EDITORIAL

Lumpers and Splitters: Who Knows? Who Cares?

Bennett L. Leventhal, M.D.

I s autism a single continuous entity or is therea discontinuous group of syndromes that canfall under the rubric of autism spectrum dis-

order (ASD)? How many clusters of signs andsymptoms constitute a “real” diagnosis? Not atall unique to ASD, these issues have been amatter of controversy for years; they are no lessso during the current concurrent development ofthe DSM-5 and the International Classification ofDisease, Eleventh Revision. Using different strate-gies, Frazier et al.1 and Mandy et al.2 try to deter-mine the “correct” model for capturing the salientfeatures of ASD while supporting the notion thatASD may be a group of heterogeneous syndromessharing some common elements. Using DSM-5field trial data, they argue for 2 parsimoniousgroups of diagnostic criteria to identify a single,continuous disorder that varies along a spectrum ofsymptom severity. The arguments are “evidencebased” and cogent, but are they new and what dothey mean for a conceptual framework for childpsychiatric disorders and practice and research?

For generations, practitioners have tried to linksyndromes, or disorders, to specific pathophysio-logic conditions that in turn can lead to specifictreatments and even prevention or cures. In thecurrent era, child and adolescent psychiatry mustcontinue to pursue a new nosology that will lead tobiomarkers or other etiologic clues that will im-prove the diagnostic process and its relation totreatment. Will this new nosology lead us to thisgoal?

One of the challenges in creating the newdiagnostic criteria is specifically determininghow many and which signs and symptoms (cri-teria) are essential to make a diagnosis. To thisend, the stalwart investigators had to strugglewith whether they should be “lumpers” or “split-ters.” Splitters tend to use fine distinctions insigns and symptoms to classify unique condi-tions separately, whereas lumpers tend to be asparsimonious as possible by condensing similar

constructs under as a few categories as possible.

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In their work, Frazier et al.1 and Mandy et al.2

support the lumpers who are creating DSM-V.They have used unique samples and methods toarrive at similar conclusions.

In the work by Mandy et al.,2 708 childrenreferred to a specialized autism clinic in Londonwere examined using the Developmental, Dimen-sional and Diagnostic Interview. Using confirma-tory factor analysis, they tested three models forASD: a single-factor model, the DSM-IV model,and the DSM-5 model. In the end, only the DSM-5model met all criteria, leaving a two-factor solutionwith social communication and repetitive behaviordimensions. This model was stable across age andsex and seemed to fit those individuals with “sub-threshold” clinical presentations.

Frazier et al.1 used a different strategy, startingwith data from an even larger sample of 14,744individuals (8,911 with ASD and 5,863 with non-ASD) from the large Interactive Autism Network(IAN), a voluntary online data repository. Multi-ple methods were used to arrive at diagnoses,and the Social Responsiveness Scale and theSocial Communication Questionnaire were usedto measure autism symptoms in IAN sub-samples. None of the subjects were examineddirectly by the investigators and only a subset ofthe total IAN group completed some of the assess-ments. For this study, latent class and exploratoryfactor analyses were used. Once again, the investi-gators found that a two-factor solution, with com-munication/interaction and restricted/repetitivebehavior dimensions, was the best fit and clearlysuperior to the prior DSM criteria.

These studies are important efforts in under-standing the nature and clustering of ASD symp-toms and provide powerful support for theDSM-5 criteria, but they are not without impor-tant problems. The two samples were drawnfrom clinical populations (the IAN “controls”were unaffected siblings) with no direct exami-nation of the IAN subjects or controls. As has

been reported by Kim et al.,3 studying only

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EDITORIAL

clinical samples may reflect a substantially biaseddistribution of the ASD phenotype, not to men-tion a significant undercounting of affected indi-viduals. Nonetheless, the parsimonious modelthat lumped all known ASD signs and symptomsinto two factors was statistically significant, witha more than satisfactory level of specificity.

The problem of “lumpers” and “splitters” isnot new to science. Indeed, Darwin wrote aboutthis in 1857 when he cautioned a colleague aboutthe significant risks of taking either position.4

McKusick in his 1969 article, “On Lumpers andSplitters, or the Nosology of Genetic Disease,”5

expressed similar concerns when he commentedon largely genetic disorders, such as ASD, thatare characterized by genetic heterogeneity andpleiotropism. Pleiotropism refers to multiple ef-fects coming from a single etiologic factor, andgenetic heterogeneity is the existence of two ormore distinct genetic substrates (including gene-by-environment interactions) for a single pheno-type. Within this model, McKusick argued thatsplitting facilitates the understanding of geneticheterogeneity and limits the examination ofpleiotropism. Conversely, lumping helps to un-ravel the mysteries of pleiotropism and possiblyobscure heterogeneity. So, which is better, lump-ing or splitting?

Frazier et al., Mandy et al., and the DSM-5have clearly spoken in favor of lumping, but atwhat cost and should we care? Of course, weshould care! First, we must recognize that com-promises are inherent to the development of ournosologic systems. Second, we must be fullyaware of the limits in the populations and datathat are being lumped and split to arrive at thenew nosology. In the studies by Frazier et al. andMandy et al., the clinical samples have methodo-logic problems that lead to important questionsand limits on the generalizability and applicabil-ity of findings. As scientists and clinicians, wemust appreciate these limits. Third, we must askwhether the lumping is consistent with our cur-rent understanding of ASD pathophysiology. Forexample, did our colleagues lump important

factors that may have distinct biological sub-

Psychiatry. 2012;51:41-50.

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strates but were unmeasured in these studies,such as eye tracking, face recognition, theory ofmind, and joint attention? By lumping, theDSM-5 might obscure several possible etiologicsubstrates for these and other phenotypic dimen-sions of ASD that may have been clearer withmore splitting; and the compromise may lead usto miss some opportunities for treatment andcure. Of course, this must be balanced againstmany factors, including improved diagnosticspecificity. Fourth, the limits inherent to the newnosology remind us of the continuing importanceof careful clinical examinations, detailed historytaking, and phenotypic specification as essentialelements of clinical practice and clinical research;for investigators, examining large, representativeepidemiologic cohorts will be essential for agreater appreciation of the full dimensionality ofASD phenotypes. With that greater appreciationof the substrates for the heterogeneous presenta-tion of ASD will come new opportunities fordecisions about whether and when we should belumpers or splitters.

Why do we really care about the details of thisexercise in nosology? Because we can be comfortedby the methodic approach to the diagnosis of ASDin the DSM-5. For many purposes, this is a big stepforward. However, we must not forget that theseare among the first steps on a long journey towardunderstanding the etiology and treatment of ASD,a high-prevalence, high-impact disorder affectingchildren and their families throughout the worldwho travel this road with us. &

Accepted October 11, 2011

Dr. Leventhal is with the Nathan Kline Institute for Psychiatric Research,Orangeburg, NY.

Disclosure: Dr. Leventhal reports no biomedical financial interests orpotential conflicts of interest.

Correspondence to Bennett L. Leventhal, M.D., Deputy Director,Nathan Kline Institute for Psychiatric Research (NKI), 140 OldOrangeburg Road, Bldg. 35, Orangeburg, NY 10962; e-mail:Bennett.Leventhal@NKI.RFMH.org

0890-8567/$36.00/©2012 American Academy of Child andAdolescent Psychiatry

DOI: 10.1016/j.jaac.2011.10.009

REFERENCES1. Frazier TW, Youngstrom E, Speer L et al. Validation of proposed

DSM-5 criteria for autism spectrum disorder. J Am Acad ChildAdolesc Psychiatry. 2012;51:28-40.

2. Mandy WP, Charman T, Skuse D. Testing the construct validity ofDSM-5 autism spectrum disorder. J Am Acad Child Adolesc

3. Kim YS, Leventhal BL, Koh YJ et al. Total population study yieldshigher prevalence of autism spectrum disorder. Am J Psychiatry.2011;168:904-912.

4. Burkhardt F, Smith S, eds. The Correspondence of Charles Darwin.Volume 6: 1856-1857. Cambridge: Cambridge University Press; 1990.

5. McKusick VA. On lumpers and splitters or the nosology of geneticdisease. Perspect Biol Med. 1969;298-312.

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