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  1. Husain SF, McIntyre RS, Tang TB, Abd Latif MH, Tran BX, Linh VG, et al.
    J Clin Neurosci, 2021 Dec;94:94-101.
    PMID: 34863469 DOI: 10.1016/j.jocn.2021.10.009
    Functional near-infrared spectroscopy (fNIRS) provides a direct and objective assessment of cerebral cortex function. It may be used to determine neurophysiological differences between psychiatric disorders with overlapping symptoms, such as major depressive disorder (MDD) and bipolar disorder (BD). Therefore, this preliminary study aimed to compare fNIRS signals during the verbal fluency task (VFT) of English-speaking healthy controls (HC), patients with MDD and patients with BD. Fifteen HCs, 15 patients with MDD and 15 patients with BD were recruited. Groups were matched for age, gender, ethnicity and education. Relative oxy-haemoglobin and deoxy-haemoglobin changes in the frontotemporal cortex was monitored with a 52-channel fNIRS system. Integral values of the frontal and temporal regions were derived as a measure cortical haemodynamic response magnitude. Both patient groups had lower frontal and temporal region integral values than HCs, and patients with MDD had lower frontal region integral value than patients with BD. Moreover, patients could be differentiated from HCs using the frontal and temporal integral values, and patient groups could be differentiated using the frontal region integral values. VFT performance, clinical history and symptom severity were not associated with integral values. These results suggest that prefrontal cortex haemodynamic dysfunction occurs in mood disorders, and it is more extensive in MDD than BD. The fNIRS-VFT paradigm may be a potential tool for differentiating MDD from BD in clinical settings, and these findings need to be verified in a larger sample of English-speaking patients with mood disorders.
  2. Husain SF, Chiang SK, Vasu AA, Goh CP, McIntyre RS, Tang TB, et al.
    J Atten Disord, 2023 Nov;27(13):1448-1459.
    PMID: 37341192 DOI: 10.1177/10870547231180111
    OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) provides direct and quantitative assessment of cortical hemodynamic response. It has been used to identify neurophysiological alterations in medication-naïve adults with attention-deficit/hyperactivity disorder (ADHD). Hence, this study aimed to distinguish both medication-naïve and medicated adults with ADHD from healthy controls (HC).

    METHOD: 75 HCs, 75 medication-naïve, and 45 medicated patients took part in this study. fNIRS signals during a verbal fluency task (VFT) were acquired using a 52-channel system and relative oxy-hemoglobin changes in the prefrontal cortex were quantified.

    RESULTS: Prefrontal cortex hemodynamic response was lower in patients than HCs (p ≤ ≤.001). Medication-naïve and medicated patients did not differ in hemodynamic response or symptom severity (p > .05). fNIRS measurements were not associated with any clinical variables (p > .05). 75.8% patients and 76% HCs were correctly classified using hemodynamic response.

    CONCLUSION: fNIRS may be a potential diagnostic tool for adult ADHD. These findings need to be replicated in larger validation studies.

  3. Wang C, Zhang Y, Lim LG, Cao W, Zhang W, Wan X, et al.
    Sci Rep, 2023 Jul 10;13(1):11141.
    PMID: 37429942 DOI: 10.1038/s41598-023-38057-1
    Living in high expressed emotion (EE) environments tends to increase the relapse rate in schizophrenia (SZ). At present, the neural substrates responsible for high EE in SZ remain poorly understood. Functional near-infrared spectroscopy (fNIRS) may be of great use to quantitatively assess cortical hemodynamics and elucidate the pathophysiology of psychiatric disorders. In this study, we designed novel low- (positivity and warmth) and high-EE (criticism, negative emotion, and hostility) stimulations, in the form of audio, to investigate cortical hemodynamics. We used fNIRS to measure hemodynamic signals while participants listened to the recorded audio. Healthy controls (HCs, [Formula: see text]) showed increased hemodynamic activation in the major language centers across EE stimulations, with stronger activation in Wernicke's area during the processing of negative emotional language. Compared to HCs, people with SZ ([Formula: see text]) exhibited smaller hemodynamic activation in the major language centers across EE stimulations. In addition, people with SZ showed weaker or insignificant hemodynamic deactivation in the medial prefrontal cortex. Notably, hemodynamic activation in SZ was found to be negatively correlated with the negative syndrome scale score at high EE. Our findings suggest that the neural mechanisms in SZ are altered and disrupted, especially during negative emotional language processing. This supports the feasibility of using the designed EE stimulations to assess people who are vulnerable to high-EE environments, such as SZ. Furthermore, our findings provide preliminary evidence for future research on functional neuroimaging biomarkers for people with psychiatric disorders.
  4. Wei L, Syed Mortadza SA, Yan J, Zhang L, Wang L, Yin Y, et al.
    Neurosci Biobehav Rev, 2018 Apr;87:192-205.
    PMID: 29453990 DOI: 10.1016/j.neubiorev.2018.02.005
    Mood disorders are a group of psychiatric conditions that represent leading global disease burdens. Increasing evidence from clinical and preclinical studies supports that innate immune system dysfunction plays an important part in the pathophysiology of mood disorders. P2X7 receptor, belonging to the ligand-gated ion channel P2X subfamily of purinergic P2 receptors for extracellular ATP, is highly expressed in immune cells including microglia in the central nervous system (CNS) and has a vital role in mediating innate immune response. The P2X7 receptor is also important in neuron-glia signalling in the CNS. The gene encoding human P2X7 receptor is located in a locus of susceptibility to mood disorders. In this review, we will discuss the recent progress in understanding the role of the P2X7 receptor in the pathogenesis and development of mood disorders and in discovering CNS-penetrable P2X7 antagonists for potential uses in in vivo imaging to monitor brain inflammation and antidepressant therapeutics.
  5. Wang C, Tee M, Roy AE, Fardin MA, Srichokchatchawan W, Habib HA, et al.
    PLoS One, 2021;16(2):e0246824.
    PMID: 33571297 DOI: 10.1371/journal.pone.0246824
    The coronavirus disease (COVID-19) pandemic has impacted the economy, livelihood, and physical and mental well-being of people worldwide. This study aimed to compare the mental health status during the pandemic in the general population of seven middle income countries (MICs) in Asia (China, Iran, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). All the countries used the Impact of Event Scale-Revised (IES-R) and Depression, Anxiety and Stress Scale (DASS-21) to measure mental health. There were 4479 Asians completed the questionnaire with demographic characteristics, physical symptoms and health service utilization, contact history, knowledge and concern, precautionary measure, and rated their mental health with the IES-R and DASS-21. Descriptive statistics, One-Way analysis of variance (ANOVA), and linear regression were used to identify protective and risk factors associated with mental health parameters. There were significant differences in IES-R and DASS-21 scores between 7 MICs (p<0.05). Thailand had all the highest scores of IES-R, DASS-21 stress, anxiety, and depression scores whereas Vietnam had all the lowest scores. The risk factors for adverse mental health during the COVID-19 pandemic include age <30 years, high education background, single and separated status, discrimination by other countries and contact with people with COVID-19 (p<0.05). The protective factors for mental health include male gender, staying with children or more than 6 people in the same household, employment, confidence in doctors, high perceived likelihood of survival, and spending less time on health information (p<0.05). This comparative study among 7 MICs enhanced the understanding of metal health in the general population during the COVID-19 pandemic.
  6. Chan MY, Efthymios M, Tan SH, Pickering JW, Troughton R, Pemberton C, et al.
    Circulation, 2020 10 13;142(15):1408-1421.
    PMID: 32885678 DOI: 10.1161/CIRCULATIONAHA.119.045158
    BACKGROUND: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery.

    METHODS: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, resampling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF.

    RESULTS: In the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-β binding protein-4, and follistatin-related protein-3, as well.

    CONCLUSIONS: Large-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation.

  7. Wu X, Azizan EAB, Goodchild E, Garg S, Hagiyama M, Cabrera CP, et al.
    Nat Genet, 2023 Jun;55(6):1009-1021.
    PMID: 37291193 DOI: 10.1038/s41588-023-01403-0
    Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.
  8. Zhou J, Azizan EAB, Cabrera CP, Fernandes-Rosa FL, Boulkroun S, Argentesi G, et al.
    Nat Genet, 2021 Sep;53(9):1360-1372.
    PMID: 34385710 DOI: 10.1038/s41588-021-00906-y
    Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.
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