osteoprotegerin and Depressive-Disorder--Major

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 min, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels, and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that, in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness.

Topics: Adult; Biomarkers; Bone and Bones; Bone Density; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Ketamine; Male; Middle Aged; Osteopontin; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B

We evaluated if plasma levels of inflammatory markers are persistently altered in severe mental disorders with psychotic symptoms or associated with state characteristics in a longitudinal study.. Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1Ra), von Willebrand factor (VWF), and osteoprotegerin (OPG) were measured in schizophrenia (n = 69) and affective (n = 55) spectrum patients at baseline and at one-year follow-up, and compared to healthy controls (HC) (n = 92) with analysis of covariance. Association between change in symptoms and inflammatory markers was analyzed with mixed-effects models.. sTNF-R1 was higher in the schizophrenia (P < 0.0001) and affective disorders (P = 0.02) compared to HC, while IL-1Ra was higher in schizophrenia (P = 0.01) compared to HC at one year follow-up. There were no significant differences between schizophrenia and affective groups; however, levels in the affective group were in between schizophrenia and HC for sTNF-R1 and IL-1Ra. There were no significant associations between change in symptoms and inflammatory markers.. Persistently increased sTNF-R1 and IL-1Ra after one year in patients with severe mental disorders primarily reflecting data from the schizophrenia group may suggest that inflammation is a trait phenomenon, and not only the result of stress-related mechanisms associated with acute episodes.

Topics: Adolescent; Adult; Bipolar Disorder; Depressive Disorder, Major; Female; Follow-Up Studies; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Osteoprotegerin; Psychotic Disorders; Receptors, Tumor Necrosis Factor, Type I; Schizophrenia; von Willebrand Factor; Young Adult

Inflammation is believed to play a role in the pathogenesis of both cardiovascular disease and depressive disorders. We hypothesized that circulating concentrations of the novel inflammatory and cardiovascular biomarkers osteoprotegerin (OPG) and adiponectin as well as high sensitivity C-reactive protein (hsCRP) are associated with the severity of depressive symptoms and presence of major depressive disorder (MDD).. In a cross-sectional population-derived study (Akershus Sleep Apnea Project) 520 persons underwent clinical examination and venous blood sampling. Medical history was obtained and the participants completed the Beck Depression Inventory (BDI). Structured clinical interviews for axis-I disorders including MDD were performed in a subgroup of 288 participants. OPG and adiponectin concentrations were determined by in-house time-resolved immunofluorometric assays.. Despite significant correlation with hsCRP (r=0.162, p<0.001), the sum-score of BDI did not correlate with OPG or adiponectin levels (r=0.011, p=0.811 and r=0.055, p=0.210, respectively). Neither circulating OPG nor adiponectin differed between persons with (n=34) and without (n=246) MDD (median±interquartile range: 1.18 (0.96-1.49) vs. 1.17 (0.93-1.57) ug/l and 7.26 (5.13-9.91) vs. 7.39 (5.23-11.37) mg/l, respectively).. Causal considerations are not possible, and results in the sub-group of diagnosed participants need careful interpretation due to small sample size.. hsCRP was independently associated with depressive symptoms, but no association between depression severity or presence of MDD and OPG- or adiponectin concentrations was observed in community-residing persons at high risk for obstructive sleep apnea.

Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Depression; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Osteoprotegerin; Psychiatric Status Rating Scales; Risk Assessment; Severity of Illness Index; Sleep Apnea, Obstructive

Major depressive disorder (MDD) has been linked with accelerated bone loss leading to the development of low bone mineral density (BMD). Several mechanisms have been discussed as causative factors, e.g. lifestyle, selective serotonin reuptake inhibitor (SSRI) intake, or the influence of proinflammatory cytokines.. In a cross-sectional study of in-patients with a current episode of MDD, without somatic comorbidities, we determined various parameters of bone metabolism, inflammatory parameters and parameters of depression. BMD was measured by dual x-ray absorptiometry.. Of 50 patients, only one had low BMD in any of the measure sites. Body mass index (BMI) correlated positively with Z-scores. 83.3% of the examined patients had elevated osteoprotegerin (OPG) levels. SSRI intake did not have an effect on BMD. BMD in the femoral neck was significantly lower in smokers. We also found a positive correlation between the level of physical activity and osteocalcin levels.. In our sample, young to middle-aged, somatically healthy, and acutely depressed patients with a history of MDD showed no reduction of BMD. This could be due to compensatory mechanisms, as suggested by elevated OPG levels. Physical activity and high BMI could also have served as protective factors. Still, as patients with MDD often suffer from comorbidities or take medication with a negative effect on bone, this population should be appreciated as a high-risk group for the development of osteopenia and osteoporosis.

Topics: Absorptiometry, Photon; Adult; Body Mass Index; Bone and Bones; Bone Density; Cytokines; Depressive Disorder, Major; Female; Humans; Male; Metabolic Diseases; Middle Aged; Osteoprotegerin; Young Adult

Low bone mineral density (BMD) is a frequent, often persistent complication in patients with major depressive disorder (MDD) and anorexia nervosa (AN) that increases the risk of pathologic fractures. The pathogenetic process underlying osteopenia in MDD and AN is still unclear, although several factors, including a dysbalance of cytokines, are associated with loss of bone mass. Alterations in the serum levels of cytokines have been observed in patients with MDD, AN, and other psychiatric disorders. Therefore, we examined serum levels of cytokines, markers of bone turnover, and BMD in 13 patients with MDD and a lifetime history of AN. Bone turnover markers (osteocalcin and C-terminal degradation products of type I collagen) and tumor necrosis factor alpha (TNF-alpha) in patients were significantly increased compared with those of the control group. Osteoprotegerin (OPG) in patients was significantly decreased. Eight of 13 patients (62%) displayed osteopenia at the lumbar spine. TNF-alpha correlated significantly with C-terminal degradation products of type I collagen, an osteoclastic marker, but significantly negatively with OPG. Our data suggest that TNF-alpha and OPG may play a role in the pathogenetic process underlying osteopenia in these patients.

Topics: Adolescent; Adult; Anorexia Nervosa; Bone Density; Bone Diseases, Metabolic; Cytokines; Depressive Disorder, Major; Female; Glycoproteins; Hormones; Humans; Lumbar Vertebrae; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha