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    Alzheimer Hastalığının Önlenmesi ve Tedavisinde Melatoninin TRPA1 Kanalları Üzerinden Potansiyel Etkileri
    (2022) Özşimşek, Ahmet; Övey, İshak Suat
    Amaç: Alzheimer hastalığı (AH) demansın en yaygın nedenidir ve ilerleyici bir nörodejeneratif hastalık olarak tanımlanır. AH ilerleyici bozukluğunun ana klinik özellikleri öğrenme ve hafıza kaybıdır. Çeşitli çalışmalar mitokondrinin AH patogenezinde kritik bir rol oynadığını göstermiştir. Bu çalışmada, Alzheimer hastalığının in vitro bir modelini oluşturarak melatoninin nöroblastom hücrelerinde mitokondriye bağımlı TRPA1 iyon kanalları üzerindeki etkisini araştırdık. Yöntem: Bir AH modeli oluşturmak için SH-SY5Y (insan nöroblastom hücre dizisi) hücrelerine okadaik asit uygulandı. Hücresel farklılaşma sonrası yedi ana grup (Grup 1 (Kontrol), Grup 2 (Mel+AH), Grup 3 (Mel+AH+AP18), Grup 4 (AH), Grup 5 (AH+AP18), Grup 6 (AH+Mel) ve Grup 7 (AH+Mel+AP18) oluşturuldu ve melatoninin nöroblastom hücrelerinde kalsiyuma bağımlı TRPA1 kanalları üzerindeki etkisi incelenerek in vitro Alzheimer hastalığı belirlendi. Bulgular: Kontrol grubuna göre melatonin+AH, AH ve AH+melatonin gruplarında Ca2+ konsantrasyonu daha yüksekti (p<0,001). Ancak Mel+AH+AP18, AH+Mel+AP18 ve kontrol arasında istatistiksel olarak anlamlı bir fark yoktu. Melatonin+AH ve AH+melatonin gruplarında Ca2+ düzeylerinin AH grubuna göre daha düşük olduğunu belirledik (p<0,001 ve p<0,05). Ayrıca sitozolik Ca 2+ konsantrasyonları melatonin+AH grubunda AH+melatonin grubuna göre daha düşük bulundu (p<0,05). Apoptoz ve oksidatif stres düzeylerini değerlendirirken, melatonin+AH, AH ve AH+melatonin gruplarında apoptoz ve hücre içi ROS değerlerinin kontrol grubuna göre daha yüksek olduğunu bulduk (p<0,001). Bu doğrultuda melatonin+AH , AH ve AH+melatonin gruplarında mitokondriyal depolarizasyon ve kaspaz 3 ve kaspaz 9 düzeyleri kontrol grubuna göre daha yüksekti (p<0,001). Ayrıca mitokondriyal depolarizasyon, kaspaz 3 ve kaspaz 9 değerleri AH grubunda melatonin+AH ve AH+melatonin gruplarına göre daha yüksek (p<0,001), mitokondriyal depolarizasyon ve kaspaz 3 düzeyleri melatonin+AH grubunda AH+melatonin grubundan daha düşüktü (p<0,001). Ancak aynı gruplarda kaspaz 9 sonuçlarında istatistiksel olarak anlamlı bir fark yoktu. Ayrıca kaspaz 9 değerleri melatonin+AH grubu, AH grubu ve AH+melatonin gruplarında sırasıyla melatonin+AH+AP18, AH+AP18 ve AH+melatonin+AP18 gruplarına göre daha düşüktü (p<0,001 ve p<0,05). Sonuç: Sonuçlarımız melatoninin, TRPA1 kanalları aracılığıyla sitozolik Ca2+ konsantrasyonunu, apoptozu ve hücre içi ROS’u azaltarak Alzheimer hastalığının tedavisinde ve profilaksisinde etkili bir seçenek olabileceğini düşündürmektedir.
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    Cavernous sinus thrombosis due to mucor infection of ethmoid sinus
    (2024) Cankaya, Seyda; Çetin, Bahar Bakır; Oktem, Ece Ozdemir; Özşimşek, Ahmet; Lakadamyalı, Hatice; Yuluğ, Burak
    [Abstract Not Available]
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    Clostridium botulinumneurotoxin A induces apoptosis and mitochondrial oxidative stress via activation of TRPM2 channel signaling pathway in neuroblastoma and glioblastoma tumor cells
    (Taylor & Francis Ltd, 2020) Akpınar, Orhan; Özşimşek, Ahmet; Güzel, Mustafa; Nazıroğlu, Mustafa
    Background TheClostridium botulinumneurotoxin A (BTX) is a polypeptide produced by the bacteriumClostridium botulinum. In addition to the therapeutic actions of BTX against pain and neuromuscular disorders, it is acted as anticancerogenic effect through excessive mitochondria reactive oxygen species (ROS) production, apoptosis, and caspase activations. The TRPM2 cation channel is activated by ROS and ADP-ribose and it is inhibited by 2-aminoethyl diphenylborinate (2-APB) and N-(p-amylcinnamoyl) anthranilic acid (ACA). The aim of this study was an investigation of involvement BTX-induced TRPM2 activation on the mitochondria ROS production and apoptosis levels in the DBTRG glioblastoma and SH-SY5Y neuroblastoma tumor cells. Material and methods The DBTRG and SH-SY5Y cells were divided into four groups as control, BTX (5 IU for 24 h), BTX + ACA (25 mu M for 30 min), and BTX + 2-APB (100 mu M for 30 min). Results BTX treatment increased mitochondrial membrane depolarization (JC-1), mitochondrial (MitROS), and cytosolic (DHR123 and DCFH-DA) ROS levels, neuronal death (propidium iodide/Hoechst) rate, caspase -3, and -9 levels in the BTX group, although their levels were diminished in the BTX + ACA and BTX + 2-APB groups. The ACA and 2-APB treatments also decreased BTX-induced increase of TRPM2 cytosolic free Ca(2+)concentration in the glioblastoma and neuroblastoma cell death. Conclusions BTX caused neuroblastoma and glioblastoma tumor cell death by activating the mitochondria ROS productionviastimulating TRPM2 signaling pathways. BTX may serve as a potential therapeutic targetviaactivation of TRPM2 for treating glioblastoma and neuroblastoma cells.
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    Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
    (2023) Yuluğ, Burak; Altay, Özlem; Li, Xiangyu; Hanoğlu, Lütfü; Çankaya, Şeyda; Lam, Simon; Velioğlu, Halil Aziz; Yang, Hong; Coşkun, Ebru; İdil, Ezgi; Nogaylar, Rahim; Özşimşek, Ahmet; Bayram, Cemil; Bolat, İsmail; Öner, Sena; Tozlu, Özlem Özdemir; Arslan, Mehmet Enes; Hacımüftüoğlu, Ahmet; Yıldırım, Serkan; Arif, Muhammad; Shoaie, Saeed; Zhang, Cheng; Nielsen, Jens; Turkez, Hasan; Boren, Jan; Uhlen, Mathias; Mardinoğlu, Adil
    Abstract Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the efect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the frst 28 days and twice daily between day 28 and day 84. The primary endpoint was the diference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efcacy of the CMA in AD patients. Results We showed a signifcant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P=0.00001, 29% improvement) in the CMA group. Moreover, there was a signifcant decline (P=0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of
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    Different metabolic and clinical profiles between patients with pure Alzheimer dementia and epileptic Alzheimer dementia: a metabolic study
    (2022) Oktem, Ece Ozdemir; Kadak, Kübra Soğukkanlı; Cakır, Tansel; Özşimşek, Ahmet; Cankaya, Seyda; Hanoğlu, Lütfü
    Aim: To investigate the clinical characteristics and cerebral FDG PET metabolisms of dementia patients who were also diagnosed with epilepsy and compare the differences with pure Alzheimer dementia patients.Methods: In this case-control study, a total of 14 patients, 7 patients with pure Alzheimer disease as a control group and 7 age and gender-matched patients with Alzheimer disease and concomitant epilepsy as a study group, were included. Detailed neurocognitive battery and brain fludeoxyglucose positron emission tomography (FDG PET-CT) were performed for all subjects.Results: In comparison of neurocognitive test scores, there was no significant difference between the study and control groups. However, geriatric depression scale scores were significantly lower in study group than the controls (p= 0.026). In cerebral FDG-PET CT profiles of subjects we detected significantly lower metabolism in left and right cerebellum, left lentiform nucleus, right thalamus and vermis in the study group (p=0.008, p=0.023, p=0.003, p=0.002, p=0.002, respectively). In the right parietotemporal cortex and right and left associative visual cortex, we found higher metabolism in the study group than controls (p=0.023, p=0.012, p=0.003, respectively).Conclusion: Epileptic patients with Alzheimer’s dementia may have distinct clinical and metabolic profiles, than pure Alzheimer’s disease patients. Even if there is no difference in the neurocognitive clinical scores of the patients, depression and related functional abnormalities may be a biomarker of epileptic AD.
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    Gerilim Tipi Baş Ağrısı Olan Bireylerde Temporomandibular Gevşetme Ve Miyofasial Gevşetme Tekniklerinin Yaşam Kalitesi, Depresyon Ve Baş Ağrısı Üzerine Etkisi
    (Yavuz YAKUT, 2024) Öz, Ayşe; Aracı, Ayça; Özşimşek, Ahmet; Taşkıran, Hanifegül; Yuluğ, Burak
    Amaç: Gerilim tipi baş ağrısı (GTBA) toplumda sıklıkla görülmektedir. Çalışmamızın amacı GTBA olan bireylerde temporomandibular eklem (TME) Yumuşak Doku Teknikleri (TME-YDT) ve miyofasial gevşetme (MFG) teknikliklerinin etkinliğini incelemektir. Yöntem: Uluslararası Baş Ağrısı Derneğinin Baş ağrısı sınıflandırması (ICHD-3)’na göre 18-65 yaşları arası GTBA tanısı alan 73 gönüllü birey dahil edildi. Bireyler randomizasyon metoduna göre Grup 1; TME-YDT, Grup 2; MFG Grubu ve Grup 3; Kontrol Grubu olmak üzere 3’e ayrıldı. Baş ağrısı, Headache Impact Test-6(HIT-6) ile; TMED Fonseca Ölçeği ile; Temporomandibular EHA cetvel yardımı ile; servikal EHA gonyometre ile; yaşam kalitesi, SF-36 Yaşam Kalite Ölçeği ile; depresyon, Beck Depresyon Ölçeği (BDÖ) ile; Anksiyete, Beck Anksiyete Ölçeği (BAÖ) ile değerlendirildi. Değerlendirmeler tedavi öncesi ve 4 haftalık tedavi sonunda yapıldı. Grup 1’e TME- YDT (anterior kaudal glide, masseter ve medial pterygoid kaslarına yumuşak doku mobilizasyonu), Temporal ve Suboksipital kaslara miyofasial gevşetme tekniği uygulandı. Grup 2’ye grup 1’e yapılan uygulamalara ek olarak Trapez, Rhomboid, Levator Scapula ve Sternocleidomasteideus kaslarına ve derin posterior servikal fasya gevşetme teknikleri uygulandı. Bulgular: Hem TME hem de MFG gruplarının FONSECA ve HIT6 total skorlarında meydana gelen değişimin kontrol grubuna göre anlamlı şekilde yüksek olduğu görüldü(p<0,05). Sonuç: GTBA tedavisinde TME yumuşak doku tekniklerinin miyofasial teknikler kadar etkili olduğu bulundu.
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    Ginkgo Biloba Özütünün in Vitro Alzheimer Hastalığı Modelinde TRPV1 Kanalları Aracılığıyla Koruyucu ve Terapötik Rolü
    (2023) Özşimşek, Ahmet; Övey, İshak Suat; Karacay, Ertan; Yuluğ, Burak
    Amaç: Ginkgo biloba’nın (GB) nöroblastom hücrelerinde mitokondriye bağımlı TRPV1 iyon kanalları üzerindeki etkisi Alzheimer hastalığı (AH) modeli oluşturularak araştırıldı. Yöntem: Bir AH modeli oluşturmak için SH-SY5Y hücrelerine okadaik asit uygulandı. Hücresel farklılaşmadan sonra yedi ana grupla organize edilen çalışma, GB’nin nöroblastom hücrelerinde AH’de kalsiyuma bağlı TRPV1 kanallarına etkisinin incelendiği in vitro çalışmadır. Bulgular: Kontrol grubu ile karşılaştırıldığında GB+AH, AH ve AH+GB gruplarında daha yüksek Ca 2+ konsantrasyonu saptandı (p<0,001). Ca 2+ düzeyi GB+AH ve AH+GB gruplarında AH grubuna göre daha düşüktü (p<0,001). Ayrıca GB+AH’de sitozolik Ca 2+ konsantrasyonu AH+GB grubuna göre daha düşüktü (p<0,05), apoptoz ve hücre içi reaktif oksijen türleri (ROS) değerleri GB+AH, AH ve AH+GB’de control grubuna göre daha yüksekti (p<0,001). Apoptoz ve hücre içi ROS değerleri AH grubunda GB+AH ve AH+GB grubuna göre daha yüksekti (p<0,001) ve AH+GB grubunda apoptoz düzeyi GB+AH grubuna göre daha yüksekti (p<0,001) ve mitokondriyal depolarizasyon, kaspaz 3 ve kaspaz 9 düzeyleri GB+AH, AH ve AH+GB gruplarında kontrol grubuna göre daha yüksekti (p<0,001). Ayrıca GB+AH+kapsazepin grubu, AH+kapsazepin grubu ve AH+GB+kapsazepin ile karşılaştırıldığında GB+AH grubu, AH grubu ve AH+GB gruplarında değerler daha düşüktü (p<0,001). Sonuç: Bu sonuçlar bize GB’nin TRPV1 kanalı üzerinden Alzheimer hastalığında tedavi edici etkisinin yanında koruyucu etkisinin olduğunu göstermektedir.
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    Investigation of the Antiepileptics on Levels of Vitamin D and Calcium
    (2022) Yuluğ, Burak; Özşimşek, Ahmet; Oktem, Ece Ozdemir
    Aim: We investigated the connection between D vitamin and factors such as the type of antiepileptic agent, patient age and gender.Methods: This retrospective case-control study enrolled a total of 301 participants, including 141 epilepsy patients with (n= 120) without drug (n=21) regimens followed up in Alanya Alaaddin Keykubat University neurology outpatient clinic and 160 healthy individuals who applied to the neurology outpatient clinic for different reasons from January 2018 to January 2021. Demographics, detailed history, use of medications, duration of antiepileptic use, plasma 25-hydroxy Vitamin D and calcium levels were determined.Results: The mean level of Vitamin D was 15.46 in the epilepsy group and 16.95 in the control group. Level of D Vitamine did not differ significantly by groups (p>0.05). There were no significant relationship regarding age and vitamin D levels in both groups while decreased Vitamin D levels were detected epileptic women. Vitamin D level was below 20 in 69.6% of healthy control group, 78.9% of carbamazepine users, 62.5% of lacosamide users, all lamotrigine users, 66.7% of levatiracetam users, and 72.4% of sodium valproate users. No significant connection were detected between levels of Vitamin D and the drug used (p>0.05) while a significant association was confirmed only between calcium levels and carbamazepine (p<0.05).Conclusion: Vitamin D and calcium levels can be found to be low in antiepileptic users; however, except for the calcium levels in the carbamazepine group, this decrease does not constitute a significant difference. 
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    Investigation of the Antiepileptics on Levels of Vitamin D and Calcium
    (2022) Yuluğ, Burak; Özşimşek, Ahmet
    Aim: We investigated the connection between D vitamin and factors such as the type of antiepileptic agent, patient age and gender. Methods: This retrospective case-control study enrolled a total of 301 participants, including 141 epilepsy patients with (n= 120) without drug (n=21) regimens followed up in Alanya Alaaddin Keykubat University neurology outpatient clinic and 160 healthy individuals who applied to the neurology outpatient clinic for different reasons from January 2018 to January 2021. Demographics, detailed history, use of medications, duration of antiepileptic use, plasma 25-hydroxy Vitamin D and calcium levels were determined. Results: The mean level of Vitamin D was 15.46 in the epilepsy group and 16.95 in the control group. Level of D Vitamine did not differ significantly by groups (p>0.05). There were no significant relationship regarding age and vitamin D levels in both groups while decreased Vitamin D levels were detected epileptic women. Vitamin D level was below 20 in 69.6% of healthy control group, 78.9% of carbamazepine users, 62.5% of lacosamide users, all lamotrigine users, 66.7% of levatiracetam users, and 72.4% of sodium valproate users. No significant connection were detected between levels of Vitamin D and the drug used (p>0.05) while a significant association was confirmed only between calcium levels and carbamazepine (p<0.05). Conclusion: Vitamin D and calcium levels can be found to be low in antiepileptic users; however, except for the calcium levels in the carbamazepine group, this decrease does not constitute a significant difference.
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    Mezensefalik Kanamalı Hastalarda Fonksiyonel Sonuçlara Yönelik Prognostik Faktörler
    (2023) Oktem, Ece Ozdemir; Kumral, Emre; Çetin, Fatma Ece; Özşimşek, Ahmet; Dorukoğlu, Mehmet Mesut; Cankaya, Seyda; Yuluğ, Burak
    Amaç: Mezensefalik kanama (MH), spontan intraparankimal kanamanın nadir görülen bir prezentasyonudur. Bu çalışma, mezensefalik kanamalardaki prognostik parametreleri değerlendirmeyi amaçlamaktadır. Yöntem: Çalışmamızda; izole mezensefalik kanamalı olgular PRISMA (Sistematik İncelemeler ve Meta-Analizler için Tercih Edilen Raporlama Öğeleri) beyanına göre kapsamlı şekilde taranmıştır. Literatürde yer alan BT veya MRG ile kanıtlanmış 62 uygun vaka ve bunlara MRG ile doğrulanmış altı vaka olmak üzere 68 hasta çalışmaya dâhil edildi. Hastalar modifiye Rankin Skalasına göre (mRS), iyi sonlanım (0–2 puan) ve kötü sonlanım (3–6 puan) olarak iki gruba ayrılarak, prognostik parametreler istatistiksel olarak karşılaştırıldı. Bulgular: Çalışılan 68 hastanın 26’sının (%38) bilinci açık, 22’si (%32) letarjik, 20’si (%29) stupor veya koma ile başvurdu. İyi prognoz gösteren olguların 26’sında (%65), kötü prognoz gösterenlerin 12’sinde (%43) idiopatik kanama gözlendi (p=0,059). Tek değişkenli analizlerde, arteriyovenöz malformasyonlar (p=0,33) ve kavernomlar (p=0,19) prognoz ile ilişkili bulunmadı. Çoklu lojistik regresyon analizlerinde; hipertansiyon (OR, 51,22; CI%95, 1,92–1370,24; P=0,019, bilinç durumu (OR, 133,54; CI%95, 1,61–1113,3; p=0,03), başvuru anındaki NIHSS (OR, 57,23; CI%95, 2,87–1141,2; p=0,008) ve ventrodorsal kanama boyutu (?1 cm) (OR, 61,83; CI%95, 2,15–1779,2; p=0,016), kötü prognoz ile ilişkili bulundu. Mezensefalik kanamadan üç ay sonra, 40 hastanın (%59) klinik olarak iyi durumda, 28 (%41) hastanın klinik olarak kötü durumda olduğu, sekiz hastanın ise (%12) kaybedildiği gözlendi. Sonuç: Bu bulgular, hemorajinin ventrodorsal boyutunun ve inme başlangıcındaki klinik şiddetin mezensefalik kanama sonrası fonksiyonel sonuç açısından olası belirleyicileri olduğunu göstermektedir.
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    The Relationship Between Serum 25-hydroxyvitamin D and Calcium Levels and Idiopathic Benign Paroxysmal Positional Vertigo
    (2022) Özşimşek, Ahmet; Karaçay, Ertan
    Aim: We aimed to compare 25-hydroxy vitamin D (25-OH vitamin D) and Ca2+ levels of patients admitted to our clinic with the complaint of dizziness and diagnosed with idiopathic benign paroxysmal positional vertigo (BPPV) with those of healthy control group without dizziness and investigate the role of Ca2+ and 25-OH vitamin D in the development of BPPV. Material and methods: This study is a retrospective case-control study. The study sample consisted of 409 patients admitted to Alanya Training and Research Hospital Neurology outpatient clinic and diagnosed with idiopathic BPPV between 01.01.2018 and 01.08.2021, and of 338 control patients without any physician consultation due to vertigo, dizziness or imbalance in the last 1 year before admission to our clinic and whose serum vitamin D levels were measured, the Chi-square and T-test were utilized for statistical analysis. Results: Mean blood 25-OH vitamin D levels were 15.74 ng/mL and 17.91 ng/ mL in BPPV and control groups, respectively. Serum 25-OH vitamin D levels were significantly lower in BPPV group than control group (p=0.01, p<0.05). Mean serum Ca2+ levels did not exhibit any difference in BPPV and control groups. Conclusion: Decreased serum levels of 25-OH vitamin D have been associated with the occurrence of BPPV independently of other key markers.
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    The relationship between the type of parkinson's disease and entrapment neuropathy in the upper extremities
    (2021) Sengeze, Nihat; Özşimşek, Ahmet; Koyuncuoğlu, Hasan Rıfat; Taşkıran, Esra
    Objective: Parkinson's disease (PD) is one of the common neurodegenerative disorders in the community. Compressive neuropathy (CN) is one of the conditions that negatively affect workforce and decreases the quality of life. We aimed to investigate the effect of repetitive mechanical movement on tremor dominant (TD) or akinetic-rigid syndrome (ARS) PD and CNs, particularly, the relationship between CN and two types of PD. In addition, we aimed to evaluate the relationship between CNs and the affected side at the onset and during the disease in both types of PD. Materials and Methods: Patients with PD who presented to our clinic from October 2017 to September 2018 were enrolled in the study. All patients who underwent electromyography to investigate CN were included in the study. The Padua classification was used in the carpal tunnel and cubital tunnel syndrome and electrophysiological findings were classified according to age and gender. According to the disease duration, patients were compared within the two groups as less than 3 years and >= 3 years. Patients were examined in two groups according to the TD and ARS type of PD and initially affected side. Results: A total of 71 patients suffering from PD were enrolled in the study, wherein 57 (80.3%) were TD, and 14 were (19.7%) ARS. An increased risk of developing carpal tunnel syndrome (CaTS) was found in the TD group with a disease duration of >= 3 years (p=0.026). Conclusion: No relationship was found between the two different types of PD or the affected side and the type of CN. However, the risk of CaTS increased in TD PD over the 3 years.
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    Topological network mechanisms of clinical response to antidepressant treatment in drug-naive major depressive disorder
    (Churchill Livingstone, 2021) Uykur, Abdullah Burak; Yıldız, Sultan; Velioğlu, Halil Aziz; Özşimşek, Ahmet; Öktem, Ece Özdemir; Bayraktaroğlu, Zübeyir; Ergün, Tarkan; Lakadamyalı, Hatice; Hanoğlu, Lütfi; Hanoğlu, Lütfi; Çankaya, Şeyda; Saatçi, Özlem; Yuluğ, Burak
    Aim: There is rapidly increasing evidence that remission of MDD is associated with substantial changes in functional brain connectivity. These New data have provided a holistic view on the mechanism of antidepressants on multiple levels that goes beyond their conventional effects on neurotransmitters. Method: The study was approved by the Local Ethics Committee of Istanbul Medipol University (10840098-604.01.01-E.65129) and followed the Helsinki Declaration principles. In our study, we have evaluated the effect of six weeks of treatment with antidepressants (escitalopram and duloxetine), and tested the underlying brain functional connectivity through a Graph analysis approach in a well-defined first-episode, drug-naive, and non-comorbid population with MDD. Results: Beyond indicating that there was a significant correlation between the antidepressant response and topological characteristics of the brain, our results suggested that global rather than regional network alterations may be implicated in the antidepressant effect. Conclusion: Despite the small-sample size and non-controlled study design, our study provides important and relevant clinical data regarding the underlying mechanisms of the antidepressants on topological dynamics in the human brain. © 2020 Elsevier Ltd