Translational studies in the complex role of neurotransmitter systems in anxiety and anxiety disorders

Discovery of innovative anxiolytics is severely hampering. Existing anxiolytics are developed decades ago and are still the therapeutics of choice. Moreover, lack of new drug targets forecasts a severe jeopardy in the future treatment of the huge population of CNS-diseased patients. We simply lack the knowledge on what is wrong in brains of anxious people (normal and diseased). Translational research, based on interacting clinical and preclinical research, is extremely urgent. In this endeavor, genetic and genomic approaches are part of the spectrum of contributing factors. We focus on three druggable targets: serotonin transporter, 5-HT1A, and GABAA receptors. It is still uncertain whether and how these targets are involved in normal and diseased anxiety processes. For serotonergic anxiolytics, the slow onset of action points to indirect effects leading to plasticity changes in brain systems leading to reduced anxiety. For GABAA benzodiazepine drugs, acute anxiolytic effects are found indicating primary mechanisms directly influencing anxiety processes. Close translational collaboration between fundamental academic and discovery research will lead to badly needed breakthroughs in the search for new anxiolytics.</p

Özet: Depresyon ve anksiyete düzeylerinin idiyopatik ani sensorinöral iflitme kayb› olan hastalar›n iyileflme durumlar›na etkileri The effects of depression and anxiety levels on the status of recovery in patients with idiopathic sudden sensorineural hear

Amaç: Çal›flman›n amac› ani idiyopatik sensorinöral iflitme kayb› olup iyileflen (n=33) ve iyileflmeyen (n=17) hastalarda ve sa¤l›kl› kontrollerde anksiyete ve depresyon semptomlar›n›n fliddet derecesini karfl›laflt›rmakt›r. Yöntem: Bu çal›flma hastanede yatan sensorinöral iflitme kay›pl› hastalarla (n=50), sa¤l›kl› kontrol grubunda (n=52) gerçeklefltirildi. Anksiyete ve depresyon semptomlar›n›n fliddet derecesi hastaneye kabul s›ras›nda uygulanan Durumsal Sürekli Kayg› Envanteri (STAI) ve Beck Depresyon Envanteri (BDI) ile de¤erlendirildi. Bafllang›çta ve tedavi sonras›nda (4. haftan›n sonunda) her bir hastan›n odyolojik de¤erlendirme formundan 50 olgunun tüm iflitme verileri elde edildi. Bulgular: ISSHL hastalar›n›n %66&apos;s› iyileflmifl, %34&apos;ü iyileflmemiflti. ISSHL hastalar›n›n ve kontrol deneklerin ortalama BDI ve STAI-II skorlar› s›ras›yla 11.4±8.6 vs. 6.8±4.3 ve 41.6±7.3 vs. 36.7±8.4 (p&lt;0.05) olup, ISSHL hastalar›n›n de¤erleri kontrol grubundan anlaml› derecede daha yüksek idi. ISSHL hastalar›nda BDI ve STSI-II skorlar› aras›nda orta derecede ve anlaml› pozitif korelasyon mevcuttu. (r=0.617, p&lt;0.05). Kontrol grubunun ortalama BDI, STAI-I ve STA-I-II skorlar›, iyileflen ve hiç iyileflmeyen gruplara göre anlaml› derecede daha düflüktü (p&lt;0.05). Ancak iyileflmifl ve hiç iyileflmemifl gruplar aras›nda ortalama BDI, STAI-I ve STAI-II skorlar› aç›s›ndan anlaml› farkl›l›k gözlemlenmedi (p&gt;0.05). Sonuç: Sa¤l›kl› kontrollere göre ISSHL hastalar› daha depresif ve endifleli bir ruh hali içindeydi. Ancak anksiyete ve depresif ruh hali ISSHL hastalar›n›n iyileflme durumunu hiçbir flekilde etkilememifltir. Doktorlar ISSHL hastalar›n›n anksiyete ve depresif semptomlar›na da dikkat etmelidir. Anahtar sözcükler: ‹diyopatik ani sensorinöral iflitme kayb›, anksiyete, depresyon. Abstract Objective: To compare the severity of anxiety and depression symptoms in idiopathic sudden sensorineural hearing loss (ISSHL) patients with (n=33) and without (n=17) recovery, and healthy control group. Methods: This study was conducted on ISSHL inpatients (n=50) and a healthy control group (n=52). Severity of the anxiety and depression symptoms was assessed using the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI) during admission. Hearing data of all 50 cases obtained at baseline and after the treatment (at the end of the 4th week) were gathered from the audiological evaluation form of each patient. Results: The rates of ISSHL patients with and without recovery were 66% and 34%, respectively. The mean BDI and STAI-II scores of the patients with ISSHL were significantly higher than those of the control group (11.4±8.6 vs. 6.8±4.3 and 41.6±7.3 vs. 36.7±8.4, respectively; p&lt;0.05). Among the ISSHL patients, there was a moderate and significant positive correlation between the BDI and STSI-II scores (r=0.617, p&lt;0.05). The mean BDI, STAI-I, and STAI-II scores of the control group were significantly lower than those of the recovery and no recovery groups (p&lt;0.05). However, the recovery and no-recovery groups did not show any difference in terms of mean BDI, STAI-I and STAI-II scores (p&gt;0.05). Conclusion: ISSHL patients had a more depressive and anxious mood compared to the healthy controls. However, anxiety and depressive mood had no effect on the recovery status of the ISSHL patients. Physicians also need to pay attention to the status of anxiety and depressive symptoms in patients with ISSHL

Evaluation of the results of MOTAKK hepatitis C virus RNA genotyping and hepatitis delta virus external quality assessment programs during 2015-2016

Background/Aims: To evaluate the HCV RNA genotyping and HDV RNA tests that are performed in molecular microbiology laboratories in Turkey as part of a national external quality assessment programme, MOTAKK (Molekuler Tanida Kalite Kontrol) (English translation: Quality control in molecular diagnostics)

Evaluation of the results of MOTAKK hepatitis C virus RNA genotyping and hepatitis delta virus external quality assessment programs during 2015-2016

Background/Aims: To evaluate the HCV RNA genotyping and HDV RNA tests that are performed in molecular microbiology laboratories in Turkey as part of a national external quality assessment programme, MOTAKK (Molekuler Tanida Kalite Kontrol) (English translation: Quality control in molecular diagnostics). Materials and Methods: Plasmas having different HCV RNA genotypes were used to prepare HCV genotype control sera. The HDV RNA main stock was prepared from patients with chronic delta hepatitis who had a significant amount of viral load detected, as per the WHO reference materials on viral load studies that were compiled for the purpose of developing HDV RNA control sera. Samples with different viral loads were prepared from this main stock by dilution. The prepared controls were delivered to the registered laboratories. The laboratories carried out the relevant tests and entered their results via the MOTAKK web page. External quality assessment (EQA) reports of the participants were uploaded to the website as well. Results: In total, there were 23 participating laboratories, out of which 20 exclusively performed HCV genotyping, and 15 and 16 only performed HDV RNA in 2015 and 2016, respectively. The success rate of the results of the HCV genotype was 56-96\% in 2015 and 30-95\% in 2016. The tube with a 30\% success rate had a recombinant type of HCV, therefore, it could not be detected in most of the laboratories. The HDV RNA results were evaluated qualitatively. Accordingly, HDV RNA detection rates of participant laboratories were 71-100\% in 2015 and 50-100\% in 2016. Conclusion: This study was the first national external quality control program in Turkey regarding HCV RNA genotyping and HDV RNA in the field of molecular microbiology, and it was implemented successfully

Evaluation of 2015-2016 MOTAKK HBV DNA and HCV RNA External Quality Assessment National Program Results

MOTAKK, as a national external quality control program has been launched to evaluate the molecular detection of viral infections including HBV DNA and HCV RNA in molecular microbiology diagnostic laboratories in Turkey. This program is prepared in compliance with ISO 17043:2010 (Conformity assessment general requirements for proficiency testing) standards, and aims to take the place of external quality control programs from abroad, contributing to standardization and accuracy of molecular diagnostic tests in our country. The aim of this study was to evaluate 2015 and 2016 results of the MOTAKK External Quality Control Program for HBV DNA and HCV RNA viral load. The calls were announced on the web page of MOTAKK (www.motakk.org). The quality control samples were sent to participating laboratories in 2015 and 2016. Main stocks were prepared from patients with chronic hepatitis B and C who had viral load detection with reference methods according to WHO reference materials for viral load studies to improve quality control sera. From these main stocks, samples with different viral loads were prepared from dilutions of plasma with HBV, HCV, HAV, HIV, Parvovirus B19 and CMV negative serologic markers. Quality control samples were sent to the participating laboratories along with the negative samples in the cold chain. The laboratories accomplished the related tests within 2-3 weeks and entered their results on the MOTAKK web page. These results were analysed according to ISO 13528 (Statistical methods for use in proficiency testing by interlaboratory comparison) and scoring reports were created by a software developed by MOTAKK and sent to participating labs. Each laboratory evaluated their own results in comparison with the other laboratory results, reassessed the tests via observing the distance from the mean result and the reference values. The number of laboratories participating in the HBV DNA and HCV RNA external quality control program was 70-73 in 2015-2016. Participants were able to comply with the program tools, registering, entering results and receiving the results reports problem. In HBV panel, 72.6-89.1% and 84.7-90.3% of the participant laboratories were in 1 standard deviation (SD) in 2015-2016, respectively. In HCV panel, 70.8-89.1% and 84.7-90.3% of the participant laboratories were in 1 SD in 2015-2016, respectively. A national external quality control program for HBV DNA and HCV RNA in Turkey has been prepared for the first time with this project and implemented successfully. All the data provided in the MOTAKK external quality control program final report, compensate all the data provided by the quality control program final reports from abroad; additionally, the report allows comparison of used technologies and commercial products