Displaying publications 1 - 20 of 128 in total

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  1. Lye, Munn-Sann, Aishah-Farhana Shahbudin, Tey, Yin-Yee, Tor, Yin-Sim, Ling, King-Hwa, Normala Ibrahim, et al.
    Neuroscience Research Notes, 2019;2(3):20-28.
    MyJurnal
    Major depressive disorder (MDD) compromises the individual’s capacity for self-care and productivity. Single nucleotide polymorphisms (SNP) of a number of genes have been associated with MDD. The zinc transporter-3 protein, encoded by the ZnT3 (SLC30A3) gene, maintains zinc-glutamate homeostasis at the glutamatergic synapse, a disruption of which increases risk of MDD. We hypothesise that variation in SLC30A3 (rs11126936)SNP increases risk of MDD. We recruited 300 MDD cases and 300 controls, matched in theratio of 1:1 by age, gender and ethnicity. PCR-restriction fragment length polymorphism analysis was used in DNA genotyping, validated by sequencing 10%of samples. Deviation from the Hardy-Weinberg equilibrium was tested using the chi-square test. Conditional logistic regression was used to estimate adjusted odds ratios, controlling for age, gender, ethnicity, occupation and family monthly income.Genotypes G/G and G/T showed two times greater odds of developing MDD compared to variant genotype T/T (OR=1.983, 95% CI=1.031-3.815; p=0.040 and OR=2.232, 95% CI=1.100-4.533; p=0.026 respectively). Carriers of genotypes G/G and G/T of the SNP rs11126936 in SLC30A3are associated with increased risk of MDD.
    Matched MeSH terms: Depressive Disorder, Major
  2. Chai WJ, Abd Hamid AI, Abdullah JM
    Front Psychol, 2018;9:401.
    PMID: 29636715 DOI: 10.3389/fpsyg.2018.00401
    Since the concept of working memory was introduced over 50 years ago, different schools of thought have offered different definitions for working memory based on the various cognitive domains that it encompasses. The general consensus regarding working memory supports the idea that working memory is extensively involved in goal-directed behaviors in which information must be retained and manipulated to ensure successful task execution. Before the emergence of other competing models, the concept of working memory was described by the multicomponent working memory model proposed by Baddeley and Hitch. In the present article, the authors provide an overview of several working memory-relevant studies in order to harmonize the findings of working memory from the neurosciences and psychological standpoints, especially after citing evidence from past studies of healthy, aging, diseased, and/or lesioned brains. In particular, the theoretical framework behind working memory, in which the related domains that are considered to play a part in different frameworks (such as memory's capacity limit and temporary storage) are presented and discussed. From the neuroscience perspective, it has been established that working memory activates the fronto-parietal brain regions, including the prefrontal, cingulate, and parietal cortices. Recent studies have subsequently implicated the roles of subcortical regions (such as the midbrain and cerebellum) in working memory. Aging also appears to have modulatory effects on working memory; age interactions with emotion, caffeine and hormones appear to affect working memory performances at the neurobiological level. Moreover, working memory deficits are apparent in older individuals, who are susceptible to cognitive deterioration. Another younger population with working memory impairment consists of those with mental, developmental, and/or neurological disorders such as major depressive disorder and others. A less coherent and organized neural pattern has been consistently reported in these disadvantaged groups. Working memory of patients with traumatic brain injury was similarly affected and shown to have unusual neural activity (hyper- or hypoactivation) as a general observation. Decoding the underlying neural mechanisms of working memory helps support the current theoretical understandings concerning working memory, and at the same time provides insights into rehabilitation programs that target working memory impairments from neurophysiological or psychological aspects.
    Matched MeSH terms: Depressive Disorder, Major
  3. Novick D, Montgomery WS, Aguado J, Peng X, Brugnoli R, Haro JM
    Asia Pac Psychiatry, 2015 Dec;7(4):427-35.
    PMID: 26047023 DOI: 10.1111/appy.12189
    This was an analysis of the impact of somatic symptoms on the severity and course of depression in Chinese patients treated for an acute episode of major depressive disorder (MDD).
    Matched MeSH terms: Depressive Disorder, Major/epidemiology*; Depressive Disorder, Major/therapy
  4. Eggart M, Todd J, Valdés-Stauber J
    PLoS One, 2021;16(6):e0253913.
    PMID: 34170963 DOI: 10.1371/journal.pone.0253913
    OBJECTIVES: Interoception refers to the sensation, interpretation, and integration of internal somatic signals. Abnormalities in self-reported interoception are prevalent features of major depressive disorder (MDD) and may affect treatment outcomes. In the present study, we investigated the psychometric properties of the revised eight-dimensional and 37-item Multidimensional Assessment of Interoceptive Awareness questionnaire (the MAIA-2) in a severely depressed sample, after translating two updated scales (Not-Distracting, Not-Worrying) into German. Specifically, we examined the measure's internal consistency reliability, sensitivity to change, and minimal important differences (MID) with a focus on patient's antidepressive responses to treatment.

    METHODS: The study enrolled 110 participants (age: M = 46.85, SD = 11.23; female: 55.45%) undergoing hospital treatment, of whom 87 were included in the pre-post analysis. Participants completed a German translation of MAIA-2 and the Beck Depression Inventory-II (pre-/post-treatment). Internal consistency reliability was determined by Cronbach's α/McDonalds's ω, sensitivity to change was determined by effect sizes, and MIDs were determined by distribution- (0.5*SD) and anchor-based approaches (mean change method; ROC curve cut-points).

    RESULTS: Depression severity reduced over the course of treatment (Median = -65.22%), and 34.48% of patients achieved remission. Reliability was appropriate for post-treatment (range of ω: .70-.90), but questionable for two pre-treatment scales (Noticing: ω = .64; Not-Distracting: ω = .66). The eight dimensions of MAIA-2 were sensitive to change (standardized response mean: .32-.81; Cohen's effect size: .30-.92). Distribution-based MIDs (.38-.61) and anchor-based mean change MIDs (remission vs. partial response: .00-.85; partial response vs. nonresponse: .08-.88) were established on the group level. For six scales, ROC cut-points (remission: .00-1.33; response: -.20-1.00) demonstrated accurate classification to treatment response groups on the individual level.

    CONCLUSIONS: This study demonstrated the applicability of the MAIA-2 questionnaire in MDD. The updated version may have led to reliability improvements regarding the revised scales, but subthreshold reliability was evident prior to treatment. The measure's dimensions were sensitive to change. MIDs were established that corresponded with antidepressive treatment outcomes. Our findings are consistent with a growing area of research which considers somatic feelings as key contributors to mental health.

    Matched MeSH terms: Depressive Disorder, Major/diagnosis; Depressive Disorder, Major/epidemiology*; Depressive Disorder, Major/physiopathology
  5. Treuer T, Liu CY, Salazar G, Kongsakon R, Jia F, Habil H, et al.
    Asia Pac Psychiatry, 2013 Dec;5(4):219-30.
    PMID: 23857712 DOI: 10.1111/appy.12090
    Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.
    Matched MeSH terms: Depressive Disorder, Major/drug therapy*; Depressive Disorder, Major/economics
  6. Aminuddin, I., Lotfi, H.A.
    MyJurnal
    The sight of clustered holes can bring about uneasiness in people, and the disgust response towards it is called trypophobia. Reactions in humans vary from nausea to severe depression. We explore the possible causes of this unique phenomenon, such as evolutionary adaptation and spectral features. We also uncover the clinical features and its relationship to other psychological conditions for example, obsessive-compulsive disorder.
    Matched MeSH terms: Depressive Disorder, Major
  7. Yin, Ping Ng, Saminah Md Kassim, Maniam, T.
    ASEAN Journal of Psychiatry, 2013;14(2):157-160.
    MyJurnal
    Objective: This case report highlights the clinical dilemmas encountered in deciding the diagnostic status of persons with unipolar depression who develop hypomania during antidepressant/electroconvulsive therapy.

    Methods: We report a case of a 52 year-old Chinese lady, diagnosed with unipolar depression, which developed hypomania after she was started on T. Fluvoxamine 100mg daily and completed 8 sessions of Electroconvulsive therapy.

    Results: Her diagnosis was revised to Bipolar Disorder and she was treated with T. Sodium Valproate 400mg twice daily after which she improved.

    Conclusion: Treatment-emergent hypomania is likely a subtype of bipolar spectrum disorder and patients with Treatment - emergent Hypomania should be treated as Bipolar Disorder.
    Matched MeSH terms: Depressive Disorder, Major
  8. Syed Nabil, Ng, Chong Guan, Rusdi Abd Rashid
    MyJurnal
    Tianeptine is an atypical tricyclic antidepressant that is prescribed mainly for the treatment of depression and anxiety disorder. There have been scattered reported cases of tianeptine dependence and abuse in the literature. We report the case of a 32-year-old gentleman with resistant major depressive disorder that was initially successfully treated with Tianeptine. When his depression relapse due to work-related issue, he step-up his dosages without supervision. He developed tolerance and withdrawal to tianeptine making it difficult for him to stop without help. This case highlights the possibility of tianeptine abuse to its high tolerability and easy access for purchase.
    Matched MeSH terms: Depressive Disorder, Major
  9. Bahari R
    MyJurnal
    Limb problem is a common complication for patients with diabetes. While the impact of diabetic limb problems
    on physical health is well known, the psychological impact of the condition is still largely unknown. People with
    diabetes with or without foot ulcers frequently suffer from major depressive disorder, and this is made worse
    by the presence of limb complications. Furthermore, depression itself can have negative consequences on the
    person’s diabetes. Hence, in caring for people with diabetic foot problem, the psychological sequelae must not
    be overlooked but managed accordingly
    Matched MeSH terms: Depressive Disorder, Major
  10. Salari N, Mohammadi M, Vaisi-Raygani A, Abdi A, Shohaimi S, Khaledipaveh B, et al.
    BMC Geriatr, 2020 02 03;20(1):39.
    PMID: 32013895 DOI: 10.1186/s12877-020-1444-0
    BACKGROUND: Depression is one of the most common psychiatric disorders in the older adult and one of the most common risk factors for suicide in the older adult. Studies show different and inconsistent prevalence rates in Iran. This study aims to determine the prevalence of severe depression in Iranian older adult through a meta-analysis approach.

    METHODS: The present meta-analysis was conducted between January 2000-August 2019. Articles related to the subject matter were obtained by searching Scopus, Sciencedirect, SID, magiran, Barakat Knowledge Network System, Medline (PubMed), and Google Scholar databases. The heterogeneity of the studies was evaluated using I2 index and the data were analyzed in Comprehensive Meta-Analysis software.

    RESULTS: In a study of 3948 individuals aged 50-90 years, the overall prevalence of severe depression in Iranian older adult was 8.2% (95% CI, 4.14-6.3%) based on meta-analysis. Also, in order to investigate the effects of potential factors (sample size and year of study) on the heterogeneity of severe depression in Iranian older adult, meta-regression was used. It was reported that the prevalence of severe depression in Iranian older adult decreased with increasing sample size and increasing years of the study, which is significantly different (P 

    Matched MeSH terms: Depressive Disorder, Major
  11. Mohd Noor N, Mohd Sidik S
    Family Physician, 2003;12:30-35.
    Introduction: Depression is an important problem in primary care practice and is the commonest psychiatric disorder among the elderly.
    Aim: To assess the prevalence of depression among the elderly patients attending a rural primary health care clinic in Malaysia and to identify its associated factors.
    Method: The Geriatric Depression Scale (GDS) questionnaire was used as a screening instrument. Patients with positive GDS scores for depression were further assessed for Major Depression.
    Results: 14% of the patients were found to have depression. The associated factors identified were gender, marital status, educational level, total family monthly income, living arrangement and if they had someone to confide in. Further clinical evaluation using the DSM IV Criteria for major depression revealed that two-thirds of the patients with depression were suffering from major depression.
    Conclusion: The prevalence of depression among the elderly patients at a rural primary health care clinic was high. Primary health care doctors and staff should take extra care to detect depression when managing elderly patients.
    Matched MeSH terms: Depressive Disorder, Major
  12. Tee, B.C., Ahmad Rasidi, M.S., Mohd Rushdan, M.N., Ismail, A., Sidi, H.
    Medicine & Health, 2014;9(1):53-61.
    MyJurnal
    Sexual dysfunction is highly prevalent in gynaecological cancer patients. Most of the time, sexual dysfunction in gynaecological cancer is underdiagnosed as there is overlapping of symptoms with other psychological morbidities, interplaying of multiple risks, patients’ reluctance to complain or incompetence of health care provider to assess. Determining the risk factors of sexual dysfunction in cancer patients enables us to pay more attention to those who are vulnerable and to device strategies for early detection, prevention and treatment of sexual dysfunction in them. The main aim of the study was to determine the prevalence of sexual dysfunction and its risk factors in gynaecological cancer patients in Hospital Sultanah Bahiyah, Alor Star, Malaysia. Sexual function of eighty-three gynaecological cancer patients who were married were assessed with self-rated MVFSFI (Malay version Female Sexual Function Index). Self-rated WHOQOL-BREF (World Health Organization- Quality of Life- 26) which assessed the domains of quality of life was used while MINI (Mini International Neuropsychiatry Interview) was used for diagnosis of major depressive disorder. The prevalence of sexual dysfunction among the married gynaecological cancer patients was 65% (54/83). Sexual dysfunction was significantly associated with low education level (OR 3.055, CI 1.009-9.250), shorter duration of cancer (OR 0.966, CI 0.966- 0.998), ongoing chemotherapy (OR 3.045, CI 1.149-8.067), pain perception (OR 3.230, CI 1.257-8.303), absence of sexual intercourse for more than one month (OR 1.862) and three domains of quality of life such as physical health, psychological health and social relationship (OR 0.942, CI 0.908-0.978; OR 0.955, CI 0.916-0.995; OR 0.933, CI 0.894-0.973, respectively). However, sexual dysfunction was not associated with major depressive disorder (χ2 ² = 1.224, p = 0.268). The prevalence of sexual dysfunction in gynaecological cancer patients was comparable to other studies of similar population. Since, the risk factors of sexual dysfunction in gynaecological cancer patients are multidimensional, the process of assessment and management need to be holistic and patient-oriented.
    Matched MeSH terms: Depressive Disorder, Major
  13. Tee, B.C., Phang, C.K., Rasidi, A., Rushdan, M., Aliyasand, I., Hatta, S.
    MyJurnal

    Major Depressive Disorder (MDD) in gynaecological cancer patients is a disabling illness with significant mental and physical suffering. Determining the risk factors of MDD in cancer patients enables us to pay more attention to those who are vulnerable and to device effective strategies for prevention, early detection, and treatment. The objective of the study is to determine the prevalence of MDD and its associated risk factors in gynaecological cancer patients at Hospital Sultanah Bahiyah, Alor Star. This is a hospital-based cross-sectional descriptive study of 120 gynaecological cancer patients in Gynae-Oncology Unit in Hospital Sultanah Bahiyah, Alor Star. Mini International Neuropsychiatry Interview (MINI) was used for diagnosis of MDD. Socio-demographic data and clinical variables were collected. MVFSFI (Malay version Female Sexual Function Index) was used to determine sexual dysfunction, and WHOQOL-BREF (World Health Organization – Quality of Life-26) was performed to assess quality of life. The prevalence of MDD in gynaecological cancer patients in the study was 18%. The variables found to be significantly associated with MDD were lack of perceived social support, greater physical pain perception, presence of past psychiatric history, and poorer quality of life. Meanwhile, sexual dysfunction was not associated with MDD. Logistic regression analysis revealed that only the psychological health domain of QOL was significantly associated with MDD, and contributed to 60% of the variation in MDD. The prevalence of MDD in gynaecological cancer patients is higher than those in the general population. In view that MDD can compromise cancer prognosis and patient’s well-being, psychosocial intervention is recommended as a part of multi- disciplinary and comprehensive management of gynaecological cancer.
    Matched MeSH terms: Depressive Disorder, Major
  14. Chong SA, Vaingankar J, Abdin E, Subramaniam M
    J Affect Disord, 2012 Apr;138(1-2):128-36.
    PMID: 22209269 DOI: 10.1016/j.jad.2011.11.038
    Reports of rates of depression among different Asian ethnic groups within the same country using standardized assessments are rare in the extant literature.
    Matched MeSH terms: Depressive Disorder, Major/ethnology; Depressive Disorder, Major/epidemiology*
  15. Park S, Hatim Sulaiman A, Srisurapanont M, Chang SM, Liu CY, Bautista D, et al.
    Psychiatry Res, 2015 Aug 30;228(3):277-82.
    PMID: 26160206 DOI: 10.1016/j.psychres.2015.06.032
    We investigated the associations between negative life events, social support, depressive and hostile symptoms, and suicide risk according to gender in multinational Asian patients with major depressive disorder (MDD). A total of 547 outpatients with MDD (352 women and 195 men, mean age of 39.58±13.21 years) were recruited in China, South Korea, Malaysia, Singapore, Thailand, and Taiwan. All patients were assessed with the Mini-International Neuropsychiatric Interview, the Montgomery-Asberg Depression Rating Scale, the Symptoms Checklist 90-Revised, the Multidimensional Scale of Perceived Social Support, and the List of Threatening Experiences. Negative life events, social support, depressive symptoms, and hostility were all significantly associated with suicidality in female MDD patients. However, only depressive symptoms and hostility were significantly associated with suicidality in male patients. Depression severity and hostility only partially mediated the association of negative life events and poor social support with suicidality in female patients. In contrast, hostility fully mediated the association of negative life events and poor social support with suicidality in male patients. Our results highlight the need of in-depth assessment of suicide risk for depressed female patients who report a number of negative life events and poor social supports, even if they do not show severe psychopathology.
    Matched MeSH terms: Depressive Disorder, Major/ethnology; Depressive Disorder, Major/psychology*
  16. He C, Levis B, Riehm KE, Saadat N, Levis AW, Azar M, et al.
    Psychother Psychosom, 2020;89(1):25-37.
    PMID: 31593971 DOI: 10.1159/000502294
    BACKGROUND: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results.

    OBJECTIVE: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10.

    METHODS: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview.

    RESULTS: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88).

    CONCLUSIONS: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.

    Matched MeSH terms: Depressive Disorder, Major/diagnosis*
  17. Umi Adzlin, S., Azizul, A., Uma, V., Nor’Izam, A.
    MyJurnal
    This case report highlights on the dilemma in making a decision for termination of pregnancy (TOP) for a muslim rape victim in Malaysian setting. We report a case of 17 year-old student at 7 weeks of pregnancy after being gang-raped, who, together with her parents, had requested for a TOP. Psychiatric assessment showed that the patient suffered from a major depressive disorder and post-traumatic stress disorder which justified termination of pregnancy on a psychological and clinical basis. However the available Malaysian Islamic fatwa had caused some uncertainties on the final decision making. This case demonstrated on the needs to understand the relevant issues beyond clinical judgment in relation to TOP in our setting which encompasses the legal provision, ethical obligation as well as the needs for a clear religious understanding and stand to support the medical decision.
    Matched MeSH terms: Depressive Disorder, Major
  18. Srisurapanont M, Bautista D, Chen CH, Wang G, Udomratn P, Eurviriyanukul K
    J Affect Disord, 2015 Jan 15;171:105-10.
    PMID: 25303026 DOI: 10.1016/j.jad.2014.09.007
    BACKGROUND: Subjective cognitive impairment (SCI) in major depressive disorder (MDD) is prevalent and correlated with disability. This study aimed to examine the prevalence rates and correlates of subjective memory deficit (SMD) and subjective concentration deficit (SCD) in medication-free, non-elderly Asians with MDD.
    METHODS: The SMD and SCD were assessed by using two items of the Symptom Checklist-90-Revised (SCL-90-R). Other measurements of interest included the Montgomery-Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale (FSS), the Sheehan Disability Scale (SDS), and the Short Form Health Survey (SF-36). Adjusted odds ratios with 95% confidence intervals were calculated.
    RESULTS: Of 515 participants from China, Korea, Malaysia, Singapore, Taiwan, and Thailand, 347 (67.4%) and 377 (73.2%) had SMD and SCD, respectively. In total, 420 participants (81.6%) had SMD alone, SCD alone, and both deficits. Severe depression and poor mental health were significant correlates of SMD. Severe depression, clinically significant disability, poor physical health, and poor mental health were significantly independent correlates of SCD. Compared with young adults (18-34 years), older adults aged 50-65 years had a significantly lower risk of SCD (OR=.33, 95% CI: .19-.57).
    LIMITATIONS: Only two SCL-90-R items were used to assess the SMD and SCD. The exclusion of MDD patients treated with psychotropic medications eliminated many patients commonly seen in typical clinic settings.
    CONCLUSION: SMD and SCD are prevalent in medication-free, non-elderly Asians with MDD. Both deficits are correlated with depression and mental health status. The independent correlation between SCD and disability underscores the crucial role of SCI in MDD.
    KEYWORDS: Asian; Cognitive impairment; Depressive disorders; SCL-90-R; Subjective
    Matched MeSH terms: Depressive Disorder, Major/ethnology*; Depressive Disorder, Major/psychology
  19. Oon-Arom A, Likhitsathian S, Maneeton B, Sulaiman AH, Shih-Yen EC, Udomratn P, et al.
    Perspect Psychiatr Care, 2020 Jan;56(1):188-193.
    PMID: 31148197 DOI: 10.1111/ppc.12403
    PURPOSE: To examine subjective depressive symptoms associated with physical pain symptoms (PPSs) in Asian patients with major depressive disorder (MDD).

    DESIGN AND METHODS: Four PPSs, including headache, chest pain, low back pain, and muscle pain, and subjective depressive symptoms were assessed using the Symptom Checklist-90-Revised.

    FINDINGS: Out of 528 participants, 390 (73.9%) had at least one PPS. After adjusting for sex, depression severity, disability, fatigue, physical health status, and mental health status, PPSs were found to be associated with crying easily, blaming oneself, feeling lonely, feeling blue, and worrying too much.

    PRACTICAL IMPLICATIONS: Almost three-quarters of Asian patients with MDD experience PPSs. PPSs are associated with some subjective feelings of depression.

    Matched MeSH terms: Depressive Disorder, Major/complications*; Depressive Disorder, Major/psychology
  20. Ayipo YO, Alananzeh WA, Ahmad I, Patel H, Mordi MN
    J Biomol Struct Dyn, 2023;41(13):6219-6235.
    PMID: 35881145 DOI: 10.1080/07391102.2022.2104376
    Serotonin (5-HT) antagonists and reuptake inhibitors (SARIs) are atypical antidepressants for managing major depressive disorder. They are oftentimes applied as adjuvants for ameliorating aftereffects of SSRI antidepressants including insomnia and sexual dysfunction. The few available candidates of this class including lorpiprazole and trazodone also display some daunting side effects, making a continuous search for improved alternatives essential. Natural β-carboline alkaloids (NβCs) are interestingly renowned with broad pharmacological spectrum against several neuropsychiatric disorders including depression. However, their potentials as SARIs remain underexplored. In this study, 982 NβCs retrieved from the Ambinter-Greenpharma (Amb) database were virtually screened for potent SARI alternatives using computational and biocheminformatics approaches: homology modelling of 5-HT1A receptor, Glide HTVS, SP and XP molecular docking, molecular dynamics (MD) simulation, ADMET and mutagenicity predictions. The homology receptor was validated as a good representative of human 5HT1A receptor using the RCSB structure validation and quality protocols. From the virtual screening against the 5-HT1A receptor, Amb ligands, Amb18709727 and Amb37857532 showed higher binding affinities by XP scores of -8.725 and -7.976 kcal/mol, and MMGBSA of -87.972 and -107.585 kcal/mol respectively compared to lorpiprazole, a reference SARI with XP score and MMGBSA of -6.512 and -62.788 kcal/mol respectively. They maintained ideal contacts with pharmacologically essential amino acid residues implicated in SARI mechanisms and expressed higher stability and compactness than lorpiprazole throughout the trajectories of 100 ns MD simulation. They also displayed interesting ADME, druggability, low toxicity and mutagenicity profiles, ideal for CNS drug prospects, thus, recommended as putative SARI candidates for further study.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Depressive Disorder, Major*
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