Psychosis spectrum features, neurocognition and functioning in a longitudinal study of youth with 22q11.2 deletion syndrome

Abstract

Background Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome. Methods 157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS−). Results We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS− group. Neurocognitive performance was generally comparable in PS+ and PS− groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS− counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change. Conclusions Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis.

Integrating Clinical Neuropsychology and Psychotic Spectrum Disorders: A Systematic Analysis of Cognitive Dynamics, Interventions, and Underlying Mechanisms

“…Studies [32,60,62,[64][65][66][67][68]72,74,78,80,81,90,[94][95][96][98][99][100][101][102] delve into cognitive impairments, brain structure changes, and neurobiological markers. Key findings include the diagnostic and prognostic significance of mismatch negativity (MMN), neuroprogressive trajectories, cortical thinning in familial high-risk individuals, and distinct illness trajectories within psychosis subgroups.…”

“…Studies [60,62,[64][65][66][67][68]72,74,78,80,81,90,[94][95][96][98][99][100][101][102] evaluate intervention strategies, emphasizing early detection, monitoring of at-risk youth, and the potential for individualized treatments based on neuroprogressive patterns.…”

“…Research [64,[66][67][68][69]72,74,[78][79][80][81]90,[94][95][96][97][98][99][100][101][102] discusses the impact of genetic and environmental factors. Findings suggest shared neurodevelopmental pathways, the significance of early areas of overlap, and the importance of considering psychotic features and medication status.…”

“…It is worthwhile to note another study that presented the functional outcome in neurocognitive tasks in combination with psychotic symptoms. The final outcome of the study [100] focuses on the differences in the trajectories of psychosis symptoms and neurocognitive performance between groups with more prominent psychosis features (PS+) and those without (PS−) among individuals with 22q11.2 deletion syndrome (22q11DS) and its impact on functional outcome. The study found that individuals with 22q11DS and more prominent psychosis features exhibit a worsening of symptoms and functional decline, which is driven by neurocognitive decline, particularly related to executive functions and specifically working memory.…”

Unique functional neuroimaging signatures of genetic versus clinical high risk for psychosis

“…This deletion of ~46 protein-coding genes occurs in approximately 1 in 4000 people (12), of whom 10-20% can be expected to develop a psychosis spectrum disorder (13,14). Approximately 30% of 22qDel carriers endorse positive psychosis symptoms of at least moderate intensity (15)(16)(17). Highly penetrant genetic risk factors like 22qDel represent important opportunities for characterizing biological pathways underlying psychosis risk in a "genetics-first" approach (18,19).…”