Experimental evidence has demonstrated that several aspects of adult neural stem cells (NSCs), including their quiescence, proliferation, fate specification and differentiation, are regulated by epigenetic mechanisms. These control the expression of specific sets of genes, often including those encoding for small non-coding RNAs, indicating a complex interplay between various epigenetic factors and cellular functions.

The kynurenine pathway (KP) is gaining more attention as a common pathway involved in age-related conditions. However, which changes in the KP occur due to normal ageing is still largely unclear. The aim of this systematic review was to summarize the available evidence for associations of KP metabolites with age. We used an broad search strategy and included studies up to October 2023. Out of 8795 hits, 55 studies were eligible for the systematic review. These studies suggest that blood levels of tryptophan decrease with age, while blood and cerebrospinal fluid levels of kynurenine and its ratio with tryptophan increase. Studies investigating associations between cerebrospinal fluid and blood levels of kynurenic acid and quinolinic acid and age reported either positive or non-significant findings. However, there is a large heterogeneity across studies. Additionally, most studies were cross-sectional, and only few studies investigated associations with other downstream kynurenines. This systematic review suggests that levels of kynurenines are positively associated with age. Larger and prospective studies are needed that also investigate a more comprehensive panel of KP metabolites and changes during the life-course.

Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R²) at the optimal p-value threshold is reported. In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R² = 6.94%, p < .0001), which was consistent across countries: Ireland (R² = 8.18%, p = .0013), Belgium (R² = 6.83%, p = .016), and the Netherlands (R² = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R² = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R² = 4.42%, p = .0024) and unipolar MDE only (R² = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.