No abstract

Bipolar disorder (BD) has been associated with a proinflammatory state in which TNF-α seems to play a relevant role. The aim of the present study was to evaluate the plasma levels of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in BD patients in mania and euthymia in comparison with control subjects. We evaluated 53 BD patients (34 in mania and 19 in euthymia) and 38 healthy subjects. All subjects were assessed by the Mini-International Neuropsychiatry Interview (MINI-Plus). Patients were also evaluated by the Young Mania Rating Scale (YMRS) and by Hamilton Depression Rating Scale (HDRS). Plasma TNF-α and its soluble receptors were measured by ELISA. The plasma TNF-α and sTNFR2 levels did not differ between groups, but higher sTNFR1 levels were found in BD patients. Of note, BD patients in mania had higher sTNFR1 levels than BD patients in euthymia and controls. The sTNFR1 and sTNFR2 levels correlated with BD duration, and sTNFR2 levels correlated with age of patients. Our data indicate a proinflammatory status in BD patients during mania and further suggest that inflammatory mechanisms may be involved with the physiopathology of BD.

Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the CNS, where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF has become a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have consistently reported altered levels of BDNF in the circulation (i.e., serum or plasma) of patients with major depression, bipolar disorder, Alzheimer's disease, Huntington's disease and Parkinson's disease. Correlations between serum BDNF levels and affective, cognitive and motor symptoms have also been described. BDNF appears to be an unspecific biomarker of neuropsychiatric disorders characterized by neurodegenerative changes.

Coronary heart disease (CHD) and depression are very common and often co-existing disorders. In addition to psychological and social morbidity, depression exacerbates adverse cardiac outcomes in CHD patients. Inflammation has been proposed as one of the mechanisms involved in the association between these two debilitating diseases. Therefore, the present study aimed to evaluate inflammatory responses as well as to investigate the pathophysiological mechanisms underlying the putative inflammatory activation in CHD patients with and without depression, by assessing the function of two important biological factors regulating inflammation, the hypothalamus-pituitary-adrenal (HPA) axis and the glucocorticoid receptor (GR). Eighty-three CHD patients with (n=28) and without (n=55) comorbid depression were recruited from primary care services in South London. Depression status was assessed by means of Clinical Interview Schedule Revised for diagnosis of depression, and Beck Depression Inventory for the presence of depressive symptoms. Serum C-reactive protein (CRP), plasma vascular endothelial growth factor (VEGF), and plasma and salivary cortisol were measured using commercially available ELISA kits. Gene expression of GR and interleukin-6 (IL-6) were conducted via qPCR. GR sensitivity was evaluated in vitro in isolated peripheral blood mononuclear cells using the dexamethasone inhibition of lipopolysaccharide-stimulated IL-6 levels. Serum levels of kynurenine pathway metabolites were measured using high performance liquid chromatography. Our results show that CHD patients with depression had higher levels of CRP, IL-6 gene expression, and VEGF compared with CHD non-depressed, as well as lower plasma and saliva cortisol levels. The CHD depressed group also exhibited a reduction in GR expression and sensitivity. Finally, tryptophan levels were significantly lower in patients with depression, who also showed an increased kynurenine/tryptophan ratio. In conclusion, CHD patients with depression had elevated levels of inflammation in the context of HPA axis hypoactivity, GR resistance, and increased activation of the kynurenine pathway. Reduced cortisol bioavailability and attenuated glucocorticoid responsiveness due to decreased expression and sensitivity of GR may lead to insufficient glucocorticoid signaling and thus elevation of inflammation in these patients.

Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with high prevalence of medical comorbidities and cognitive impairment. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Cytokines are proteins involved in the regulation and the orchestration of the immune response. We performed a review on the involvement of cytokines in BD. We also discuss the cytokines involvement in the neuroprogression of BD. It has been demonstrated that increased expression of cytokines in the central nervous system in postmortem studies is in line with the elevated circulating levels of proinflammatory cytokines in BD patients. The proinflammatory profile and the immune imbalance in BD might be regarded as potential targets to the development of new therapeutic strategies.

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Patients with migraine often report cognitive complaints, especially regarding attention and memory.ObjectiveTo perform a systematic review of the studies available on cognitive evaluation in patients with migraine.MethodsWe evaluated all articles containing the key words: "Migraine", "Cognition" and "Cognitive Impairment."ResultsThe search strategy resulted in 23 articles. Fifteen out of the 23 studies (65.3%) retrieved reported abnormalities on neuropsychological tests in migraine patients, notably tests of memory, attention and information processing speed. Most of the studies showing cognitive changes in migraine were carried out in neurological care facilities. Conversely, among community-based studies, migraine patients were less likely to present cognitive changes.ConclusionPatients with migraine, especially those followed at neurology clinics, show an elevated risk of mild changes in several cognitive domains. Further studies with greater methodological refinement are warranted in order to clearly establish whether this cognitive dysfunction is associated with an underlying migraine pathophysiological process.

Recent evidence has suggested that inflammatory and immune mechanisms may play a role in the pathophysiology of bipolar disorder (BD). Only a few studies have assessed the profile of chemokines, a family of chemotactic cytokines related to the recruitment of leukocytes, in BD. The objective of our study was to evaluate the plasma levels of chemokines in BD patients in different mood states in comparison with healthy controls. Seventy BD type I patients (35 in euthymia and 35 in mania), and 50 healthy controls matched by age, gender, and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of CCL2, CCL3, CCL11, CCL24, CXCL8, and CXCL10 were measured by enzyme-linked immunosorbent assay. BD patients presented higher plasma levels of CCL11 (1.69-fold increase; p < 0.001), CCL24 (1.40-fold increase; p = 0.02), CXCL10 (1.45-fold increase; p < 0.001) and decreased plasma levels of CXCL8 (8.68-fold decrease p < 0.001). Logistic regression stressed the main effect of increased plasma levels of CXCL10 (OR = 1.009, 95 % CI = 1.000-1.018, p = 0.042) and CCL11 (OR = 1.002, 95 % CI = 1.001-1.003, p = 0.003) and decreased plasma levels of CXCL8 (OR = 0.995, 95 % CI = 0.990-0.999, p = 0.013) to BD. This study reinforces the view that BD is associated with an immune dysfunction.