The classification of depression: are we still confused?

Recent developments in the classification of major depressivedisorder are reviewed in light of the predictions made by Kendellin the 1970s. Particularly, the institution of operationaldiagnoses along with the contentious issues of subdividingmajor depressive disorder and its characterisation on a dimensionalas opposed to a categorical scale.

A history of confusion

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A history of confusion

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In 1976, Robert Kendell published a seminal article in the Journal outlining the many problems (the `contemporary confusion')relating to the classification of depression.¹ Some of these,he argued, also had implications for the classification of mental illness as a whole. Farmer & McGuffin² revisited andupdated the issues in 1989 against the background of the Diagnostic and Statistical Manual 4th Edition (DSM–IV) and the thenimpending publication of the International Classification ofDiseases 10th Edition (ICD–10). Now, 30 years after Kendell'soriginal paper and as we enter the run up to DSM–V andICD–11, another update is timely.

In the mid-1970s the problems outlined by Kendell included howto validate diagnosis in the absence of any known pathologicalmechanism, how to subdivide depressive disorders and how toresolve uncertainty over the use of categories or dimensions.In particular, Kendell noted that the introduction of research operational criteria to define psychiatric disorders couldhave an impact on improving the reliability and the internationalstandardisation of diagnosis – an issue of major importanceat the time. He hoped that improving diagnostic reliabilitybetween researchers would be the first step in ensuring thevalidity of diagnosis, recognising that this could not be fullyachieved until the aetiopathology of depression is elucidated.What Kendell did not foresee in 1976 was the profound effectoperational definitions would have on national and internationalnosologies. The DSM was produced in completely operationalisedformat in 1980, while the World Health Organization's ICD was produced in operationalised form for research purposes in 1993.

The operationalised approach to defining diagnostic categorieshas become so firmly entrenched in modern psychiatry that fewwho use the two classification systems routinely in researchor clinical practice stop to reflect on them, let alone questiontheir scientific veracity. Operational definitions providea `top down', rigid and explicit set of rules for making a diagnosis.This allows good interrater reliability, whereby researchersor clinicians can achieve good agreement about the presenceor absence of a disorder, and it is also relatively straightforwardto generate standardised diagnostic interviews with computerisedscoring algorithms to apply the criteria. Alongside these strengths,however, there are crucial weaknesses that should be kept in mind.³

One disadvantage of operational definitions is that individualswho do not precisely fulfil criteria are often placed in a`not otherwise specified' category. In some instances, thedefinitions are so narrow that ragbag, `atypical' categories(e.g. DSM–III psychosis not otherwise specified) cancontain more individuals than `typical' categories (e.g. DSM–III schizophrenia).³ Conversely, some definitions of disorder,for example DSM–III major depression, are broad and tendto be `unstable', showing disappointing retest reliability.⁴ Operational definitions are also somewhat limited in the numberand type of item included in their combinatorial rules. Theynecessarily focus on more positive, concrete phenomena, inevitablyleaving some pathological experiences or observations unaccountedfor.

One specific example of the problems the operational criteriaapproach can cause is when people with bipolar disorder are`misclassified' as unipolar, and thus receive inappropriatetreatments that can be ineffectual and in some cases harmful.⁵This can happen when patients report clear-cut depressive episodesbut only experience hypomanic periods which do not meet thethreshold for bipolar disorder. Clearly, this is a situationthat clinician and researcher alike strive to avoid; however,the rigidity of the operational criteria in the DSM and ICDhamper such efforts.

Another concern regarding operational criteria is the `obstinatechallenge' of bringing diagnoses and aetiology together.⁶The authors of DSM–III and its subsequent versions aimedto be `atheoretical', deliberately attempting to avoid includingputative causal mechanisms in their classification schemes.McHugh suggests that this makes our current systems akin tobird and botanical field guides in that they enhance the accuracyof identification without explaining distinctions. In contrast,in general medicine, classification is organised around systems (respiratory, renal, etc.) and aetiologies (vascular, neoplastic,infectious, etc).

Subdivisions and overlaps

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Subdivisions and overlaps

Kendell proposed that a bipolar/unipolar subdivision of affectivedisorder had a persuasive research base¹ and further supportingevidence, including data from genetic studies, had firmly establishedthe taxonomy in the later review by McGuffin & Farmer.²The authors proposed a two-threshold model whereby unipolarand bipolar disorder are quantitatively rather than qualitativelydifferent, with both disorders lying on the same continuumof liability but bipolar disorder being the more extreme orsevere form. Recent genetic advances have shown this model tobe overly simplistic. In particular, a twin analysis convincinglyrefuted the two-threshold approach, whereby the data were betterexplained by a model of a distinct, but partly overlapping,set of genes.⁷ The genetic correlation between mania and depressionwas 0.65 but approximately 71% of the genetic variance of liabilityfor mania was not shared with depression. A separate set oftwin analyses, that involved relaxing the inbuilt hierarchyof diagnosis in DSM–IV, strongly suggested that thereare also partly distinct and partly overlapping genes contributingto bipolar disorder and schizophrenia.⁸ Although consideredcontroversial at the time, this was soon followed by supportingmolecular genetic evidence from linkage and association studies.⁹Yet other twin studies suggest that there is also considerableoverlap between risk factors for anxiety and depression.¹⁰

The genetic overlap between depression and anxiety is hardlysurprising given the high rates of comorbidity that exist betweenthe two disorders, as findings from the National ComorbiditySurvey testify.¹¹ This poses important questions for the treatmentof comorbidity¹² and also future diagnostic systems. Moffittand colleagues recently attempted to address this issue froma prospective, longitudinal approach.¹³ They reported that72% of individuals with generalised anxiety disorder (GAD) were diagnosed with comorbid depression and 48% of individuals withdepression also had GAD. Evidently there is a strong associationbetween the disorders in this large sample, and it would beinformative to ascertain how near the diagnostic thresholdsthose not classified as comorbid are. The authors claim thatthere is sufficient evidence to use the umbrella term of `distressdisorders' to cover both syndromes of depression and anxiety.They go on to say that the current hierarchical superiorityof depression over anxiety may also be questionable as thetwo disorders show symmetrical developmental trajectories, sothere is no evidence to prioritise one over the other. Theseconclusions should be of interest to those researchers chargedwith revising the classification systems of depression andanxiety. However, the key point from a clinical perspectiveis that the rates of comorbidity in depression are often underestimated,and that the treatment and management of depression is likelyto vary dependent on whether the comorbidity is with anxietyor with other common psychiatric disorders.

Another pertinent issue concerning how depression is subdividedarises from the recent revival of interest in the concept ofmelancholia. The rationale behind this resurgence is that majordepressive disorder is too heterogeneous a concept, while amelancholic subtype offers a reliable, valid and more homogenousgroup with specific treatment recommendations, specifically tricyclic antidepressants and electroconvulsive therapy. Theeditor of Acta Psychiatrica Scandinavica even felt sufficientlycompelled by the concept of melancholia to devote an entirerecent issue to the topic.¹⁴ The intentions of the authorsto help homogenise depression for both clinical and researchpurposes are admirable. However, some of the fundamental assumptions, such as the underlying neurobiology of melancholia being well-definedand distinct from other mood disorders, is somewhat dubious,as is the evidence presented in the issue, particularly regardingthe epidemiological findings. It appears as though melancholiais merely another term for severe major depressive disorder,and there seems little point in reintroducing the term as aconfusing synonym for an already well-established concept.

Categories v. dimensions

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Categories v. dimensions

The operational approach to defining depression is categoricalin that it defines cases or non-cases of disorder. However,when originally proposed by Hempel, he accepted that the individualitems of psychopathology that make up each definition weredimensional, where experience ranged in severity from mild,self-limiting and present in the general population to severe, persistent and pathological.¹⁵ Hempel suggested that foreach criterion the rater had to ask `does the respondent exhibitthis amount of (symptom) X?' In terms of criteria for depression,this translates as `has the individual experienced at least2 weeks of unremitting low mood?' This imposes a severity thresholdon a continuous variable: in this case, mood. Thus, recognitionthat symptoms of mental health are continuously distributedacross individuals within the general population as well asin those with disorders has been implicit since operationaldefinitions were first proposed. However, depression is a ubiquitoussyndrome that is associated with various mental disorders (schizophrenia,substance misuse, eating disorders, anxiety) along with physicaldisorders such as Parkinson's disease, myocardial infarction,stroke and obesity. Not all of these different manifestationsof depression respond well to antidepressant medication, suggestingthat they may be aetiologically distinct. Depression also rangesin severity and symptom profile from the severe psychotic typeof disorder found in bipolar illness to mild neurotic depressivesymptoms associated with some personality disorders. Recent taxonomic studies exploring whether there is a discontinuitybetween clinical depression and subthreshold depressive symptomshave been inconclusive.¹⁶

In fact, the ICD–10 classification of depression incorporatesa quasi-dimensional approach, inasmuch as there are mild, moderateand severe forms which some authorities suggest have implicationsfor treatment. For example, the UK National Institute for Healthand Clinical Excellence (NICE) guidelines indicate that thepreferred first line of treatment for mild depression shouldbe psychological therapy and that drug treatment should be reservedfor those with moderate or severe forms of illness.

Arguing for dimensions v. categories becomes somewhat spurious since both approaches are necessary.¹⁷ Certainly, there isa clinical requirement to define cases of a particular disorder,since this determines management and prognosis as well as facilitatingservice planning. However, defining psychopathology dimensionally probably has greater utility for basic science research especially neuropsychology and genetics. The dimensional structures ofthe psychopathology of unipolar depression,¹⁸ as well astheir bipolar counterparts (L. Forty, personal communication,2007), have already been established using multivariate statisticalapproaches. Thus, there is an accepted dimensional structurefor depression that can provide the continuous measures requiredin certain spheres of research. This indicates that DSM–Vand ICD–11 probably need to incorporate both categories and dimensions; not one or the other.¹⁹

Conclusions

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Conclusions

So what has changed over the past 30 years? Is there still confusionover the classification of depression? The answer to the firstquestion is that the main taxonomies have not been altereddrastically. An operationalised approach to diagnosis is stillpredominant in the main nosologies, although this may be challengedin the next revision of the DSM.⁶ The subdivision of unipolarand bipolar depression is well established by the researchevidence and the melancholic definition of depression is also receiving a resurgence in research interest. However, new aetiologicalclues about shared and specific risk factors for depression,mania and schizophrenia are emerging from genetic and neuroimagingresearch and this may increasingly challenge traditional classifications.It is possible that we could see wholesale shifts in classificatorygroups, as has happened in other branches of medicine (e.g.peptic ulcer being reclassified from inflammatory to infectiousdiseases).

Similarly, after much debate comparing dimensional v. categorical approaches to diagnosis, it is now evident that both have theirspecific applications and both are necessary to psychiatry.It seems highly likely at the time of writing that DSM–Vwill be cast in both dimensional and categorical formats.

Are we still confused? Since it remains the case that we stillhave little understanding of the precise aetiology of depression,the answer to this question is surely `yes'. Our current nosologiesremain as `working hypotheses' and have no greater validitythan the definitions of depression that existed when Kendellwrote in 1976. Consequently, the `true' classification of depressionremains as elusive as it was 30 years ago, though this is byno means reason to give up hope for the future.

ACKNOWLEDGMENTS

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ACKNOWLEDGMENTS

The article was conceived and drafted by J.C., with criticalappraisal and some revision and additions by P.M. and A.E.F.J.C. is funded by an MRC PhD studentship.

REFERENCES

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