Hospital admissions for asthma and chronic obstructive airways disease in east London hospitals and proximity of residence to main roads.
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Adolescent↗
Biomedical subjects
J C Wakefield
Publications and source records attributed to J C Wakefield.
Philosophy of science and the progressiveness of the DSM's theory-neutral nosology: response to Follette and Houts, Part 1.
Follette and Houts [Follette, W. C., Houts, A. C. (1996). Models of scientific progress and the role of theory in taxonomy development: a case study of the DSM. Journal of Consulting and Clinical Psychology, 64, 1120-1132] argue on philosophy-of-science grounds that the DSM's theory-neutral nosology is scientifically unprogressive because of its growing number of categories and lack of a unifying explanatory theory. They suggested replacing the DSM by competing theory-laden diagnostic manuals. I argue: (1) the ways things can go wrong with the mind are inherently diverse, so a unified theory of mental disorders is unlikely; (2) the claim that an increase in categories is inconsistent with scientific progress is empirically false; (3) the claim that the DSM's new categories expand the domain of disorder is largely false; (4) progress in a theoretically fragmented field requires a shared theory-neutrally defined domain; (5) theory-neutral diagnosis and integration of etiological theories is preferable for now to competition among theory-based diagnostic manuals; (6) philosophy of science supports use of a theory-neutral nosology for now.
Humans↗
The concept of disorder as a foundation for the DSM's theory-neutral nosology: response to Follette and Houts, Part 2.
Follette and Houts [Follette, W. C., Houts, A. C. (1996). Models of scientific progress and the role of theory in taxonomy development: a case study of the DSM. Journal of Consulting and Clinical Psychology, 64, 1120-1132] argue that 'mental disorder' and 'function' are value concepts that offer no scientific basis for the DSM's theory-neutral nosology or for distinguishing disorders from other behavioral problems. They also claim that the DSM presupposes a biological theory of etiology, thus is not really theory-neutral. They recommend replacing the DSM by theory-laden diagnostic manuals. I argue: (1) DSM criteria do not imply a biological model of disorder, (2) 'mental disorder' and 'function' have scientific content that allows one to distinguish disorder from nondisorder, (3) the evolutionary 'harmful dysfunction' analysis of disorder [Wakefield, J. C. (1992a). The concept of mental disorder: on the boundary between biological facts and social values. American Psychologist, 47, 373-388] coherently demarcates disorder from nondisorder, (4) the proposed behaviorist alternative to the DSM illustrated by the articles in Follette's special section [Follette, W. C. (Ed.) (1996a). Special section on the development of theoretically coherent alternatives to the DSM system. Journal of Consulting and Clinical Psychology, 64, 1117-1201] is incoherent because it does not distinguish disorder from nondisorder.
Humans↗
Evolutionary versus prototype analyses of the concept of disorder.
The harmful dysfunction (HD) analysis of the concept of disorder (J. C. Wakefield, 1992a) holds that disorders are harmful failures of internal mechanisms to perform their naturally selected functions. S. O. Lilienfeld and L. Marino (1995) proposed instead that disorder is a Roschian prototype concept without defining properties. Against the HD analysis, they argued that many disorders are not failures of naturally selected functions because they are either designed reactions (e.g., fever) or failures of functions that are not naturally selected (e.g., reading disorder). The HD analysis is defended here against these and other objections and compared with the Roschian account. It is argued that the objections are based on conceptual confusions and can be turned around to provide strong new support for the HD analysis. A series of conceptual experiments demonstrates the superior explanatory power of the HD analysis and disconfirms the Roschian account.
Biological Evolution↗
Mental disorder as a black box essentialist concept.
This is a reply to commentaries on the target article (J. C. Wakefield, 1999) on the evolutionary foundations of the concept of mental disorder in defense of the harmful dysfunction analysis (HDA) of disorder. The author argues that the HDA is adequate to explain disorder and nondisorder judgments and is not disconfirmed by any of the claimed counterexamples put forward by the commentators; the commentators' proposed alternatives to the HDA are inadequate to explain disorder and nondisorder judgments; and the concept of natural function is a factual, scientific concept, contrary to K. W. M. Fulford's (1999) claim that it is inherently evaluative. The foundations of the HDA are clarified by providing a black box essentialist analysis (H. Putnam, 1975; J. C. Wakefield, 1997, in press) of the concept of natural function that underlies the concept of disorder.
Biological Evolution↗
DSM-IV diagnostic criterion for clinical significance: does it help solve the false positives problem?
OBJECTIVE: A major change in DSM-IV is the inclusion in almost one-half of the diagnostic criteria sets of a clinical significance criterion, which requires that symptoms cause "clinically significant distress or impairment in social, occupational, or other important areas of functioning." In response to concerns that the DSM criteria are overly inclusive, the clinical significance criterion attempts to minimize false positive diagnoses in situations in which the symptom criteria do not necessarily indicate pathology. This article examines whether the clinical significance criterion achieves its purpose and considers its broader impact on diagnostic validity. METHOD: The effect of the clinical significance criterion on the diagnostic validity of DSM-IV criteria for a wide range of disorders was examined. RESULTS: For many diagnoses to which the clinical significance criterion was added, the symptom criteria are inherently associated with significant impairment, so the clinical significance criterion is redundant and therefore does not affect caseness. For some diagnoses, the clinical significance criterion is potentially helpful in eliminating false positives by elevating the level of required distress. However, there may be advantages to obtaining the same results by modifying some of the symptom criteria. Often the clinical significance criterion has led to the possibility of false negative diagnoses. CONCLUSIONS: In the process of revising DSM-IV, the generic use of the clinical significance criterion should be reconsidered. For each DSM diagnosis, it should be determined whether there is a need to raise the threshold of any of the existing symptom criteria or to add a criterion that excludes normal reactions to psychosocial stress.
False Negative Reactions↗
The Bayesian analysis of a pivotal pharmacokinetic study.
The aim of this paper is to carry out a detailed Bayesian population pharmacokinetic analysis of a three-period cross-over study of the drug fluticasone propionate carried out in 12 healthy male volunteers. The study was carried out to characterize the pharmacokinetics of the drug, in particular to investigate dose proportionality. We examine the appropriateness of modelling assumptions via a variety of diagnostic techniques. We also examine the effect of deleting time points at which the concentration was recorded as below the limit of quantification, as opposed to including these points as censored observations. We assess dose proportionality before carrying out a final combined analysis of data from all three doses.
Adult↗
Adaptations, exaptations, and spandrels.
Adaptation and natural selection are central concepts in the emerging science of evolutionary psychology. Natural selection is the only known causal process capable of producing complex functional organic mechanisms. These adaptations, along with their incidental by-products and a residue of noise, comprise all forms of life. Recently, S. J. Gould (1991) proposed that exaptations and spandrels may be more important than adaptations for evolutionary psychology. These refer to features that did not originally arise for their current use but rather were co-opted for new purposes. He suggested that many important phenomena--such as art, language, commerce, and war--although evolutionary in origin, are incidental spandrels of the large human brain. The authors outline the conceptual and evidentiary standards that apply to adaptations, exaptations, and spandrels and discuss the relative utility of these concepts for psychological science.
Adaptation, Physiological↗
The DSM's theory-neutral nosology is scientifically progressive: response to Follette and Houts (1996).
W. C. Follette and A. C. Houts (1996) argued on philosophy-of-science grounds that the Diagnostic and Statistical Manual of Mental Disorders (DSM) is scientifically unprogressive and should be replaced by competing theory-laden manuals. The author responds to their various arguments as follows: (a) The ways things can go wrong with the mind are inherently diverse, so failure to reduce the DSM's categories to 1 parsimonious theory is not necessarily scientifically unprogressive; (b) it is empirically untrue that growth in the number of a taxonomy's categories is inconsistent with scientific progress; (c) progress in theoretically fragmented fields requires shared theory-neutral categories, not theory-laden definitions of basic concepts; (d) at present in the mental health field, theoretical integration is scientifically more progressive than competition, and integration is promoted by the DSM's theory-neutral nosology; and (e) Follette and Houts's proposed behaviorist alternative to the DSM is incoherent.
Humans↗
Diagnosing DSM-IV--Part I: DSM-IV and the concept of disorder.
In this first article in a two-article series, I diagnose' a problem with DSM-IV, specifically, the overinclusiveness of its diagnostic criteria. Using the harmful dysfunction analysis of the concept of disorder (Wakefield, 1992a, American Psychologist, 47, 373-388) as a framework, I argue that DSM-IV criteria for many diagnostic categories fail to satisfy the analysis' dysfunction' requirement, that is, the criteria do not distinguish harmful conditions due to internal dysfunctions from harmful conditions that are nondisordered 'problems in living'. The overinclusiveness problem, I suggest, can be partly dealt with by giving up purely symptomatic criteria and contextualizing diagnosis to take into account the relationship between triggering causes and resulting symptoms. In Part II (Wakefield, 1997, Behaviour Research and Therapy, 35, 651-665, I examine Eysenck's (1986, Contemporary directions in psychopathology: Toward the DSM-IV) proposal for a dimensional diagnostic system to supplant DSM-IV.
Humans↗
Diagnosing DSM-IV--Part II: Eysenck (1986) and the essentialist fallacy.
In Part I (Wakefield, 1997, Behaviour Research and Therapy, 35, 633-649) of this two-article series, I used the harmful dysfunction analysis of the concept of disorder (Wakefield, 1992a, American Psychologist, 47, 373-388) to 'diagnose' a problem with DSM-IV. I argued that DSM-IV diagnostic criteria often violate the 'dysfunction' requirement by invalidity classifying harms not caused by dysfunctions as disorders. In Part II, I examine Eysenck's (Eysenck, 1986, Contemporary directions in psychopathology: Toward the DSM-IV) argument that DSM commits a 'categorical fallacy' and should be replaced by dimensional diagnoses based on Eysenckian personality traits. I argue that Eysenck's proposed diagnostic criteria violate the 'harm' requirement by invalidly classifying symptomless conditions as disorders. Eysenck commits an 'essentialist fallacy'; he misconstrues 'disorder' as an essentialist theoretical concept when in fact it is a hybrid theoretical-practical or 'cause-effect' concept. He thus ignores the harmful effects essential to disorder that are captured in DSM's symptom-based categories.
Humans↗
When is development disordered? Developmental psychopathology and the harmful dysfunction analysis of mental disorder.
One goal of developmental psychopathology is to understand the origins and course of mental disorders. I argue that pursuit of this goal requires a valid conceptual understanding of disorder and that this understanding can be provided by the "harmful dysfunction" analysis of the concept of disorder. The harmful dysfunction analysis holds that a disorder is a condition that is both harmful according to social values and caused by an internal dysfunction, that is, by a failure of an internal mechanism to perform a function for which it was naturally selected. This analysis explains why many of the distinctive features of developmental psychopathology are appropriate to the study of disorder. It is argued that the harmful dysfunction analysis is a necessary supplement to other proposed criteria for disorder, such as developmental deviation or predictive validity.
Adolescent↗
Modeling of trough plasma bismuth concentrations.
Disposition pharmacokinetics of bismuth following oral dosing of ranitidine bismuth citrate are complicated and variable. An analysis of data from healthy volunteers suggests a model with three disposition compartments and first-order absorption. Patient data are pooled from 10 separate studies and consist of 1140 trough concentrations measured in 802 patients following dosing of 2 to 12 weeks duration. There are therefore insufficient data to obtain reliable parameter estimates for the full model and we use instead a much reduced model and an informative prior based on the volunteer data. Individual parameter estimates from this model can then be used to establish covariate relationships. Trough concentrations were influenced by the coadministration of clarithromycin and by creatinine clearance. A simulation study was carried out to check the validity of the estimates obtained from the reduced model. We carry out analysis via Bayesian sampling-based techniques. Throughout, we use predictive distributions for both diagnostic and inference purposes. In particular, we determine predicted distributions for the Cmax, Cmin and AUC characteristics of new individuals.
Bayes Theorem↗
A comparison of a Bayesian population method with two methods as implemented in commercially available software.
In this paper we describe and discuss three specific estimation procedures that are available within commercially available population software packages. The first version of NONMEM (l) was released in 1979 and later versions are the standard analysis tools in both industry and academia. Recently, two commercially available pieces of software have become available. PPHARM was released during 1994 and POPKAN was released in 1995. We provide descriptions and critique the FOCE method within NONMEM, the two-step algorithm within PPHARM and the Markov chain Monte Carlo method that is utilized by POPKAN. We use simulated data generated from a monoexponential model to evaluate the parameter estimation capabilities of these methods within the three software tools. In particular we investigate the effect on parameter estimation of increasing both interindividual and intraindividual variability.
Bayes Theorem↗
When an irresistible epistemology meets an immovable ontology.
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Behavior↗
CooC and CooD are required for assembly of CS1 pili.
Many strains of enterotoxigenic Escherichia coli (ETEC) isolated from patients with diarrhoeal disease exhibit CS1 pili on their surfaces. These appendages, which are thought to be important for colonization of the upper intestine, are composed largely of multiple identical protein subunits encoded by cooA. We have sequenced the DNA directly downstream of cooA and identified two open reading frames, cooC and cooD, transcribed in the same direction as cooB and cooA. Following cooD is DNA homologous to an insertion sequence, so cooB, A, C and D appear to encode all the information needed for E. coli K-12 to synthesize CS1 pili. Complementation analysis of mutants cloned in E. coli K-12 and constructed in an ETEC-derived strain indicates that cooC and cooD are not required for stability of the major CS1 pilin protein or for its transport to the periplasm, but, like cooB, both are needed for assembly of cooA into pili.
Amino Acid Sequence↗
Limits of operationalization: a critique of Spitzer and Endicott's (1978) proposed operational criteria for mental disorder.
Spitzer and Endicott (1978) proposed an operational definition of mental disorder that is a more rigorous version of the brief definitions that appeared in the 3rd and revised 3rd editions of the Diagnostic and Statistical Manual of Mental Disorders. The heart of their proposal is a translation of the concept of dysfunction into operational terms. I argue that their definition fails to capture the concept of dysfunction and is subject to many counterexamples. I use my harmful dysfunction account of disorder (Wakefield, 1992a, 1992b), which interprets dysfunction in evolutionary terms, to explain both the appeal and the problems of Spitzer and Endicott's definition and to provide support for the harmful dysfunction view. I conclude that the failure of Spitzer and Endicott's sophisticated attempt at operationalization indicates that nonoperational definitions that use functional concepts must play a role in formulating valid diagnostic criteria.
Adaptation, Psychological↗
The concept of mental disorder. On the boundary between biological facts and social values.
Although the concept of mental disorder is fundamental to theory and practice in the mental health field, no agreed on and adequate analysis of this concept currently exists. I argue that a disorder is a harmful dysfunction, wherein harmful is a value term based on social norms, and dysfunction is a scientific term referring to the failure of a mental mechanism to perform a natural function for which it was designed by evolution. Thus, the concept of disorder combines value and scientific components. Six other accounts of disorder are evaluated, including the skeptical antipsychiatric view, the value approach, disorder as whatever professionals treat, two scientific approaches (statistical deviance and biological disadvantage), and the operational definition of disorder as "unexpectable distress or disability" in the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987). The harmful dysfunction analysis is shown to avoid the problems while preserving the insights of these other approaches.
Activities of Daily Living↗