Ensayos de inmunoprecipitación de proteína

The recent publication of DSM-5 has had an ambivalent role in the ED nosology discourse. On the one hand, it has answered some of the concerns that had been raised with regards to the diagnostic criteria contained in DSM-IV. On the other, it has reignited the debate over the empirical validity and suitability of current diagnoses to define different ED, therefore posing similar conundrums to both research and clinical practice as those that had been raised by DSM-IV (Thomas et al., 2010). As Kraemer recently put it “the value of a diagnosis lies in how closely a diagnosis corresponds to a distinct disorder” (Kraemer, 2013, p.413) and much debate has, in the past years, revolved around the extent to which current diagnoses are suitable to characterise different ED. In what follows, I will review some: (i) conceptual issues attached to the notion of diagnosis and key points in the debate between continuous vs. categorical approaches to psychiatric diagnosis; and, finally; (ii) limitations of current ED classification, (iii), and literature suggesting an evidence-based approach to classification.

Psychiatric diagnoses: nature, advantages and disadvantages

The Diagnostic and Statistical Manual of mental health disorders third edition (DSM-III) with its specific sets of diagnostic criteria for the definition of mental illness has introduced a categorical understanding of psychiatric diagnoses, which on the one hand has favoured the proliferation of epidemiological research around mental health, whilst on the other, it has been argued, has limited a better understanding of psychiatric conditions.

Diagnostic manuals since DSM-III have employed categorical approaches for the definition of psychopathology through the assessment of the level of symptoms, the extent of impairment, the duration of problem, and of the exclusion of symptoms which are believed to trump/precede or otherwise explain those of the presumed diagnosis (Mirowsky & Ross, 1989). Robins and Guze have arguably pioneered such categorical approach by proposing 5 criteria of diagnostic validity: clinical description, laboratory study, distinction from other disorders, and follow-up and family study, which they have used to argue that a difference existed between good-prognosis schizophrenia and mild schizophrenia (Robins & Guze, 1970).

The introduction of such categorical understanding of psychiatric diagnosis has had numerous advantages for psychiatric research. It has broadly facilitated communication within the field as well as understanding across disciplines, such as epidemiology and public policy. Universal definitions of mental illnesses have also allowed better societal understanding of mental health and to some extent have lowered the levels of stigma attached to psychiatric illness.

Critics of the categorical approach have however highlighted the extent to which the ‘reification’ of psychiatric diagnosis (Mirowsky & Ross, 1989) and of the ‘disease entity’ paradigm somehow restrict a true understanding of psychiatric illness by limiting it to “fictitious constructs which in reality have fluid boundaries” (K. Jaspers, as quoted in (K. Jaspers, as quoted in (Maj, 2013)). Recent scientific developments in neuroscience and genetics demonstrating shared similarities amongst individuals with different conditions, as well as the concept of psychiatric comorbidity itself have been proposed as evidence of the potential limitations of applying categorical approaches to the study of mental illness (Kendell, 2003). Whereas in medicine qualitative differences allow for categorical distinctions between different conditions sharing similar symptoms, in psychiatric research (with the exception of few cases that have been identified as having defined biological aetiologies, i.e. Down syndrome) such distinction is not possible.

Within such framework, it has been argued, the application of a dimensional approach to the definition of psychopathology, one which allows for ‘zones of rarity’ or overlapping symptoms, could result in greater potential for the differentiation not only between different psychiatric illness, but also between psychiatric illnesses and normality (Kendell, 2003).

Some have argued against the existence of a clear distinction between illness and normality in psychiatry. In 2000, Widiger & Clark stated that “[…] the challenge facing the developers of DSM-V may not be to differentiate more clearly between normal and pathologic expressions of behavior; rather, it may be to determine whether or not a qualitative distinction can in fact be made” (Widiger & Clark, 2000) . Much of the debate which has informed the changes in diagnostic criteria for ED in DSM-5 has stemmed from studies (which are summarised in the following section) showing that lowering thresholds for the definition of ED did not yield differences in levels of comorbid behaviours.

A categorical approach has been maintained by the new diagnostic system, with advantages and disadvantages for the delivery of care. On the one hand, where impairment to the individual exists in presence of sub-threshold behaviours, but the current diagnostic systems do not allow for the formulation of a diagnosis, lack of access to treatment could significantly increase disease burden. On the other hand, the maintenance of a categorical system facilitates the selection of more severe cases avoiding an over- medicalization of society. Lower diagnostic thresholds, more consistent with dimensional approaches, could in fact result in over-diagnosis and in excessive disadvantages for the individual (i.e. stigma, unemployment) and society (i.e. expansion of treatment provision and costs associated with it).

It has been argued that categorical and continuous approaches to the definition of mental illness are not mutually exclusive and that “discrete entities and dimension of continuous variation are […] compatible with a

of psychiatric morbidity” (Kendell, 2003, p.7). However, current diagnostic models do not yet reflect this approach although literature investigating dimensional approaches to diagnoses has flourished. In the following sections, I will review literature exposing the limitations of the current diagnostic system with respect to ED and I will present the results of studies which have attempted to endorse a dimensional approach to the understanding of ED.

Limitation of current ED diagnostic criteria

As described in the previous sections, ED are defined by a combination of cognitions, behaviours, and physical correlates. However, little empirical evidence exists to support the current clustering of symptoms and the threshold that have been employed to define clinical relevance. Whilst two of the most criticised DSM-IV requirements: amenorrhea for AN, and the frequency criteria for BN and BED; have been dropped or modified in DSM- 5, concerns remain around the definition of ED symptomatology.

ED diagnoses, it has been argued, lack empirical derivation criteria (Wonderlich, Joiner Jr., Keel, Williamson, & Crosby, 2007). For instance, the choice of both specific frequency and duration cut-offs for symptoms of BN and BED in DSM-IV has been subject of much debate. The choice of a cut-off of twice a week for 3 months for BN and 6 months for BED was deemed arbitrary (Trace et al., 2012; Wilson & Sysko, 2009), and the use of a different duration criteria for the two disorders was not clear (Wilson & Sysko, 2009). Whilst DSM-5 has uniformed the above-mentioned criteria into a single one requiring episodes to occur ‘once per week for at least three months’, it can be argued that this change in criterion still does not reflect some of the recent findings in the literature, so is not evidence based.

Wilson and Sysko conducted a literature review of studies exploring the consequences of lowering the frequency criteria for BN and BED. They concluded that whilst the majority of studies used the proposed DSM-5

criteria to define sub-threshold variants of the two diagnoses, those investigating psychiatric comorbidity in individuals with ED symptoms present at even lower frequency did not find significant differences in this group from those seen in individuals bingeing/purging more often (Wilson & Sysko, 2009). More recently, a study by Field and colleagues on a sample of 8,594 female adolescents (mean age 12, SD 1.6) found that both BN and BED were longitudinally associated with a number of negative outcomes (e.g. binge drink frequently, start using drug, developing depressive symptoms) whether a weekly or monthly cut-off in determining bingeing and purging was used (A. E. Field et al., 2012).

DSM-5 has also replaced the ‘less than 85% of expected body weight’ cut off of DSM-IV for AN (American Psychiatric Association, 2000), with a new definition stating that the criterion is fulfilled if the patient is at “significantly low body weight in the context of age, sex, developmental trajectory and physical health”. Significantly low weight is defined as a weight that is less than minimally normal, or, for children and adolescents, less than that minimally expected” (American Psychiatric Association, 2013). Previous literature has shown that loosening the weight criterion in AN did not result in differences in psychopathology, disorder duration, or outcome (Crow, Stewart Agras, Halmi, Mitchell, & Kraemer, 2002; McIntosh et al., 2004; Watson & Andersen, 2003). The terminology ‘significantly low body weight’ therefore still assigns an important role to low weight, as opposed to the psychopathology leading to weight loss, without assessing evidence of whether cognitions and co-morbid psychopathology play an equally important role in contributing to the definition of the disorder. Whilst starvation symptoms are certainly an aggravating factor in AN they do not necessarily start at a low BMI, especially when patients’ premorbid weight is in the overweight or obese ranges (Lebow, Sim, & Luenzmann, 2013).

Alternatives to categorical definitions of ED

Several studies have tried to address the above-mentioned limitations of current diagnostic criteria. Clinical studies have shown that often diagnostic-cross over is only caused by the change of one symptom, whilst all others remain unchanged (Wildes & Marcus, 2013) and it has been speculated that ED dimensions might be better at explaining ED than diagnoses.

One attempt at departing from the limitations posed by diagnostic categories was advanced by Fairburn & Bohn in the shape of a singular “transdiagnostic” definition of EDs encompassing AN, BN and BED. This solution was advanced in light of the recognition ‘that far more unites the various forms of eating disorder than separates them’ and that patients tend to cross-over diagnoses (Fairburn & Bohn, 2005). Somehow developing this hypothesis, Franko & Omori in a study of 207 first year female college student found that comorbidity between eating pathology was associated with psychological comorbidity along a gradient of severity without a clear distinction from normality according to current diagnostic criteria (Franko & Omori, 1999). Whilst both these studies substantiate claims of a dimensional nature of ED on a continuum from normality along the lines of the hypothesis also advanced by Widiger & Clark (2000), other studies have investigated the extent to which it is possible and useful to distinguish between different ED.

Proponents of latent class analysis (LCA) have attempted to group observed data according to their unobserved common latent features. Several studies have used LCA to define common dimensions of disordered eating across their sample. A U.S.-based study of 2,163 Caucasian female twins has identified the presence of 6 classes: one characterised by normal weight, but disordered eating behaviours (e.g. binge eating, purging); two by low weight but no other disordered eating behaviours or psychopathology, and three which reflected the DSM-IV diagnoses of AN, BN and BED(C M Bulik, Sullivan, & Kendler, 2000). A clinical study of 1,179 individuals suggested

the existence of four latent classes, with class one showing features similar to AN-R; class two to AN-BP and BN-P with multiple purging methods; class three AN-R without any obsessive compulsive traits; and class four BN-P with vomiting as the only purging method (Keel et al., 2004). Results of these studies suggest that a wider range of classes could be found in general population samples and that the use of clinical sample could bias results in favour of existing diagnostic definitions. Latent class analysis has however been criticised on the grounds that optimal number of classes or dimensions is unclear (Williamson, Gleaves, & Stewart, 2005). Whilst broadening the scope for the understanding of ED, employing a LC approach to the study of ED does not surpass the inherent assumption of categorical models of the existence of well-defined groups of symptoms.

Taxometric analysis has attempted to analyse whether ED symptoms vary in type as well as in degree; in other words, whether ED dimensions can be complemented and better explained by categories. So far, results from the literature have been mixed. Williamson and colleagues have identified three latent features: 1) binge eating, 2) fear of fat- ness/compensatory behaviours, and 3) drive for thinness. Confirmatory analysis on external validators showed that whilst group 3 (corresponding to AN patients) existed on a continuum from normality, it differed from the group reporting binge eating. Therefore, they suggested the coexistence of categories alongside dimensions (Williamson et al., 2002). Others, using taxometric analyses to identify differences in the cognitive profile of ED individuals suggested that dietary restraint, body dissatisfaction, and drive for thinness happened on a continuum from normalcy, differing in degree, but not in kind, from those with lower levels of the cognitions (Holm-Denoma, Richey, & Joiner, 2010). Finally, more recently a study of 528 adults using Factor Mixture Analysis (FMA) showed the existence of 3 ED classes (2 reflecting bulimic symptoms and differentiated by greater weight phobia and purging methods and one resembling healthy individuals) and one severity dimension given by a symptom count across diagnoses (Keel, Crosby,