Developmentally Moderated Expressions of the Neuropathology Underlying Schizophrenia

Abstract

A gradually accumulating body of literature suggests that behavioral dysfunction precedes the onset of the schizophrenic syndrome by many years. Thus, a comprehensive neurodevelopmental model of schizophrenia must encompass these early manifestations of dysfunction as well as the postmorbid period. This article draws on previous research findings as well as recently proposed neurodevelopmental models to offer some further hypotheses about the neurodevelopmental process underlying the changing life-course manifestations of the diathesis for schizophrenia. It is proposed that normal maturational events in the central nervous system moderate the behavioral expression of a congenital neuropathology that affects subcortical regions of the brain that are part of multiple neural circuits. Specifically, it is suggested that the diathesis for schizophrenia involves a functional excess of dopamine activity in the basal ganglia that serves to disrupt these circuits. Findings from empirical research suggest a modal developmental trajectory for schizophrenia in which neuromotor dysfunction is most pronounced in early childhood and late in life, whereas florid psychotic symptomatology is most pronounced in late adolescence and early adulthood. The literature on normal central nervous system development suggests that the feedback circuit linking motor cortex with subcortical structures is maximally metabolically activated, relative to other circuits, early and late in the life course. Thus, subcortical dopamine excess may be predominantly expressed in motoric symptoms during these periods. In contrast, late adolescence and early adulthood are marked by low motor cortex metabolic activity relative to other cortical regions, in particular limbic and frontal regions. In addition, hormonal changes appear to result in a maximal activation of the dopamine system during this developmental period. Thus, it is hypothesized that during this period the neural circuitry abnormality will be primarily behaviorally expressed in psychotic symptoms. Some implications of the model for the study of movement abnormalities and psychotic symptoms are discussed.

The Psychomotor Theory of Human Mind

“…The findings appeared to be specific for schizotypic personality disorder, especially for the right-hand responses, indicating problems in left-brain functioning, which is frequently reported to be dysfunctional in schizophrenia (see Miller et al, 1995), as it is for the schizotypal subjects (Mikhailova et al, 1996;Sailsbury et al, 1996). Interestingly enough, the heightened dopamine-receptor activation was reported to induce both movement abnormalities and schizophrenia-spectrum symptoms (see Walker, 1994). There are many reports indicating a coupling of schizophrenia with the motor system.…”

Cross-Cutting Advancements Usher in a New Era for Motor Research in Psychosis

“…34 This trend is likely to continue, as recent years have seen adaptation for use of the noted instrumental assessments inside the scanner. 35 Although abnormal motor behaviors have been detected long before the onset of the first positive symptoms in psychosis, [36][37][38] until now the potential for translational applications has been somewhat unclear. However, as motor behaviors are integrally tied to many of the same processes that, in part, drive the onset and maintenance of psychosis (eg, aberrant DA activity in basal ganglia circuits), there are several areas of rich potential here.…”

“…39,40 Further, the area of prodromal research has provided another promising translational application. During the adolescent prodromal period, when DA abnormalities escalate, 41 and potentially interact with extant early vulnerabilities (eg, signs of general motor system impairment pinpointed in archival and childhood home-video designs), 38 emerging specific motor signs such as hyperkinetic movements may serve as a highly sensitive prognostic indicator of basal ganglia dysfunction. 42 In support of this theory, prospective investigations in youth with prodromal syndromes have observed that the presence of specific motor abnormalities significantly increases the odds of developing psychosis in a brief 2-year period.…”

The persistence of developmental markers in childhood and adolescence and risk for schizophrenic psychoses in adult life. A 34-year follow-up of the Northern Finland 1966 birth cohort

“…In infants, the motor region is one of the most myelinated and metabolically active areas of the cerebral cortex, dominated by dopamine metabolism. The feedback circuit linking the motor cortex with subcortical structures is maximally activated in early life, and an abnormality is more likely to be manifested in motor dysfunction (Walker, 1994). Neuronal circuits involving both prefrontal areas and the basal ganglia are critically implicated in movement.…”

“…Walker's (1994) classic study of home movies obtained from families where one child later 5 developed schizophrenia indicated that gross but transient abnormal motor behaviour was most pronounced during the first two years of life, but found some evidence of "catching-up" in later years of childhood. In the UK 1958 birth cohort (Crow et al, 1995) problems in social adjustment and school performance detected in preschizophrenic children at age 7 were still present (manifest as differences in group means) at follow-up at the age of 11.…”