P.A. Sáiz Martinez

Regulation of inflammatory pathways in schizophrenia: A comparative study with bipolar disorder and healthy controls

BACKGROUND Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear. MAIN AIM To 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). METHODS Cross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)]. STATISTICAL ANALYSIS ANCOVA (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. RESULTS Pro-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). CONCLUSIONS This 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.

Early versus late stage schizophrenia. What markers make the difference

Abstract Objectives: To identify the psychopathological, cognitive, functional, physical health and inflammatory markers that differentiate between early-stage schizophrenia (ESSCH) and late-stage schizophrenia (LSSCH). Methods: Cross-sectional, naturalistic study of 104 patients with SCH. The sample was divided in two groups: 35 ESSCH (≤7 years’ duration of illness) and 69 LSSCH (>10 years’ duration of illness). Statistical analysis: chi-square test and Students t-test and ANCOVA (or Quade test) controlling for age, sex, BMI and number of cigarettes/day. Finally, a binomial logistic regression was made. Results: ESSCH show greater negative symptom severity (t = 2.465, p = 0.015), lower levels of IκBα (F = 7.644, p = 0.007), were more frequently classified as normal weight (40% vs 18.8%, p = 0.032) compared with LSSCH. The binomial logistic regression model included age (B = 0.127, p = 0.001) and IκBα (B = 0.025, p = 0.002) and accounted for 38.9% of the variance (model df =7, chi-square =41.841, p < 0.0001). Conclusions: Age and IκBα are the unique markers that differentiate between ESSCH patients whose duration of illness is less than 7 years and LSSCH patients. These results support the hypothesis of toxicity of episodes and highlight the importance of preventing new episodes.

Tobacco Use and Clinical Symptoms in a Sample of Outpatients Diagnosed with Schizophrenia

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. Objectives To assess the clinical changes associated with tobacco cessation in a sample of smoking outpatients with schizophrenia. Methods Sample: 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. Results 23.1% 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. Conclusions Tobacco 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.