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Automated Depression Detection Using Deep Representation and Sequence Learning with EEG Signals

Ay B, Yildirim O, Talo M, Baloglu UB, Aydin G, Puthankattil SD, et al.

J Med Syst, 2019 May 28;43(7):205.
PMID: 31139932 DOI: 10.1007/s10916-019-1345-y

Depression affects large number of people across the world today and it is considered as the global problem. It is a mood disorder which can be detected using electroencephalogram (EEG) signals. The manual detection of depression by analyzing the EEG signals requires lot of experience, tedious and time consuming. Hence, a fully automated depression diagnosis system developed using EEG signals will help the clinicians. Therefore, we propose a deep hybrid model developed using convolutional neural network (CNN) and long-short term memory (LSTM) architectures to detect depression using EEG signals. In the deep model, temporal properties of the signals are learned with CNN layers and the sequence learning process is provided through the LSTM layers. In this work, we have used EEG signals obtained from left and right hemispheres of the brain. Our work has provided 99.12% and 97.66% classification accuracies for the right and left hemisphere EEG signals respectively. Hence, we can conclude that the developed CNN-LSTM model is accurate and fast in detecting the depression using EEG signals. It can be employed in psychiatry wards of the hospitals to detect the depression using EEG signals accurately and thus aid the psychiatrists.

Matched MeSH terms: Depression/physiopathology*
Neurophysiological correlates of depressive symptoms in young adults: A quantitative EEG study

Lee PF, Kan DPX, Croarkin P, Phang CK, Doruk D

J Clin Neurosci, 2018 Jan;47:315-322.
PMID: 29066239 DOI: 10.1016/j.jocn.2017.09.030

BACKGROUND: There is an unmet need for practical and reliable biomarkers for mood disorders in young adults. Identifying the brain activity associated with the early signs of depressive disorders could have important diagnostic and therapeutic implications. In this study we sought to investigate the EEG characteristics in young adults with newly identified depressive symptoms.
METHODS: Based on the initial screening, a total of 100 participants (n = 50 euthymic, n = 50 depressive) underwent 32-channel EEG acquisition. Simple logistic regression and C-statistic were used to explore if EEG power could be used to discriminate between the groups. The strongest EEG predictors of mood using multivariate logistic regression models.
RESULTS: Simple logistic regression analysis with subsequent C-statistics revealed that only high-alpha and beta power originating from the left central cortex (C3) have a reliable discriminative value (ROC curve >0.7 (70%)) for differentiating the depressive group from the euthymic group. Multivariate regression analysis showed that the single most significant predictor of group (depressive vs. euthymic) is the high-alpha power over C3 (p = 0.03).
CONCLUSION: The present findings suggest that EEG is a useful tool in the identification of neurophysiological correlates of depressive symptoms in young adults with no previous psychiatric history.
SIGNIFICANCE: Our results could guide future studies investigating the early neurophysiological changes and surrogate outcomes in depression.

Matched MeSH terms: Depression/physiopathology*
Fulltext Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms

Lim LW, Prickaerts J, Huguet G, Kadar E, Hartung H, Sharp T, et al.

Transl Psychiatry, 2015;5:e535.
PMID: 25826110 DOI: 10.1038/tp.2015.24

Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.

Matched MeSH terms: Depression/physiopathology*
New insights on brain-derived neurotrophic factor epigenetics: from depression to memory extinction

Poon CH, Heng BC, Lim LW

Ann N Y Acad Sci, 2021 01;1484(1):9-31.
PMID: 32808327 DOI: 10.1111/nyas.14458

Advances in characterizing molecular profiles provide valuable insights and opportunities for deciphering the neuropathology of depression. Although abnormal brain-derived neurotrophic factor (BDNF) expression in depression has gained much support from preclinical and clinical research, how it mediates behavioral alterations in the depressed state remains largely obscure. Environmental factors contribute significantly to the onset of depression and produce robust epigenetic changes. Epigenetic regulation of BDNF, as one of the most characterized gene loci in epigenetics, has recently emerged as a target in research on memory and psychiatric disorders. Specifically, epigenetic alterations of BDNF exons are heavily involved in mediating memory functions and antidepressant effects. In this review, we discuss key research on stress-induced depression from both preclinical and clinical studies, which revealed that differential epigenetic regulation of specific BDNF exons is associated with depression pathophysiology. Considering that BDNF has a central role in depression, we argue that memory extinction, an adaptive response to fear exposure, is dependent on BDNF modulation and holds promise as a prospective target for alleviating or treating depression and anxiety disorders.

Matched MeSH terms: Depression/physiopathology
The antidepressant effects of ventromedial prefrontal cortex stimulation is associated with neural activation in the medial part of the subthalamic nucleus

Lim LW, Janssen ML, Kocabicak E, Temel Y

Behav Brain Res, 2015 Feb 15;279:17-21.
PMID: 25446757 DOI: 10.1016/j.bbr.2014.11.008

The nucleus accumbens (NAc), ventromedial prefrontal cortex (vmPFC), and cingulate gyrus (Cg) are key regions in the control of mood-related behaviors. Electrical stimulation of these areas induces antidepressant-like effects in both patients and animal models. Another structure whose limbic connections are receiving more interest in the context of mood-related behaviors is the medial part of the subthalamic nucleus (STN). Here, we tested the hypothesis that the mood-related effects of NAc, vmPFC, and Cg are accompanied by changes in the neural activity of the STN. We performed high-frequency stimulation (HFS) of the NAc, vmPFC, and Cg. Animals were behaviorally tested for hedonia and forced swim immobility; and the cellular activities in the different parts of the STN were assessed by means of c-Fos immunoreactivity (c-Fos-ir). Our results showed that HFS of the NAc and vmPFC, but not Cg reduced anhedonic-like and forced swim immobility behaviors. Interestingly, there was a significant increase of c-Fos-ir in the medial STN with HFS of the vmPFC, but not the NAc and Cg as compared to the sham. Correlation analysis showed that the medial STN is associated with the antidepressant-like behaviors in vmPFC HFS animals. No behavioral correlation was found with respect to behavioral outcome and activity in the lateral STN. In conclusion, HFS of the vmPFC induced profound antidepressant-like effects with enhanced neural activity in the medial part of the STN.

Matched MeSH terms: Depression/physiopathology*
Fulltext Mood and memory function in ovariectomised rats exposed to social instability stress

Al-Rahbi B, Zakaria R, Othman Z, Hassan A, Muthuraju S, Wan Mohammad WM

Biomed Res Int, 2013;2013:493643.
PMID: 23841073 DOI: 10.1155/2013/493643

This study aims to compare the effects of social instability stress on memory and anxiety- and depressive-like behaviour between sham-operated controls and ovariectomised (OVX) rats. Forty adult female Sprague-Dawley rats (8 weeks old) were randomly divided into four groups, (n = 10 per group). These were non-stressed sham-operated control rats, stressed sham-operated control rats, non-stressed OVX rats, and stressed OVX rats. The rats were subjected to social instability stress procedure for 15 days. Novel object recognition, open field, and forced swim tests were conducted after the stress procedure. Serum estradiol, ACTH and corticosterone levels were measured using commercially available ELISA kits. Lower serum estradiol level and uterine weight with higher weight gain were observed in OVX rats compared to sham-operated controls. Serum ACTH, and corticosterone levels were higher in stressed compared to non-stressed groups. Memory deficit and anxiety- and depressive-like behaviour were significantly increased in stressed compared to non-stressed OVX rats but these changes were not seen in sham-operated controls. These results suggest that the high circulating corticosterone acts synergistically with low circulating estradiol to exert negative effects on mood and memory function.

Matched MeSH terms: Depression/physiopathology
Fulltext Depression, distress and self-efficacy: The impact on diabetes self-care practices

Devarajooh C, Chinna K

PLoS One, 2017;12(3):e0175096.
PMID: 28362861 DOI: 10.1371/journal.pone.0175096

The prevalence of type 2 diabetes is increasing in Malaysia, and people with diabetes have been reported to suffer from depression and diabetes distress which influences their self-efficacy in performing diabetes self-care practices. This interviewer administered, cross sectional study, conducted in the district of Hulu Selangor, Malaysia, involving 371 randomly selected patients with type 2 diabetes, recruited from 6 health clinics, aimed to examine a conceptual model regarding the association between depression, diabetes distress and self-efficacy with diabetes self-care practices using the partial least square approach of structural equation modeling. In this study, diabetes self-care practices were similar regardless of sex, age group, ethnicity, education level, diabetes complications or type of diabetes medication. This study found that self-efficacy had a direct effect on diabetes self-care practice (path coefficient = 0.438, p<0.001). Self-care was not directly affected by depression and diabetes distress, but indirectly by depression (path coefficient = -0.115, p<0.01) and diabetes distress (path coefficient = -0.122, p<0.001) via self-efficacy. In conclusion, to improve self-care practices, effort must be focused on enhancing self-efficacy levels, while not forgetting to deal with depression and diabetes distress, especially among those with poorer levels of self-efficacy.
Study site: 6 primary health clinics (Klinik Kesihatan), Hulu Selangor. Selangor. Malaysia

Matched MeSH terms: Depression/physiopathology*
Fulltext Irritable Bowel Syndrome, Depression, and Neurodegeneration: A Bidirectional Communication from Gut to Brain

Aziz MNM, Kumar J, Muhammad Nawawi KN, Raja Ali RA, Mokhtar NM

Nutrients, 2021 Aug 31;13(9).
PMID: 34578939 DOI: 10.3390/nu13093061

Patients with irritable bowel syndrome (IBS) are increasingly presenting with a wide range of neuropsychiatric symptoms, such as deterioration in gastroenteric physiology, including visceral hypersensitivity, altered intestinal membrane permeability, and gastrointestinal motor dysfunction. Functional imaging of IBS patients has revealed several abnormalities in various brain regions, such as significant activation of amygdala, thinning of insular and anterior cingulate cortex, and increase in hypothalamic gray matter, which results in poor psychiatric and cognitive outcomes. Interrelations between the enteric and central events in IBS-related gastrointestinal, neurological, and psychiatric pathologies have compelled researchers to study the gut-brain axis-a bidirectional communication that maintains the homeostasis of the gastrointestinal and central nervous system with gut microbiota as the protagonist. Thus, it can be disrupted by any alteration owing to the gut dysbiosis or loss of diversity in microbial composition. Available evidence indicates that the use of probiotics as a part of a balanced diet is effective in the management of IBS and IBS-associated neurodegenerative and psychiatric comorbidities. In this review, we delineate the pathogenesis and complications of IBS from gastrointestinal and neuropsychiatric standpoints while also discussing the neurodegenerative events in enteric and central nervous systems of IBS patients and the therapeutic potential of gut microbiota-based therapy established on clinical and preclinical data.

Matched MeSH terms: Depression/physiopathology
Vitamin D and Depression: The Evidence from an Indirect Clue to Treatment Strategy

Wong SK, Chin KY, Ima-Nirwana S

Curr Drug Targets, 2018;19(8):888-897.
PMID: 28914205 DOI: 10.2174/1389450118666170913161030

Depression is a common psychiatric disorder that decreases the quality of life and increases the mortality of patients. It incurs significant healthcare costs if left untreated. Even though intervention with antidepressants can reduce depressive symptoms, side effects are often an issue and relapse is very common. Vitamin D, commonly known as the sunshine vitamin, is an essential fat-soluble vitamin for the absorption of calcium to prevent rickets (children) and osteomalacia (adults). Evidence on a possible relationship between vitamin D deficiency and depression is growing. In this review, the authors summarized the evidence on the association between vitamin D status and depression in human observational studies, followed by clinical trials to evaluate the effects of vitamin D supplementation in treating depression. In conclusion, vitamin D deficiency may be associated with an increased risk or severity of depression. Supplementation of vitamin D may confer protection for depressed patients.

Matched MeSH terms: Depression/physiopathology
Pathophysiology of depression: role of sleep and the melatonergic system

Srinivasan V, Pandi-Perumal SR, Trakht I, Spence DW, Hardeland R, Poeggeler B, et al.

Psychiatry Res, 2009 Feb 28;165(3):201-14.
PMID: 19181389 DOI: 10.1016/j.psychres.2007.11.020

Profound disturbances in sleep architecture occur in major depressive disorders (MDD) and in bipolar affective disorders. Reduction in slow wave sleep, decreased latency of rapid eye movement (REM) sleep and abnormalities in the timing of REM/non-REM sleep cycles have all been documented in patients with MDD. It is thus evident that an understanding of the basic mechanisms of sleep regulation is essential for an analysis of the pathophysiology of depressive disorders. The suprachiasmatic nucleus (SCN), which functions as the body's master circadian clock, plays a major role in the regulation of the sleep/wakefulness rhythm and interacts actively with the homeostatic processes that regulate sleep. The control of melatonin secretion by the SCN, the occurrence of high concentrations of melatonin receptors in the SCN, and the suppression of electrical activity in the SCN by melatonin all underscore the major influence which this neurohormone has in regulating the sleep/wake cycle. The transition from wakefulness to high sleep propensity is associated with the nocturnal rise of endogenous melatonin secretion. Various lines of evidence show that depressed patients exhibit disturbances in both the amplitude and shape of the melatonin secretion rhythm and that melatonin can improve the quality of sleep in these patients. The choice of a suitable antidepressant that improves sleep quality is thus important while treating a depressive disorder. The novel antidepressant agomelatine, which combines the properties of a 5-HT(2C) antagonist and a melatonergic MT(1)/MT(2) receptor agonist, has been found very effective for resetting the disturbed sleep/wake cycle and in improving the clinical status of MDD. Agomelatine has also been found useful in treating sleep problems and improving the clinical status of patients suffering from seasonal affective disorder.

Matched MeSH terms: Depression/physiopathology*
Increased psychosocial risk, depression and reduced quality of life living with autosomal dominant polycystic kidney disease

Simms RJ, Thong KM, Dworschak GC, Ong AC

Nephrol Dial Transplant, 2016 07;31(7):1130-40.
PMID: 26268712 DOI: 10.1093/ndt/gfv299

BACKGROUND: The psychosocial impact of living with autosomal dominant polycystic kidney disease (ADPKD) is poorly understood. In this study, we assessed the overall quality of life (QOL), mood, perceived social support and psychosocial risk of having a diagnosis of ADPKD in a patient cohort from a major UK nephrology centre serving a large catchment population.
METHODS: A postal questionnaire was sent to 349 patients registered at the Sheffield Kidney Institute with chronic kidney disease but not on renal replacement therapy (RRT). The questionnaire incorporated three validated forms: kidney disease quality-of-life short form (KDQOL SF1.3) to assess QOL; nine-item patient health questionnaire (PHQ9) to screen for depression; multidimensional scale of perceived social support (MSPSS) to evaluate perceived social support; as well as a novel genetic psychosocial risk instrument (GPRI-ADPKD) designed to study the specific psychosocial impact of coping with a diagnosis of ADPKD.
RESULTS: The overall response rate was 53%. Patients with a lower estimated glomerular filtration rate (<30 mL/min) or larger kidneys (mean length on ultrasound ≥17 cm) reported reduced QOL and increased psychosocial risk. Clinically significant depression was reported in 22% and 62% felt guilty about passing ADPKD on to their children. In multivariate analysis, female gender was associated with overall poorer psychosocial well-being, whereas increasing age, lower kidney function, larger kidneys and loss of a first degree relative from ADPKD were additional risk factors for QOL, depression or psychosocial risk, respectively.
CONCLUSIONS: Our results reveal a significantly poorer QOL and increasing psychosocial risk with markers of disease progression in patients, particularly women, with ADPKD prior to starting RRT. The future management strategy of ADPKD should address these issues and provide for better individual and family support throughout the patient journey.

Matched MeSH terms: Depression/physiopathology
Differences in psychological factors, disability and fatigue according to the grade of chronification in non-specific low back pain patients: A cross-sectional study

Adnan R, Van Oosterwijck J, Danneels L, Willems T, Meeus M, Crombez G, et al.

J Back Musculoskelet Rehabil, 2020;33(6):919-930.
PMID: 33016899 DOI: 10.3233/BMR-191548

BACKGROUND: Differences in pain processing, muscle structure and function have been reported in patients with low back pain (LBP) with different grades of pain chronicity.
OBJECTIVE: The present study aims to examine differences in psychological factors, disability and subjective fatigue between subgroups of LBP based on their chronification grade.
METHODS: Twenty-one healthy controls (HC) and 54 LBP patients (categorized based on the grades of chronicity into recurrent LBP (RLBP), non-continuous chronic LBP (CLBP), or continuous (CLBP)) filled out a set of self-reporting questionnaires.
RESULTS: The Hospital Anxiety and Depression Scale (HADS) and Multidimensional Pain Inventory (MPI) scores indicated that anxiety, pain severity, pain interference and affective distress were lower in HC and RLBP compared to non-continuous CLBP. Anxiety scores were higher in non-continuous CLBP compared to RLBP, continuous CLBP and HC. The Pain Catastrophizing Scale for Helplessness (PSCH) was higher in non-continuous CLBP compared to HC. The Survey of Pain Attitudes (SOPA) showed no differences in adaptive and maladaptive behaviors across the groups. The Pain Disability Index (PDI) measured a higher disability in both CLBP groups compared to HC. Moreover, the Rolland Morris Disability Questionnaire (RMDQ) showed higher levels of disability in continuous CLBP compared to non-continuous CLBP, RLBP and HC. The Checklist Individual Strength (CIS) revealed that patients with non-continuous CLBP were affected to a higher extent by severe fatigue compared to continuous CLBP, RLBP and HC (subjective fatigue, concentration and physical activity). For all tests, a significance level of 0.05 was used.
CONCLUSIONS: RLBP patients are more disabled than HC, but have a tendency towards a general positive psychological state of mind. Non-continuous CLBP patients would most likely present a negative psychological mindset, become more disabled and have prolonged fatigue complaints. Finally, the continuous CLBP patients are characterized by more negative attitudes and believes on pain, enhanced disability and interference of pain in their daily lives.

Matched MeSH terms: Depression/physiopathology
Fulltext Network analysis of the depressive symptom profiles in Asian patients with depressive disorders: Findings from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD)

Park SC, Jang EY, Xiang YT, Kanba S, Kato TA, Chong MY, et al.

Psychiatry Clin Neurosci, 2020 Jun;74(6):344-353.
PMID: 32048773 DOI: 10.1111/pcn.12989

AIM: We aimed to estimate the network structures of depressive symptoms using network analysis and evaluated the geographic regional differences in theses network structures among Asian patients with depressive disorders.
METHODS: Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), the network of the ICD-10 diagnostic criteria for depressive episode was estimated from 1174 Asian patients with depressive disorders. The node strength centrality of all ICD-10 diagnostic criteria for a depressive episode was estimated using a community-detection algorithm. In addition, networks of depressive symptoms were estimated separately among East Asian patients and South or Southeast Asian patients. Moreover, networks were estimated separately among Asian patients from high-income countries and those from middle-income countries.
RESULTS: Persistent sadness, fatigue, and loss of interest were the most centrally situated within the network of depressive symptoms in Asian patients with depressive disorders overall. A community-detection algorithm estimated that when excluding psychomotor disturbance as an outlier, the other nine symptoms formed the largest clinically meaningful cluster. Geographic and economic variations in networks of depressive symptoms were evaluated.
CONCLUSION: Our findings demonstrated that the typical symptoms of the ICD-10 diagnostic criteria for depressive episode are the most centrally situated within the network of depressive symptoms. Furthermore, our findings suggested that cultural influences related to geographic and economic distributions of participants could influence the estimated depressive symptom network in Asian patients with depressive disorders.

Matched MeSH terms: Depression/physiopathology*
Fulltext Validation of Brunei's Malay EQ-5D Questionnaire in Patients with Type 2 Diabetes

Koh D, Abdullah AM, Wang P, Lin N, Luo N

PLoS One, 2016;11(11):e0165555.
PMID: 27835652 DOI: 10.1371/journal.pone.0165555

BACKGROUND: The Malay spoken in Brunei a South East Asian country where Malay is the national language is distinctive and different from Malay spoken in Malaysia, Singapore and Indonesia. This study aimed to develop a Brunei Malay version of the 5-level EQ-5D questionnaire (EQ-5D-5L) and to assess its psychometric properties among patients with type 2 diabetes mellitus (T2DM).
METHODS: The Brunei Malay EQ-5D-5L was developed by culturally adapting two existing Malay versions. A total of 154 Bruneians with T2DM completed the questionnaire in two different points of time with one week apart. Known-groups validity of the utility-based EQ-5D-5L index and visual analogue scale (EQ-VAS) was evaluated by comparing subgroups of patients known to differ in health status. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC) or Cohen's kappa.
RESULTS: As hypothesized, patients known to have 'better' health had higher EQ-5D-5L index scores than those having 'worse' health in all 7 known-groups comparisons. The hypothesized difference in the EQ-VAS scores was observed in only 4 of the 7 known-groups comparisons. Kappa values ranged from 0.206 to 0.446 for the EQ-5D-5L items; the ICC value for the EQ-5D-5L index and EQ-VAS was 0.626 and 0.521, respectively.
CONCLUSIONS: The utility-based EQ-5D-5L index appears to be valid and reliable for measuring the health of Brunei patients with T2DM. The validity of the EQ-VAS in Brunei requires further investigation.

Matched MeSH terms: Depression/physiopathology
Fulltext Antidepressant-like effects of fish, krill oils and Vit B12 against exposure to stress environment in mice models: current status and pilot study

Zadeh-Ardabili PM, Rad SK, Rad SK, Movafagh A

Sci Rep, 2019 Dec 27;9(1):19953.
PMID: 31882885 DOI: 10.1038/s41598-019-56360-8

Oxidative stress has significant role in pathophysiology of any kind of depression through actions of free radicals, non-radical molecules, and unbalancing antioxidant systems in body. In the current study, antidepressant responses of fish oil (FO), Neptune krill oil (NKO), vitamin B12 (Vit B12), and also imipramine (IMP) as the reference were studied. Natural light was employed to induce stress in the animals followed by oral administration of the drugs for 14 days. The antidepressant effect was assessed by tail suspension test (TST) and forced swimming test (FST), antioxidant enzymes and oxidative stress markers were then measured in the brain tissue of the animals. The administration of FO and NKO could significantly reduce the immobility of the animals; while, increasing climbing and swimming time compared to the normal saline in CUS-control group in TST and FST, similarly to IMP but not with Vit B12. Vit B12 could not effect on SOD activity and H2O2 level, but, cause decrease of the malondialdihydric (MDA) level and CAT activity, as well as increased the GPx and GSH activities. The rest treatments led to decrease of MDA, H2O2 levels and CAT activity and increase of GPx, SOD, GSH activities.

Matched MeSH terms: Depression/physiopathology
Alpha-asarone attenuates depression-like behavior in nicotine-withdrawn mice: Evidence for the modulation of hippocampal pCREB levels during nicotine-withdrawal

Chellian R, Pandy V, Mohamed Z

Eur J Pharmacol, 2018 Jan 05;818:10-16.
PMID: 29042206 DOI: 10.1016/j.ejphar.2017.10.025

In the present study, the effect α-asarone on nicotine withdrawal-induced depression-like behavior in mice was investigated. In this study, mice were exposed to drinking water or nicotine solution (10-200µg/ml) as a source of drinking for forty days. During this period, daily fluid consumption, food intake and body weight were recorded. The serum cotinine level was estimated before nicotine withdrawal. Naïve mice or nicotine-withdrawn mice were treated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) for eight consecutive days and the forced swim test (FST) or locomotor activity test was conducted. In addition, the effect of α-asarone or bupropion on the hippocampal pCREB, CREB and BDNF levels during nicotine-withdrawal were measured. Results indicated that α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment did not significantly alter the immobility time in the FST or spontaneous locomotor activity in naïve mice. However, the immobility time of nicotine-withdrawn mice was significantly attenuated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment in the FST. Besides, α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment significantly attenuated the hippocampal pCREB levels in nicotine-withdrawn mice. Overall, the present results indicate that α-asarone treatment attenuated the depression-like behavior through the modulation of hippocampal pCREB levels during nicotine-withdrawal in mice.

Matched MeSH terms: Depression/physiopathology

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