Associations Between PPAR-γ and Executive Function in Adolescents With Major Depressive Disorder With and Without...

Major depressive disorder (MDD) is characterized by cognitive and immune-metabolic dysfunctions, which may be exacerbated in the presence of psychotic features (MDD-PF). Although peroxisome proliferator-activated receptor gamma (PPAR-γ) has anti-inflammatory and neuroprotective roles in adult depression, its function in adolescent MDD and MDD-PF is unclear. This study examined serum PPAR-γ levels and their links to executive functioning and inflammatory markers.

This cross-sectional, case-control study included 81 participants (MDD: 30, MDD-PF: 26, HC: 25; ages 10-18). Executive functions were evaluated using the questionnaire and neuropsychological tests. Fasting serum PPAR-γ levels were measured using ELISA, whereas haematological and metabolic parameters were determined through laboratory analyses.

Serum PPAR-γ levels were significantly higher in both the MDD and MDD-PF groups compared to HC group (p < 0.05). The MDD-PF group exhibited the most pronounced executive dysfunction on BRIEF subscales and showed the poorest performance on neuropsychological tests, particularly in verbal learning, visual memory and processing speed. In the MDD group, PPAR-γ levels were positively correlated with cognitive performance measures such as verbal memory, attention accuracy and cognitive flexibility and negatively correlated with error indices. In contrast, in the MDD-PF group, PPAR-γ levels were negatively associated with executive dysfunction reported in shift, initiate, working memory, plan/organize and metacognition.

Higher PPAR-γ levels may be associated with a potentially compensatory or neuroprotective pattern, particularly in adolescents with MDD, whereas the inverse correlations observed in the MDD-PF group may indicate a different or disrupted regulatory pattern in more severe presentations. Overall, PPAR-γ may be linked to executive functioning in adolescent depression, warranting confirmation in larger longitudinal studies.