Cerebrospinal fluid cytokines in geriatric patients with depressive disorders: A retrospective case-control study.

Central nervous system inflammation might play a role in patients with depressive disorders. This hypothesis is supported by studies reporting increased cerebrospinal fluid levels of the inflammatory markers interleukin (IL)-6, IL-8 and tumor necrosis factor alpha (TNF-α) in patients with ongoing depression. In this case-control study, we aimed to examine whether these findings also applied to depressed patients in a geriatric population. Cerebrospinal fluid cytokine analyses were performed on 15 patients (age >60 years) with depressive disorders and 45 age- and sex matched controls (patients with headache or idiopathic facial palsy). IL-6, IL-8, IL-10, TNF-α, monocyte chemoattractant protein-1 and transforming growth factor beta 1 were included in the statistical analyses. Patients with depression had significantly lower cerebrospinal fluid levels of IL-6 as compared to controls (p = 0.014) in the univariate analysis. The finding was, however, no longer statistically significant after correction for age and body mass index (p = 0.097). Overall, this study indicates that the cytokines included in this study are not significantly altered in geriatric patients with depression. Future studies exploring cerebrospinal fluid cytokine levels should include corrections for possible confounding factors.

High-sensitivity C-reactive protein is related to age and gender in an acute psychiatric inpatient population.

Increased levels of high-sensitivity C-reactive protein (hsCRP) is associated with several psychiatric disorders. Demographic factors such as age and gender might affect this association, but the results are conflicting. The aim of this study was to explore a relationship between age, gender and hsCRP in an acute psychiatric inpatient population. We included 484 patients admitted to an acute psychiatric ward. Based on age distribution percentiles (25%, 50% and 75 %), we categorized patients into three age groups; ≦31 years old, 31-47 years old and ≧ 48 years old. Differences in serum levels of hsCRP between the age groups were assessed in the total sample, within males and females, and within diagnostic groups. There were significant differences in hsCRP across age groups. The effect was stronger in males than females. The significant differences between age groups were kept among patients with substance use disorders and bipolar disorders, but not among schizophrenia spectrum disorders, unipolar depression, neurotic disorders and personality disorders. Our findings suggest that the previously known association between age and hsCRP is present within an acute psychiatric population. However, this association was not found for all psychiatric diagnoses.

The association between cytokines and psychomotor speed in a spectrum of psychotic disorders: A longitudinal study.

BACKGROUND: In schizophrenia, impaired psychomotor speed is a common symptom predicting worse functional outcome. Inflammation causes changes in white matter integrity, which may lead to reduced psychomotor speed. Therefore, we wanted to investigate if peripheral inflammation assessed with cytokines affected performance on psychomotor speed in patients with a spectrum of psychotic disorders. METHODS: The current study is a prospective cohort study, including participants from a pragmatic, randomised controlled trial comparing three atypical antipsychotics in patients with a spectrum of psychotic disorders. For the purposes of this sub-study, we analysed drug treatment groups collectively. Psychomotor speed was assessed at baseline, and at weeks 6, 12, 26 and 52 of follow-up, using the neuropsychological tests trail making test (TMT) A and B, and symbol coding. Serum concentration of the following cytokines were measured: interleukin (IL)-ß, IL-2, IL-4, IL-6, IL-10, IL12 p70, IL-17a, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Blood samples were collected at baseline and after 1, 3, 6, 12, 26, 39 and 52 weeks. We analysed the effect of cytokines levels on psychomotor speed over time in linear mixed effects models. RESULTS: In our linear mixed effects models controlling for possible confounders, IFN-γ had a significant negative effect on TMT-A and symbol coding performance. None of the other tests for psychomotor speed were significantly associated with cytokines. Overall psychomotor speed performance increased significantly across the study period while cytokine levels remained stable. CONCLUSION: Our study indicates a negative association between IFN-γ and psychomotor speed, which might be of importance when understanding the mechanisms behind psychomotor deviations in psychotic disorders.

Cytokines in agitated and non-agitated patients admitted to an acute psychiatric department: A cross-sectional study.

BACKGROUND: Different psychiatric diagnostic groups have been reported to have cytokine levels deviating from healthy controls. In acute clinical settings however, the specific challenging symptoms and signs are more important than a diagnostic group. Thus, exploration of cytokines and immune activity and their role in specific symptoms is important. Reports in this field so far are sparse. OBJECTIVE: In the present study, we aimed to examine the association between immune activity measured as levels of cytokines and agitation (independent of diagnostic group) in patients admitted to an acute psychiatric inpatient department. METHODS: A total of 316 patients admitted to an acute psychiatric inpatient department were included. Thirty-nine patients with psychosis were subject to subgroup analyses. Agitation was assessed by the Positive and Negative Syndrome Scale, Excitement Component (PANSS-EC). Based on PANNS-EC patients were stratified into two groups: 67 agitated patients and 249 non-agitated patients. Serum concentrations of the following immune markers were measured: interleukin (IL) -1ß, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (IFN) -γ and transforming growth factor (TGF) -ß. RESULTS: Serum levels of TNF-α were significantly higher in patients with agitation compared to those without, both when all patients were included in the analyses (p = 0.004) and in the psychosis group (p = 0.027). After correcting for multiple testing, only the findings in the total population remained significant. CONCLUSIONS: Our findings suggest an association between TNF-α and agitation in an acute psychiatric population. A similar trend was reproduced to the psychosis subgroup. This suggests that agitation might be an independent entity associated with cytokines across different diagnostic groups.

Biomarkers of Autoimmunity in Acute Psychiatric Disorders.

OBJECTIVE: Previous studies have suggested that autoantibodies associated with systemic autoimmune disorders are more prevalent in patients with psychotic and affective disorders compared with healthy control subjects. However, most positive studies addressing this issue have been limited by small sample sizes and lack of correction for confounding factors. The authors aimed to assess the prevalence of several autoantibodies in patients admitted to acute psychiatric inpatient care and investigate whether patients with psychotic and affective disorders have an increased prevalence of autoantibodies compared with psychiatric patients admitted for other reasons. METHODS: Five hundred eighty-five patients were screened for the presence of antinuclear antibodies (ANA), anticardiolipin and antibeta2-glycoprotein, antithyroid peroxidase (anti-TPO), antitissue transglutaminase IgA, antigliadin deamidated peptide IgG, and rheumatoid factor IgM (RF). Differences in prevalence between patients with nonaffective psychoses (N=105), bipolar disorders (N=78), unipolar depressive disorders (N=146), and other reasons for admission (N=256) were assessed using chi-square tests and logistic regression models. RESULTS: One or more autoantibodies were present in 26.2% of the patients, including ANA (9.4%), RF (9.2%), and anti-TPO (5.6%). Autoantibody prevalence increased with age (odds ratio=1.21, 95% CI=1.09-1.35) and smoking status (odds ratio=1.99, 95% CI=1.04-3.82) but was not associated with a diagnosis of a psychotic or affective disorder. CONCLUSIONS: Autoimmune autoantibodies seem to be equally prevalent in patients with acute psychiatric conditions with and without psychotic and affective disorders. This result challenges the idea that these autoantibodies have specificity for certain psychiatric disorders.

Cytokines in Relation to Motor Activity in an Acute Psychiatric Population.

Background: Deviations in motor activity are important clinical features of several psychiatric disorders in an acute state. Immune activity is associated with several psychiatric disorders and may affect motor activity. We aimed to examine the association between immune activity measured as serum levels of cytokines and deviations in motor activity, in an acute psychiatric setting. Methods: Data on motor activity and immune markers were available on 277 patients admitted to an acute psychiatric inpatient department. The degree of increased or decreased motor activity was clinically assessed at admission. Serum concentrations of the following immune markers were measured: interleukin (IL) -1ß, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (IFN) -γ, and transforming growth factor (TGF) -ß. Results: Scores of increased motor activity were negatively correlated with IFN-γ (rho = -0.128, p = 0.033) in an acute psychiatric population. There was also a trend towards an association between motor activity and TGF-ß (rho = 0.118, p = 0.050). In a multiple-linear-regression model correcting for age, gender, and body-mass index (BMI, kg/m2), the association did not remain significant. No significant correlations between motor retardation and circulating cytokines were found. Conclusions: After adjustment for potential confounders our study did not reveal any significant association between cytokines and motor activity. However, there is an indication of increased Th17 and decreased Th1 responses in relation to increased motor activity in line with the few previous reports in the field. The phenomenon however needs further exploration.

Association of psychosis, affective disorders and diseases affecting the immune system.

Purpose of the article: There are indications of altered immune activity in depressed and psychotic patients compared to healthy controls in several studies. To explore the clinical importance of this phenomenon we examined the relation between different disorders affecting the immune system and psychoses and depression, respectively. MATERIALS AND METHODS: A total of 276 patients consecutively admitted to a psychiatric acute ward were included in the study. Of these 41 patients fulfilled the criteria for ICD-10 F20-29 (psychotic) diagnosis and 157 patients a F30-39 (affective) diagnosis. Information on diseases affecting the immune system in patients themselves and family members of the patients were obtained by a self-report questionnaire. RESULTS: Comparing the two groups showed a significant correlation between the F20-29 group and eczema (r = -0.116, p = .037). Comparing what patients reported for family members showed a significantly higher frequency of epilepsy (p = .033) in the F20-29 group. Summarizing all immunological diseases for family members showed a significantly higher frequency in the F30-39 group compared to the F20-29 group (χ2 = 4, 82, df = 1, p = .028). CONCLUSIONS: There may be differences between the F20-29 and F30-39 groups and their family members regarding risk for diseases affecting the immune system. This is in line with different activity of the immune system measured in blood for the disorders and may add information regarding etiology and pathology of these psychiatric diseases. Further studies including a greater number of subjects, as well as confirmation of the immunological diseases through blood samples are needed.