Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study.
ABSTRACT Premorbid cognitive deficits in schizophrenia are well documented and have been interpreted as supporting a neurodevelopmental etiological model. The authors investigated the following three unresolved questions about premorbid cognitive deficits: What is their developmental course? Do all premorbid cognitive deficits follow the same course? Are premorbid cognitive deficits specific to schizophrenia or shared by other psychiatric disorders?
Participants were members of a representative cohort of 1,037 males and females born between 1972 and 1973 in Dunedin, New Zealand. Cohort members underwent follow-up evaluations at specific intervals from age 3 to 32 years, with a 96% retention rate. Cognitive development was analyzed and compared in children who later developed schizophrenia or recurrent depression as well as in healthy comparison subjects.
Children who developed adult schizophrenia exhibited developmental deficits (i.e., static cognitive impairments that emerge early and remain stable) on tests indexing verbal and visual knowledge acquisition, reasoning, and conceptualization. In addition, these children exhibited developmental lags (i.e., growth that is slower relative to healthy comparison subjects) on tests indexing processing speed, attention, visual-spatial problem solving ability, and working memory. These two premorbid cognitive patterns were not observed in children who later developed recurrent depression.
These findings suggest that the origins of schizophrenia include two interrelated developmental processes evident from childhood to early adolescence (ages 7-13 years). Children who will grow up to develop adult schizophrenia enter primary school struggling with verbal reasoning and lag further behind their peers in working memory, attention, and processing speed as they get older.
- SourceAvailable from: James H Maccabe[show abstract] [hide abstract]
ABSTRACT: CONTEXT Clear evidence from many prospective, population-based studies indicates that patients who develop psychosis in adulthood experienced various cognitive deficits during childhood and adolescence. However, it is unclear whether these deficits become more severe during adolescence. OBJECTIVE To assess the influence of cognitive developmental trajectories in adolescence and young adulthood on the risk for psychosis in adulthood. DESIGN Longitudinal cohort study. SETTING Academic research. POPULATION-BASED COHORTS Four population-based cohorts of adolescent boys and young men born in Sweden in 1953, 1967, 1972, and 1977, totaling 10 717 individuals, and followed up through December 31, 2006. EXPOSURE Scores on tests of verbal, spatial, and inductive ability at age 13 years and in equivalent tests at army conscription (age 18 years). MAIN OUTCOME MEASURE Hospital admissions for nonaffective or affective psychoses in adulthood. RESULTS A relative decline (compared with the unaffected population) in verbal ability between ages 13 and 18 years was associated with increased risk for schizophrenia and for other nonaffective and affective psychoses (adjusted hazard ratio for schizophrenia for an increase of 1 SD in verbal ability, 0.59; 95% CI, 0.40-0.88; P = .009). Decline between ages 13 and 18 years was a much stronger predictor of psychosis than the verbal ability score at age 18 years alone. The association remained significant after adjustment for urbanicity, parental educational level, and family history of psychosis and persisted when cases with onset before age 25 years were excluded, indicating that this was not a prodromal effect. CONCLUSIONS A relative decline in cognitive performance in adolescence and young adulthood, particularly in verbal ability, is associated with increased risk for psychosis in adulthood, and a relative decline in verbal ability between ages 13 and 18 years is a stronger predictor of psychosis than verbal ability at age 18 years alone. This suggests an impairment of late neurodevelopment affecting the acquisition of verbal skills in adolescent boys and young men who later develop psychosis.JAMA psychiatry (Chicago, Ill.). 01/2013;
- [show abstract] [hide abstract]
ABSTRACT: OBJECTIVE Psychotic experiences in children are associated with an elevated risk of developing psychosis. The authors investigated whether the pattern of cognitive deficits present in psychosis also exists in children with psychotic experiences within the general population. METHOD The authors examined the longitudinal relationships between key cognitive domains, selected a priori based on their association with schizophrenia, and onset of psychotic experiences in children from the Avon Longitudinal Study of Parents and Children and whether these associations were independent of one another. RESULTS Lower performance in the domains of processing speed at age 8 years (odds ratio=1.24, 95% CI=1.12-1.36) and attention at age 11 (odds ratio=1.14, 95% CI=1.04-1.25) and decline of processing speed between the ages of 8 and 11 (odds ratio=1.29, 95% CI=1.15-1.45) were associated with higher risk of psychotic experiences at age 12. When adjusting for the other cognitive domains, processing speed at age 8 (odds ratio=1.20, 95% CI=1.09-1.33) was the measure most strongly associated with psychotic experiences. CONCLUSIONS Defective processing speed is a particularly strong predictor of psychotic experiences in children. Furthermore, the pattern of associations between cognition and psychotic experiences in children within the general population is similar to the one between cognition and schizophrenia. These findings have potentially important implications for understanding the pathogenesis of psychotic disorders and the specific deficits that seem to place children at higher risk of psychopathology.American Journal of Psychiatry 05/2013; 170(5):550-7. · 14.72 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: OBJECTIVE Retinal and cerebral microvessels are structurally and functionally homologous, but unlike cerebral microvessels, retinal microvessels can be noninvasively measured in vivo by retinal imaging. The authors tested the hypothesis that individuals with schizophrenia exhibit microvascular abnormality and evaluated the utility of retinal imaging as a tool for schizophrenia research. METHOD Participants were members of the Dunedin Study, a population-representative cohort followed from birth with 95% retention. Study members underwent retinal imaging at age 38. The authors assessed retinal arteriolar and venular caliber for all members of the cohort, including individuals who developed schizophrenia. RESULTS Study members who developed schizophrenia were distinguished by wider retinal venules, suggesting microvascular abnormality reflective of insufficient brain oxygen supply. Analyses that controlled for confounding health conditions suggested that wider retinal venules are not simply an artifact of co-occurring health problems in schizophrenia patients. Wider venules were also associated with a dimensional measure of adult psychosis symptoms and with psychosis symptoms reported in childhood. CONCLUSIONS The findings provide initial support for the hypothesis that individuals with schizophrenia show microvascular abnormality. Moreover, the results suggest that the same vascular mechanisms underlie subthreshold symptoms and clinical disorder and that these associations may begin early in life. These findings highlight the promise of retinal imaging as a tool for understanding the pathogenesis of schizophrenia.American Journal of Psychiatry 09/2013; · 14.72 Impact Factor