Immune-inflammatory markers of response to repetitive transcranial magnetic stimulation in depression: A scoping review.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a safe, effective and non-invasive form of neuromodulatory therapy in patients with major depressive disorder (MDD). MDD is associated with increased peripheral and brain inflammation. The current paper aims to provide an overview of research examining the relationship between immune and inflammatory markers and response to rTMS in MDD. METHODS: A scoping review method was adopted in keeping with the PRISMA-ScR guidelines. Twelve relevant studies were retrieved from the PubMed and Scopus databases and rated for study quality using a modified version of the BIOCROSS tool. RESULTS: Response to rTMS in MDD was associated with basal and post-treatment levels of the inflammatory markers amyloid A, antithrombin III, oxidised phosphatidylcholine, and the microRNA miR-146a-5p. Inconsistent results were observed for the cytokines interleukin-1ß, interleukin-2 and tumour necrosis factor-α. Increased baseline levels of interleukin-6 and C-reactive protein were linked to a poorer response to rTMS. DISCUSSION: These results suggest that rTMS may have effects on immune-inflammatory pathways that are distinct from those of antidepressants and electroconvulsive therapy. Because of certain methodological limitations in the included studies, these results should be interpreted with caution.

The influence of cultural and religious factors on cross-national variations in the prevalence of chronic back and neck pain: an analysis of data from the global burden of disease 2019 study.

Introduction: Low back pain and neck pain are among the most commonly reported forms of chronic pain worldwide, and are associated with significant distress, disability and impairment in quality of life. Though these categories of pain can be analyzed and treated from a biomedical perspective, there is evidence that they are both related to psychological variables such as depression and anxiety. The experience of pain can be significantly influenced by cultural values. For example, cultural beliefs and attitudes can influence the meaning attached to the experience of pain, the responses of others to a sufferer's pain, and the likelihood of seeking medical care for particular symptoms. Likewise, religious beliefs and practices can influence the both experience of pain and the responses to it. These factors have also been associated with variations in the severity of depression and anxiety. Methods: In the current study, data on the estimated national prevalence of both low back pain and neck pain, obtained from the 2019 Global Burden of Disease Study (GBD 2019), is analyzed in relation to cross-national variations in cultural values, as measured using Hofstede's model (n =115 countries) and in religious belief and practice, based on the most recent Pew Research Center survey (n = 105 countries). To address possible confounding factors, these analyses were adjusted for variables known to be associated with chronic low back or neck pain, namely smoking, alcohol use, obesity, anxiety, depression and insufficient physical activity. Results: It was found that the cultural dimensions of Power Distance and Collectivism were inversely correlated with the prevalence of chronic low back pain, and Uncertainty Avoidance was inversely correlated with the prevalence of chronic neck pain, even after adjustment for potential confounders. Measures of religious affiliation and practice were negatively correlated with the prevalence of both conditions, but these associations were not significant after adjusting for cultural values and confounders. Discussion: These results highlight the existence of meaningful cross-cultural variations in the occurrence of common forms of chronic musculoskeletal pain. Psychological and social factors that could account for these variations are reviewed, along with their implications for the holistic management of patients with these disorders.

Prior infection with intestinal coronaviruses moderates symptom severity and mortality in patients with COVID-19: A hypothesis and preliminary evidence.

The pandemic of acute respiratory illness caused by the novel betacoronavirus SARS-CoV-2, officially designated COVID-19, has attained the proportions of a global health crisis. Though all nations of the world have been affected by this disease, there have been marked cross-national variations in prevalence, severity and mortality rates. Various explanations, based on demographic, social and climatic factors, have been suggested to account for this variability, but these remain unverified to date. Based on recent research findings suggesting that human enterocytes may serve as a point of entry for SARS-CoV-2, leading to intestinal viral replication, this paper puts forward the hypothesis that prior intestinal infection with coronaviruses, either symptomatic or asymptomatic, may moderate this process and minimize the severity of SARS-CoV-2 infection. This hypothesis is supported by evidence on the gastrointestinal manifestations of SARS-CoV-2 and related infections, on the geographical patterns observed in the variability of COVID-19 mortality, and on the occurrence and geographical distribution of outbreaks of diarrheal disease, as well as asymptomatic infection, with human coronaviruses as verified by direct or serological testing. Preliminary supporting evidence based on national and international health statistics is presented, along with suggestions on more robust methods by which this hypothesis may be tested. If the proposal put forth in this paper can be confirmed either wholly or in part, it would have significant implications in terms of strategies aimed at minimizing the severity of COVID-19 in a clinical setting.

An exploratory study of immune markers in acute and transient psychosis.

The aim of this study was to look into the balance of pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (TGF-ß) cytokines and their association with stress, alterations in HPA axis activity and the disease severity in acute psychosis. Socio-demographic and clinical details were collected from 41 in-patients with a diagnosis of Acute and Transient Psychotic Disorder. Holmes and Rahe Stress Scale for stress in the preceding year, and Brief Psychiatric Rating Scale at baseline and follow up (4-12 weeks) for psychopathology were applied. IL-6, TNF-α (pro-inflammatory), TGF-ß (anti-inflammatory) and Cortisol (morning and afternoon values) were measured at baseline and follow up. A total of 30 out of 41 cases recruited had follow up data available. The levels of IL-6 (p<0.001), TNF-α (p<0.001) and TGF-ß (p<0.001) at baseline were all found to be significantly elevated compared to 42 age and gender matched healthy controls. There was a significant increase in the levels of TNF-α (p=0.020) and morning levels of cortisol (p=0.009) and a significant decrease in the levels of TGF-ß (p=0.004) and afternoon levels of cortisol (p=0.043) from baseline to follow up. This study showed that there was an increased level of both pro and anti-inflammatory cytokines at baseline and a prolonged pro - inflammatory compared to anti - inflammatory response which warrants larger prospective studies and comparative studies to patients with schizophrenia and bipolar disorders.

CometQ: An automated tool for the detection and quantification of DNA damage using comet assay image analysis.

BACKGROUND AND OBJECTIVE: DNA damage analysis plays an important role in determining the approaches for treatment and prevention of various diseases like cancer, schizophrenia and other heritable diseases. Comet assay is a sensitive and versatile method for DNA damage analysis. The main objective of this work is to implement a fully automated tool for the detection and quantification of DNA damage by analysing comet assay images. METHODS: The comet assay image analysis consists of four stages: (1) classifier (2) comet segmentation (3) comet partitioning and (4) comet quantification. Main features of the proposed software are the design and development of four comet segmentation methods, and the automatic routing of the input comet assay image to the most suitable one among these methods depending on the type of the image (silver stained or fluorescent stained) as well as the level of DNA damage (heavily damaged or lightly/moderately damaged). A classifier stage, based on support vector machine (SVM) is designed and implemented at the front end, to categorise the input image into one of the above four groups to ensure proper routing. Comet segmentation is followed by comet partitioning which is implemented using a novel technique coined as modified fuzzy clustering. Comet parameters are calculated in the comet quantification stage and are saved in an excel file. RESULTS: Our dataset consists of 600 silver stained images obtained from 40 Schizophrenia patients with different levels of severity, admitted to a tertiary hospital in South India and 56 fluorescent stained images obtained from different internet sources. The performance of "CometQ", the proposed standalone application for automated analysis of comet assay images, is evaluated by a clinical expert and is also compared with that of a most recent and related software-OpenComet. CometQ gave 90.26% positive predictive value (PPV) and 93.34% sensitivity which are much higher than those of OpenComet, especially in the case of silver stained images. The results are validated using confusion matrix and Jaccard index (JI). Comet assay images obtained after DNA damage repair by incubation in the nutrient medium were also analysed, and CometQ showed a significant change in all the comet parameters in most of the cases. CONCLUSIONS: Results show that CometQ is an accurate and efficient tool with good sensitivity and PPV for DNA damage analysis using comet assay images.

Is Depression an Inflammatory Disease? Findings from a Cross-Sectional Study at a Tertiary Care Center.

BACKGROUND: Evidence linking inflammation and depression is marred by several methodological inconsistencies. Further, varying information is present on the role of gender as a potential confounder in this association. AIMS: To assess systemic inflammation in drug naοve depression by measuring selected pro-inflammatory (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and anti-inflammatory cytokines (transforming growth factor-beta [TGF-ß]) and comparing them with a matched control group. We also aimed at exploring the differences in these markers between genders. SETTING AND DESIGN: The study was a cross-sectional one carried out a teaching cum Tertiary Care Hospital. MATERIALS AND METHODS: We recruited 55 drug naοve cases diagnosed with major depression and compared them for inflammatory markers with a matched apparently healthy control group (n = 42) at baseline. The inflammatory markers were also compared between the genders. Baseline depression and stress levels were assessed using standard measures. STATISTICAL ANALYSIS USED: Mann-Whitney U-test. RESULTS: In comparison with healthy controls, drug naοve depressed individuals demonstrated significantly raised baseline levels of TNF-α and IL-6 (P < 0.001 for both) but no difference in levels of TGF-ß (P = 0.433). Neither the baseline depression nor the stress scores correlated with any of the inflammatory markers (P = 0.955 and 0.816 for TNF-α respectively). Males and females were comparable on the levels of markers studied (P = 0.986, 0.415, and 0.430 for TNF-α, IL-6 and TGF-ß respectively). CONCLUSION: There is evidence for higher baseline inflammation in depression prior to starting anti-depressant therapy. Gender does not mediate this observed link between inflammation and depression.

Evaluation of interleukin-6 and serotonin as biomarkers to predict response to fluoxetine.

OBJECTIVE: Only 30% of major depressive disorder (MDD) patients achieve complete remission with a serotonergic antidepressant (selective serotonin reuptake inhibitor). We investigated the potential of serotonin (5-HT) and interleukin-6 (IL-6) to serve as functional biomarkers of fluoxetine response. METHODS: Serum IL-6 and 5-HT were measured in 73 MDD patients (39 responders and 34 non-responders) pre- and 6 weeks post-treatment and in 44 normal controls with ELISA. Fluoxetine and norfluoxetine were measured using LC MS/MS. RESULTS: IL-6 levels were significantly higher in MDD patients when compared with controls (p < 0.01), and 5-HT levels were significantly lower in non-responders compared with controls (p = 0.0131). Pre- and post-treatment levels of both biomarkers individually and in combination did not significantly differ between responders and non-responders. Area under the receiver operating characteristics curve for the biomarkers was 0.5. Significant correlation was seen between the percentage change in IL-6 and percentage change in Hamilton Rating Scale for Depression score in responders. Fluoxetine and norfluoxetine concentrations were not significantly different in responders and non-responders, and there was no correlation between fluoxetine concentrations and percentage reduction in 5-HT from week 0 to 6. CONCLUSION: 5-HT and IL-6 may not serve as useful markers of response to fluoxetine because of inconsistent results across different studies. Copyright © 2016 John Wiley & Sons, Ltd.

Recurrent unipolar mania: A comparative, cross-sectional study.

INTRODUCTION: A significant number of patients experience recurrent episodes of mania without depressive episodes. Evidence from the available literature suggests that these patients differ from typical "bipolar" or "manic-depressive" patients, but results have been inconsistent. The current study aims to add to this literature by comparing the demographic, clinical and risk factor profiles of patients with recurrent mania with and without depression. METHODS: 66 patients with a diagnosis of bipolar I disorder were divided into "unipolar mania" (recurrent mania alone, MA) and "bipolar" (both mania and depression, MD) sub-groups. Comorbid diagnoses were assessed using the Mini International Neuropsychiatric Interview (MINI), and genetic and environmental risk factors were explored using the Diagnostic Interview for Genetic Studies (DIGS), Childhood Trauma Questionnaire (CTQ), and an additional questionnaire designed for the purpose of the study. Differences between the MA and MD groups in terms of demographic variables, clinical profile, comorbidities and antecedent risk factors were explored. RESULTS: Patients with both mania and depression had higher frequencies of lifetime suicide attempts, antidepressant treatment, and catatonic symptoms. There was some evidence of an association between overcrowding in childhood and the presence of depressive episodes. No other differences in demographic, clinical or risk factor variables could be found between the two groups. DISCUSSION: Our results are consistent with the view that unipolar mania is not a distinctive disorder, or even a distinctive subtype of bipolar disorder. However, this conclusion is provisional as it is based only on clinical and demographic data.

Bilateral self-enucleation in acute transient psychotic disorder: the influence of sociocultural factors on psychopathology.

Self-inflicted eye injuries are rare but a devastating consequence of a serious mental disorder. Bilateral self-enucleation also known as oedipism has been documented in ancient texts and myths. Various biologic, psychologic, and social theories have been put forward to explain this rare phenomenon. In this report, we describe a case of oedipism, which highlights the influence of sociocultural factors on the psychopathology in acute transient psychotic disorder.