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Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

ABSTRACT: In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (N_spared = 40, N_impaired = 13). Impaired patients showed significantly increased negative symptomatology (p_fdr = 0.003), reduced cognitive performance (p_fdr < 0.001) and general functioning (p_fdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

SUBMITTER: Wenzel J

PROVIDER: S-EPMC8209013 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Glucose abnormalities and cognitive alterations are present before the onset of schizophrenia. We aimed to study whether glucose metabolism parameters are associated with cognitive functioning in recent-onset psychosis (ROP) patients while adjusting for hypothalamic-pituitary adrenal (HPA) axis measures. Methods:Sixty ROP outpatients and 50 healthy subjects (HS) were studied. Cognitive function was assessed with the MATRICS Consensus Cognitive Battery. Glycated haemoglobin (HbA1c), glucose, insulin, and C-peptide levels were determined in plasma. The HOMA-insulin resistance index was calculated. Salivary samples were obtained at home on another day to assess the cortisol awakening response and cortisol levels during the day. Univariate analyses were conducted to explore the association between glucose metabolism parameters and cognitive tasks. For those parameters that were more clearly associated with the cognitive outcome, multiple linear regression analyses were conducted to adjust for covariates. Each cognitive task was considered the dependent variable. Covariates were age, sex, education level, diagnosis, antipsychotic and benzodiazepine treatment, body mass index (BMI), smoking, and HPA axis measures. Potential interactions between diagnosis and glucose parameters were tested. Results:There were no significant differences in HPA axis measures or glucose parameters, with the exception of C-peptide (that was higher in ROP patients), between groups. ROP patients had a lower performance than HS in all cognitive tasks (p < 0.01 for all tasks). Of all glucose metabolism parameters, HbA1c levels were more clearly associated with cognitive impairment in cognitive tasks dealing with executive functions and visual memory in both ROP patients and HS. Multivariate analyses found a significant negative association between HbA1c and cognitive functioning in five cognitive tasks dealing with executive functions, visual memory and attention/vigilance (a ROP diagnosis by HbA1c negative interaction was found in this latter cognitive domain, suggesting that HBA1c levels are associated with impaired attention only in ROP patients). Conclusions:Our study found that HbA1c was negatively associated with cognitive functioning in both ROP patients and HS in tasks dealing with executive functions and visual memory. In ROP patients, HbA1c was also associated with impaired attention. These results were independent of BMI and measures of HPA axis activity.

Project description:Background:We previously demonstrated that the high heterogeneity of response to computerized Auditory Training (AT) in psychosis can be ascribed to individual differences in sensory processing efficiency and neural plasticity. In particular, we showed that Auditory Processing Speed (APS) serves as a behavioral measure of target engagement, with faster speed predicting greater transfer effects to untrained cognitive domains. Here, we investigate whether the ability of APS to function as a proxy for target engagement is unique to AT, or if it applies to other training interventions, such as Executive Functioning Training (EFT). Additionally, we examine whether changes in APS are durable after these two forms of training. Methods:One hundred and twenty-five participants with Recent Onset Psychosis (ROP) were randomized to AT (n = 66) and EFT (n = 59), respectively. APS was captured at baseline, after treatment, and at 6-month follow-up. Mixed models repeated measures analysis with restricted maximum likelihood was used to examine whether training condition differentiated APS trajectories. Within-group correlational analyses were used to study the relationship between APS and performance improvements in each of the training exercises. Results:The two groups were matched for age, gender, education, and baseline APS. Participants showed high inter-individual variability in APS at each time point. The mixed model showed a significant effect of time (F = 5.99, p = .003) but not a significant group-by-time effect (F = .73, p = .48). This was driven by significant APS improvements AT patients after treatment (d = .75) that were maintained after 6 months (d = .63). Conversely, in EFT patients, APS improvements did not reach statistical significance after treatment (p = .33) or after 6 months (p = .24). In AT patients, baseline APS (but not APS change) highly predicted peak performance for each training exercise (all r's >.42). Conclusions:Participant-specific speed in processing basic auditory stimuli greatly varies in ROP, and strongly influences the magnitude of response to auditory but not executive functioning training. Importantly, enhanced auditory processing efficiency persists 6 months after AT, suggesting the durability of neuroplasticity processes induced by this form of training. Future studies should aim to identify markers of target engagement and durability for cognitive training interventions that target sensory modalities beyond the auditory domain.

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Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

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