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L-Theanine Relieves Positive, Activation, and Anxiety Symptoms in Patients With Schizophrenia and Schizoaffective Disorder: An 8-Week, Randomized, Double-Blind, Placebo-Controlled, 2-Center Study

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L-Theanine Relieves Positive, Activation, and Anxiety Symptoms in Patients With Schizophrenia and Schizoaffective Disorder: An 8-Week, Randomized, Double-Blind, Placebo-Controlled, 2-Center Study

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Abstract

L-theanine is a unique amino acid present almost exclusively in the tea plant. It possesses neuroprotective, mood-enhancing, and relaxation properties. This is a first study designed to evaluate the efficacy and tolerability of L-theanine augmentation of antipsychotic treatment of patients with chronic schizophrenia and schizoaffective disorder. 60 patients with DSM-IV schizophrenia or schizoaffective disorder participated in an 8-week, double-blind, randomized, placebo-controlled study. 400 mg/d of L-theanine was added to ongoing antipsychotic treatment from February 2006 until October 2008. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), the Hamilton Anxiety Rating Scale (HARS), the Cambridge Neuropsychological Test Automated Battery (CANTAB) for neurocognitive functioning, and additional measures of general functioning, side effects, and quality of life. 40 patients completed the study protocol. Compared with placebo, L-theanine augmentation was associated with reduction of anxiety (P = .015; measured by the HARS scale) and positive (P = .009) and general psychopathology (P < .001) scores (measured by the PANSS 3-dimensional model). According to the 5-dimension model of psychopathology, L-theanine produced significant reductions on PANSS positive (P = .004) and activation factor (P = .006) scores compared to placebo. The effect sizes (Cohen d) for these differences ranged from modest to moderate (0.09-0.39). PANSS negative and CANTAB task scores, general functioning, side effect, and quality of life measures were not affected by L-theanine augmentation. L-theanine was found to be a safe and well-tolerated medication. L-theanine augmentation of antipsychotic therapy can ameliorate positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients. Further long-term studies of L-theanine are needed to substantiate the clinically significant benefits of L-theanine augmentation.

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... As demonstrated in Table 1, eighteen studies examined the influence of antipsychotic drugs on cognition (R. W. Buchanan et al., 2007;Chengappa et al., 2012;Evins, Amico, Posever, Toker, & Goff, 2002;Goff et al., 2008;Goff et al., 1999;Goff, Tsai, Manoach, & Coyle, 1995;Kelly et al., 2015;LaPorte, Lahti, Koffel, & Tamminga, 1996;Y. Levkovitz et al., 2010;Lieberman et al., 2009;Peloian & Pierre, 2008;Ritsner et al., 2011;Silver, Goodman, Isakov, Knoll, & Modai, 2005;Strzelecki, Kaluzynska, Jozefowicz, Pawelczyk, & Rabe-Jablonska, 2011;Tsai, Yang, Chung, Lange, & Coyle, 1998;Vayisoglu et al., 2013;Verhoeven, Egger, ter Horst, Fekkes, & Tuinier, 2007;Weiser et al., 2012). Effect sizes ranged between medium and large for significant findings. ...
... Of the fourteen studies that investigated memory, twelve studies found no significant changes (R. W. Buchanan et al., 2007;Chengappa et al., 2012;Goff et al., 2008;Kelly et al., 2015;LaPorte et al., 1996;Y. Levkovitz et al., 2010;Lieberman et al., 2009;Peloian & Pierre, 2008;Ritsner et al., 2011;Silver et al., 2005;Vayisoglu et al., 2013;Weiser et al., 2012). One study found that aripiprazole, which protects cortical neurons from glutamate toxicity (Koprivica et al., 2011) and is a partial agonist at the D2 and the 5-HT2a and 2c receptors (Verhoeven et al., 2007), improved immediate and delayed verbal recall after 14 weeks in a sample of 11 patients (effect size not available; Verhoeven et al., 2007). ...
... Fourteen studies examined executive functions; four studies found significant improvements (Chengappa et al., 2012;Y. Levkovitz et al., 2010;Strzelecki et al., 2011;Tsai et al., 1998) and ten found no change in performance (R. W. Buchanan et al., 2007;Evins et al., 2002;Goff et al., 2008;Kelly et al., 2015;Lieberman et al., 2009;Ritsner et al., 2011;Silver et al., 2005;Vayisoglu et al., 2013;Verhoeven et al., 2007;Weiser et al., 2012). One study showed a significant time x treatment interaction for cognitive shifting, cognitive planning and overall executive functioning composite score with the use of minocycline (Y. ...
Article
Thomas, E.H.X., K. Bozaoglu, S.L. Rossell and C. Gurvich. The Influence of the Glutamatergic System on Cognition in Schizophrenia: A Systematic Review. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2016. Previous literature showing the role of the glutamatergic system on cognition in schizophrenia has been inconclusive. 44 relevant pharmacological, candidate gene and neuroimaging studies were identified through systematic search following PRISMA guidelines. To be included, studies must have observed at least one objective measure of cognitive performance in patients with schizophrenia and either manipulated or measured the glutamatergic system. Of the cognitive domains observed, memory, working memory and executive functions appear to be most influenced by the glutamatergic pathway. In addition, evidence from the literature suggests that presynaptic components synthesis and uptake of glutamate is involved in memory, while postsynaptic signaling appears to be involved in working memory. In addition, it appears that the glutamatergic pathway is particularly involved in cognitive flexibility and learning potential in regards to executive functioning. The glutamatergic system appears to contribute to the cognitive deficits in schizophrenia, whereby different parts of the pathway are associated with different cognitive domains. This review demonstrates the necessity for cognition to be examined by domain as opposed to globally.
... In the present study, systemic administration of QA produced significant decline in DA, NE and 5-HT and elevation in level of HVA and DOPAC whereas L-theanine attenuated QA induced striatal neurotransmitters alterations i.e. restored monoamines levels, adenosine levels and reduced glutamate hyperactivity, indicating its potential neuromodulatory role. Previously, L-theanine has been reported to enhance brain neurotransmitters DA, NE and 5-HT, GABA levels and reduction in glutamate hyperactivity (Kiramura and Murata, 1986;Kakuda et al., 2002;Ritsner et al., 2010). Adenosine in physiological conditions prevents from detrimental effects of glutamate pre-synaptically as well as post-synaptically (Latini and Pedata, 2001;Blum et al., 2003). ...
... However, thorough mechanisms need to be identified. L-theanine has been reported to posse's neuroprotection against cerebral ischemia and excitotoxic event induced by kainic acid and glutamate (Kakuda et al., 2000(Kakuda et al., , 2002Ritsner et al., 2010) by inhibition of glutamate transporter (Kiramura and Murata, 1986). Moreover, Ltheanine has ability to enhance the level of brain NE, dopamine, 5-HT, GABA, promotes brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) and nerve growth factor (NGF) formation (Kiramura and Murata, 1986;Ritsner et al., 2010;Yamada et al., 2005). ...
... L-theanine has been reported to posse's neuroprotection against cerebral ischemia and excitotoxic event induced by kainic acid and glutamate (Kakuda et al., 2000(Kakuda et al., , 2002Ritsner et al., 2010) by inhibition of glutamate transporter (Kiramura and Murata, 1986). Moreover, Ltheanine has ability to enhance the level of brain NE, dopamine, 5-HT, GABA, promotes brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) and nerve growth factor (NGF) formation (Kiramura and Murata, 1986;Ritsner et al., 2010;Yamada et al., 2005). L-theanine decreases iNOS and neuronal nitric oxide synthase (nNOS) protein activity (Di et al., 2010). ...
Article
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L-theanine has been documented to possess anti-oxidant, anti-inflammatory and neuroprotective potential in various animal models of neurological disorders. The present study was anticipated to investigate the effect of L-theanine against quinolinic acid induced motor deficits, oxido-nitrosative stress, neuro-inflammation and neurotransmitters alteration in rats. Rats were stereotaxically injected QA (200 nmol/2 µl saline; intrastriatal); bilaterally on 0 day and L-theanine (25 & 50 mg/kg; p.o.) was administered for 21 days starting from day 1 of QA injection. Either, L-NAME (10 mg/kg; i.p.), a nitric oxide synthase inhibitor and L-arginine (50 mg/kg; i.p.), a nitric oxide synthase precursor were administered with L-theanine in respective groups. Behavioral observations were evaluated on weekly basis using rota-rod, grip strength, narrow beam walking and open field test. QA treatment induces significant alteration in body weight, motor coordination, oxidative defense, pro-inflammatory cytokines and striatal neurotransmitters level. L-theanine treatment alone, at both the tested doses, significantly attenuated QA induced alterations. In addition, treatment of L-theanine with L-NAME significantly enhances the protective effect of L-theanine whereas treatment of L-theanine with L-arginine significantly ameliorated the protective effect of L-theanine. The protective effect of L-theanine is attributed to its anti-oxidant, anti-inflammatory and modulatory effect on nitric oxide pathway and neurotransmitters level in striatum. This suggests use of L-theanine in the clinical settings of HD.
... There is long-term potential for L-theanine supplementation for acute and chronic stress management based on the results of this study and previous work [32,33]. Following the MAT task, there was a significant increase in self-reported state anxiety and no significant changes to trait anxiety. ...
... There have, however, been studies investigating the effects of 8-10 weeks of 250-900 mg/day of L-theanine supplementation in patient populations. 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. ...
... To support the continued use of L-theanine supplementation, L-theanine supplementation is generally well tolerated in humans [13], with no studies reporting toxicity in human or animal models [39]. In clinical populations receiving 400-900 mg/day of L-theanine supplementation for 8 weeks for treatment of general anxiety disorder [32] and schizophrenia [33] did not result in serious adverse events compared to placebo. Additionally, the US Food and Drug Administration states that daily consumption of L-theanine should not be greater than 1200 mg/day [39] and Health Canada suggests 200-250 mg/day with no known contraindications or adverse reactions [40]; therefore, as the dosage investigated in this study is below the FDA limit and within the limits of the Health Canada recommendation, the single dose of 200 mg of AlphaWave Ò L-Theanine is deemed to be safe and well tolerated. ...
Article
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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.
... There are several antipsychotic drugs that act on the glutamatergic metabolic system; NMDA antagonists have previously been shown to mimic symptoms of schizophrenia and NMDA agonists are hoped to improve symptoms. As demonstrated in Table 1, eighteen studies examined the influence of antipsychotic drugs on cognition (Buchanan et al., 2007;Chengappa et al., 2012;Evins et al., 2002;Goff et al., 2008;Goff et al., 1999;Goff et al., 1995;Kelly et al., 2015;LaPorte et al., 1996;Levkovitz et al., 2010;Lieberman et al., 2009;Peloian and Pierre, 2008;Ritsner et al., 2011;Silver et al., 2005;Strzelecki et al., 2011;Tsai et al., 1998;Vayisoglu et al., 2013;Verhoeven et al., 2007;Weiser et al., 2012). Effect sizes ranged between medium and large for significant findings. ...
... Of the thirteen studies that investigated memory, eleven studies found no significant changes (Buchanan et al., 2007;Chengappa et al., 2012;Goff et al., 2008;Kelly et al., 2015;LaPorte et al., 1996;Lieberman et al., 2009;Peloian and Pierre, 2008;Ritsner et al., 2011;Silver et al., 2005;Vayisoglu et al., 2013;Weiser et al., 2012). One study found that aripiprazole, which protects cortical neurons from glutamate toxicity (Koprivica et al., 2011) and is a partial agonist at the D2 and the 5-HT2a and 2c receptors (Verhoeven et al., 2007), improved immediate and delayed verbal recall after 14 weeks in a sample of 11 patients (effect size not available; Verhoeven et al., 2007). ...
... Fourteen studies examined executive functions; four studies found significant improvements (Chengappa et al., 2012;Levkovitz et al., 2010;Strzelecki et al., 2011;Tsai et al., 1998) and ten found no change in performance (Buchanan et al., 2007;Evins et al., 2002;Goff et al., 2008;Kelly et al., 2015;Lieberman et al., 2009;Ritsner et al., 2011;Silver et al., 2005;Vayisoglu et al., 2013;Verhoeven et al., 2007;Weiser et al., 2012). One study showed a significant time x treatment interaction for cognitive shifting, cognitive planning and overall executive functioning composite score with the use of minocycline (Levkovitz et al., 2010). ...
Article
Background Patients with schizophrenia have been estimated to be one to two standard deviations below the scores of healthy controls in terms of cognitive function. Cognitive performance is also impaired in unaffected biological relatives compared to the general population, indicating a genetic contribution to the cognitive impairment. It has been suggested that the glutamatergic system influences cognition and several investigations have explored the relationship between glutamate and cognitive deficits in schizophrenia. However, previous literature indicating a role of the glutamatergic system in cognitive deficits in schizophrenia has been inconclusive. The aim of this study was to systematically review candidate gene studies influencing the glutamatergic pathway and explore the impact on cognition in schizophrenia. Methods 11 relevant candidate gene studies were identified through systematic search following PRISMA guidelines and were reviewed. Ovid MEDLINE, PsychINFO and EMBASE were searched using the following truncation keyword search terms ‘schizophrenia’, ‘glutamat’, ‘cognit’, ‘adult’, ‘human’, ‘patient’ and ‘control.’ To be included, studies must have observed at least one objective measure of cognitive performance in patients with schizophrenia and had to be candidate gene studies focused on the glutamatergic pathway. Animal studies and studies that did not have a schizophrenia or schizoaffective patient study group were excluded. Results Results were examined according to cognitive domain. Of the cognitive domains observed, memory and working memory were most consistently influenced by genetic variation along the glutamatergic pathway. DTNBP1 were associated with verbal and visual memory and working memory performance (n = 565). GRM3 was significantly associated with episodic memory (n = 508). DTNBP1 is involved in the storage and release of GRM3, which encodes mGlu3 (shown to modulate glutamate neurotransmission and synaptic plasticity). G72 activates DAAO, which is involved in the metabolism of D-serine and was significantly associated with episodic memory and working memory (n = 292). NRG1, ErbB4 and AKT1 genes were significantly associated with working memory only (n = 661). NRG1 has a biological role in brain development and neural function which has been shown to be partially mediated by the NMDA-glutamate pathway, with ErbB4 and AKT1 directly linked to NRG1 downstream. Discussion Findings from this systematic review suggest that the glutamatergic system contributes to the cognitive deficits in schizophrenia, in particular in the areas of memory and working memory. Literature suggests that DTNBP1 and GRM3 are involved in the presynaptic components synthesis and uptake in the glutamatergic pathway, while NRG1 and its downstream signalling are involved in post-synaptic scaffold and signalling. As the difference between memory and working memory appears to be NRG1 and its downstream effects, results indicate presynaptic components synthesis and uptake of glutamate is involved in memory, while post-synaptic scaffold and signalling appears to be involved in working memory. Different parts of the glutamatergic pathway appear to be associated with different cognitive domains, highlighting the importance for cognition to be examined by domain as opposed to globally. By breaking down cognition into multiple domains, it will be easier to identify the molecular mechanisms affecting different cognitive phenotypes in schizophrenia.
... 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. ...
... 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. ...
... Interestingly, employing 1 H magnetic resonance spectroscopy (MRS), the researchers found that L -theanine modulated glutamate + glutamine concentrations in the frontal and parietal regions of the brain, which could be a possible mechanism underlying its therapeutic properties [47]. Ritsner and colleagues found in a double-blind randomized placebocontrolled clinical trial recruiting 60 patients diagnosed with chronic schizophrenia and schizoaffective disorder that L -theanine supplementation for 8 weeks combined with the respective ongoing antipsychotic treatment was able to significantly reduce anxiety and significantly improve general psychopathological scores [25]. Another publication [32] from the same research group, analysing a subset of 40 participants from the clinical trial referred above, observed improvements in circulating levels of brain-derived neurotrophic factor and cortisol to dehydroepiandrosterone sulfate ratio after L -theanine supplementation. ...
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.
... Following removal of duplicates (n = 40), reviews, letters to the editor and articles not written in English (n = 177), the number of articles was reduced to 44. Nine articles [38,44,[46][47][48][49][50][51][52] met the inclusion criteria ( Fig. 1). Seven studies recruited participants with no known preexisting mental health issues, while two studies used participants with an existing mental health condition [44,49]. ...
... Nine articles [38,44,[46][47][48][49][50][51][52] met the inclusion criteria ( Fig. 1). Seven studies recruited participants with no known preexisting mental health issues, while two studies used participants with an existing mental health condition [44,49]. The total number of participants for all included studies was 270 with 134 males and 88 females ( Table 1). ...
... Five of the studies [46-48, 51, 52] used a crossover design with all the participants exposed to each of the experimental treatments conditions. The other four studies [38,44,49,50] used a parallel design to compare between an L-THE group and a placebo group. Seven of the studies compared L-THE to placebo while the study by Lu et al. [48] compared L-THE against a prescribed anti-anxiety pharmaceutical (Alprazolam; 1 mg; Xanax®, Pharmacia and UpJohn Ltd) as well as against placebo. ...
Article
Full-text available
The green tea amino acid, L-theanine (L-THE) is associated with several health benefits, including improvements in mood, cognition and a reduction of stress and anxiety-like symptoms. This systematic review evaluated the effect of pure L-THE intake, in the form of orally administered nutritional supplements, on stress responses and anxiety levels in human randomised controlled trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, 9 peer-reviewed journal articles were identified where L-THE as a supplement was compared to a control. Our findings suggest that supplementation of 200-400 mg/day of L-THE may assist in the reduction of stress and anxiety in people exposed to stressful conditions. Despite this finding, longer-term and larger cohort clinical studies, including those where L-THE is incorporated into the diet regularly, are needed to clinically justify the use of L-THE as a therapeutic agent to reduce stress and anxiety in people exposed to stressful conditions.
... Ten experimental studies (Einöther et al., 2010;Giesbrecht et al., 2010;Haskell et al., 2008;Kelly et al., 2008;Kimura et al., 2007;Ota et al., 2014;Owen et al., 2008;Park et al., 2011;Ritsner et al., 2011;Yoto et al., 2012) focussed on the effects of l-theanine intake. Nine (Einöther et al., 2010;Giesbrecht et al., 2010;Haskell et al., 2008;Kelly et al., 2008;Kimura et al., 2007;Ota et al., 2014;Owen et al., 2008;Park et al., 2011;Yoto et al., 2012) of these employed within-subject designs and healthy participants for acute effects, whereas one randomised controlled trial investigated these long-term effects in a population of patients with the diagnosis of schizophrenia or a Mancini et al. ...
... Phytomedicine xxx (2017) xxx-xxx Mancini et al. Phytomedicine xxx (2017) xxx-xxx schizoaffective disorder (Ritsner et al., 2011) , . Three studies (Kimura et al., 2007;Ota et al., 2014;Ritsner et al., 2011) investigated the isolated effects of l-theanine; one explored the effect of l-theanine combined with GTE (Park et al., 2011) (and was already summarised in the previous chapter), while the other six (Einöther et al., 2010;Giesbrecht et al., 2010;Haskell et al., 2008;Kelly et al., 2008;Owen et al., 2008;Yoto et al., 2012) included caffeine, as l-theanine naturally occurs together with caffeine. ...
... Phytomedicine xxx (2017) xxx-xxx schizoaffective disorder (Ritsner et al., 2011) , . Three studies (Kimura et al., 2007;Ota et al., 2014;Ritsner et al., 2011) investigated the isolated effects of l-theanine; one explored the effect of l-theanine combined with GTE (Park et al., 2011) (and was already summarised in the previous chapter), while the other six (Einöther et al., 2010;Giesbrecht et al., 2010;Haskell et al., 2008;Kelly et al., 2008;Owen et al., 2008;Yoto et al., 2012) included caffeine, as l-theanine naturally occurs together with caffeine. Of these studies, only the outcomes for l-theanine alone or for l-theanine and caffeine together were extracted (and identified accordingly)-the outcome caused by caffeine alone was not extracted. ...
Article
Background: Green tea (Camellia sinensis) is a beverage consumed for thousands of years. Numerous claims about the benefits of its consumption were stated and investigated. As green tea is experiencing a surge in popularity in Western culture and as millions of people all over the world drink it every day, it is relevant to understand its effects on the human brain. Purpose: To assess the current state of knowledge in the literature regarding the effects of green tea or green tea extracts, l-theanine and epigallocatechin gallate both components of green tea-on general neuropsychology, on the sub-category cognition and on brain functions in humans. Methods: We systematically searched on PubMed database and selected studies by predefined eligibility criteria. We then assessed their quality and extracted data. We structured our effort according to the PRISMA statement. Outcome: We reviewed and assessed 21 studies, 4 of which were randomised controlled trials, 12 cross-over studies (both assessed with an adapted version of the DELPHI-list), 4 were cross-sectional studies and one was a cohort study (both assessed with an adapted version of the Newcastle-Ottawa assessment scale). The average study quality as appraised by means of the DELPHI-list was good (8.06/9); the studies evaluated with the Newcastle-Ottawa-scale were also good (6.7/9). Conclusions: The reviewed studies presented evidence that green tea influences psychopathological symptoms (e.g. reduction of anxiety), cognition (e.g. benefits in memory and attention) and brain function (e.g. activation of working memory seen in functional MRI). The effects of green tea cannot be attributed to a single constituent of the beverage. This is exemplified in the finding that beneficial green tea effects on cognition are observed under the combined influence of both caffeine and l-theanine, whereas separate administration of either substance was found to have a lesser impact.
... * Hiroshi Kunugi hkunugi@ncnp.go.jp anxiety (Hidese et al. 2016;Rogers et al. 2008;Unno et al. 2013b;Yoto et al. 2012), depressive symptoms (Cross et al. 2011;Hidese et al. 2016), and schizophrenic symptoms (Kardashev et al. 2015;Ota et al. 2015;Ritsner et al. 2011;White et al. 2016) in humans. Although previous research has indicated that L-theanine modulates the activity of brain neurotransmitters such as serotonin, dopamine, and γaminobutyric acid (GABA) (Yamada et al. 2007;Yokogoshi et al. 1998a, b), the molecular basis underlying these effects remains poorly understood. ...
... In the PET experiment, significantly elevated hippocampal [ 18 F]FDG uptake was observed in Ltheanine-treated animals relative to that in saline-treated animals, suggesting that L-theanine enhances hippocampal activity. Consistent with the findings of previous studies (Kardashev et al. 2015;Ritsner et al. 2011;Rogers et al. 2008;Unno et al. 2013b;Wise et al. 2012;Yoto et al. 2012), we observed anxiolytic effects of L-theanine in the present study. However, we failed to obtain evidence for antidepressant-like effects of L-theanine in WKY rats, possibly because the WKY rat has been regarded as an animal model of refractory depression. ...
Article
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Rationale and objectivesThe amino acid l-theanine (N-ethyl-l-glutamine) has historically been considered a relaxing agent. In the present study, we examined the effects of repeated l-theanine administration on behavior, levels of amino acids in the cerebrospinal fluid (CSF), and hippocampal activity in Wistar Kyoto (WKY) rats, an animal model of anxiety and depressive disorders. Methods Behavioral tests were performed after 7–10 days of l-theanine (0.4 mg kg−1 day−1) or saline administration, followed by CSF sampling for high-performance liquid chromatography (HPLC) analysis. An independent set of animals was subjected to [18F]fluorodeoxyglucose positron emission tomography (PET) scanning after the same dose of l-theanine or saline administration for 7 days. ResultsIn the elevated plus maze test, the time spent in the open arms was significantly longer in the l-theanine group than in the saline group (P = 0.035). In addition, significantly lower CSF glutamate (P = 0.039) and higher methionine (P = 0.024) concentrations were observed in the l-theanine group than in the saline group. A significant increase in the standard uptake value ratio was observed in the hippocampus/cerebellum of the l-theanine group (P < 0.001). Conclusions These results suggest that l-theanine enhances hippocampal activity and exerts anxiolytic effects, which may be mediated by changes in glutamate and methionine levels in the brain. Further study is required to more fully elucidate the mechanisms underlying the effects of l-theanine.
... 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. ...
... 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.
... Likewise, improvements in cognitive performance, subject alertness and complex senses interactions have also been documented [62][63][64]. On the other hand, findings from Ritsner and colleagues found no evidence that L-THE (400 mg/day) improved cognitive function, attention or learning [65]. However, these studies were performed on schizophrenic patients compared to healthy subjects examined in other reported studies. ...
... However, these studies were performed on schizophrenic patients compared to healthy subjects examined in other reported studies. Current evidence also suggests that L-THE is a useful "add on" to the prophylactic management of schizophrenia using antipsychotic treatments, as L-THE can augment the effect of antipsychotic therapy by ameliorating positive activation and anxiety symptoms in schizophrenia and schizoaffective disorder patients [65]. ...
Article
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Tea has been consumed for thousands of years and is an integral part of people’s daily routine, as an everyday drink and a therapeutic aid for health promotion. Consumption of tea has been linked to a sense of relaxation commonly associated with the content of the non-proteinogenic amino acid theanine, which is found within the tea leaves. The aim of this review article is to outline the current methods for synthesis, extraction and purification of theanine, as well as to examine its potential benefits related to human health. These include improvements in cognitive and immune function, cancer prevention, reduced cardiovascular risk and its potential usefulness as a functional food product.
... Banji et al. (175) also demonstrated that induced cerebellar damage in mice instigated motor clumsiness, similar to that seen in ASC, the motor clumsiness was then reduced by treating the mice with green tea extract (Camellia sinensis). l-Theanine is a major amino acid component found almost exclusively in green tea (176)(177)(178) and blocks the binding of l-glutamic acid to glutamate receptors in the brain (176,178,179), thereby perhaps aiding the improvement in motor activity by increasing inhibition of movement. ...
... Banji et al. (175) also demonstrated that induced cerebellar damage in mice instigated motor clumsiness, similar to that seen in ASC, the motor clumsiness was then reduced by treating the mice with green tea extract (Camellia sinensis). l-Theanine is a major amino acid component found almost exclusively in green tea (176)(177)(178) and blocks the binding of l-glutamic acid to glutamate receptors in the brain (176,178,179), thereby perhaps aiding the improvement in motor activity by increasing inhibition of movement. ...
Article
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Present diagnostic criteria for autism spectrum conditions (ASC) include social communication and interaction difficulties, repetitive behaviour and movement, and atypical sensory responsivity. Few studies have explored the influence of motor coordination and sensory responsivity on severity of ASC symptoms. In the current study, we explore whether sensory responsivity and motor coordination differences can account for the severity of autistic behaviours in children with ASC. 36 children took part: 18 (13 male, 5 female) with ASC (ages 7-16: mean age 9.93 years) and 18 (7 male, 11 female) typically developing (TD) children (ages 6-12; mean age 9.16 years). Both groups completed a battery of assessments that included motor coordination, sensory responsivity, receptive language, non- verbal reasoning and social communication measures Children with ASC also completed the Autism Diagnostic Observation Schedule and Autism Diagnostic Interview – Revised.. Results showed that children with ASC scored significantly lower on receptive language, coordination and sensory responsivity and a sensorimotor subscale, Modulation of Activity (MoA) compared to the TD group. In the ASC group, MoA significantly predicted ASC severity across all ASC measures; receptive language and sensory responsivity significantly predicted parental reported autism measures; and coordination significantly predicted examiner observed reported scores. Additionally, specific associations were found between the somatosensory perceptive modalities and ASC severity. The results show that sensorimotor skills are associated with severity of ASC symptoms; furthering the need to research sensorimotor integration in ASC and also implying that diagnosis of ASC should also include the assessment of both coordination deficit and atypical sensory responsivity.
... Banji et al. (175) also demonstrated that induced cerebellar damage in mice instigated motor clumsiness, similar to that seen in ASC, the motor clumsiness was then reduced by treating the mice with green tea extract (Camellia sinensis). l-Theanine is a major amino acid component found almost exclusively in green tea (176)(177)(178) and blocks the binding of l-glutamic acid to glutamate receptors in the brain (176,178,179), thereby perhaps aiding the improvement in motor activity by increasing inhibition of movement. ...
... Banji et al. (175) also demonstrated that induced cerebellar damage in mice instigated motor clumsiness, similar to that seen in ASC, the motor clumsiness was then reduced by treating the mice with green tea extract (Camellia sinensis). l-Theanine is a major amino acid component found almost exclusively in green tea (176)(177)(178) and blocks the binding of l-glutamic acid to glutamate receptors in the brain (176,178,179), thereby perhaps aiding the improvement in motor activity by increasing inhibition of movement. ...
Article
Full-text available
In addition to difficulties in social communication, current diagnostic criteria for autism spectrum conditions (ASC) also incorporate sensorimotor difficulties; repetitive motor movements and atypical reactivity to sensory input (APA, 2013). This paper explores whether sensorimotor difficulties are associated with the development and maintenance of symptoms in ASC. Firstly, studies have shown difficulties coordinating sensory input into planning and executing movement effectively in ASC. Secondly, studies have shown associations between sensory reactivity and motor coordination with core ASC symptoms, suggesting these areas each strongly influence the development of social and communication skills. Thirdly, studies have begun to demonstrate that sensorimotor difficulties in ASC could account for reduced social attention early in development, with a cascading effect on later social, communicative and emotional development. These results suggest that sensorimotor difficulties not only contribute to non-social difficulties such as narrow circumscribed interests, but also to the development of social behaviours such as effectively coordinating eye contact with speech and gesture, interpreting others’ behaviour and responding appropriately. Further research is needed to explore the link between sensory and motor difficulties in ASC, and their contribution to the development and maintenance of ASC.
... Banji et al. (175) also demonstrated that induced cerebellar damage in mice instigated motor clumsiness, similar to that seen in ASC, the motor clumsiness was then reduced by treating the mice with green tea extract (Camellia sinensis). l-Theanine is a major amino acid component found almost exclusively in green tea (176)(177)(178) and blocks the binding of l-glutamic acid to glutamate receptors in the brain (176,178,179), thereby perhaps aiding the improvement in motor activity by increasing inhibition of movement. ...
... Banji et al. (175) also demonstrated that induced cerebellar damage in mice instigated motor clumsiness, similar to that seen in ASC, the motor clumsiness was then reduced by treating the mice with green tea extract (Camellia sinensis). l-Theanine is a major amino acid component found almost exclusively in green tea (176)(177)(178) and blocks the binding of l-glutamic acid to glutamate receptors in the brain (176,178,179), thereby perhaps aiding the improvement in motor activity by increasing inhibition of movement. ...
Article
Full-text available
In addition to difficulties in social communication, current diagnostic criteria for autism spectrum conditions (ASC) also incorporate sensorimotor difficulties; repetitive motor movements and atypical reactivity to sensory input (APA, 2013). This paper explores whether sensorimotor difficulties are associated with the development and maintenance of symptoms in ASC. Firstly, studies have shown difficulties coordinating sensory input into planning and executing movement effectively in ASC. Secondly, studies have shown associations between sensory reactivity and motor coordination with core ASC symptoms, suggesting these areas each strongly influence the development of social and communication skills. Thirdly, studies have begun to demonstrate that sensorimotor difficulties in ASC could account for reduced social attention early in development, with a cascading effect on later social, communicative and emotional development. These results suggest that sensorimotor difficulties not only contribute to non-social difficulties such as narrow circumscribed interests, but also to the development of social behaviours such as effectively coordinating eye contact with speech and gesture, interpreting others’ behaviour and responding appropriately. Further research is needed to explore the link between sensory and motor difficulties in ASC, and their contribution to the development and maintenance of ASC.
... Participants were randomly assigned into two groups using a simple randomization plan based on a random number list in a ratio of 1:1, the "N-group" (n = 17), which didn't receive the nutritional supplement for two months, and the "THE-group" (n = 17), which received the nutritional supplements L-Theanine (200 mg/day) and vitamin B6 (2.8 mg/day) for two months. Based on the previous clinical trials on neurodevelopmental disorders, dose selection for L-Theanine and vitamin B6 was considered safe and well tolerated to our patients [19,[21][22][23][24][25][26][27]. ...
... 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]. Recently, a 20-week open label proof-of-concept study was undertaken involving 28 participants with pharmacologicalresistant OCD treated with a nutraceutical combination: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-50 phosphate, and selenium. ...
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.
... В этом отношении теанин подобен D-циклосерину, для которого ранее показана способность в терапевтических дозах уменьшать выраженность негативной симптоматики при шизофрении [57]. В одной из первых работ на эту тему [58] изучали эффективность и переносимость теанина при лечении пациентов с хронической шизофренией и шизоаффективными расстройствами. Группа из 60 больных получала теанин по 400 мг/сут на протяжении 8 нед на фоне антипсихотической терапии. ...
... 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.
... Another study evaluated serum levels of various neurochemicals from the same 40 patients that completed the previous trial. 23 Analysis of the serum levels showed the beneficial effects of L-theanine to be associated with circulating levels of brain-derived neurotrophic factor and the cortisol-to-dehydroepiandrosterone ratio. ...
Article
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The syndrome of schizophrenia is marked by changes in the a"icted person's functioning, perception, thinking, and behaviour. !e mainstay of treatment involves antipsychotic medications (either the older generation, and /or more commonly, the newer atypical antipsychotic medications), often combined with other psychiatric medications (e.g., anxiolytics, hypnotics, mood stabilizers, and/ or antidepressants), as well as some psychoeducation. The "typical" schizophrenic patient seeking out the author's care has either been ill for a brief time (perhaps a year or less) or many years, has relapsed once or several times following the abrupt discontinuation of medication, has developed physical problems from medication (e.g., weight gain and tardive dyskinesia), and has accumulated a host of disabling behavioural and emotional coping strategies. Speci#c orthomolecular substances can reduce symptoms of psychosis, attenuate weight gain, and help to reduce symptoms of tardive dyskinesia and even neuroleptic-induced akathisia. Unfortunately, the long-Term use of antipsychotic and other psychiatric drugs given to assuage symptoms of schizophrenia often cause devastating impacts on the bodies and brains of the individuals that take them. !is makes it di$cult, if not impossible for the orthomolecular approach to help patients fully recover.
... 20 In one study, 400 mg/day of l-theanine was added to the anti-psychotic drug regimen; it was found that l-theanine can improve positive, activation, and anxiety symptoms in schizophrenia. 21 ...
Article
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Schizophrenia is a severe illness that affects 24 million individuals around the globe. Individuals with schizophrenia have been known to make poor nutritional choices. In fact, they are known to consume a lot more sugar and fat, and less fruits and vegetables. In this paper, I show how diet can reduce the symptoms of schizophrenia; that is, that consumption of certain foods can lessen the symptoms of schizophrenia. Further, I create an optimal diet for individuals with schizophrenia.
... As shown in Table 1, a small number of clinical trials have investigated the effects of L-theanine on cognition in humans. One trial was conducted on patients with schizophrenia or schizoaffective disorder (Ritsner et al., 2011). The researchers found that eight-week treatments of L-theanine at high dose of 400 mg (equivalent to the amount of L-theanine in 200 g of dried green tea leaf) reduced anxiety symptoms among these patients. ...
Article
Epigallocatechin gallate (EGCG) - the primary polyphenol found in green teaextract is one of the widely researched polyphenolic compounds in food industry due toits strong anti-oxidant properties. The propensity of EGCG to interact non-covalentlywith macromolecules like proteins and polymers has been well documented. Here wepresent the review of the formation of colloidal particles from non-covalent interactionsof EGCG with cellulose derivative which could be further utilized to generate novelmicro-structures for encapsulation applications.
... Patients with schizophrenia or schizoaffective disorder were randomized to receive L-theanine or placebo while continuing their antipsychotic medications. 21 Patients who received Ltheanine experienced moderate reductions in symp toms of psychosis and anxiety, and there were no differences in quality-of-life measures between the groups. ...
... Anxiolytic and anti-stress effects of LT have been reported in a nonclinical population of pharmacy students (Unno et al., 2013b), and an open label (n = 20) depression study (250 mg/day adjunctive to antidepressants) (Hidese et al., 2016). Further, a 2-week RCT (n = 60) investigation of LT in schizophrenia (400 mg/day, adjunctive to antipsychotics) found significant anxiolytic effects, although it is uncertain whether the separation observed in this study was more related to differences in baseline score than response to treatment (as response slopes show little observable separation; and the data is not clearly reported) (Ritsner et al., 2011). The current study did not replicate these previous, positive findings. ...
... The extent to which undifferentiated anxiety contributes to a poorer outcome and increased psychosocial impairment found for schizophrenia patients with anxiety disorders, needs to be researched, since there is growing evidence that comorbid anxiety has a negative impact on patients' recovery and functioning [10-14, 50, 51]. Recognising and treating comorbid undifferentiated anxiety, as for syndromal anxiety [51][52][53][54][55][56][57][58][59][60], should achieve improved outcomes. ...
Article
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Background: Literature on anxiety in schizophrenia is confined to well-established diagnostic syndromes and the diagnostic category of unspecified anxiety disorder has not been quantitatively verified in this population. This study examined whether anxiety that is not differentiated into the well-established syndromes is empirically discernible from syndromal anxiety and no anxiety in acute-phase schizophrenia. Methods: After sampling 111 acute-phase schizophrenia patients, they were stratified into three groups: syndromal anxiety; undifferentiated anxiety; and without anxiety disorder. The groups were compared statistically in two data sets on measures for anxiety, psychotic severity, depressive features, akathisia and medication use. Results: On two measures of anxiety and for both data sets, the groups were significantly different without evidence of a confounding influence by akathisia, medication, or psychotic severity. The undifferentiated group was different from the syndromal group on the Staden Schizophrenia Anxiety Rating Scale (S-SARS) for both data sets (mean difference = 7.46, p < 0.001; mean difference = 7.69, p < 0.002) and on the Hamilton Anxiety Rating Scale for the one data set (mean difference = 14.68, p < 0.001) but not for the replicative data set (mean difference = 1.49, p = 0.494). The undifferentiated anxiety group was different from the no anxiety group for the respective data sets on both anxiety scales (S-SARS: mean difference = 8.67, p < 0.001; mean difference = 8.64, p < 0.001)(HAM-A: mean difference = 6.05, p < 0.001; mean difference = 8.67, p = 0.002). When depressive features had a confounding effect, it was small relative to the group differences. Conclusions: The results suggest some patients in acute-phase schizophrenia present with undifferentiated anxiety that is discernible from both syndromal anxiety and those without an anxiety disorder. This finding may serve as empirical grounds for clinicians to recognise undifferentiated anxiety in acute-phase schizophrenia, and for further research into the clinical importance of undifferentiated anxiety in this population.
... For dichotomous outcomes (discontinuation and adverse events), we calculated pooled estimates of risk ratios (RRs). We used an empirical cutoff of 8 weeks (16)(17)(18) to define short-or long-term treatment and explored the impacts of treatment length based on subgroup analysis. ...
Article
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Purpose: To compare the efficacy and tolerability of different administration strategies of aripiprazole. Methods: We searched MEDLINE, EMBASE, the Cochrane Central, Web of Science, China National Knowledge Infrastructure(CNKI), and Wanfang Data Knowledge Service Platform(Wanfang) for randomized controlled trials (RCTs) of aripiprazole, using the terms: (aripiprazole) AND (schizophr* OR schizoaff*) AND (“syndrome scale” OR PANSS) AND (clini* OR trial). We retrieved study design, participant characteristics, comparison groups, and outcomes from each study. Results: In total, nine RCTs were selected for meta-analysis, which covered ~1,187 participants. We defined two treatment groups that represent different treatment strategies: (1) the high-dose group (the high-dose strategy) rapidly increased to doses higher than 15 mg/day in 2 weeks or began with doses higher than 15 mg/day, otherwise the group was defined as (2) the low-dose group (the low-dose strategy). If the initial or target doses of aripiprazole in a study were all higher than 15 mg/day, the high- and low-dose groups were created based on the relative level of the dose. The high-dose group showed significantly greater reductions in Positive and Negative Syndrome Scale (PANSS) total scores (standardized mean differences = −8.31, 95% confidence interval [CI] = −16.48, −0.13; P < 0.01; I2 = 96%) than the low-dose group. The high-dose group showed superior effects compared with the low-dose group in long-term studies (more than 8 weeks) (standardized mean differences = −13.81, 95% CI = −25.07, −2.55; P < 0.01; I2 = 96%). With exception of somnolence, we did not find significant differences in side effects or discontinuation due to adverse events. Sensitivity analyses produced similar results. Conclusion: The high-dose treatment strategy of aripiprazole for patients with schizophrenia or schizoaffective disorder may bring more benefits without obvious side effects.
... The ability to recognize facial expressions is impaired when a person is tired [35]. In addition to its antistress effect, theanine may have beneficial effects on people with depressive symptoms [36] or schizophrenia [37,38]. Theanine may affect mood and improve facial expression recognition. ...
Article
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Tea is a beverage commonly consumed worldwide. Matcha is a type of green tea produced by drying and grinding tea leaves (Camellia sinensis L.) into a fine powder. Matcha contains catechin, theanine, and caffeine, which affect cognitive function. Epidemiological studies conducted in Japan have shown that green tea consumption improves cognitive impairment. Previously, we found that daily matcha intake improves attention and executive function in middle-aged and older people. However, its effect on cognitive function in younger adults remains unclear. Moreover, it is unclear which cognitive functions are impaired by stress. This study aimed to clarify whether the administration of matcha improves the attentional function of young adults after mild acute stress and which cognitive function is improved. We included 42 participants aged 25–34 years who consumed 2 g of matcha daily for two weeks. The Uchida–Kraepelin test was used to induce mild acute psychological stress and evaluated memory, attention, facial expression recognition, working memory, visual information, and motor function. Reaction times on the Stroop test for attentional function were significantly lower in the matcha group than in the placebo group. Correct hits in the emotion perception test increased significantly for participants in the matcha group compared to those in the placebo group. We found no significant between-group differences in the other tests. In conclusion, after 2 weeks of matcha intake, the attentional function was maintained after mild acute psychological stress. Thus, matcha might improve cognitive function during or after stress conditions in young adults.
... 94 L-Theanine (c-glutamylethylamide), an amino acid also found in green tea, is reported to have protective effects against psychiatric disorders such as anxiety, panic, and depression 95 and is used as a therapeutic supplement for patients diagnosed with schizophrenia. 96,97 Grapes contain the stilbenoid resveratrol that inhibits norepinephrine and serotonin reuptake, thereby decreasing anxiety and depressive behaviors. 88,98 ...
Article
The performance of the human brain is based on an interplay between the inherited genotype and external environmental factors, including diet. Food and nutrition, essential in maintenance of brain performance, also aid in prevention and treatment of mental disorders. Both the overall composition of the human diet and specific dietary components have been shown to have an impact on brain function in various experimental models and epidemiological studies. This narrative review provides an overview of the role of diet in 5 key areas of brain function related to mental health and performance, including: (1) brain development, (2) signaling networks and neurotransmitters in the brain, (3) cognition and memory, (4) the balance between protein formation and degradation, and (5) deteriorative effects due to chronic inflammatory processes. Finally, the role of diet in epigenetic regulation of brain physiology is discussed.
... Otras sustancias que han sido estudiadas son la L-teanina, un aminoácido que se encuentra en la planta de té que se asocia con disminución de la ansiedad, de la psicopatología general y de los síntomas positivos (Ota, 2015;Ritsner, 2011). De igual manera, se han estudiado las benzodiacepinas, que parecen no tener efecto en los síntomas, manteniéndose la recomendación de su uso para las indicaciones habituales (Dold, 2013) y la galantamina, que parece no tener algún efecto en los síntomas de la esquizofrenia (Buchanan, 2017;Conley, 2009;Dyer, 2008;Lindenmayer, 2011 ...
Book
This book describes the main coadjuvant treatments, both pharmacological and non-pharmacological in psychiatry. Several of its chapters include treatments for children and adolescents, in neurodevelopmental, internalized and externalized disorders, It offers options for treating patients with schizophrenia, bipolar disorder, and in particular for major depressive disorder.
... 121 Bei Patienten mit Schizophrenie konnten ähnliche Effekte sogar in einer doppelblind-kontrollierten Placebo Studie beobachtet werden (Effekte sind anregend und angstlösend). 122 Da Theanin inzwischen vielseitig in der Therapie eingesetzt wird, kann es auch für den Endverbraucher als sicher beurteilt werden. ...
Article
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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.
... In patients with chronic schizophrenia and schizoaffective disorders, moreover, ongoing antipsychotic effectiveness was facilitated by oral intake of theanine given at a dose of 400 mg/day for eight weeks in a fashion related to reduced anxiety [73]. The beneficial effectiveness was positively correlated with serum levels of brain-derived neurotrophic factor in schizophrenic and schizoaffective patients orally given theanine for eight weeks [74]. ...
Article
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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 a clinical study with double-blinded and randomized protocols for evaluation of the efficacy and tolerability of the psychiatric treatment of patients with chronic schizophrenia and schizoaffective disorders, oral intake of theanine leads to promotion of ongoing antipsychotic effectiveness in a manner associated with reduced anxiety when given at a dose of 400 mg/day for 8 weeks ( Ritsner et al., 2011). A possible positive correlation is seen between serum levels of brain-derived neurotrophic factor and the effectiveness of theanine in schizophrenic and schizoaffective patients with oral administration for 8 weeks ). ...
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.
... In a study of 20 university students performing stressful pharmacy practice, researchers measured salivary α-amylase activity and discovered that L-Th ingestion significantly decreased subjective stress by reducing glutamate release [13], which likely occurred through suppressing the autonomic nervous system and hypothalamus-pituitary-adrenal axis excitability. Other studies have found similar L-Thinduced stress reduction in participants, including those with schizophrenia and schizoaffective disorder [14][15][16]. ...
Article
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Although the benefits of drinking tea have been acclaimed in the East for centuries, the scientific community of the Western world has only recognized these benefits in the last three decades. Most studies have focused on the positive effects of green tea on human physical health, especially the heart health. However, green tea has been found to benefit human psychological health as well, which in turn is related to one’s physical health including the heart health. For decades, research has confirmed the link between coronary heart disease (CHD) and mental illness. Thus, it behooves us to know more about the effects of green tea on the mental health, a significant correlate of the heart health. This article summarizes some interesting properties of green tea that affect human psychological health and recognizes some potential adverse effects of overconsumption.
... Recent advancement in tea research illuminates the tremendous health importance of Ltheanine. It may contribute to a reduction in the risk of cardiovascular disease [5] and certain forms of cancer [8][9][10][11][12], as well as to the promotion other physiological functions such as anti-hypertensive effect, anti-stress/ anti-anxiety [13], hepatoprotective effect [14,15], beneficial effects in Attention Deficit Hyperactivity Disorder (ADHD) [16] and Schizophenia [17], improvement of Immune System [18][19][20] and neuroprotective power [21][22][23]. Other hand Zarse K et al reported the evidence of L-theanine regarding the promotion of longevity in mammals [24]. ...
Article
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To date quality and selling price of a tea mainly depends on its flavour, taste and texture but not on its medicinal properties though a Chinese scientist in 780 AD suggested and acclaimed tea as a divine remedy and supreme gift of God for preserving mental tranquillity. Different studies have been showed that L-theanine is the key component of tea which can make us mentally calm, cool and relaxed. At the same time it can protect us from different ailments. There is a notion that L-theanine is present only in green teas, but that is not accurate. Both black and green teas have been found to contain the compound. However, the L-theanine content varies dramatically from tea to tea. Therefore, in this backdrop we aim at quantization of L-theanine in black tea prepared from five different tea clonal varieties, e.g. AV2, B777, HV39, B157 and P312 of all the four flushes. Our study highlighted that black tea of first flush (Spring flush) have highest L-theanine content (~1.3%) than other three flushes. It was also observed that among the five clonal varieties released for Darjeeling, B777 contain highest amount of L-theanine than other clones under study. Thus L-theanine content in tea along with other bioactive components can be considered as an index of tea quality and price determination in tea auction.
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Theanine, an additive, holds several effects on the central nervous system without toxicity and affects CNS drugs. Theanine bilaterally alters β wave of the EEG with or without caffeine and pentobarbital-induced locomotor activity. Theanine also enhances hypnosis of pentobarbital sodium (PB) and antidepression of midazolam, suggesting there are complicated interactions between theanine and CNS drugs. On the other side, theanine induces glycine release. Glycine potentiates the strychnine toxicity via NMDA receptor activation. Moreover, PB facilitates GABAA receptor activation by GABA, and it is commonly prescribed for strychnine poison. However, what the role that theanine plays in the anticonvulsion of PB against strychnine poison is still unknown. Theanine, pentobarbital sodium or strychnine was injected intraperitoneally. EEG was monitored by BIOPAC 16 EEG amplifiers. LD50 of strychnine and hypnotic ED50 of pentobarbital sodium with or without theanine for mice were tested according to Bliss' case. (1) Theanine enhanced the strychnine toxicity. Both theanine and strychnine 1.0 mg/kg increased the power of the β wave. Theanine aggravated that of strychnine 1.0 mg/kg. Theanine attenuated the LD50 of strychnine. (2) Theanine enhanced the anticonvulsion of PB. Theanine increased the power of α, β wave and decreased hypnotic ED50 of PB; PB attenuated strychnine-induced EEG excitation and mortality with or without theanine, and theanine enhanced the effects of PB. Further, theanine enhanced the anticonvulsion of PB dose-dependently against the strychnine toxicity but not the lethal toxicity of strychnine. These results indicated theanine interacted with PB and strychnine. Theanine enhanced both the strychnine toxicity and anticonvulsion of PB against strychnine poison.
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Green tea is usually prepared by adding boiling water to dried tea leaves, which aremade from the plant Camellia Sinensis. Worldwide, tea is the second most popularbeverage after water. Similar to alcohol and coffee, drinking of green tea can producepleasant feelings. In other words, consumption of green tea is partly due to its biologicaleffects on cognitive function and emotions. To date, extensive epidemiological, clinicaland experimental studies have shown that green tea drinking is beneficial to many aspectsof physical health. There is also emerging evidence suggesting that key compounds ofgreen tea may promote mental status and health of the central nervous system. The mostpromising candidates are L-theanine and green tea catechins. This commentary reviewsrecent findings from experimental and epidemiological studies on the neurological effectsof green tea, and discusses possible mechanisms of action.
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Pregnenolone (PREG) and L-Theanine (LT) have shown ameliorative effects on various schizophrenia symptoms. This is the first study to evaluate the efficacy and safety of augmentation of antipsychotic treatment among patients with chronic schizophrenia or schizoaffective disorder with PREG - LT. Double-blind, placebo-controlled trial of PREG - LT or placebo augmentation was conducted for 8 weeks with 40 chronic DSM-IV schizophrenia and schizoaffective disorder patients with suboptimal response to antipsychotics. Oral PREG (50 mg/day) with LT (400 mg/day) or placebo were added to a stable regimen of antipsychotic medication from March 2011 to October 2013. The participants were rated using the Scale for the Assessment of Negative Symptoms (SANS), Hamilton Scale for Anxiety (HAM-A), and Positive and Negative Syndrome Scale (PANSS) scales bi-weekly. The decrease of SANS and HAM-A scores were the co-primary outcomes. Secondary outcomes included assessments of general functioning and side effects. Negative symptoms such as blunted affect, alogia, and anhedonia (SANS) were found to be significantly improved, with moderate effect sizes among patients who received PREG-LT, in comparison with the placebo group. Add-on PREG-LT also significantly associated with a reduction of anxiety scores such as anxious mood, tension, and cardiovascular symptoms (HAM-A), and elevation of general functioning (GAF). Positive symptoms, antipsychotic agents, concomitant drugs, and illness duration did not associate significantly with effect of PREG-LT augmentation. PREG-LT was well-tolerated. Pregnenolone with L-Theanine augmentation may offer a new therapeutic strategy for treatment of negative and anxiety symptoms in schizophrenia and schizoaffective disorder. Further studies are warranted. clinicaltrials.gov Identifier: NCT01831986.
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Pharmacologic treatments intended to reduce neurotransmission through the dopamine D2 receptor have been the only proven therapeutic mechanism for schizophrenia and schizoaffective disorder (SZ/SA). However, in light of these psychoses' multifactorial geneses and pathogeneses, it is unlikely that the available antipsychotic drugs are equally effective at suppressing every symptom of these disorders. This has prompted the use of polypharmacy strategies, including multi-target pharmacotherapy, which is treatment incorporating one or more add-on medications and supplements. This review presents the current state of evidence underpinning the augmentation of antipsychotics with old (antidepressants, lithium, antiepileptic agents, and benzodiazepines) and new molecules and compounds in treating sufferers of SZ/SA.
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Public and clinician interest in complementary and alternative medicine (CAM) has grown in recent decades, and has been driven in part by concerns about medication side effects, nonresponse to standard medications, and the high cost of prescription medications. CAM (natural products and therapies) for many people already plays a central role in the treatment of psychiatric disorders. As an area of special interest within psychiatry, the concept of integrative psychiatry (IP) supports the development of a treatment approach that more fully incorporates evidence-based use of medicinal herbs, nutrients, and mind–body practices with pharmacotherapy and psychological therapies. The Sequential Treatment Alternatives to Relieve Depression (STAR*D) trial highlighted the benefits and limitations of combining or switching antidepressants (Rush et al., 2006). Treatment resistance is an indication of our incomplete understanding of the neurobiological basis of mood disorders. For example, paradigms for treating affective disorders are expanding beyond monoamine neurotransmission models to incorporate other regulatory systems (Rizvi & Kennedy, 2011). The increase in information about the effects of immune function, autonomic nervous system balance, neuroendocrine systems, antioxidants (cellular defense and repair), mitochondrial energy transport, the arachidonic acid cascade, second messengers, and gene activation opens the way for new therapeutic approaches, including the use of CAM treatments that may modulate a broad array of the neuropathological underpinnings of psychiatric disorders. www.tasmanpsychiatry.com
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Anxiety symptoms can occur in up to 65 % of patients with schizophrenia, and may reach the threshold for diagnosis of various comorbid anxiety disorders, including obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). We review the clinical presentation, diagnosis, neurobiology, and management of anxiety in patients with schizophrenia, with a particular focus on pharmacotherapy. The prevalence of any anxiety disorder (at syndrome level) in schizophrenia is estimated to be up to 38 %, with social anxiety disorder (SAD) being the most prevalent. Severity of positive symptoms may correlate with severity of anxiety symptoms, but anxiety can occur independently of psychotic symptoms. While anxiety may be associated with greater levels of insight, it is also associated with increased depression, suicidality, medical service utilization, and cognitive impairment. Patients with anxiety symptoms are more likely to have other internalizing symptoms as opposed to externalizing symptoms. Diagnosis of anxiety in schizophrenia may be challenging, with positive symptoms obscuring anxiety, lower levels of emotional expressivity and communication impeding diagnosis, and conflation with akathisia. Higher diagnostic yield may be achieved by assessment following the resolution of the acute phase of psychosis as well as by the use of screening questions and disorder-specific self-report instruments. In schizophrenia patients with anxiety, there is evidence of underactive fear circuitry during anxiety-provoking stimuli but increased autonomic responsivity and increased responsiveness to neutral stimuli. Recent findings implicate the serotonin transporter (SERT) genes, brain-derived neurotropic factor (BDNF) genes, and the serotonin 1a (5HT1a) receptor, but are preliminary and in need of replication. There are few randomized controlled trials (RCTs) of psychotherapy for anxiety symptoms or disorders in schizophrenia. For pharmacotherapy, data from a few randomized and open trials have shown that aripiprazole and risperidone may be efficacious for obsessive-compulsive and social anxiety symptoms, and quetiapine and olanzapine for generalized anxiety. Older agents such as trifluoperazine may also reduce comorbid anxiety symptoms. Alternative options include selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics, although evidence is based on a few randomized trials, small open trials, and case series, and caution is needed with regards to cytochrome P450 interactions and QTc interval prolongation. Buspirone and pregabalin augmentation may also be considered. Diagnosis and treatment of anxiety symptoms and disorders in schizophrenia is an important and often neglected aspect of the management of schizophrenia.
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Pharmacologic actions to reduce neurotransmission through the D2 receptor have been the only proven therapeutic mechanism for schizophrenia (SZ) and schizoaffective (SA) disorder. However, in view of the multifactorial genesis and pathogenesis of these psychoses, it is unlikely that any antipsychotic drug would work equally well against all symptoms and behavioral disturbances. The absence of a single therapeutic target for SZ/SA disorder has prompted the use of polypharmacy strategies including multi-target pharmacotherapy, consisting of various add-on medications and supplements. Multi-target polypharmacy strategies include the off-label prescription of adjunctive agents such as antidepressants, mood stabilizers, and benzodiazepines already in use, and novel potential adjunctive agents (newer molecules or compounds) based on several non-dopaminergic hypotheses (serotonergic, noradrenergic, glutamatergic, gamma-aminobutyric acid related, and cholinergic neurotransmission, neuroprotective mechanisms and brain neuroplasticity). This chapter is an overview of the current state of evidence for the augmentation of antipsychotics with antidepressants, lithium, antiepileptic agents, benzodiazepines, and new molecules and compounds for the treatment of people with SZ/SA disorder with a special focus on research data published within the past 5–7 years. Using these agents for the augmentation of antipsychotics based on a multi-target drug treatment approach entails the combination of two or more drugs/agents with different mechanisms of action on the central nervous system in an attempt to enhance efficacy.
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Background Anxiety is a response for inability to overcome problems that commonly occurs in medical students, thus affecting their academic performances. The content of l-theanine in Camellia sinensis (C. sinensis) tea is able to cause a relaxing effect to reduce anxiety. Objectives The purpose of this study was to determine the effect of Camellia sinensis (C. sinensis) tea consumption on anxiety level in medical students. Method This was an analytic observational with cross-sectional approach within 332 undergraduate students at Medical Faculty ULM in December 2021. They were selected using simple random sampling technique. Data were collected online via Google form. A questionnaire and The Zung Self-rating Anxiety Scale were applied to figure out characteristics of respondents including tea consumption status, and to determine the anxiety status, respectively. Data were then analyzed using a multinomial logistic regression test. Results This study demonstrated that consuming tea occasionally (≥1 glass per week) showed a lower risk of mild-moderate anxiety by 9% (adj. OR 0.91, 95%CI: 0.47-1.77) and of marked-severe anxiety by 46% (adj. OR 0.55, 95%CI: 0.12-2.43) compared to non-tea drinkers. Meanwhile, consuming 1 glass and 2–3 glasses of tea per day showed a 20% (adj. OR 0.80, 95%CI: 0.36-1.79) and a 54% (adj. OR 0.46, 95%CI: 0.15-1.37) lower risk of mild-moderate anxiety, respectively compared to non-tea drinkers. However, this association was not statistically significant (p>0.05). Conclusions These results indicate that there is a tendency of a decreased risk of anxiety for the increased consumption of C. sinensis tea.
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Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, or lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, and cancer. Their additional clinical benefits include reducing levels of TNF and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. Incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products and their integration with self-care and mHealth can expand precision/personalized medicine strategies for chronic diseases via molecular-behavioral combination therapies.
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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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The author presents the perspective that orthomolecular treatments possess psychoactive effects that result in potentially desirable physiological changes (e.g., sedation, psychomotor slowing, activation, and/or altered sense perception). The psychoactive effects of a broad range of commonly-recommended orthomolecular interventions are listed. This perspective can be integrated into a more expansive understanding of how orthomolecular interventions work, without claiming specific biochemical alterations. Lastly, several key advantages are delineated to support the use of orthomolecular interventions for their psychoactive effects.
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This chapter will present clinical evidence for the efficacy of herbal treatments which address symptoms of anxiety primarily via their effects on cognitive functioning. Brahmi (Bacopa monnieri) Ginkgo (Ginkgo Biloba) Lemon Balm (Melissa officinalis) Tea (Camellia sinensis) Sage (Salvia spp.) Rosemary (Rosmarinus officinalis)
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L-theanine, an important constituent of the tea, is consumed daily throughout the world and is said to greatly contribute to the umami taste of tea. The objective of this review is to summarize the currently available information of L-theanine with reference to health benefits. Relevant keywords like " Tea " , " L-theanine " and " health benefits " were used for the extraction and subsequent analysis of the biomedical literature in the field. Two search engines, Google and Pubmed were used for that purpose. It is expected that the review update the basic features of L-theanine as well as, the current status pertaining to the role of the L-theanine in human health.
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Objective: Between 30% and 62% of patients with schizophrenia present with co-morbid anxiety disorders that are associated with increased overall burden. Our aim was to summarize current and potential interventions for anxiety in schizophrenia. Design: Structured review, summarizing pharmacological and psychosocial interventions used to reduce anxiety in schizophrenia and psychosis. Results: Antipsychotics have been shown to reduce anxiety, increase anxiety, or have no effect. These may be augmented with another antipsychotic, anxiolytic, or antidepressant. Novel agents, such as L-theanine, pregabalin, and cycloserine, show promise in attenuating anxiety in schizophrenia. Psychosocial therapies have been developed to reduce the distress of schizophrenia. Cognitive behavioural therapy (CBT) has shown that benefit and refinements in the therapy have been successful, for example, for managing worry in schizophrenia. CBT usually involves more than 16 sessions, as short courses of CBT do not attenuate the presentation of anxiety in schizophrenia. To address time and cost, the development of manualized CBT to address anxiety in schizophrenia is being developed. Conclusions: The presence of coexisting anxiety symptoms and co-morbid anxiety disorders should be ascertained when assessing patients with schizophrenia or other psychoses as a range of pharmacological and psychosocial treatments are available.
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L-theanine (L-Th), a non-protein amino acid present in tea, is a valuable nutraceutical product with unique health benefits and used as an additive in food industry. L-Th enhances the umami taste but its use is limited due to its inadequate production. Different extraction approaches from tea shoots, chemical synthesis to microbial transformation have been tried to meet its demand. In vitro, in vivo as well as clinical studies have shown its positive effect in regulating CNS disorders. L-Th has become choice ingredient in CNS active products due to its anti-stress and neuroprotective role in dementias particularly in retrogression of Alzheimer's. L-Th biochemically modulates various anti-neoplastic agents by increasing their bioavailability in tumour cells. The review, is an effort to condense the recent research on L-Th highlighting its biological resource, plausible role in tea plant, production approaches, its physiological role on human health and future prospects.
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Anhedonia, the inability to feel or experience pleasure, is a major problem for recovering addicts. Anhedonia can persist long after all traces of the offending drug are gone, and it can cause suicidal thinking and behaviors. We believe that anhedonia is not a distinct disorder but is a symptom of hypodopaminergic traits (genetic), epigenetic states, or a combination of the two. The 2011 endorsement of the American Society of Addiction Medicine’s new definition of addiction as a brain disorder has caught up with the science. Addiction involves an extended neuro-circuitry of the brain, and anhedonia is a condition that involves some of those same regions, including dopaminergic pathways in the mesocorticolimbic system. Andedonia, commonly reported by addicts in detox centers or early abstinence, may be directly tied to the drug-induced dopaminergic changes. It has been our position for decades that brain dopaminergic deficiencies result in reward- circuitry impairments, ultimately leading to Reward Deficiency Syndrome (RDS). The prefrontal cortex and cingulate gyrus contribute to drug relapse, and the nucleus accumbens (NAc) is a locus for craving behavior. While dopaminergic activity is very complex and may evoke differential physiological processes as it relates to pain and pleasure mechanisms (e.g., “liking” and “wanting”), anhedonic behavior has at its root a hypodopaminergic phenotype. In this chapter we discuss polymorphisms of reward genes in terms of inducing this hypodopaminergic phenotype (interaction of both genes and environment) and attempt to show their impact on the induction of anhedonia as a symptom of drug-induced withdrawal. Understanding of putative neurogenetic antecedents to RDS behaviors may provide a gene map for accessing the risk of an individual in developing anhedonia, especially following long-term drug abuse. We encourage the scientific community to carry on required studies to test this hypothesis. It is our belief that one mode of treatment to attenuate anhedonia is to provide natural activation of dopaminergic receptors (D2/D3) at the brain sites for craving and relapse in order to increase dopamine sensitivity.
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The aim of this study is to evaluate the anti-inflammatory and protective effects of l-theanine in inflammatory bowel disease (IBD) and to identify the underlying molecular mechanisms. Rats were pre-treated with l-theanine at 0, 50, 200, or 800 mg/kg/day. IBD was induced in rats using dextran sulfate sodium (DSS). Histopathological analysis suggests that l-theanine can suppress DSS-induced IBD with significant inhibition of inflammation in large and small intestinal tissues. Moreover, the 200 mg/kg/day l-theanine-treated DSS group had higher body and small intestine weights, a lower disease activity index and expression of inflammatory factors than the DSS group without pre-treatment. In RNA sequencing and tandem mass tag labeling analyses, large number of mRNAs and proteins expression level differed when compared with the DSS-induced rats with and without 200 mg/kg/day l-theanine pre-treatment. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis indicates the anti-inflammatory activities of l-theanine in DSS-induced IBD, with a high representation of genes in “Cholesterol metabolism” and “Retinol metabolism” pathways. Analysis of protein–protein interaction networks further indicates the involvement of these two pathways. These studies suggest that medium-dose l-theanine pre-treatment could ameliorate DSS-induced IBD through molecular mechanisms involving cholesterol and retinol metabolism.
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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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L-theanine (N-ethyl-L-glutamine) or theanine is a major amino acid uniquely found in green tea. L-theanine has been historically reported as a relaxing agent, prompting scientific research on its pharmacology. Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors. In addition has been shown to exert neuroprotective effects in animal models possibly through its antagonistic effects on group 1 metabotrophic glutamate receptors. Behavioural studies in animals suggest improvement in learning and memory. Overall, L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent and warrants further investigation in animals and humans.
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Using time-lapse maps, we visualized the dynamics of schizophrenia progression, revealing spreading cortical changes that depend on the type of antipsychotic treatment. Dynamic, 4-dimensional models of disease progression were created from 4 repeated high-resolution brain magnetic resonance imaging scans of 36 first-episode schizophrenia patients (30 men/6 women; mean age: 24.2 +/- 5.1 SD years) randomized to haloperidol (HAL) (n = 15) or olanzapine (OLZ) treatment (n = 21), imaged at baseline, 3, 6, and 12 months (144 scans). Based on surface-based cortical models and point-by-point measures of gray matter volume, we generated time-lapse maps for each treatment. Disease trajectories differed for atypical versus typical neuroleptic drugs. A rapidly advancing parietal-to-frontal deficit trajectory, in HAL-treated patients, mirrored normal cortical maturation but greatly intensified. The disease trajectory advanced even after symptom normalization, involving the frontal cortex within 12 months with typical drug treatment. Areas with fastest tissue loss shifted anteriorly in the first year of psychosis. This trajectory was not seen with OLZ. Whether this association reflects either reduced neurotoxicity or neuroprotection cannot be addressed with neuroimaging; changes may relate to glial rather than neural components. These maps revise current models of schizophrenia progression; due to power limitations, the findings require confirmation in a sample large enough to model group x time interactions.
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The CANTAB battery was administered to a large group (n = 787) of elderly volunteers in the age range from 55 to 80 years. This battery, which is based on tests used to identify the neural substrates of learning and memory in non-human primates, has now been extensively used in the assessment of various forms of dementia and also validated on patients with neurosurgical lesions of the frontal and temporal lobes. The tests employed were pattern and spatial recognition, simultaneous and delayed matching to sample, learning of visuospatial paired associates, a matching to sample, reaction time task and a test of spatial working memory. The sample was banded into different IQ bands based on performance on 5 standard tests of intelligence. The MMSE was also administered to exclude cases of possible dementia (n = 16) in the normal sample. In general, performance declined with age and IQ, but these factors did not interact. A factor analysis (with varimax rotation) identified 4 factors with eigenvalues greater than 1, which accounted for over 60% of the variance. Factor 1 was equated with general learning and memory ability and loaded significantly with the Intelligence scores; factor 2 was related to speed of responding and loaded most heavily with Age. Comparisons were also made of performance on CANTAB of those subjects with dementing scores on the MMSE and the lowest 5th percentile of the population sample. The results are discussed in terms of the utility of the CANTAB battery for the assessment of dementia and of the implications for theories of changes in cognitive function during normal aging.
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The Extrapyramidal Symptom Rating Scale (ESRS) was developed to assess four types of drug-induced movement disorders (DIMD): Parkinsonism, akathisia, dystonia, and tardive dyskinesia (TD). Comprehensive ESRS definitions and basic instructions are given. Factor analysis provided six ESRS factors: 1) hypokinetic Parkinsonism; 2) orofacial dyskinesia; 3) trunk/limb dyskinesia; 4) akathisia; 5) tremor; and 6) tardive dystonia. Two pivotal studies found high inter-rater reliability correlations in both antipsychotic-induced movement disorders and idiopathic Parkinson disease. For inter-rater reliability and certification of raters, >or=80% of item ratings of the complete scale should be +/-1 point of expert ratings and >or=70% of ratings on individual items of each ESRS subscale should be +/-1 point of expert ratings. During a cross-scale comparison, AIMS and ESRS were found to have a 96% (359/374) agreement between TD-defined cases by DSM-IV TD criteria. Two recent international studies using the ESRS included over 3000 patients worldwide and showed an incidence of TD ranging from 10.2% (2000) to 12% (1998). ESRS specificity was investigated through two different approaches, path analyses and ANCOVA PANSS factors changes, which found that ESRS measurement of drug-induced EPS is valid and discriminative from psychiatric symptoms.
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In an investigation of the mechanisms of the neuroprotective effects of theanine (gamma-glutamylethylamide) in brain ischemia, inhibition by theanine of the binding of [H-3](RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [H-3]kainate, and [H-3](E)-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1-H-indole-2- carboxylic acid (MDL 105,519) to glutamate receptors was studied in terms of its possible inhibiting effects on the three receptor subtypes (AMPA, kainate, and NMDA glycine), with rat cortical neurons. Theanine bound the three receptors, but its IC50 of theanine was 80- to 30,000-fold less than that of L-glutamic acid.
Article
L-Theanine is an amino acid found in green tea leaf and in its infusion, and is known to control excitement caused by caffeine. It is also known that the oral administration of L-theanine to rats results in a decrease of serotonin and increase of catecholamines in their brain. L-Theanine has been confirmed to be safe in animal experiments. We found recently that oral intake of L-theanine caused a feeling of relaxation among the human volunteers examined. These observations led us to do experiments on the effects of administration of L-theanine on the brain electric waves. Eight female university students were selected as volunteers. Four of them were ranked to be Grade I (the highest anxiety) and the remaining four, Grade V (the lowest anxiety) in an investigation done by the manifest anxiety scale method. A dose of oral administration of 200 mg of L-theanine dissolved in 100 ml of water resulted in the generation of α-electric waves in the occipital and parietal regions of the brains of the subjects. The emission intensity of α-brain waves (integrated as a function of investigation times and area) was significantly greater in the group of Grade I than that of Grade V. These results indicate the possibility for L-theanine to be applied to foods and beverages as a new type of functional food ingredient for its relaxation effect.
Article
Theanine is the main amino acid component in tea. It usually constitutes between 1 and 2% of the dry weight of the tea leaves. It is as prevalent in tea as all other free amino acids combined. Both enantiomers of theanine were found to have a similar sweet taste, with little or no aftertaste. It was found that black and half-green teas (except for Formosa Oolong) contained as much, or more, theanine as green teas. No correlation was found between the absolute concentration of theanine in tea and its enantiomeric composition. An inverse correlation was found between certain grades of tea (e.g., pekoe, Flowery Orange Pekoe, etc.) and the percent of d-theanine present. This could provide the basis for a reproducible, scientific method to grade and/or evaluate teas. Theanine slowly racemizes in aqueous solution. It also undergoes hydrolysis, particularly at basic pH values. By monitoring these processes, information may be gleaned on the production, storage, handling, and shipping of tea and tea products. Keywords: Racemization; beverage; d-amino acid; tea grades; cyclodextrin column; column switching
Article
Theanine enhanced doxorubicin (DOX) induced antitumor activity by increasing the concentration of DOX in the tumor through the inhibition of efflux of DOX from tumor cells. As theanine reduced the level of glutamate via suppression of the glutamate transporter in tumor cells, we studied the change in the intracellular concentration of glutathione (GSH) and the correlation with the GSH S-conjugate export (GS-X) pump. The reduction in the concentration of glutamate in tumor cells caused by theanine, induced decreases in the intracellular GSH and GS-DOX levels. The expression of MRP5 in M5076 cells, was confirmed. We concluded that the GS-DOX conjugate was transported extracellularly via the MRP5/GS-X pump in M5076 cells and that theanine affected this route. Namely, theanine increases the concentration of DOX in a tumor in vivo through inhibition of the glutamate transporter via the GS-X pump.
Article
Since ancient times, it has been said that drinking green tea brings relaxation. The substance that is responsible for a sense of relaxation, is theanine. Theanine is a unique amino acid found almost solely in tea plants and the main component responsible for the exotic taste of ‘green’ tea. It was found that L-theanine administered intraperitoneally to rats reached the brain within 30 min without any metabolic change. Theanine also acts as a neurotransmitter in the brain and decreased blood pressure significantly in hypertensive rats. In general, animals always generate very weak electric pulses on the surface of the brain, called brain waves. Brain waves are classified into four types, namely α,β,δ and θ-waves, based on mental conditions. Generation of α-waves is considered to be an index of relaxation. In human volunteers, α-waves were generated on the occipital and parietal regions of the brain surface within 40 min after the oral administration of theanine (50–200 mg), signifying relaxation without causing drowsiness. With the successful industrial production of L-theanine, we are now able to supply Suntheanine™ (trade name of L-theanine) which offers a tremendous opportunity for designing foods and medical foods targeting relaxation and the reduction of stress. Taiyo Kagaku Co., Ltd, Japan won the 1998 ‘Food Ingredient Research Award’ for development of Suntheanine™ at Food Ingredients in Europe (Frankfurt). The judges felt it was a particularly well-documented and fascinating piece of research.
Article
We discuss the possibility of multiple underlying etiologies of the condition currently labeled as schizophrenia. We support this hypothesis with a theoretical model of the prefrontal–limbic system.We show how the dynamical behavior of this model depends on an entire set of physiological parameters, representing synaptic strengths, vulnerability to stress-induced cortisol, dopamine regulation and rates of autoantibody production. Malfunction of such different parameters produces similar outward dysregulation of the system, which may readily lead to diagnostic difficulties for a clinician.Techniques that provide a spectrum/profile of neural and steroid functions may be helpful in clarifying these diagnostic dilemmas.
Article
Because of the debate about whether second-generation antipsychotic drugs are better than first-generation antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the effects of these two types of drugs in patients with schizophrenia. We compared nine second-generation antipsychotic drugs with first-generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. We included 150 double-blind, mostly short-term, studies, with 21 533 participants. We excluded open studies because they systematically favoured second-generation drugs. Four of these drugs were better than first-generation antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride -0.31 [95% CI -0.44 to -0.19, p<0.0001], clozapine -0.52 [-0.75 to -0.29, p<0.0001], olanzapine -0.28 [-0.38 to -0.18, p<0.0001], and risperidone -0.13 [-0.22 to -0.05, p=0.002]). The other second-generation drugs were not more efficacious than the first-generation drugs, even for negative symptoms. Therefore efficacy on negative symptoms cannot be a core component of atypicality. Second-generation antipsychotic drugs induced fewer extrapyramidal side-effects than did haloperidol (even at low doses). Only a few have been shown to induce fewer extrapyramidal side-effects than low-potency first-generation antipsychotic drugs. With the exception of aripiprazole and ziprasidone, second-generation antipsychotic drugs induced more weight gain, in various degrees, than did haloperidol but not than low-potency first-generation drugs. The second-generation drugs also differed in their sedating properties. We did not note any consistent effects of moderator variables, such as industry sponsorship, comparator dose, or prophylactic antiparkinsonian medication. Second-generation antipsychotic drugs differ in many properties and are not a homogeneous class. This meta-analysis provides data for individualised treatment based on efficacy, side-effects, and cost.
Article
The pre-test-post-test design (PPD) is predominant in trials of psychotherapeutic treatments. Missing data due to withdrawals present an even bigger challenge in assessing treatment effectiveness under the PPD than under designs with more observations since dropout implies an absence of information about response to treatment. When confronted with missing data, often it is reasonable to assume that the mechanism underlying missingness is related to observed but not to unobserved outcomes (missing at random, MAR). Previous simulation and theoretical studies have shown that, under MAR, modern techniques such as maximum-likelihood (ML) based methods and multiple imputation (MI) can be used to produce unbiased estimates of treatment effects. In practice, however, ad hoc methods such as last observation carried forward (LOCF) imputation and complete-case (CC) analysis continue to be used. In order to better understand the behaviour of these methods in the PPD, we compare the performance of traditional approaches (LOCF, CC) and theoretically sound techniques (MI, ML), under various MAR mechanisms. We show that the LOCF method is seriously biased and conclude that its use should be abandoned. Complete-case analysis produces unbiased estimates only when the dropout mechanism does not depend on pre-test values even when dropout is related to fixed covariates including treatment group (covariate-dependent: CD). However, CC analysis is generally biased under MAR. The magnitude of the bias is largest when the correlation of post- and pre-test is relatively low.
Article
The transmethylation hypothesis of schizophrenia was reviewed with considerations that large doses of methionine when combined with a monoamine oxidase inhibitor lead to exacerbation of psychotic symptoms in a significant percentage of chronic schizophrenic patients. It was noted that nicotinic acid in the dosage of 3,000 mg/day can neither prevent nor counteract the psychopathology thus induced.
Article
The Calgary Depression Scale (CDS) is a nine item structured interview scale, in which each item has a four point measure, each point anchored by descriptors. The scale has been specifically developed to assess depression in schizophrenics. This article describes the testing of the reliability and validity of the CDS. The scale is assessed and compared to three established measures, the Hamilton Depression Rating Scale (HDRS) the Beck Depression Inventory (BDI) and a depression measure derived from the Brief Psychiatric Rating Scale (BPRS). Confirmatory factor analysis demonstrated that the CDS is unidimensional, measuring the same construct in both in- and outpatients. The scale has high internal consistency, significant strong correlations with scores on the Hamilton, Beck and BPRS depression measures, and the presence of a major depressive episode. All items of the CDS significantly discriminate between the presence and absence of a major depressive episode. It is concluded that the CDS is a parsimonious reliable scale which is suitable for assessing depression across both the acute and residual stages of schizophrenia.
Article
Chlorpromazine (CPZ) equivalents are often used as a relative measure of the antipsychotic potency of neuroleptics. We review the CPZ equivalents of 33 neuroleptics and illustrate why imprecisions or discrepancies will be difficult to eliminate from these values. We nevertheless underline that CPZ equivalents can be clinically useful, since they facilitate the choice of doses of different neuroleptics that should induce comparable antipsychotic effects.
Article
The effects of i.p. administered theanine (L-N-ethylglutamine), a constituent of Japanese green tea, on the levels of norepinephrine (NE) and serotonin (5-HT) in the brain of rats with or without coadministration of caffeine were investigated, and compared with those of glutamine.Theanine decreased the NE level, whereas no change was observed with glutamine or caffeine.The decrease of NE induced by theanine was reversed by caffeine. In rats pretreated with pargline, a monoamine oxidase inhibitor, theanine significantly increased the NE level compared with the control. However, it did not enhance the NE levels increased by caffeine. Thus, theanine may decrease the NE levels by releasing this neurotransmitter.Theanine did not alter the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in rats pretreated with or without pargyline, indicating that this amide affects neither 5-HT synthesis nor its degradation. Caffeine increased the levels of 5-HT and 5-HIAA in normal rats to similar extents.This effect was depressed by theanine. In rats pretreated with pargyline, the levels of 5-HT and 5-HIAA were not altered by caffeine, and theanine did not modify the outcome. It may be concluded that the action of theanine is related to the possible inhibition of 5-HT release by caffeine. The effect of glutamine on the levels of 5-HT was somewhat different form that of theanine.
Article
Theanine (N-ethylglutamine), a flavourous constituent of tea leaves, was studied in respect of the influence on the central nervous system in mice.Theanine was shown to inhibit the convulsive action of caffeine, but was ineffective against pentetrazole, picrotoxin, strychnine, pipradrol and bemegride as well as L-glutamine. Neither theanine nor L-glutamine effected on the prolongation of the sleeping time after the injection of hexobarbital sodium in mice. Using 14C-labeled theanine, it was found that the intraperitoneally administered theanine was taken up by brain tissue with out undergoing the metabolic changes in a 30minutes. The intracerebral level of γaminobutyric acid was shown to increase significantly at 30minutes following the intraperitoneal administration of theanine in mice.
Article
There is growing interest in deficit symptoms in studies of the course and treatment response of schizophrenia. However, existing clinical assessment instruments focus primarily on productive symptoms. The authors describe the Quality of Life Scale (QLS), a 21-item scale based on a semistructured interview designed to assess deficit symptoms and thereby fill an important gap in the range of instruments now available. Data regarding reliability and training in the use of the QLS are presented. A factor analysis of the items yields results compatible with the conceptual model on which the scale is based. The factor analysis was also performed separately by sex and was fundamentally similar for men and women.
Article
In order to examine the effect of neuroleptic medication on the factor structure of schizophrenic symptomatology, 517 DSM-III-R schizophrenic in-patients enrolled in a multicenter phase II drug study were evaluated on their pre-existing neuroleptic at screening on the Positive and Negative Syndrome Scale (PANSS) and after a one-week drug-free period. Separate principal components analyses of the PANSS were done at each time point. PANSS total and component scores were assessed for differences utilizing paired t-tests. Both factor analyses confirmed the five factor model (negative, positive, cognitive, excitement and depression components) explaining 51.7 and 56.2% of the variances at each time point. After medication wash-out psychopathology significantly worsened as measured by total PANSS score and by each of the components. The overall worsening of component scores appeared global and uniform, as evidenced by the fact that at washout, the proportion of individual component scores to total psychopathology remained constant for most components. The lack of change of most components in proportion to the psychopathology total is evidence for the stability of these individual psychopathological dimensions of patients while on and off neuroleptics. The results further support the validity of the five-factor model of schizophrenic psychopathology as measured by the PANSS.
Article
The abilities of green tea extract and its three major components to inhibit lipid peroxidation in low-density lipoprotein (LDL) catalyzed by copper were tested in vitro using malondialdehyde as a parameter of antioxidant activity. The results demonstrated that green tea extract markedly delays peroxidation with a dose-dependent pattern. Of the three components, polyphenols had the strongest action. Similar action was also shown in the theanine-treated group but was weaker than in the former, whereas caffeine had a very limited effect. Based on these data, it is concluded that green tea extract can effectively inhibit peroxidation and that this activity is due largely to the polyphenols it contains. According to the ultraviolet spectra, copper chelation is suggested to be one of the possible mechanisms of LDL antiperoxidation.