owing to poor repeatability. After excluding the bi-exponential model, analysis using Akaike Information Criteria showed that the stretched exponential model provided the better fit to the majority of pixels in 64% of lesions., Conclusions: The stretched exponential model provides the optimal fit to DW-MRI data from ovarian, omental and peritoneal lesions and lymph nodes in pre-treatment and post-treatment measurements with good repeatability., Key Points: • DW-MRI data in ovarian cancer show deviation from mono-exponential behaviour • Parameters derived from the stretched exponential model showed good repeatability (CV 7%) • The bi-exponential model was unsuitable because of poor parameter repeatability • The stretched exponential model showed comparable repeatability to the mono-exponential model • The extra parameter (α) provides scope for investigation of heterogeneity or response.

The revision effort leading to the publication of the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was flawed in process, goals and outcome. The revision process suffered from lack of an adequate public record of the rationale for changes, thus shortchanging future scholarship. The goals, such as dimensionalising diagnosis, incorporating biomarkers and separating impairment from diagnosis, were ill-considered and mostly abandoned. However, DSM-5's greatest problem, and the target of the most vigorous and sustained criticism, was its failure to take seriously the false positives problem. By expanding diagnosis beyond plausible boundaries in ways inconsistent with DSM-5's own definition of disorder, DSM-5 threatened the validity of psychiatric research, including especially psychiatric epidemiology. I present four examples: increasing the symptom options while decreasing the diagnostic threshold for substance use disorder, elimination of the bereavement exclusion from major depression, allowing verbal arguments as evidence of intermittent explosive disorder and expanding attention-deficit/hyperactivity disorder to adults before addressing its manifest false positives problems.

Aims: To formulate harmful dysfunction (HD) diagnostic criteria for alcohol use disorder (AUD) and test whether they increase validity relative to standard DSM criteria, as evidenced by lowered prevalence, increased validator levels including service use, severity and family history and enhanced specificity., Design: DSM-IV AUD, DSM-IV dependence, DSM-5 AUD and HD AUD definitions were compared on eight validity related tests using nationally representative community data., Setting: United States., Participants: National Epidemiologic Survey of Alcoholism and Related Conditions (NESARC) respondents, aged 18-54 years (wave 1, n = 29 673; wave 2, n = 24 244)., Measures: NESARC DSM-IV and DSM-5 criteria were taken from published studies. Whereas DSM-5 diagnosis requires any two AUD symptoms, HD criteria were constructed from NESARC items to require symptoms of both impaired-control dysfunction [withdrawal, drink to prevent/stop withdrawal, cannot stop/reduce drinking, or craving (wave 2 only)] and harm (sacrificed important activities, problems caring for home/family, job/school problems, health problems, psychological problems or problems with family/friends). Validators included service use, severity and family history, among others. Specificity was tested using a teen transient drinker criterion group., Findings: Compared with DSM-5 AUD (DSM-IV results were similar), HD criteria yielded lower prevalence (95% confidence intervals): HD life-time 6.7% (6.2, 7.2%), 1-year 2.3% (2.0, 2.5%); and DSM-5 life-time 38.2% (36.5, 39.9%), 1-year 12.4% (11.7, 13.1%). HD AUD was higher than DSM-5 on pathology validators, including: life-time alcohol-related service use: HD 41.0% (38.1, 43.9%), DSM-5 11.5% (10.7, 12.3%); severity (number of life-time alcohol symptoms): HD 20.8 (20.4, 21.2), DSM-5 10.6 (10.4, 10.8); and family history of alcohol problems: HD 50.1% (47.3, 52.9), DSM-5 32.8% (31.6, 34.0). HD criteria eliminated 83% of a DSM-5 teen transient drinker false-positives criterion group., Conclusions: Prevalence estimates of alcohol use disorder are lowered and diagnostic validity improved when using 'harmful dysfunction' diagnostic criteria compared with standard DSM criteria, partly by reducing misdiagnosis of teenage transient drinkers., (© 2015 Society for the Study of Addiction.)