Depression is associated with increased disease activity and higher disability in a large Italian cohort of patients with rheumatoid arthritis

Abstract Introduction: Depression is a quite common comorbidity in patients with rheumatoid arthritis (RA) and is thought to influence its severity. This study aims to estimate, in a large cohort of Italian patients with RA, the prevalence of depression and to investigate the clinical correlates of depression in terms of disease activity and disability. Methods: This is a cross-sectional study enrolling 490 outpatients with RA (80% female, mean age 59.5). The Hospital Anxiety and Depression Scale (HADS) was used to assess the presence of depression with a cut-off of 11. We collected data about disease activity and disability with DAS28, TJC-68, PhGA, PGA, VAS, DAS28, SDAI, CDAI and HAQ. Results: Prevalence of depression was 14.3% (95% CI: 11-17%). Depressed patients, when compared with not depressed ones, were found to have higher scores for TJC-68 ( p = 0.011), PhGA ( p = 0.001), PGA ( p = 0.001), VAS ( p = 0.001), DAS28 ( p = 0.007), SDAI ( p = 0.001), CDAI ( p = 0.001) and HAQ ( p = 0.001). Out of the 70 depressed patients, 30 subjects, already known to be depressed in the past, were still depressed at the time of the assessment, with only 11 (15.7%) under antidepressants. A multivariate analysis showed that male sex, higher PGA score, use of antidepressants and higher HAQ score were significantly associated with an increased risk of depression. Conclusions: Our study shows that depression is common in RA and may affect its activity mainly via an alteration in the perception of the disease. Although its important implications, depression is still under-diagnosed and its management is inadequate.

Childhood trauma and glucose metabolism in patients with first-episode psychosis.

Although the associations between first-episode psychosis (FEP) and metabolic abnormalities on one side, and childhood trauma (CT) and risk of developing psychosis on the other are both well established, evidence on the relationship between CT and metabolic dysregulation in terms of abnormal glucose metabolism is very limited. We tested whether, already at illness onset, FEP patients with a history of CT show dysregulation of a broad range of glucose metabolism markers. In particular, in 148 FEP patients we evaluated serum concentrations of c-peptide, insulin, plasminogen-activator-inhibitor-1 (PAI-1), resistin, visfatin, glucagon, glucagon-like peptide-1 (GLP-1), gastric-inhibitor-peptide (GIP), leptin, and ghrelin. We also assessed CT with the Childhood Experience of Care and Abuse Questionnaire, and stressful life events (SLEs) with a semi-structured interview. Psychopathology, cannabis and tobacco habits, Body Mass Index (BMI) were recorded. Serum concentrations of markers were analyzed from peripheral blood. Ninety-five patients (56 % males, mean age 29.5) reported CT. Multivariate models showed that CT is associated only with the concentrations of c-peptide and insulin after adjusting for age, sex, BMI and SLEs. FEP patients who had experienced CT showed higher c-peptide and insulin serum concentrations. Our study reports that CT might be associated with the metabolic abnormalities in the first stage of psychosis, suggesting that a thorough anamnestic evaluation at psychosis onset that would include the history of CT could be helpful for clinicians in order to implement early programmes of healthy lifestyle education and to guide choice of therapeutic interventions for trauma.

Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues.

There is an increasing interest in understanding the biological mechanism underpinning fibromyalgia (FM) and chronic fatigue syndrome (CFS). Despite the presence of mixed findings in this area, a few biological systems have been consistently involved, and the increasing number of studies in the field is encouraging. This chapter will focus on inflammatory and oxidative stress pathways and on the neuroendocrine system, which have been more commonly examined. Chronic inflammation, together with raised levels of oxidative stress and mitochondrial dysfunction, has been increasingly associated with the manifestation of symptoms such as pain, fatigue, impaired memory, and depression, which largely characterise at least some patients suffering from CFS and FM. Furthermore, the presence of blunted hypothalamic-pituitary-adrenal axis activity, with reduced cortisol secretion both at baseline and in response to stimulation tests, suggests a role for the hypothalamic-pituitary-adrenal axis and cortisol in the pathogenesis of these syndromes. However, to what extent these systems' abnormalities could be considered as primary or secondary factors causing FM and CFS has yet to be clarified.

No association between NRG1 and ErbB4 genes and psychopathological symptoms of schizophrenia.

Neuregulin 1 (NRG1) and v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ErbB4) have been extensively studied in schizophrenia susceptibility because of their pivotal role in key neurodevelopmental processes. One of the reasons for the inconsistencies in results could be the fact that the phenotype investigated has mostly the diagnosis of schizophrenia per se, which is widely heterogeneous, both clinically and biologically. In the present study we tested, in a large cohort of 461 schizophrenia patients recruited in Scotland, whether several SNPs in NRG1 and/or ErbB4 are associated with schizophrenia symptom dimensions as evaluated by the Positive and Negative Syndrome Scale (PANSS). We then followed up nominally significant results in a second cohort of 439 schizophrenia subjects recruited in Germany. Using linear regression, we observed two different groups of polymorphisms in NRG1 gene: one showing a nominal association with higher scores of the PANSS positive dimension and the other one with higher scores of the PANSS negative dimension. Regarding ErbB4, a small cluster located in the 5' end of the gene was detected, showing nominal association mainly with negative, general and total dimensions of the PANSS. These findings suggest that some regions of NRG1 and ErbB4 are functionally involved in biological processes that underlie some of the phenotypic manifestations of schizophrenia. Because of the lack of significant association after correction for multiple testing, our analyses should be considered as exploratory and hypothesis generating for future studies.