Displaying publications 1 - 20 of 128 in total

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  1. Ayipo YO, Ahmad I, Chong CF, Zainurin NA, Najib SY, Patel H, et al.
    J Biomol Struct Dyn, 2024;42(2):993-1014.
    PMID: 37021485 DOI: 10.1080/07391102.2023.2198016
    The human serotonin transporters (hSERTs) are neurotransmitter sodium symporters of the aminergic G protein-coupled receptors, regulating the synaptic serotonin and neuropharmacological processes related to neuropsychiatric disorders, notably, depression. Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and (S)-citalopram are competitive inhibitors of hSERTs and are commonly the first-line medications for major depressive disorder (MDD). However, treatment-resistance and unpleasant aftereffects constitute their clinical drawbacks. Interestingly, vilazodone emerged with polypharmacological (competitive and allosteric) inhibitions on hSERTs, amenable to improved efficacy. However, its application usually warrants adjuvant/combination therapy, another subject of critical adverse events. Thus, the discovery of alternatives with polypharmacological potentials (one-drug-multiple-target) and improved safety remains essential. In this study, carbazole analogues from chemical libraries were explored using docking and molecular dynamics (MD) simulation. Selectively, two IBScreen ligands, STOCK3S-30866 and STOCK1N-37454 predictively bound to the active pockets and expanded boundaries (extracellular vestibules) of the hSERTs more potently than vilazodone and (S)-citalopram. For instance, the two ligands showed docking scores of -9.52 and -9.59 kcal/mol and MM-GBSA scores of -92.96 and -65.66 kcal/mol respectively compared to vilazodone's respective scores of -7.828 and -59.27 against the central active site of the hSERT (PDB 7LWD). Similarly, the two ligands also docked to the allosteric pocket (PDB 5I73) with scores of -8.15 and -8.40 kcal/mol and MM-GBSA of -96.14 and -68.46 kcal/mol whereas (S)-citalopram has -6.90 and -69.39 kcal/mol respectively. The ligands also conferred conformational stability on the receptors during 100 ns MD simulations and displayed interesting ADMET profiles, representing promising hSERT modulators for MDD upon experimental validation.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Depressive Disorder, Major*
  2. 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*
  3. Edwards MJ, Wilson GC, Keitsch S, Soddemann M, Wilker B, Müller CP, et al.
    J Neurochem, 2022 Nov;163(4):357-369.
    PMID: 36227646 DOI: 10.1111/jnc.15708
    Major depressive disorder (MDD) is a severe disease of unknown pathogenesis with a lifetime prevalence of ~10%. Therapy requires prolonged treatment that often fails. We have previously demonstrated that ceramide levels in the blood plasma of patients and in mice with experimental MDD are increased. Neutralization of blood plasma ceramide prevented experimental MDD in mice. Mechanistically, we demonstrated that blood plasma ceramide accumulated in endothelial cells of the hippocampus, inhibited phospholipase D (PLD) and thereby decreased phosphatidic acid in the hippocampus. Here, we demonstrate that phosphatidic acid binds to and controls the activity of phosphotyrosine phosphatase (PTP1B) in the hippocampus and thus determines tyrosine phosphorylation of a variety of cellular proteins including TrkB. Injection of PLD, phosphatidic acid, or inhibition of PTP1B abrogated MDD and normalized cellular tyrosine phosphorylation, including phosphorylation of TrkB and neurogenesis in the hippocampus. Most importantly, these treatments also rapidly normalized behavior of mice with experimental MDD. Since phosphatidic acid binds to and inhibits PTP1B, the lack of phosphatidic acid results in increased activity of PTP1B and thereby in reduced tyrosine phosphorylation of TrkB and other cellular proteins. Thus, our data indicate a novel pathogenetic mechanism of and a rapidly acting targeted treatment for MDD.
    Matched MeSH terms: Depressive Disorder, Major*
  4. Badamasi IM, Lye MS, Ibrahim N, Abdul Razaq NA, Ling KH, Stanslas J
    Pharmacogenomics J, 2021 Aug;21(4):498-509.
    PMID: 33731884 DOI: 10.1038/s41397-021-00228-6
    The polymorphisms of the 5HTR1A and 5HTR2A receptor genes (rs6295C/G and rs6311G/A) have been evaluated for association with SSRI treatment outcome in various populations with different results. The present study was carried out to determine the association between genotypes of HTR1A-rs6295 and HTR2A-rs6311 with SSRI treatment outcome among the ethnic Malay patients diagnosed with first-episode major depressive disorder (MDD). The patients were recruited from four tertiary hospitals in the Klang Valley region of Malaysia. Predefined efficacy phenotypes based on 25% (partial early response) and 50% (clinical efficacy response) reduction in Montgomery Asberg Depression Rating Scale-self Rated score (MADRS-S) were adopted for assessment of treatment efficacy in this study. Self-reporting for adverse effects (AE) was documented using the Patient Rated Inventory of Side Effect (PRISE) after treatment with SSRI for up to 6 weeks. Adjusted binary logistic regression between genotypes of the polymorphism obtained using sequencing technique with the treatment outcome phenotypes was performed. The 142 patients recruited were made up of 96 females (67.6%) and 46 males (32.4%). Clinical efficacy and Partial early response phenotypes were not significantly associated with genotypes of HTR1A and HTR2A polymorphism. The GG genotype of HTR2A polymorphism has decreased odds for dizziness (CNS) and increased odds for poor concentration. The GA genotype increases the odd for excessive sweating, diarrhoea, constipation and blurred vision. The CC genotype of HTR1A-rs6295 decreases the odd for nausea/vomiting and increases the odd for anxiety. Thus, some genotypes of HTR1A and HTR2A polymorphism were associated with SSRI treatment outcomes in ethnic Malay MDD patients.
    Matched MeSH terms: Depressive Disorder, Major/drug therapy*; Depressive Disorder, Major/genetics*
  5. Johnson D, Thurairajasingam S, Letchumanan V, Chan KG, Lee LH
    Nutrients, 2021 May 20;13(5).
    PMID: 34065187 DOI: 10.3390/nu13051728
    The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota-gut-brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic-pituitary-adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.
    Matched MeSH terms: Depressive Disorder, Major/microbiology*; Depressive Disorder, Major/therapy*
  6. Lye MS, Tor YS, Tey YY, Shahabudin A, Loh SP, Ibrahim N, et al.
    J Mol Neurosci, 2021 May;71(5):981-990.
    PMID: 33034825 DOI: 10.1007/s12031-020-01719-0
    Heritability of major depressive disorder (MDD) is between 36 and 44%, suggesting that up to nearly half of the phenotypic variability is attributable to genes. A number of genetic polymorphisms have been shown to predispose certain individuals to depression. Of particular interest are the polymorphisms of the vitamin D receptor (VDR) gene. Although the VDR gene has been well characterized and a vast number of polymorphisms have been identified, the association between BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) single-nucleotide polymorphisms (SNPs), together with their haplotypes, and MDD risk have yet to be established. We conducted a matched case-control study with a total of 600 participants comprising 300 major depressive disorder (MDD) cases and 300 controls matched by age, gender and ethnicity in a 1:1 ratio, in four public hospitals in Kuala Lumpur and Selangor. Three adjacent SNPs of the VDR gene-BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236)-were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios and 95% confidence intervals (CIs) were obtained from conditional logistic regression using Stata 16. Linkage disequilibrium and haplotype association with MDD were analyzed using the online SNPStats program. None of the genotypes of the three SNPs was significantly associated with risk of developing MDD after adjusting for confounding factors. However, the TAC (BAt) haplotype was associated with increased odds of MDD (adjusted OR = 2.17, 95% CI = 1.30-3.61, p = 0.003) using CCT (baT) as reference haplotype. The findings suggest that the BsmI-ApaI-TaqI TAC (BAt) haplotype of the VDR gene increases susceptibility to MDD.
    Matched MeSH terms: Depressive Disorder, Major/genetics*
  7. 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
  8. Kato T, Ishigooka J, Miyajima M, Watabe K, Fujimori T, Masuda T, et al.
    Psychiatry Clin Neurosci, 2020 Dec;74(12):635-644.
    PMID: 32827348 DOI: 10.1111/pcn.13137
    AIM: Previous studies conducted primarily in the USA and Europe have demonstrated the efficacy and safety of lurasidone 20-120 mg/day for the treatment of bipolar I depression. The aim of the current study was to evaluate the efficacy and safety of lurasidone monotherapy for the treatment of bipolar I depression among patients from diverse ethnic backgrounds, including those from Japan.

    METHODS: Patients were randomly assigned to double-blind treatment for 6 weeks with lurasidone, 20-60 mg/day (n = 184) or 80-120 mg/day (n = 169), or placebo (n = 172). The primary end-point was change from baseline to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

    RESULTS: Lurasidone treatment significantly reduced mean MADRS total scores from baseline to Week 6 for the 20-60-mg/day group (-13.6; adjusted P = 0.007; effect size = 0.33), but not for the 80-120-mg/day group (-12.6; adjusted P = 0.057; effect size = 0.22) compared with placebo (-10.6). Treatment with lurasidone 20-60 mg/day also improved MADRS response rates, functional impairment, and anxiety symptoms. The most common adverse events associated with lurasidone were akathisia and nausea. Lurasidone treatments were associated with minimal changes in weight, lipids, and measures of glycemic control.

    CONCLUSION: Monotherapy with once daily doses of lurasidone 20-60 mg, but not 80-120 mg, significantly reduced depressive symptoms and improved functioning in patients with bipolar I depression. Results overall were consistent with previous studies, suggesting that lurasidone 20-60 mg/day is effective and safe in diverse ethnic populations, including Japanese.

    Matched MeSH terms: Depressive Disorder, Major/drug therapy*; Depressive Disorder, Major/ethnology
  9. Khairuddin S, Ngo FY, Lim WL, Aquili L, Khan NA, Fung ML, et al.
    J Clin Med, 2020 Oct 12;9(10).
    PMID: 33053848 DOI: 10.3390/jcm9103260
    Major depression contributes significantly to the global disability burden. Since the first clinical study of deep brain stimulation (DBS), over 406 patients with depression have now undergone this neuromodulation therapy, and 30 animal studies have investigated the efficacy of subgenual cingulate DBS for depression. In this review, we aim to provide a comprehensive overview of the progress of DBS of the subcallosal cingulate in humans and the medial prefrontal cortex, its rodent homolog. For preclinical animal studies, we discuss the various antidepressant-like behaviors induced by medial prefrontal cortex DBS and examine the possible mechanisms including neuroplasticity-dependent/independent cellular and molecular changes. Interestingly, the response rate of subcallosal cingulate Deep brain stimulation marks a milestone in the treatment of depression. DBS among patients with treatment-resistant depression was estimated to be approximately 54% across clinical studies. Although some studies showed its stimulation efficacy was limited, it still holds great promise as a therapy for patients with treatment-resistant depression. Overall, further research is still needed, including more credible clinical research, preclinical mechanistic studies, precise selection of patients, and customized electrical stimulation paradigms.
    Matched MeSH terms: Depressive Disorder, Major
  10. Coleman JRI, Peyrot WJ, Purves KL, Davis KAS, Rayner C, Choi SW, et al.
    Mol Psychiatry, 2020 Jul;25(7):1430-1446.
    PMID: 31969693 DOI: 10.1038/s41380-019-0546-6
    Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.
    Matched MeSH terms: Depressive Disorder, Major/genetics*; Depressive Disorder, Major/epidemiology*
  11. Wu Y, Levis B, Riehm KE, Saadat N, Levis AW, Azar M, et al.
    Psychol Med, 2020 06;50(8):1368-1380.
    PMID: 31298180 DOI: 10.1017/S0033291719001314
    BACKGROUND: Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.

    METHODS: We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

    RESULTS: 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).

    CONCLUSIONS: PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

    Matched MeSH terms: Depressive Disorder, Major/classification; Depressive Disorder, Major/diagnosis*
  12. Mandal T, Bairy LK, Sharma PSVN
    Eur J Clin Pharmacol, 2020 Jun;76(6):807-814.
    PMID: 32253447 DOI: 10.1007/s00228-020-02866-4
    PURPOSE: Ethnicity plays a key role in deciding the direction of the association between serotonin transporter gene polymorphisms and treatment response of selective serotonin reuptake inhibitors (SSRIs). The present study explored the association of 5HTTLPR and 5HTTLPR-rs25531 polymorphisms with the treatment response of escitalopram in South Indian patients with major depressive disorder.

    METHODS: A total of 148 depressive patients receiving escitalopram 10-20 mg/day were genotyped for 5HTTLPR and rs25531 polymorphisms. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression Scale (CGI). At the end of week 12, patients were defined as responders and non-responders based on HDRS17 and MADRS scores. Chi-square test and logistic regression analysis were performed to investigate the genotypic influence on treatment response. Comparison of continuous variables among different groups was done using Student's t test or one-way ANOVA.

    RESULTS: Out of 148 study subjects, 65 (43.9%) were responders and 83 (56.08%) were non-responders. We observed a significant (p value

    Matched MeSH terms: Depressive Disorder, Major/drug therapy*
  13. Lee KW, Ching SM, Devaraj NK, Chong SC, Lim SY, Loh HC, et al.
    PMID: 32466479 DOI: 10.3390/ijerph17113767
    Previous literature has reported that patients with diabetes in pregnancy (DIP) are at risk of developing antepartum depression but the results have been inconsistent in cohort studies. We conducted a systematic review and performed a meta-analysis to quantify the association between DIP and risk of antepartum depression in cohort studies. Medline, Cinahl, and PubMed databases were searched for studies investigating DIP involving pregnant women with pre-existing diabetes and gestational diabetes mellitus and their risk of antepartum depression that were published in journals from inception to 27 December 2019. We derived the summary estimates using a random-effects model and reported the findings as pooled relative risks (RR) and confidence interval (CI). Publication bias was assessed using a funnel plot and was quantified by Egger and Begg's tests. Ten studies, involving 71,036 pregnant women were included in this meta-analysis. The pooled RR to develop antepartum depression was (RR = 1.430, 95% CI: 1.251-1.636) among women with gestational diabetes mellitus. Combining pregnant women with pre-existing diabetes mellitus and gestational diabetes mellitus, they had a significant increased risk of developing antepartum depression (RR = 1.431, 95% CI: 1.205-1.699) compared with those without it. In comparison, we found no association between pre-existing diabetes mellitus in pregnancy (RR = 1.300, 95% CI: 0.736-2.297) and the risk of developing antepartum depression. This study has a few limitations: first, different questionnaire and cut-off points were used in evaluation of depression across the studies. Second, there was a lack of data on history of depression prior to pregnancy, which lead to confounding bias that could not be solved by this meta-analysis. Third, data were dominated by studies in Western countries; this is due to the studies from Eastern countries failing to meet our inclusion criteria for statistical analysis. Women with gestational diabetes mellitus have an increased risk of developing antepartum depression compared to those without the disease. Therefore, more attention on the mental health status should be given on pregnant women diagnosed with pre-existing diabetes mellitus and gestational diabetes mellitus.
    Matched MeSH terms: Depressive Disorder, Major*
  14. Tay AK, Mung HK, Miah MAA, Balasundaram S, Ventevogel P, Badrudduza M, et al.
    PLoS Med, 2020 Mar;17(3):e1003073.
    PMID: 32231364 DOI: 10.1371/journal.pmed.1003073
    BACKGROUND: This randomised controlled trial (RCT) aims to compare 6-week posttreatment outcomes of an Integrative Adapt Therapy (IAT) to a Cognitive Behavioural Therapy (CBT) on common mental health symptoms and adaptive capacity amongst refugees from Myanmar. IAT is grounded on psychotherapeutic elements specific to the refugee experience.

    METHODS AND FINDINGS: We conducted a single-blind RCT (October 2017 -May 2019) with Chin (39.3%), Kachin (15.7%), and Rohingya (45%) refugees living in Kuala Lumpur, Malaysia. The trial included 170 participants receiving six 45-minute weekly sessions of IAT (97.6% retention, 4 lost to follow-up) and 161 receiving a multicomponent CBT also involving six 45-minute weekly sessions (96.8% retention, 5 lost to follow-up). Participants (mean age: 30.8 years, SD = 9.6) had experienced and/or witnessed an average 10.1 types (SD = 5.9, range = 1-27) of traumatic events. We applied a single-blind design in which independent assessors of pre- and posttreatment indices were masked in relation to participants' treatment allocation status. Primary outcomes were symptom scores of Post Traumatic Stress Disorder (PTSD), Complex PTSD (CPTSD), Major Depressive Disorder (MDD), the 5 scales of the Adaptive Stress Index (ASI), and a measure of resilience (the Connor-Davidson Resilience Scale [CDRS]). Compared to CBT, an intention-to-treat analysis (n = 331) at 6-week posttreatment follow-up demonstrated greater reductions in the IAT arm for all common mental disorder (CMD) symptoms and ASI domains except for ASI-3 (injustice), as well as increases in the resilience scores. Adjusted average treatment effects assessing the differences in posttreatment scores between IAT and CBT (with baseline scores as covariates) were -0.08 (95% CI: -0.14 to -0.02, p = 0.012) for PTSD, -0.07 (95% CI: -0.14 to -0.01) for CPTSD, -0.07 for MDD (95% CI: -0.13 to -0.01, p = 0.025), 0.16 for CDRS (95% CI: 0.06-0.026, p ≤ 0.001), -0.12 (95% CI: -0.20 to -0.03, p ≤ 0.001) for ASI-1 (safety/security), -0.10 for ASI-2 (traumatic losses; 95% CI: -0.18 to -0.02, p = 0.02), -0.03 for ASI-3 (injustice; (95% CI: -0.11 to 0.06, p = 0.513), -0.12 for ASI-4 (role/identity disruptions; 95% CI: -0.21 to -0.04, p ≤ 0.001), and -0.18 for ASI-5 (existential meaning; 95% CI: -0.19 to -0.05, p ≤ 0.001). Compared to CBT, the IAT group had larger effect sizes for all indices (except for resilience) including PTSD (IAT, d = 0.93 versus CBT, d = 0.87), CPTSD (d = 1.27 versus d = 1.02), MDD (d = 1.4 versus d = 1.11), ASI-1 (d = 1.1 versus d = 0.85), ASI-2 (d = 0.81 versus d = 0.66), ASI-3 (d = 0.49 versus d = 0.42), ASI-4 (d = 0.86 versus d = 0.67), and ASI-5 (d = 0.72 versus d = 0.53). No adverse events were recorded for either therapy. Limitations include a possible allegiance effect (the authors inadvertently conveying disproportionate enthusiasm for IAT in training and supervision), cross-over effects (counsellors applying elements of one therapy in delivering the other), and the brief period of follow-up.

    CONCLUSIONS: Compared to CBT, IAT showed superiority in improving mental health symptoms and adaptative stress from baseline to 6-week posttreatment. The differences in scores between IAT and CBT were modest and future studies conducted by independent research teams need to confirm the findings.

    TRIAL REGISTRATION: The study is registered under Australian New Zealand Clinical Trials Registry (ANZCTR) (http://www.anzctr.org.au/). The trial registration number is: ACTRN12617001452381.

    Matched MeSH terms: Depressive Disorder, Major/psychology; Depressive Disorder, Major/therapy*
  15. 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
  16. Ho KC, Russell V, Nyanti L, Chan MW, Hassali MA, Dawood OT, et al.
    Asian J Psychiatr, 2020 Feb;48:101899.
    PMID: 31901584 DOI: 10.1016/j.ajp.2019.101899
    INTRODUCTION: Most primary care in Malaysia is provided by general practitioners in private practice. To date, little is known about how Malaysian General Practitioners (GPs) manage patients with depression. We surveyed privately practising primary care physicians in the state of Penang, Malaysia, in relation to their experience of the Malaysian Clinical Practice Guideline (CPG) in Major Depressive Disorder, their current practice and perceived barriers in managing depression effectively.

    MATERIAL AND METHODS: A questionnaire based on the study aims and previous literature was developed by the authors and mailed to all currently registered GPs in private clinics in Penang. Survey responses were analysed using SSPS version 21.

    RESULTS: From a total of 386 questionnaires distributed, 112 (29%) were returned. Half of the respondents were unaware of the existence of any CPG for depression. One quarter reported not managing depression at all, while one third used anxiolytic monotherapy in moderate-severe depression. Almost 75 % of respondents reported making referrals to specialist psychiatric services for moderate-severe depression. Time constraints, patient non-adherence and a lack of depression management skills were perceived as the main barriers to depression care.

    CONCLUSIONS: Our findings highlight the need to engage privately practising primary care physicians in Malaysia to improve their skills in the management of depression. Future revisions of the Malaysian Depression CPG should directly involve more GPs from private practices at the planning, development and implementation stages, in order to increase its impact.

    Matched MeSH terms: Depressive Disorder, Major/therapy*
  17. Wu Y, Levis B, Sun Y, Krishnan A, He C, Riehm KE, et al.
    J Psychosom Res, 2020 02;129:109892.
    PMID: 31911325 DOI: 10.1016/j.jpsychores.2019.109892
    OBJECTIVE: Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D).

    METHODS: Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores.

    RESULTS: There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)).

    CONCLUSION: Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity.

    Matched MeSH terms: Depressive Disorder, Major/diagnosis*
  18. Husain SF, Tang TB, Yu R, Tam WW, Tran B, Quek TT, et al.
    EBioMedicine, 2020 Jan;51:102586.
    PMID: 31877417 DOI: 10.1016/j.ebiom.2019.11.047
    BACKGROUND: Functional near infrared spectroscopy (fNIRS) provides a direct and quantitative assessment of cortical haemodynamic function during a cognitive task. This functional neuroimaging modality may be used to elucidate the pathophysiology of psychiatric disorders, and identify neurophysiological differences between co-occurring psychiatric disorders. However, fNIRS research on borderline personality disorder (BPD) has been limited. Hence, this study aimed to compare cerebral haemodynamic function in healthy controls (HC), patients with major depressive disorder (MDD) and patients with BPD.

    METHODS: fNIRS signals during a verbal fluency task designed for clinical assessment was recorded for all participants. Demographics, clinical history and symptom severity were also noted.

    FINDINGS: Compared to HCs (n = 31), both patient groups (MDD, n = 31; BPD, n = 31) displayed diminished haemodynamic response in the frontal, temporal and parietal cortices. Moreover, haemodynamic response in the right frontal cortex is markedly lower in patients with MDD compared to patients with BPD.

    INTERPRETATION: Normal cortical function in patients with BPD is disrupted, but not as extensively as in patients with MDD. These results provide further neurophysiological evidence for the distinction of patients with MDD from patients with BPD.

    Matched MeSH terms: Depressive Disorder, Major/complications*; Depressive Disorder, Major/physiopathology*
  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. Tan HJR
    Case Rep Psychiatry, 2020;2020:8820849.
    PMID: 33110667 DOI: 10.1155/2020/8820849
    This is a case of a 38-year-old married woman presenting with major depressive disorder one month after the birth of her third child. The depressive episode began in the context of interpersonal difficulties with her husband. In addition, she was also battling an internal conflict of continuing to pursue her career dream as an obstetrician and fulfilling her responsibility as a wife and a mother. Interpersonal psychotherapy (IPT) was selected as the treatment choice as an evidence-based peripartum treatment that could specifically address the two presenting problem areas, i.e., marital interpersonal dispute and role transition. This paper provides an illustration of IPT sessions conducted with verbatim selections of the sessions.
    Matched MeSH terms: Depressive Disorder, Major
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