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Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study

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Abstract

Objective: l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. Methods: Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). Results: HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. Conclusion: Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.

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... 46 l-Theanine, an amino acid, was associated with significant improvements in executive functioning and verbal memory after 8 weeks of open-label administration (N = 20) in a sample with mild depression (mean HDRS = 12.5). 45 Finally, following 12 weeks of intranasal insulin treatment in participants (N = 35) with treatment-resistant depression (mean MADRS = 25.9), no effects on cognition were found. ...
... 46 Finally, l-theanine is an amino acid that is contained in green tea and has been suggested to have psychotropic effects. 45 l-Theanine was correlated with improved cognition; however, the study was limited by its small sample (N = 20) and open-label design. 45 It is difficult to make definitive conclusions regarding the procognitive efficacy of non-antidepressant agents as there are few clinical trials focusing on these. ...
... 45 l-Theanine was correlated with improved cognition; however, the study was limited by its small sample (N = 20) and open-label design. 45 It is difficult to make definitive conclusions regarding the procognitive efficacy of non-antidepressant agents as there are few clinical trials focusing on these. Future studies should continue to assess the effectiveness of these agents using larger samples, controlled trials, and objective cognitive measures as primary outcome measures. ...
Article
Objective: To assess the efficacy of modafinil, a wakefulness-promoting drug, in major depressive disorder (MDD), with a specific focus on the putative procognitive effects of modafinil. Data sources: A database search of MEDLINE, PsycINFO, and Embase was conducted. No date limits were applied (the end date of the search was October 26, 2018), and only articles in English were included. The following search terms were used: modafinil, depression, depress*, major depressive disorder, cognition, cognitive dysfunction, and cogniti*. Study selection: Studies included were placebo-controlled or open-label trials of modafinil in MDD populations. Participants had to be diagnosed with MDD via DSM-IV or DSM-5 criteria, and no other interventions other than standard antidepressant treatment could be used in the trial. Overall, 540 articles were screened, 22 full-text research articles for inclusion criteria were assessed, and 12 studies were included in this review. Data extraction: Two independent reviewers extracted data and assessed the quality of publications. Results: Modafinil was associated with improvements in executive functioning after 4 weeks of open-label adjunctive treatment in currently depressed participants. Furthermore, in a placebo-controlled study of remitted MDD participants, modafinil led to rapid improvements in episodic and working memory after a single dose. There were contradictory findings on the subjective effects of modafinil on concentration. Conclusions: Modafinil shows preliminary evidence of alleviating specific cognitive symptoms in MDD patients, especially in the short term. However, more research using placebo-controlled longitudinal designs is needed to assess the benefits of modafinil, as there are very few studies addressing modafinil and cognition in MDD.
... Overall, several studies have shown that the administration of Ltheanine improved anxiety and stress outcomes, alongside improvements in other manifestations such as depression and psychopathological symptoms (Table 1). Such findings were obtained through the employment of several validated psychometric tools, including the Hamilton Anxiety Rating Scale (HARS), Tension Anxiety Scores, Pittsburgh Sleep Quality Index (PSQI), Positive and Negative Syndrome Scale (PANSS) [24,25], and others. ...
... Additionally, verbal memory and executive function were improved in individuals diagnosed with Major Depressive Disorder (MDD) supplemented with 250 mg of L -theanine and tested for the Brief Assessment of Cognition in Schizophrenia (BACS) [24]. Healthy individuals supplemented with 200 mg of L -theanine showed improvement in the tranquil-troubled subscale of the Visual Analogue Mood Scale (VAMS) [26]. ...
... Most of the studies appraised in our review recruited from 12 to 60 participants, were double-blinded and tested the effects of L -theanine in doses ranging from 15 to 400 mg [24][25][26][27]29,[31][32][33][34][35]. In addition, two of the studies appraised [28,30] investigated the effects of L -theanine combined with tea intake. ...
Article
Anxiety disorders are highly prevalent in modern societies, and are ranked the sixth most important contributor of non-fatal negative health outcomes. L-theanine is an amino acid naturally found in green tea (Camellia sinensis) and some other plant extracts, and recent clinical studies have proposed promising adjuvant effects of L-theanine for the negative impact of anxiety and psychological stress on health. In this integrative narrative review, we aimed to appraise and further discuss the effects of L-theanine administration on anxiety disorders and psychological stress. Published data suggests that L-theanine administered at daily doses ranging from 200 to 400 mg for up to 8 weeks are safe and induce anxiolytic and anti-stress effects in acute and chronic conditions. L-theanine at doses lower and higher than these may also show promising therapeutic potential; however, a more thorough investigation through randomized double-blind placebo-controlled crossover clinical trials are necessary to elucidate its effects for longer periods, providing further insights for meta-analyses and the development of recommendation guidelines. Additionally, animal studies investigating a higher dosage, its combination with other pharmacological compounds and associated metabolic comorbidities are recommended, as cases of hepatotoxicity associated with the consumption of green tea extract have been reported.
... 46 l-Theanine, an amino acid, was associated with significant improvements in executive functioning and verbal memory after 8 weeks of open-label administration (N = 20) in a sample with mild depression (mean HDRS = 12.5). 45 Finally, following 12 weeks of intranasal insulin treatment in participants (N = 35) with treatment-resistant depression (mean MADRS = 25.9), no effects on cognition were found. ...
... 46 Finally, l-theanine is an amino acid that is contained in green tea and has been suggested to have psychotropic effects. 45 l-Theanine was correlated with improved cognition; however, the study was limited by its small sample (N = 20) and open-label design. 45 It is difficult to make definitive conclusions regarding the procognitive efficacy of non-antidepressant agents as there are few clinical trials focusing on these. ...
... 45 l-Theanine was correlated with improved cognition; however, the study was limited by its small sample (N = 20) and open-label design. 45 It is difficult to make definitive conclusions regarding the procognitive efficacy of non-antidepressant agents as there are few clinical trials focusing on these. Future studies should continue to assess the effectiveness of these agents using larger samples, controlled trials, and objective cognitive measures as primary outcome measures. ...
Article
Full-text available
Objective: To review the efficacy of antidepressants and other therapeutic agents for the treatment of cognitive impairment in adults with major depressive disorder (MDD). Data sources: We conducted a database search of MEDLINE, PsycINFO, and Embase through Ovid on May 7, 2019. The year of publication was not restricted. The search terms "Major Depressive Disorder," "depress*," "cognit*," and "therapeutics" were used. Study selection: The studies included in this review were clinical trials of antidepressants and other therapeutic agents in MDD populations. Participants were aged between 18 and 65 years and had a DSM-III, -IV, or -5 diagnosis of MDD. In total, 2,045 research papers were screened, 53 full-text articles were assessed, and 26 articles were eligible to be included in this systematic review. Data extraction: The data and quality of research papers were assessed and screened by 2 independent reviewers. Discrepancies were resolved through a third reviewer. Results: Overall, studies demonstrated that tricyclic antidepressants do not have procognitive effects, while vortioxetine and bupropion have demonstrated procognitive effects in MDD populations relative to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Several non-antidepressant agents, such as modafinil, amphetamines, and erythropoietin, have also demonstrated significant positive effects on cognition in depression. Conclusions: Present-day antidepressants and other agents have demonstrated procognitive effects in MDD, but the findings between various agents are mixed. Further research looking at objective measures of cognitive performance would be helpful to obtain more definitive results regarding the efficacy of therapeutics for cognitive impairment in MDD.
... Eight clinical trials met the selection criteria and were included in this review [44][45][46][47][48][49][50][51]. The details of these studies are presented in Table 1. ...
... Nutrients examined so far are Omega-3 fatty acids, vitamin B, amino acids and derivates (S-adenosylmethionine, N-acetylcysteine, l-theanine, creatine), and a combination of nutritional products (citicoline). With one exception [50], all studies are randomized, double-blind, placebo-controlled trials. ...
... In a recent open-label trial with 20 outpatients with MDD, ltheanine was added to treatment for 8 weeks [50]. Most patients had mild MDD, and 60% of them were taking antidepressants at baseline. ...
Article
Bipolar disorder and major depression are associated with significant disability, morbidity, and reduced life expectancy. People with mood disorders have shown higher ratios of unhealthy lifestyle choices, including poor diet quality and suboptimal nutrition. Diet and nutrition impact on brain /mental health, but cognitive outcomes have been less researched in psychiatric disorders. Neurocognitive dysfunction is a major driver of social dysfunction and a therapeutic target in mood disorders, although effective cognitive-enhancers are currently lacking. This narrative review aimed to assess the potential cognitive benefits of dietary and nutritional interventions in subjects diagnosed with mood disorders. Eight clinical trials with nutrients were identified, whereas none involved dietary interventions. Efficacy to improve select cognitive deficits has been reported, but results are either preliminary or inconsistent. Methodological recommendations for future cognition trials in the field are advanced. Current evidence and future views are discussed from the perspectives of precision medicine, clinical staging, and nutritional psychiatry.
... Moreover, L-theanine has been suggested to have potential therapeutic effects in psychiatric disorders [39]. In accordance with this, we have reported multiple favourable effects of four weeks L-theanine administration (250 mg/day) in patients with major depressive disorder (MDD), although this was an open-label study [40]. ...
... With the except of Hidese et al. [40], most human studies have focused on the effects of acute Ltheanine administration. The present study aimed to examine the effects of four weeks L-theanine administration (200 mg/day, four weeks) in a healthy population, i.e., individuals without any major psychiatric disorder. ...
... The sample size was determined by using G*Power software (3.1 version, Franz Faul, University of Kiel, Kiel, Germany) [41,42]. The current sample (30 L-theanine and 30 placebo) had a power of > 0.80, based on the effect size (0.61) of L-theanine on depression score in our previous study [40]. Individuals who had been treated for any psychiatric disorder, assessed according to the criteria of the Japanese version of the Mini-International Neuropsychiatric Interview [43,44] and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [45], were excluded. ...
Article
Full-text available
This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine the possible effects of four weeks L-theanine administration on stress-related symptoms and cognitive functions in healthy adults. Participants were 30 individuals (nine men and 21 women; age: 48.3 ± 11.9 years) who had no major psychiatric illness. L-theanine (200 mg/day) or placebo tablets were randomly and blindly assigned for four-week administration. For stress-related symptoms, Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased after L-theanine administration (p = 0.019, 0.006, and 0.013, respectively). The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration (all p < 0.05). For cognitive functions, verbal fluency and executive function scores improved after L-theanine administration (p = 0.001 and 0.031, respectively). Stratified analyses revealed that scores for verbal fluency (p = 0.002), especially letter fluency (p = 0.002), increased after L-theanine administration, compared to the placebo administration, in individuals who were sub-grouped into the lower half by the median split based on the mean pretreatment scores. Our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments and cognitive impairments.
... An open-label study was conducted to evaluate the effects of theanine on depressive symptoms on twenty individuals with major depressive disorders [30]. L-theanine (250 mg/day) was added to participants' current medication for eight weeks. ...
... Other functionalities of tea-theanine include improving memory by facilitating hippocampal synaptic efficiency. In the study mentioned above performed by Hidese et al. [30], cognitive function was improved after L-theanine treatment (250 mg/day) as shown by decreased response latency (P = 0.001) and error rate (P = 0.036) in the Stroop test, and increased verbal memory (P = 0.005) and executive function (P = 0.016) in the Brief Assessment of Cognition in Schizophrenia test [30]. A lower dose of L-theanine (200 mg/day) was applied to 30 healthy participants without clinical depression in a randomised, placebo-controlled, crossover, and double-blind trial [8]. ...
... Other functionalities of tea-theanine include improving memory by facilitating hippocampal synaptic efficiency. In the study mentioned above performed by Hidese et al. [30], cognitive function was improved after L-theanine treatment (250 mg/day) as shown by decreased response latency (P = 0.001) and error rate (P = 0.036) in the Stroop test, and increased verbal memory (P = 0.005) and executive function (P = 0.016) in the Brief Assessment of Cognition in Schizophrenia test [30]. A lower dose of L-theanine (200 mg/day) was applied to 30 healthy participants without clinical depression in a randomised, placebo-controlled, crossover, and double-blind trial [8]. ...
Article
Tea (Camellia sinensis) is widely considered to promote feelings of calming and soothing. This effect is attributed to L-theanine (L-γ-glutamylethylamide) in tea, a non-protein amino acid mainly derived from tea leaves. As a naturally occurring structural analogue of glutamate, L-theanine competes for the receptors with glutamate and is able to pass the blood-brain barrier to exert its relaxation effect. This review focuses on the relaxation effect of L-theanine, including animal models and the latest human trials as well as the potential molecular mechanisms regarding neuron stem cells. The biological efficacy of dietary L-theanine in the food matrix has been further discussed in this review in relation to the physiological changes in the gastrointestinal tract and bindings of L-theanine with other food components.
... Nearly 7% of older adults in the world are affected by depression (2). Experimental research has highlighted the potential anti-depressant effects of tea polyphenols and suggest that regular tea consumption may reduce the risk and severity of depression in humans (3)(4)(5)(6)(7)(8)(9)(10). Epidemiological evidence for the benefits of tea consumption on mental health and wellbeing is however inconclusive (11,12). ...
... In mice models, tea polyphenols especially green tea catechins, such as epigallocatechin gallate (ECCG) exert anti-inflammatory actions (3,4) and lower depression (5, 6) by, among other mechanisms, inhibition of the hypothalamic-pituitary-adrenal axis (7). Clinical studies show that L-theanine, a unique component in green tea, ameliorate stress-related symptoms and depressive disorders (8,9). Evidence from human electroencephalograph (EEG) studies show that L-theanine significantly increases activity in the alpha frequency band indicating mental relaxation (10). ...
Article
Objectives Experimental evidence suggest that tea polyphenols have anti-depressant effect and tea consumption may reduce the risk and severity of depression. We investigated whether tea consumption was associated with changes in depressive symptoms over time among Asian older adults.DesignPopulation-based prospective cohort study with mean 4 years of follow up.SettingSingapore Longitudinal Ageing Study (SLAS) of community-living older persons.Participants3177 participants overall (mean age 67 years) and 3004 participants who were depression-free at baseline.MeasurementsBaseline tea consumption which include Chinese (black, oolong or green) tea or Western (mixed with milk) tea and change in Geriatric Depression Scale (GDS) measure of depression. Incident depression was defined by GDS≥5, and GDS depression improvement or deterioration by GDS change of ≥4 points. Estimated odds ratio and 95% confidence intervals (OR, 95%CI) were adjusted for baseline age, sex, ethnicity, education, housing type, single/divorced/widowed, living alone, physical and social activity, smoking, alcohol, number of comorbidities, MMSE, and baseline GDS level.ResultsCompared to non-tea drinkers, participants who consumed ≥3 cups of tea of all kinds were significantly less likely to have worsened GDS symptoms: OR=0.32, 95% CI=0.12, 0.84. Among baseline depression-free participants, the risk of incident GDS (≥5) depression was significantly lower (OR=0.34, 95%CI=0.13, 0.90) for daily consumption of all types of tea, and Chinese (black, oolong or green) tea (OR=0.46, 95%CI=0.21,0.99).Conclusion This study suggests that tea may prevent the worsening of existing depressive symptoms and the reduce the likelihood of developing threshold depression.
... In addition, histamine is strongly suggested to have a pivotal role in the regulation of sleep and wakefulness via H 1 or H 3 receptor [33]. Theanine has been suggested to improve sleep quality based on actigraph-based sleep studies [34] and based on the Pittsburgh Sleep Quality index [35], but the mechanism remains unclear. The high histamine levels in the SAMP10 mice could not be explained by HDC expression levels, as HDC expression in the hypothalamus was higher in the ddY mice than in the group reared SAMP10 mice. ...
... Actually, theanine has been reported to have beneficial effects on depressive disorder, anxiety, sleep disorders, and cognitive decline in patients with major depressive disorder, and on stress-related symptoms and cognitive functions in healthy adults [35,46]. The results of our study are considered to be important clues for elucidating how theanine acts in the brain to ameliorate stress-related symptoms. ...
Article
Full-text available
By comprehensively measuring changes in metabolites in the hippocampus of stress-loaded mice, we investigated the reasons for stress vulnerability and the effect of theanine, i.e., an abundant amino acid in tea leaves, on the metabolism. Stress sensitivity was higher in senescence-accelerated mouse prone 10 (SAMP10) mice than in normal ddY mice when these mice were loaded with stress on the basis of territorial consciousness in males. Group housing was used as the low-stress condition reference. Among the statistically altered metabolites, depression-related kynurenine and excitability-related histamine were significantly higher in SAMP10 mice than in ddY mice. In contrast, carnosine, which has antidepressant-like activity, and ornithine, which has antistress effects, were significantly lower in SAMP10 mice than in ddY mice. The ingestion of theanine, an excellent antistress amino acid, modulated the levels of kynurenine, histamine, and carnosine only in the stress-loaded SAMP10 mice and not in the group-housing mice. Depression-like behavior was suppressed in mice that had ingested theanine only under stress loading. Taken together, changes in these metabolites, such as kynurenine, histamine, carnosine, and ornithine, were suggested to be associated with the stress vulnerability and depression-like behavior of stressed SAMP10 mice. It was also shown that theanine action appears in the metabolism of mice only under stress loading.
... Furthermore, it has been reported that theanine's effects on neurotransmitters in the brain, such as dopamine [66], suppress excitation by caffeine [69], improve memory [70], have a high affinity for the glutamine transporter [70], and enact a neurogenic effect [71]. As regards the actions of theanine in humans, a relaxing effect [26], stress reduction [24,25], and a reduction in depression and schizophrenia [72] have been reported. On the other hand, little attention has been paid to the functionality of arginine in green tea, but it has been revealed to have an excellent stress-reducing effect, similar to that of theanine [27,28]. ...
... Theanine intake significantly suppresses histamine levels in stressloaded SAMP10 mice [86], suggesting that the histaminergic system is an important target for theanine. In addition, theanine has been suggested to improve sleep quality [72,97]. It is interesting that histamine likely plays a pivotal role in the regulation of sleep-wakefulness via the H1 and/or H3 receptors [96]. ...
Article
Full-text available
Epidemiological studies have demonstrated that the intake of green tea is effective in reducing the risk of dementia. The most important component of green tea is epigallocatechin gallate (EGCG). Both EGCG and epigallocatechin (EGC) have been suggested to cross the blood–brain barrier to reach the brain parenchyma, but EGCG has been found to be more effective than EGC in promoting neuronal differentiation. It has also been suggested that the products of EGCG decomposition by the intestinal microbiota promote the differentiation of nerve cells and that both EGCG and its degradation products act on nerve cells with a time lag. On the other hand, the free amino acids theanine and arginine contained in green tea have stress-reducing effects. While long-term stress accelerates the aging of the brain, theanine and arginine suppress the aging of the brain due to their anti-stress effect. Since this effect is counteracted by EGCG and caffeine, the ratios between these green tea components are important for the anti-stress action. In this review, we describe how green tea suppresses brain aging, through the activation of nerve cells by both EGCG and its degradation products, and the reductions in stress achieved by theanine and arginine.
... Participants receiving green tea were shown to have reduced HRSD-17 suggests that regular daily tea intake may contribute to a reduction in risk of depressive symptoms in healthy people. An open-label study investigated the effects of theanine on depressive symptoms in 20 individuals with major depressive disorders, who, at the beginning of the trial, had shown no remission under their antidepressant medication [70]. The administration of L-theanine (250 mg/day) for 8 weeks in addition to the current medication of the participants significantly reduced their Hamilton Depression Rating Scale (HAMD-21) score [70]. ...
... An open-label study investigated the effects of theanine on depressive symptoms in 20 individuals with major depressive disorders, who, at the beginning of the trial, had shown no remission under their antidepressant medication [70]. The administration of L-theanine (250 mg/day) for 8 weeks in addition to the current medication of the participants significantly reduced their Hamilton Depression Rating Scale (HAMD-21) score [70]. A possible explanation of the antidepressive effects of L-theanine could be related to stress reduction. ...
Article
The available evidence, which derives from studies investigating mechanistic effects of tea, research on animal models as well as epidemiological studies and intervention trials in humans, suggests that compounds contained in tea may have the potential to aid in the prevention of depression or in its treatment as an addition to established therapies. A wide range of potentially antidepressive biological activities of tea components have been reported. However, the mechanisms of tea phytochemicals possibly capable of decreasing the risk of depressive symptoms are complex, multifaceted and not well understood. Potent pharmacological effects on circumscribed neurobiological systems may be produced not by individual tea components but rather by the synergistic action of various compounds on multiple pathophysiological mechanisms involved in depression. While epidemiological studies have generally demonstrated beneficial effects of tea consumption on mood and depressive symptoms, cross-sectional studies are unable to prove a cause-effect relationship. If positive effects on mood could be firmly established, tea drinking could support mental health. However, the moderate antidepressive effects observed in healthy people are not necessarily indicative of possible clinical effects in major depressive disorder. Randomized controlled intervention studies are needed to establish a causal relationship between bioactive compounds in tea and depression.
... L-theanine is available commercially in purified form as a nutritional supplement [18]. Potential cognitive benefits of daily supplementation of L-theanine have been increasingly studied in recent years in healthy adults [19], and in different neuropsychiatric populations including patients with generalized anxiety disorder [16], major depressive disorder [20], schizophrenia [21] and attention deficit hyperactivity disorder [17]. Williams et al. [22], in a systematic review, suggest that L-theanine supplementation may reduce stress and anxiety levels, however no pooled effect sizes were calculated possibly due to paucity and heterogeneity of the eligible randomized controlled trials [22]. ...
... L-theanine is often advertised with claims of enhancing alertness and attention [16,20,21]. Several single-dose, placebo-controlled trials have investigated the acute attentional effects of L-theanine on healthy human volunteers using behavioral, neurophysiological and functional neuroimaging indices of selective attention [23][24][25][26][27][28][29][30]. ...
Article
Objective: L-theanine, a non-proteinic amino acid found in tea, is known to enhance attention particularly in high doses, with no reported adverse effects. We aimed to determine whether oral administration of L-theanine acutely enhances neurophysiological measures of selective attention in a dose-dependent manner. Methods: In a double-blind, placebo-controlled, counterbalanced, 4-way crossover study in a group of 27 healthy young adults, we compared the effects of 3 doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water) on latencies of amplitudes of attentive and pre-attentive cognitive event-related potentials (ERPs) recorded in an auditory stimulus discrimination task, before and 50 min after dosing. Results: Compared to the placebo, 400 mg of theanine showed a significant reduction in the latency of the parietal P3b ERP component (p < 0.05), whereas no significant changes were observed with lower doses. A subsequent exploratory regression showed that each 100-mg increase in dose reduces the P3b latency by 4 ms (p < 0.05). No dose–response effect was observed in P3b amplitude, pre-attentive ERP components or reaction time. Discussion: The findings indicate L-theanine can increase attentional processing of auditory information in a dose-dependent manner. The linear dose–response attentional effects we observed warrant further studies with higher doses of L-theanine.
... In human adults subjected to physical and psychological stress tasks, oral intake of theanine more effectively ameliorates increases in both anxiety and blood pressure than the intake of the other green tea ingredient caffeine (Yoto et al., 2012). In patients suffering from major depressive disorders, several beneficial improvements are seen in depressive symptoms, anxiety, sleep disturbance and cognitive impairments when they are orally given theanine for 8 weeks (Hidese et al., 2017). In boys with attention deficit hyperactivity disorder (ADHD), daily oral intake of theanine for 6 weeks improves the quality of sleep (Lyon et al., 2011). ...
... These include anxiety disorders, panic disorder, obsessive compulsive disorder and bipolar disorder (Lardner, 2014). In an open clinical study on patients suffering from major depressive disorder, oral intake of theanine at 250 mg/day for 8 weeks promotes the therapeutic efficacy of the current medication for depressive symptoms, anxiety, sleep disturbance and cognitive impairment as described above (Hidese et al., 2017). ...
Article
The green tea amino acid theanine is abundant in green tea rather than black and oolong teas, which are all made of the identical tea plant “Chanoki” (Camellia sinensis). Theanine has a molecular structure close to glutamine (GLN) compared to glutamic acid (Glu), in terms of the absence of a free carboxylic acid moiety from the gamma carbon position. Theanine efficiently inhibits [3H]GLN uptake without affecting [3H]Glu uptake in rat brain synaptosomes. In contrast to GLN, however, theanine markedly stimulates the abilities to replicate and to commit to a neuronal lineage following prolonged exposure in cultured neural progenitor cells (NPCs) prepared from embryonic and adult rodent brains. Upregulation of transcript expression is found for one of the GLN transporter isoforms, Slc38a1, besides the promotion of both proliferation and neuronal commitment along with acceleration of the phosphorylation of mechanistic target of rapamycin (mTOR) and relevant downstream proteins, in murine NPCs cultured with theanine. Stable overexpression of Slc38a1 similarly facilitates both cellular replication and neuronal commitment in pluripotent embryonic carcinoma P19 cells. In P19 cells with stable overexpression of Slc38a1, marked phosphorylation is seen for mTOR and downstream proteins in a manner insensitive to further additional phosphorylation by theanine. Taken together, theanine would exhibit a novel pharmacological property to up-regulate Slc38a1 expression for activation of the intracellular mTOR signaling pathway required for neurogenesis after sustained exposure in undifferentiated NPCs in the brain. In this review, a novel neurogenic property of the green tea amino acid theanine is summarized for embryonic and adult neurogenesis with a focus on the endogenous amino acid GLN on the basis of our accumulating evidence to date.
... L-Theanine is an amino acid primarily found in the green tea plant (Camelia sinensis) and some other plant extracts that are generally well tolerated. It has been associated with several health benefits, including improvements in mood, cognition and a reduction of stress and anxiety-like symptoms [17][18][19][20]. ...
... Lyon et al. [22] have also demonstrated that L-theanine is safe and effective in improving some aspects of sleep quality in boys diagnosed with ADHD [22]. Moreover, published data regarding adult patients suggests that L-theanine administered at daily doses ranging from 200 to 400 mg for up to 8 weeks are safe and induce anxiolytic and anti-stress effects in acute and chronic conditions [17][18][19]42]. Another randomized, placebo-controlled study conducted on patients with schizophrenia and schizoaffective disorder had speculated that L-theanine augmentation of antipsychotic therapy could improve their positive, activation and anxiety symptoms [23]. ...
Article
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Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics and co-occurring disorders. It has been suggested that anxiety occurs in 2-45% patients affected by Tourette syndrome. Despite dietary and nutritional factors have been found to affect a range of neurological conditions, no more studies have investigated the relationship between nutritional supplements and tics. Objective: To evaluate the effectiveness of supplementation of both L-Theanine and Vitamin B6 in reducing tics and co-occurring disorders in a sample of youth with chronic tic disorder (CTD) or Tourette syndrome with anxiety symptoms. Design: A open-label trial. Patients affected by Tourette syndrome were randomized to receive nutritional supplements based on L-Theanine and vitamin B6, or psychoeducation (PE). Participants: 34 children (30 boys and 4 girls) aged between 4 and 17 years affected by Tourette syndrome or chronic tic disorder, associated with anxiety symptoms. Results: Patients in both groups showed a reduction in the severity of tic and anxiety symptoms. Supplementation with L-Theanine and vitamin B6 was significantly more effective than psychoeducation in reducing tics and co-occurring disorders, as measured by neuropsychological findings. Conclusions: Supplementation of both L-Theanine and Vitamin B6 may help in the treatment of tic disorders associated with anxious symptoms. Between-group differences in clinician-rated severity did reach statistical significance only for tics. Despite this finding, further placebo-controlled trials are needed.
... К настоящему времени проведено только одно исследование действия теанина на состояние больных с депрессией [56]. Были отобраны 20 пациентов с диагнозом большого депрессивного расстройства (БДР). ...
... К сожалению, отсутствуют данные о влиянии теанина на такие тревожные расстройства, как панические и генерализованные. Однако косвенные данные о влиянии теанина на хроническую тревожность при БДР [56] и шизофрении [58,61] являются обнадеживающими. Увеличение уровня BDNF под действием теанина, возможно, также связано с его антистрессорным действием, поскольку стресс подавляет экспрессию BDNF [62]. ...
Article
Theanine is an analog of glutamate and the major aminoacid in green tea. It has received growing attention in recent years because of its beneficial effects on the central nervous system. Theanine was shown to increase levels of brain-derived neurotrophic factor and to stimulate neurogenesis. Anti-stress and calming effects of theanine are the most apparent and well-studied. A number of studies showed neuroprotective effects of theanine after an ischemic cerebral injury or the exposure to toxic chemicals. It also improved cognitive function including attention, memory and learning. Recent studies demonstrated a promising role of theanine in augmentation therapy for major depressive disorder and schizophrenia. Theoretical grounds for using theanine in treatment of bipolar disorder, anxiety disorder and some neurodegenerative disorders are discussed.
... Thus, in a 6-week RTC study it was shown that C. sativus (a capsule/30 mg/day) improved mild depression via producing a significantly better outcome on the Hamilton depression rating scale compared to placebo [10]. In another preliminary double-blind and randomized study, Saffron (at 30 mg/day or 15 mg bid dose) was found to be effective similar to fluoxetine (at 20 mg/day or 10 mg bid dose) in the treatment of mild to moderate depression for 6 and 8-weeks, respectively [11,12]. In a double-blind randomized clinical trial study after taken the hydroalcoholic extract of C. sativus (40 or 80 mg) and fluoxetine (30 mg/ day) for 6 weeks, it has been reported that C. sativus 80 mg plus fluoxetine was found to be more effective than that of C. sativus 40 mg and fluoxetine to treat mild to moderate depression [13]. ...
... Where L-theanine emerges to be a nonproteinous amino acid and has a fantastic property of crossing the blood-brain barrier and proven to be elevated to the brain in a dose-dependent manner. Many preclinical studies on rats have been made to check the attenuation of hippocampal CA1 long-term potentiation after the exposure to the stress-induced suppression of recognition memory was rescued by L-theanine [62]. The cognitive dysfunction on the mice was found to be more effective by the treatment of L-theanine and its antidepressant effects. ...
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Depression is a condition of no mood and loss of interest in any activity that can diminish a person’s thinking, conduct, tendencies, emotional state, and a sense of well-being. Although there is a conventional class of medication which have been beneficial in the treatment of depression, current studies have reported having side effects which can be minimized by the intervention of herbs and phytochemicals. Most of the studies have proven the various mechanisms and have started to research a very ground-breaking method by glancing the ancient treatmen. Where this new approach of using the herbs and phytochemicals has shown better results alone and in combination with conventional drugs which has shown lesser adverse effects. The practice of phytomedicine is an additional option for the treatment of depression. In the various segments of treating the depression, the mainstream can be a breakthrough including phytoconstituents. In this aspect, there are many contributions for the treatment of the depression acting to the neuronal level signaling and the phytoconstituents also have shown some basic mechanisms in the treatment of depression as that of the conventional medications following some primary hypothesis and signaling pathways and life interactions that effects the brain in either way to treat the depression in all sort of way. Clinical evidence is required to provide backing to the safety and effectiveness of herbs and phytochemicals alone or in combination with currently available drugs to overcome the reported side effects during the treatment of depression.
... Oral intake of theanine was more effective in alleviating the elevations of both anxiety and blood pressure than caffeine in human adults with stressful tasks [68]. In an open clinical study on patients with major depressive disorder, similarly, several improvements were seen in the therapeutic efficacy of the current medication in terms of depressive symptoms, anxiety, sleep disturbance, and cognitive impairments after daily oral ingestion of theanine at a dose of 250 mg/day for eight weeks [69]. In boys previously diagnosed with attention deficit hyperactivity disorder (ADHD) at ages of eight to 12 years old, the quality of sleep was markedly improved after daily oral intake of theanine at a dose of 400 mg/day for six weeks in a randomized, double-blinded, and placebo-controlled study [70]. ...
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Theanine is an amino acid abundant in green tea with an amide moiety analogous to glutamine (GLN) rather than glutamic acid (Glu) and GABA, which are both well-known as amino acid neurotransmitters in the brain. Theanine has no polyphenol and flavonoid structures required for an anti-oxidative property as seen with catechins and tannins, which are more enriched in green tea. We have shown marked inhibition by this exogenous amino acid theanine of the uptake of [3H]GLN, but not of [3H]Glu, in rat brain synaptosomes. Beside a ubiquitous role as an endogenous amino acid, GLN has been believed to be a main precursor for the neurotransmitter Glu sequestered in a neurotransmitter pool at glutamatergic neurons in the brain. The GLN transporter solute carrier 38a1 (Slc38a1) plays a crucial role in the incorporation of extracellular GLN for the intracellular conversion to Glu by glutaminase and subsequent sequestration at synaptic vesicles in neurons. However, Slc38a1 is also expressed by undifferentiated neural progenitor cells (NPCs) not featuring a neuronal phenotype. NPCs are derived from a primitive stem cell endowed to proliferate for self-renewal and to commit differentiation to several daughter cell lineages such as neurons, astrocytes, and oligodendrocytes. In vitro culture with theanine leads to the marked promotion of the generation of new neurons together with selective upregulation of Slc38a1 transcript expression in NPCs. In this review, we will refer to a possible novel neurogenic role of theanine for brain wellness through a molecular mechanism relevant to facilitated neurogenesis with a focus on Slc38a1 expressed by undifferentiated NPCs on the basis of our accumulating findings to date.
... In an open-label trail, Ltheanine was administered to patients with depression disorder, and results showed that the supplementation led to the reduction of Hamilton Depression Rating Scale score and Pittsburgh Sleep Quality Index from baseline. (19) Another open-label trial showed that subjects administered with pyrroloquinoline quinone posted improved Depression scores in POMS and in four of five items in Oguri-Shirakawa-Azumi Sleep Inventory for Middle-aged and Aged version (OSA-MA) from baseline. (20) Thus, sleep quality, which is strongly related to depression or mental stress, is also important to manage mood, and an object to research with functional food. ...
Article
This study investigated the effect of a dietary supplement containing astaxanthin-rich extract derived from Paracoccus carotinifaciens (astaxanthin supplement) on the status of stress and sleep in individuals aged 20–64 years. Twenty-five subjects orally administered 12 mg astaxanthin/day of astaxanthin supplement for 8 weeks (astaxanthin group) and 29 subjects given a placebo (placebo group) were evaluated with Profile of Mood States 2nd Edition for stress and Oguri–Shirakawa–Azumi Sleep Inventory for Middle-aged and Aged version for sleep. We did not observe any significant intergroup differences in the stress and sleep. A subgroup analysis was performed after dividing the subjects into two groups: those who scored >65 and those who scored ≤65 in the ”Depression–Dejection” dimension of Profile of Mood States 2nd Edition. The sleep of subjects who scored >65 (”Depression–Dejection”) showed significant improvement in the astaxanthin group compared with the placebo group, whereas no significant improvement was observed in stress and the other subjects. Our results indicate that people who tend to be strongly depressed may experience improved sleep after ingesting astaxanthin supplement. On the basis of the parameters tested, administration of astaxanthin supplement was not associated with any problems related to safety. Clinical registration: This study has been registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000038619) on August 24, 2018 as ”A study to evaluate the effect of intake of astaxanthin on the status of stress and sleep in adults,” Identification No. UMIN000033863.
... TEA has been reported to possess antidepressant effects in humans and animal studies. Indeed, Hidese and co-workers showed that 8 weeks administration of TEA (250 mg/day) had beneficial effects on depressive symptoms, anxiety, sleep disorders, and cognitive impairment in patients with mild major depressive disorders [46]. The antidepressant-like activity of repeated TEA (0.4-20 mg/kg) administration was also confirmed in vivo using the open-field test, the forced swim test, the elevated plus-maze test, the prepulse inhibition of acoustic startle, the tail suspension test" and the reserpine test [47,48]. ...
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Mood disorders represent one of the most prevalent and costly psychiatric diseases worldwide. The current therapies are generally characterized by several well-known side effects which limit their prolonged use. The use of herbal medicine for the management of several psychiatric conditions is becoming more established, as it is considered a safer support to conventional pharmacotherapy. The aim of this study was to investigate the possible anxiolytic and antidepressant activity of a fixed combination of L-theanine, Magnolia officinalis, and Melissa officinalis (TMM) in an attempt to evaluate how the multiple modulations of different physiological systems may contribute to reducing mood disorders. TMM showed an anxiolytic-like and antidepressant-like activity in vivo, which was related to a neuroprotective effect in an in vitro model of excitotoxicity. The effect of TMM was not altered by the presence of flumazenil, thus suggesting a non-benzodiazepine-like mechanism of action. On the contrary, a significant reduction in the effect was observed in animals and neuronal cells co-treated with AM251, a cannabinoid receptor type 1 (CB1) antagonist, suggesting that the endocannabinoid system may be involved in the TMM mechanism of action. In conclusion, TMM may represent a useful and safe candidate for the management of mood disorders with an innovative mechanism of action, particularly as an adjuvant to conventional therapies.
... participants with MDD ( Hidese et al., 2016). A further open label study in 17 patients with schizophrenia has reported improvements in subjective sleep quality (as per the PSQI) after 8-week of LT (250 mg/ day) supplementation ( Ota et al., 2015). ...
... On the other hand, acute and chronic toxicity tests conducted on the safety of theanine have not yet established a toxicity threshold (Türközü, & Şanlier, 2017), and the no observable adverse effect level (NOAEL) of theanine is 4000 mg/kg/day in rats (Borzelleca, Peters, & Hall, 2006). Additionally, 250-400 mg per day for a consecutive 8 weeks is a widely used functional dose in human clinical study (Hidese et al., 2017;Miodownik et al., 2011;Ritsner et al., 2011;Tsuchiya et al., 2016). The cumulative dose in these clinical trail (400 mg/ day × 7 days × 8 weeks = 22.4 g) is higher than the speculated dose in our study (960 mg/day × 7 days = 6.72 g) in a human with an average body weight of 60 kg. ...
Article
Thermal stress evokes heat shock response and activates hypothalamic-pituitaryadrenal (HPA) axis. Additionally, liver injury is an important adverse effect of thermal stress. Considering the anti-stress effects of theanine, an amino acid found in tea plants, we hypothesized that theanine may protect against heat stress. Mice were administered intragastrically with theanine prior to whole body thermal exposure. Theanine prevented the heat-induced upregulation of heat shock proteins and reduced the heat-induced liver damage and oxidative stress. Theanine significantly prevented the heat-induced effects on inflammatory and acute phase responses as measured by plasma inflammatory cytokine concentrations, hepatic inflammatory cytokine mRNA levels, plasma nitric oxide and C-reactive protein levels. Additionally, theanine supplementation suppressed heat stress-related disorders associated with normalizing HPA axis hyperactivity. These findings suggest that theanine can have beneficial effects against heat stress and may be an attractive dietary application for people who are at high risk of developing heat stress.
... 107 In einer achtwöchigen Studie konnten mit 250mg Theanin/Tag starke Erfolge in der Therapie mit klinisch depressiven Personen (MDD) erzielt werden: Nach acht Wochen wurde die Aminosäure als sicher angesehen, mit zahlreichen therapeutischen Effekten gegen Angstzustände, Schlafstörungen und kognitive Beeinträchtigungen. 120 Auch bei ADHS-gestörten Kindern konnte eine Dosis von 400mg als sicher erachtet werden sowie den Schlaf verbessern. 121 Bei Patienten mit Schizophrenie konnten ähnliche Effekte sogar in einer doppelblind-kontrollierten Placebo Studie beobachtet werden (Effekte sind anregend und angstlösend). ...
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Die hier vorgestellten Produkte mit Schwerpunkt Nachhaltigkeit und Evidenz-basierten Inhaltsstoffen (Energy-Drink & Protein-Riegel) erhalten im Verbrauchermarkt aufsteigendes Interesse. Dies liegt unter anderem daran, dass Nahrungsmittel mit gesundheits- und leistungsfördernden Eigenschaften benötigt werden, um der steigenden Anzahl an Krankheiten präventiv entgegenzuwirken. Besonders wichtig ist die adäquate Zufuhr von Proteinen und sekundären Pflanzenstoffe, um langfristig gesund zu bleiben. Im Gegensatz zu anderen bereits bestehenden Unternehmen liegt der Fokus dieses Konzepts auf der wissenschaftlichen Bestätigung zur Wirksamkeit der einzelnen Inhaltsstoffe. Damit soll dem Käufer ein optimales Preis-Leistungsverhältnis, auch in Bezug auf den Geschmack, geboten werden. Zusätzlich steht der Ressourcen-schonende Umgang mit Rohstoffen und Verpackungsmaterialien im Vordergrund, sodass zukunftsfähiges Handeln ermöglicht wird. Gerade in einer Zeit von hohen menschengemachten Umweltbelastungen, wie beispielsweise durch Plastikaufkommen in den Meeren, ist eine moralische Firmenpolitik notwendiger denn je.
... The BACS was originally developed for use in clinical trials targeting cognition in schizophrenia. However, recent studies have demonstrated its suitability for effectively capturing neurocognitive deficits in patients with MDD (Hidese et al. 2017;Terachi et al. 2017). The BACS is composed of several individual tests that give rise to six cognitive domains: ...
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Background Neuropsychological deficits are present across various cognitive domains in major depressive disorder (MDD). However, a consistent and specific profile of neuropsychological abnormalities has not yet been established. Methods We assessed cognition in 170 patients with non-psychotic MDD using the Brief Assessment of Cognition in Schizophrenia and the scores were compared with those of 42 patients with schizophrenia as a reference for severity of cognitive impairment. Hierarchical cluster analysis was conducted to determine whether there are discrete neurocognitive subgroups in MDD. We then compared the subgroups in terms of several clinical factors and social functioning. Results Three distinct neurocognitive subgroups were found: (1) a mild impairment subgroup with near-normative performance and mild dysfunction in motor speed; (2) a selective impairment subgroup, which exhibited preserved working memory and executive function, but moderate to severe deficits in verbal memory, motor speed, verbal fluency, and attention/information processing speed; and (3) a global impairment subgroup with moderate to severe deficits across all neurocognitive domains, comparable with deficits in schizophrenia. The global impairment subgroup was characterized by lower pre-morbid intelligence quotient (IQ). Moreover, a significant difference between groups was observed in premorbid IQ ( p = 0.003), antidepressant dose ( p = 0.043), antipsychotic dose ( p = 0.013), or anxiolytic dose ( p < 0.001). Conclusions These results suggest the presence of multiple neurocognitive subgroups in non-psychotic MDD with unique profiles, one of which exhibits deficits comparable to those of schizophrenia. The results of the present study may help guide future efforts to target these disabling symptoms using different treatments.
... Tea consumption is shown to reduce the risk of depression [15], and green tea catechins have been shown to decrease depressive syndromes in experimental animals [16]. Thea has been reported to have beneficial effects on depressive syndromes, anxiety, and sleep disturbance in patients with a major depressive disorder [17]. In addition, caffeine is suggested to be a therapeutic agent for motivational dysfunction in depression [18]. ...
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The young leaves of green tea become lighter in color than usual when protected from sunlight by a shading net for about two weeks while growing. These leaves are called “shaded white leaf tea” or SWLT. In the eluate of SWLT, the amount of amino acids (361 mg/L) was significantly higher than that in regular tea (53.5 mg/L). Since theanine and arginine, the first and second most abundant amino acids in SWLT, have significant antistress effects, we examined the antistress effect of SWLT on humans. SWLT or placebo green tea (3 g) was eluted with room-temperature water (500 mL). Participants consumed the tea for one week prior to pharmacy practice and continued for 10 days in the practice period. The state-trait anxiety inventory, an anxiety questionnaire, tended to be scored lower in the SWLT group than the placebo, but other stress markers showed no differences. The effect of the difference in SWLT components examined with mice showed that aspartic acid and asparagine, which are abundant in SWLT, counteracted the antistress effects of theanine and arginine. Large amounts of caffeine also interfered with SWLT’s antistress effect. Thus, SWLT, which is high in caffeine and amino acids, suppressed depressant behavior in mice.
... The Stroop Test is a neuropsychiatric test that shows activities of the frontal area. It has been used for measuring selective attention capacity, disruptive impact resistance, and speed of information processing in patients with stroke, depression, and obsessive-compulsive disorder (Hidese et al. 2016). This test was also used successfully for measuring attention in patients with OSAS. ...
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Chronic rhinosinusitis with nasal polyposis is a chronic inflammatory disease of the respiratory mucosa of the nasal cavity and paranasal sinuses. The aim of this study was investigate the effect of nasal obstruction related to chronic rhinosinusitis with nasal polyposis on cognitive functions. Patients with chronic rhinosinusitis with nasal polyposis causing bilateral total or near total nasal obstruction were enrolled in the study. Symptoms of nasal congestion, loss of smell, postnasal drip, headaches, snoring, concentration difficulties and blunted affect were evaluated by Visual Analog Scale. Brief symptom inventory test, Stroop test, visual aural digit span, serial digit learning test and P300 test were used to evaluate cognitive functions. Three months after treatment, the tests done before surgery were repeated and the results were compared. A total of 30 patients were included in the study. On the Visual Analog Scale, all symptoms showed significant postoperative improvement in all patients (p < 0.001 for all symptoms). Preoperative nasal congestion accompanied with impaired concentration were detected in 27 patients (90%), and these symptoms recovered in all these patients after treatment (p = 0.035) (correlation coefficient 0.4). Only 22 patients completed the neuropsychological tests. The mean preoperative Stroop test (23.16 ± 5.30), visual aural digit span test (24.68 ± 3.52), and serial digit learning test (16.18 ± 5.35) scores were showed significant improvement compared with mean postoperative Stroop test (21.12 ± 5.69), visual aural digit span test (26.45 ± 2.98), and serial digit learning test (19.31 ± 4.47) scores (p = 0.047, p = 0.022, p = 0.005 respectively). The postoperative P300 latency values improved in 19 (63%) patients. The preoperative and postoperative latency values for P300 showed a significant difference (p = 0.029), whereas the preoperative and postoperative amplitude values for P300 did not differ (p = 0.096). In conclusion, the results of this study indicate that chronic rhinosinusitis with nasal polyposis (CRSwNP) has negative effects on cognitive functions, such as the ability to focus and maintain concentration. These cognitive functions improve after the patients undergo endoscopic sinus surgery to treat their CRSwNP.
... 42,43 Though the BACS-J is a test of neurocognition for schizophrenia, it has also been used for MDD. [44][45][46] It is composed of six subscales: verbal memory, working memory, motor speed, verbal fluency, attention and speed of information processing, and executive function. A higher score of the condition on hospitalization allows for the administration of more appropriate treatment on a priority basis. ...
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Objective: Substantial research has revealed cognitive function impairments in patients with major depressive disorder (MDD). However, the relationship between MDD cognitive function impairment and brain activity is yet to be elucidated. This study aimed to reveal this relationship using near-infrared spectroscopy (NIRS) to extensively measure frontotemporal cortex function. Methods: We recruited 18 inpatients with MDD and 22 healthy controls. Regional oxygenated hemoglobin changes (oxy-Hb) were measured during a verbal fluency task and its relationship to cognitive function was assessed. Cognitive function was assessed using the Japanese version of the Brief Assessment of Cognition in Schizophrenia. Results: Compared to healthy controls, patients with MDD displayed poorer motor speed, attention and speed of information processing, and executive function. In the bilateral prefrontal and temporal surface regions, regional oxy-Hb changes were significantly lower in patients with MDD than in healthy individuals. Moreover, we observed a correlation between reduced activation in the left temporal region and poor motor speed in patients with MDD. Conclusion: We suggest that reduced activation in the left temporal region in patients with MDD could be a biomarker of poor motor speed. Additionally, NIRS may be useful as a noninvasive, clinical measurement tool for assessing motor speed in these patients.
... In their study, patients were given 250 mg of L-theanine daily for eight weeks, and they observed that the depression score was significantly reduced after chronic administration of L-theanine; finally, they reported L-theanine's safety and beneficial effects on symptoms of depression. 57 The study lacked a placebo group; so, further placebo-controlled studies are needed to consolidate and validate the effects. ...
Article
Depression is a chronic and debilitating psychiatric disorder that affects 300 million people worldwide. Pharmacotherapy is one of the treatments. Due to delay in initiating treatment efficacy and the incomplete response to mono-drug therapy in one-third of patients, new approaches need to be considered. One of the ways to overcome this resistance to treatment and to enhance standard medical practice is to add complementary medicines. We aimed to document research progress from studies on integrative medicine for the treatment of depression. Review of PubMed and Scopus databases on the topic and a personal collection of the relevant publications are the sources for this study. Some of the nutraceuticals and complementary medicines in the treatment of depression will be reviewed. Supplements discussed in this review include S-adenosyl-methionine (SAMe), Crocus sativus (Saffron), carnosine, theanine, palmitoylethanolamide (PEA), tryptophan and 5-hydroxytryptophan (5-HTP), gemfibrozil, curcumin (the main active ingredient in turmeric), Hypericum perforatum (St John's wort), Lavandula angustifolia (Lavender), and Cinnamomum tamala. Despite evidence in favor of the antidepressant effect of several supplements, their efficacy and tolerability should be evaluated and validated by further high-quality studies.
... Four major hallmarks of the pathophysiology of major depressive disorders (MDDs) are central dopamine levels, inflammation, stress responses via the HPA axis and the autonomic nervous system, and dysfunction of BDNF [41]. MDD is considered, in some sense, to be a chronic inflammatory disease with altered levels of serum cytokines [42,43]. One animal study showed an association between MDD and several inflammatory pathways, including the nuclear factor κβ (NF-κβ), tumor necrosis factor (TNF), and Tolllike receptor pathways [42]. ...
... L-theanine from Camellia sinensis (L.) Kuntze is recommended in memory, cognition, and sleep disorders. It modulates multiple receptors like serotonergic, cholinergic, dopaminergic, NMDA, and GABAergic [72,73]. ...
Article
Ageing comes with degeneration in many biological activities like impairment of cognition, intelligence, attention, and memory. The decline in all those mental capabilities would be due to the abnormal changes in neuronal architecture with increasing age, chronic oxidative stress and inflammatory state of the tissue, nutritional deficiency. Nootropics or smart drugs enhance memory, attention, creativity, and cognitive performance by affecting the synthesis and receptor binding of neurotransmitters in the brain, especially dopamine, serotonin, gamma-aminobutyric acid, glutamate, and acetylcholine. Nootropics have shown their positive effects in parkinson's, autism, alzheimer's, huntington's disorders, where impaired memory is the primary concern. Synthetic class of nootropics has limitations and reported exacerbation of other brain disorders (off label effects) or therapeutic failure in some instances. Nutraceuticals are dietary derived vitamins, minerals, herbal products, proteins, marine products, and probiotics. The health benefits derived from Nutraceuticals are increasing brain blood flow, reducing inflammation in nervous tissues, detoxifying toxins from the brain, balancing neurotransmitter turnover rate, correcting neuronal and receptor damages and facilitating synaptic transmission, good antioxidant properties and power of improving neuroplasticity of the brain that combat neurodegeneration. The demands for effective nootropics will remain high as the number of cases are increased tremendously.
... In a study using LTA to treat GAD patients, the self-evaluated sleep satisfaction of patients was enhanced with the improved insomnia symptoms (Sarris et al. 2019). The study of Hidese et al. (2017) showed that 20 subjects with MDD had a significant decrease in the Pittsburgh Sleep Quality Index (PSQI) after administration of LTA (250 mg/d) for one month. Another study of 17 patients with schizophrenia showed that after 8 weeks of supplementation with LTA (250 mg/d), the PSQI was improved (Ota et al. 2015). ...
Article
Sleep disorders have received widespread attention nowadays, which have been promoted by the accelerated pace of life, unhealthy diets and lack of exercise in modern society. The chemical medications to improve sleep has shown serious side effects and risks with high costs. Therefore, it is urgent to develop efficient nutraceuticals from natural sources to ensure sleep quality as a sustainable strategy. As the second most consumed beverage worldwide, the health-promoting effects of tea have long been widely recognized. However, the modulatory effect of teas on sleep disorders has received much less attention. Tea contains various natural sleep-modulating active ingredients such as L-theanine (LTA), caffeine, tea polyphenols (TPP), tea pigments, tea polysaccharides (TPS) and γ-aminobutyric acid (GABA). This review focuses on the potential influence and main regulating mechanisms of different tea active ingredients on sleep, including being absorbed by the small intestine and then cross the blood-brain barrier to act on neurons in the brain as neurotransmitters, manipulating the immune system and further affect sleep-wake cycle by regulating the levels of cytokines, and controlling the gut microbes to maintain the homeostasis of circadian rhythm. Current research progress and limitations are summarized and several future development directions are also proposed. This review hopes to provide new insights into the future elucidation of the sleep-regulating mechanisms of different teas and their natural active ingredients and the development of tea-based functional foods for alleviating sleep disorders. • Highlights • • Natural sleep-modulating active ingredients in tea have been summarized. • • Influences of drinking tea or tea active ingredients on sleep are reviewed. • • Three main regulating mechanisms of tea active ingredients on sleep are explained. • • The associations among nervous system, immune system and intestinal microbiota are investigated. • • The potential of developing delivery carriers for tea active ingredients is proposed.
... Drinking tea may produce positive influences on both the material and spirit parts. For example, tea-drinking processes can make people enjoy the cheerful feelings, and at the same time, theanine, a nonproteinic amino acid special to tea, has positive effects on the emotional status [168]. ...
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Background Tea trees originated in southwest China 60 million or 70 million years ago. Written records show that Chinese ancestors had begun drinking tea over 3000 years ago. Nowadays, with the aging of populations worldwide and more people suffering from non-communicable diseases or poor health, tea beverages have become an inexpensive and fine complementary and alternative medicine (CAM) therapy. At present, there are 3 billion people who like to drink tea in the world, but few of them actually understand tea, especially on its development process and the spiritual and cultural connotations. Methods We searched PubMed, Google Scholar, Web of Science, CNKI, and other relevant platforms with the key word “tea”, and reviewed and analyzed tea-related literatures and pictures in the past 40 years about tea’s history, culture, customs, experimental studies, and markets. Results China is the hometown of tea, tea trees, tea drinking, and tea culture. China has the oldest wild and planted tea trees in the world, fossil of a tea leaf from 35,400,000 years ago, and abundant tea-related literatures and art works. Moreover, tea may be the first Chinese herbal medicine (CHM) used by Chinese people in ancient times. Tea drinking has many benefits to our physical health via its antioxidant, anti-inflammatory, immuno-regulatory, anticancer, cardiovascular-protective, anti-diabetic, and anti-obesity activities. At the moment, COVID-19 is wreaking havoc across the globe and causing severe damages to people’s health and lives. Tea has anti-COVID-19 functions via the enhancement of the innate immune response and inhibition of viral growth. Besides, drinking tea can allow people to acquire a peaceful, relaxed, refreshed and cheerful enjoyment, and even longevity. According to the meridian theory of traditional Chinese medicine, different kinds of tea can activate different meridian systems in the human body. At present, black tea (fermented tea) and green tea (non-fermented tea) are the most popular in the world. Black tea accounts for over 90% of all teas sold in western countries. The world’s top-grade black teas include Qi Men black in China, Darjeeling and Assam black tea in India, and Uva black tea in Sri Lanka. However, all top ten famous green teas in the world are produced in China, and Xi Hu Long Jing tea is the most famous among all green teas. More than 700 different kinds of components and 27 mineral elements can be found in tea. Tea polyphenols and theaflavin/thearubigins are considered to be the major bioactive components of black tea and green tea, respectively. Overly strong or overheated tea liquid should be avoided when drinking tea. Conclusions Today, CAM provides an array of treatment modalities for the health promotion in both developed and developing countries all over the world. Tea drinking, a simple herb-based CAM therapy, has become a popular man-made non-alcoholic beverage widely consumed worldwide, and it can improve the growth of economy as well. Tea can improve our physical and mental health and promote the harmonious development of society through its chemical and cultural elements.
... More research needs to be conducted to better understand the potential impact of paraxanthine supplementation on these health markers. L-theanine administration also decreased triglyceride levels, which operated in contrast to an earlier open-label study in patients with major depressive disorder, which showed an increase in triglycerides and a decrease in HDL after supplementing with 250 mg L-theanine for 8 weeks [37]. While blood creatinine levels are an indicator of whole-body muscle mass, the increase in gastrocnemius and soleus muscle mass in the paraxanthine group did not result in significantly different creatinine levels between groups. ...
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Paraxanthine is a natural dietary ingredient and the main metabolite of caffeine in humans. Compared to caffeine, paraxanthine exhibits lower toxicity, lesser anxiogenic properties, stronger locomotor activating effects, greater wake promoting properties, and stronger dopaminergic effects. The purpose of this study was to evaluate the potential beneficial effects of paraxanthine supplementation on muscle mass, strength, and endurance performance in comparison to the control and other ingredients commonly used by athletes: L-theanine, alpha-GPC, and taurine. Male Swiss Albino mice from five groups (n = 8 per group) were orally administered paraxanthine (20.5 mg/kg/day, human equivalence dose (HED) 100 mg), L-theanine (10.28 mg/kg/day, HED 50 mg), alpha-GPC (41.09 mg/kg/day, HED 200 mg), taurine (102.75 mg/kg/day, HED 500 mg), or control (carboxy methyl cellulose) for 4 weeks. Exercise performance was evaluated using forelimb grip strength and treadmill endurance exercise. All animals were subject to treadmill training for 60 min 5 days per week. Blood draws were utilized to analyze lipid profile, liver health, renal function, and nitric oxide levels. Paraxanthine significantly increased forelimb grip strength by 17% (p < 0.001), treadmill exercise performance by 39% (p < 0.001), gastrocnemius and soleus muscle mass by 14% and 41% respectively (both p < 0.001), and nitric oxide levels by 100% compared to control (p < 0.001), while reducing triglyceride (p < 0.001), total cholesterol (p < 0.001), LDL (p < 0.05), and increasing HDL (p < 0.001) compared to control, and compared to L-theanine, alpha-GPC, and taurine. Results from this initial investigation indicate that, when compared to the control, L-theanine, alpha-GPC, and taurine, paraxanthine is an effective ingredient for various aspects of sports performance and may enhance cardiovascular health.
... Besides, the other component of green tea, which is also believed to have neuroprotective effects and might play a significant role in alleviating psychiatric symptoms such as fatigue, depression, stress, anxiety cognition and sleep disorders, is a major amino acid of green tea, L-theanine, known as a likely analog of glutamate, and thus it might be able to affect the neuroexcitatory because of glutamatergic activation. A recent systematic review on nine RCT revealed that orally administered L-theanine for 200-400 mg/day up to eight weeks could help decrease the levels of stress and anxiety among the subjects exposed to stressful situations (Williams et al., 2020;Lopes Sakamoto et al., 2019;Hidese et al., 2017). It is worth noting that compared to other types of teas, the L-theanine content of green tea as an unfermented tea seems to be higher (Lopes Sakamoto et al., 2019). ...
Article
Purpose It is argued that COVID-19 patients show various neuropsychiatric symptoms, including fatigue, depression and anxiety. On the other hand, epidemiological and experimental evidence indicated that green tea could potentially have antiviral effects and ameliorate psychiatric disorders. However, there is a lack of clinical evidence. The purpose of this study was to investigate whether drinking green tea can clinically improve psychiatric complications of COVID-19 infection. Design/methodology/approach This study included 40 patients with laboratory confirmed mild-to-moderate COVID-19 disorder in the current randomized open-label controlled trial. Patients were instructed to include three cups/day of green tea (intervention) or black tea (control) to their usual diet for four weeks immediately after diagnosis of the disease. At the study baseline and after the intervention, the enrolled patients’ fatigue, depression and anxiety were assessed by the Chalder Fatigue Scale, Beck Depression Inventory-Fast Screen and State-Trait Anxiety Inventory questionnaires. Findings A total of 19 COVID-19 cases in the intervention group (mean age = 52 years) and 14 cases (mean age = 50 years) in the control group completed the study. Analysis of covariance adjusted for baseline levels, and confounders revealed that those who consumed three cups/day of green tea compared to the patients who received black tea experienced significantly lower fatigue, depression and state and trait anxiety levels (adjusted means for fatigue = 12.3 vs 16.2 ( P = 0.03), depression = 0.53 vs 1.8 ( P = 0.01), 37.4 vs 45.5 ( P < 0.01) and 37.9 vs 45.2 ( P < 0.01)). Research limitations/implications The open-label design may bias the evaluation of the self-reported status of fatigue, depression or anxiety as the main outcomes assessed. Moreover, as this study did not include patients with severe COVID-19, this might affect the generalizability of the present results. Thus, the recommendation of daily drinking green tea may be limited to the subjects diagnosed with mild-to-moderate type of infection or those with long-term neuropsychiatric complications owing to COVID-19. Besides, considering the ethical issues, this study could not exclude the drug therapy’s confounding effects; thereby, this point should be considered when interpreting the current results. Besides, it is worth noting that Guilan province in the north of Iran is recognized as a tea (and particularly green tea) producing region; thereby, it is an available and relatively inexpensive product. Considering this issue, the recommendation to consume this medicinal plant in adjunct to the routine treatment approach among patients with mild-to-moderate COVID-19 based on its beneficial effects may be widely accepted. Practical implications Green tea consumption could be considered an option to combat COVID-19 associated psychological complications, including fatigue, depression and anxiety among patients suffering from mild-to-moderate type of this viral infection. Originality/value To the best of the authors’ knowledge, in this study, for the first time, the effects of green tea compared to black tea on COVID-19 associated fatigue, depression and anxiety status within an open-label controlled trial have been investigated.
... In patients with schizophrenia and schizoaffective disorder, 8 weeks of 400 mg/day of L-theanine supplementation resulted in no treatment-related AEs being reported [33]. In an open-label study involving patients with major depressive disorder [38], 8 weeks of 250 mg/day of L-theanine supplementation saw a decrease in highdensity lipoprotein (HDL) cholesterol. However, the authors noted that HDL cholesterol was still considered normal (57.6 mg/dL) and well above the lower-limit safety range (40 mg/dL). ...
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Introduction: Stress is a complex life occurrence essential for survival and goal achievement but can be damaging in excess. Because of the high prevalence of stress in North America, a safe supplement that effectively reduces stress is in demand. The objective of this study was to investigate the efficacy and safety of AlphaWave® L-Theanine on whole-scalp and frontal alpha power, midline theta power, and salivary cortisol in healthy, moderately stressed adults. Methods: This was a randomized, triple-blind, placebo-controlled, crossover study that consisted of two study periods with a 7-day washout. A single dose of AlphaWave® L-Theanine (200 mg) or placebo was administered. To induce stress, a mental arithmetic test (MAT) was administered before and after the dose. Electroencephalogram, salivary cortisol, blood pressure, heart rate, self-reported stress, adverse events, clinical chemistry, and hematology were assessed to evaluate efficacy and safety. Results: Increases in heart rate, blood pressure, and self-reported stress and state anxiety indicated that participants experienced stress during the MAT. AlphaWave® L-Theanine led to a greater increase in frontal region and whole-scalp alpha power 3 h post-dose compared to placebo (p ≤ 0.050). Within groups, there were increases in alpha power, at 3 h with AlphaWave® L-Theanine, over the whole recording and during the eyes-open portions (p ≤ 0.048) of the alpha task. The changes in alpha wave activity are supported by greater decreases in salivary cortisol 1 h post-dose (p < 0.001) with AlphaWave® L-Theanine compared to placebo. Conclusion: This study was conducted during the SARS-CoV-2 pandemic, which has had a rapid and significant effect on both physical and mental health around the world. A single dose of AlphaWave® L-Theanine significantly increased frontal region alpha power compared to placebo in response to an acute stress challenge. These changes are indicative of relaxation in the brain and suggest a calming response. AlphaWave® L-Theanine was found to be safe and well tolerated by participants. Trial registration: ClinicalTrials.gov identifier NCT04706494.
... Thus, modulation of glutamatergic dysfunction has been proposed as a potential pharmacological intervention to prevent or reverse THC-induced psychopathology. Specifically, L-theanine, an amino acid analogue of L-glutamate and L-glutamine derived from green tea leaves, has been investigated due to its established therapeutic properties in anxiety, schizophrenia and depressive phenotypes [92][93][94][95]. Research in our laboratory has recently demonstrated that co-administration of L-theanine with THC in a neurodevelopmental rodent model of adolescent THC exposure, was able to powerfully block a wide range of THC-induced behavioral abnormalities into adulthood, including anhedonia, anxiety and impairments in memory and sensorimotor gating [96]. ...
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Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes. This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and cognitive impairments. Clinical and pre-clinical research continues to identify a wide array of underlying neuropathophysiological sequelae and mechanisms that may underlie THC-related psychiatric risk vulnerability, particularly following adolescent cannabis exposure. A common theme among these studies is the ability of developmental THC exposure to induce long-term adaptations in the mesocorticolimbic system which resemble pathological endophenotypes associated with these disorders. This narrative review will summarize recent clinical and pre-clinical evidence that has elucidated these THC-induced developmental risk factors and examine how specific pharmacotherapeutic interventions may serve to reverse or perhaps prevent these cannabis-related risk outcomes.
... The PSQI includes a 19-item questionnaire that evaluates sleep quality and efficiency during the prior month [27]. The HAMD scale is one of the most widely applied clinical measures of depression in psychiatric studies and has strong psychometric reliability and validity [28,29]. Thus, we assessed sleep quality and depression by the PSQI and HAMD scales in this study, finding that the quality of sleep in participants was satisfactory and that no participants developed depression. ...
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Background The plasma concentration of patients treated with efavirenz (EFV) 600 mg was found to exceed the upper limit of the proposed therapeutic window in most Chinese HIV-infected individuals; thus, dosage reduction of EFV to 400 mg daily warranted consideration. This study aimed to assess the pharmacodynamics of EFV 400 mg for HIV-1-infected patients in China. Method Twenty cART-naïve individuals were enrolled in this study. EFV 400 mg combined with tenofovir (TDF) and lamivudine (3TC) as an initial antiretroviral regimen was administered for 48 weeks. EFV concentration and T cell subsets as well as HIV RNA load were evaluated at baseline and at 4, 12, 24, and 48 weeks. Moreover, neuropsychiatric adverse effects were also assessed by the Hamilton depression (HAMD) scale and Pittsburgh sleep quality index (PSQI). Results Eighteen males and two females whose median age was 26 (interquartile range [IQR]: 23–32) years completed 48 weeks of follow-up. The median EFV concentrations were 1.88 (IQR: 1.54–2.42), 1.74 (IQR: 1.36–1.93), 1.93 (IQR: 1.66–2.22), and 1.85 (IQR: 1.54–2.14) mg/L at weeks 4, 12, 24, and 48, respectively. The viral load was 4.59 (IQR: 4.10–5.19) log 10 copies/mL at baseline, and it decreased by 4.6 (IQR: 3.98–5.18) log 10 copies/mL from baseline to week 48. Three of 20 (15%), 10 of 20 (50.0%), 17 of 20 (85%), and 18 of 19 (95%) participants had a plasma viral load less than 50 copies/mL at weeks 4, 12, 24, and 48, respectively. The median CD4 cell count was 330 (IQR: 237–410) cells/μL at baseline, and it increased to 473 (IQR: 344–574) cells/μL at 48 weeks. The HAMD score was 5 (IQR: 3–9.8) and 3 (IQR: 2.25–4) at baseline and 48 weeks, respectively. The PSQI score was 4 (IQR: 2–5.8) and 3 (IQR: 2–4) at baseline and 48 weeks, respectively. Dizziness was the most common event, occurring in 70% of patients within the first 2 weeks of treatment. Conclusion Patients prescribed with EFV 400 mg-containing agents demonstrated favourable virological and immunological responses. And the plasma EFV concentration was within the recommended therapeutic range, with fewer adverse reactions than with EFV 600 mg. EFV 400 mg was effective and safe in Chinese HIV-infected patients. Trial registration NCT04596488 ; Registered 21 October, 2020; Retrospectively registered.
... The PSQI includes a 19-item questionnaire that evaluates sleep quality and e ciency during the prior month [27]. The HAMD scale is one of the most widely applied clinical measures of depression in psychiatric studies and has strong psychometric reliability and validity [28,29]. Thus, we assessed sleep quality and depression by the PSQI and HAMD scales in this study, nding that the quality of sleep in participants was satisfactory and that no participants developed depression. ...
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Background: The plasma concentration of patients treated with efavirenz (EFV) 600 mg was found to exceed the upper limit of the proposed therapeutic window in most Chinese HIV-infected individuals; thus, dosage reduction of EFV to 400 mg daily warranted consideration. This study aimed to assess the pharmacodynamics of EFV 400 mg for HIV-1-infected patients in China. Method: Twenty cART-naïve individuals were enrolled in this study. EFV 400 mg combined with tenofovir (TDF) and lamivudine (3TC) as an initial antiretroviral regimen was administered for 48 weeks. EFV concentration and T cell subsets as well as HIV RNA load were evaluated at baseline and at 4, 12, 24, and 48 weeks. Moreover, neuropsychiatric adverse effects were also assessed by the Hamilton depression (HAMD) scale and Pittsburgh sleep quality index (PSQI). Results: Eighteen males and two females whose median age was 26 (interquartile range [IQR]: 23-32) years completed 48 weeks of follow-up. The median EFV concentrations were 1.88 (IQR: 1.54-2.42), 1.74 (IQR: 1.36-1.93), 1.93 (IQR: 1.66-2.22), and 1.85 (IQR: 1.54-2.14) mg/L at weeks 4, 12, 24, and 48, respectively. The viral load was 4.59 (IQR: 4.10-5.19) lg copies/mL at baseline, and it decreased by 4.6 (IQR: 3.98-5.18) lg copies/mL from baseline to week 48. Three of 20 (15%), 10 of 20 (50.0%), 17 of 20 (85%), and 18 of 19 (95%) participants had a plasma viral load less than 50 copies/mL at weeks 4, 12, 24, and 48, respectively. The median CD4 cell count was 330 (IQR: 237-410) cells/µL at baseline, and it increased to 473 (IQR: 344-574) cells/µL at 48 weeks. The HAMD score was 5 (IQR: 3-9.8) and 3 (IQR: 2.25-4) at baseline and 48 weeks, respectively. The PSQI score was 4 (IQR: 2-5.8) and 3 (IQR: 2-4) at baseline and 48 weeks, respectively. Dizziness was the most common event, occurring in 70% of patients within the first two weeks of treatment. Conclusion: Patients prescribed EFV 400 mg-containing agents demonstrated favourable virological and immunological responses. The plasma EFV concentration was within the recommended therapeutic range, with fewer adverse reactions than with EFV 600 mg. EFV 400 mg was effective and safe in Chinese HIV-infected patients. Trial registration: NCT04596488; Registered 21 October, 2020; Retrospectively registered
... PSQI included 19 items questionnaire that evaluating sleep quality, duration, e ciency and so on during the prior month [22] . And HAMD was one of the most widely applied clinical measures of depression in psychiatric studies that had strong psychometric reliability and validity [23,24] . Thus we assessed the sleep quality and depression by PSQI and HAMD in this study, nding the quality of sleep in participants was satisfactory and nobody developed depression. ...
Preprint
Full-text available
Background The plasma concentration of efavirenz (EFV) 600mg dose was found to exceed the upper limit of proposed therapeutic window in most Chinese HIV-infected individuals, thus dosage reduction of EFV to 400mg daily warrant consideration. This study aimed at assessing the pharmacodynamics of EFV 400mg for HIV-infected patients in China. Method Twenty cART-naïve individuals were enrolled in this study. EFV 400mg combined with tenofovir (TDF) and lamivudine (3TC) as initial antiretroviral regimens were administered for 48 weeks. EFV concentration and T-cell subsets as well as HIV RNA load were evaluated at baseline, 4, 12, 24, 48 weeks. Moreover, the neuropsychiatric adverse effects were also assessed by Hamilton depression scale (HAMD) and Pittsburgh sleep quality index (PSQI). Results Eighteen males and two females whose median age was 26 (interquartile range [IQR]: 23-32) years completed 48 weeks of follow-up. The median EFV concentration was 1.88 (IQR: 1.54-2.42), 1.74 (IQR: 1.36-1.93), 1.93 (IQR: 1.66-2.22), 1.85 (IQR: 1.54-2.14) mg/L at week 4, 12, 24, 48, respectively. The viral load was 4.59 (IQR: 4.10-5.19) lg copies/mL at baseline and it decreased by 4.6 (IQR: 3.98-5.18) lg copies/mL from baseline to weeks 48. 3 of 20 (15%), 10 of 20 (50.0%), 17 of 20 (85%), 18 of 19 (95%) participants had a plasma viral load less than 50 copies/mL at weeks 4, 12, 24, 48 respectively. The median CD4 cell count was 330 (IQR: 237-410) cells/µL at baseline and it increased to 473 (IQR: 344-574) cells/µL at 48 weeks. The score of HAMD was 5 (IQR: 3-9.8), 3 (IQR: 2.25-4) at baseline and 48 weeks. And the score of PSQI was 4 (IQR: 2-5.8), 3 (IQR: 2-4) at baseline and 48 weeks. Dizziness was the most common event, occurring in 70% patients within the first two weeks of treatment. Conclusion Patients prescribed with EFV 400mg-containing agents demonstrated favorable virological and immunological responses. And the plasma EFV concentration was within the recommended therapeutic range with less adverse reactions. EFV 400mg was effective and safe in Chinese HIV-infected patients.
... L-тіанін -широко відомий компонент зеленого чаю, природний аналог глутамінової кислоти (глутамату), однак забезпечує абсолютно іншу фармакологічну дію. Він також підвищує активність в ЦНС ГАМК та іншої гальмівної амінокислоти -гліцину (Катасонов А.Б., 2018), а крім цього, стимулює синтез основних біогенних амінів у мозку -серотоніну і дофаміну, що в клінічних умовах супроводжується антидепресивною дією (Hidese S. et al., 2017). Результати досліджень 2020 р. доводять, що вживання 200-400 мг/добу L-тіаніну допомагає зменшити вплив стресу і вгамувати занепокоєння у людей, які перебувають в екстремальних умовах (�illia�s J. et al., 2020). ...
Chapter
Drug addiction is prevalent among individuals of modern society, being a major cause of disability and premature loss of life. Although the drug addiction have profound social, economical and health impact in the world population, its management remains a challenge as available pharmacological treatments remains ineffective for most people. The limited efficacy and adverse effects have led to a search for alternative therapies to treat drug addiction. In this context, natural products are an important source for new chemical substances with a potential therapeutic applicability. Therefore, this chapter will present data obtained after an extensive literature search regarding the use of medicinal plants as a pharmacological alternative for drug addiction treatment.
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L-theanine (γ-Glutamylethylamide) is a non-protein water soluble amino acid (AA) mostly occurred in leaves of Camellia sinensis (green tea). This is a key component of green tea, and is considered as the most abundant form of total amino acids in green tea (i.e. about 50%). L-theanine is an exclusive taste ingredient of tea producing an attractive flavor and aroma in tea. It has worth notice biological effects like antioxidant, growth promoter, immune booster, anti-stresser, hepactoprotective, antitumor, anti-aging, antimicrobial, anti-inflammatory and anti-anxiety activities. It could reduce the oxidative impairment by reducing the synthesis of reactive oxygen species (ROS), oxidative parameters and lipid damage as well as increasing the activity of antioxidant enzymes. The oral ingestion of L-theanine enhanced γδ T-cell proliferation. Therefore, it is being considered an essential compound of green tea’ that has ability to improve immune function. The L-theanine can be used as a potential treatment for hepatic injury and immune-related liver diseases via the downregulation of the inflammatory response through the initiation of nitric oxide (NO) synthesis and glutathione (GSH) production are likely to be critical for the control of hepatic diseases as well as for the improvement of immune function. In addition it could be used as a best natural feed additive with potent anti-stressor via decreasing the levels of corticosterone (CORT), dopamine (DA) and noradrenaline (NA). After systematically reviewed the literature it is noticed that, mostly studies done on mice, pig, human and butterfly; while dietary supplementation studies of L-theanine in animal and poultry especially among broilers is very limited due to less awareness of this amino acid. So, the aim of this review is to encourage the veterinarian and poultry researchers to conduct more research at the molecular level about this amino acid to expose its’ more beneficial effects and its’ mechanism of absorption for potential use of this unique green tea amino acid in poultry nutrition.
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Chapter
Depression characterized as a mental disorder occupies the fourth position in the list of frequent global brain-related diseases. It is believed to occupy the second position in that list by 2030. Depression has been defined in terms of neurological disorders adversely influencing the physiological activities as well as functions of the brain. The disease manifests in the affected individual in the form of loss of sleep, appetite, attention, thinking, and concentration. Such persons develop a tendency of a feeling of being dejected and stay disappointed. As a result, they imbibe tendencies to suicide. Globally, this disease causes morbidity and mortality. The compounds used to treat depression are called antidepressants. These antidepressants have been shown to be useful in the treatment of pain and anxiety syndromes. Based on the mechanism of their actions, these antidepressants have been placed in five different groups: (i) the antidepressants with tricyclic chemical structure (tricyclic antidepressants – TCAs); (ii) the compounds selectively inhibiting serotonin reuptake (selective serotonin reuptake inhibitors); (iii) the molecules acting as inhibitors of the enzyme, monoamine oxidase (MAOIs); (iv) the chemical agents inhibiting the reuptake of serotonin norepinephrine (SNRIs); and (v) the non-TCA antidepressants. Many of these antidepressants are synthetic in nature and pose harmful effects on the health of users through many ways including generation of oxidative stress, which is responsible for brain dysfunction. In this regard, the phytochemicals and medicinal herbs are believed to offer most viable options because they possess enormous antioxidant potential, easy availability, low cost, least toxicity, and high therapeutic potential. The phytoconstituents have recently been utilized as a complementary therapeutic agent, which may help cure depression and check the recurrence of psychoneurotic disorders. The present chapter illustrates recent advances in research concerning phytochemicals acting as antidepressants. Also, their chemical structures, biological functions, mode of actions, role in regulation of pathophysiology, and toxicity, if any, have been included.
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L‐theanine, originally found in green tea, elicits various physiological effects, such as promoting relaxation, improving concentration and learning ability, and providing antianxiety‐like and antidepressant‐like properties. This study aims to investigate the effects of L‐theanine (2 mg/kg) on monoamine levels in an animal model of depression. The effect of l‐theanine on the symptoms of depression was examined through the open‐field test, sucrose preference test, and forced swim test. The monoamine neurotransmitters that involve serotonin (5‐HT), norepinephrine (NE), and dopamine (DA) were measured in the limbic–cortical–striatal–pallidal–thalamic (LCSPT)‐circuit related brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (ST), amygdala, and hippocampus (HIP). L‐theanine ameliorated the depressive‐like behaviors in the chronic unpredictable mild stress (CUMS) rat model. In the PFC, NAC, and HIP, L‐theanine administration significantly increased the levels of 5‐HT, NE, and DA. In the ST, the levels of 5‐HT and DA were increased after the administration of L‐theanine. However, in the HIP, only the level of DA significantly changed after the treatment of L‐theanine. Taken together, these results indicated that L‐theanine has possibly antidepressant‐like effects in the CUMS rat model, which could be mediated by the monoamine neurotransmitters in the LCSPT‐circuit related brain regions.
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Evidence suggests interactive effects of the tea components caffeine and L-theanine on behaviour, yet no data exists exploring the impact of the two on cerebral blood flow (CBF). The current placebo-controlled, double-blind, counterbalanced, crossover study examined the effects of caffeine and L-theanine on CBF and extended previous cognitive and mood findings by using lower doses than previous studies of a similar methodology, which more closely reflect the ratios present in tea. Twelve habitual consumers and 12 non-habitual consumers of caffeine each received 75 mg caffeine, 50 mg L-theanine, 75 mg caffeine plus 50 mg L-theanine, and placebo in a counterbalanced order across four separate visits. CBF was measured via near-infrared spectroscopy with cognition and mood assessed at baseline and 30 min post-dose. Salivary caffeine and peripheral haemodynamics were co-monitored. Caffeine reduced oxygenated haemoglobin (oxy-Hb), increased deoxygenated haemoglobin (deoxy-Hb), improved performance on attention tasks and increased overall mood ratings. Increases in deoxy-Hb following caffeine were more pronounced in non-consumers. Some evidence for increased deoxy-Hb remained when caffeine was combined with L-theanine, but this effect was attenuated and the effects of caffeine on oxy-Hb, cognition and mood were eradicated. Combining L-theanine with caffeine, at levels and ratios equivalent to one to two cups of tea, eliminated the vasoconstrictive effect and behavioural effects of caffeine. This supports previous findings of an interaction between these substances, despite a lack of effects of L-theanine in isolation. However, at the levels tested here, this did not lead to a positive impact on behaviour.
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The burden of depressive disorders and the frequent inadequacy of their current pharmacological treatments are well established. The anaesthetic and hallucinogenic drug ketamine has provoked much interest over the past decade or so as an extremely rapidly acting antidepressant that does not modify 'classical' monoaminergic receptors. Current evidence has shown several ways through which it might exert therapeutic antidepressant actions: blockade of glutamatergic NMDA receptors and relative upregulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtypes may alter cortical connectivity patterns; through intracellular changes in protein expression, including the proteins mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF); and alteration of intracellular signalling cascades. The clinical evidence demonstrates rapid improvements in mood and suicidal thinking in most participants, although study numbers have generally been small and many trials are unblinded and methodologically weak. There is a small body of work to suggest ketamine might also augment electroconvulsive therapy and potentially have a role as a surgical anaesthetic in depressed patients. A major problem is that the effects of ketamine appear temporary, disappearing after days to weeks (although longer benefits have been sustained in some), and attempts to circumvent this through pharmacological augmentation have been disappointing thus far. These exciting data are providing new insights into neurobiological models of depression, and potentially opening up a new class of antidepressants, but there are significant practical and ethical issues about any future mainstream clinical role it might have.
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This review aimed to address the question of whether cognitive impairment should be considered a core feature of depression that may be a valuable target for treatment. We conducted a systematic review and meta-analysis of cognitive function, assessed with a single neuropsychological test battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), in patients with depression during symptomatic and remitted states. Inclusion of studies comparing patients remitted from depression and controls enabled us to investigate whether cognitive impairment persists beyond episodes of low mood in depression. Our meta-analysis revealed significant moderate cognitive deficits in executive function, memory and attention in patients with depression relative to controls (Cohen's d effect sizes ranging from -0.34 to -0.65). Significant moderate deficits in executive function and attention (Cohen's d ranging from -0.52 to -0.61) and non-significant small/moderate deficits in memory (Cohen's d ranging from -0.22 to -0.54) were found to persist in patients whose depressive symptoms had remitted, indicating that cognitive impairment occurs separately from episodes of low mood in depression. Both low mood and cognitive impairment are associated with poor psychosocial functioning. Therefore, we argue that remediation of cognitive impairment and alleviation of depressive symptoms each play an important role in improving outcome for patients with depression. In conclusion, this systematic review and meta-analysis demonstrates that cognitive impairment represents a core feature of depression that cannot be considered an epiphenomenon that is entirely secondary to symptoms of low mood and that may be a valuable target for future interventions.
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Theanine (n-ethylglutamic acid), a non-proteinaceous amino acid component of green and black teas, has received growing attention in recent years due to its reported effects on the central nervous system. It readily crosses the blood-brain barrier where it exerts a variety of neurophysiological and pharmacological effects. Its most well-documented effect has been its apparent anxiolytic and calming effect due to its up-regulation of inhibitory neurotransmitters and possible modulation of serotonin and dopamine in selected areas. It has also recently been shown to increase levels of brain-derived neurotrophic factor. An increasing number of studies demonstrate a neuroprotective effects following cerebral infarct and injury, although the exact molecular mechanisms remain to be fully elucidated. Theanine also elicits improvements in cognitive function including learning and memory, in human and animal studies, possibly via a decrease in NMDA-dependent CA1 long-term potentiation (LTP) and increase in NMDA-independent CA1-LTP. Furthermore, theanine administration elicits selective changes in alpha brain wave activity with concomitant increases in selective attention during the execution of mental tasks. Emerging studies also demonstrate a promising role for theanine in augmentation therapy for schizophrenia, while animal models of depression report positive improvements following theanine administration. A handful of studies are beginning to examine a putative role in attention deficit hyperactivity disorder, and theoretical extrapolations to a therapeutic role for theanine in other psychiatric disorders such as anxiety disorders, panic disorder, obsessive compulsive disorder (OCD), and bipolar disorder are discussed.
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Background/Objectives Ingestion of the non-proteinic amino acid l-theanine (γ-glutamylethylamide) has been shown to influence oscillatory brain activity in the alpha band (8–14 Hz) in humans during resting electroencephalographic (EEG) recordings and also during cognitive task performance. We have previously shown that ingestion of a 250-mg dose of l-theanine significantly reduced tonic (background) alpha power during a demanding intersensory (auditory-visual) attentional cueing task. Further, cue-related phasic changes in alpha power, indexing the shorter-term anticipatory biasing of attention between modalities, were stronger on l-theanine compared to placebo. This form of cue-contingent phasic alpha activity is also known to index attentional biasing within visual space. Specifically, when a relevant location is pre-cued, anticipatory alpha power increases contralateral to the location to be ignored. Here we investigate whether the effects of l-theanine on tonic and phasic alpha activity, found previously during intersensory attentional deployment, occur also during a visuospatial task. Subjects/Methods 168-channel EEG data were recorded from thirteen neurologically normal individuals while engaged in a highly demanding visuo-spatial attention task. Participants underwent testing on two separate days, ingesting either a 250-mg colorless and tasteless solution of l-theanine mixed with water, or a water-based solution placebo on each day in counterbalanced order. We compared the alpha-band activity when subjects ingested l-Theanine vs. Placebo. Results We found a significant reduction in tonic alpha for the l-theanine treatment compared to placebo, which was accompanied by a shift in scalp topography, indicative of treatment-related changes in the neural generators of oscillatory alpha activity. However, l-theanine did not measurably affect cue-related anticipatory alpha effects. Conclusions This pattern of results implies that l-theanine plays a more general role in attentional processing, facilitating longer-lasting processes responsible for sustaining attention across the timeframe of a difficult task, rather than affecting specific moment-to-moment phasic deployment processes.
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While the hippocampal formation and the prefrontal cortex each have a well-established role in cognitive and mnemonic processes, the extent and manner in which these structures interact to achieve these functions has not been fully delineated. Recent research in rodents compellingly supports the idea that the projection of neurons extending from the CA1 region of the hippocampus and from the subiculum to the prefrontal cortex, referred to here as the H-PFC pathway, is critically involved in aspects of cognition related to executive function and to emotional regulation. Concurrently, it is becoming evident that persons suffering from schizophrenia, depression, and post-traumatic stress disorder display structural anomalies and aberrant functional coupling within the hippocampal-prefrontal circuit. Considering that these disorders involve varying degrees of cognitive impairment and emotional dysregulation, dysfunction in the H-PFC pathway might therefore be the common element of their pathophysiology. This overlap might also be intertwined with the pathway's evident susceptibility to stress and with its relationship to the amygdala. In consequence, the H-PFC pathway is a potentially crucial element of the pathophysiology of several psychiatric diseases, and it offers a specific target for therapeutic intervention, which is consistent with the recent emphasis on reframing psychiatric diseases in terms of brain circuits.
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The construct of major depressive disorder makes no etiological assumptions about populations with diverse symptom clusters. "Depressed mood" and "loss of interest or pleasure in nearly all activities" are core features of major depressive episode, though a strong case can be made to pay increasing attention to symptoms of fatigue, sleep disturbance, anxiety, and neurocognitive and sexual dysfunction in the diagnosis and evaluation of treatment outcome. Mood, guilt, work, and interest, as well as psychic anxiety, are consistently identified across validated subscales of the Hamilton Depression Rating Scale as prevalent and sensitive to change with existing treatments. A major limitation of these antidepressant therapies is their narrow spectrum of action. While the core "mood and interest" symptoms have been the main focus of attention, the associated symptoms listed above are often unaffected or exacerbated by current treatments. Careful clinical evaluation should address all of these dimensions, recognizing that improvement may occur sooner in some symptoms (eg, mood) compared with others (eg, sleep disturbance).
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Disturbances of the serotoninergic neutrotransmitter system have been implicated in the pathogenesis of mood disorders. A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has been recently reported to be associated with both unipolar and bipolar disorder. In this study, we investigated the possibility that the 5-HTTLPR might be associated with depressive symptomatology in a sample of mood disorder subjects. One hundred and thirty-two psychiatric inpatients affected by major depressive (n = 67) and bipolar (n = 65) disorder (DSM-IV) were assessed at admission by the Hamilton Depression Rating Scale (HAMD-21, divided into Core, Sleep, Activity, Psychic anxiety, Somatic anxiety and Delusion clusters) and were typed using PCR techniques. The only prior treatment permitted was low dose benzodiazepines (<5 mg diazepam or equivalent); no prior (<2 weeks) antidepressant or neuroleptic treatment was allowed. 5-HTTLPR variants were not associated with total depressive symptomatology as measured by HAMD. The short 5-HTTLPR variant was marginally associated with higher psychic anxiety scores (F = 7.11, d.f. = 1,262, P = 0.008). The association was stronger among bipolars and early onset subjects. 5-HTTLPR variants were not associated with the remaining symptom clusters. The upstream regulatory region of the serotonin transporter gene has not, therefore, a major influence on the depressive symptomatology in mood disorder subjects.
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Recent studies suggest brain oscillations as a mechanism for cerebral integration. Such integration can exist across a number of functional domains, with different frequency rhythms associated with each domain. Here, evidence is summarized which shows that delta oscillations depend on activity of motivational systems and participate in salience detection. Theta oscillations are involved in memory and emotional regulation. Alpha oscillations participate in inhibitory processes which contribute to a variety of cognitive operations such as attention and memory. The importance of inhibitory functions associated with alpha oscillations increases during the course of evolution. In ontogenesis, these functions develop later and may be more sensitive to a variety of detrimental environmental influences. In a number of developmental stages and pathological conditions, a deficient alpha and/or increased slow-wave activity are associated with cognitive deficits and a lack of inhibitory control. It is shown that slow-wave and alpha oscillations are reciprocally related to each other. This reciprocal relationship may reflect an inhibitory control over motivational and emotional drives which is implemented by the prefrontal cortex.
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: Ingestion of the nonproteinic amino acid theanine (5-N-ethylglutamine) has been shown to increase oscillatory brain activity in the so-called alpha band (8-14 Hz) during resting electroencephalographic recordings in humans. Independently, alpha band activity has been shown to be a key component in selective attentional processes. Here, we set out to assess whether theanine would cause modulation of anticipatory alpha activity during selective attentional deployments to stimuli in different sensory modalities, a paradigm in which robust alpha attention effects have previously been established. : Electrophysiological data from 168 scalp electrode channels were recorded while participants performed a standard intersensory attentional cuing task. : As in previous studies, significantly greater alpha band activity was measured over parieto-occipital scalp for attentional deployments to the auditory modality than to the visual modality. Theanine ingestion resulted in a substantial overall decrease in background alpha levels relative to placebo while subjects were actively performing this demanding attention task. Despite this decrease in background alpha activity, attention-related alpha effects were significantly greater for the theanine condition. : This increase of attention-related anticipatory alpha over the right parieto-occipital scalp suggests that theanine may have a specific effect on the brain's attention circuitry. We conclude that theanine has clear psychoactive properties, and that it represents a potentially interesting, naturally occurring compound for further study, as it relates to the brain's attentional system.
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This report describes the GRID-Hamilton Depression Rating Scale (GRID-HAMD), an improved version of the Hamilton Depression Rating Scale that was developed through a broad-based international consensus process. The GRID-HAMD separates the frequency of the symptom from its intensity for most items, refines several problematic anchors, and integrates both a structured interview guide and consensus-derived conventions for all items. Usability was established in a small three-site sample of convenience, evaluating 29 outpatients, with most evaluators finding the scale easy to use. Test-retest (4-week) and interrater reliability were established in 34 adult outpatients with major depressive disorder, as part of an ongoing clinical trial. In a separate study, interrater reliability was found to be superior to the Guy version of the HAMD, and as good as the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D), across 30 interview pairs. Finally, using the SIGH-D as the criterion standard, the GRID-HAMD demonstrated high concurrent validity. Overall, these data suggest that the GRID-HAMD is an improvement over the original Guy version as well as the SIGH-D in its incorporation of innovative features and preservation of high reliability and validity.
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Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. Previous studies suggested that l-theanine affects the glutamatergic neurotransmission and ameliorates symptoms in patients with schizophrenia. The aims of the present study were twofold: to examine the possible effects of l-theanine on symptoms in chronic schizophrenia patients and to evaluate the changes in chemical mediators, including glutamate + glutamine (Glx), in the brain by using 1H magnetic resonance spectroscopy (MRS). The subjects were 17 patients with schizophrenia and 22 age- and sex-matched healthy subjects. l-Theanine (250 mg/day) was added to the patients' ongoing antipsychotic treatment for 8 weeks. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), Pittsburgh Sleep Quality Index scores and MRS results. There were significant improvements in the PANSS positive scale and sleep quality after the l-theanine treatment. As for MRS, we found no significant differences in Glx levels before and after the 8 week l-theanine treatment. However, significant correlations were observed between baseline density of Glx and change in Glx density by l-theanine. Our results suggest that l-theanine is effective in ameliorating positive symptoms and sleep quality in schizophrenia. The MRS findings suggest that l-theanine stabilises the glutamatergic concentration in the brain, which is a possible mechanism underlying the therapeutic effect.
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sPsychotropic dose equivalence is an important concept when estimating the approximate psychotropic doses patients receive, and deciding the approximate titration dose when switching from one psychotropic agent to another. It is also useful from a research viewpoint when defining and extracting specific subgroups of subjects. Unification of various agents into a single standard agent facilitates easier analytical comparisons. On the basis of differences in psychopharmacological prescription features, those of available psychotropic agents and their approved doses, and racial differences between Japan and other countries, psychotropic dose equivalency tables designed specifically for Japanese patients have been widely used in Japan since 1998. Here we introduce dose equivalency tables for (1) antipsychotics, (2) antiparkinsonian agents, (3) antidepressants, and (4) anxiolytics, sedatives and hypnotics available in Japan. Equivalent doses for the therapeutic effects of individual psychotropic compounds were determined principally on the basis of randomized controlled trials conducted in Japan, and consensus among dose equivalency tables reported previously by psychopharmacological experts. Since these tables are intended to merely suggest approximate standard values, physicians should use them with discretion.
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Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after weaning on stress-induced impairment of recognition memory, the advantageous effect of theanine intake on recognition memory was examined in young rats, which were fed water containing 0.3% theanine for 3 weeks after weaning. The rats were subjected to object recognition test. Object recognition memory was maintained in theanine-administered rats 48 hours after the training, but not in the control rats. When in vivo dentate gyrus long-term potentiation (LTP) was induced, it was more greatly induced in theanine-administered rats than in the control rats. The levels of brain-derived neurotropic factor and nerve growth factor in the hippocampus were significantly higher in theanine-administered rats than in the control rats. The present study indicates the advantageous effect of theanine intake after weaning on recognition memory. It is likely that theanine intake is of advantage to the development of hippocampal function after weaning.
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Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30sec used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1 s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-D-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect.
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The present work was aimed to study the protective effect of L-theanine on chronic restraint stress (CRS)-induced cognitive impairments in mice. The stress was produced by restraining the animals in well-ventilated polypropylene tubes (3.2cm in diameter ×10.5cm in length) for 8h once daily for 21 consecutive days. L-theanine (2 and 4mg/kg) was administered 30 minutes before the animals subjected to acute immobilized stress. At week 4, mice were subjected to Morris water maze and step-through tests to measure the cognitive function followed by oxidative parameters and corticosterone as well as catecholamines (norepinephrine and dopamine) subsequently. Our results showed that the cognitive performances in CRS group were markedly deteriorated, accompanied by noticeable alterations in oxidative parameters and catecholamine levels in the hippocampus and the cerebral cortex as well as corticosterone and catecholamine levels in the serum. However, not only did L-theanine treatment exhibit a reversal of the cognitive impairments and oxidative damage induced by CRS, but also reversed the abnormal level of corticosterone in the serum as well as the abnormal levels of catecholamines in the brain and the serum. This study indicated the protective effect of L-theanine against CRS-induced cognitive impairments in mice.
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Synaptic plasticity confers environmental adaptability through modification of the connectivity between neurons and neuronal circuits. This is achieved through changes to synapse-associated signaling systems and supported by complementary changes to cellular morphology and metabolism within the tripartite synapse. Mounting evidence suggests region-specific changes to synaptic form and function occur as a result of chronic stress and in depression. The prefrontal cortex (PFC) and hippocampus represent the best studied regions where functional and structural findings are consistent with a deficit in long-term potentiation (LTP), and neuronal and glial growth at excitatory synapses. Correlating these changes may be those to glutamate receptors (AMPARs and NMDARs), growth factor signaling (BDNF-TrkB) and several signal transduction pathways (NOS-NO, cAMP-PKA, Ras-ERK, PI3K-Akt, GSK-3, mTOR and CREB). In contrast other brain regions such as the amygdala may feature a somewhat opposite synaptic pathology including reduced inhibitory tone. Deficits in synaptic plasticity may further correlate disrupted brain redox and bioenergetics in stress and depression. Moreover, at a functional level region-specific changes to synaptic plasticity in depression may relate to maladapted neurocircuitry and parallel reduced cognitive control over negative emotion.
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l-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that l-theanine has been shown to inhibit caffeine's stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that l-theanine may suppress opioid withdrawal signs. Additionally, l-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties. Thus, in these studies we determined whether l-theanine attenuates opioid-withdrawal signs in morphine-dependent rhesus monkeys, a model for spontaneous opioid withdrawal in human opioid addicts. We also evaluated whether l-theanine decreases anxiety-like behavior in mice, using the elevated plus maze and marble burying assays. l-theanine significantly attenuated designated opioid withdrawal signs, including fighting, rigid abdominal muscles, vocalizing on palpation of abdomen, pacing, retching, wet-dog shakes, and masturbation. It had a relatively quick onset of action that persisted for at least 2.5h. l-theanine also produced anxiolytic-like effects in the elevated plus maze and the marble burying assay in naïve mice at doses that did not significantly affect motor behavior. The results of these studies suggest that l-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors.