[show abstract][hide abstract] ABSTRACT: BACKGROUND: Volumetric studies examining brain structure in depression subtypes are limited and inconclusive. The aim of the current study was to compare the volumes of brain regions previously implicated in depression among patients with melancholic major depressive disorder (MDD), patients with psychotic MDD and normal controls. METHODS: Twenty two patients with melancholic MDD, 17 with psychotic MDD and 18 normal controls were included in the study. Hippocampal (HV), amygdala (AV), anterior (ASCV) and posterior (PSCV) subgenual cortex volumes were measured on magnetic resonance volumetric images. RESULTS: There were no volumetric differences between patients with melancholic and psychotic subgroups. We identified larger AVs and smaller left ASCVs in both patient groups compared to controls with medium to large effect sizes. Regression analysis revealed that AVs were predicted by the presence of depression, late depression-onset, insomnia and left hippocampal tail volume in patients, but not in controls. There were no differences in HVs, right ASCVs and PSCVs across the 3 groups. LIMITATIONS: Small sample size, a possible inclusion of paracingulate gyrus in ASCV and PSCV tracings, significant differences in education level and medication status are discussed as limitations. CONCLUSIONS: Diagnostically delineated melancholic and psychotic MDD patients do not differ in medial temporal and cingulate volumes. However, significant volumetric differences were detected between both patient-groups and controls.
Journal of affective disorders 09/2012; · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: We evaluated the cross-sectional relationship of duration and dosage of valproate monotherapy on bone mineral density (BMD) in adult patients with epilepsy.
The BMD at lumbar level (L2-L4) was measured in consecutive adult epileptic patients receiving long-term (> or =2 years) valproate monotherapy by dual energy X-ray absorptiometry (DXA). Blood samples were collected for total serum calcium, phosphorus, magnesium, 25-hydroxyvitamin D(3) and parathormone. Osteopenia and osteoporosis were defined according to the World Health Organization operational BMD definition. Cross-sectional associations were evaluated using Spearman's correlation coefficient.
A total of 41 patients were studied (mean age 32.3+/-8.2 years, 12 men, mean duration of valproate monotherapy 10.6+/-7.4 years). Osteopenia was present in 24% of subjects, while no case of osteoporosis was documented. Duration and dosage of valproate monotherapy did not correlate with BMD. No association was documented between duration or dosage of valproate monotherapy and biochemical parameters.
Duration of valproate monotherapy does not correlate with decreased BMD in adult patients with epilepsy. No case of osteoporosis was identified in patients treated with valproate for a mean period of more than ten years. These findings indicate that bone metabolism may not be affected by valproate monotherapy.
Journal of the neurological sciences 03/2010; 290(1-2):131-4. · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: Depression represents the most frequent psychiatric disorder in nephrology. Cytokines, and especially IL-6, were found to be elevated in depressed patients with normal renal function. The objective of this pilot study was to examine the relationship between depression and cytokines (IL-6, TNF-alpha, and IL-10) in patients with end-stage kidney disease (ESKD).
We studied 44 stable patients with ESKD for 71 +/- 66 months (32 males; 64 +/- 13 years; 27 on hemodialysis and 17 on peritoneal dialysis). The control group included 20 healthy age- and gender-matched individuals (12 males; 60 +/- 12 years). Depression was assessed by the Zung Self-Rating Depression Scale (ZS). Nephelometry for high-sensitivity CRP and ELISA kits for IL-6, IL-10 and TNF-alpha were used.
Compared to controls, patients with ESKD had higher ZS scores (56.8 +/- 16.8 vs. 44 +/- 12.7, p < 0.01), WBC (7,987 +/- 2,347 vs. 6,413 +/- 870/mm(3), p < 0.01), ESR (36.3 +/- 15.8 vs. 9.4 +/- 3.3 mm, p < 0.001), TNF-alpha (52 +/- 18.4 vs. 10.7 +/- 2.8 pg/ml, p < 0.001) and IL-6 (6.3 +/- 4 vs. 1.8 +/- 0.4 pg/ml, p < 0.001). No differences in high-sensitivity CRP and IL-10 were noted between the ESKD and control groups. Serum IL-6 levels were the only parameter positively correlated with the values of the ZS score in ESKD patients (r = 0.34, p < 0.02).
IL-6 may play a role in the pathogenesis of depression in patients with ESKD.
American Journal of Nephrology 02/2010; 31(4):303-8. · 2.62 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective: Alcohol intake is a major cause of liver cirrhosis as well as chronic liver disease, and commonly coexists with mood disorders such as depression and anxiety. The aim of the present study was to investigate the possible correlation between liver dysfunction related to alcohol intake with anxiety and depressive-like symptomatology prior to and after the detoxification period. Methods: One hundred alcohol abusing/dependent subjects (81 males and 19 females) were treated on an inpatient basis according to a standard detoxification protocol and measurements of serum levels of hepatic enzymes (ASAT, ALAT, γGT), and measures of anxiety (HARS), depression (HDRS) and global functioning (GAS) were also obtained at baseline and at weekly intervals over a period of 4 weeks. Results: Increased levels of hepatic enzymes were observed upon admission that were significantly reduced (P<0.001) following completion of the detoxification treatment. In addition, the psychopathological profile was improved at the end of the detoxification period and a significant correlation was obtained between the levels of hepatic enzymes and the global functioning of alcohol-dependent individuals. Conclusion: This observation further supports a relationship between the depressogenic action of alcohol and the disordered liver function observed in alcohol-dependent individuals, with possible implications in the diagnosis and treatment of mood disorders associated to alcohol abuse.
[show abstract][hide abstract] ABSTRACT: There is evidence to support that oxidative stress is increased in Parkinson's disease (PD) and contributes to degeneration of dopaminergic neurons. Uric acid (UA), a natural antioxidant in blood and brain tissue, scavenging superoxide, peroxynitrite and hydroxyl radical, was found reduced in the serum of PD patients. In addition low plasma uric acid (UA) levels have been associated with an increased risk of PD.
The aim of our study was to investigate serum UA levels in PD patients compared with age-matched healthy controls and their possible relationship with several clinical parameters of PD and pharmaceutical treatment.
We measured serum UA levels in 43 PD patients and 47 healthy volunteers, age and sex-matched. UA levels were correlated with disease duration, severity and treatment.
Low UA levels were observed in PD patients compared with controls (p=0.009). Age, Body Mass Index (BMI) and UPDRS III score did not significantly affect serum UA concentrations, whereas gender was found to contribute significantly to UA level (p<0.000). Strong and significant inverse correlations of UA with disease duration (R(s)=-0.397, p=0.009) and daily levodopa dosage (R(p)=-0.498, p=0.026) were observed. These associations were significant for men (R(s)=-0.441, p=0.04 and R(s)=-0.717, p=0.03 respectively), but not for women (R(s)=-0.221, p=0.337 and R(s)=-0.17, p=0.966 respectively).
Our results suggest that there may be increased consumption of UA as a scavenger in PD, possibly heightened by dopaminergic drug treatment. Given the antioxidant properties of UA, manipulation of its concentrations should be investigated for potential therapeutic strategies of the disease.
Clinical neurology and neurosurgery 07/2009; 111(9):724-8. · 1.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Low and not high cholesterol seems to predict high mortality in hemodialysis (HD) patients. The confirmation of this reverse epidemiology as well as its possible interconnection with the increased inflammatory activity observed in this population is being explored in the present study. A group of 136 HD patients was prospectively studied for 2 years, and cardiovascular disease (CVD) as well as all-cause mortality and morbidity were recorded. Baseline lipid profile, inflammatory status, and patients' characteristics were studied as potential survival and hospitalization predictors. During the 24-month follow-up, 21 deaths (52.4% due to CVD) and 38 hospitalizations (55.3% due to CVD) were recorded. In multivariate Cox regression analysis, decreased interleukin-10 (IL-10) and decreased total serum cholesterol (TChol) were the only independent predictors of CVD mortality while C-reactive protein and decreased TChol predicted all-cause mortality. Interleukin-10 at baseline was 11.29 +/- 21.49 vs. 5.51 +/- 4.57 pg/mL (P<0.018) and TChol 167.37 +/- 47.84 vs.122.04 +/- 26.48 mg/dL (P<0.000) in survivors vs. nonsurvivors from CVD, while C-reactive protein at baseline was 9.37 +/- 11.54 vs. 23.15 +/- 18.76 mg/L (P<0.000) and TChol 169.26 +/- 46.42 vs. 133.26 +/- 46.33 mg/dL (P<0.003) in survivors vs. nonsurvivors from any cause of death. Using the same method of statistical analysis, IL-6 and decreased soluble gp130 (sgp130)--an antagonist of IL-6 action--were found to be the only independent prognostic factors for hospitalization due to CVD while decreased soluble gp130 remained the sole predictor of hospitalization due to any cause. In conclusion, reverse epidemiology regarding cholesterol is confirmed in the present study. Furthermore, inflammatory activity also predicts, independently of or in conjunction with low-cholesterol, CVD and all-cause morbidity and mortality in HD patients.
Hemodialysis International 04/2009; 13(2):197-204. · 1.44 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background – Interleukin (IL)-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines. IL-10 is a pleiotropic cytokine produced by both lymphocytes and mononuclear phagocytes including microglia. Recent studies demonstrated the neuroprotective effect of IL-10. There is little information about the involvement of IL-12 or IL-10 in the pathophysiology of Parkinson’s disease (PD).Objectives – The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with PD and to investigate whether IL-10, an immunosuppressive cytokine, may have a neuroprotective effect in the pathogenesis of PD.Patients and methods – We measured using immunoassay serum IL-12 and IL-10 levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects (controls) age and sex matched. IL-12 and IL-10 levels were tested for correlation with sex, age, disease duration, Hoehn and Yahr stage and the UPDRS III score.Results – The PD group presented with significantly increased IL-10 levels when compared with the control group (P = 0.02). The increase observed was not affected by the treatment status. A strong and significant correlation between IL-10 and IL-12 levels was observed in patients with PD (RS = 0.7, P < 0.000001).Conclusions – Our findings suggest that IL-10 may be involved in the pathogenetic mechanisms of PD. The elevation of IL-10 and the significant correlation between IL-10 and IL-12, a proinflammatory cytokine, may suggest that immunological disturbances and neuroprotective mechanisms are involved in patients with PD.
[show abstract][hide abstract] ABSTRACT: Interleukin (IL)-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines. IL-10 is a pleiotropic cytokine produced by both lymphocytes and mononuclear phagocytes including microglia. Recent studies demonstrated the neuroprotective effect of IL-10. There is little information about the involvement of IL-12 or IL-10 in the pathophysiology of Parkinson's disease (PD).
The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with PD and to investigate whether IL-10, an immunosuppressive cytokine, may have a neuroprotective effect in the pathogenesis of PD.
We measured using immunoassay serum IL-12 and IL-10 levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects (controls) age and sex matched. IL-12 and IL-10 levels were tested for correlation with sex, age, disease duration, Hoehn and Yahr stage and the UPDRS III score.
The PD group presented with significantly increased IL-10 levels when compared with the control group (P = 0.02). The increase observed was not affected by the treatment status. A strong and significant correlation between IL-10 and IL-12 levels was observed in patients with PD (R(S) = 0.7, P < 0.000001).
Our findings suggest that IL-10 may be involved in the pathogenetic mechanisms of PD. The elevation of IL-10 and the significant correlation between IL-10 and IL-12, a proinflammatory cytokine, may suggest that immunological disturbances and neuroprotective mechanisms are involved in patients with PD.
[show abstract][hide abstract] ABSTRACT: The aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists.
Plasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI).
Hcy levels were significantly increased in MS patients compared to controls (13.5 +/- 4.7 mumol/l vs 8.5 +/- 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate.
Moderately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding.
Annals of General Psychiatry 10/2008; 7:17. · 1.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Immune activation has been shown to be involved in the pathophysiology of anxiety states and major depression and pregnancy is associated with a characteristic immune activation to sustain the fetus. Despite the possibility of a relation between immune parameters and postpartum mood disturbance, few studies have explored this association. Further, no study to-date has examined CSF.
Fifty-six Greek parturients were recruited and a detailed medical and obstetric history was recorded. All of them completed the Postpartum Blues Questionnaire (on admission and on days 1-4 postpartum) and the Edinburgh Postnatal Depression Scale (at first and sixth week postpartum). At delivery, a blood sample and a CSF sample while puncturing for epidural analgesia were taken from 33 participants; blood samples only were obtained from the rest of the 23 parturients. TNF-a and IL-6 were quantified with an ELISA assay.
A multiple regression analysis of psychometric scores depending on cytokine levels revealed that cytokine levels were positively associated with depressive mood during the first four days postpartum (p=0.035 for CSF IL-6, p=0.025 for CSF TnF-a, p=0.023 for serum TnF-a) and also at sixth week postpartum (p=0.012 for CSF IL-6, p=0.072 for CSF TnF-a). Pregnancy duration had an adverse association to psychometric scores.
It is suggested that immune mechanisms may play a role in the etiopathology of postpartum depressive mood shifts. The role of a "rebound" reaction of the maternal immune system postnatal should be further investigated.
Journal of affective disorders 09/2008; 115(1-2):287-92. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: We tested the hypothesis that mood, clinical manifestations and cognitive impairment of levodopa-treated Parkinson's disease (PD) patients are associated with vitamin B12 and folate deficiency. To this end, we performed this cross-sectional study by measuring serum folate and vitamin B12 blood levels in 111 consecutive PD patients. Levodopa-treated PD patients showed significantly lower serum levels of folate and vitamin B12 than neurological controls, while depressed patients had significantly lower serum folate levels as compared to non-depressed. Cognitively impaired PD patients exhibited significantly lower serum vitamin B12 levels as compared to cognitively non-impaired. In conclusion, lower folate levels were associated with depression, while lower vitamin B12 levels were associated with cognitive impairment. The effects of vitamin supplementation merit further attention and investigation.
Parkinsonism & Related Disorders 06/2008; 14(4):321-5. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits.
Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured.
The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group.
MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.
European Archives of Psychiatry and Clinical Neuroscience 03/2008; 258(4):217-25. · 3.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Interleukin-15 promotes T-cell proliferation, induction of cytolytic effector cells including natural killer (NK) and cytotoxic cells and stimulates B-cell to proliferate and secrete immunoglobulins. RANTES is a C-C beta chemokine with strong chemoattractant activity for T lymphocytes and monocytes.
The objective of our study was to find out whether IL-15 and RANTES are involved in the possible inflammatory reactions of PD.
We measured by immunoassay serum IL-15 and RANTES levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects age and sex-matched. IL-15 and RANTES levels were correlated with sex, age, disease duration. H-Y stage and the UPDRS III score in all the studied groups and were also correlated with treatment status in PD patients.
The PD group presented with significantly increased RANTES levels as compared to the control group (P = 0.0009). No difference was observed as regards IL-15 levels. A strong and significant correlation between RANTES levels and UPDRS III score was observed in PD patients (R(s) = 0.42, P = 0.007). Untreated patients had significantly higher RANTES levels as compared to the controls.
Our findings may suggest a recruitment of activated monocytes, macrophages and T lymphocytes to sites of inflammation in the central nervous system of PD patients.
[show abstract][hide abstract] ABSTRACT: Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells. Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a C-C beta-chemokine with strong chemo-attractant activity for T-lymphocytes and monocytes. We examined serum levels of RANTES in 20 patients with amyotrophic lateral sclerosis (ALS), 14 patients with non-inflammatory neurological disorders (NIND) and 13 control subjects (CTRL) and cerebrospinal fluid (CSF) levels of RANTES in ALS and NIND group patients in order to investigate whether RANTES as index of immune activation is present in ALS patients. Patients with ALS had higher RANTES levels compared with the NIND patients and CTRL subjects (p = 0.005 and p = 0.02, respectively). CSF RANTES levels were also higher compared with the NIND patients (p = 0.007). No correlation of serum and CSF RANTES levels with disease duration was found. These results may suggest an activated microglia induced recruitment of peripheral inflammatory cells to sites of inflammation in ALS patients.
Amyotrophic lateral sclerosis: official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 11/2007; 8(5):283-7. · 2.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver disease. The aim of the present study was to investigate the possible correlation, between liver dysfunction biological markers and vitamin B12, with interleukin-6, in the serum of alcohol-dependent individuals without liver disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males and 10 females) treated on an inpatient basis according to a standard detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT, gamma-GT), as well as the concentration of B12 and IL-6, were determined on admission. A strong positive correlation has been observed between IL-6 and B12, ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The results confirmed that in alcohol-dependent individuals, the median serum concentration of IL-6, before the beginning of the treatment, had a significant positive correlation with the liver dysfunction biological markers and B12. In conclusion, IL-6 might be used as an additional diagnostic marker for the degree of liver dysfunction in alcohol dependent individuals.
[show abstract][hide abstract] ABSTRACT: Serum folate and vitamin B12 levels were measured in 67 consecutive Parkinson's disease patients treated either with levodopa + dopa decarboxylase inhibitor (DDC-i) plus catechol-O-methyltransferase inhibitors (COMT-i) or only with levodopa + DDC-i. The data were compared to 67 age-matched controls. Our findings show that levodopa-treated Parkinson's disease patients have low folate (p < 0.0007) and vitamin B12 levels (p < 0.0003). They also demonstrate that the addition of a COMT-i to levodopa + DDC-i treatment causes lower serum vitamin B12 (p < 0.03) and folate levels (p < 0.005) than levodopa + DDC-i treatment alone. We suggest supplementary treatment with vitamin B12 and folic acid in these situations.
European Neurology 01/2007; 58(2):96-9. · 1.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Telomerase preserves telomeres' function and structure preventing cellular senescence. Its activity is reduced in peripheral blood mononuclear cells (PBMC) of haemodialysis (HD) patients. The purpose of this study is to investigate the potential correlation between increased oxidative stress/inflammation and telomerase activity in PBMC of HD patients.
Telomerase activity was measured by PCR-ELISA in PBMC isolated from a group of 42 HD patients and 39 subjects with estimated glomerular filtration rate >or=80 mL/min (control group). Serum oxidized low-density lipoprotein (ox-LDL), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were also measured in both groups by ELISA.
Ox-LDL was negatively correlated to percentage telomerase activity in PBMC (r = -0.506, P = 0.000 in the whole group of 81 HD and normal subjects and r = -0.559, P < 0.001 in HD patients). TNF was also inversely associated with percentage telomerase activity in the whole group studied (r = -0.492, P = 0.000) while IL-10 was not. In stepwise multiple linear regression, taking into consideration the most important characteristics of the HD patients and control group, the only significant predictors for percentage telomerase activity in PBMC were ox-LDL and TNF (beta = -0.421, t = -4.083, P = 0.000 and beta = -0.381, t = -3.691, P = 0.000, respectively) while examining separately HD patients, the predictors for the same parameter were ox-LDL and HD duration (beta = -0.671, t = -4.709, P = 0.000 and beta = -0.349, t = -2.447, P = 0.023, respectively).
Ox-LDL serum level is inversely correlated to telomerase activity in PBMC of HD patients. Our study proposes a new consequence of increased oxidative stress in HD patients: the premature cellular senescence potentially related to atherosclerosis through LDL oxidation.