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Magnesium enhances the effects of reboxetine on cognitive functions in rats
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P.1.j. Basic and clinical neuroscience − Cognitive neuroscience
P.1.j.019 Jumping to conclusions in obsessive compulsive disorder M.E. Ortigosa Luque1 , M. Valverde Barea2 , F. Cartas Moreno2 ° Princesa de Espa˜na, Jaen, Spain; 2 Hosp. Princesa de Espa˜na, psychiatry, Jaen, Spain
1 Hosp.
Introduction: In Obsessive compulsive disorder, sometimes, observed symptoms that could be psychotic. These observations make us wonder if there is a continuum between obsession, overvalued idea and delirium. There is a cognitive bias called Jumping to conclusions in psychosis. We think it is necessary to explore whether this bias is present in Obsessive compulsive disorder [1]. Objectives: We want to show the presence or not of a cognitive bias in obsessive compulsive disorder; jump to conclusions, present in psychosis, by testing The picture to decision task (TDT). Methods: 20 patients diagnosed with Obsessive compulsive disorder (according DSM-5 criteria) attended the Community care center of Ja´en (Spain). 12 men and 8 women. Test were passed: OCI-R, Community assesment of psychic experiences (CAPE), Beads task and The picture to decision task (TDT). Pearson‘s correlation was performed by relating the different variables studied, after this we made the linear regression where the dependent variable is TDT and independent CAPE negative and OCI-R accumulation. Results: First we studied the relationship between the dimensions of the CAPE and the OCI-R finding that the positive dimension of the CAPE had a positive relationship with the subscale order OCI-R (Pearson = 0.61, p = 0.005) and neutralization subscale (Pearson = 0.51, p = 0.05). In the case of the negative dimension of CAPE related to the accumulation subscale of OCI-R (Pearson = 0.55, p = 0.05). No relation between the depressive dimension with any of the subdivisions obtained from OCI-R was found. As for the possible relationship between OCI-R subscales and measures to jump to conclusions (Draw to decision; DTD) It shows that only the accumulation dimension relate negatively with DTD without tracks (Pearson = −0.052, p = 0.05) and the DTD with tracks (Pearson = −0.59, p = 0.005). The relationship between the dimensions of the CAPE and the DTD showed that only the negative side of the CAPE was associated with DTD without tracks (Pearson = −0.49, p = 0.05) and with the DTD with tracks (Pearson = −0.48, p = 0.05). To determine which dimensions are independently associated with DTD a linear regression was performed where the dependent variable was DTD and the independent variables were negative CAPE and OCI-R accumulation. Once we showed that only the accumulation dimension was associated independently with the DTD with tracks (beta = −0.47, p = 0.05). Partnering with free DTD was lost and none of the dimensions associated with free DTD. Conclusions: In the results obtained an association between dimensions CAPE observed with OCI-R subscales, that is, we see a possible association between what could be signs of psychotic symptoms manifested, or rather, with experiences that could enter into what the psychotic spectrum. Added to this it is that jumping to conclusions is present in obsessive compulsive disorder and a higher score on the item accumulation jump to conclusions was greater. Although this was done with the Beads task and was not positive jump to conclusions in patients suffering from Obsessive compulsive disorder [2].
References [1] Rubio, J.l., Ruiz-Veguilla, M., Hernandez, L., Barrig´on, M.L., Salcedo, M.D., Moreno, J.M., G´omez, E., Moritz, S., Ferrin, M., 2011. Jumping to conclusions in psychosis: a faulty appraisal. Schizophr Res 133(1−3), 199–204. [2] Jacobsen, P., Freeman, D., Salkovskis, P., 2012. Reasoning bias and belief conviction in obsessive compulsive disorder and delusions: jumping to conclusions across disorders? Br J Clin Psychol 51(1), 84−99.
P.1.j.021 Magnesium enhances the effects of reboxetine on cognitive functions in rats L. Mititelu Tartau1 , G. Rusu1 , A.C. Cristofor1 , R. Chirita2 , R.V. Lupusoru3 , E.G. Popa4 ° 1 University of Medicine and Pharmacy Iasi Gr. T. Popa, Faculty of Medicine- PharmacologyAlgesiology, Iasi, Romania; 2 University of Medicine and Pharmacy Iasi Gr. T. Popa, Faculty of Medicine- Psychiatry, Iasi, Romania; 3 University of Medicine and Pharmacy Iasi Gr. T. Popa, Faculty of Medicine- Patho-Physiology, Iasi, Romania; 4 University of Medicine and Pharmacy Iasi Gr. T. Popa, Faculty of Pharmacy - Pharmaceutical Technology, Iasi, Romania The antidepressant drug reboxetine is a norepinephrine reuptake inhibitor used especially in the treatment of major and unipolar depressions [1]. Magnesium is one of the most wide-spread elements in the environment, being the fourth major cation in the organism (after sodium, potassium and chloride), and the second most abundant within the cells. It plays a pivotal role in the homeostasis, being involved as enzyme co-factor in more than 300 biochemical reactions in the body [2]. Aim: Experimental researches on the effects of reboxetine and magnesium chloride association on the cognitive functions in old rats. Material and Method: The experiment was carried out on white male Wistar old rats (300–350 g, 15 months), distributed into 4 groups of 6 animals each, treated orally (using an eso-gastric device) one daily consecutive administration, for one month, as follows: group I (Control): distilled water 0.3 ml/100 g weight; group II (RBX): reboxetine 5 mg/kbw; group III (Mg): magnesium chloride 1 mmol/kbw, group IV (RBX+Mg): reboxetine 5 mg/kbw + magnesium chloride 1 mmol/kbw. The animal spatial memory performance was assessed by recording spontaneous alternation behavior in a single session in the T-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during an eight minutes session. The following parameters were counted: number of arm visits, the percent of time spent inside the arms, the number of the returns inside the same arm, the number of alternations, the alternation percentage. The alternation percentage was calculated according the following formula: [(number of alternations)/(total number of arm visits − 2)] × 100 [3]. Data were presented as ± standard deviation and significance was tested by SPSS 17.0 for Windows statistics software, with ANOVA method and Newman–Keuls test as post-hoc. P-values less than 0.05 were considered statistically significant comparing with those of control group. Experimental protocol was implemented, according to recommendations of the ‘Grigore T. Popa’ University Committee for Research and Ethical Issues. Results: In our experimental conditions the administration of reboxetine (2 mg/kbw) determined an increase of spontaneous alternation rate, statistically significant comparing with control group, but did not influence the period latency to choose a goal arm. The chronic use of magnesium chloride (1 mmol/kbw)
P.1.j. Basic and clinical neuroscience − Cognitive neuroscience induced an increase of spontaneous alternation percentage, statistically significant compared to control group in the T-maze test. Its effects were more accentuated than those of reboxetine on the same time interval of determinations. The association of reboxetine with magnesium chloride resulted in a significant increase of spontaneous alternation rate, statistically significant (p < 0.01) compared to both reboxetine and magnesium chloride single administration in this experimental behavioral model in rats. Conclusion: Magnesium chloride chronic administration enhanced the facilitating effect of reboxetine on spatial learning and short-term memory consolidation, suggesting an improvement of cognitive behavior in rats. References [1] Eyding, D., Lelgemann, M., Grouven, U., H¨arter, M., Kromp, M., Kaiser, T., Kerekes, M.F., Gerken, M., Wieseler, B., 2010, Reboxetine for acute treatment of major depression: systematic review and metaanalysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials, BMJ, 341:c4737. [2] Romani, A.M.P., 2013. Chapter 4 Magnesium Homeostasis in Mammalian Cells In Banci, Lucia (Ed.), Metallomics and the Cell. Metal Ions in Life Sciences, 12. Springer. [3] Hart, P.C., Bergner, C.L., Smolinsky, A.N., Dufour, B.D., Egan, R.J., Laporte, J.L., Kalueff, A.V., 2010. Experimental models of anxiety for drug discovery and brain research, Methods Mol Biol 602, 299–321.
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analysis of variance (ANOVA) and chi-square tests for dichotomous variables. Differences between each of the groups were analyzed with the two-sample t-test. ANOVA was also performed to analyze the serum IL-6 and TNF-a levels among all groups. Correlation between serum IL-6 and TNF-a levels and demographic and neuropsychological variables was analyzed using Pearson’s correlation coefficient. Results: The AD group showed significantly higher serum TNF-a (P < 0.05) and IL-6 (P < 0.05) levels as compared to the control group. However, no significant differences for these levels were observed in the MCI group as compared to both the AD and control groups. After adjusting for age, significant difference in IL-6 (p < 0.05) was maintained, but not in TNF-a (p = 0.082) among the three groups. TNF-a levels and IL-6 levels were negatively correlated with MMSE-K and positively with Global Deterioration Scale (GDS) scores. There was significant correlation between TNF-a and IL-6 levels (p < 0.001). Conclusions: Serum IL-6 levels were higher in patients with AD than those of subjects with MCI and healthy controls. Serum TNF-a and IL-6 levels were negatively correlated with cognitive function. The present study suggests serum IL-6 might have the role of a biomarker for AD. References
P.1.j.022 Serum tumor necrosis factor-alpha and interleukin-6 levels in Alzheimer’s disease and mild cognitive impairment H. Kim1 ° , K.J. Lee1 1 Inje University Ilsan Paik Hospital, Dept. of Psychiatry, Goyang, South-Korea Background: Neuroinflammation has been recognized as a feature of Alzheimer’s disease (AD); mild cognitive impairment (MCI) has been believed to share several pathological features with AD. Inflammatory components associated with neuroinflammation in AD include glial cells like microglia and astrocytes, the complement system, and cytokines and chemokines. Among the proinflammatory cytokines, tumor necrosis factor (TNF)-a and Interleukin (IL)-6 may potentially significantly contribute to the neuroinflammatory processes observed in AD. TNF-a, which has been extensively studied for both AD and mild cognitive impairment (MCI) [1], is one of the main proinflammatory cytokines that plays a central role in initiating and regulating the cytokine cascade during an inflammatory response [2,3]. The aim of the present study was to compare serum cytokine levels among patients with AD, subjects with MCI, and healthy controls, and to assess the correlation between cytokine levels and cognitive performance in these subjects. Methods: Participants included 35 patients with AD, 29 subjects with MCI, and 28 healthy controls from the psychiatric department of the Inje University Ilsan Paik Hospital in South Korea. Demographic and neuropsychological information were obtained. Peripheral cytokine levels, specifically tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels were measured for all subjects. Blood samples were taken intravenously from an upper limb in the morning, after the patient had fasted for 12 h or longer. Samples were stored in Vacutainer® tubes containing citrate, cooled with ice, and immediately centrifuged at 3,000 rpm for 10 min. Overall cognitive function and disease severity were measured using the Korean version of the Mini-Mental States Examination (MMSE-K), the Clinical Dementia Rating (CDR), and the Global Deterioration Scale (GDS). Demographic and neuropsychological variables were compared across groups using
[1] Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G.M., et al., 2000. Inflammation and Alzheimer’s disease. Neurobiol Aging 21(3), 383–421. [2] Gruen, J.R., Weissman, S.M., 1997. Evolving views of the major histocompatibility complex. Blood 90(11), 4252−65. [3] Makhatadze, N.J., 1998. Tumor necrosis factor locus: genetic organisation and biological implications. Hum Immunol. 59(9), 571−9.
P.1.j.023 Effect of caffeine on neuropsychological performance in healthy volunteers: a double-blind placebo-controlled study Y. Konishi1 ° , H. Hori1 , K. Ide1 , A. Katsuki1 , K. Atake1 , R. Igata1 , R. Yoshimura1 1 University of Occupational and Environmental Health- Japan, Psychiatry, Kitakyushu, Japan Background: Caffeine is contained in the various food and beverages such as coffee and tea. Coffee and tea are usually used to enhance or/and maintain working performance. Whether caffeine improve neurocognitive functions or not remains unclear. The aim of the study was to elucidate the point using 200 mg of pure caffeine in a double-blind, placebo-controlled fashion. Two hundreds mg of caffeine is equivalent to two or three cups of regular coffee. Subjects and Method: This study was conducted by a doubleblind, randomized, placebo-controlled trial. 30 healthy volunteers (male/female; 14/16, age; 31.6±9.3 years, height; 164.1±8.3 cm, body weight; 57.4±8.7 kg) participated in this study. The patients were randomly assigned either the caffeine group (N = 15) or the placebo group (N = 15) with the envelope method. The protocol was as follows. In short, a non-caffeine period of 3 days was provided prior to the study. They were randomly assigned to receive 200-mg doses of caffeine or placebo. Before and 120 minutes after administrating caffeine or placebo, we drew blood samples. The plasma caffeine concentration was measured using highperformance liquid chromatography (HPLC). Thirty minutes after administration, participants were evaluated their cognitive functions by Symbol Digit Coding Test (SDC), Stroop Test (ST), Shifting Attention Test (SAT) and Four Part Continuous Performance Test (FPCPT) using Cognitrax, which is a software for testing
P.1.j. Basic and clinical neuroscience − Cognitive neuroscience
P.1.j.019 Jumping to conclusions in obsessive compulsive disorder M.E. Ortigosa Luque1 , M. Valverde Barea2 , F. Cartas Moreno2 ° Princesa de Espa˜na, Jaen, Spain; 2 Hosp. Princesa de Espa˜na, psychiatry, Jaen, Spain
1 Hosp.
Introduction: In Obsessive compulsive disorder, sometimes, observed symptoms that could be psychotic. These observations make us wonder if there is a continuum between obsession, overvalued idea and delirium. There is a cognitive bias called Jumping to conclusions in psychosis. We think it is necessary to explore whether this bias is present in Obsessive compulsive disorder [1]. Objectives: We want to show the presence or not of a cognitive bias in obsessive compulsive disorder; jump to conclusions, present in psychosis, by testing The picture to decision task (TDT). Methods: 20 patients diagnosed with Obsessive compulsive disorder (according DSM-5 criteria) attended the Community care center of Ja´en (Spain). 12 men and 8 women. Test were passed: OCI-R, Community assesment of psychic experiences (CAPE), Beads task and The picture to decision task (TDT). Pearson‘s correlation was performed by relating the different variables studied, after this we made the linear regression where the dependent variable is TDT and independent CAPE negative and OCI-R accumulation. Results: First we studied the relationship between the dimensions of the CAPE and the OCI-R finding that the positive dimension of the CAPE had a positive relationship with the subscale order OCI-R (Pearson = 0.61, p = 0.005) and neutralization subscale (Pearson = 0.51, p = 0.05). In the case of the negative dimension of CAPE related to the accumulation subscale of OCI-R (Pearson = 0.55, p = 0.05). No relation between the depressive dimension with any of the subdivisions obtained from OCI-R was found. As for the possible relationship between OCI-R subscales and measures to jump to conclusions (Draw to decision; DTD) It shows that only the accumulation dimension relate negatively with DTD without tracks (Pearson = −0.052, p = 0.05) and the DTD with tracks (Pearson = −0.59, p = 0.005). The relationship between the dimensions of the CAPE and the DTD showed that only the negative side of the CAPE was associated with DTD without tracks (Pearson = −0.49, p = 0.05) and with the DTD with tracks (Pearson = −0.48, p = 0.05). To determine which dimensions are independently associated with DTD a linear regression was performed where the dependent variable was DTD and the independent variables were negative CAPE and OCI-R accumulation. Once we showed that only the accumulation dimension was associated independently with the DTD with tracks (beta = −0.47, p = 0.05). Partnering with free DTD was lost and none of the dimensions associated with free DTD. Conclusions: In the results obtained an association between dimensions CAPE observed with OCI-R subscales, that is, we see a possible association between what could be signs of psychotic symptoms manifested, or rather, with experiences that could enter into what the psychotic spectrum. Added to this it is that jumping to conclusions is present in obsessive compulsive disorder and a higher score on the item accumulation jump to conclusions was greater. Although this was done with the Beads task and was not positive jump to conclusions in patients suffering from Obsessive compulsive disorder [2].
References [1] Rubio, J.l., Ruiz-Veguilla, M., Hernandez, L., Barrig´on, M.L., Salcedo, M.D., Moreno, J.M., G´omez, E., Moritz, S., Ferrin, M., 2011. Jumping to conclusions in psychosis: a faulty appraisal. Schizophr Res 133(1−3), 199–204. [2] Jacobsen, P., Freeman, D., Salkovskis, P., 2012. Reasoning bias and belief conviction in obsessive compulsive disorder and delusions: jumping to conclusions across disorders? Br J Clin Psychol 51(1), 84−99.
P.1.j.021 Magnesium enhances the effects of reboxetine on cognitive functions in rats L. Mititelu Tartau1 , G. Rusu1 , A.C. Cristofor1 , R. Chirita2 , R.V. Lupusoru3 , E.G. Popa4 ° 1 University of Medicine and Pharmacy Iasi Gr. T. Popa, Faculty of Medicine- PharmacologyAlgesiology, Iasi, Romania; 2 University of Medicine and Pharmacy Iasi Gr. T. Popa, Faculty of Medicine- Psychiatry, Iasi, Romania; 3 University of Medicine and Pharmacy Iasi Gr. T. Popa, Faculty of Medicine- Patho-Physiology, Iasi, Romania; 4 University of Medicine and Pharmacy Iasi Gr. T. Popa, Faculty of Pharmacy - Pharmaceutical Technology, Iasi, Romania The antidepressant drug reboxetine is a norepinephrine reuptake inhibitor used especially in the treatment of major and unipolar depressions [1]. Magnesium is one of the most wide-spread elements in the environment, being the fourth major cation in the organism (after sodium, potassium and chloride), and the second most abundant within the cells. It plays a pivotal role in the homeostasis, being involved as enzyme co-factor in more than 300 biochemical reactions in the body [2]. Aim: Experimental researches on the effects of reboxetine and magnesium chloride association on the cognitive functions in old rats. Material and Method: The experiment was carried out on white male Wistar old rats (300–350 g, 15 months), distributed into 4 groups of 6 animals each, treated orally (using an eso-gastric device) one daily consecutive administration, for one month, as follows: group I (Control): distilled water 0.3 ml/100 g weight; group II (RBX): reboxetine 5 mg/kbw; group III (Mg): magnesium chloride 1 mmol/kbw, group IV (RBX+Mg): reboxetine 5 mg/kbw + magnesium chloride 1 mmol/kbw. The animal spatial memory performance was assessed by recording spontaneous alternation behavior in a single session in the T-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during an eight minutes session. The following parameters were counted: number of arm visits, the percent of time spent inside the arms, the number of the returns inside the same arm, the number of alternations, the alternation percentage. The alternation percentage was calculated according the following formula: [(number of alternations)/(total number of arm visits − 2)] × 100 [3]. Data were presented as ± standard deviation and significance was tested by SPSS 17.0 for Windows statistics software, with ANOVA method and Newman–Keuls test as post-hoc. P-values less than 0.05 were considered statistically significant comparing with those of control group. Experimental protocol was implemented, according to recommendations of the ‘Grigore T. Popa’ University Committee for Research and Ethical Issues. Results: In our experimental conditions the administration of reboxetine (2 mg/kbw) determined an increase of spontaneous alternation rate, statistically significant comparing with control group, but did not influence the period latency to choose a goal arm. The chronic use of magnesium chloride (1 mmol/kbw)
P.1.j. Basic and clinical neuroscience − Cognitive neuroscience induced an increase of spontaneous alternation percentage, statistically significant compared to control group in the T-maze test. Its effects were more accentuated than those of reboxetine on the same time interval of determinations. The association of reboxetine with magnesium chloride resulted in a significant increase of spontaneous alternation rate, statistically significant (p < 0.01) compared to both reboxetine and magnesium chloride single administration in this experimental behavioral model in rats. Conclusion: Magnesium chloride chronic administration enhanced the facilitating effect of reboxetine on spatial learning and short-term memory consolidation, suggesting an improvement of cognitive behavior in rats. References [1] Eyding, D., Lelgemann, M., Grouven, U., H¨arter, M., Kromp, M., Kaiser, T., Kerekes, M.F., Gerken, M., Wieseler, B., 2010, Reboxetine for acute treatment of major depression: systematic review and metaanalysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials, BMJ, 341:c4737. [2] Romani, A.M.P., 2013. Chapter 4 Magnesium Homeostasis in Mammalian Cells In Banci, Lucia (Ed.), Metallomics and the Cell. Metal Ions in Life Sciences, 12. Springer. [3] Hart, P.C., Bergner, C.L., Smolinsky, A.N., Dufour, B.D., Egan, R.J., Laporte, J.L., Kalueff, A.V., 2010. Experimental models of anxiety for drug discovery and brain research, Methods Mol Biol 602, 299–321.
S335
analysis of variance (ANOVA) and chi-square tests for dichotomous variables. Differences between each of the groups were analyzed with the two-sample t-test. ANOVA was also performed to analyze the serum IL-6 and TNF-a levels among all groups. Correlation between serum IL-6 and TNF-a levels and demographic and neuropsychological variables was analyzed using Pearson’s correlation coefficient. Results: The AD group showed significantly higher serum TNF-a (P < 0.05) and IL-6 (P < 0.05) levels as compared to the control group. However, no significant differences for these levels were observed in the MCI group as compared to both the AD and control groups. After adjusting for age, significant difference in IL-6 (p < 0.05) was maintained, but not in TNF-a (p = 0.082) among the three groups. TNF-a levels and IL-6 levels were negatively correlated with MMSE-K and positively with Global Deterioration Scale (GDS) scores. There was significant correlation between TNF-a and IL-6 levels (p < 0.001). Conclusions: Serum IL-6 levels were higher in patients with AD than those of subjects with MCI and healthy controls. Serum TNF-a and IL-6 levels were negatively correlated with cognitive function. The present study suggests serum IL-6 might have the role of a biomarker for AD. References
P.1.j.022 Serum tumor necrosis factor-alpha and interleukin-6 levels in Alzheimer’s disease and mild cognitive impairment H. Kim1 ° , K.J. Lee1 1 Inje University Ilsan Paik Hospital, Dept. of Psychiatry, Goyang, South-Korea Background: Neuroinflammation has been recognized as a feature of Alzheimer’s disease (AD); mild cognitive impairment (MCI) has been believed to share several pathological features with AD. Inflammatory components associated with neuroinflammation in AD include glial cells like microglia and astrocytes, the complement system, and cytokines and chemokines. Among the proinflammatory cytokines, tumor necrosis factor (TNF)-a and Interleukin (IL)-6 may potentially significantly contribute to the neuroinflammatory processes observed in AD. TNF-a, which has been extensively studied for both AD and mild cognitive impairment (MCI) [1], is one of the main proinflammatory cytokines that plays a central role in initiating and regulating the cytokine cascade during an inflammatory response [2,3]. The aim of the present study was to compare serum cytokine levels among patients with AD, subjects with MCI, and healthy controls, and to assess the correlation between cytokine levels and cognitive performance in these subjects. Methods: Participants included 35 patients with AD, 29 subjects with MCI, and 28 healthy controls from the psychiatric department of the Inje University Ilsan Paik Hospital in South Korea. Demographic and neuropsychological information were obtained. Peripheral cytokine levels, specifically tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels were measured for all subjects. Blood samples were taken intravenously from an upper limb in the morning, after the patient had fasted for 12 h or longer. Samples were stored in Vacutainer® tubes containing citrate, cooled with ice, and immediately centrifuged at 3,000 rpm for 10 min. Overall cognitive function and disease severity were measured using the Korean version of the Mini-Mental States Examination (MMSE-K), the Clinical Dementia Rating (CDR), and the Global Deterioration Scale (GDS). Demographic and neuropsychological variables were compared across groups using
[1] Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G.M., et al., 2000. Inflammation and Alzheimer’s disease. Neurobiol Aging 21(3), 383–421. [2] Gruen, J.R., Weissman, S.M., 1997. Evolving views of the major histocompatibility complex. Blood 90(11), 4252−65. [3] Makhatadze, N.J., 1998. Tumor necrosis factor locus: genetic organisation and biological implications. Hum Immunol. 59(9), 571−9.
P.1.j.023 Effect of caffeine on neuropsychological performance in healthy volunteers: a double-blind placebo-controlled study Y. Konishi1 ° , H. Hori1 , K. Ide1 , A. Katsuki1 , K. Atake1 , R. Igata1 , R. Yoshimura1 1 University of Occupational and Environmental Health- Japan, Psychiatry, Kitakyushu, Japan Background: Caffeine is contained in the various food and beverages such as coffee and tea. Coffee and tea are usually used to enhance or/and maintain working performance. Whether caffeine improve neurocognitive functions or not remains unclear. The aim of the study was to elucidate the point using 200 mg of pure caffeine in a double-blind, placebo-controlled fashion. Two hundreds mg of caffeine is equivalent to two or three cups of regular coffee. Subjects and Method: This study was conducted by a doubleblind, randomized, placebo-controlled trial. 30 healthy volunteers (male/female; 14/16, age; 31.6±9.3 years, height; 164.1±8.3 cm, body weight; 57.4±8.7 kg) participated in this study. The patients were randomly assigned either the caffeine group (N = 15) or the placebo group (N = 15) with the envelope method. The protocol was as follows. In short, a non-caffeine period of 3 days was provided prior to the study. They were randomly assigned to receive 200-mg doses of caffeine or placebo. Before and 120 minutes after administrating caffeine or placebo, we drew blood samples. The plasma caffeine concentration was measured using highperformance liquid chromatography (HPLC). Thirty minutes after administration, participants were evaluated their cognitive functions by Symbol Digit Coding Test (SDC), Stroop Test (ST), Shifting Attention Test (SAT) and Four Part Continuous Performance Test (FPCPT) using Cognitrax, which is a software for testing