Exploring the effects of COVID-19 on verbal memory function in schizophrenia: Multiple case study and brief literature review.

Individuals recovering from COVID-19 may experience persistent impairment in verbal memory performance, potentially due to illness-related hippocampal injury. Although verbal memory dysfunction is central to schizophrenia, the interactions between this vulnerability and COVID-19 remain unclear, with no imaging studies addressing the issue to-date. To explore this gap and generate hypotheses for future research, we adopted a multiple case study approach. Two pairs of individuals with an ICD-10 diagnosis of schizophrenia were selected, each consisting of one case with a positive COVID-19 anamnesis and one without. We calculated the Reliable Change Index to estimate the clinical significance of verbal memory performance changes, with annualized change rates in hippocampal volumes assessed against normative data. Compared to their matches, COVID-19 positive cases did not show mutually consistent changes in verbal memory performance: one case experienced a significant decline in verbal memory and learning, while the other showed a general normalization of test scores. Left hippocampal volumes showed a comparatively slowed increase, while the right hippocampi decreased in volume, although these atrophy rates did not exceed those expected in general population samples. Based on these findings, we hypothesize that COVID-19 alone does not lead to verbal memory decline in schizophrenia. Instead, the relationship between the diseases may depend on additional factors. Our case pairs differed in body mass index, systolic blood pressure, sex, phase of illness, and whole grey matter volume trajectories, leading us to hypothesize that these variables represent additional predictors or moderators of this relationship.

Longitudinal course of core cognitive domains in first-episode acute and transient psychotic disorders compared with schizophrenia.

Acute and transient psychotic disorder (ATPD) is characterized by acute onset of psychotic symptoms and early recovery. Contrastingly, schizophrenia (SZ) is a chronic mental disorder characterized by impaired functioning including a deficit in cognition. In SZ, the cognitive deficit is among the core symptoms, but in ATPDs, the existing evidence brings mixed results. Our primary aim was to compare three core cognitive domains (executive functioning/abstraction, speed of processing and working memory) of patients diagnosed with ATPD and SZ over a 12-month period. Moreover, we explored how these diagnostic subgroups differed in their clinical characteristics. We recruited 39 patients with a diagnosis of SZ and 31 with ATPD with schizophrenic symptoms. All patients completed clinical and neuropsychological assessments. At baseline, we used a one-way ANCOVA model with a group as the between-subjects factor. Mixed-model repeated-measures ANOVAs with time as the within-subjects factor and group as the between-subjects factor were run to test the overtime differences. At baseline, we did not find any differences in cognition - with sex, education and age as covariates - between ATPDs and SZ. After one year, all patients showed an improvement in all three domains, however, there were no significant overtime changes between ATPDs and SZ. Regarding clinical profiles, ATPDs demonstrated less severe psychopathology and better functioning compared to SZ both at baseline and after 12 months. The medication dosage differed at retest, but not at baseline between the groups. Our findings suggest clinical differences and a similar trajectory of cognitive performance between these diagnostic subgroups.

Cognitive flexibility in schizophrenia: A confirmatory factor analysis of neuropsychological measures.

Cognitive flexibility (CF) is the ability to adapt cognitive strategies according to the changing environment. The deficit in CF has often been linked to various neurological and psychiatric disorders including schizophrenia. However, the operationalization and assessment of CF have not been unified and the current research suggests that the available instruments measure different aspects of CF. The main objective of the present study was to compare three frequently used neuropsychological measures of CF-Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Stroop Color and Word Test (SCWT) in a population of patients (N = 220) with first-episode schizophrenia spectrum disorders in order to evaluate their convergent validity. The hypothesis of an underlying latent construct was tested via a confirmatory factor analysis. We used a one-factor CF model with scores from WCST, SCWT and TMT as observed variables. The established model showed a good fit to the data (χ2 = 1.67, p = 0.43, SRMR = 0.02, RMSEA = 0.0, CFI = 1.00). The highest factor loading was found in WCST as CF explained most of the variance in this neuropsychological measure compared to the other instruments. On the other hand, a TMT ratio index and a SCWT interference demonstrated lowest loadings in the model. The findings suggest that not all the frequently used measures share an underlying factor of CF or may capture different aspects of this construct.

Smoking and attention in schizophrenia spectrum disorders: What are we neglecting?

Introduction: Individuals with schizophrenia spectrum disorders (SSDs) record elevated rates of smoking, which is often attributed to their effort to self-medicate cognitive and attentional symptoms of their illness. Empirical evidence for this hypothesis is conflicting, however. In this study, we aimed to test predictions derived from the cognitive self-medication hypothesis. We predicted that cigarette smoking status and extent would predict the attentional performance of participants with SSDs. Simultaneously, we wished to address methodological gaps in previous research. We measured distinct attentional components and made adjustments for the effects of other, attention-modulation variables. Methods: Sixty-one smokers (82.0% males, 26.73 ± 6.05 years) and 61 non-smokers (50.8% males, 27.10 ± 7.90 years) with recent-onset SSDs completed an X-type Continuous Performance Test, which was used to derive impulsivity and inattention component scores. Relationships between the two component scores and cigarette smoking status and extent were assessed using hierarchical regression. Effects of estimated premorbid intellectual functioning and antipsychotic medication dosage were held constant. Results: Smokers had significantly higher inattention component scores than non-smokers when covariates were controlled (p = 0.026). Impulsivity remained unaffected by smoking status (p = 0.971). Cigarette smoking extent, i.e., the number of cigarettes smoked per day, was not associated with either inattention (p = 0.414) or impulsivity (p = 0.079). Conclusion: Models of smoking-related attentional changes can benefit from the inclusion of sample-specific component scores and attention-modulating covariates. Under these conditions, smokers with SSDs can show a partial attentional benefit. However, the limited scope of this benefit suggests that the cognitive self-medication hypothesis requires further testing or reconsidering.

Inflammation and cognitive performance in first-episode schizophrenia spectrum disorders: The moderating effects of childhood trauma.

In this study, we aimed to determine whether childhood trauma moderated the relationship between inflammation and cognitive functioning in persons with first-episode schizophrenia spectrum disorders (SSDs). We included data from 92 individuals who participated in the nationwide Early-Stage Schizophrenia Outcome study. These individuals completed the Childhood Trauma Questionnaire, provided a fasting blood sample for high-sensitivity C-reactive protein analysis, and underwent extensive neuropsychological testing. The intervening effects of age, sex, education, smoking status, and body mass index were controlled. Results indicated that childhood trauma levels significantly moderated the relationship between inflammation and four cognitive domains: speed of processing, working memory, visual memory, and verbal memory. Inflammation also predicted verbal memory scores irrespective of childhood trauma levels or the covariates. Upon further exploration, the significant moderation effects appeared to be primarily driven by males. In conclusion, a history of childhood trauma may be an important determinant in evaluating how inflammation relates to the cognitive performance of people with first-episode SSDs, particularly in speed of processing, working memory, visual memory, and verbal memory. We recommend that future researchers examining the effect of inflammation on cognitive functioning in SSDs include trauma as a moderating variable in their models and further examine additional moderating effects of sex.

The relationships between cognitive reserve, cognitive functioning and quality of life in first-episode schizophrenia spectrum disorders.

Cognitive reserve (CR) has been conceptualized as an individual's ability to optimize or maximize performance through differential recruitment of brain networks. As such, CR may contribute to the heterogeneity of cognitive deficits observed in schizophrenia. This study aimed to assess the relationships between CR, cognition and quality of life in first-episode (FES) patients. A total of 137 patients with either ICD-10 schizophrenia or "acute and transient psychotic disorders" diagnosis, and 62 healthy controls had completed a comprehensive assessment of six cognitive domains: speed of processing, attention, working memory/flexibility, verbal memory, visual memory, and abstraction/executive functioning. CR was calculated from the participants' education, premorbid IQ, and socioeconomic status. The results suggested that in patients, CR was positively related to cognitive performance in all domains, explaining 42.6% of the variance observed in cognition overall. Effects of CR in the control group were limited to three domains: speed of processing, abstraction/executive function and working memory/flexibility. These results suggest that CR largely contributes to cognitive variations present in FES patients. In addition, CR was negatively related to the social construct of patients' quality of life, and positively to symptom severity and general functioning.

Cognitive profiles of healthy siblings of first-episode schizophrenia patients.

AIM: Cognitive deficit in psychotic illness is intensively studied, different cognitive subtypes have been suggested. In recent years, there has been an increase in the number of studies in patients with schizophrenia and their relatives searching for endophenotypes of the disease. The aim of our study was to investigate cognitive performance and cognitive subtypes in the siblings of the patients. METHODS: Four groups of subjects were included: patients with a first episode of psychotic illness, the siblings of these patients, and two control groups. All the study subjects (N = 84) had a battery of neuropsychological tests that measured basic cognitive domains - memory, executive functions, attention, visual-spatial skills, language skills and psychomotor speed - administered to them. The data were assessed with pairwise t-tests for group comparisons. The siblings were distributed into three groups according to their cognitive performance: non-deficit, partial deficit, and global deficit. Subsequently, the patients were assigned into three groups corresponding to their siblings' performance. RESULTS: Our results revealed attenuation of abstract thinking in the siblings compared to the controls. As expected, the patients showed impairment across all cognitive domains. The patients and siblings demonstrated similar profiles in each subtype, in the severity of their impairment, and in their patterns of cognitive performance. CONCLUSIONS: Our results suggest that the cognitive profile can be considered as an endophenotype of psychotic disorders.

Neuroactive Steroids and Cognitive Functions in First-Episode Psychosis Patients and Their Healthy Siblings.

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.

Cognitive Profiles and Functional Connectivity in First-Episode Schizophrenia Spectrum Disorders - Linking Behavioral and Neuronal Data.

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.