(Developmental) Motor Signs: Reconceptualizing a Potential Transdiagnostic Marker of Psychopathological Vulnerability

Motor signs are increasingly acknowledged as candidate transdiagnostic endophenotypic features in different clinical stages of severe mental disorders, such as schizophrenia spectrum and mood disorders.^1–4 At the same time, motor signs in children and adolescents are widely recognized as proxy features of an altered neurodevelopmental trajectory associated with a higher risk of psychopathological manifestations. These motor abnormalities, spanning from developmental motor delays (eg, sitting, walking) to motor signs (eg, dyscoordination, psychomotor retardation, and psychomotor agitation), presumably reflect complex, cumulative and diachronically stratified interactions between genetic load for severe mental illness and early environmental adversities.

Indeed, there is a robust empirical evidence from familial high-risk studies indicating that the genetic risk for schizophrenia is associated with a delayed/altered motor development, whereas comparable evidence for the genetic risk for unipolar and bipolar depression is much less robust. For example, longitudinal studies indicate that impaired motor coordination in offspring of patients with schizophrenia is predictive of subsequent psychosis.^5–7 Similarly, the recent Danish VIA7⁸ study found that offspring of parents with schizophrenia (but not those of parents with bipolar disorder) had 2.02 times higher odds of having motor performance in the clinical range at the Movement Assessment Battery for Children (ie, the gold standard for the diagnostic assessment of Developmental Coordination Disorder in children and adolescents). This is partly echoed in preliminary studies based on polygenic risk scores, which showed that the higher is the score for schizophrenia the more severe is the delay in motor development in first years of age,⁹ a pattern less evident for bipolar score⁹ and in agreement with the finding of less severe motor signs in the premorbid developmental anamnesis of mood disorders.¹⁰

With respect to early environmental risk factors, there is empirical evidence that early adversities such as obstetric complications and prenatal infections, which are epidemiologically associated with higher longitudinal risk for motor deviances in the general population,¹¹ are also overrepresented in the anamnesis of patients with schizophrenia¹² and with major depression.¹³ Clearly, the complexity of the relationship between childhood motor signs and longitudinal risk for psychiatric disorders is amplified by the interaction of genetic and environmental risk factors across development. For example, in addition to the presumed genetic load, the presence of psychiatric conditions in mothers may be associated with increased rates of risky behaviors and subsequent higher risk of in utero exposures to drugs or infections, as well as obstetric complications.¹⁴ Moreover, parental mental illness may be associated with subsequent suboptimal (eg, hypostimulating or intrusive and overemotional) parenting, limiting the supervised sensory-motor exploration of the surrounding world that represents the experiential basis for motor development.^15,16

Along these lines, capitalizing on the Adolescent Brain Cognitive Development (ABCD) study, Damme and colleagues¹⁷ further confirmed a shared vulnerability between depression and psychosis risk for motor signs across development. Specifically, they found that: (1) developmental motor delay was associated in early adolescence with increased rates of psychotic-like experiences, depression symptoms, and familial risk; (2) motor delay was more frequent in case of familiarity for both depression and psychosis risk in comparison with familiarity for isolated conditions; (3) adolescent motor dyscoordination reflected risk for psychosis, while psychomotor agitation and retardation reflected depression risk, and psychomotor agitation reflected transdiagnostic risk for both conditions. Finally, fMRI data indicated that cortico-striatal connectivity was related to depression and psychotic risk, but cortico-cerebellar connectivity was linked to psychotic risk only. Therefore, Damme and colleagues¹⁷ concluded that motor signs may be a transdiagnostic marker of vulnerability for psychopathology, with early developmental motor delays probably reflecting pluripotent, familial risk features, whereas dyscoordination would specifically reflect psychosis risk.

However, the association between dyscoordination and psychosis risk is worth further discussion for at least 2 key reasons. First, the motor signs examined in the study, ie, dyscoordination, psychomotor retardation, and psychomotor agitation, are not a homogenous semeiologic constellation. Indeed, dyscoordination is to a certain extent the purest form of motor sign par excellence and is the cardinal feature of DSM-5 diagnosis of Developmental Coordination Disorder in children. On the contrary, the other psychomotor signs (ie, retardation or agitation) are not just pure motor features since they rather reflect a switch in the psychic tempo. For example, psychomotor retardation may reflect a global slowing leading to subsequent executive functional delays and even intellectual disability. Second, motor dyscoordination, also known as dyspraxia, is an established prognostic risk factor in offspring of schizophrenic parents for the longitudinal development of schizophrenic psychosis.^7,8

On the basis of such longitudinal association, recent papers^18–20 addressed this theoretical and clinical question: is dyscoordination (ie, dyspraxia or clumsiness) in childhood and adolescence just a direct proxy (among others) of an altered neurodevelopment associated with increased longitudinal psychotic risk, or, rather, dyscoordination represents a pathophysiological mechanism directly involved in the etiopathogenesis of psychosis? The hypothesized specific role of such motor component is based on the common role played by altered corollary discharge mechanisms in both childhood motor dyscoordination²¹ and in the development of psychosis (in this latter case through intermediate phenomena as reduced Sense of Agency).^18–20 Indeed, corollary discharges are copies of motor commands used to form a prediction of the sensation from self-generated movements and are allegedly involved in the development and maintenance of the implicit Sense of Agency, ie, the subjective experience of volitionally controlling one’s own acts that arises when the predicted sensation matches the actual sensation. Psychotic states are usually antedated by an attenuation of the sense of mineness (aka Sense of Ownership) and agentive me-ness (aka Sense of Agency) of experience which might reach the extreme of an external misattribution of the source of self-generated actions.²² Although disorders of the Senses of Agency and Ownership are somehow implicit to the traditional notion of Schneiderian first-rank symptoms, they have been only recently rediscovered as relevant tools for understanding the genesis of psychotic phenomena. For example, agency disturbances have been hypothesized as propaedeutic to the emergence of prototypical schizophrenia spectrum psychotic phenomena such as passivity delusions (where the person experiences her own thoughts, feelings, or actions as under external control) and auditory verbal hallucinations (eg, hearing one’s thoughts spoken aloud or externalized commenting “voices”). Crucially, not-yet psychotic early distortions of the Senses of Agency and Ownership embrace a substantial fraction of anomalous subjective experiences (aka Self-disorders).²³

Adopting a bottom-up perspective that could bridge the neurophysiological and the phenomenological, subjective level, corollary discharges are a plausible construct to ground at a neural level the developmental process of embodiment.²⁴ Such process is essential to maintain the implicit sense of mineness of psychomotor experience, lending coherence and fluidity to our immediate interaction with the surrounding world. Therefore, early impairments of corollary discharge may reverberate in initial distortions of the subjective experience facilitating the emergence of those subtler, subclinical modes of experience that precede (often of several years) the onset of positive symptoms, ie, Self-disorders. Self-disorders are trait-like nonpsychotic anomalies of subjective experience that have been recursively corroborated, also at a meta-analytical level, as schizophrenia spectrum vulnerability phenotypes,²⁵ encompassing varieties of depersonalization and similar experiential distortions characterized by a diminished sense of existing as an embodied, coherent subject, vitally immersed in the world and author of his own actions.

In sum, in line with Damme and colleagues¹⁷ results and combing the neurodevelopmental and vulnerability-stress model of schizophrenia, childhood motor signs of dyscoordination may reflect a schizotaxic vulnerability associated with putative genetic risk.²⁶ The subjective, experiential counterpart of such developmental dyscoordination would be represented by the progressive disturbance of the embodiment process (ie, disembodiment), which could then result in Self-disorders in later developmental phases.²⁷ Contrary to schizophrenia, such atypical or altered neurodevelopmental process is generally less prominent in mood disorders, in which motor signs seem better understood as concomitant features rather than developmental antecedents.^10,28

Finally, in pragmatic terms, while in the general population the positive predictive value of motor signs is relatively low due to the low base rate for the development of psychosis, in risk enriched populations such as family high risk and clinical/ultra-high risk, the prognostic value of motor signs is likely to be much stronger. In this respect, a finer-grained assessment of motor signs, particularly developmental ones (eg, delays in motor development), could empower the prognostic precision of available psychosis risk models.