Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies).

The Interaction Effect of Sleep Deprivation and Treadmill Exercise in Various Durations on Spatial Memory with Respect to the Oxidative Status of Rats.

Sleep deprivation (SD) has deleterious effects on cognitive functions including learning and memory. However, some studies have shown that SD can improve cognitive functions. Interestingly, treadmill exercise has both impairment and improvement effects on memory function. In this study, we aimed to investigate the effect of SD for 4 (short-term) and 24 (long-term) hours, and two protocols of treadmill exercise (mild short-term and moderate long-term) on spatial memory performance, and oxidative and antioxidant markers in the serum of rats. Morris Water Maze apparatus was used to assess spatial memory performance. Also, SD was done using gentle handling method. In addition, the serum level of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) was measured. The results showed that 24 h SD (but not 4 h) had negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Long-term moderate (but not short-term mild) treadmill exercise had also negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Interestingly, both protocols of treadmill exercise reversed spatial memory impairment and oxidative stress induced by 24 h SD. In conclusion, it seems that SD and treadmill exercise interact with each other, and moderate long-term exercise can reverse the negative effects of long-term SD on memory and oxidative status; although, it disrupted memory function and increased oxidative stress by itself.

Intricate role of sleep deprivation in modulating depression: focusing on BDNF, VEGF, serotonin, cortisol, and TNF-α.

In this review article, we aimed to discuss intricate roles of SD in modulating depression in preclinical and clinical studies. Decades of research have shown the inconsistent effects of SD on depression, focusing on SD duration. However, inconsistent role of SD seems to be more complicated, and SD duration cannot be the only one factor. Regarding this issue, we chose some important factors involved in the effects of SD on cognitive functions and mood including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), serotonin, cortisol, and tumor necrosis factor-alpha (TNF-α). It was concluded that SD has a wide-range of inconsistent effects on BDNF, VEGF, serotonin, and cortisol levels. It was noted that BDNF diurnal rhythm is significantly involved in the modulatory role of SD in depression. Furthermore, the important role of VEGF in blood-brain barrier permeability which is involved in modulating depression was discussed. It was also noted that there is a negative correlation between cortisol and BDNF that modulates depression. Eventually, it was concluded that TNF-α regulates sleep/wake cycle and is involved in the vulnerability to cognitive and behavioral impairments following SD. TNF-α also increases the permeability of the blood-brain barrier which is accompanied by depressive behavior. In sum, it was suggested that future studies should focus on these mechanisms/factors to better investigate the reasons behind intricate roles of SD in modulating depression.

Night shift hormone: How does melatonin affect depression?

Melatonin is the main hormone secreted by the pineal gland that modulates the circadian rhythm and mood. Previous studies have shown the therapeutic effects of melatonin, or its important analogue, agomelatine, on depression. In this review study, we aimed to discuss the potential mechanisms of melatonin involved in the treatment of depression. It was noted that disrupted circadian rhythm can lead to depressive state, and melatonin via regulating circadian rhythm shows a therapeutic effect. It was also noted that melatonin induces antidepressant effects via promoting antioxidant system and neurogenesis, and suppressing oxidative stress, neuroinflammation, and apoptosis. The interaction effect between melatonin or agomelatine and serotonergic signaling has a significant effect on depression. It was noted that the psychotropic effects of agomelatine are induced by the synergistic interaction between melatonin and 5-HT2C receptors. Agomelatine also interacts with glutamatergic signaling in brain regions involved in regulating mood and circadian rhythm. Interestingly, it was concluded that melatonin exerts both pro- and anti-inflammatory effects, depending on the grade of inflammation. It was suggested that synergistic interaction between melatonin and 5-HT2C receptors may be able to induce therapeutic effects on other psychiatric disorders. Furthermore, dualistic role of melatonin in regulating inflammation is an important point that can be examined at different levels of inflammation in animal models of depression.

St. John's wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems?

St. John's wort (Hypericum perforatum) is a herbaceous plant containing many bioactive molecules including naphthodianthrones, phloroglucinol derivatives, flavonoids, bioflavonoids, proanthocyanidins, and chlorogenic acid. Evidence has shown the therapeutic effects of St. John's wort and especially its two major active components, hyperforin and hypericin, on different psychiatric and mood disorders such as posttraumatic stress disorder (PTSD), attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and anxiety disorders. St. John's wort also induces antidepressant effects. In this review study, we aimed to discuss the role of St. John's wort in modulating depression, with respect to the role of different neurotransmitter systems in the brain. We discussed changes in the neurotransmitter levels in depression, and following use of St. John's wort. It was concluded that changes in the function and level of neurotransmitters in depression are complex. Also, St. John's wort can induce inconsistent effects on neurotransmitter levels. We also found that glutamate and acetylcholine may be the most important neurotransmitters to study in future works, because the function of both neurotransmitters in depression is unclear. In addition, St. John's wort induces a dualistic modulation on the activity of cholinergic signaling, which can be an interesting topic for future studies.

Treatment with RehaCom computerized rehabilitation program improves response control, but not attention in children with attention-deficit/hyperactivity disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children. ADHD impairs attention, response control, emotion regulation, and other cognitive functions. On the other hand, RehaCom is a cognitive rehabilitation software that has therapeutic effects on cognitive dysfunctions in many diseases such as stroke, multiple sclerosis, and schizophrenia. The goal of the present study was to investigate the effect of treatment with RehaCom on auditory and visual response control, and auditory and visual attention in children with ADHD. Forty patients were selected. The participants were assigned to control (n = 20) and experimental (n = 20) groups, while only the participants in the experimental group were trained by RehaCom for five weeks (ten 45-min sessions, two sessions per week). At weeks 0 and 5, performance of the participants of experimental group was compared with the participants of control group. The results showed that treatment with RehaCom significantly improved auditory and visual response control in children with ADHD, with no effect on auditory and visual attention. In conclusion, RehaCom may alter brain's structural and functional properties that are related to response control. We suggest that attention deficit in ADHD may be a result of more complicated dysfunctions in the brain, that are not affected by RehaCom.

Modulating role of serotonergic signaling in sleep and memory.

Serotonin is an important neurotransmitter with various receptors and wide-range effects on physiological processes and cognitive functions including sleep, learning, and memory. In this review study, we aimed to discuss the role of serotonergic receptors in modulating sleep-wake cycle, and learning and memory function. Furthermore, we mentioned to sleep deprivation, its effects on memory function, and the potential interaction with serotonin. Although there are thousands of research articles focusing on the relationship between sleep and serotonin; however, the pattern of serotonergic function in sleep deprivation is inconsistent and it seems that serotonin has not a certain role in the effects of sleep deprivation on memory function. Also, we found that the injection type of serotonergic agents (systemic or local), the doses of these drugs (dose-dependent effects), and up- or down-regulation of serotonergic receptors during training with various memory tasks are important issues that can be involved in the effects of serotonergic signaling on sleep-wake cycle, memory function, and sleep deprivation-induced memory impairments. This comprehensive review was conducted in the PubMed, Scopus, and ScienceDirect databases in June and July 2021, by searching keywords sleep, sleep deprivation, memory, and serotonin.

Inconsistent effects of sleep deprivation on memory function.

In this review article, we aimed to discuss the role of sleep deprivation (SD) in learning and memory processing in basic and clinical studies. There are numerous studies investigating the effect of SD on memory, while most of these studies have shown the impairment effect of SD. However, some of these studies have reported conflicting results, indicating that SD does not impair memory performance or even improves it. So far, no study has discussed or compared the conflicting results of SD on learning and memory. Thus, this important issue in the neuroscience of sleep remains unknown. The main goal of this review article is to compare the similar mechanisms between the impairment and the improvement effects of SD on learning and memory, probably leading to a scientific solution that justifies these conflicting results. We focused on the inconsistent effects of SD on some mechanisms involved in learning and memory, and tried to discuss the inconsistent effects of SD on learning and memory.