Recently, there were some reports that major depression is accompanied by significant alterations in the percentage and number of peripheral blood mononuclear cells (PBMCs), such as increased number of CD4+ T cells, B cells (e.g. CD19+, CD21+), number of leukocytes, monocytes and neutrophils and an increased CD4+/CD8+ T-cell ratio. The aims of the present study were to examine the number and percentage of PBMCs in major and treatment-resistant depressed (TRD) patients and the effects of antidepressant treatments on those PBMCs. Major depression was characterized by a significantly higher number of leukocytes and CD4+ T-cells, a higher percentage of CD2+ T cells and CD4+ T cells, and a higher CD4+/CD8+ T-cell ratio than normal controls. Patients with TRD had a significantly higher percentage of CD4+ T cells and CD4+/CD8+ T-cell ratio, and a significantly lower percentage of CD8+ T cells than non-TRD patients and normal controls. There were significant negative correlations between the length of the index episode or duration of illness and number or percentage of monocytes. Subchronic treatment with antidepressants significantly reduced the number of leukocytes and neutrophils, but had no effect either on the absolute number of the other PBMCs or on the CD4+/CD8+ T-cell ratio. The results suggest that (i) the higher CD4+/CD8+ T-cell ratio in major depression is a trait marker of that illness and of treatment resistance; (ii) the increased numbers of leukocytes and neutrophils are state markers of depression and are reduced by 'subchronic' antidepressant therapy; (iii) the number and percentage of monocytes decrease with respect to duration of illness and length of the index depressive episode. © 1997 by John Wiley & Sons, Ltd.
The 35% CO 2 challenge is known to induce symptoms of a panic attack both in panic disorder (PD) patients and healthy volunteers. Although the challenge applies more to PD patients, studies in healthy volunteers provide the opportunity to isolate the physical symptoms from thedisorder and to focus on the direct effect from the challenge on stress responsive systems. One of the main stress responsive systems is the hypothalamic-pituitary-adrenal (HPA) axis. It remains unclear whether panic symptoms are accompanied by HPA axis activation. Differences in design have hampered any comparison between studies. For example, both serum and salivary cortisol have been used to provide an index of HPA axis activation. Furthermore, indications for central HPA axisdisturbance have been suggested. The current study aimed to study the HPA axis response following the induction of panic symptoms in healthy volunteers, both at the pituitary level and at the adrenal level. Furthermore, both serum and salivary cortisol levels were determined. Subjective feelings of anxiety and, correspondingly, cortisol and ACTH levels, were found to be significantly increased following the 35% CO 2 challenge. Cortisol and ACTH responses to CO 2 were also associated. A significant cortisol increase was observed in both serum and salivasamples, although these were more pronounced when considering the free fraction serum values. We conclude that the induction of panic symptoms results in HPA axis activation, both at the pituitary and adrenal level. The question remains as to whether positive responders to the 35% CO 2 inhalation (more specifically PD patients) show a morepronounced HPA axis response.
There is now some evidence that chronic fatigue syndrome (CFS) is accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS is accompanied by an immune response to neoepitopes of a variety of modified lipids and proteins indicating damage caused by oxidative and nitrosative stress. Toward this end we examined serum antibodies to fatty acids (oleic, palmitic and myristic acid), by-products of lipid peroxidation, i.e. azelaic acid and malondialdehyde (MDA), acetylcholine, S-farnesyl-L-cysteine, and N-oxide modified amino-acids in 14 patients with CFS, 14 subjects with partial CFS and 11 normal controls. We found that the prevalences and mean values for the serum IgM levels directed against oleic, palmitic and myristic acid, MDA, azelaic acid, S-farnesyl-L-cysteine, and the N-oxide derivates, nitro-tyrosine, nitro-phenylalanine, nitro-arginine, nitro-tryptophan, and nitro-cysteinyl were significantly greater in CFS patients than in normal controls, whereas patients with partial CFS took up an intermediate position. There were significant and positive correlations between the serum IgM levels directed against fatty acids, MDA and azelaic acid and the above N-oxide-derivates and the severity of illness (as measured by the FibroFatigue scale) and symptoms, such as aches and pain, muscular tension and fatigue. The results show that CFS is characterized by an IgM-related immune response directed against disrupted lipid membrane components, by-products of lipid peroxidation, S-farnesyl-L-cysteine, and NO-modified amino-acids, which are normally not detected by the immune system but due to oxidative and nitrosative damage have become immunogenic.
ABSTRACT To define the mechanism(s) for the decrease of somatomedin concentrations in acute protein malnutrition, we have assessed the relationships between serum immunoreactive somatomedin-C/insulin-like growth factor-I (Sm-C/IGF-I), serum immunoreactive GH and total (MgCl 2 -treated homogenates) as well as free (water-treated homogenates) liver somatogenic (GH) binding sites in growing rats fed a 5% protein diet for 12 or 24 h and given an s.c. injection(s) of rat GH (rGH) or saline. Control rats were fed a 15% protein diet and injected with rGH or saline. After 12 and 24 h of protein restriction, body weight was 6·9 and 8·2% below controls respectively ( P < 0·001), while Sm-C/IGF-I concentrations were reduced by 58 and 66% respectively ( P < 0·001 vs controls). Serum GH concentrations were not affected by the low protein intake. Furthermore, injection(s) of 50–100 μg rGH failed to raise serum Sm-C/IGF-I concentrations in the protein-deficient animals. The number of total and free GH-binding sites was modestly (15–20%) decreased at 12 and 24 h in the protein-restricted rats. Serum Sm-C/IGF-I concentrations correlated weakly with free and total binding sites ( r = 0·48 and 0·38 respectively). Affinity constants of GH-binding sites were not changed by protein restriction. The profound reduction in Sm-C/IGF-I concentrations within a few hours of beginning protein restriction, and the discordance between this reduction and the small decline in somatogenic binding sites, suggests that, in addition to GH receptor loss, a postreceptor defect may participate in the GH resistance occurring in the early stages of protein deficiency. J. Endocr . (1988) 118, 113–120
The mechanisms by which administration of interferon-α induces neuropsychiatric side effects, such as depressive symptoms and changes in cognitive function, are not clear as yet. Direct influence on serotonergic neurotransmission may contribute to these side effects. In addition, the enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan into kynurenine, may play an important role, first, because IDO activation leads to reduced levels of tryptophan, the precursor of serotonin (5-HT), and thus to reduced central 5-HT synthesis. Second, kynurenine metabolites such as 3-hydroxy-kynurenine (3-OH-KYN) and quinolinic acid (QUIN) have toxic effects on brain function. 3-OH-KYN is able to produce oxidative stress by increasing the production of reactive oxygen species (ROS), and QUIN may produce overstimulation of hippocampal N-methyl-d-aspartate (NMDA) receptors, which leads to apoptosis and hippocampal atrophy. Both ROS overproduction and hippocampal atrophy caused by NMDA overstimulation have been associated with depression.
This prospective study was conducted in order (1) to examine which postdexamethasone cortisol value -i.e., 8 a.m., 4 p.m. or peak cortisol – is most suitable as a laboratory test to help confirm the diagnosis of melancholia and (2) to investigate the influence of the dexamethasone levels in the results of the dexamethasone suppression test (DST). To this end we administered the DST to 48 controls and 115 depressed inpatients categorized according to DSM-III. The 8 a.m. and 4 p.m. dexamethasone levels were determined in 100 subjects. We found that an 8 a.m. postdexamethasone cortisol value ≧3.5 µg/dl was of the most significant diagnostic value in order to separate melancholia from normal controls and/or minor depressives. The 8 a.m. and 4 p.m. dexamethasone values did not differ between healthy controls, minor and severely depressed patients. Although cortisol nonsuppressors exhibited significantly lower dexamethasone values, the predictive value of the DST for melancholia was not affected by the large variation in the bioavailability of dexamethasone.
