The character of cognitive deficit in schizophrenia is not clear due to the heterogeneity in research results. In heterogeneous conditions, the cluster solution allows the classification of individuals based on profiles. Our aim was to examine the cognitive profiles of first-episode schizophrenia spectrum disorder (FES) subjects based on cluster analysis, and to correlate these profiles with clinical variables and resting state brain connectivity, as measured with magnetic resonance imaging. A total of 67 FES subjects were assessed with a neuropsychological test battery and on clinical variables. The results of the cognitive domains were cluster analyzed. In addition, functional connectivity was calculated using ROI-to-ROI analysis with four groups: Three groups were defined based on the cluster analysis of cognitive performance and a control group with a normal cognitive performance. The connectivity was compared between the patient clusters and controls. We found different cognitive profiles based on three clusters: Cluster 1: decline in the attention, working memory/flexibility, and verbal memory domains. Cluster 2: decline in the verbal memory domain and above average performance in the attention domain. Cluster 3: generalized and severe deficit in all of the cognitive domains. FES diagnoses were distributed among all of the clusters. Cluster comparisons in neural connectivity also showed differences between the groups. Cluster 1 showed both hyperconnectivity between the cerebellum and precentral gyrus, the salience network (SN) (insula cortex), and fronto-parietal network (FPN) as well as between the PreCG and SN (insula cortex) and hypoconnectivity between the default mode network (DMN) and seeds of SN [insula and supramarginal gyrus (SMG)]; Cluster 2 showed hyperconnectivity between the DMN and cerebellum, SN (insula) and precentral gyrus, and FPN and IFG; Cluster 3 showed hypoconnectivity between the DMN and SN (insula) and SN (SMG) and pallidum. The cluster solution confirms the prevalence of a cognitive decline with different patterns of cognitive performance, and different levels of severity in FES. Moreover, separate behavioral cognitive subsets can be linked to patterns of brain functional connectivity.

Background: Neuroactive steroids (NAS) affect neurotransmitter systems and cognition; thus, they play role in etiopathogenesis of psychiatric disorders. Aims: The primary aim was to examine cognition and effects of NAS on cognitive functioning in first-episode psychosis patients and in their healthy siblings. The secondary aims were to verify whether cognitive deficit is an endophenotype of psychosis and whether higher NAS levels represent a high-risk factor for psychosis. Methods: Studied participants were 1) patients with first episode of psychosis, 2) healthy siblings of the patients, and 3) matching healthy controls. Study procedures included administration of a battery of neuropsychological tests assessing six cognitive domains and examination of NAS plasma levels [cortisol (CORT), 11-deoxycorticosterone (DOC), testosterone (TEST), dehydroepiandrostendione (DHEA), dihydrotestosterone (DHT), and progesterone (PROG)]. Results: A total of 67 subjects were analyzed (16 patients, 22 siblings, and 29 controls). Significant group differences were found in most of the cognitive domains; the patients had the lowest scores. The Kruskal–Wallis test revealed significant group differences in CORT levels ( p < 0.01), TEST ( p < 0.01), and DHT ( p < 0.001); no difference was found in PROG, DHEA, and DOC. All cognitive domains, except for attention, were affected by the NAS levels. CORT levels of patients correlated with speed of processing ( r = 0.55) and working memory ( r = 0.52), while PROG levels correlated with abstraction ( r = −0.63). In siblings, there was a negative correlation between TEST levels and verbal memory ( r = −0.51) and PROG with attention ( r = −0.47). Conclusions: Our results verified that individual domains of cognitive deficit (abstraction and verbal memory) can be considered as an endophenotype of psychosis. Higher levels of cortisol and testosterone in siblings are consistent with high-risk states for psychosis. Multiple interactions between NAS and cognitive functioning, particularly memory functions, were observed. Study limitations (small sample size and administration of antipsychotic medication) did not allow us to establish unequivocally NAS as an endophenotype.

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