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P.1.j.010 Neuropsychological profiles in periventricular nodular heterotopia
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P.1.j. Basic and clinical neuroscience − Cognitive neuroscience
cognitive insight is influenced by several clinical and therapeutic characteristics of the patient to be taken into account in the management of the illness. References [1] Koren D., Seidman L.J., Poyurovsky M., 2004. The neuropsychological basis of insight in first-episode schizophrenia: a pilot metacognitive study. Schizophr Res 70, 195–202. [2] Quiles C., Prouteau A., Verdoux H., 2013. Characteristics and impact of metacognitive deficits in schizophrenia. L’enc´ephale 39, 123–129. [3] Saperstein M.A., Thysen I., Medalia A., 2012. The Measure of insight into cognition: Reliability and validity of clinician-rated and selfreport scales of neurocognitive insight of schizophrenia. Schizophrenia Research 134, 54−58.
P.1.j.009 Neurocognitive subtypes in patients with schizophrenia and their associated clinical features J. Ospina-Duque1 ° , A. Rangel2 , J. Garcia2 , C. Palacio1 , E.T. Al3 Group on Psychiatry. School of Medicine University of Antioquia, Department of Psychiatry, Medellin, Colombia; 2 School of Medicine University of Antioquia, Department of Psychiatry, Medellin, Colombia; 3 Universidad de Antioquia Universidad Pontificia Bolivariana y Universidad Nacional, Departments of Psychiatry Biology and Basic Science, Medellin, Colombia 1 Research
Background: The vast majority of patients with schizophrenia have cognitive deficits. As neuropsychological variables are more suitable for empirical research (e.a. as endophenotypes) several groups have proposed the neurocognitive subtyping of schizophrenia [1]. Once identified, these neurocognitive subtypes would permit to examine their relationships with clinical and non-clinical variables, in order to improve diagnostic accuracy, prognosis and treatment [2]. Objective: To identify empirically-based neurocognitive subtypes in patients with chronic schizophrenia and determine its association with clinical characteristics. Methods: This is a cross-sectional study that is part of a larger research on neuropsychological endophenotypes in schizophrenia. The sample consists of 253 subjects with schizophrenia. Inclusion criteria were: age 18 to 65 years old, diagnosis of schizophrenia according to DSM-IV-TR [3] and clinical stability during the last month. Patients with hospitalization in the last month and some characteristics that could impede realization of tests or alter their results, such as illiteracy, visual or hearing disabilities, use of benzodiazepines in the past month, use of psychoactive substances (except nicotine) in the past six months, electro convulsive therapy in the past six months, significant traumatic brain injury (loss of consciousness for more than 15 minutes or neurological squeals) or neurological diseases such as epilepsy, dementia, mental retardation or other neurodegenerative disorders were excluded. Patients were assessed using neuropsychological tests for sustained attention, executive function, facial emotion recognition, verbal learning and working memory. In order to identify the neurocognitive subtypes of schizophrenia, a latent class analysis was performed using Latent Gold 4.5 statistical program. Once neurocognitive subtypes were identified their association with clinical characteristics was examined. Results: We identified four neurocognitive subtypes: (a) Global Cognitive Deficit; (b) Memory and Executive Function Deficit; (c) Memory and Facial Emotion Recognition Deficit; and
(d) A group Without Cognitive Deficit. Patients with the subtypes ‘Memory and Executive Function Deficit’ and ‘Global Cognitive Deficit’ had a higher frequency of male sex, unemployment, severe impairment, and good adherence to treatment than the patients with the subtype ‘Without Cognitive Deficit’. Patients with the ‘Global Cognitive Deficit’ subtype had a lower frequency of past major depressive episodes (OR 0.39; 95% CI: 0.16 to 0.97) and suicide attempts. The patients with ‘Memory and Facial Recognition Deficit’ had a higher probability of severe impairment (OR 5.52; 95% CI: 1.89 to 16.14) and of being unemployed (OR 2.43; 95% CI: 1.06 to 5.55), but also a lower probability of past depressive episodes (OR 0.21; 95% CI: 0.07 to 0.66). Patients without cognitive impairment had a history of increased affective symptomatology. Conclusion: Our results suggest the existence of a spectrum of cognitive impairment in subjects with schizophrenia, which is divided into four neurocognitive subtypes according to the degree and type of commitment, which in turn are related to factors of functional impairment, severity and affective symptomatology. Using neuropsychological characteristics can provide valuable information for improving classification, course assessment and treatment of schizophrenia [3]. References [1] Szendi I, Racsm´any M, Cimmer C, Csifcs´ak G, Kov´acs ZA, Szekeres G, et al., 2010. Two subgroups of schizophrenia identified by systematic cognitive neuropsychiatric mapping. European Archives of Psychiatry and Clinical Neuroscience;260(3):257−66. [2] Hill SK, Ragland JD, Gur RC, Gur RE., 2002. Neuropsychological profiles delineate distinct profiles of schizophrenia, an interaction between memory and executive function, and uneven distribution of clinical subtypes. Journal of Clinical and Experimental Neuropsychology;24(6):765−80. [3] Jablensky A., 2006. Subtyping schizophrenia: implications for genetic research. Molecular Psychiatry.;11(9):815−36.
P.1.j.010 Neuropsychological profiles in periventricular nodular heterotopia K. Kurzbuch1 ° , E. Pauli1 , B.S. Chang2 , K. Romatoski2 , M.E. Barnard2 , B.S. Kasper1 1 University of Erlangen, Dept. of Neurology/Epilepsy Center, Erlangen, Germany; 2 Beth Israel Deaconess Medical Center/Harvard Medical School, Dept. of Neurology, Boston, USA Purpose: Periventricular nodular heterotopia (PNH) is a developmental cerebral malformation caused by aberrant neural migration and is often accompanied by epilepsy. A common form of PNH is inherited in an X-linked fashion via filamin A mutation and therefore mainly, but not exclusively, affects females. On MRI, patients typically show bilateral, often confluent, nodules of heterotopic gray matter along the lateral ventricular walls. Knowledge about cognitive functioning of these patients remains incomplete, but is generally described as normal, except for reading impairment [1,2]. In this study, neuropsychological features of a larger PNH cohort are reported. Methods: 25 patients with PNH and epilepsy were included. Following cognitive functions were examined by standard neuropsychological tests: Intelligence, working memory, focused attention, visuospatial memory, incidental memory, verbal memory, figural short term memory, naming, fluency and reading. Volumetric analyses of the fractional heterotopic tissue in relation to cortical volume were achieved in 8 patients.
P.1.j. Basic and clinical neuroscience − Cognitive neuroscience Results: Average intelligence quotient was M = 95.4 (SD = 15.9), ranging from 50 to 124. Neuropsychological assessment showed a group performance within the average to low range in all cognitive subtests: digit span forward (z = −0.6; SD = 1.0), digit span backward (z = −0.7; SD = 1.2), focused attention (z = −0.9; SD = 1.2), visuospatial memory (z = 0.0; SD = 0.8), incidental memory (z = −0.1; SD = 0.8), verbal memory (z = −0.9; SD = 1.0), figural short term memory (z = −0.4; SD = 1.2), naming (z = −1.0; SD = 1.0), fluency (z = −0.9; SD = 1.1), reading (z = −0.9; SD = 1.1). Regarding individual patients’ results, the performance span showed to be extensive, ranging from significant impairment to unimpaired cognition (e.g. z = −3.0 to z = 1.5). Furthermore, individual cognitive profiles revealed interesting performance patterns with specific deficits among a generally unimpaired performance or vice versa. Fractional PNH volumes ranged from 0.5% to 2.9%, with a mean of 1.3% (SD = 0.8). Intelligence and cognitive performance seem not correlated to fractional volumes of heterotopic tissue. Regression analysis showed that heterotopia volume explains only 10% of variance in cognitive functioning, including reading performance. Conclusion: Our data illustrated an overall average to mildly impaired cognitive performance for the whole PNH group, but a remarkable variation of capacity regarding individual patients. Individuals might attain good subtest results despite being globally impaired, or show selective impairment despite appearing ‘normal’ by global impression. Cognitive profiles, including reading ability, did not correlate to fractional PNH volume in 8 subjects analyzed. Thus, we observed good performance in patients with more severe PNH, but also impaired performance in patients with slight PNH. Whether differences are explained by epilepsy severity, duration or other factors remains to be clarified. The results underline the importance of a more systematic approach to individual neuropsychological testing in patients with PNH in order to reveal individual specific cognitive impairment, but also resources of capacity. References [1] Chang BS, Ly J, Appignani B, Bodell A, Apse KA, Ravenscroft RS, Sheen VL, Doherty MJ, Hackney DB, O’Connor M, Galaburda AM, Walsh CA. Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia. Neurology 2005; 64:799–803. [2] Chang BS, Katzir T, Liu T, Corriveau K, Barzillai M, Apse KA, Bodell A, Hackney D, Alsop D, Wong S, Walsh CA. A structural basis for reading fluency. Neurology 2007; 69: 2146–2154.
P.1.j.011 Positive modulation at alpha5 GABAA receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats T. Timic Stamenic1 ° , S. Joksimovic1 , M. Milic1 , B. Batinic2 , M.M. Poe3 , J.M. Cook3 , M.M. Savic1 1 University of Belgrade, Institute of Pharmacology, Belgrade, Serbia; 2 University of Belgrade, Institute of Physiology, Belgrade, Serbia; 3 University of Wisconsin − Milwaukee, Department of Chemistry and Biochemistry, Milwaukee, USA Purpose of the study: It is postulated that cognitive impairments in schizophrenia are caused in part by hypofunction of NMDA receptors. NMDA receptor antagonist, MK-801, induces dosedependent changes in animal behavior and disrupts learning and memory [1]. Although potentiating effects of negative modulators at a5 GABAA receptors on memory processes have been
S325
repeatedly shown, the role of these receptors in cognitive deficits associated with schizophrenia is somewhat controversial. Recently, it has been shown that SH-053−2 F-R-CH3 , a positive, rather than negative, allosteric modulator at a5 GABAA receptors, could be beneficial in resolving pathological changes observed in one of the established animal models of schizophrenia [2]. The aim of our study was to examine the influence of SH-I-75, as one of the most selective positive allosteric modulators at a5 GABAA receptors and a close congener of SH-053−2 F-R-CH3 , on cognitive deficits induced by MK-801 in rats. Methods used: The water maze apparatus consisted of a circular 2 m diameter pool filled to a height of 30 cm with water, containing the escape platform (10x15 cm) submerged 2 cm below the water surface. Male Wistar rats received treatment 20 min before a swimming block, each day for 5 consecutive days (acquisition). Treatments were saline, 0.1 mg/kg MK-801 and combinations of 0.1 mg/kg MK-801 with 0.5, 2 or 5 mg/kg SH-I75. To assess reference memory at the end of learning, a probe trial was given 24 h after the last acquisition day. The behavior was recorded by a digital camera and analyzed by the tracking software. Summary of results: In acquisition study two-way ANOVA with repeated measures showed that factor Days was significant [F(4,132) = 3.857, p = 0.005] for mean speed, while factors Treatment and Days were significant for latency [F(4,33) = 6.354, p < 0.001; F(4,132) = 42.928, p < 0.001, respectively] and total distance [F(4,33) = 6.137, p < 0.001; F(4,132) = 42.749, p < 0.001, respectively]. SNK post hoc comparisons showed that there were differences between control rats and all other treatments. In probe trial, one-way ANOVA was significant for several parameters [time in peripheral ring F(4,33) = 10.571, p < 0.001; distance traveled in the target zone F(4,33) = 12.480, p < 0.001; path efficiency to first entry to the target zone F(4,33) = 3.110, p = 0.028]. For time in peripheral ring, post hoc test reveled differences between control rats and all treatments, while for path efficiency to first entry to the target zone only rats treated with MK-801 and 2 mg/kg SH-I-75 differed from control rats (p < 0.05). Rats treated with MK-801 swam significantly less in the target zone when compared to control rats [mean± SEM distance (m) for control and MK-801 treated rats: 2.20±0.39 vs. 1.06±1.19; p = 0.001]; moreover, the animals treated with combination of MK-801 and SH-I75 tended to swim even less than those treated with MK-801 alone (mean distances for 0.1 mg/kg MK-801 combined with 0.5 mg/kg, 2 mg/kg and 5 mg/kg SH-I-75: 0.60±0.08 m, 0.44±0.16 m and 0.44±0.10 m, with p values in comparison with MK-801: 0.120, 0.099, 0.163, respectively). Conclusions: Positive modulation of a5 GABAA receptors elicited by SH-I-75 did not affect acquisition impairment induced by MK-801, but did further increase the memory retrieval impairment assessed during probe trial. References [1] van der Staay, F.J., Rutten, K., Erb, C., Blokland, A., 2011 Effects of the cognition impairer MK-801 on learning and memory in mice and rats. Behav Brain Res. 220, 215–229. [2] Gill, K.M., Lodge, D.J., Cook, J.M., Aras, S., Grace, A.A., 2011 A novel a5GABA(A)R-positive allosteric modulator reverses hyperactivation of the dopamine system in the MAM model of schizophrenia. Neuropsychopharmacology 36, 1903–1911.
P.1.j. Basic and clinical neuroscience − Cognitive neuroscience
cognitive insight is influenced by several clinical and therapeutic characteristics of the patient to be taken into account in the management of the illness. References [1] Koren D., Seidman L.J., Poyurovsky M., 2004. The neuropsychological basis of insight in first-episode schizophrenia: a pilot metacognitive study. Schizophr Res 70, 195–202. [2] Quiles C., Prouteau A., Verdoux H., 2013. Characteristics and impact of metacognitive deficits in schizophrenia. L’enc´ephale 39, 123–129. [3] Saperstein M.A., Thysen I., Medalia A., 2012. The Measure of insight into cognition: Reliability and validity of clinician-rated and selfreport scales of neurocognitive insight of schizophrenia. Schizophrenia Research 134, 54−58.
P.1.j.009 Neurocognitive subtypes in patients with schizophrenia and their associated clinical features J. Ospina-Duque1 ° , A. Rangel2 , J. Garcia2 , C. Palacio1 , E.T. Al3 Group on Psychiatry. School of Medicine University of Antioquia, Department of Psychiatry, Medellin, Colombia; 2 School of Medicine University of Antioquia, Department of Psychiatry, Medellin, Colombia; 3 Universidad de Antioquia Universidad Pontificia Bolivariana y Universidad Nacional, Departments of Psychiatry Biology and Basic Science, Medellin, Colombia 1 Research
Background: The vast majority of patients with schizophrenia have cognitive deficits. As neuropsychological variables are more suitable for empirical research (e.a. as endophenotypes) several groups have proposed the neurocognitive subtyping of schizophrenia [1]. Once identified, these neurocognitive subtypes would permit to examine their relationships with clinical and non-clinical variables, in order to improve diagnostic accuracy, prognosis and treatment [2]. Objective: To identify empirically-based neurocognitive subtypes in patients with chronic schizophrenia and determine its association with clinical characteristics. Methods: This is a cross-sectional study that is part of a larger research on neuropsychological endophenotypes in schizophrenia. The sample consists of 253 subjects with schizophrenia. Inclusion criteria were: age 18 to 65 years old, diagnosis of schizophrenia according to DSM-IV-TR [3] and clinical stability during the last month. Patients with hospitalization in the last month and some characteristics that could impede realization of tests or alter their results, such as illiteracy, visual or hearing disabilities, use of benzodiazepines in the past month, use of psychoactive substances (except nicotine) in the past six months, electro convulsive therapy in the past six months, significant traumatic brain injury (loss of consciousness for more than 15 minutes or neurological squeals) or neurological diseases such as epilepsy, dementia, mental retardation or other neurodegenerative disorders were excluded. Patients were assessed using neuropsychological tests for sustained attention, executive function, facial emotion recognition, verbal learning and working memory. In order to identify the neurocognitive subtypes of schizophrenia, a latent class analysis was performed using Latent Gold 4.5 statistical program. Once neurocognitive subtypes were identified their association with clinical characteristics was examined. Results: We identified four neurocognitive subtypes: (a) Global Cognitive Deficit; (b) Memory and Executive Function Deficit; (c) Memory and Facial Emotion Recognition Deficit; and
(d) A group Without Cognitive Deficit. Patients with the subtypes ‘Memory and Executive Function Deficit’ and ‘Global Cognitive Deficit’ had a higher frequency of male sex, unemployment, severe impairment, and good adherence to treatment than the patients with the subtype ‘Without Cognitive Deficit’. Patients with the ‘Global Cognitive Deficit’ subtype had a lower frequency of past major depressive episodes (OR 0.39; 95% CI: 0.16 to 0.97) and suicide attempts. The patients with ‘Memory and Facial Recognition Deficit’ had a higher probability of severe impairment (OR 5.52; 95% CI: 1.89 to 16.14) and of being unemployed (OR 2.43; 95% CI: 1.06 to 5.55), but also a lower probability of past depressive episodes (OR 0.21; 95% CI: 0.07 to 0.66). Patients without cognitive impairment had a history of increased affective symptomatology. Conclusion: Our results suggest the existence of a spectrum of cognitive impairment in subjects with schizophrenia, which is divided into four neurocognitive subtypes according to the degree and type of commitment, which in turn are related to factors of functional impairment, severity and affective symptomatology. Using neuropsychological characteristics can provide valuable information for improving classification, course assessment and treatment of schizophrenia [3]. References [1] Szendi I, Racsm´any M, Cimmer C, Csifcs´ak G, Kov´acs ZA, Szekeres G, et al., 2010. Two subgroups of schizophrenia identified by systematic cognitive neuropsychiatric mapping. European Archives of Psychiatry and Clinical Neuroscience;260(3):257−66. [2] Hill SK, Ragland JD, Gur RC, Gur RE., 2002. Neuropsychological profiles delineate distinct profiles of schizophrenia, an interaction between memory and executive function, and uneven distribution of clinical subtypes. Journal of Clinical and Experimental Neuropsychology;24(6):765−80. [3] Jablensky A., 2006. Subtyping schizophrenia: implications for genetic research. Molecular Psychiatry.;11(9):815−36.
P.1.j.010 Neuropsychological profiles in periventricular nodular heterotopia K. Kurzbuch1 ° , E. Pauli1 , B.S. Chang2 , K. Romatoski2 , M.E. Barnard2 , B.S. Kasper1 1 University of Erlangen, Dept. of Neurology/Epilepsy Center, Erlangen, Germany; 2 Beth Israel Deaconess Medical Center/Harvard Medical School, Dept. of Neurology, Boston, USA Purpose: Periventricular nodular heterotopia (PNH) is a developmental cerebral malformation caused by aberrant neural migration and is often accompanied by epilepsy. A common form of PNH is inherited in an X-linked fashion via filamin A mutation and therefore mainly, but not exclusively, affects females. On MRI, patients typically show bilateral, often confluent, nodules of heterotopic gray matter along the lateral ventricular walls. Knowledge about cognitive functioning of these patients remains incomplete, but is generally described as normal, except for reading impairment [1,2]. In this study, neuropsychological features of a larger PNH cohort are reported. Methods: 25 patients with PNH and epilepsy were included. Following cognitive functions were examined by standard neuropsychological tests: Intelligence, working memory, focused attention, visuospatial memory, incidental memory, verbal memory, figural short term memory, naming, fluency and reading. Volumetric analyses of the fractional heterotopic tissue in relation to cortical volume were achieved in 8 patients.
P.1.j. Basic and clinical neuroscience − Cognitive neuroscience Results: Average intelligence quotient was M = 95.4 (SD = 15.9), ranging from 50 to 124. Neuropsychological assessment showed a group performance within the average to low range in all cognitive subtests: digit span forward (z = −0.6; SD = 1.0), digit span backward (z = −0.7; SD = 1.2), focused attention (z = −0.9; SD = 1.2), visuospatial memory (z = 0.0; SD = 0.8), incidental memory (z = −0.1; SD = 0.8), verbal memory (z = −0.9; SD = 1.0), figural short term memory (z = −0.4; SD = 1.2), naming (z = −1.0; SD = 1.0), fluency (z = −0.9; SD = 1.1), reading (z = −0.9; SD = 1.1). Regarding individual patients’ results, the performance span showed to be extensive, ranging from significant impairment to unimpaired cognition (e.g. z = −3.0 to z = 1.5). Furthermore, individual cognitive profiles revealed interesting performance patterns with specific deficits among a generally unimpaired performance or vice versa. Fractional PNH volumes ranged from 0.5% to 2.9%, with a mean of 1.3% (SD = 0.8). Intelligence and cognitive performance seem not correlated to fractional volumes of heterotopic tissue. Regression analysis showed that heterotopia volume explains only 10% of variance in cognitive functioning, including reading performance. Conclusion: Our data illustrated an overall average to mildly impaired cognitive performance for the whole PNH group, but a remarkable variation of capacity regarding individual patients. Individuals might attain good subtest results despite being globally impaired, or show selective impairment despite appearing ‘normal’ by global impression. Cognitive profiles, including reading ability, did not correlate to fractional PNH volume in 8 subjects analyzed. Thus, we observed good performance in patients with more severe PNH, but also impaired performance in patients with slight PNH. Whether differences are explained by epilepsy severity, duration or other factors remains to be clarified. The results underline the importance of a more systematic approach to individual neuropsychological testing in patients with PNH in order to reveal individual specific cognitive impairment, but also resources of capacity. References [1] Chang BS, Ly J, Appignani B, Bodell A, Apse KA, Ravenscroft RS, Sheen VL, Doherty MJ, Hackney DB, O’Connor M, Galaburda AM, Walsh CA. Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia. Neurology 2005; 64:799–803. [2] Chang BS, Katzir T, Liu T, Corriveau K, Barzillai M, Apse KA, Bodell A, Hackney D, Alsop D, Wong S, Walsh CA. A structural basis for reading fluency. Neurology 2007; 69: 2146–2154.
P.1.j.011 Positive modulation at alpha5 GABAA receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats T. Timic Stamenic1 ° , S. Joksimovic1 , M. Milic1 , B. Batinic2 , M.M. Poe3 , J.M. Cook3 , M.M. Savic1 1 University of Belgrade, Institute of Pharmacology, Belgrade, Serbia; 2 University of Belgrade, Institute of Physiology, Belgrade, Serbia; 3 University of Wisconsin − Milwaukee, Department of Chemistry and Biochemistry, Milwaukee, USA Purpose of the study: It is postulated that cognitive impairments in schizophrenia are caused in part by hypofunction of NMDA receptors. NMDA receptor antagonist, MK-801, induces dosedependent changes in animal behavior and disrupts learning and memory [1]. Although potentiating effects of negative modulators at a5 GABAA receptors on memory processes have been
S325
repeatedly shown, the role of these receptors in cognitive deficits associated with schizophrenia is somewhat controversial. Recently, it has been shown that SH-053−2 F-R-CH3 , a positive, rather than negative, allosteric modulator at a5 GABAA receptors, could be beneficial in resolving pathological changes observed in one of the established animal models of schizophrenia [2]. The aim of our study was to examine the influence of SH-I-75, as one of the most selective positive allosteric modulators at a5 GABAA receptors and a close congener of SH-053−2 F-R-CH3 , on cognitive deficits induced by MK-801 in rats. Methods used: The water maze apparatus consisted of a circular 2 m diameter pool filled to a height of 30 cm with water, containing the escape platform (10x15 cm) submerged 2 cm below the water surface. Male Wistar rats received treatment 20 min before a swimming block, each day for 5 consecutive days (acquisition). Treatments were saline, 0.1 mg/kg MK-801 and combinations of 0.1 mg/kg MK-801 with 0.5, 2 or 5 mg/kg SH-I75. To assess reference memory at the end of learning, a probe trial was given 24 h after the last acquisition day. The behavior was recorded by a digital camera and analyzed by the tracking software. Summary of results: In acquisition study two-way ANOVA with repeated measures showed that factor Days was significant [F(4,132) = 3.857, p = 0.005] for mean speed, while factors Treatment and Days were significant for latency [F(4,33) = 6.354, p < 0.001; F(4,132) = 42.928, p < 0.001, respectively] and total distance [F(4,33) = 6.137, p < 0.001; F(4,132) = 42.749, p < 0.001, respectively]. SNK post hoc comparisons showed that there were differences between control rats and all other treatments. In probe trial, one-way ANOVA was significant for several parameters [time in peripheral ring F(4,33) = 10.571, p < 0.001; distance traveled in the target zone F(4,33) = 12.480, p < 0.001; path efficiency to first entry to the target zone F(4,33) = 3.110, p = 0.028]. For time in peripheral ring, post hoc test reveled differences between control rats and all treatments, while for path efficiency to first entry to the target zone only rats treated with MK-801 and 2 mg/kg SH-I-75 differed from control rats (p < 0.05). Rats treated with MK-801 swam significantly less in the target zone when compared to control rats [mean± SEM distance (m) for control and MK-801 treated rats: 2.20±0.39 vs. 1.06±1.19; p = 0.001]; moreover, the animals treated with combination of MK-801 and SH-I75 tended to swim even less than those treated with MK-801 alone (mean distances for 0.1 mg/kg MK-801 combined with 0.5 mg/kg, 2 mg/kg and 5 mg/kg SH-I-75: 0.60±0.08 m, 0.44±0.16 m and 0.44±0.10 m, with p values in comparison with MK-801: 0.120, 0.099, 0.163, respectively). Conclusions: Positive modulation of a5 GABAA receptors elicited by SH-I-75 did not affect acquisition impairment induced by MK-801, but did further increase the memory retrieval impairment assessed during probe trial. References [1] van der Staay, F.J., Rutten, K., Erb, C., Blokland, A., 2011 Effects of the cognition impairer MK-801 on learning and memory in mice and rats. Behav Brain Res. 220, 215–229. [2] Gill, K.M., Lodge, D.J., Cook, J.M., Aras, S., Grace, A.A., 2011 A novel a5GABA(A)R-positive allosteric modulator reverses hyperactivation of the dopamine system in the MAM model of schizophrenia. Neuropsychopharmacology 36, 1903–1911.