Abstract
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.
Highlights
Complex etiopathological mechanisms of schizophrenia are still poorly understood and their key features are yet to be identified
Six patients and one sibling were excluded from the analyses due to the following reasons: manifested psychotic symptoms during cognitive testing, nonnative Czech speaker, history of multiple episodes, and incorrect diagnosis
Results of the post hoc Dunn test with the Benjamini– Hochberg correction revealed that visual memory performance of controls was statistically superior to that of patients (p < 0.05), performance of siblings was significantly better than that of patients (p < 0.05), and no difference between siblings and controls was observed
Summary
Complex etiopathological mechanisms of schizophrenia are still poorly understood and their key features are yet to be identified. A more general term, “neuroactive steroids” (NAS) is used for all substances that interact with the CNS in two different modes. Through binding with intracellular steroid receptors, NAS can change gene expression. Interacting with membrane neurotransmitter receptors, NAS can modulate psychopathology of psychiatric disorders [7, 8]. NAS may exhibit therapeutic potential, and their antidepressant, anxiolytic, and antipsychotic effects have been reported [9,10,11]. Alterations of NAS are currently being studied intensively to investigate their role in the pathophysiology of schizophrenia, with an accumulating amount of evidence suggesting their involvement [12, 15, 16]. Neuroactive steroids (NAS) affect neurotransmitter systems and cognition; they play role in etiopathogenesis of psychiatric disorders
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