Longitudinal Motor Trajectories and 2-Year Cognitive and Functional Outcomes in First-Episode Psychosis.

Dynamic, differentiated clinical trajectories and prediction in clinical high risk for psychosis.

Cognitive profiles in first-episode psychosis: The impact of genetics, environment, and cognitive reserve as risk and protective factors.

BACKGROUND Cognitive impairment is a core but heterogeneous feature of first-episode psychosis (FEP). Genetic liability, environmental exposures, and protective mechanisms such as cognitive reserve (CR) have been implicated in cognition. We examined whether cognitive profiles in FEP differed according to polygenic risk scores (PRS), individual and cumulative environmental exposures measured with the Maudsley Environmental Risk Score (ERS), and CR. METHODS A total of 114 individuals with non-affective FEP underwent neuropsychological assessments at baseline and two-year follow-up; environmental exposures were assessed and PRS were calculated at baseline. Cognitive clusters were derived using Partition Around Medoids clustering. Cluster transitions were examined, and logistic regression and mediation analyses tested associations with cognitive outcomes. RESULTS At baseline, two cognitive clusters were identified: cognitively intact (n=50) and cognitively impaired (n=64); at follow-up, participants were similarly classified as cognitively intact (n=78) or cognitively impaired (n=36). At both time points, the cognitively intact group showed higher BW (both p≤0.005) and higher CR (both p<0.001). In multivariable logistic regression predicting follow-up cognitive status, BW (p=0.006) and CR (p=0.009) were significant predictors; the model showed good discrimination (AUC=0.854, p<0.001) and an overall classification accuracy of 85%. When examining cognitive trajectories (stable intact, n=43; stable impaired, n=29; improved, n=35; excluding the small worsened group n=7), ANOVAs revealed significant group differences in BW (p<0.001) and CR (p<0.001). Mediation analyses further supported an indirect effect of BW on cognition via CR, consistent with partial mediation. No significant associations were observed between cognitive clustering and PRS or the ERS. CONCLUSIONS Cognitive heterogeneity in FEP appears closely linked to early developmental markers and protective mechanisms.

Neurocognitive profiles in early childhood in relation to clinical and functional outcomes in middle childhood in offspring at familial high-risk of schizophrenia or bipolar disorder: The Danish High-Risk and Resilience Study.

BACKGROUND Widespread neurocognitive impairments exist in children at familial high-risk of schizophrenia (FHR-SZ), whereas evidence is mixed in children at FHR of bipolar disorder (FHR-BP). Neurocognitive heterogeneity is well-established, but associations with longitudinal clinical and functional outcomes remain unexplored. METHODS In this prospective cohort study, 274 children (FHR-SZ, n = 170, FHR-BP, n = 104, 46.7% female, mean age 12.0 years, SD 0.25) provided neurocognitive data at baseline and clinical data at 4-year follow-up. The assessed neurocognitive functions included intelligence, processing speed, attention, memory, and executive functions. Axis I mental disorders, psychotic experiences, and functioning were ascertained through child and caregiver interviews. Dimensional psychopathology was reported by the caregiver. Three baseline neurocognitive subgroups (mildly impaired, typical, and above-average) derived from hierarchical cluster analysis across FHR-groups constituted categorical predictors with clinical and functional measures at follow-up as outcomes. RESULTS Compared with children in the typical subgroup and after accounting for sex, outcome of interest and Any Axis I disorder at baseline, and FHR-group, children in the mildly impaired subgroup at baseline had a threefold increased risk of any externalizing mental disorder (OR 2.9, 95% CI 1.3-6.5, p = .007) and a twofold increased risk of psychotic experiences (OR 2.0, 95% CI 1.0-3.8, p = .04) during middle childhood. Additionally, they had significantly higher dimensional symptom severity (Cohen's d range 0.27-0.43, p < .05) and poorer global functioning (Cohen's d = 0.48, p < .001) at follow-up. Neurocognitive subgroup membership was non-differentially associated with clinical and functional outcomes across FHR-groups. CONCLUSIONS A significantly impaired neurocognitive profile in early childhood confers risk for detrimental clinical and functional outcomes in middle childhood beyond that which can be attributed to pre-existing clinical and functional states and constitutes a cross-diagnostic, neurodevelopmental risk marker in these FHR-groups. Early neurocognitive profiling is warranted, and future studies should investigate long-term associations with mental disorders.

Longitudinal Brain Correlates of Cognitive Performance in Early Psychosis

DMPFC-somatomotor connectivity is longitudinally associated with cognitive performance in early psychosis, suggesting a novel, reliable target for intervention for cognitive deficits in early psychosis.

Post-stroke depression, but not anxiety, is independently associated with executive and visuospatial function: a five-year longitudinal cohort study

Background. Post-stroke anxiety and depression frequently co-occur, and whether each is independently associated with cognitive impairment remains unclear because most studies model one without adjusting for the other variable. In a five-year cohort, we tested whether anxiety and depression have distinct cognitive correlates and whether early affective status predicted subsequent cognitive recovery. Methods. Patients from the STROKDEM cohort were assessed at 6, 12, 36, and 60 months post-stroke for anxiety, depression, and five cognitive domains (memory, executive functioning, attention, visuospatial functioning, and language). Two symmetric random-intercept linear mixed models regressed each affective score on the cognitive domains while adjusting for other scores. Repeated-measures correlations, multiple imputations for attrition, and exploratory trajectory and prognostic models were also used. Results. After mutual adjustment and correction, depression was independently associated with executive and visuospatial function, whereas anxiety showed no independent cognitive correlation. Repeated-measures correlation confirmed this dissociation. The anxiety findings were stable across the sensitivity analyses and multiple imputations. Attrition was selective for baseline cognition, and exploratory associations between early affect and cognitive recovery did not survive multiple imputations and were inconclusive. Limitations. Attrition was substantial and selective on baseline cognition; the persistent anxiety subgroup was small, limiting the power for trajectory analyses; and psychiatric history, psychotropic medication, and cognitive reserve beyond education were unavailable. Conclusions. The cognitive burden of post-stroke affective disorders is carried by depression, rather than anxiety. Because anxiety-related cognitive impairment largely reflects comorbid depression, screening for depression rather than anxiety alone may better identify stroke survivors at risk of cognitive impairment.

Early-stage trajectories of social-occupational functioning and long-term functional outcome prediction in early psychosis: A 12-year follow-up of the randomized controlled trial on extended early intervention

Abstract Background Functional impairment in psychosis often persists despite symptomatic remission. There is a paucity of research examining early-course psychosocial functioning trajectories, and none has been conducted to examine relationship between the trajectories and prospective long-term functional outcomes in early psychosis sample. Methods We conducted 12-year follow-up of a randomized controlled trial on extended early intervention for first-episode psychosis to identify early-course social-occupational functioning trajectories and their baseline predictors and associations with 12-year outcomes. Participants who completed Social and Occupational Functioning Scale (SOFAS) scores at three or more timepoints between baseline and 3-year follow-up were included in the study. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive early-course social-occupational functioning trajectories based on SOFAS scores over 3-year follow-up. Results A total of 148 participants were included in this study, with 106 patients having completed the 12-year follow-up. Our results identified four distinct trajectories, including persistently-good class, gradually-improved class, suboptimal-stable class, and persistently-poor class. Patients in persistently-poor class had more severe negative symptoms at baseline compared to patients in persistently-good class. Patients with persistently-poor trajectory had worse long-term outcomes than those with other classes in the majority of functional measures at 12-year follow-up. Conclusions The majority of patients were classified in early-stage suboptimal or poor functional trajectories. Above one-fourth of the participants exhibited persistently-poor social-occupational functioning trajectory, which predicted worse functional outcomes at 12-year follow-up. These findings highlighted the importance of tracking functional changes during the initial years of illness.