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1.
Schizophr Res ; 269: 144-151, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38795661

ABSTRACT

BACKGROUND: Yoga has shown promise as an add-on therapy for patients with schizophrenia. However, most studies have been short-term, with methodological limitations. METHODS: We conducted a six-month parallel-group randomized-controlled trial (with rater blinding) to evaluate the effectiveness of a yoga-based intervention in improving symptoms and quality of life in patients with schizophrenia. We recruited 110 patients from an urban tertiary hospital and a semi-urban community centre who met DSM 5 criteria for schizophrenia and were on stable medication for at least six weeks. Participants were randomly assigned to either yoga add-on therapy (YT) or treatment-as-usual (TAU) groups. Clinical assessments were conducted at baseline and at one, three and six months. The primary outcome was changes in positive/negative symptom scores and secondary outcomes included changes in quality of life, perceived stress and socio-occupational functioning. RESULTS: Intention to treat analysis with a longitudinal mixed model approach revealed a significant group-by-time interaction with the YT group showing medium effect improvements in negative symptoms (η2p = 0.06) and small effect improvements in positive symptoms (η2p = 0.012), WHOQOL-BREF quality of life [psychological well-being (η2p = 0.015) and environmental health (η2p = 0.048)] when compared to TAU. The patients successfully learned and performed yoga practices without reporting any significant adverse effects. DISCUSSION: Our findings suggest that yoga-based intervention may be a valuable adjuvant therapy for medication-stabilized patients with schizophrenia, especially in ameliorating negative symptoms and enhancing quality of life. Future controlled trials, including active physical interventions, are crucial to validate yoga's efficacy, optimize clinical use, and elucidate underlying mechanisms.


Subject(s)
Quality of Life , Schizophrenia , Yoga , Humans , Schizophrenia/therapy , Male , Female , Adult , Middle Aged , Outcome Assessment, Health Care , Combined Modality Therapy , Treatment Outcome
2.
Ann Indian Acad Neurol ; 27(1): 40-45, 2024.
Article in English | MEDLINE | ID: mdl-38495245

ABSTRACT

Background: Progressive supranuclear palsy (PSP) is the most common primary tauopathy. The definite diagnosis of PSP is established by histopathologic changes in the brain. There are no reliable blood-based biomarkers to aid the diagnosis of this fatal disease at an early stage. Also, the precise etiopathology of PSP and its variants is inadequately understood. Objective: Blood-based molecules such as neurofilament light chain (NfL) and insulin-like growth factor-1 (IGF-1) are shown as important markers of neurodegenerative and aging processes, respectively. These two biomarkers have not been analyzed simultaneously in PSP patients. Methods: To address this knowledge gap, 40 PSP patients and equal number of healthy individuals were recruited and serum levels of NfL and IGF-1 were assayed in all the study participants by enzyme-linked immunosorbent assay (ELISA). Motor and nonmotor symptoms were evaluated in PSP patients using various scales/questionnaires. Cardiac autonomic function tests were performed in a subset of patients (n = 27). Results: A significantly high serum level of NfL (P < 0.01) and a reduced level of IGF-1 (P = 0.02) were observed in PSP patients compared to healthy controls. Besides, a negative correlation (r = -0.54, P < 0.01) between NfL and IGF-1 levels was observed in PSP patients. Conclusion: The finding of this study reinforces the important role of blood NfL level as a potential biomarker of PSP. Further, the current study provides novel insights into the reciprocal correlation between NfL and IGF-1 in PSP patients. Combined analysis of blood levels of these two functionally relevant markers might be useful in the prediction and diagnosis of PSP.

4.
Brain Behav Immun ; 115: 505-516, 2024 01.
Article in English | MEDLINE | ID: mdl-37972879

ABSTRACT

Neurodevelopmental disorders (NDDs) are a spectrum of conditions with commonalities as well as differences in terms of phenome, symptomatome, neuropathology, risk factors and underlying mechanisms. Immune dysregulation has surfaced as a major pathway in NDDs. However, it is not known if neurodevelopmental disorders share a common immunopathogenetic mechanism. In this study, we explored the possibility of a shared immune etiology in three early-onset NDDs, namely Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD) and Intellectual Disability Disorder (IDD). A panel of 48 immune pathway-related markers was assayed in 135 children with NDDs, represented by 45 children with ASD, ADHD and IDD in each group, along with 35 typically developing children. The plasma levels of 48 immune markers were analyzed on the Multiplex Suspension Assay platform using Pro Human cytokine 48-plex kits. Based on the cytokine/chemokine/growth factor levels, different immune profiles were computed. The primary characteristics of NDDs are depletion of the compensatory immune-regulatory system (CIRS) (z composite of IL-4, IL-10, sIL-1RA, and sIL-2R), increased interleukin (IL)-1 signaling associated with elevated IL-1α and decreased IL-1-receptor antagonist levels, increased neurogenesis, M1/M2 macrophage polarization and increased IL-4 as well as C-C Motif Chemokine Ligand 2 (CCL2) levels. With a cross-validated sensitivity of 81.8% and specificity of 94.4%, these aberrations seem specific for NDDs. Many immunological abnormalities are shared by ASD, ADHD and IDD, which are distinguished by minor differences in IL-9, IL-17 and CCL12. In contrast, machine learning reveals that NDD group consists of three immunologically distinct clusters, with enhanced neurogenesis, Th-1 polarization, or IL-1 signaling as the defining features. NDD is characterized by immune abnormalities that have functional implications for neurogenesis, neurotoxicity, and neurodevelopment. Using machine learning, NDD patients could be classified into subgroups with qualitatively distinct immune disorders that may serve as novel drug targets for the treatment of NDDs.


Subject(s)
Autism Spectrum Disorder , Neurodevelopmental Disorders , Child , Humans , Interleukin-4 , Neurogenesis , Biomarkers , Macrophages , Chemokines
5.
Cureus ; 15(7): e41377, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37546047

ABSTRACT

Background Stress leads to immune system dysregulation and dyshomeostasis at the gene level. Mind-body practices are known to influence genomic expression, leading to better health and quality of life. Objective To assess the effect of Advanced Meditation Program (AMP) on the mRNA expression of pro-inflammatory and antioxidative genes among those already practicing Sudarshan Kriya Yoga (SKY). Methods A total of 97 healthy volunteers participated in the study, distributed into two groups. The Group I SKY practitioners attended a four-day AMP (50 participants with an average age of 38.8 ± 11.9 consisting of 37 females and 13 males); they are first-time participants of the AMP. Group II SKY practitioners, on the other hand, consisted of 47 participants with an average age of 36.4 ± 9.3 with 43 females and four males. At day 0, day 5, and day 90, the mRNA expression of pro-inflammatory genes, namely interleukin (IL) 1ß, IL6, and the tumor necrosis factor (TNF), and the expression of antioxidative genes, namely superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) was observed. The data were analysed in two phases due to the emergence of coronavirus disease 2019 (COVID-19): (i) pre-COVID-19 and (ii) during COVID-19. Results In the pre-COVID-19 data set, IL1ß, IL6, and TNF were found to have decreased in both groups. There is a significant increase in the expression of SOD and catalase in Group I and a decrease in Group II by day 90. During COVID-19, pro-inflammatory genes increased in Group I and had no significant change in Group II. All three antioxidant genes had decreased expression by day 90 in Group I; SOD decreased in Group II. Interpretation and conclusions Reduced expression of pro-inflammatory genes and increase in the expression of antioxidative genes during the pre-COVID-19 time suggest that the practice of SKY and added AMP may enhance antioxidative defense and may reduce the chance of getting diseases related to inflammation in the body.

6.
Asian J Psychiatr ; 86: 103636, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37290243

ABSTRACT

BACKGROUND: Schizophrenia is a complex neuropsychiatric disorder for which several etiopathological theories have been proposed, one of the prominent ones being immune dysfunction. Recent studies on yoga as an add-on therapy have shown improvement in negative symptoms, cognition, and quality of life in schizophrenia patients. However, the biological mechanism/s of action of yoga in schizophrenia are not clear. The current study was aimed at exploring the effects of long-term (6 months) add-on yoga therapy on the immune inflammatory pathway in schizophrenia patients. METHODS: Sixty schizophrenia patients were randomized to add-on yoga therapy (YT=30) and treatment-as-usual (TAU=30) groups of which 21 patients in YT and 20 in TAU group completed the study. Blood samples and clinical assessments were obtained at baseline and at the end of 6 months. The plasma levels of nine cytokines (IL-2, IL-4, IL-5, IL-10, IL-12(p70), IL-13, GM-CSF, IFN-γ, and TNF-α) were quantified using multiplex suspension array. The clinical assessments included SAPS, SANS, BPRS, PSS, CGI, SOFS and WHOQUOL-BREF. RESULTS: Patients in the yoga group showed significant reductions in plasma TNF-α (Z = 2.99, p = 0.003) and IL-5 levels (Z = 2.20, p = 0.03) and greater clinical improvements in SAPS, SANS, PSS, and SOFS scores as compared to TAU group. Further, plasma TNF-α levels exhibited a positive correlation with negative symptoms (rs =0.45, p = 0.02) and socio-occupational functioning (rs =0.61, p = 0.002) in the YT group. CONCLUSIONS: The findings of the study suggest that improvements in schizophrenia psychopathology with yoga interventions are associated with immuno-modulatory effects.


Subject(s)
Antipsychotic Agents , Schizophrenia , Yoga , Humans , Yoga/psychology , Antipsychotic Agents/therapeutic use , Schizophrenia/drug therapy , Quality of Life , Interleukin-5/therapeutic use , Tumor Necrosis Factor-alpha , Treatment Outcome
7.
Asian J Psychiatr ; 77: 103261, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36181754

ABSTRACT

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity underlying cognitive deficits, including working memory deficits (WMD), in schizophrenia. Methodological challenges and inconsistencies are reported with peripheral BDNF levels. Left dorsolateral prefrontal cortex (DLPFC) is proposed to underlie WMD, though inconsistently. We aimed to explore the correlations between brain activation during working memory task-based functional Magnetic Resonance Imaging (fMRI) and BDNF gene expression in schizophrenia patients with WMD. METHODS: 26 patients with schizophrenia with established WMD were recruited for the study. Blood samples were collected to study lymphocyte BDNF gene expression. Patients underwent task-based fMRI to examine the working memory performance and related brain activation. Whole-brain analysis was performed with 2-back > 0-back and 2-back > rest contrast. The peak intensity values of the activation were used for correlation analysis. RESULTS: Whole brain analysis with 2-back > rest contrast revealed maximum activation in left DLPFC, Brodmann area 9 (t = 10.54, FWE corrected p < 0.05). The baseline BDNF gene expression correlated positively with the peak intensity of brain activation in left DLPFC (r = 0.365, p = 0.033). Negative symptom score negatively correlated with BDNF gene expression (r = -0.499, p = 0.005) and left DLPFC fMRI activation (r = -0.393, p = 0.023) respectively. CONCLUSION: We found a significant positive association between BDNF gene expression and the activation of the DLPFC during the working memory task. This novel observation needs further systematic evaluation to establish the potential role of peripheral BDNF expression in WMD in schizophrenia.


Subject(s)
Schizophrenia , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Gene Expression , Humans , Magnetic Resonance Imaging , Memory Disorders , Memory, Short-Term/physiology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/metabolism , Schizophrenia/complications , Schizophrenia/diagnostic imaging , Schizophrenia/genetics
9.
Eur J Neurol ; 29(7): 2074-2083, 2022 07.
Article in English | MEDLINE | ID: mdl-35322935

ABSTRACT

BACKGROUND: The IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL-33/ST2 axis can induce autoimmune reaction and inflammatory responses. Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy, mostly caused by post-infection autoimmunity. The role of IL-33/ST2 axis is not known in GBS. This study aimed to explore the role of IL-33/ST2 axis in GBS. METHODS: Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159, rs7044343, rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753) coding for suppressor of tumorigenicity 2 (ST2) were genotyped in 179 GBS patients and 186 healthy controls by TaqMan Allelic Discrimination Assay. Plasma levels of IL-33 and sST2 were measured in a subset of GBS patients (n = 80) and healthy controls (n = 80) by ELISA. RESULTS: The frequencies of CC genotype of rs10192157 (p = 0.043) and TT genotype of rs10206753 (p = 0.036) SNPs of Il1rl1 gene differed significantly between GBS patients and healthy controls. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk for GBS. In addition, the plasma sST2 levels were significantly elevated in GBS patients compared to healthy subjects (24,934.31 ± 1.81 pg/ml vs. 12,518.97 ± 1.51 pg/ml, p < 0.001). Plasma sST2 levels showed a significant correlation with the disability scores at the peak of neurological deficit in GBS patients. CONCLUSIONS: The IL-33/ST2 axis is suggested to influence the immunopathogenesis of GBS. Genetic variants of Il1rl1 gene might serve as a risk determinant of GBS and plasma sST2 levels might emerge as a biomarker of severity of GBS, if replicated further by other studies.


Subject(s)
Guillain-Barre Syndrome , Interleukin-1 Receptor-Like 1 Protein , Interleukin-33 , Genotype , Guillain-Barre Syndrome/immunology , Humans , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-33/genetics , Polymorphism, Single Nucleotide
10.
Medicine (Baltimore) ; 98(43): e17399, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31651843

ABSTRACT

INTRODUCTION: Schizophrenia is one of the most severe mental disorders with a prevalence of about 1% and a leading cause of disability among young adults. Pharmacotherapy is the mainstay in the management of schizophrenia. However, even with the best of medication, several problems like refractoriness, negative symptoms, frequent relapses, and cognitive impairments persist. METHODS: This is a randomized-controlled clinical study including patients from an urban tertiary hospital and a semi-urban community center, with a between-group, repeated-measures, longitudinal design. This study will recruit 160 patients with DSM 5 diagnosis of schizophrenia who are on stable medication for a minimum of 6 weeks; they will be randomly assigned into 2 arms viz., yoga therapy (YT), and treatment-as-usual (TAU) with 80 patients in each arm. Participants will undergo Clinical, Laboratory, and Radiological assessments at baseline and at intervals of 1 month, 3 months, and 6 months from the baseline. It is hypothesized that yoga will improve psychopathology and emotion processing, increase serum brain derived neurotrophic factor (BDNF) and plasma oxytocin levels and effect changes in cerebral activation in areas of the brain associated with schizophrenia. DISCUSSION: This study aims to measure the efficacy of a Yoga-based intervention as an adjunct in patients with schizophrenia as well as the mechanisms of these effects. TRIAL REGISTRATION: Registered retrospectively with Clinical Trial Registry - India (CTRI) with registration number CTRI/2017/08/009219.


Subject(s)
Neuronal Plasticity , Schizophrenia/physiopathology , Schizophrenia/therapy , Schizophrenic Psychology , Yoga/psychology , Adolescent , Adult , Female , Humans , Longitudinal Studies , Male , Middle Aged , Randomized Controlled Trials as Topic , Single-Blind Method , Treatment Outcome , Urban Population , Young Adult
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