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Neurodevelopmental disorder spectrum: the search for the ‘d’ factor

Fifteen years ago, an international multidisciplinary committee revisited the definition of cerebral palsy (CP). We initially considered a non-categorical approach to neurodevelopmental disorders but decided to retain a focus on CP as a descriptive (non-causal) entity to characterize a prevalent, clinically important group for the benefit of diagnostics, counselling, management, service provision, policy making, and research, and aid the potential for linking future research (from epidemiology to intervention) with previously published work. The updated definition underlined neurodevelopmental impairments that can occur in CP in addition to the hallmark disorders of movement and posture. Thus, CP was described as a group of disorders that can be categorized in various ways, depending on the purpose for classification. The usefulness of the construct has been confirmed in subsequent clinical, research, and societal contexts. It was recently suggested that CP be called ‘a spectrum disorder’, to further stress its heterogeneity. This welcome reminder focuses attention on the complexity of the disorder. Admittedly, the argument that ‘it is never the same disorder twice’ might be the rule rather than the exception in medicine. We might similarly talk about a migraine spectrum, multiple sclerosis spectrum, stroke spectrum disorder, or indeed, use ‘spectrum’ to describe any condition (medical or not) in which heterogeneity exists. In practice, an aetiological work-up remains essential in individuals with CP. Widely used typology schemes effectively address the diversity of presentation and validated easy-to-use classification systems usefully capture varying degrees of functioning in several aspects of daily life. However, reframing CP as a spectrum might, confusingly, erase its distinction from ‘marginal’ conditions (e.g. developmental coordination disorder [DCD]) and potentially blend CP with non-clinical problems that do not cause activity limitations and participation restrictions. Furthermore, a move to spectrum disorder terminology would be unlikely to improve the management of individuals with CP, enhance research or services, or reduce stigma. The analogy with autism spectrum disorder (ASD) is interesting. This construct is much newer and has a different history, with the recent convergence of previously separate conditions under one ‘spectrum’. Autism was originally understood to be a rare, distinctive, severe disorder of communication and interpersonal interaction. ASD now also includes groups of people with less impairing behavioural disorders and other individuals who were formerly classified based on their cognitive impairments. Recalibrating autism as ASD may have improved clinical recognition of its manifestations and needs, thereby enhancing clinical utility, advocacy, and access to services. Yet, conflation under a single nosological entity may be at odds with the search for specific neurobiological pathways and biomarkers for many generic neurodevelopmental disorders, including CP, ASD, DCD, attention-deficit/ hyperactivity disorder, and intellectual disability. Better understanding of the underlying mechanisms of these disorders has resulted in the development of improved management practices. The aetiology of the disorder may be a particularly important factor influencing prognosis and open the way towards targeted therapies. Emblematic examples include Rett syndrome (previously listed as a sub-diagnosis under ASD, but now understood as a discrete neurological disorder) and epilepsy, for which aetiology-based approach allows precision medicine. But while this may be true, a strong overlap in risk factors and comorbidities between neurodevelopmental disorders, as well as statistical modelling based on ‘big data’, might suggest other potentially helpful links to an even wider spectrum, encompassing many of the current categories. Common causal processes (a yet insufficiently characterized variable) could initiate the various disorders. Alternatively, a degree of shared symptoms (e.g. hypotonia, executive dysfunction) might result from common typical impairments that are secondary to the various neurodevelopmental disorders. The hypothesis of a single measurable general dimension accounting for disordered thought processes across psychopathology, termed the ‘p’ factor, is being discussed in psychiatry. At this stage of clinical, neuroscience, and genomics research, it might prove fruitful to look for diagnostic elements of a unidimensional developmental ‘d’ factor to account for the spectrum of neurodevelopmental disorders, with a view to designing and evaluating transdiagnostic therapies.