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Gut permeability and low-grade inflammation in bipolar disorder
- M. Couce, G. Paniagua, L. González-Blanco, A. García-Fernández, C. Martínez-Cao, P. Sáiz, J. Bobes, M. P. García-Portilla
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S385-S386
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Introduction
Systemic inflammation has been increasingly related to bipolar disorder -BD- (Tanaka et al. Neurosci Res 2017;115 59-63). Intestinal bacterial translocation has been postulated as one of the causes of this inflammation (Nguyen et al. J Psychiatr Res 2018;99 50-61). A possible pathway is through the lipopolysaccharide, which is presented to CD14 through lipopolysaccharide binding protein (LBP) leading to a release of systemic inflammatory markers like C-reactive protein (CPR) (Funda et al. Infect Immun 2001;69 3772-81).
Objectives1) Describe gut permeability in patients with BD through the determination of intestinal inflammatory markers (LBP, sCD14) in plasma; 2) Analyze variables associated with intestinal inflammation.
MethodsCross-sectional study of 38 patients with BD [mean age=45.50 (SD=10.93; range 23-68); males=15 (39.5%)], recruited from mental health outpatient clinics in Oviedo (Spain).
Assessment: Pro-inflammation biomarkers [CRP (mg/dL), Erythrocyte Sedimentation Rate (ESR) (mm/h), Neutrophil/Lymphocyte, Monocyte/Lymphocyte, Platelet/Lymphocyte and Systemic Immune Inflammation Indexes]. Indirect markers of intestinal bacterial translocation [LBP, soluble CD14 (sCD14)]. Dichotomous variables were created for LBP, considering LBP ≥15 μg/dL as increased gut permeability; and for CPR, considering CRP≥0.3 as systemic inflammation. Metabolic syndrome [ATPIII criteria: glucose, HDL, triglycerides (mg/dl), arterial pressure (mmHg), abdominal circumference (cm)], body mass index (BMI) (kg/m2), smoking, cannabis or alcohol use.
Statistical analyses: t-Student test, multiple linear regression analyses.
ResultsAverage LBP was 14.60 μg/dL (SD=6.4) and 15 patients (39.5%) had increased gut permeability. Moreover, average CPR was 0.40 mg/dL (SD=0.58) and 16 patients (47.1%) showed systemic inflammation. There were no patients with increased levels of sCD14.
Associations were found between LBP and CPR (r=0.357; p=0.032), cannabis use in the last month (t=-2.293; p=0.029), BMI (r=0.433; p=0.008) and abdominal obesity (t=3.006; p=0.005); but no with age or sex.
Subsequently, a multiple linear regression model for LBP was calculated with variables previously mentioned, and age (based on expert criteria). The overall regression was statistically significant (R2=0.49, F=9.273, p<0.001). It was found that CPR, abdominal obesity, and cannabis use in the last month significantly predicted LBP levels (table 1).
Table 1. Multiple linear regression analyses to LBP B SE β t p CPR 4.842 1.529 0.439 3.167 0.004 Abdominal obesity 4.810 1.849 0.362 2.601 0.014 Cannabis use -5.048 2.273 -0.296 -2.221 0.034 ConclusionsMore than one third of patients with BD had increased gut permeability. Almost 50% had systemic inflammation. Intestinal permeability was directly related to abdominal obesity and systemic inflammation, but inversely related to cannabis use.
Disclosure of InterestNone Declared
Suicidal behaviour and cognition: A systematic review with special focus on prefrontal deficits
- J. Fernández-Sevillano, A. González-Pinto, J. Rodríguez-Revuelta, S. Alberich-Mesa, L. González-Blanco, I. Zorrilla-Martínez, Á. Velasco, P. López-Pena, I. Abad-Acebedo, P.A. Saiz
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S584
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Introduction
Suicidal behaviour and cognition: A systematic review with special focus on prefrontal deficits Introduction: Suicide is a major health concern worldwide, thus, identifying risk factors would enable a more comprehensive understanding and prevention of this behaviour. Neuropsychological alterations could lead to difficulties in interpreting and managing life events resulting in a higher risk of suicide.
ObjectivesObjective: Bibliographic review about the influence of neuropsychological deficits on suicidal behaviour.
MethodsMethod: A systematic literature search from 2000 to 2020 was performed in Medline (Pubmed), Web of Science, SciELO Citation Index, PsycInfo, PsycArticles and Cochrane Library databases regarding studies comparing cognition of attempters versus non-attempters that share same psychiatric diagnosis. Results: 1.885 patients diagnosed with an Affective Disorder (n = 1512) and Schizophrenia/ Schizoaffective Disorder (n = 373) were included.
ResultsIn general comparison, attention was found to be clearly dysfunctional. Regarding diagnosis, patients with Schizophrenia and previous history of suicidal behaviour showed a poorer performance in executive function. Patients with current symptoms of an Affective Disorder and a previous history of suicidal attempt had poorer performance in attention and executive function. Similarly, euthymic affective patients with history of suicidal behaviour had worse decision-making, attention and executive function performance compared to euthymic non-attempters.
ConclusionsPatients who have attempted suicide have a poorer neuropsychological functioning than non-attempters with a similar psychiatric disorder in attention and executive function. These alterations increase vulnerability for suicide.
Conflict of interestJessica Fernández-Sevillano is beneficiary of the Pre-PhD Training Programme of the Basque Government. Dr. Gonzalez-Pinto has received grants and served as consultant, advisor or CME speaker for the following entities: Almirall, AstraZeneca, Bristol-Myers
Tobacco Use and Clinical Symptoms in a Sample of Outpatients Diagnosed with Schizophrenia
- P.A. Sáiz Martinez, S. Fernández-Artamendi, S. Al-Halabí, E. Díaz-Mesa, L. García-Álvarez, E. Martínez, L. Nogueiras, M. Pouso, R. Ramos, T. Rodríguez, G. Díaz-Flórez, M. Arrojo, P. García-Portilla, J. Bobes
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- European Psychiatry / Volume 30 / Issue S1 / March 2015
- Published online by Cambridge University Press:
- 15 April 2020, p. 1
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Introduction
The self-medication hypothesis suggests that patients diagnosed with schizophrenia might smoke as an attempt to self-medicate theirsymptoms. As a consequence, smoking cessation could worsen their clinical status.
ObjectivesTo assess the clinical changes associated with tobacco cessation in a sample of smoking outpatients with schizophrenia.
MethodsSample: 63 smoking outpatients with DSM-IV Schizophrenia from three Mental Health Centers located in Northern Spain [77.0% males; mean age (SD) = 43.90 (8.72); average daily cigarette use (SD) = 27.99 (12.55)]. Instruments: (1) Clinical symptoms: Positive and Negative Symptoms Scale (PANSS), Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI). (2) Pattern of tobacco use: n° cigarettes/day; Expired carbon monoxide (CO ppm). Design: A quasi-experimental design with two groups was implemented: control group (GC − 18 patients not willing to stop smoking), and treatment group [TG − 45 patients in smoking cessation supported by nicotine patches or vareniclina (12 weeks)]. Patients were evaluated at baseline and at week 11 (end of program). Paired sample t-test was used to detect changes in clinical symptoms from baseline to follow-up.
Results23.1% stopped smoking (from TG). No significant differences were found between baseline and follow-up scores (p>.05) among smokers and abstinent in PANSS subscales, HDRS and CGI.
ConclusionsTobacco cessation did not have a significant effect on the clinical symptoms of this group of patients. Further studies should analyze the stability of these outcomes at longer follow-ups to confirm our results.
Childhood trauma in suicide attempters: Case-control study
- L. Jimenez-Trevino, L. Gonzalez-Blanco, M.P. Garcia-Portilla, H. Blasco Fontecilla, J. Lopez Castroman, P. Courtet, V. Carli, M. Sarchiapone, E. Baca-Garcia, P. Saiz Martinez, J. Bobes Garcia
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- European Psychiatry / Volume 33 / Issue S1 / March 2016
- Published online by Cambridge University Press:
- 23 March 2020, p. S111
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Introduction
An expanding body of research suggests that childhood trauma and adverse experiences can lead to a variety of negative health outcomes, including substance abuse, depressive disorders, and attempted suicide among adolescents and adults. Alcoholism, depressed affect, and illicit drug use, which are strongly associated with such experiences, appear to partially mediate this relationship as observed in population studies.
ObjectivesWe have tested the association between early trauma and suicide attempts in a sample of suicide attempters from the Eureca International Project and a matched healthy control sample.
MethodsWe have studied the prevalence of childhood stressful events compared with healthy controls in a multicentre sample of 791 suicide attempters (SA) and 630 healthy controls (C), we have measured childhood parental neglect, physical abuse, sexual abuse, and emotional abuse, using the Childhood Trauma Questionnaire (CTQ). Chi2 tests were performed using SPSS v15.0.
ResultsA significant increase in prevalence of childhood trauma was found in the suicide attempters sample for all types of trauma: childhood physical abuse: 25.3% (SA) vs. 11.1% (C) (Chi2 test: 120,108 P = 0.000); childhood sexual abuse: 18.2% (SA) vs. 2.4% (C) (Chi2 test: 88,212 P = 0.000); parental neglect 25.3% (SA) vs. 1.1% (C) (Chi2 test: 164,910 P = 0.000); childhood emotional abuse: 34.9% (SA) vs. 5.6% (C) (Chi2 test: 176,546 P = 0.000).
Suicide attempters were increasingly overrepresented compared with controls if experiencing more than 1 trauma: represented 77% of the sample who suffered 1 type of childhood trauma vs. more than 90% of the sample with 2 or more types of trauma.
ConclusionsA powerful graded relationship exists between adverse childhood experiences and risk of attempted suicide.
Disclosure of interestThe authors have not supplied their declaration of competing interest.
Neutrophin signalling in first-episode psychosis: relationship with treatment response 1 year after the illness onset
- M. Martinez-cengotitabengoa, K. Macdowell, S. Alberich, M. Parellada, P. Saiz, R. Rodriguez, E. Berrocoso, M. Bernardo, A. Gonzalez-pinto, J.C. Leza
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- Journal:
- European Psychiatry / Volume 33 / Issue S1 / March 2016
- Published online by Cambridge University Press:
- 23 March 2020, p. s258
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Introduction
Pro/antiinflammatory imbalance has been found in first-episode psychotic (FEP) patients, even 12 months later. Current research is every time more focused in the need to find biomarkers to understand the underlying pathophysiological mechanisms of this severe illness.
ObjectivesTo assess peripherical levels of neurotrophins and their receptors and their correlation with inflammation, clinical symptomatology and response to antipsychotic treatment, over the time.
MethodologyNinety-four FEP patients and 80 matched healthy controls were included. Blood samples were taken at baseline to measure BDNF and NGF and their receptor levels (TrkB-full, TrkB-truncated and TrkA) and pro/antiinflammatory parameters (NFkB, COX-2, iNOS, PPARgamma, 15d-PG12). Patients were followed-up during 12 months.
ResultsBDNF TrkB-full receptor and NFG TrkA receptor levels increased during the follow-up whereas BDNF TrkB-truncated form receptor decreased. After adjusting for confounding variables, baseline levels of proinflamatory variables were significantly related to TrkB-full/TrkB-truncated ratio (FL/T), suggesting that a higher proinflammatory status is related to a higher FL/T ratio expression. Furthermore, baseline FL/T ratio could have a predictor role of patient's functionality 1 year after the illness onset, depending on whether patient is treated or not with antipsychotic drugs.
ConclusionInflammatory processes, neurotrophic pathways and functional status of FEP patients seem to be related which is of great traslational relevance. Specific, the expression of the 2 isoforms of BDNF receptor should be taken into account before starting an antipsychotic drug treatment.
Disclosure of interestThe authors have not supplied their declaration of competing interest.
Regulation of inflammatory pathways in schizophrenia: A comparative study with bipolar disorder and healthy controls
- L. García-Álvarez, J.R. Caso, M.P. García-Portilla, L. de la Fuente-Tomás, L. González-Blanco, P. Sáiz Martínez, J.C. Leza, J. Bobes
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- Journal:
- European Psychiatry / Volume 47 / January 2018
- Published online by Cambridge University Press:
- 01 January 2020, pp. 50-59
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Background
Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear.
Main aimTo identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC).
MethodsCross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)].
Statistical analysisANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD.
ResultsPro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040).
ConclusionsThis study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.