Antioxidant Biomolecules and Their Potential for the Treatment of Difficult-to-Treat Depression and Conventional Treatment-Resistant Depression.

Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.

Validation of the Mnemonic Similarity Task - Context Version

Objective: Pattern separation (PS) is the ability to represent similar experiences as separate, non-overlapping representations. It is usually assessed via the Mnemonic Similarity Task - Object Version (MST-O) which, however, assesses PS performance without taking behavioral context discrimination into account, since it is based on pictures of everyday simple objects on a white background. We here present a validation study for a new task, the Mnemonic Similarity Task - Context Version (MST-C), which is designed to measure PS while taking behavioral context discrimination into account by using real-life context photographs. Methods: Fifty healthy subjects underwent the two MST tasks to assess convergent evidence. Instruments assessing memory and attention were also administered to study discriminant evidence. The test-retest reliability of MST-C was analyzed. Results: Weak evidence supports convergent validity between the MST-C task and the MST-O as measures of PS (rs = 0.464; p < 0.01); PS performance assessed via the MST-C did not correlate with memory or attention; a moderate test-retest reliability was found (rs = 0.595; p < 0.01). Conclusion: The MST-C seems useful for assessing PS performance conceptualized as the ability to discriminate complex and realistic spatial contexts. Future studies are welcome to evaluate the validity of the MST-C task as a measure of PS in clinical populations.

Validation of the Mnemonic Similarity Task - Context Version.

OBJECTIVE: Pattern separation (PS) is the ability to represent similar experiences as separate, non-overlapping representations. It is usually assessed via the Mnemonic Similarity Task - Object Version (MST-O) which, however, assesses PS performance without taking behavioral context discrimination into account, since it is based on pictures of everyday simple objects on a white background. We here present a validation study for a new task, the Mnemonic Similarity Task - Context Version (MST-C), which is designed to measure PS while taking behavioral context discrimination into account by using real-life context photographs. METHODS: Fifty healthy subjects underwent the two MST tasks to assess convergent evidence. Instruments assessing memory and attention were also administered to study discriminant evidence. The test-retest reliability of MST-C was analyzed. RESULTS: Weak evidence supports convergent validity between the MST-C task and the MST-O as measures of PS (rs = 0.464; p < 0.01); PS performance assessed via the MST-C did not correlate with memory or attention; a moderate test-retest reliability was found (rs = 0.595; p < 0.01). CONCLUSION: The MST-C seems useful for assessing PS performance conceptualized as the ability to discriminate complex and realistic spatial contexts. Future studies are welcome to evaluate the validity of the MST-C task as a measure of PS in clinical populations.