Cognitive Inflexibility Predicts Negative Symptoms Severity in Patients with First-Episode Psychosis: A 1-Year Follow-Up Study.

Negative symptoms and cognitive deficits play a major role in psychosis and significantly influence the functional outcomes of patients, particularly those with a first episode of psychosis (FEP). However, limited research has explored the predictive capacity of cognitive deficits during FEP for subsequent negative symptomatology. Drawing from the Athens FEP research study, we conducted a retrospective longitudinal study in 80 individuals with FEP. All patients were drug naive at admission. Cognitive tests were administered at 1-month and 1-year post-admission, while negative symptomatology was assessed at the same time points using PANSS by trained raters. We considered confounding factors such as age, gender, duration of untreated psychosis (DUP), treatment received, premorbid social adjustment, and premorbid IQ. Univariate regression analysis identified cognitive domains that correlated with negative symptomatology. These, along with the confounders, were incorporated into a multiple regression, with the 1-year PANSS negative scale serving as the dependent variable. Employing the backward elimination technique, we found a statistically significant inverse relationship between the categories completed in the Wisconsin card sorting test (WCST) and the 1-year PANNS negative scale (p = 0.01), beyond the associations with DUP and the 1-month PANSS negative scale. Our results suggest that cognitive flexibility, a key component of executive functions, predicts negative symptom severity one year after FEP.

Diminished social motivation in early psychosis is associated with polygenic liability for low vitamin D.

Insufficiency of vitamin D levels often occur in individuals with schizophrenia and first-episode psychosis (FEP). However, it is unknown whether this represents a biological predisposition, or it is essentially driven by illness-related alterations in lifestyle habits. Lower vitamin D has also been associated with adverse neurodevelopmental outcomes and predominant negative psychotic symptoms. This study aimed to investigate the contribution of polygenic risk score for circulating 25-hydroxyvitamin D concentration (PRS-vitD) to symptom presentation among individuals with FEP enrolled in the Athens First-Episode Psychosis Research Study (AthensFEP n = 205) and the Psychosis Incident Cohort Outcome Study (PICOS n = 123). The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale at baseline and follow-up assessments (AthensFEP: 4-weeks follow-up, PICOS: 1-year follow-up). Premorbid intelligence and adjustment domains were also examined as proxy measures of neurodevelopmental deviations. An inverse association between PRS-vitD and severity of negative symptoms, in particular lack of social motivation, was detected in the AthensFEP at baseline (adjusted R2 = 0.04, p < 0.001) and follow-up (adjusted R2 = 0.03, p < 0.01). The above observation was independently validated in PICOS at follow-up (adjusted R2 = 0.06, p < 0.01). No evidence emerged for a relationship between PRS-vitD and premorbid measures of intelligence and adjustment, likely not supporting an impact of lower PRS-vitD on developmental trajectories related to psychotic illness. These findings suggest that polygenic vulnerability to reduced vitamin D impairs motivation and social interaction in individuals with FEP, thereby interventions that encourage outdoor activities and social engagement in this patient group might attenuate enduring negative symptoms.