Search results for: antidepressant

Authors: Dorota Witkowska, Paweł Gosek, Lukasz Swiecicki, Wojciech Jernajczyk, Bruce J. West, Miroslaw Latka

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In clinical practice, the selection of an antidepressant often degrades to lengthy trial-and-error. In this work we employ a normalized wavelet power of alpha waves as a biomarker of antidepressant treatment response. This novel EEG metric takes into account both non-stationarity and intersubject variability of alpha waves. We recorded resting, 19-channel EEG (closed eyes) in 22 inpatients suffering from unipolar (UD, n=10) or bipolar (BD, n=12) depression. The EEG measurement was done at the end of the short washout period which followed previously unsuccessful pharmacotherapy. The normalized alpha wavelet power of 11 responders was markedly different than that of 11 nonresponders at several, mostly temporoparietal sites. Using the prediction of treatment response based on the normalized alpha wavelet power, we achieved 81.8% sensitivity and 81.8% specificity for channel T4.

Keywords: alpha waves, antidepressant, treatment outcome, wavelet

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Authors: D. L. Tambe, S. Dighe Nachiket

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Objective: Depression is a common but serious illness and the phenothiazine derivatives shows prominent effect against the depression hence work was undertaken to validate this use scientifically. Material and Methods: Synthesis of phenothiazine derivatives are done by the substitution of various groups, but the basic scheme of synthesis is started with synthesis of 4-(Cyclohexylidene) Benzoic acid using PABA. After that with the further six step of synthesis of 3-(10H-phenothiazin-2-yl)-N, 5-diphenyl-4H-1, 2, 4-triazol-4-amine is done which is final product. Antidepressant activity of all the synthesized compounds was evaluated by despair swim test by using Sprague Dawley Rats. Standard drug imipramine was used as the control. In the despair swim test, all the synthesized derivatives showed antidepressant activity. Results: Among the all phenothiazine derivatives four compounds (6.6-7.2 (14H –phenyl ), 9.43 (1H OH), 8.50 (1H NH phenothiazine),6.85-8.21(14H phenyl), 8.50 (1H NH phenothiazine), 11.82 (1H – OH), 6.6-7.2 (8H –phenyl ), 9.43 (1H OH), 8.50 (1H NH phenothiazine), 4.2 (1H NH) and 6.85-8.21(8H phenyl), 8.50 (1H NH phenothiazine), 3.9 (1H NH) 11.82 (1H – OH) showed significant antidepressant activity comparing with control drug imipramine. Conclusion: Various Novel phenothiazine derivatives show more potent antidepressant activity and it plays more beneficial role in human health for the treatment of depression.

Keywords: antidepressant activities, despair swim test, phenothiazine, Sprague Dawley Rats

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Authors: Dung V. H. Pham, Kathryn Cullen

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Introduction: 40% of adolescents with major depression (MDD) are unresponsive to 1st line antidepressant treatment. The neural mechanism underlying treatment-responsive and treatment-resistant depression in adolescent are unclear. Amygdala is important for emotion processing and has been implicated in mood disorders. Past research has shown abnormal amygdala connectivity in adolescents with MDD. This research study changes in amygdala resting-state functional connectivity to find neural correlates of successful antidepressant treatment. Methods: Thirteen adolescents aged 12-19 underwent rfMRI before and after 8-week antidepressant treatment and completed BDI-II at each scan. A whole-brain approach, using anatomically defined amygdala ROIs (1) identified brain regions that are highly synchronous with the amygdala, (2) correlated neural changes with changes in overall depression and specific symptom clusters within depression. Results: Some neural correlates were common across domains: (1) decreased amygdala RSFC with the default mode network (posterior cingulate, precuneus) is associated with improvement in overall depression and many symptom clusters, (2) increased amygdala RSFC with fusiform gyrus is associated with symptom improvement across many symptom clusters. We also found unique neural changes associated with symptom improvement in each symptom cluster. Conclusion: This is the first preliminary study that looks at neural correlates of antidepressant treatment response to overall depression as well as different clusters of symptoms of depression. The finding suggests both overlapping and distinct neural mechanisms underlying improvement in each symptom clusters within depression. Some brain regions found are also implicated in MDD among adults in previous literature.

Keywords: depression, adolescents, fMRI, antidepressants

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Authors: A. Mech

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Repetitive transcranial magnetic stimulation has proven to be a valuable treatment option for patients who have failed to respond to multiple courses of antidepressant medication. In fact, the American Psychiatric Association recommends TMS after one failed treatment course of antidepressant medication. Genetic testing has proven valuable for pharmacokinetic variables, which, if understood, could lead to more efficient dosing of psychotropic medications to improve outcomes. Pharmacodynamic testing can identify biomarkers, which, if addressed, can improve patients' outcomes in antidepressant therapy. Monotherapy treatment of major depressive disorder with methylated B vitamin treatment has been shown to be safe and effective in patients with MTHFR polymorphisms without waiting for multiple trials of failed medication treatment for depression. Such treatment has demonstrated remission rates similar to antidepressant clinical trials. Combining pharmacodynamics testing with repetitive TMS treatment with NeuroStar has shown promising potential for enhancing remission rates and durability of treatment. In this study, a retrospective chart review (ongoing) of patients who obtained repetitive TMS treatment enhanced by dietary supplementation guided by Pharmacodynamic testing, displayed a greater remission rate (90%) than patients treated with only NeuroStar TMS (62%).

Keywords: improved remission rate, major depressive disorder, pharmacodynamic testing, rTMS outcomes

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Authors: Sangeeta Pilkhwal Sah, C. S. Mathela, Kanwaljit Chopra

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Valeriana wallichii DC, an ayurvedic traditional medicine, popularly named as Indian valerian exist as three chemotypes. GC-MS analysis of V. wallichii essential oil in present study showed maaliol as the major constituent followed by the presence of β-gurjunene, acoradiene, guaiol and α-santalene. The results thus confirmed it to be a maaliol chemotype. Further, the antidepressant-like effect of root essential oil (10, 20 and 40 mg/kg p.o.) was investigated in both acute and chronic treatment study using forced swim test in mice. Single administration of different doses produced an inverted U shaped curve and significantly inhibited the immobility period (39.7% and 58%) at doses 10 and 40 mg/kg respectively. Standard drug imipramine significantly decreased immobility period (59.8%). None of the doses altered locomotor activity except a significant decrease of 44.9% was observed with 40 mg/kg (p < 0.05). Similarly, daily administration of essential oil for 14 days produced a dose dependent effect with significantly reduced immobility period (70.9%) at 40 mg/kg dose only whereas imipramine produced 86% decrease (p < 0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (10%) and dopamine (23%) (p < 0.05) was found at 40 mg/kg dose, while no change was observed at 10 and 20 mg/kg doses. The antidepressant-like effect of essential oil (40 mg/kg) was prevented by pretreatment of mice with L-arginine (750 mg/kg i.p.) and sildenafil (5 mg/kg i.p). On the contrary, pretreatment of mice with L-NAME (10 mg/kg i.p.) or methylene blue (10 mg/kg i.p.) potentiated the antidepressant action of essential oil (20 mg/kg). The findings thus demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.

Keywords: Valeriana wallichii DC chemotype, essential oil, forced swim test, nitric oxide modulators, neurotransmitters

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Authors: Ogbonna Olelewe

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This quality improvement project seeks to address the background and significance of promoting antidepressant (AD) medication adherence to reduce depression symptoms in patients diagnosed with major depression. This project aims to substantiate using daily encrypted short message service (SMS) text reminders to take prescribed antidepressant medications with the goal of increasing medication adherence to reduce depression scores in patients diagnosed with major depression, thereby preventing relapses and increasing remission rates. Depression symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) scale. The PHQ-9 provides a total score of depression symptoms from mild to severe, ranging from 0 to 27. A -pretest/post-test design was used, with a convenience sample size of 35 adult patients aged 18 years old to 45 years old, diagnosed with MDD, and prescribed at least one antidepressant for one year or more. Pre- and post-test PHQ-9 scores were conducted to compare depression scores before and after the four-week intervention period. The results indicated improved post-intervention PHQ-9 scores, improved AD medication adherence, and a significant reduction in depression symptoms.

Keywords: major depressive disorder, antidepressants, short message services, text reminders, Medication adherence/non-adherence, Patient Health Questionnaire 9

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Authors: Samiah Rehman, Kashmira J. Gohil

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Objective: Dracaena trifascaita extract (DTE) possesses strong antioxidant and anti-inflammatory properties that play a vital role in the treatment of mental disorders like depression. The present study was designed to evaluate the antidepressant effects of hydroalcoholic extracts of DT on behavioral models of depression. Methodology: Animals were randomly divided into 6 groups of 5 each: Group 1 and 2 received distilled water and standard drug, imipramine: 25mg/kg, respectively. Groups 4, 5 and 6 received DTE treatment orally at doses of 200 ,400 and 600mg/ kg, respectively, for 14 days. Time of immobility was noted by force swimming test (FST)and tail suspension test (TST) on the 1st,7th and 14th days. Results: The time of immobility was reduced in the treatment group as compared to the control and standard. DTE600 mg/kg showed the highest and most significant antidepressant effects as compared to the standard drug imipramine. (25mg/kg). Conclusion: DTE has good potential as an alternative therapy for depression.

Keywords: Dracaena trifasciata, antidepressants, force swimming test, tail suspension test, herbal drug of depression

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Authors: D: Gupta, M. Radhakrishnan, Y. Kurhe, D. Thangaraj

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Depression is among the leading causes of death worldwide. The current pharmacotherapy is associated with poor compliance, resistance and relapse, which necessitate the development of novel compounds with better efficacy. The present study designed and synthesized EQC-34 (N-cyclohexyl-3-ethoxyquinoxalin-2-carboxamide) as novel serotonin type-3 (5HT3) antagonist and evaluated its antidepressant-like effects using neurobehavioral mouse model. 5HT3 antagonism (as pA2 value) was determined on the longitudinal smooth muscle of guinea-pig ileum against 2-methyl-5HT (a 5HT3 agonist). The doses were calculated by dose response of basal locomotor activity. Consequently, effects of EQC-34 on neurobehavioral parameters were measured in forced swim (FST) and tail suspension test (TST). The possible mechanism was estimated by interaction study with fluoxetine (a selective serotonin reuptake inhibitor) and mCPBG (1-(m-chlorophenyl)-biguanide, a selective 5HT3 agonist), and confirmed by potentiation of head twitch response by 5hydroxy-L-tryptophan (5HTP). EQC-34 (1-4 mg/kg, i.p.) produced significant decreased behavioral despair effects in FST and TST. It potentiated fluoxetine response, while mCPBG reduced EQC-34 activity in FST. Further, EQC-34 potentiated 5HTP induced head twitch response. EQC-34 revealed potential antidepressant-like effects, which may involve 5HT3 receptor mediated facilitation of 5HT neurotransmission, thereby reversing the pathological deficiency of monoamines (5HT) observed in depression. Thus, it may be further investigated as promising agent to improve therapeutics of depression.

Keywords: depression, forced swim test, 5HT3 receptor antagonist, serotonin

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Authors: Kye Gilder, Kevin Shan, Amy Halseth, Steve Smith

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This study assessed the effect of prolonged-release naltrexone 32 mg/bupropion 360 mg (NB) on cardiovascular (CV) events in overweight/obese participants at elevated CV risk. Participants must lose ≥2% body weight at 16 wks, without a sustained increase in blood pressure, to continue drug. Only serious adverse events (SAE) and adverse events leading to discontinuation of study drug (AELDSD) were collected. The study was terminated early after second interim analysis with 50% of all CV events. Data on CV endpoints has been published. Current analyses focused on AEs in participants on antidepressants at baseline, as these individuals were excluded from Phase 3 trials. Intent-to-treat (ITT) population (placebo [PBO] N=4450, NB N=4455) was 54.5% female, 83.5% white, mean age of 61 yrs, mean BMI 37.3 kg/m2, 22.8% with a history of depression, 23.1% on antidepressants, including 15.4% on an SSRI. SAEs in participants receiving antidepressants was similar between NB (10.7%) and PBO (9.9%) and also similar to overall population (9.5% NB, 8.1% PBO). SAEs in those on SSRIs were similar, 10.1% NB and PBO 9.4%. For those on SSRIs or other antidepressants, AELDSDs were similar to overall population and were primarily GI disorders. Obesity increases the risk of developing depression. For participants taking NB and antidepressants, including SSRIs, there is a similar AE profile as the overall population and data revealed no evidence of an additional health risk with combined use.

Keywords: antidepressant, Contrave, Mysimba, obesity, pharmacotherapy

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Authors: Rachid Mosbah, Aziez Chettoum, Zouhir Djerrou, Alberto Mantovani

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Selective serotonin reuptake inhibitors (SSRI) are a class of molecules used in treating depression, anxiety, and mood disorders. Paroxetine (PRT) is one of the mostly prescribed antidepressant which has attracted great attention regarding its side effects in recent years. This study was planned to assess the adverse effects of PRT on the biochemical parameters and reproductive system. Fourteen male Wistar rats were randomly allocated into two groups (7 rats or each): control and treated with PRT at dose of 5mg/kg.bw for two weeks. At the end of the experiment, blood was collected from retro orbital plexus for measuring the biochemical parameters, whereas the reproductive organs were removed for measuring semen quality and the histological investigations. Results showed that PRT induced significant changes in some biochemical parameters and alteration of semen quality including sperm count, spermatids number and sperm viability, motility, and abnormalities. The histopathological examinations of testis and epididymis revealed an alteration of spermatogenesis, cellular disorganization and vacuolization, enlargement of interstitial space, shrinkage and degenerative changes in the epithelium of seminiferous and epididymal tubules with few to nil numbers of spermatozoa in their lumen. In conclusion, PRT treatment caused changes in some biochemical parameters and sperm profile as well as histopathologic effects of reproductive organs.

Keywords: antidepressant, biochemical parameters, reproductive function, paroxetine

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Authors: Horia Păunescu

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Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was "blinded" to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests.Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: antidepressant, depressant, forced swim, NSAIDs

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Authors: Abdulwahhab Khedr, Tamer Shehata, Hanaa El-Ghamry

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Venlafaxine HCl is a novel antidepressant drug used in the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. Conventional therapeutic regimens with venlafaxine HCl immediate-release dosage forms require frequent dosing due to short elimination half-life of the drug and reduced bioavailability. Hence, this study was carried out to develop sustained-release dosage forms of venlafaxine HCl to reduce its dosing frequency, to improve patient compliance and to reduce side effects of the drug. The polymers used were hydroxypropylmethyl cellulose, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, Carbopol 940 and ethyl cellulose. The physical properties of the prepared tablets including tablet thickness, diameter, weight uniformity, content uniformity, hardness and friability were evaluated. Also, the in-vitro release of venlafaxine HCl from different matrix tablets was studied. Based on physical characters and in-vitro release profiles, certain formulae showing promising sustained-release profiles were subjected to film coating with 15% w/v EC in dichloromethane/ethanol mixture (1:1 ratio) using 1% w/v HPMC as pore former and 30% w/w dibutyl phthalate as plasticizer. The optimized formulations were investigated for drug-excipient compatibility using FTIR and DSC studies. Physical evaluation of the prepared tablets fulfilled the pharmacopoeial requirements for tablet friability test, where the weight loss of the prepared formulae did not exceed 1% of the weight of the tested tablets. Moderate release was obtained from tablets containing HPMC. FTIR and DSC studies for such formulae revealed the absence of any type of chemical interaction between venlafaxine HCl and the used polymers or excipients. Forced swimming test in rats was used to evaluate the antidepressant activity of the selected matrix tablets of venlafaxine HCl. Results showed that formulations significantly decreased the duration of animals’ immobility during the 24 hr-period of the test compared to non-treated group.

Keywords: antidepressant, sustained-release, matrix tablet, venlafaxine hydrochloride

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Authors: Aniket Kumar, Jacob Peedicayil

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Major depressive disorder (MDD) is a common and important psychiatric disorder. Several clinical features of MDD suggest an epigenetic basis for its pathogenesis. Since epigenetics (heritable changes in gene expression not involving changes in DNA sequence) may underlie the pathogenesis of MDD, epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) and histone deactylase inhibitors (HDACi) may be useful for treating MDD. The available literature indexed in Pubmed on preclinical drug trials of epigenetic drugs for the treatment of MDD was investigated. The search terms we used were ‘depression’ or ‘depressive’ and ‘HDACi’ or ‘DNMTi’. Among epigenetic drugs, it was found that there were 3 preclinical trials using HDACi and 3 using DNMTi for the treatment of MDD. All the trials were conducted on rodents (mice or rats). The animal models of depression that were used were: learned helplessness-induced animal model, forced swim test, open field test, and the tail suspension test. One study used a genetic rat model of depression (the Flinders Sensitive Line). The HDACi that were tested were: sodium butyrate, compound 60 (Cpd-60), and valproic acid. The DNMTi that were tested were: 5-azacytidine and decitabine. Among the three preclinical trials using HDACi, all showed an antidepressant effect in animal models of depression. Among the 3 preclinical trials using DNMTi also, all showed an antidepressant effect in animal models of depression. Thus, epigenetic drugs, namely, HDACi and DNMTi, may prove to be useful in the treatment of MDD and merit further investigation for the treatment of this disorder.

Keywords: DNA methylation, drug discovery, epigenetics, major depressive disorder

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Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

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Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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Authors: Mia Schneeweiss, Joseph Merola

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Atopic dermatitis (AD) is a chronic inflammatory skin condition with a prevalence of 9.6 million in children under the age of 18 in the US, 3.2 million of those suffer severe AD. AD has significant effects on the quality of life and psychiatric comorbidity in affected patients. We sought to quantify the use of psychotropic medications and mental health services in children. We used longitudinal claims data form commercially insured patients in the US between 2003 and 2016 to identify children aged 18 or younger with a diagnosis of AD associated with an outpatient or inpatient encounter. A 180-day enrollment period was required before the first diagnosis of AD. Among those diagnosed, we computed the use of psychiatric services and dispensing of psychotropic medications during the following 6 months. Among 1.6 million children <18 years with a diagnosis of AD, most were infants (0-1 years: 17.6%), babies (1-2 years: 12.2%) and young children (2-4 years: 15.4). 5.1% were in age group 16-18 years. Among younger children 50% of patients were female, after the age of 14 about 60% were female. In 16-18 years olds 6.4% had at least one claim with a recorded psychopathology during the 6-month baseline period; 4.6% had depression, 3.3% anxiety, 0.3% panic disorder, 0.6% psychotic disorder, 0.1% anorexia. During the 6 months following the physician diagnosis of AD, 66% used high-potency topical corticosteroids, 3.5% used an SSRI, 0.3% used an SNRI, 1.2% used a tricyclic antidepressant, 1.4% used an antipsychotic medication, and 5.2% used an anxiolytic agent. 4.4% had an outpatient visit with a psychiatrist and 0.1% had been hospitalized with a psychiatric diagnosis. In 14-16 years olds, 4.7% had at least one claim with a recorded psychopathology during the 6-month baseline period; 3.3% had depression, 2.5% anxiety, 0.2% panic disorder, 0.5% psychotic disorder, 0.1% anorexia. During the 6 months following the physician diagnosis of AD, 68% used high-potency topical corticosteroids, 4.6% used an SSRI, 0.6% used an SNRI, 1.5% used a tricyclic antidepressant, 1.4% used an antipsychotic medication, and 4.6% used an anxiolytic agent. 4.7% had an outpatient visit with a psychiatrist and 0.1% had been hospitalized with a psychiatric diagnosis. In 12-14 years olds, 3.3% had at least one claim with a recorded psychopathology during the 6-month baseline period; 1.9% had depression, 2.2% anxiety, 0.1% panic disorder, 0.7% psychotic disorder, 0.0% anorexia. During the 6 months following the physician diagnosis of AD, 67% used high-potency topical corticosteroids, 2.1% used an SSRI, 0.1% used an SNRI, 0.7% used a tricyclic antidepressant, 0.9 % used an antipsychotic medication, and 4.1% used an anxiolytic agent. 3.8% had an outpatient visit with a psychiatrist and 0.05% had been hospitalized with a psychiatric diagnosis. In younger children psychopathologies were decreasingly common: 10-12: 2.8%; 8-10: 2.3%; 6-8: 1.3%; 4-6: 0.6%. In conclusion, there is substantial psychiatric comorbidity among children, <18 years old, with diagnosed atopic dermatitis in a US commercially insured population. Meaningful psychiatric medication use (>3%) starts as early as 12 years old.

Keywords: pediatric atopic dermatitis, phychotropic medication use, psychiatric comorbidity, claims database

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Authors: Selam Mulugeta, Barkot Milkias, Mesfin Araya, Abel Worku, Eyasu Mulugeta

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In Ethiopia, there is inadequate information on non-adherence to antidepressant treatment in patients with depressive disorders. Having awareness of the pattern of adherence is important in future prognosis, quality of life, and functionality in these patients. This hospital-based cross-sectional quantitative study was done on a sample of 216 consecutive outpatients with depressive disorders. Data were collected using questionnaires through in-person and phone call interviews. The 8-item Morisky scale was used to assess the pattern of medication adherence. Other specially developed tools were used to obtain sociodemographic and clinical information from electronic medical records and patient interviews. Data were analyzed using the Statistical Package for the Social Sciences Version - 25. Univariate and multivariable analyses were carried out to assess factors associated with non-adherence. 90% of the participants had a primary diagnosis of major depressive disorder. Based on the 8-item Morisky Medication Adherence Scale, the prevalence of non-adherence was found to be 84.7%. Living distance between 11 to 50 km from the hospital (AOR= 11, 95% CI (29,46.6)), post-secondary level of education (AOR= 8.3, 95% CI (1, 64.4)) and taking multiple medications (AOR= 6.1, 95% CI (1, 34.9)) were found to have significantly increased odds of non-adherence. Non-adherence was significantly associated with factors such as increased living distance from the hospital, relatively higher educational level, and polypharmacy. Proper and patient-centered psychoeducation, addressing the communication gap between patients and doctors, adherence to prescribing guidelines, avoiding polypharmacy unless indicated & working on accessibility of treatment is essential to decrease non-adherence.

Keywords: depressive disorders, Ethiopia, medication adherence, Addis Ababa

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Jiangang Shen

Abstract:

Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

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Authors: Neşe Alkan

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Purpose: The point that applied/clinical psychology, which is the practice and research discipline of the mental health field, has reached today can be summarized as the necessity of handling the psychological well-being of people from multiple perspectives and the goal of moving it to a higher level. Clients' subjective assessment of their own condition and wellbeing is an integral part of evidence-based interventions. There is a need for tools through which clients can evaluate the effectiveness of the psychotherapy/intervention performed with them and their contribution to the wellbeing and wellbeing of this process in a valid and reliable manner. The aim of this research is to meet this need, to test the reliability and validity of the index in Turkish, and explore its usability in the practices of both researchers and psychotherapists. Method: A total of 213 adults aged between 18-54, 69.5% working and 29.5% university students, were included in the study. Along with their demographic information, the participants were administered a set of scales: wellbeing, life satisfaction, spiritual satisfaction, shopping addiction, and loneliness, namely via an online platform. The construct validity of the wellbeing scale was tested with exploratory and confirmatory factor analyses, convergent and discriminant validity were tested with two-way full and partial correlation analyses and, measurement invariance was tested with one-way analysis of variance. Results: Factor analyzes showed that the scale consisted of six dimensions as it is in its original structure. The internal consistency of the scale was found to be Cronbach α = .82. Two-way correlation analyzes revealed that the wellbeing scale total score was positively correlated with general life satisfaction (r = .62) and spiritual satisfaction (r = .29), as expected. It was negatively correlated with loneliness (r = -.51) and shopping addiction (r = -.15). While the scale score did not vary by gender, previous illness, or nicotine addiction, it was found that the total wellbeing scale scores of the participants who had used antidepressant medication during the past year were lower than those who did not use antidepressant medication (F(1,204) = 7.713, p = .005). Conclusion: It has been concluded that the 12-item wellbeing scale consisting of six dimensions can be used in research and health sciences practices as a valid and reliable measurement tool. Further research which examines the reliability and validity of the scale in different widely used languages such as Spanish and Chinese is recommended.

Keywords: wellbeing, intervention effectiveness, reliability and validity, effectiveness

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Authors: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

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Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

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Authors: Rita Hairani, Warinthorn Chavasiri

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Naphthoquinones are secondary metabolites widespread in nature and can be produced by plants, fungi and actinomycetes. The interest of naphthoquinones is not only limited as organic dyes, but also their wide variety of biological activities such as antitumor, antibacterial, and cytotoxic activities. Typical 1,2-naphthoquinones such as mansonones can be found in Mansonia gagei Drumm. (“chan-cha-mod”), Sterculaceae family. This plant has been used traditionally to treat some diseases such as antiemetic and antidepressant. In this study, some natural mansonones isolated from the CH2Cl2 extract of M. gagei heartwood have been assessed for their antibacterial activities using agar well diffusion method. According to the antibacterial activity results of four natural mansonones (mansonones C, E, G and H), mansonones E and G showed higher activities than the others against Staphylococcus aureus, Propionibacterium acnes and Salmonella typhi, respectively. Since mansonone G exhibited good antibacterial activity and was obtained in the highest yield, we decided to derivertize mansonone G into five ether analogues. Based on the antibacterial activities of these synthesized compounds, four ether analogues (compounds 1-4) revealed higher antibacterial activities than its natural mansonone G against S. aureus and S. typhi.

Keywords: Mansonia gagei Drumm., antibacterial activities, mansonone G, ether analogues

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Authors: David Tresner-Kirsch

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Reconciling patient medication lists from multiple sources is a critical task supporting the safe delivery of patient care. Manual reconciliation is a time-consuming and error-prone process, and recently attempts have been made to develop efficiency- and safety-oriented automated support for professionals performing the task. An important capability of any such support system is automated alignment – finding which medications from a list correspond to which medications from a different source, regardless of misspellings, naming differences (e.g. brand name vs. generic), or changes in treatment (e.g. switching a patient from one antidepressant class to another). This work describes a new algorithmic solution to this alignment task, using a greedy matching approach based on string similarity, edit distances, concept extraction and normalization, and synonym search derived from the RxNorm nomenclature. The accuracy of this algorithm was evaluated against a gold-standard corpus of 681 medication records; this evaluation found that the algorithm predicted alignments with 99% precision and 91% recall. This performance is sufficient to support decision support applications for medication reconciliation.

Keywords: clinical decision support, medication reconciliation, natural language processing, RxNorm

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Authors: Samia A. El-Fiky, Fouad A. Abou-Zaid, Ibrahim M. Farag, Naira M. El-Fiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: chromosome aberrations, clomipramine, mice, histopathology, sperm abnormalities

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Authors: Kedar S. Prabhavalkar, Nimmy Baby Poovanpallil

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Lamotrigine is approved for maintenance treatment of bipolar I disorder. However, its role in the treatment of acute bipolar depression is not well clear. Its efficacy in the treatment of major depressive disorders including refractory unipolar depression suggested the use of lamotrigine as an augmentation drug for acute bipolar depression. The present study aims to evaluate and perform a comparative analysis of the therapeutic effects of lamotrigine, an epileptic mood stabilizer, when used alone and in combination with duloxetine in treating acute bipolar depression at different doses of lamotrigine. Male swiss albino mice were used. For evaluation of efficacy of combination, immobility period was analyzed 30 min after the treatment from forced swim and tail suspension tests. Further amount of sucrose consumed in sucrose preference test was estimated. The combination of duloxetine and lamotrigine showed potentiation of antidepressant activity in acute models. Decrease in immobility time and increase in the amount of sucrose consumption in stressed mice were higher in combined group compared to lamotrigine monotherapy group. Brain monoamine levels were also attenuated more with combination compared to monotherapy. Results of the present study suggest potential role of lamotrigine and duloxetine combination in the treatment of acute bipolar depression.

Keywords: lamotrigine, duloxetine, acute bipolar depression, augmentation

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Authors: José Neves, M. Rosário Martins, Fátima Candeias, Diana Ferreira, Sílvia Arantes, Júlio Cruz-Morais, Guida Gomes, Joaquim Macedo, António Abelha, Henrique Vicente

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Some plants of genus Schinus have been used in the folk medicine as topical antiseptic, digestive, purgative, diuretic, analgesic or antidepressant, and also for respiratory and urinary infections. Chemical composition of essential oils of S. molle and S. terebinthifolius had been evaluated and presented high variability according with the part of the plant studied and with the geographic and climatic regions. The pharmacological properties, namely antimicrobial, anti-tumoural and anti-inflammatory activities are conditioned by chemical composition of essential oils. Taking into account the difficulty to infer the pharmacological properties of Schinus essential oils without hard experimental approach, this work will focus on the development of a decision support system, in terms of its knowledge representation and reasoning procedures, under a formal framework based on Logic Programming, complemented with an approach to computing centered on Artificial Neural Networks and the respective Degree-of-Confidence that one has on such an occurrence.

Keywords: artificial neuronal networks, essential oils, knowledge representation and reasoning, logic programming, Schinus molle L., Schinus terebinthifolius Raddi

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Authors: D. S. Mohale, A.V. Chandewar

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Study was undertaken to investigate the effect of imipramine on various biochemical parameters and oxidative stress markers in short and long term depression on rats. Rats were subjected for short (21 days) and long term (84 days) social isolation for and checked for depression on force swim test and tail suspension method. Various markers of oxidative stress like lipid peroxidation (LPO), reduced glutathione (GSH), Supersoxide dismutase (SOD), catalase (CAT) and biochemical parameters like Serum glutamate oxaloacetate transaminase (SGOT), Serum glutamate pyruate transaminase (SGPT), and blood glucose were determined in depressed, control, imipramine and Vitamin E treated group. The rats displayed an increase in depression on force swim test and tail suspension method relative to control. There was significant increase in the level of LPO and decrease in the levels of GSH, SOD and CAT after short and long term depression. Increased oxidative stress in depression which may leads to alteration of biochemical parameters. Treatment with imipramine an tricyclic antidepressant significantly decreases in level of LPO, SGOT, SGPT and increase in the levels of GSH, SOD and CAT in long term depression.

Keywords: depression, oxidative stress, lipid peroxidation, reduced glutathione

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Authors: Berit Johannessen

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Introduction: Depression and dementia are the two most common psychiatric disorders of older people. The use of antidepressants does not always have the desired effect and serious side effects are common. Aroma therapists claim that the essential oil of Bergamot has an antidepressant effect. Aromatherapy is defined as holistic or complementary medicine and is rarely used in the Norwegian public health service, but in recent years, there has been an increasing interest in, and use of complementary and alternative therapies (CAM) in the Norwegian population, and aromatherapy is one of the most widely used. Focus for this study: How do nurses experience the use of Bergamot essential oil for patients suffering from dementia and depression? Method: Action research study including 12 patients and 8 nurses. The patients were strategically selected by the nurses and were given Bergamot in a fan diffuser every day for 12 weeks. The patients' mood and behavior patterns were reported daily and the nurse`s experiences were reported weekly. Individual interviews with the nurses were conducted at the end of the project. Results: The nurses reported that bergamot had positive impact on patients mood and wellbeing, and was considered as an effective method for six patients, four had uncertain effect and two had no effect. They also reported less use of medication and that the fan diffusers were easy and pleasant to administer. They found the use of natural remedies as Bergamot inspiring and wanted to learn more about aromatherapy and its use in nursing. Some were disturbed by the smell and some had to deal with critical and negative colleagues. Conclusion: Nurses experienced aromatherapy using bergamot oil in fan diffusers as a simple and useful procedure for patients suffering from dementia and depression. The effects were varying. Further research is needed.

Keywords: aromatherapy, bergamot, dementia, depression

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Authors: Nafiseh Noormohammadi, Ahmad Sobhani Najafabadi

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Hypericins (hypericin and pseudohypericin) are natural napthodianthrone derivatives produced by Hypericum perforatum (St. John’s Wort), which have many medicinal properties such as antitumor, antineoplastic, antiviral, and antidepressant activities. Production and accumulation of hypericin in the plant are influenced by both genetic and environmental conditions. Despite the existence of different high-throughput data on the plant, genetic dimensions of hypericin biosynthesis have not yet been completely understood. In this research, 21 high-quality RNA-seq data on different parts of the plant were integrated into metabolic data to reconstruct a coexpression network. Results showed that a cluster of 30 transcripts was correlated with total hypericin. The identified transcripts were divided into three main groups based on their functions, including hypericin biosynthesis genes, transporters, detoxification genes, and transcription factors (TFs). In the biosynthetic group, different isoforms of polyketide synthase (PKSs) and phenolic oxidative coupling proteins (POCPs) were identified. Phylogenetic analysis of protein sequences integrated into gene expression analysis showed that some of the POCPs seem to be very important in the biosynthetic pathway of hypericin. In the TFs group, six TFs were correlated with total hypericin. qPCR analysis of these six TFs confirmed that three of them were highly correlated. The identified genes in this research are a rich resource for further studies on the molecular breeding of H. perforatum in order to obtain varieties with high hypericin production.

Keywords: hypericin, St. John’s Wort, data mining, transcription factors, secondary metabolites

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Authors: Nur Hidayah Kaz Abdul Aziz, Norhalida Hashim, Zurina Hassan

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Peripartum period is a time where women are vulnerable to depression, and stress may further increase the risk of its occurrence. Use of selective serotonin reuptake inhibitors (SSRI) in the treatment of postpartum depression is a common practice. Comparison of antidepressant treatment, however, is rarely studied between gestated and nulliparous animals exposed to stress. This study was aimed to investigate the effect of parity and stress, as well as fluoxetine (an SSRI) treatment after stress exposure on the behavior of rats. Gestating and nulliparous Sprague Dawley rats were either subjected to chronic stressors or left undisturbed throughout the gestation period. After parturition, all stressors were stopped and some of the stressed rats were treated with fluoxetine (10mg/kg). Hence, the final groups formed were: 1. Non-stressed nulliparous rats, 2. Non-stressed dams, 3. Stressed nulliparous rats, 4. Stressed dams, 5. Fluoxetine-treated stressed nulliparous rats, and 6. Fluoxetine-treated stressed dams. Rats were tested in open field test (OFT), novel object recognition test (NOR) and forced swim test (FST) after weaning of pups. Gestational stress significantly reduced the locomotor activity of rats in OFT (p<0.05), while fluoxetine significantly increased the activity in nulliparous rats (p<0.001) but not the dams. While no differences were observed in NOR, stress and parity inhibited the rats from performing swimming behavior in FST. However, climbing and immobile behaviors in FST were found to have no significant differences, although there is a tendency of effect of treatment for immobility parameter (p=0.06) where fluoxetine-treated stressed dams were being the least immobile. In conclusion, the effects of parity and stress, as well as fluoxetine treatment, depended on the type of behavioral test performed.

Keywords: stress, parity, SSRI, behavioral tests

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Authors: Jana Tchekalarova, Milena Atanasova, Katerina Georgieva

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Melatonin deficit can cause a disturbance in emotional status and circadian rhythms of the endocrine system in the body. Both pharmacological and alternative approaches are applied for correction of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we tested and compare the beneficial effect of agomelatine (40 mg/kg, i.p. for 3 weeks) and endurance training on depressive behavior in two models of melatonin deficit in rat. The role of disturbed circadian rhythms of plasma melatonin and corticosterone secretion in the mechanism of these treatments was also explored. The continuous exercise program attenuated depressive responses associated with disrupted diurnal rhythm of home-cage motor activity, anhedonia in the sucrose preference test, and despair-like behavior in the forced swimming test were attenuated by agomelatine exposed to chronic constant light (CCL) and long-term exercise in pinealectomized rats. Parallel to the observed positive effect on the emotional status, agomelatine restored CCL-induced impairment of circadian patterns of plasma melatonin but not that of corticosterone. In opposite, exercise training diminished total plasma corticosterone levels and corrected its flattened pattern while it was unable to correct melatonin deficit in pinealectomy. These results suggest that the antidepressant-like effect of pharmacological and alternative approach might be mediated via two different mechanism, correction of the disturbed circadian rhythm of melatonin and corticosterone, respectively. Therefore, these treatment approaches might have a potential therapeutic application in different subpopulations of people characterized by a melatonin deficiency. This work was supported by the National Science Fund of Bulgaria (research grant # № DN 03/10; DN# 12/6).

Keywords: agomelatine, exercise training, melatonin deficit, corticosterone

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