scholarly journals Immunological investigations of the cerebrospinal fluid in patients with recent onset psychotic disorders: A study protocol

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257946
Author(s):  
Rose Jeppesen ◽  
Sonja Orlovska-Waast ◽  
Nina Vindegaard Sørensen ◽  
Rune Haubo Bojesen Christensen ◽  
Michael Eriksen Benros
Keyword(s):  
Cerebrospinal Fluid ◽  
Rating Scales ◽  
Psychotic Disorders ◽  
Treatment Options ◽  
Healthy Controls ◽  
Recent Onset ◽  
Level Of Functioning ◽  
Broad Array ◽  
Icd 10 ◽  
Immunological Alterations

Background Though many previous studies have indicated immunological alterations in psychotic disorders, the role and prevalence of neuroinflammation is still unknown. Studies previously investigating immune related biomarkers in the cerebrospinal fluid (CSF) of these patients are mainly small studies on few markers, and many have not compared patients to healthy controls. Methods We will conduct a large case-control study including at least 100 patients with recent onset psychotic disorders and 100 sex- and age matched healthy controls. The cases will include patients diagnosed with a psychotic disorder according to ICD-10 (F20/F22-29) within a year prior to inclusion. We will collect both CSF, blood and fecal samples, to gain insight into possible immunological alterations. The psychopathology of all participants will thoroughly be evaluated using the SCAN interview, and multiple rating scales covering different symptom groups. All participants will partake in a detailed neurological examination, including the Neurological Evaluation Scale assessing neurological soft signs. Additionally, we will assess cognitive functioning, evaluate quality of life and level of functioning, and collect data on a broad array of possible confounders. Our primary outcomes will include CSF leucocytes, CSF/serum albumin ratio, CSF total protein, IgG index, CSF levels of IL-6 and IL-8, and presence of antineuronal autoantibodies in CSF and blood. For our secondary outcomes, exploratory analyses will be performed on a broader panel of neuroimmunological markers. All participants will be invited for a follow-up visit to assess longitudinal changes. The current study is part of a larger CSF biobank build-up for severe mental disorders (PSYCH-FLAME). Discussion This study will represent the largest investigation of CSF in patients with psychotic disorders compared to healthy controls to date. We expect the study to contribute with new, important knowledge on pathophysiological mechanisms, and to help pave the way for future investigations of individualized treatment options. Trial registration The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945).

scholarly journals Neuroimmunological investigations of cerebrospinal fluid in patients with recent onset depression – a study protocol

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Nina Vindegaard Sørensen ◽  
Sonja Orlovska-Waast ◽  
Rose Jeppesen ◽  
Rune Haubo Christensen ◽  
Michael Eriksen Benros
Keyword(s):  
Cerebrospinal Fluid ◽  
Rating Scales ◽  
Smoking Status ◽  
White Cell Count ◽  
Healthy Controls ◽  
Proinflammatory Response ◽  
Recent Onset ◽  
Protein Levels ◽  
Wide Range ◽  
Icd 10

Abstract Background A proinflammatory response has been suggested to be involved in the pathophysiology of depression in a subgroup of patients. However, comprehensive largescale studies on neuroimmunological investigations of the cerebrospinal fluid (CSF) are lacking and no largescale longitudinal CSF studies comparing patients with depression to healthy controls currently exist. Methods A longitudinal case-control study including at least 100 patients with first time depression (ICD-10: F32) within the past year with ongoing symptoms and at least 100 sex and age matched healthy controls with collection of CSF, blood, and fecal samples. All individuals will be evaluated by neurological examination including neurological soft signs, interviewed for psychopathology assessment and have symptomatology evaluated by relevant rating scales. Level of functioning and quality of life will be evaluated by a panel of interview questions and rating scales, and cognitive function assessed by a relevant test battery. In addition, a large number of potential confounders will be registered (BMI, smoking status, current medication etc.). Primary outcomes: CSF white cell count, CSF/serum albumin ratio, CSF total protein levels, IgG index, CSF levels of IL-6 and IL-8, and the prevalence of any CNS-reactive autoantibody in CSF and/or blood. Secondary outcomes: exploratory analyses of a wide range of neuroimmunological markers and specific autoantibodies. Power calculations are computed for all primary outcomes based on previous CSF studies including patients with depression and healthy controls. Discussion This study will represent the hitherto largest investigation of CSF in patients with recent onset depression compared to healthy controls. We expect to elucidate neuroimmunological alterations in individuals with depression and characterize an immunological profile paving the way for the development of effective treatments based on biomarkers. Trial registration The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945).

Plasma thiol/disulphide homeostasis changes in patients with restless legs syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ertan Kucuksayan ◽  
Serkan Ozben ◽  
Selma Topaloglu Tuac ◽  
Mesrure Koseoglu ◽  
Ozcan Erel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Restless Legs Syndrome ◽  
Rating Scales ◽  
Spectrophotometric Analysis ◽  
Healthy Controls ◽  
Restless Legs ◽  
Severity Rating ◽  
Total Thiol ◽  
Disease Rating ◽  
Positive Correlations

Abstract Objectives Restless legs syndrome (RLS) is a common neurological condition. Oxidative stress plays an important role in its pathogenesis. Thiol-disulphide homeostasis (TDH) is a new biomarker of oxidative stress. We studied plasma TDH to determine whether TDH could be used as a new biomarker for RLS and evaluated correlations between TDH and various disease severity rating scales. Methods A total of 25 RLS patients and 25 healthy controls were included into the study. TDH status was determined using an automated spectrophotometric analysis method and correlations were analyzed between the TDH status and various disease rating scales in the RLS patients. Results Plasma total (401 ± 27 μmol/L) and native thiol (354 ± 30 μmol/L) levels were significantly lower, but disulphide level (24 ± 6 μmol/L) was significantly (<0.0001) higher in the RLS patients compared to the controls (455 ± 36, 424 ± 37, 15 ± 5 μmol/L, respectively). The disulphide/native thiol and disulphide/total thiol ratios increased, in contrast, native thiol/total thiol ratio decreased significantly in the RLS patients compared to the healthy controls (<0.0001). The disulphide levels correlated positively with age and various rating scores of the RLS patients. International Restless Legs Syndrome Study Group (IRLSSG) rating score and age correlated negatively with the total and native thiol levels. Conclusions Our findings indicate increased oxidative stress in the RLS patients reflected by decreased native and total thiol, and increased disulphide levels and positive correlations between the disulphide levels and various rating scores. We suggest dynamic TDH status to be used as a novel biomarker for the diagnosis and follow-up of the RLS patients.

scholarly journals Cerebrospinal Fluid α-Synuclein Species in Cognitive and Movements Disorders

2021 ◽  
Vol 11 (1) ◽  
pp. 119
Author(s):  
Vasilios C. Constantinides ◽  
Nour K. Majbour ◽  
George P. Paraskevas ◽  
Ilham Abdi ◽  
Bared Safieh-Garabedian ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Multiple System Atrophy ◽  
Progressive Supranuclear Palsy ◽  
Movement Disorders ◽  
Corticobasal Degeneration ◽  
Healthy Controls ◽  
Frontotemporal Degeneration ◽  
Blood Contamination ◽  
Dementia Patients ◽  
Specificity And Sensitivity

Total CSF α-synuclein (t-α-syn), phosphorylated α-syn (pS129-α-syn) and α-syn oligomers (o-α-syn) have been studied as candidate biomarkers for synucleinopathies, with suboptimal specificity and sensitivity in the differentiation from healthy controls. Studies of α-syn species in patients with other underlying pathologies are lacking. The aim of this study was to investigate possible alterations in CSF α-syn species in a cohort of patients with diverse underlying pathologies. A total of 135 patients were included, comprising Parkinson’s disease (PD; n = 13), multiple system atrophy (MSA; n = 9), progressive supranuclear palsy (PSP; n = 13), corticobasal degeneration (CBD; n = 9), Alzheimer’s disease (AD; n = 51), frontotemporal degeneration (FTD; n = 26) and vascular dementia patients (VD; n = 14). PD patients exhibited higher pS129-α-syn/α-syn ratios compared to FTD (p = 0.045), after exclusion of samples with CSF blood contamination. When comparing movement disorders (i.e., MSA vs. PD vs. PSP vs. CBD), MSA patients had lower α-syn levels compared to CBD (p = 0.024). Patients with a synucleinopathy (PD and MSA) exhibited lower t-α-syn levels (p = 0.002; cut-off value: ≤865 pg/mL; sensitivity: 95%, specificity: 69%) and higher pS129-/t-α-syn ratios (p = 0.020; cut-off value: ≥0.122; sensitivity: 71%, specificity: 77%) compared to patients with tauopathies (PSP and CBD). There are no significant α-syn species alterations in non-synucleinopathies.

scholarly journals The inflammatory profile of cerebrospinal fluid, plasma, and saliva from patients with severe neuropathic pain and healthy controls-a pilot study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mika Jönsson ◽  
Björn Gerdle ◽  
Bijar Ghafouri ◽  
Emmanuel Bäckryd
Keyword(s):  
Cerebrospinal Fluid ◽  
Neuropathic Pain ◽  
Pain Intensity ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Partial Least Square Regression ◽  
Therapeutic Interventions ◽  
Healthy Controls ◽  
Inflammatory Profile

Abstract Background Neuropathic pain (NeuP) is a complex, debilitating condition of the somatosensory system, where dysregulation between pro- and anti-inflammatory cytokines and chemokines are believed to play a pivotal role. As of date, there is no ubiquitously accepted diagnostic test for NeuP and current therapeutic interventions are lacking in efficacy. The aim of this study was to investigate the ability of three biofluids - saliva, plasma, and cerebrospinal fluid (CSF), to discriminate an inflammatory profile at a central, systemic, and peripheral level in NeuP patients compared to healthy controls. Methods The concentrations of 71 cytokines, chemokines and growth factors in saliva, plasma, and CSF samples from 13 patients with peripheral NeuP and 13 healthy controls were analyzed using a multiplex-immunoassay based on an electrochemiluminescent detection method. The NeuP patients were recruited from a clinical trial of intrathecal bolus injection of ziconotide (ClinicalTrials.gov identifier NCT01373983). Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was used to identify proteins significant for group discrimination and protein correlation to pain intensity. Proteins with variable influence of projection (VIP) value higher than 1 (combined with the jack-knifed confidence intervals in the coefficients plot not including zero) were considered significant. Results We found 17 cytokines/chemokines that were significantly up- or down-regulated in NeuP patients compared to healthy controls. Of these 17 proteins, 8 were from saliva, 7 from plasma, and 2 from CSF samples. The correlation analysis showed that the most important proteins that correlated to pain intensity were found in plasma (VIP > 1). Conclusions Investigation of the inflammatory profile of NeuP showed that most of the significant proteins for group separation were found in the less invasive biofluids of saliva and plasma. Within the NeuP patient group it was also seen that proteins in plasma had the highest correlation to pain intensity. These preliminary results indicate a potential for further biomarker research in the more easily accessible biofluids of saliva and plasma for chronic peripheral neuropathic pain where a combination of YKL-40 and MIP-1α in saliva might be of special interest for future studies that also include other non-neuropathic pain states.

scholarly journals Emotion regulation across the psychosis continuum

2019 ◽  
Vol 32 (1) ◽  
pp. 219-227 ◽  
Author(s):  
Hannah C. Chapman ◽  
Katherine F. Visser ◽  
Vijay A. Mittal ◽  
Brandon E. Gibb ◽  
Meredith E. Coles ◽  
...  
Keyword(s):  
Emotion Regulation ◽  
Psychotic Disorders ◽  
Psychiatric Symptoms ◽  
Healthy Controls ◽  
Community Members ◽  
Targeted Treatments ◽  
Regulation Strategies ◽  
Dose Dependent Decrease ◽  
Study Participants ◽  
Prodromal Syndrome

AbstractEmotion regulation dysfunction is characteristic of psychotic disorders, but little is known about how the use of specific types of emotion regulation strategies differs across phases of psychotic illness. This information is vital for understanding factors contributing to psychosis vulnerability states and developing targeted treatments. Three studies were conducted to examine emotion regulation across phases of psychosis, which included (a) adolescent community members with psychotic-like experiences (PLEs; n = 262) and adolescents without PLEs (n = 1,226); (b) adolescents who met clinical high-risk criteria for a prodromal syndrome (n = 29) and healthy controls (n = 29); and (c) outpatients diagnosed with schizophrenia or schizoaffective disorder (SZ; n = 61) and healthy controls (n = 67). In each study, participants completed the Emotion Regulation Questionnaire and measures of psychiatric symptoms and functional outcome. The three psychosis groups did not differ from each other in reported use of suppression; however, there was evidence for a vulnerability-related, dose-dependent decrease in reappraisal. Across each sample, a lower use of reappraisal was associated with poorer clinical outcomes. Findings indicate that emotion regulation abnormalities occur across a continuum of psychosis vulnerability and represent important targets for intervention.

Comparisons of Narrative Psychotherapy to Conventional CBT for the Psychotherapy of Psychosis and Bipolar Disorder

2017 ◽  
Vol 41 (S1) ◽  
pp. s779-s779
Author(s):  
L. Mehl-Madrona ◽  
B. Mainguy
Keyword(s):  
Bipolar Disorder ◽  
Narrative Therapy ◽  
Rating Scales ◽  
Psychotic Disorders ◽  
Rating Scale ◽  
Therapy Group ◽  
Well Being ◽  
Outcome Data ◽  
Symptom Scale ◽  
Young Mania

IntroductionThere is ongoing debate about about both the value of psychotherapy in psychotic disorders and the best type of psychotherapy to use if necessary.MethodsWe conducted narrative psychotherapy with 18 adults, all diagnosed as having bipolar disorder with psychotic features and/or schizo-affective disorder. Outcome data consisted of the Positive and Negative Symptom Scale, the Clinical Global Impressions Scale, the Young Mania Rating Scale, the Hamilton Anxiety and Depression Scales, the My Medical Outcome Profile, Version 2(MYMOP2), and the Outcome Rating Scales of Duncan and Miller. We compare the outcomes of our patients to those of a matched comparison group receiving conventional psycho-education and cognitive behavioural therapy. Patients were seen for a minimum of 16 weeks over an average of 22 weeks. Average age was 31.5 years with a standard deviation of 8.1 years.ResultsThe narrative therapy group showed statistically significant reductions in all outcome measures compared to the conventional treatment group. They continued treatment significantly longer and had fewer re-hospitalizations. They were less distressed by voices.ConclusionsA narrative psychotherapy approach using dialogical theory and therapy ideas is a reasonable approach for the psychotherapy of psychosis. Review of psychotherapy notes showed that narrative approaches allowed the therapist to align with the patient as collaborator in considering the story presented and was therefore less productive of defensiveness and self-criticism than conventional approaches. The therapy included techniques for negotiating changes in illness narratives, identity narratives, and treatment narratives that were more conducive of well-being and recovery.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Microscopic Particles in Two Fractions of Fresh Cerebrospinal Fluid in Twins with Schizophrenia or Bipolar Disorder and in Healthy Controls

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45994 ◽  
Author(s):  
Viktoria Johansson ◽  
Rolf Nybom ◽  
Lennart Wetterberg ◽  
Christina M. Hultman ◽  
Tyrone D. Cannon ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cerebrospinal Fluid ◽  
Healthy Controls

scholarly journals Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis

2021 ◽  
Vol 11 (2) ◽  
pp. 238
Author(s):  
Keld-Erik Byg ◽  
Helle H. Nielsen ◽  
Tobias Sejbaek ◽  
Jonna Skov Madsen ◽  
Dorte Aalund Olsen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Light Chain ◽  
Plasma Levels ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker ◽  
Fluid Levels

Background: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. Results: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (n = 20) median 2304 pg/mL (interquartile range (IQR) 630–19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194–402) in healthy controls (n = 11) (p = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5–49.3) compared to 6.2 pg/mL (IQR 4.3–8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2–9.0) in healthy controls (p = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (p = 0.009 and p = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. Conclusions: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.

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