Cognitive impairment is a major determinant of disability in bipolar disorder (BD) and a defining feature of both mild cognitive impairment (MCI) and Alzheimer's disease (AD). Lithium, a first-line maintenance treatment for BD, is implicated in neuroprotective mechanisms including glycogen synthase kinase-3β inhibition, amyloid and tau modulation, and neurogenesis promotion. The overarching aim of this systematic review is to evaluate the long-term effects of lithium on cognition across BD, MCI, and early-to-moderate AD using randomized controlled trial (RCT) evidence. Online databases were searched from inception through May 2025 for RCTs reporting lithium's effect on cognitive outcomes in BD, MCI, or early-to-moderate AD with ≥8weeks of follow-up. Risk of bias was assessed using the Cochrane RoB 2 tool. Eight RCTs met the inclusion criteria, ranging from 10weeks to 3years in duration. Across four BD trials, lithium did not exhibit consistent improvement or worsening on composite cognitive scores. Three of four MCI/AD trials reported attenuated global cognitive deterioration with low-dose lithium, especially when exposure was ≥12months. Methodological limitations included small sample sizes, exploratory endpoints, and variable measures for cognitive function as well as lithium strategies. Lithium demonstrates preliminary signals of slower cognitive decline in MCI/AD. Available evidence suggests lithium has neutral effects on cognitive impairment in BD. Future adequately powered RCTs with cognition as a primary endpoint, functional measures, and biomarker outcomes are warranted to clarify lithium's role as a maintenance treatment in psychiatric disorders and its potential neuroprotective effects in neurodegenerative diseases.

Autistic traits (ATs) are associated with difficulties in social functioning, but their impact on the quantity and the quality of daily-life social interactions is not yet fully understood. Hereby, we examined the relationship between AT and daily-life social interactions in adolescents and young adults. Data were derived from the TwinssCan cohort (N=593). ATs were assessed using the Autism Spectrum Quotient (AQ), while the quantity and the quality of daily-life social interactions were evaluated using the Experience Sampling Methodology. Multilevel regressions were performed, with the AQ as the independent variable and each social/solitary quantity/quality variable as the dependent variable. Models were adjusted for age, sex, and general psychopathology, measured with the Symptom Checklist-90. No significant association was found between AQ total scores and quantity of social interactions. However, AQ total scores were significantly associated with quality of social interactions. Higher ATs were associated with an increased preference to be alone (B=0.04, 95% CI 0.01-0.07), less pleasure while in-company (B=-0.02, 95% CI -0.04 to -0.01), less feeling of safety while in-company (B=-0.02, 95% CI -0.04 to -0.002), and less feeling of belongingness (B=-0.02, 95% CI -0.03 to -0.001). ATs were differently associated with the quality of social interactions depending on the familiarity. No significant associations were found between ATs and solitary qualities. Our findings highlight the importance of evaluating ATs during clinical assessments, especially in adolescents and young adults, to evaluate the impact on social interactions and the potential psychopathological consequences.