Search

ABSTRACT: The proposed changes to DSM-5 will create new categories of mental disorder (referred to here generically as Prolonged Grief Disorder'' [PGD]) to diagnose individuals experiencing prolonged intense grief reactions to the loss of a loved one. Individuals could be diagnosed even if they have no depressive or anxiety symptoms but only symptoms typical of grief (e.g., yearning, avoidance of reminders, disbelief, feelings of emptiness). The main challenge for such proposals is to establish that the proposed diagnostic criteria validly discriminate a genuine psychiatric disorder of grief from intense normal grief. With this test in mind, I evaluate the soundness of four empirical arguments and one conceptual argument that have been put forward to support such proposals: (1) PGD has discriminant validity because distinctive, pathognomonic symptoms distinguish it from normal grief; (2) PGD has discriminant validity because it identifies grief symptoms that are of greater absolute severity than in normal grief; (3) PGD has predictive validity because it implies a chronic, interminable process of grieving, thus a derailment of the normal process of grief resolution; (4) PGD has predictive validity because it predicts negative mental and physical health outcomes unlikely in normal grief; and (5) PGD has conceptual validity because grief is analogous to a wound or, alternatively, lengthy grief is analogous to a wound that does not heal. Upon close examination, each of these arguments turns out to have serious empirical or conceptual deficiencies. I conclude that the proposed diagnostic criteria for PGD fail to discriminate disorder from intense normal grief and are likely to yield massive false-positive diagnoses. Consequently, the proposal to add pathological grief categories to DSM-5 should be withdrawn pending further research to identify more valid criteria for diagnosing PGD. [ABSTRACT FROM AUTHOR]

ABSTRACT: The DSM-IV diagnostic criteria for major depressive disorder exclude bereavement-related depressive episodes that are brief and lack certain severe symptoms and are thus better explained as normal grief responses. However, the DSM-5 Task Force proposes to eliminate this exclusion because of a lack of evidence that such episodes differ relevantly from standard major depression. Using the two-wave longitudinal Epidemiologic Catchment Area Study, we compared 1-yr depression recurrence rates at wave 2 of four groups at wave 1 baseline: (1) those with no history of depressive disorder (n = 18,239), (2) those who had only lifetime excludable bereavement-related depression (n = 25), (3) those with brief-episode (<=2 months duration) lifetime standard depressive disorder (n = 446), and (4) those with nonbrief lifetime standard depressive disorder (n = 581). The recurrence rate in the excludable-depression group (3.7%) was not significantly different from the no-history group (1.7%) but was significantly and substantially lower than in the brief and nonbrief standard depression groups (14.4% and 16.2%, respectively). These findings confirm findings reported by Mojtabai (Arch Gen Psychiatry 68:920-928, 2011) using a different data set and time frame and thus substantially strengthen the support for the validity of bereavement exclusion and for its preservation in the DSM-5. [ABSTRACT FROM AUTHOR]

Abstract The Diagnostic and Statistical Manual of Mental Disorders (DSM) is currently undergoing a revision that will lead to a fifth edition in 2013. Proposed changes for DSM-5 include the creation of several new categories of depressive disorder. Some nosologists have expressed concern that the proposed changes could yield many 'false-positive diagnoses' in which normal distress is mislabeled as a mental disorder. Such confusion of normal distress and mental disorder undermines the interpretability of clinical trials and etiological research, causes inefficient allocation of resources, and incurs risks of unnecessary treatment. To evaluate these concerns, I critically examine five proposed DSM-5 expansions in the scope of depressive and grief disorders: (1) a new mixed anxiety/depression category; (2) a new premenstrual dysphoric disorder category; (3) elimination of the major depression bereavement exclusion; (4) elimination of the adjustment disorder bereavement exclusion, thus allowing the diagnosis of subsyndromal depressive symptoms during bereavement as adjustment disorders; and (5) a new category of adjustment disorder related to bereavement for diagnosing pathological non-depressive grief. I examine each proposal's face validity and conceptual coherence as well as empirical support where relevant, with special attention to potential implications for false-positive diagnoses. I conclude that mixed anxiety/depression and premenstrual dysphoric disorder are needed categories, but are too broadly drawn and will yield substantial false positives; that the elimination of the bereavement exclusion is not supported by the evidence; and that the proposed elimination of the adjustment-disorder bereavement exclusion, as well as the new category of grief-related adjustment disorder, are inconsistent with recent grief research, which suggests that these proposals would massively pathologize normal grief responses. [ABSTRACT FROM AUTHOR]

The DSM's major-depression 'bereavement exclusion' eliminates bereavement-related depressive episodes (BRDs) from diagnosis unless they are 'complicated' by prolonged duration or certain severe symptoms. The exclusion was substantially narrowed in DSM-IV to decrease false-negative diagnoses, but the impact of this change remains unknown. We divided BRDs in the National Comorbidity Survey into uncomplicated versus complicated categories using broader DSM-III-R and narrower DSM-IV exclusion criteria. Using 6 pathology validators (symptom number, melancholic depression, suicide attempt, interference with life, medication for depression, and hospitalization for depression), we compared the validity of the 2 exclusion criteria sets using 2 tests: (1) which criteria set yielded less pathological uncomplicated cases or more pathological complicated cases; (2) which yielded the largest separation between uncomplicated and complicated pathology levels. Results of both tests indicated that the narrower DSM-IV criteria substantially decreased the exclusion's validity. These results suggest caution regarding the current proposal to eliminate the bereavement exclusion in DSM-5. [ABSTRACT FROM AUTHOR]

The author critiques Gordon's influential analysis of the National Association of Social Workers' working definition of social work practice (WD). Gordon's critique contains well-founded objections leading to the elimination of the WD's method, purpose, and sanction components. However, Gordon's implied conclusion that social work can be defined by a broad value (i.e., self-realization) and a distinctive knowledge domain (i.e., social transactions) involves fundamental errors repeated in subsequent definitional attempts. Rather than being distinguished by a unique knowledge domain, social work, like other professions, must be defined by a value that is distinctive of the profession yet shared by all social work fields. [ABSTRACT FROM AUTHOR]

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.)

Christopher Boorse's biostatistical theory of medical disorder claims that biological part-dysfunction (i.e., failure of an internal mechanism to perform its biological function), a factual criterion, is both necessary and sufficient for disorder. Jerome Wakefield's harmful dysfunction analysis of medical disorder agrees that part-dysfunction is necessary but rejects the sufficiency claim, maintaining that disorder also requires that the part-dysfunction causes harm to the individual, a value criterion. In this paper, I present two considerations against the sufficiency claim. First, I analyze Boorse's central argument for the sufficiency claim, the "pathologist argument," which takes pathologists' intuitions about pathology as determinative of medical disorder and conclude that it begs the question and fails to support the sufficiency claim. Second, I present four counterexamples from the medical literature in which salient part-dysfunctions are considered nondisorders, including healthy disease carriers, HIV-positive status, benign mutations, and situs inversus totalis, thus falsifying the sufficiency claim and supporting the harm criterion., (© The Author 2014. 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.)

Objective: To evaluate the predictive validity of a proposed benign major depressive disorder (MDD) subtype, single-episode 'uncomplicated MDD', defined as MDD that remits within 6 months and lacks severe impairment, psychotic ideation, suicidal ideation, psychomotor retardation, and feeling worthless., Method: Using two-wave National Epidemiologic Survey on Alcohol and Related Conditions data, four groups differing in wave 1 lifetime MDD history (no history [n = 27 609]; single-episode uncomplicated [n = 418]; other single-episode [n = 1943]; multiple episode [n = 2473]) were evaluated for 3-year follow-up rates of major depressive episode (MDE), generalized anxiety disorder (GAD), and suicide attempt., Results: Follow-up rates for no-MDD-history, single-episode uncomplicated MDD, other single-episode MDD, and multiple-episode MDD, respectively, were depressive episode 6.1%, 6.9%, 19.5%, 27.1%; GAD 2.7%, 4.3%, 7.8%, 11.2%; and suicide attempt 0.3%, 0.1%, 0.8%, 1.7%. For all validators, 3-year rates for single-episode uncomplicated cases were not significantly different from no-MDD-history rates, but significantly lower than both single- and multiple-episode other-MDD rates. Mild MDD, defined by having only five or six symptoms, did not yield similarly benign results; logistic regression showed 'uncomplicated' provides incremental validity over 'mild' in explaining validator rates. Validator differences were not explainable by treatment-rate differences., Conclusion: Single-episode uncomplicated MDD is a benign subtype lacking typical MDD negative sequelae. The planned DSM-5.1 revision should reinstitute an extended bereavement exclusion applied to all stressors., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Genotyping of classical human leukocyte antigen (HLA) alleles is an essential tool in the analysis of diseases and adverse drug reactions with associations mapping to the major histocompatibility complex (MHC). However, deriving high-resolution HLA types subsequent to whole-genome single-nucleotide polymorphism (SNP) typing or sequencing is often cost prohibitive for large samples. An alternative approach takes advantage of the extended haplotype structure within the MHC to predict HLA alleles using dense SNP genotypes, such as those available from genome-wide SNP panels. Current methods for HLA imputation are difficult to apply or may require the user to have access to large training data sets with SNP and HLA types. We propose HIBAG, HLA Imputation using attribute BAGging, that makes predictions by averaging HLA-type posterior probabilities over an ensemble of classifiers built on bootstrap samples. We assess the performance of HIBAG using our study data (n=2668 subjects of European ancestry) as a training set and HLA data from the British 1958 birth cohort study (n≈1000 subjects) as independent validation samples. Prediction accuracies for HLA-A, B, C, DRB1 and DQB1 range from 92.2% to 98.1% using a set of SNP markers common to the Illumina 1M Duo, OmniQuad, OmniExpress, 660K and 550K platforms. HIBAG performed well compared with the other two leading methods, HLA*IMP and BEAGLE. This method is implemented in a freely available HIBAG R package that includes pre-fit classifiers for European, Asian, Hispanic and African ancestries, providing a readily available imputation approach without the need to have access to large training data sets.

Community prevalence rates of alcohol use disorders (AUDs) provided by epidemiological studies using DSM-based diagnostic criteria pose several challenges: the rates appear implausibly high to many epidemiologists; they do not converge across similar studies; and, due to low service utilization by those diagnosed as disordered, they yield estimates of unmet need for services so high that credibility for planning purposes is jeopardized. For example, two early community studies using DSM diagnostic criteria, the Epidemiologic Catchment Area Study (ECA) and the National Comorbidity Survey (NCS), yielded lifetime AUD prevalence rates of 14 and 24%, respectively, with NCS unmet need for services 19% of the entire population. Attempts to address these challenges by adding clinical significance requirements to diagnostic criteria have proven unsuccessful. Hypothesizing that these challenges are due to high rates of false-positive diagnoses of problem drinking as AUDs, we test an alternative approach. We use the harmful dysfunction (HD) analysis of the concept of mental disorder as a guide to construct more valid criteria within the framework of the standard out-of-control model of AUD. The proposed HD criteria require harm and dysfunction, where harm can be any negative social, personal, or physical outcome, and dysfunction requires either withdrawal symptoms or inability to stop drinking. Using HD criteria, ECA and NCS lifetime prevalences converge to much-reduced rates of 6 and 6.8%, respectively. Due to higher service utilization rates, NCS lifetime unmet need is reduced to 3.4%. Service use and duration comparisons suggest that HD criteria possess increased diagnostic validity. Moreover, HD criteria eliminate 90% of transient teenage drinking from disorder status. The HD version of the out-of-control model thus potentially resolves the three classic prevalence challenges while offering a more rigorous approach to distinguishing AUDs from problematic drinking.

According to the introduction to the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, each disorder must satisfy the definition of mental disorder, which requires the presence of both harm and dysfunction. Constructing criteria sets to require harm is relatively straightforward. However, establishing the presence of dysfunction is necessarily inferential because of the lack of knowledge of internal psychological and biological processes and their functions and dysfunctions. Given that virtually every psychiatric symptom characteristic of a DSM disorder can occur under some circumstances in a normally functioning person, diagnostic criteria based on symptoms must be constructed so that the symptoms indicate an internal dysfunction, and are thus inherently pathosuggestive. In this paper, we review strategies used in DSM criteria sets for increasing the pathosuggestiveness of symptoms to ensure that the disorder meets the requirements of the definition of mental disorder. Strategies include the following: requiring a minimum duration and persistence; requiring that the frequency or intensity of a symptom exceed that seen in normal people; requiring disproportionality of symptoms, given the context; requiring pervasiveness of symptom expression across contexts; adding specific exclusions for contextual scenarios in which symptoms are best understood as normal reactions; combining symptoms to increase cumulative pathosuggestiveness; and requiring enough symptoms from an overall syndrome to meet a minimum threshold of pathosuggestiveness. We propose that future revisions of the DSM consider systematic implementation of these strategies in the construction and revision of criteria sets, with the goal of maximizing the pathosuggestiveness of diagnostic criteria to reduce the potential for diagnostic false positives.

Valid diagnostic criteria support generalizations about treatment effectiveness, allowing progress in developing empirically supported treatments. The DSM-5 revision provides an opportunity to consider whether diagnostic changes are increasing validity. In this paper, I first offer broad suggestions for conceptually advancing diagnostic validity while awaiting greater etiological understanding. These include, for example, improving "conceptual validity" (disorder/nondisorder differentiation); extending diagnosis beyond disorders to include mismatches between normal variation and social demands ("psychological justice"); placing disorder etiology in evolutionary context as harmful failure of biologically designed functioning ("harmful dysfunction"); and taking an integrative theoretical approach to human meaning systems. The paper then examines the DSM-5's controversial decision to eliminate the major depression bereavement exclusion (BE), detailing the evidence and attendant debate. Elimination was defended by citing several hypotheses (e.g., excluded cases are similar to other MDD; exclusions risk missing suicidal cases; medication works with excluded cases), all of which were either empirically falsified or based on faulty arguments. Most dramatically, excluded cases were empirically demonstrated to have no more depression on follow-up than those who never had MDD. I conclude that BE elimination undermined rather than increased conceptual validity and usefulness for treatment research. Finally, I draw some general lessons from the DSM-5 BE debacle., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The In Review articles in this issue on normality and disorder by Dr Rachel Cooper and Dr Derek Bolton explore the importance of a value component of harm in the concept of mental disorder. They focus on the Diagnostic and Statistical Manual of Mental Disorder's clinical significance criterion, requiring that symptoms cause significant distress or role impairment, as the expression of the harm component. As Dr Bolton argues, harm in the form of distress or role impairment has always been intimately tied to the concept of disorder and treatment decisions; as Dr Cooper argues, without the harm requirement, any disliked anomaly may be labelled a disorder. Moreover, as Cooper argues, a harm requirement is not incompatible with a natural kinds approach to distinguishing among disorders or to a categorical approach to disorder; the lack of zones of rarity on the harm continuum does not preclude categorical underlying causal processes. However, neither paper systematically develops arguments regarding the other component of disorder, the requirement that the harm must be caused by underlying dysfunction. The dysfunction component distinguishes disorders from the many other negative conditions in life. Cooper's identification of dysfunction with symptom severity ignores the fact that normal suffering can be severe, and Bolton's attempt to encompass risk of harm within harm yields an implausibly expansive conception of disorder. While the harm component is essential, clarification of the dysfunction component of the concept of disorder, pursued in part 2 of this In Review in the December 2013 issue, is also essential to establishing a coherent and plausibly limited domain of psychiatric disorder within the broader arena of harmful conditions.

Objective: To evaluate whether the DSM's distinction between uncomplicated (normal) vs. complicated (disordered) bereavement-related depressive episodes can be validly extended to non-bereavement stressor-related depression (SRD). Previous findings supporting the uncomplicated/complicated SRD distinction's discriminant validity were criticized as tautological because of definitional biases (e.g., 'uncomplicated' requires brief duration, yet duration was a validator). We tested whether uncomplicated/complicated SRD validator differences are tautological or real., Method: Using National Comorbidity Survey data, we compared uncomplicated SRDs, complicated SRDs, and endogenous/psychotic MDD on levels of eight pathology validators. We identified definitional biases affecting six validators, and corrected them by deleting the biasing definitional components and recalculating validator levels., Results: After correction of biases, uncomplicated SRDs had significantly lower pathology levels than both complicated SRDs and endogenous/psychotic MDD on seven of eight validators, disconfirming the tautology hypothesis. Regression analysis revealed that 'uncomplicated' cannot be equated with 'mild'. Extending the 'uncomplicated' durational threshold from 2 to 6 months yielded equal or stronger discriminant validity, suggesting the arbitrariness of the current durational criterion., Conclusion: Uncomplicated SRDs' lower pathology levels are because of real syndromal differences, not definitional tautologies. The uncomplicated/complicated distinction has discriminant validity when extended to non-bereavement SRDs as an indicator of normality vs. disorder., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate whether the DSM distinction between uncomplicated (normal) and complicated (disordered) bereavement-related depression (BRD) has discriminant validity on a range of pathology indicators. The DSM's major depression bereavement exclusion (BE) excludes BRDs from diagnosis when they are uncomplicated (defined by brief duration, non-severe impairment, and lack of certain pathosuggestive symptoms) but classifies all other ("complicated") BRDs as major depression. A previous report seemed to support the uncomplicated/complicated distinction's discriminant validity. However, those arguing for eliminating the BE from DSM-5 dismiss the findings as 'tautological,' attributing the validator differences to definitional biases (e.g. 'uncomplicated' requires 'no suicidal ideation,' yet 'lifetime suicide attempt' was a validator). This study empirically tests whether the uncomplicated/complicated differences are real or tautological., Method: Using National Comorbidity Survey data, confounds between definitional criteria for 'uncomplicated' and pathology validators were identified and corrected by deleting the biasing criteria and recalculating the corresponding validator's outcome., Results: Six validators (interference with life, suicide attempt, melancholic depression, duration, hospitalization, and number of symptoms) were reanalyzed using unbiased definitions for 'uncomplicated.' All still yielded significantly lower pathology levels for uncomplicated BRDs, disconfirming the 'tautology' hypothesis. Regression analysis revealed that 'uncomplicated' offered incremental validity over severity alone in predicting pathology, so 'uncomplicated' cannot be equated with 'mild.', Conclusion: Uncomplicated BRDs' lower pathology validator levels are because of real syndromal differences, not definitional tautologies, supporting the BE's validity., (© 2012 John Wiley & Sons A/S.)

Objective: Functional MR techniques report on a variety of biologic features of tumors: dynamic contrast-enhanced, diffusion-weighted, and intrinsic susceptibility-weighted MRI and MR spectroscopy reflect, at a simplistic level, vascularity, cellularity, hypoxic status, and metabolism, respectively. This article reviews the evidence for each of the functional MR readouts to determine these clinical end points and thus influence the management of ovarian, endometrial, and cervical cancer., Conclusion: These techniques may be implemented in gynecologic malignancies to detect, characterize, and stage tumors as well as potentially to predict the outcome and measure response to treatment.

High community prevalence estimates of DSM-defined major depressive disorder (MDD) have led to proposals to raise MDD's diagnostic threshold to more validly distinguish pathology from normal-range distress. However, such proposals lack empirical validation. We used MDD recurrence rates in the longitudinal 2-wave Epidemiologic Catchment Area Study to test the predictive validity of three proposals to narrow MDD diagnosis: a) excluding "uncomplicated" episodes (i.e., episodes that last no longer than 2 months and do not include suicidal ideation, psychotic ideation, psychomotor retardation, or feelings of worthlessness); b) excluding mild episodes (i.e., episodes with only five to six symptoms); and c) excluding nonmelancholic episodes. For each proposal, we used lifetime MDD diagnoses at wave 1 to distinguish the group proposed for exclusion, other MDD, and those with no MDD history. We then compared these groups' 1-year MDD rates at wave 2. A proposal was considered strongly supported if at wave 2 the excluded group's MDD rate was not only significantly lower than the rate for other MDD but also not significantly greater than the no-MDD-history group. Results indicated that all three excluded groups had significantly lower recurrence rates than other MDD (uncomplicated vs. complicated, 3.4% vs. 14.6%; mild vs. severe, 9.6% vs. 20.7%; nonmelancholic vs. melancholic, 10.6% vs. 19.2%, respectively). However, only uncomplicated MDD's recurrence rate was also not significantly greater than the MDD occurrence rate for the no-MDD-history group (3.4% vs. 1.7%, respectively). This low recurrence rate resulted from an interaction between uncomplicated duration and symptom criteria. Multiple-episode uncomplicated MDD did not entail significantly elevated recurrence over single-episode cases (3.7% vs. 3.0%, respectively). Uncomplicated MDD's general-distress symptoms, transient duration, and lack of elevated recurrence suggest it may generally represent nonpathologic intense sadness that should be addressed in treatment guidelines and considered for exclusion from MDD diagnosis to increase the validity of the MDD/normal sadness boundary., (Copyright © 2013 World Psychiatric Association.)

In the conclusion to this multi-part article I first review the discussions carried out around the six essential questions in psychiatric diagnosis - the position taken by Allen Frances on each question, the commentaries on the respective question along with Frances' responses to the commentaries, and my own view of the multiple discussions. In this review I emphasize that the core question is the first - what is the nature of psychiatric illness - and that in some manner all further questions follow from the first. Following this review I attempt to move the discussion forward, addressing the first question from the perspectives of natural kind analysis and complexity analysis. This reflection leads toward a view of psychiatric disorders - and future nosologies - as far more complex and uncertain than we have imagined.

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM--whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article took up the first two questions. Part II will take up the second two questions. Question 3 deals with the question as to whether DSM-V should assume a conservative or assertive posture in making changes from DSM-IV. That question in turn breaks down into discussion of diagnoses that depend on, and aim toward, empirical, scientific validation, and diagnoses that are more value-laden and less amenable to scientific validation. Question 4 takes up the role of pragmatic consideration in a psychiatric nosology, whether the purely empirical considerations need to be tempered by considerations of practical consequence. As in Part 1 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part 1 of this article took up the first two questions. Part 2 took up the second two questions. Part 3 now deals with Questions 5 & 6. Question 5 confronts the issue of utility, whether the manual design of DSM-III and IV favors clinicians or researchers, and what that means for DSM-5. Our final question, Question 6, takes up a concluding issue, whether the acknowledged problems with the earlier DSMs warrants a significant overhaul of DSM-5 and future manuals. As in Parts 1 & 2 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.