Major depression is characterized by multifarious symptoms and symptoms clusters, such as the melancholic and anxiety symptom clusters. There is a strong comorbidity and a biological similarity between major depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).The aim of the present study was to examine "psychosomatic" symptoms reminiscent of ME/CFS in major depression.Toward this end, we examined the 12-item Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale and the Hamilton Depression Rating Scale (HDRS) in 103 major depressed patients by means of multivariate pattern recognition methods. results: Our findings support the existence of two factors, i.e. a fatigue and somatic (F&S) factor, i.e aches and pain, muscular tension, fatigue, concentration difficulties, failing memory, irritability, irritable bowel, headache, and a subjective experience of infection; and a depression factor, i.e. sadness, irritability, sleep disorders, autonomic symptoms, and a subjective experience of infection. Cluster analysis performed on the 12 FF items found two different clusters, which were separated by highly significant differences in the F&S items, the most significant being a subjective experience of infection, aches and pain, muscular tension, fatigue, concentration difficulties and failing memory. Multivariate analyses showed that the differences between both clusters were quantitatively, and not qualitatively, and reflected the severity of the F&S dimension. There was a strong association between the F&S symptoms and melancholia and chronic depression. Treatment resistant depression was characterized by higher scores on the depression factor score. There was a strong correlation between the HDRS score and the FF items, fatigue, a subjective experience of infection, and sadness. Our findings show that F&S symptoms are a major feature of depression and largely predict severity of illness, and chronic and melancholic depression.It is concluded that the diagnostic criteria of depression and melancholia and rating scales to measure severity of illness should be modified to include the F&S symptom profile.
Both corticotropin releasing hormone (CRH) and serotonin (5-HT) participate in the stress response and are known to modulate cytokine release by human immune cells. Extracellular 5-HT concentrations at or above the serum values have negative immunoregulatory effects by inhibiting the production of interferon-gamma (IFNgamma), a pro-inflammatory cytokine produced by Th-1-like lymphocytes, whereas 5-HT has no significant effects on the production of interleukin-10 (IL-10), an anti-inflammatory cytokine. In one study, CRH significantly decreases IFNgamma production by cultured human peripheral blood immunocytes, whereas in other studies CRH increases the production of cytokines, such as IL-1, IL-2 and IL-6. The aims of the present study were to examine i) the effects of CRH, 10-9 M, 10(-8) M and 10(-7) M, on the stimulated production of IFNgamma, IL-10 and tumor necrosis factor-alpha (TNFalpha) by human whole blood; and ii) whether CRH, 10(-9) M, 10(-8) M and 10(-7) M, may antagonize some of the negative immunoregulatory effects of 5-HT, 1.5 microg/mL or 15 microg/mL. We found that CRH, 10(-9) M, 10(-8) M and 10(-7) M, had no significant effects either on the stimulated production of IFNgamma, IL-10 or TNFalpha or on the IFNg/IL-10 production ratio, which reflects the pro-inflammatory capacity of the culture. 5-HT, 1,5 microg/dL and 15 microg/dL, significantly suppressed the production of IFNgamma and TNFalpha and the IFNg/IL-10 production ratio. CRH, 10(-7) M, significantly reversed the 5-HT (1.5 microg/mL and 15 microg/mL)-induced suppression of IFNg production. CRH at all concentrations significantly blocked the 5-HT (1.5 microg/mL and 15 microg/mL)-induced suppression of TNFalpha production. The results suggest that CRH has no significant direct effects on the production of IFNgamma, IL-10 and TNFalpha, but antagonizes the negative immunoregulatory effects of 5-HT on the production of IFNgamma and TNFalpha and on the IFNgamma/IL-10 production ratio.
ABSTRACT Objective Schizophrenia and deficit schizophrenia are accompanied by neurocognitive impairments. The aim of this study was to examine whether a general factor underpins impairments in key Cambridge Neuropsychological Test Automated Battery (CANTAB) probes, verbal fluency (VFT), world list memory (WLM), true recall, and Mini Mental State Examination (MMSE). Methods We recruited 80 patients with schizophrenia and 40 healthy controls. All patients were assessed using CANTAB tests, namely paired-association learning (PAL), rapid visual information (RVP), spatial working memory (SWM), one touch stocking (OTS), intra/extradimensional set shifting (IED), and emotional recognition test (ERT). Results We found that a general factor, which is essentially unidimensional, underlies those CANTAB, VFT, WLM, True Recall, and MMSE scores. This common factor shows excellent psychometric properties and fits a reflective model and, therefore, reflects a general cognitive decline (G-CoDe) comprising deficits in semantic and episodic memory, recall, executive functions, strategy use, rule acquisition, visual sustained attention, attention set-shifting, and emotional recognition. Partial least Square analysis showed that 40.5% of the variance in G-Code is explained by CCL11, IgA to tryptophan catabolites, and increased oxidative toxicity; and that G-CoDe explains 44.8% of the variance in a general factor extracted from psychosis, hostility, excitation, mannerism, negative symptoms, formal thought disorders, and psychomotor retardation; and 40.9% in quality of life scores. The G-CoDe is significantly greater in deficit than in nondeficit schizophrenia. Conclusions A common core shared by a multitude of neurocognitive impairments (G-CoDe) mediates the effects of neurotoxic pathways on the phenome of (deficit) schizophrenia.
To investigate the relationships between the immune apparatus, major depression, and HPA-axis and noradrenergic activity, the authors measured the lymphocyte stimulation responses to the mitogens phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (CON A), post-dexamethasone cortisol (DST) values and 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion in 24-hour urine samples from 48 patients. We found that lymphocyte responses to PHA and PWM in melancholic and psychotic depressives were significantly lower than in minor depressives. The lymphocyte responses to PHA, PWM and CON A showed significantly negative correlations with age, DST results and HRSD score. Responses to PHA were significantly negatively correlated with MHPG excretion. Up to +/- 33% of the variance in the three mitogenic lymphocyte responses could be explained by canonical correlation with age, DST results and MHPG values.
Chronic fatigue syndrome (CFS) is a medically unexplained disorder, characterized by profound fatigue, infectious, rheumatological and neuropsychiatric symptoms. There is, however, some evidence that CFS is accompanied by signs of increased oxidative stress and inflammation in the peripheral blood. This paper examines the role of the inducible enzymes cyclo-oxygenase (COX-2) and inducible NO synthase (iNOS) in the pathophysiology of CFS. Toward this end we examined the production of COX-2 and iNOS by peripheral blood lymphocytes (PBMC) in 18 CFS patients and 18 normal volunteers and examined the relationships between those inflammatory markers and the severity of illness as measured by means of the FibroFatigue scale and the production of the transcription factor nuclear factor kappa beta (NFkappabeta). We found that the production of COX-2 and iNOS was significantly higher in CFS patients than in normal controls. There were significant and positive intercorrelations between COX-2, iNOS and NFkappabeta and between COX-2 and iNOS, on the one hand, and the severity of illness, on the other. The production of COX-2 and iNOS by PBMCs was significantly related to aches and pain, muscular tension, fatigue, concentration difficulties, failing memory, sadness and a subjective experience of infection. The results suggest that a) an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS; b) the inflammatory response in CFS is driven by the transcription factor NFkappabeta; c) symptoms, such as fatigue, pain, cognitive defects and the subjective feeling of infection, indicates the presence of a genuine inflammatory response in CFS patients; and d) CFS patients may be treated with substances that inhibit the production of COX-2 and iNOS.
We have studied the characteristics of insulin therapy and home blood glucose monitoring of 1.200 diabetic patients (590 males, 610 females), mainly type I adults (age: 43 +/- 19 years, mean +/- 1 SD), attending a licensed diabetes center in Belgium which benefits from a National Health Service convention system for providing education and home blood glucose monitoring kits and disposables to diabetic subjects. 50% of these patients were treated with 2 daily insulin injections, while 22% were treated with 3 and 24% with 4 daily injections. 4% of the subjects were treated with a continuous subcutaneous insulin infusion. Patients treated with four daily injections were younger than those treated with other insulin schemes (p < 0.001). Home blood glucose monitoring strip consumption was 2.2 patient-1 day-1. The mean HbA1C level was 8.63 +/- 1.55% [8.54 +/- 1.46 in males and 8.72 +/- 1.62% in females (NS)]. In more than one third of the subjects treated with injections, HbA1C was lower than 8% HbA1C was also below 8% in 50% of patients using 1100-1200 strips year-1.
