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Age effects on basic symptoms in the community: A route to gain new insight into the neurodevelopment of psychosis?

ABSTRACT: Reports of limited clinical significance of attenuated psychotic symptoms before age 15/16 indicate an important role of neurodevelopment in the early detection of psychoses. Therefore, we examined if age also exerts an influence on the prevalence and clinical significance of the 14 cognitive and perceptive basic symptoms (BS) used in psychosis-risk criteria and conceptualized as the most direct self-experienced expression of neurobiological aberrations. A random representative general population sample of the Swiss canton Bern (N = 689, age 8-40 years, 06/2011-05/2014) was interviewed for BS, psychosocial functioning, and current mental disorder. BS were reported by 18% of participants, mainly cognitive BS (15%). In regression analyses, age affected perceptive and cognitive BS differently, indicating an age threshold for perceptive BS in late adolescence (around age 18) and for cognitive BS in young adulthood (early twenties)-with higher prevalence, but a lesser association with functional deficits and the presence of mental disorder in the below-threshold groups. Thereby, interaction effects between age and BS on functioning and mental disorder were commonly stronger than individual effects of age and BS. Indicating support of the proposed "substrate-closeness" of BS, differential age effects of perceptual and cognitive BS seem to follow normal brain maturation processes, in which they might occur as infrequent and temporary non-pathological disturbances. Their persistence or occurrence after conclusion of main brain maturation processes, however, might signify aberrant maturation or neurodegenerative processes. Thus, BS might provide important insight into the pathogenesis of psychosis and into differential neuroprotective or anti-inflammatory targets.

SUBMITTER: Schultze-Lutter F

PROVIDER: S-EPMC7069926 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In community studies, both attenuated psychotic symptoms (APS) and basic symptoms (BS) were more frequent but less clinically relevant in children and adolescents compared to adults. In doing so, they displayed differential age thresholds that were around age 16 for APS, around age 18 for perceptive BS, and within the early twenties for cognitive BS. Only the age effect has previously been studied and replicated in clinical samples for APS. Thus, we examined the reported age effect on and age thresholds of 14 criteria-relevant BS in a patient sample at clinical-high risk of psychosis (N = 261, age 15-40 yrs.), recruited within the European multicenter PRONIA-study. BS and the BS criteria, "Cognitive Disturbances" (COGDIS) and "Cognitive-perceptive BS" (COPER), were assessed with the "Schizophrenia Proneness Instrument, Adult version" (SPI-A). Using logistic regressions, prevalence rates of perceptive and cognitive BS, and of COGDIS and COPER, as well as the impact of social and role functioning on the association between age and BS were studied in three age groups (15-18 years, 19-23 years, 24-40 years). Most patients (91.2%) reported any BS, 55.9% any perceptive and 87.4% any cognitive BS. Furthermore, 56.3% met COGDIS and 80.5% COPER. Not exhibiting the reported differential age thresholds, both perceptive and cognitive BS, and, at trend level only, COPER were less prevalent in the oldest age group (24-40 years); COGDIS was most frequent in the youngest group (15-18 years). Functional deficits did not better explain the association with age, particularly in perceptive BS and cognitive BS meeting the frequency requirement of BS criteria. Our findings broadly confirmed an age threshold in BS and, thus, the earlier assumed link between presence of BS and brain maturation processes. Yet, age thresholds of perceptive and cognitive BS did not differ. This lack of differential age thresholds might be due to more pronounced the brain abnormalities in this clinical sample compared to earlier community samples. These might have also shown in more frequently occurring and persistent BS that, however, also resulted from a sampling toward these, i.e., toward COGDIS. Future studies should address the neurobiological basis of CHR criteria in relation to age.

Project description:The thalamus is composed of multiple nuclei densely connected with the cortex in an organized manner, forming parallel thalamocortical networks critical to sensory, motor, and cognitive functioning. Thalamocortical circuit dysfunction has been implicated in multiple neurodevelopmental disorders, including schizophrenia, which also often exhibit sex differences in prevalence, clinical characteristics, and neuropathology. However, very little is known about developmental and sex effects on thalamocortical networks in youth. The present study characterized the effects of age, sex and psychosis symptomatology in anatomically constrained thalamocortical networks in a large community sample of youth (n = 1100, aged 8-21) from the Philadelphia Neurodevelopmental Cohort (PNC). Cortical functional connectivity of seven anatomically defined thalamic nuclear groups were examined: anterior, mediodorsal, ventral lateral, ventral posterolateral, pulvinar, medial and lateral geniculate nuclear groups. Age and sex effects were characterized using complementary thalamic region-of-interest (ROI) to cortical ROI and voxel-wise analyses. Effects of clinical symptomatology were analyzed by separating youth into three groups based on their clinical symptoms; typically developing youth (n = 298), psychosis spectrum youth (n = 320), and youth with other psychopathologies (n = 482). As an exploratory analysis, association with PRIME scores were used as a dimensional measure of psychopathology. Age effects were broadly characterized by decreasing connectivity with sensory/motor cortical areas, and increasing connectivity with heteromodal prefrontal and parietal cortical areas. This pattern was most pronounced for thalamic motor and sensory nuclei. Females showed greater connectivity between multiple thalamic nuclear groups and the visual cortex compared to males, while males showed greater connectivity with the inferior frontal and orbitofrontal cortices. Youth with psychosis spectrum symptoms showed a subtle decrease in thalamic connectivity with the premotor and prefrontal cortices. Across all youth, greater PRIME scores were associated with lower connectivity between the prefrontal cortex and mediodorsal thalamus. By characterizing typical development in anatomically constrained thalamocortical networks, this study provides an anchor for conceptualizing disruptions to the integrity of these networks observed in neurodevelopmental disorders.

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Age effects on basic symptoms in the community: A route to gain new insight into the neurodevelopment of psychosis?

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