137 2008-126X Iran University of Medical Sciences 1869 Computational Neuroscience Assessing the Effects of Alzheimer Disease on EEG Signals Using the Entropy Measure: A Meta-analysis Ahmadieh Hajar b Ghassemi Farnaz c b Department of Biomedical Engineering, Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran, Iran. c Department of Biomedical Engineering, Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran, Iran. 1 3 2022 13 2 153 164 23 07 2020 03 10 2020 Introduction: Alzheimer disease (AD) is the most prevalent neurodegenerative disorder and a type of dementia. About 80% of dementia in older adults is due to AD. According to multiple research articles, AD is associated with several changes in EEG signals, such as slow rhythms, reduction in complexity and functional associations, and disordered functional communication between different brain areas. This research focuses on the entropy parameter. Methods: In this study, the keywords “Entropy,” “EEG,” and “Alzheimer” were used. In the initial search, 102 articles were found. In the first stage, after investigating the Abstracts of the articles, the number of them was reduced to 62, and upon further review of the remaining articles, the number of articles was reduced to 18. Some papers have used more than one entropy of EEG signals to compare, and some used more than one database. So, 25 entropy measures were considered in this meta-analysis. We used the Standardized Mean Difference (SMD) to find the effect size and compare the effects of AD on the entropy of the EEG signal in healthy people. Funnel plots were used to investigate the bias of meta-analysis. Results: According to the articles, entropy seems to be a good benchmark for comparing the EEG signals between healthy people and AD people.  Conclusion: It can be concluded that AD can significantly affect EEG signals and reduce the entropy of EEG signals.
2175 Behavioral Neuroscience The Protective Effects of Crocin on Input-Output Functions and Long-term Potentiation of Hippocampal CA1 Area in Rats Exposed to Chronic Social Isolated Stress Khani Fatemeh d Radahmadi Maryam e Alaei Hojjatallah f d Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. e Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. f Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. 1 3 2022 13 2 165 174 20 05 2021 07 12 2021 Introduction: The lack of social communication is associated with the primary risk of proper brain functions. It is reported that crocin helps relieve this problem. The present study examined the protective effect of two doses of crocin on Long-term potentiation (LTP) of hippocampal cornu ammonis 1 (CA1) area as a cellular mechanism in rats exposed to chronic social isolated stress. Methods: Rats were assigned to the control, sham, isolation stress, and two stress groups (receiving 30 and 60 mg/kg crocin). Chronic isolation stress (CIS) was induced 6 h/d, and crocin was administrated for 21 days. The field excitatory postsynaptic potential (fEPSP) slope and amplitude were measured by input/output functions and LTP induction in the CA1 area of the hippocampus. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex. Results: The slope and amplitude of fEPSP severity were impaired in both input/output and LTP responses in the CIS group. Crocin at a dose of 30 and particularly 60 mg/kg improved input/output and LTP responses in the CIS group. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. In contrast, only a high dose of crocin decreased hippocampal corticosterone levels in the CIS condition. Finally, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups.  Conclusion: The chronic isolation stress impaired neural excitability and Long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and Long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex.  1900 Behavioral Neuroscience Cardiovascular Effect of Dorsal Periaqueductal Gray During Lipopolysaccharide-induced Hypotension Mirzaii-Dizgah Iraj g Shafei Mohammad Naser h Mohebbati Reza i Alikhani Vida j g Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran h Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran i Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran j Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 1 3 2022 13 2 175 184 16 08 2020 25 08 2020 Introduction: The central mechanism related to the cardiovascular response to lipopolysaccharide (LPS)-induced hypotension is not entirely known, but it is suggested that numerous brain areas such as dorsal periaqueductal gray (dPAG) are involved in this process. In the current work, the cardiovascular effect of the dPAG during LPS-induced hypotension is investigated. Methods: The study animals (rats) were divided into four groups: control (saline microinjected into dPAG), lidocaine 2%, LPS (intravenously injected), and lidocaine + LPS. Catheterization of the femoral artery and vein was performed to record blood pressure and LPS injection, respectively. Saline and lidocaine were microinjected into the dPAG nucleus then the LPS injection was performed. The changes (∆) in systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were measured and compared with those of the control and LPS groups. Results: LPS significantly declined ∆MAP and ∆SBP (P<0.05) but did not change the ∆HR compared to the control. Lidocaine did not significantly affect basic ∆SBP, ∆MAP, and ∆HR compared to the control. Injection of lidocaine before LPS significantly attenuated the reduction of ∆SBP and ∆MAP evoked by LPS (P<0.05). Conclusion: Our data showed that blockade of the dPAG by lidocaine significantly ameliorates the hypotension induced by LPS. this finding confirms the involvement of the dPAG in cardiovascular regulation during LPS-induced hypotension.  1474 Clinical Neuroscience Assessing the Changes of Cortical Thickness in Alzheimer Disease With MRI Using Freesurfer Software Sattari Nasim k Faeghi Fariborz l Shekarchi Babak m Heidari Mohammad Hossein n k Department of Radiology, School of Allied Medical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran. l Department of Radiology, School of Allied Medical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran. m Department of Radiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran. n Department of Basic Sciences, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 1 3 2022 13 2 185 192 10 04 2019 04 08 2020 Introduction: In this study, we intend to determine the correlation between the thickness of the cerebral cortex and the severity of the cognitive disorder in Alzheimer disease (AD). Methods: A total of 20 (14 women and 6 men) patients diagnosed with AD with a Mean age of 72.95 years, and 10 (7 women and 3 men) cognitively normal (CN) subjects with a Mean age of 70.50 years were included in the study. Of the AD patient and CN subjects, 70% were female, and 30% were male. All individuals underwent 1.5 T Magnetic resonance imaging (MRI). The MRI scanning protocol included 3D MPRAGE (3D-T1W) sequence. All images were analyzed using Freesurfer v5.3, and then the brain cortical thickness in 7 cortical areas (inferior temporal, middle temporal, superior temporal, parahippocampal, pars triangularis, rostral middle frontal, and superior frontal) was calculated. Results: The analysis of covariance (ANCOVA) was conducted to compare the mean thickness of each region between the patient and the control group. There was a significant difference in the mean cortical thickness in all regions. In all cases, the mean cortical thickness in CN subjects was greater than in AD patients. However, the mean thickness of pars triangularis left hand in CN subjects was not significantly greater than that in AD patients. The receiver operating characteristic system (ROC) was designed to evaluate the predictive power of the patients and the healthy people. We have selected a thousand cut-off points from 1.5 to 3.5 mm for cortical thickness. When the cut-off points were within 2.276878–2.299680 mm in the left hemisphere, Youden’s index was maximum. The sensitivity and specificity, in this case, were 80%. Also, when the cut-off points were within the range of 2.263278–2.282278 mm in the right hemisphere, the sensitivity and specificity were 90% and 80%, respectively. Conclusion: This study demonstrates the importance of quantifying the cortical thickness changes in the early diagnosis of AD. In addition, examining the pattern of changes and quantifying the reduction in the thickness of the cortex is a crucial tool for displaying the local and global atrophy of the brain. Also, this pattern can be used as an alternative marker for the diagnosis of dementia. Finally, to the best of our knowledge, our study is the first to report finding on the cortical thickness that would help the clinician have a better differential diagnosis. Also, this study has checked the possibility of early diagnosis of the disease. 1643 Behavioral Neuroscience Role of Amygdala-Infralimbic Cortex Circuitry in Glucocorticoid-induced Facilitation of Auditory Fear Memory Extinction Vafaei Abbas Ali o Rashidy-Pour Ali p Trahomi Parnia Omoumi Samira Dadkhah Masoomeh o Research Center of Physiology, Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. p Research Center of Physiology, Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Student Research Committee, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Student Research Committee, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran. 1 3 2022 13 2 193 206 29 10 2019 10 03 2021 Introduction: The basolateral amygdala (BLA) and infralimbic area (IL) of the medial prefrontal cortex (mPFC) are two interconnected brain structures that mediate both fear memory expression and extinction. Besides the well-known role of the BLA in the acquisition and expression of fear memory, projections from IL to BLA inhibit fear expression and have a critical role in fear extinction. However, the details of IL-BLA interaction have remained unclear. Here, we investigated the role of functional reciprocal interactions between BLA and IL in mediating fear memory extinction. Methods: Using lidocaine (LID), male rats underwent unilateral or bilateral inactivation of the BLA and then unilateral intra-IL infusion of corticosterone (CORT) prior to extinction training of the auditory fear conditioning paradigm. Freezing behavior was reported as an index for conditioned fear. Infusions were performed before the extinction training, allowing us to examine the effects on fear expression and further extinction memory. Experiments 1-3 investigated the effects of left or right infusion of CORT into IL and LID unilaterally into BLA on fear memory extinction. Results: Intra-IL infusion of CORT in the right hemisphere reduced freezing behavior when administrated before the extinction training. Auditory fear memory extinction was impaired by asymmetric inactivation of BLA and CORT infusion in the right IL; however, the same effect was not observed with symmetric inactivation of BLA.  Conclusion: IL-BLA neural circuit may provide additional evidence for the contribution of this circuit to auditory fear extinction. This study demonstrates dissociable roles for right or left BLA in subserving the auditory fear extinction. Our finding also raises the possibility that left BLA-IL circuitry may mediate auditory fear memory extinction via underlying mechanisms. However, further research is required in this area. 1687 Cellular and molecular Neuroscience The Effect of Different Concentrations of Methylprednisolone on Survival, Proliferation, and Migration of Neural Stem/Progenitor Cells Bagheri Zohreh Shamsi Fatemeh Zeraatpisheh Zahra Salmannejad Mahin Soltani Ahmad Aligholi Hadi Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Department of Neurosciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. Department of Neurosciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Department of Neurosurgery, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Department of Neurosciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. 1 3 2022 13 2 207 214 07 01 2020 26 07 2020 Introduction: The present study addressed whether methylprednisolone (MP) as an anti-inflammatory drug used in neurodegenerative diseases and neural stem/progenitor cells (NS/PCs) is safe.  Methods: First, embryonic rat NS/PCs were exposed to different concentrations of MP, and then we evaluated their survival by MTT assay, proliferation by analyzing the number and diameter of neurospheres, and the migration of the cells by neurosphere assay. Results: The viability of NS/PCs was reduced following exposure to 10, 15, and 20 µg/mL of MP. In addition, although the number of neurospheres did not change, exposure to different concentrations of MP resulted in the formation of smaller neurospheres. Despite these undesirable effects, the highest concentration of MP (20 μg/mL) increased the migration capacity of the NS/PCs. Conclusion: The combination of MP and NS/PCs is not recommended due to the adverse effects of MP on the survival and proliferation of NS/PCs. 1809 Cellular and molecular Neuroscience Neurofeedback Training Versus Perceptual-motor Exercises Interventions in Visual Attention for Children With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial Ghadamgahi Sani Neda Akbarfahimi Malahat Akbari Shadi Alizadeh Zarei Mehdi Taghizadeh Ghorban Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran. Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran. Department of Cognitive Neuroscience, Faculty of Education and Psychology, University of Tabriz, Tabriz, Iran. Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran. Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran. 1 3 2022 13 2 215 224 05 06 2020 21 02 2021 Introduction: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders characterized by poor attention and subsequently lower learning abilities than normal children. This study aimed to compare the effectiveness of neurofeedback and perceptual-motor exercises as two common nonpharmacological treatments for visual attention. Methods: A total of 40 combined medicated ADHD children (aged 5-12 years) were randomly allocated into two groups: neurofeedback training and perceptual-motor exercises. Visual attention and motor proficiency were assessed before and after the treatment by continuous performance test (CPT) and Bruininks-Oseretsky Test (BOT), respectively. Results: According to repeated measures analysis of variance (ANOVA), both groups showed significant improvement in three attention-related areas of CPT, including reaction time, omission, and commission errors (P<0.001), while the difference between the two groups was not significant (P>0.05). However, in the perceptual-motor exercises group, motor proficiency improved significantly (P<0.01). Conclusion: Neurofeedback training intervention, as well as perceptual-motor exercises, are effective in improving ADHD symptoms, and given the similar effect of both interventions and their lack of side effects, perceptual-motor exercises appear to be the more appropriate option for reducing symptoms of ADHD, because of its additional effect on motor proficiency, rich content of purposeful activities, and social interactions. 1604 Behavioral Neuroscience Minocycline Improves Memory by Enhancing Hippocampal Synaptic Plasticity and Restoring Antioxidant Enzyme Activity in a Rat Model of Cerebral Ischemia-Reperfusion Parvardeh Siavash Sheikholeslami Mohammad Abbas Ghafghazi Shiva Pouriran Ramin Mortazavi Seyed Erfan Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 1 3 2022 13 2 225 236 21 09 2019 25 08 2020 Introduction: Oxidative stress plays a crucial role in the impairment of synaptic plasticity following cerebral ischemia, ultimately resulting in memory dysfunction. Hence, the applying antioxidant agents could be beneficial in managing memory deficits after brain ischemia. Minocycline is a tetracycline antibiotic with antioxidant effect. The main objective of this work was to assess the minocycline effect on the impairment of synaptic plasticity and memory after cerebral ischemia-reperfusion in rats. Methods: Transient occlusion of common carotid arteries was used to induce ischemia-reperfusion injury in rats. Single or multiple (once daily for 7 days) dose(s) of minocycline were administered before (pretreatment) or after (treatment) brain ischemia. Seven days after ischemia-reperfusion, passive avoidance performance, long-term hippocampal potentiation, and the activity of antioxidant enzymes were assessed.  Results: The passive avoidance test showed that minocycline (20 and 40 mg/kg) significantly increased step-through latency while reducing the duration of staying in a dark chamber in the treatment (but not pretreatment) group. In electrophysiological experiments, the rats treated (but not pretreated) with minocycline (40 mg/kg) showed a significant increase in the amplitude of the field excitatory postsynaptic potentials in the dentate gyrus area of the hippocampus. The treatment (but not pretreatment) with minocycline (20 and 40 mg/kg) resulted in a significant increase in the activity of catalase, glutathione peroxidase, and superoxide dismutase in the hippocampus.  Conclusion: It was determined that minocycline attenuates memory dysfunction after cerebral ischemia-reperfusion in rats by improving hippocampal synaptic plasticity and restoring antioxidant enzyme activity.  1503 Clinical Neuroscience Repetitive Transcranial Magnetic Stimulation in Delirium: A Double-blind, Randomized, Sham-controlled, Pilot Study Yaghoubi Emad Shariat Seyed Vahid Rashedi Vahid Ghanbari Jolfaei Atefeh Department of Psychiatry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Mental Health Research Center, Iran University of Medical Sciences, Tehran, Iran. School of Behavioral Sciences and Mental Health (Tehran Institute of Psychiatry), Iran University of Medical Sciences, Tehran, Iran. Mental Health Research Center, Iran University of Medical Sciences, Tehran, Iran. 1 3 2022 13 2 237 246 14 05 2019 14 11 2020 Introduction: Delirium is a fatal but potentially reversible disorder of the central nervous system that imposes high costs on health systems. This study aims to evaluate the effect of intermittent theta-burst stimulation on the severity and course of delirium disorder. Methods: This is a double-blind, randomized, sham-controlled pilot study. The study participants were randomly allocated into the active (active intermittent theta-burst stimulation) and sham groups. The severity of delirium was assessed 15 minutes before the intervention and 15 minutes after that by the Neelon and Champagne (NEECHAM) confusion scale. Results: In the active group, total and subscale scores of NEECHAM significantly decreased after intervention (P<0.05). Although no statistical difference was found in the control group regarding the subscale scores of NEECHAM, the difference in the total scores before and after the sham intervention was statistically significant. Conclusion: Carrying one session of repetitive transcranial magnetic stimulation on the left dorsolateral prefrontal cortex can reduce the delirium severity in a short period, although it will not decrease the number of delirium cases three days after the intervention. 1611 Cellular and molecular Neuroscience Reprogramming by Cytosolic Extract of Human Embryonic Stem Cells to Improve Dopaminergic Differentiation Potential of Human Adipose Tissue-derived Stem Cells Mobasseri Sehar Javeri Arash Fakhr Taha Masoumeh Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. 1 3 2022 13 2 247 256 23 09 2019 25 08 2020 Introduction: The extract of pluripotent stem cells induces dedifferentiation of somatic cells with restricted plasticity.  Methods: In this study, we used the extract of human embryonic stem cells (hESC) to dedifferentiate adipose tissue-derived stem cells (ADSCs) and examined the impact of this reprogramming event on the dopaminergic differentiation of the cells. For this purpose, cytoplasmic extract of ESCs was prepared by repeated freezing and thawing cycles. The plasma membrane of hADSCs was reversibly permeabilized by streptolysin O (SLO), exposed to hESC extract, and resealed by a CaCl2-containing medium.  Results: As revealed by qPCR analysis, expression of OCT4, SOX2, NANOG, LIN28A, and KLF4 mRNAs were downregulated in the ADSCs one week after extract incubation, while all mRNAs except for KLF4 were upregulated at the end of the second week. For dopaminergic differentiation, control and reprogrammed ADSCs were induced by a serum-free neurobasal medium containing B27 and a cocktail of sonic hedgehog (SHH), basic fibroblast growth factor (bFGF), fibroblastic growth factor 8 (FGF8), and brain-derived neurotrophic factor (BDNF) for 12 days. After differentiation, the expression levels of some neuronal and dopaminergic-related genes, including PAX6, NESTIN, NEFL, GLI1, LMXB1, EN1, NURR1, and TH, significantly increased in the reprogrammed ADSCs compared to the control group. On the whole, two weeks after reprogramming by ESC extract, ADSCs showed an improved dopaminergic differentiation potential.  Conclusion: These findings suggest that the cytoplasmic extract of hESCs contains some regulatory factors which induce the expression of pluripotency-associated markers in somatic cells and that the exposure to ESC extract may serve as a simple and rapid strategy to enhance the plasticity of somatic stem cells for cell replacement therapy purposes. 1736 Computational Neuroscience Different Olfactory Perception in Heroin Addicts Using Functional Magnetic Resonance Imaging Haghshenas Bilehsavar Shirin Batouli Seyed Amir Hossein Soukhtanlou Mohammad Alavi Sasan Oghabian Mohammad Ali Department of Neuroimaging and Analysis, Tehran University of Medical Sciences, Tehran, Iran. Department of Neuroimaging and Analysis, Tehran University of Medical Sciences, Tehran, Iran. Department of Psychology and Education, Alborz Campus, University of Tehran, Tehran, Iran. Department of Addiction, School of Behavioural Sciences and Mental Health (Institute of Tehran Psychiatry), Iran University of Medical Sciences, Tehran, Iran. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 1 3 2022 13 2 257 268 22 03 2020 09 05 2020 Introduction: Addiction is a mental disorder that has many adverse effects on brain health. It alters brain structure and deteriorates brain functionality. Impairment of brain cognition in drug addiction is illustrated in many previous works; however, olfactory perception in addiction and, in particular, its neuronal mechanisms have rarely been studied.  Methods: In this experiment, we recruited 20 heroin addicts and 20 normal controls of the same sex, age, handedness, and socioeconomic status and compared their brain function while perceiving non-craving odors during the functional magnetic resonance imaging (fMRI). We intended to define the default olfactory system performance in addicts compared to healthy people.  Results: Our study showed an overall larger activation in addicts when processing olfactory stimuli. In particular, and when comparing the two groups, the right anterior cingulate and right superior frontal gyrus had higher activations than normal, whereas the left lingual gyrus and left cerebellum showed stronger activations in the addicts.  Conclusion: The result of this study can unveil the missing components in addiction brain circuitry. This information is helpful in better understanding the neural mechanisms of addiction and may be advantageous in designing programs for addiction prevention or clinical treatment. 2018 Clinical Neuroscience Psychiatric Onset Alexander Disease: An Important Challenge in Neuropsychiatric Diagnosis: A Case Report Arshiany Hedieh Ezzatian Behzad Artounian Valentin Alizadeh Fatemeh Mohammadian Fatemeh Department of Psychiatry, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran. Department of Psychiatry, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. Department of Genomic Psychiatry and Behavioral Genomics, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. Department of Genomic Psychiatry and Behavioral Genomics, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. 1 3 2022 13 2 269 274 05 12 2020 02 01 2021 Introduction: Alexander disease is a heterogeneous group of diseases with various manifestations based on the age of disease onset. This rare leukodystrophy syndrome with mutations in the GFAP gene could present with developmental delay and seizure in the infantile form to ataxia and bulbar palsy in adulthood. However, psychiatric symptoms are not well-defined and are usually evaluated after disease diagnosis, not before disease investigations. Case Report : Our patient is a 52-year-old Iranian woman with a history of depression since 17 years ago, a suicidal attempt two years ago, and ingestion of a large amount of opium with the intention of suicide 2 months ago. She was presented with disorientation and probably a delirious state in the last interview. Eventually, in comprehensive investigations, white matter hyperintensity in MRI and leukodystrophy was diagnosed to determine the cause of these changes, we did a gene study, found whole exon deletion of the GFAP gene, and made a diagnosis of late-onset Alexander disease. Conclusion: Neurological-onset manifestation of Alexander disease, specifically late-onset form, is the most common clinical picture of disease and was seen in about 90% of patients, but psychiatric symptoms are not well-known, and psychiatric-onset disease was not described yet. Various gene mutations were described in late-onset Alexander disease; however, the large whole exon deletion which was revealed in our patient is a novel mutation and significantly needs to be explored. Here authors describe a late-onset Alexander disease with psychiatric-onset symptoms and novel large exon deletion in the GFAP gene.