Ecological momentary assessment of anxiety and depression in individuals with early-treated phenylketonuria

Background. In addition to cognitive difficulties, individuals with early-treated phenylketonuria (PKU) may be at increased risk for anxiety and depression. However, previous findings are mixed, potentially due to reliance on retrospective self-report measures that are vulnerable to recall bias and lose resolution of day-to-day symptom fluctuations. The present study used ecological momentary assessment (EMA) to evaluate anxiety and depressive symptoms in adults with PKU in real-world settings. Methods. A sample of 30 adults with early-treated PKU and a demographically-similar sample of 30 adults without PKU completed smartphone-based EMA assessments four times daily over seven consecutive days (nTotal=1,384). Anxiety and depression symptoms and processing speed task performance were assessed at each timepoint. Previous week retrospective measures of mood symptoms were also collected following the EMA period. Results. EMA compliance was high (82.4%). Momentary analyses revealed that PKU participants reported significantly greater anxiety and depression symptoms as well as poorer processing speed performance compared to healthy controls. In contrast, no significant group differences were identified using retrospective mood measures. Within the PKU group, Phe levels were not significantly associated with mood symptom severity or processing speed. Conclusions. EMA detected PKU-related differences in psychological symptoms that were not identified by traditional retrospective assessments. These findings highlight the feasibility and sensitivity of EMA for characterizing everyday functioning in individuals with PKU. EMA may provide a more accurate assessment of symptom burden and may be particularly valuable for studying rare clinical populations, where intensive longitudinal data collection can maximize information gained from relatively small samples.