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P.1.i.004 Resting-state functional connectivity in temporal lobe epilepsy patients with affective symptoms
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P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation
Additionally, both AD and ADT were found to have decreased axial diffusivity in left uncinate fasciculus, compared to TDC (p = 0.006 and p = 0.040, respectively). Conclusions: Our resultssuggested that the right caudate shape can be a sensitive neuroimaging marker for coexisting tic disorder in ADHD, and the aberrant anatomical connectivity in left frontotemporal network is a distinguishing one between ADHD and TDC. References [1] Castellanos, F.X., Giedd, J.N., Hamburger, S.D., Marsh, W.L., & Rapoport, J.L. (1996), Brain morphometry in Tourette’s syndrome. The influence of comorbid attention-deficit/hyperactivity disorder. Neurology, vol. 47, no. 6, pp. 1581–1583. [2] Castellanos, F.X., Lee, P.P., Sharp, W., Jeffries, N.O., Greenstein, D.K., Clasen, L.S., Blumenthal, J.D., James, R.S., Ebens, C.L., Walter, J.M., Zijdenbos, A., Evans, A.C., Giedd, J.N., & Rapoport, J.L. (2002) Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA: the journal of the American Medical Association, vol. 288, no. 14, pp. 1740–1748.
P.1.i.003 Clinical characteristics of vascular depression in Korean elderly people
Results: Vascular depression group was significantly poorer performance in verbal fluency, Bos-ton naming test, Mini-Mental State Examination, trail making test B and stroop test (p < 0.05). Fur-thermore, trail making test B and stroop test performance was correlated with white matter hyper-intensity severity. However, Hamilton Depression Scale score was not significantly different between non vascular group and vascular group. In terms of the subitem score of Hamilton Depression Scale was not significantly different between two groups. There was no significant correlation between the total Hamilton Depression Scale score and the Fazekas Scale score. Conclusion: In this study, we try to find out the clinical characteristics of vascular depression among Korean population. Several findings from our study suggest that white matter hyperintensity is associ-ated with neuropsychological performance, especially executive function. Moreover, executive dys-function might contribute to poor treatment outcome of vascular depression group. Meanwhile, in this study, there were no clinically significant differences in terms of depression severity between non vascular group and vascular group. Furthermore, there were no significant correlation between depression severity and the degree of white matter hyperintensity severity.
T. Jun1 ° , H.J. Go2 1 Catholic University of Korea, Seoul, South-Korea; 2 Catholic University of Korea Daejeon St. Mary’s Hospital, Psychiatry, Daejeon, South-Korea
P.1.i.004 Resting-state functional connectivity in temporal lobe epilepsy patients with affective symptoms
Objectives: Geriatric depression is associated with high morbidity and mortality, and is also associated with poor psychosocial dysfunction and high socioeconomic burden. In addition, despite the development of psychopharmacology in treating depression, there are still many patients with geriatric depression who showed inadequate treatment response to standard antidepressant treatment. Those who show inadequate response are known to be associated with higher rate of relapse of depression. Recently many research data are accumulated that reports that neurodegenerative changes with age are related to poor treatment response of the patients with geriatric depression. Especially, there are increasing findings that showed white matter hyperintensity suggesting ischemic changes of the brain could be related to the development of late life depression which is refractory to treatment. This study was done in Korean elderly people in order to examine the relationship of white matter hyperintensity with clinical neuropsychological function and depression symptom se-verity. Methods: A total of 148 subjects diagnosed first major depressive episode after age of 60 years were included. Those who had other neurological and medical conditions that could cause impaired cognitive function, who had other psychiatric illness, who had unstable medical condition, and who had significant laboratory abnormalities were excluded from this study. Brain magnetic resonance imaging scan was rated with the modified Fazekas White Matter Rating Scale by researcher blinded to clinical information. Cognitive function was evaluated with a comprehensive neurological battery and depression severity was assessed by Hamilton De-pression Scale. Subjects were divided into vascular depression group and non vascular group ac-cording to the degree of white matter hyperintensity. Independent t-test was used to compare clini-cal difference between two groups and correlation analysis was used to identify whether white matter hyperintensity severity is correlated with neuropsychological function and depression symp-tom.
L. Shmeleva1 ° , M. Kissin1 1 Saint-Petersburg State I. Pavlov Medical University, Department of Psychiatry, Saint-Petersburg, Russia Introduction: Affective symptoms, especially depression and anxiety, are the most frequently psychiatric symptoms in patients with temporal lobe epilepsy (TLE) [1]. On the other hand, resting state functional connectivity disturbances and disconnections in biological neuronal networks are two remarkable characteristics of TLE [2]. The aim of the study was to investigate functional connectivity (FC) in resting-state networks (RSNs) in TLE patients with anxiety-depressive symptoms. Materials and Methods: 54 patients with TLE, confirmed by EEG, between 18 and 50, without any significant brain alterations and history of other psychiatric disorders were included in this study. The psychiatric interview with use of scales (Beck Depression Inventory, Hospital Anxiety Depressive Scale, Hamilton ˚ Anxiety Scale and Montgomery–Asberg Depressive Rating Scale) was used to assess affective symptoms. All subjects underwent 9-min resting-state fMRI session. The subjects were asked to stay at rest during the procedure without task, keeping eyes closed. The data was processed and analyzed using SPM8 and ‘GIFT’ toolbox. Independent component analysis was used to isolate RSNs. The resulted maps were compared in groups using one-way ANOVA and two-sample t-test. The results were considered as statistically significant according to threshold of p < 0.005 with a 10-voxel cluster size [3]. Results: Based on clinical examination and EEG results, all patients were divided into three groups: patients with current affective disorders and left sided epileptic focus localization [leftsided ‘affective’ group (LSAG), n = 18], patients with affective disorders and right-sided focus localization [right-sided ‘affective’ group (RSAG), n = 18], and patients without affective disorders
P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation [non-affective group (NAG), n = 18]. In both groups with affective symptoms, a moderate level of depressive and anxiety symptoms (HAMA: 25.4±2.6; MADRS: 20.1±2.6) was found. There are 8 RSNs were identified: visual, audial, sensomotor, frontotemporal dorsal and ventral, frontoparietal right and left, default mode networks. The main interest of this study was to identify FC features more in key nodes of DMN then in other RSN’s. This interest was based on knowledge, that that key nodes of DMN, localized as well in temporal lobe, are involved in emotional processing and may play a significant role in the origin of affective symptoms. Conclusions: Significantly increased FC was identified in the left insula, superior parietal cortex, left frontal cortex, right precuneus, right parahippocampal gyrus, right frontal cortex in patient’s groups with affective symptoms in comparison NAG. Increased FC in these nodes of neuronal networks can be explained by the presence of affective symptoms in this groups and their association with epileptic processes themselves. These significant advances in imaging represent not only an opportunity to investigate psychopathological features of TLE, but perhaps may play important role in aspects of complex therapy. To finalize, TLE can be considered as a good model to investigate and analyze FC features within the RSNs and may improve our understanding of neuropathological mechanisms not only in epilepsy, but also in many other brain and mental disorder. References [1] Kemmotsu, N., Kucukboyaci, N.E., Cheng, C.E., Girard, H.M., Tecoma, E.S., Iragui, V.J., McDonald, C.R., 2013. Alterations in functional connectivity between the hippocampus and prefrontal cortex as a correlate of depressive symptoms in temporal lobe epilepsy. Epilepsy Behav. 29, 552−9. [2] Luo, C., Qiu, C., Guo, Z., Fang, J., Li, Q., Lei, X., Xia, Y., Lai, Y., Gong, Q., Zhou, D., Yao, D. Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study. PLoS One, 7 doi: 10.1371/ journal.pone.0028196. [3] Lieberman, M.D., Cunningham, W.A., 2009. Type I and Type II error concerns in fMRI research: re-balancing the scale. Soc. Cogn. Affect. Neurosci. 4, 423−8.
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Methods: Thirty-one euthymic BD type I patients (16 females; mean age 26.4 years) and thirty-one healthy controls (16 females, mean age 26.8 years) matched by age and gender underwent 1 Hproton 3T MRS to measure levels of GABA, glutamate (Glu) and glutamine (Gln) in the prefrontal cortex (PFC) (2×2×4.5 cm3 ) using JPRESS sequence TE variable. Spectra with CRLBs>15 were excluded. All BD subjects to be included in this study had to be in euthymia (Young mania rating scale <7 and Hamilton depression rating scale <7 for at least 3 months). All healthy controls had no current or past history of psychiatric disorder according to the evaluation conducted by trained psychiatrists using The Mini International Neuropsychiatric Interview (MINI). Similarly, all subjects had no family history (first degree relatives) of mood or psychotic disorders and had not been in use of psychotropic medicine or substance abuse over the last three months. Results: Neither age or gender influenced metabolite levels in the PFC. GABA/Cre and Glu/Cre levels in BD were not different from controls; Gln/Cre levels were 13% higher in BD (F = 4.9 p = 0.03) than in healthy controls, moreover, Gln/Glu ratio was 27% higher in BD (F = 7.48 p = 0.008). Medication use (benzodiazepines, lithium, anticonvulsants and antipsychotics) did not influenced metabolite levels. Bipolar disorder subjects had worse working memory performance than controls. Working memory tests (SCWT) negatively correlated with GABA/Cre levels in healthy controls (p = 0.01 R .44) but not with BD subjects. Conclusion: This was the biggest sample size GABA and glutamine MRS study in BD type I done so far. Previous MRS studies in BD subjects evaluating glutamate and glutamine levels did not show a clear pattern in the hippocampus, occipital and frontal cortex. Moreover they included subjects during different mood episodes in the same sample. We did not find alteration on GABA levels in the PFC compared to controls but we found higher levels of Gln in medicated euthymic BD. The present findings reinforce a key role for glutamatergic system dysfunction in the pathophysiology of BD. References
P.1.i.005 Prefrontal cortex gamma-aminobutyric acid levels in bipolar I disorder determined using proton magnetic resonance spectroscopy M. Soeiro-de-Souza1 ° , M.C.G. Otaduy1 , R.A. Moreno1 , D.H. Moreno1 , H. Vallada1 1 Institute of Psychiatry of S˜ao Paulo Medical School, Psychiatry, S˜ao Paulo, Brazil Bipolar disorder (BD) has been consistently associated with glutamatergic abnormalities in the tripartite synapse [1]. Evidences from magnetic resonance spectroscopy (MRS) studies report altered glutamate (Glu) and glutamine in subjects with BD [2]. Glutamate excess is known to lead to excitotoxicity and apoptosis [3], associated with changes in intracellular calcium regulation. Abnormalities associated with g-aminobutyric acid (GABA), the major inhibitory neurotransmitter in central nervous system, have been heterogeneously described in BD. Moreover, medications that modulate GABA function have been used to treat BD mood episodes. Magnetic resonance spectroscopy (MRS) allows detecting in vivo measurements of brain metabolites, and the few studies that measured GABA in BD had controversial results, due to differences in technics, voxel, clinical symptoms, medications and region of interest.
[1] Machado-Vieira R, Manji HK, Zarate CA. The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disorders. Neuroscientist. 2009 Oct; 15(5): 525−39. ¨ ur D. Magnetic resonance spectroscopy studies of [2] Y¨uksel C, Ong¨ glutamate-related abnormalities in mood disorders. Biol Psychiatry. 2010 Nov 1; 68(9): 785−94. [3] Hashimoto R, Hough C, Nakazawa T, Yamamoto T, Chuang DM. Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J Neurochem. 2002 Feb; 80(4): 589−97.
P.1.i.006 Brain white matter connectivity associated with treatment response to paliperidone ER treatment in patients with schizophrenia M. Kim1 ° , B. Kim1 , J. Kim2 , T. Choi1 , T. Kim3 , S. Lee1 1 CHA University, Psychiatry, Sungnam, South-Korea; 2 Bundang Jaesaeng Hospital, Psychiatry, Sungnam, South-Korea; 3 Seoul Veterans Hospital, Psychiatry, Seoul, South-Korea Objective: Schizophrenia is a chronic and disabling psychiatric brain disorder that affects approximately 1% of the world’s population [1]. Although atypical antipsychotics were expected to be effective in improving various domains of symptoms in
P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation
Additionally, both AD and ADT were found to have decreased axial diffusivity in left uncinate fasciculus, compared to TDC (p = 0.006 and p = 0.040, respectively). Conclusions: Our resultssuggested that the right caudate shape can be a sensitive neuroimaging marker for coexisting tic disorder in ADHD, and the aberrant anatomical connectivity in left frontotemporal network is a distinguishing one between ADHD and TDC. References [1] Castellanos, F.X., Giedd, J.N., Hamburger, S.D., Marsh, W.L., & Rapoport, J.L. (1996), Brain morphometry in Tourette’s syndrome. The influence of comorbid attention-deficit/hyperactivity disorder. Neurology, vol. 47, no. 6, pp. 1581–1583. [2] Castellanos, F.X., Lee, P.P., Sharp, W., Jeffries, N.O., Greenstein, D.K., Clasen, L.S., Blumenthal, J.D., James, R.S., Ebens, C.L., Walter, J.M., Zijdenbos, A., Evans, A.C., Giedd, J.N., & Rapoport, J.L. (2002) Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA: the journal of the American Medical Association, vol. 288, no. 14, pp. 1740–1748.
P.1.i.003 Clinical characteristics of vascular depression in Korean elderly people
Results: Vascular depression group was significantly poorer performance in verbal fluency, Bos-ton naming test, Mini-Mental State Examination, trail making test B and stroop test (p < 0.05). Fur-thermore, trail making test B and stroop test performance was correlated with white matter hyper-intensity severity. However, Hamilton Depression Scale score was not significantly different between non vascular group and vascular group. In terms of the subitem score of Hamilton Depression Scale was not significantly different between two groups. There was no significant correlation between the total Hamilton Depression Scale score and the Fazekas Scale score. Conclusion: In this study, we try to find out the clinical characteristics of vascular depression among Korean population. Several findings from our study suggest that white matter hyperintensity is associ-ated with neuropsychological performance, especially executive function. Moreover, executive dys-function might contribute to poor treatment outcome of vascular depression group. Meanwhile, in this study, there were no clinically significant differences in terms of depression severity between non vascular group and vascular group. Furthermore, there were no significant correlation between depression severity and the degree of white matter hyperintensity severity.
T. Jun1 ° , H.J. Go2 1 Catholic University of Korea, Seoul, South-Korea; 2 Catholic University of Korea Daejeon St. Mary’s Hospital, Psychiatry, Daejeon, South-Korea
P.1.i.004 Resting-state functional connectivity in temporal lobe epilepsy patients with affective symptoms
Objectives: Geriatric depression is associated with high morbidity and mortality, and is also associated with poor psychosocial dysfunction and high socioeconomic burden. In addition, despite the development of psychopharmacology in treating depression, there are still many patients with geriatric depression who showed inadequate treatment response to standard antidepressant treatment. Those who show inadequate response are known to be associated with higher rate of relapse of depression. Recently many research data are accumulated that reports that neurodegenerative changes with age are related to poor treatment response of the patients with geriatric depression. Especially, there are increasing findings that showed white matter hyperintensity suggesting ischemic changes of the brain could be related to the development of late life depression which is refractory to treatment. This study was done in Korean elderly people in order to examine the relationship of white matter hyperintensity with clinical neuropsychological function and depression symptom se-verity. Methods: A total of 148 subjects diagnosed first major depressive episode after age of 60 years were included. Those who had other neurological and medical conditions that could cause impaired cognitive function, who had other psychiatric illness, who had unstable medical condition, and who had significant laboratory abnormalities were excluded from this study. Brain magnetic resonance imaging scan was rated with the modified Fazekas White Matter Rating Scale by researcher blinded to clinical information. Cognitive function was evaluated with a comprehensive neurological battery and depression severity was assessed by Hamilton De-pression Scale. Subjects were divided into vascular depression group and non vascular group ac-cording to the degree of white matter hyperintensity. Independent t-test was used to compare clini-cal difference between two groups and correlation analysis was used to identify whether white matter hyperintensity severity is correlated with neuropsychological function and depression symp-tom.
L. Shmeleva1 ° , M. Kissin1 1 Saint-Petersburg State I. Pavlov Medical University, Department of Psychiatry, Saint-Petersburg, Russia Introduction: Affective symptoms, especially depression and anxiety, are the most frequently psychiatric symptoms in patients with temporal lobe epilepsy (TLE) [1]. On the other hand, resting state functional connectivity disturbances and disconnections in biological neuronal networks are two remarkable characteristics of TLE [2]. The aim of the study was to investigate functional connectivity (FC) in resting-state networks (RSNs) in TLE patients with anxiety-depressive symptoms. Materials and Methods: 54 patients with TLE, confirmed by EEG, between 18 and 50, without any significant brain alterations and history of other psychiatric disorders were included in this study. The psychiatric interview with use of scales (Beck Depression Inventory, Hospital Anxiety Depressive Scale, Hamilton ˚ Anxiety Scale and Montgomery–Asberg Depressive Rating Scale) was used to assess affective symptoms. All subjects underwent 9-min resting-state fMRI session. The subjects were asked to stay at rest during the procedure without task, keeping eyes closed. The data was processed and analyzed using SPM8 and ‘GIFT’ toolbox. Independent component analysis was used to isolate RSNs. The resulted maps were compared in groups using one-way ANOVA and two-sample t-test. The results were considered as statistically significant according to threshold of p < 0.005 with a 10-voxel cluster size [3]. Results: Based on clinical examination and EEG results, all patients were divided into three groups: patients with current affective disorders and left sided epileptic focus localization [leftsided ‘affective’ group (LSAG), n = 18], patients with affective disorders and right-sided focus localization [right-sided ‘affective’ group (RSAG), n = 18], and patients without affective disorders
P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation [non-affective group (NAG), n = 18]. In both groups with affective symptoms, a moderate level of depressive and anxiety symptoms (HAMA: 25.4±2.6; MADRS: 20.1±2.6) was found. There are 8 RSNs were identified: visual, audial, sensomotor, frontotemporal dorsal and ventral, frontoparietal right and left, default mode networks. The main interest of this study was to identify FC features more in key nodes of DMN then in other RSN’s. This interest was based on knowledge, that that key nodes of DMN, localized as well in temporal lobe, are involved in emotional processing and may play a significant role in the origin of affective symptoms. Conclusions: Significantly increased FC was identified in the left insula, superior parietal cortex, left frontal cortex, right precuneus, right parahippocampal gyrus, right frontal cortex in patient’s groups with affective symptoms in comparison NAG. Increased FC in these nodes of neuronal networks can be explained by the presence of affective symptoms in this groups and their association with epileptic processes themselves. These significant advances in imaging represent not only an opportunity to investigate psychopathological features of TLE, but perhaps may play important role in aspects of complex therapy. To finalize, TLE can be considered as a good model to investigate and analyze FC features within the RSNs and may improve our understanding of neuropathological mechanisms not only in epilepsy, but also in many other brain and mental disorder. References [1] Kemmotsu, N., Kucukboyaci, N.E., Cheng, C.E., Girard, H.M., Tecoma, E.S., Iragui, V.J., McDonald, C.R., 2013. Alterations in functional connectivity between the hippocampus and prefrontal cortex as a correlate of depressive symptoms in temporal lobe epilepsy. Epilepsy Behav. 29, 552−9. [2] Luo, C., Qiu, C., Guo, Z., Fang, J., Li, Q., Lei, X., Xia, Y., Lai, Y., Gong, Q., Zhou, D., Yao, D. Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study. PLoS One, 7 doi: 10.1371/ journal.pone.0028196. [3] Lieberman, M.D., Cunningham, W.A., 2009. Type I and Type II error concerns in fMRI research: re-balancing the scale. Soc. Cogn. Affect. Neurosci. 4, 423−8.
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Methods: Thirty-one euthymic BD type I patients (16 females; mean age 26.4 years) and thirty-one healthy controls (16 females, mean age 26.8 years) matched by age and gender underwent 1 Hproton 3T MRS to measure levels of GABA, glutamate (Glu) and glutamine (Gln) in the prefrontal cortex (PFC) (2×2×4.5 cm3 ) using JPRESS sequence TE variable. Spectra with CRLBs>15 were excluded. All BD subjects to be included in this study had to be in euthymia (Young mania rating scale <7 and Hamilton depression rating scale <7 for at least 3 months). All healthy controls had no current or past history of psychiatric disorder according to the evaluation conducted by trained psychiatrists using The Mini International Neuropsychiatric Interview (MINI). Similarly, all subjects had no family history (first degree relatives) of mood or psychotic disorders and had not been in use of psychotropic medicine or substance abuse over the last three months. Results: Neither age or gender influenced metabolite levels in the PFC. GABA/Cre and Glu/Cre levels in BD were not different from controls; Gln/Cre levels were 13% higher in BD (F = 4.9 p = 0.03) than in healthy controls, moreover, Gln/Glu ratio was 27% higher in BD (F = 7.48 p = 0.008). Medication use (benzodiazepines, lithium, anticonvulsants and antipsychotics) did not influenced metabolite levels. Bipolar disorder subjects had worse working memory performance than controls. Working memory tests (SCWT) negatively correlated with GABA/Cre levels in healthy controls (p = 0.01 R .44) but not with BD subjects. Conclusion: This was the biggest sample size GABA and glutamine MRS study in BD type I done so far. Previous MRS studies in BD subjects evaluating glutamate and glutamine levels did not show a clear pattern in the hippocampus, occipital and frontal cortex. Moreover they included subjects during different mood episodes in the same sample. We did not find alteration on GABA levels in the PFC compared to controls but we found higher levels of Gln in medicated euthymic BD. The present findings reinforce a key role for glutamatergic system dysfunction in the pathophysiology of BD. References
P.1.i.005 Prefrontal cortex gamma-aminobutyric acid levels in bipolar I disorder determined using proton magnetic resonance spectroscopy M. Soeiro-de-Souza1 ° , M.C.G. Otaduy1 , R.A. Moreno1 , D.H. Moreno1 , H. Vallada1 1 Institute of Psychiatry of S˜ao Paulo Medical School, Psychiatry, S˜ao Paulo, Brazil Bipolar disorder (BD) has been consistently associated with glutamatergic abnormalities in the tripartite synapse [1]. Evidences from magnetic resonance spectroscopy (MRS) studies report altered glutamate (Glu) and glutamine in subjects with BD [2]. Glutamate excess is known to lead to excitotoxicity and apoptosis [3], associated with changes in intracellular calcium regulation. Abnormalities associated with g-aminobutyric acid (GABA), the major inhibitory neurotransmitter in central nervous system, have been heterogeneously described in BD. Moreover, medications that modulate GABA function have been used to treat BD mood episodes. Magnetic resonance spectroscopy (MRS) allows detecting in vivo measurements of brain metabolites, and the few studies that measured GABA in BD had controversial results, due to differences in technics, voxel, clinical symptoms, medications and region of interest.
[1] Machado-Vieira R, Manji HK, Zarate CA. The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disorders. Neuroscientist. 2009 Oct; 15(5): 525−39. ¨ ur D. Magnetic resonance spectroscopy studies of [2] Y¨uksel C, Ong¨ glutamate-related abnormalities in mood disorders. Biol Psychiatry. 2010 Nov 1; 68(9): 785−94. [3] Hashimoto R, Hough C, Nakazawa T, Yamamoto T, Chuang DM. Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J Neurochem. 2002 Feb; 80(4): 589−97.
P.1.i.006 Brain white matter connectivity associated with treatment response to paliperidone ER treatment in patients with schizophrenia M. Kim1 ° , B. Kim1 , J. Kim2 , T. Choi1 , T. Kim3 , S. Lee1 1 CHA University, Psychiatry, Sungnam, South-Korea; 2 Bundang Jaesaeng Hospital, Psychiatry, Sungnam, South-Korea; 3 Seoul Veterans Hospital, Psychiatry, Seoul, South-Korea Objective: Schizophrenia is a chronic and disabling psychiatric brain disorder that affects approximately 1% of the world’s population [1]. Although atypical antipsychotics were expected to be effective in improving various domains of symptoms in