The Absence of Items Addressing Increased Appetite or Weight in Depressive-Symptom Questionnaires: Implications for Understanding the Link between Major Depressive Disorder, Antidepressants, and Obesity.

Major depressive disorder (MDD) and obesity have a complex bidirectional relationship. However, most studies do not assess increased appetite or weight as a depressive symptom due to limitations in rating scales. Here we aimed to analyze frequently employed depressive-symptom scales and discuss the relevance of weight and appetite assessment items. To elaborate this perspective, we searched for validated questionnaires and scales evaluating depressive symptoms in English. We analyzed appetite and weight items from 20 depressive-symptoms rating scales. Only 8 of 20 rating scales assessed for increased weight or appetite. The scales reported in the literature as the most employed in antidepressants efficacy trials do not assess increased appetite or weight. The current use of rating scales limits our understanding of the relationship between MDD, antidepressants, and obesity. It is necessary to improve our weight and appetite measurements in MDD to clarify the respective impact of depressive symptoms and antidepressants on weight change.

The Wnt signaling pathway in major depressive disorder: A systematic review of human studies.

Despite uncertainty about the specific molecular mechanisms driving major depressive disorder (MDD), the Wnt signaling pathway stands out as a potentially influential factor in the pathogenesis of MDD. Known for its role in intercellular communication, cell proliferation, and fate, Wnt signaling has been implicated in diverse biological phenomena associated with MDD, spanning neurodevelopmental to neurodegenerative processes. In this systematic review, we summarize the functional differences in protein and gene expression of the Wnt signaling pathway, and targeted genetic association studies, to provide an integrated synthesis of available human data examining Wnt signaling in MDD. Thirty-three studies evaluating protein expression (n = 15), gene expression (n = 9), or genetic associations (n = 9) were included. Only fifteen demonstrated a consistently low overall risk of bias in selection, comparability, and exposure. We found conflicting observations of limited and distinct Wnt signaling components across diverse tissue sources. These data do not demonstrate involvement of Wnt signaling dysregulation in MDD. Given the well-established role of Wnt signaling in antidepressant response, we propose that a more targeted and functional assessment of Wnt signaling is needed to understand its role in depression pathophysiology. Future studies should include more components, assess multiple tissues concurrently, and follow a standardized approach.