Peter Malik

Tryptophan Metabolism in Post-Withdrawal Alcohol-Dependent Patients

AIMS The aim of the study was to investigate the parameters of tryptophan and phenylalanine metabolism and their associations to immune system activation and to behavioural symptoms during medium-term withdrawal (4-12 weeks of abstinence) in alcohol-dependent patients. METHODS Biochemical assays and clinical assessments at the beginning of treatment (fourth week of alcohol abstinence in average) and prior to the discharge after 8 weeks of treatment. RESULTS Kynurenine to tryptophan ratio (Kyn/Trp) slightly correlated with neopterin levels in early post-withdrawal period (Week 4 of abstinence) but this association disappeared after 12 weeks of abstinence. Phenylalanine and tyrosine concentrations as well as phenylalanine to tyrosine ratio (Phe/Tyr) decreased between Weeks 4 and 12 of abstinence. Kynurenine and Kyn/Trp increased significantly at 12th week of abstinence when compared with the beginning of the study (Week 4 of abstinence). At Week 12, Kyn/Trp significantly correlated with such behavioural symptoms as fatigue, irritability and sleep disturbances. CONCLUSIONS Tryptophan breakdown in early stages may be influenced by the increased activity of indoleamine 2,3-dioxygenase but the increase of Kyn/Trp between Weeks 4 and 12 of abstinence seems to be independent of immune changes and correlates with behavioural symptoms in later stages of the post-withdrawal course. A possible role of kynurenine metabolites in mediation of the increased stress sensibility in post-withdrawal alcohol-dependent patients is discussed.

Bioprofiling of platelets in medicated patients with depression

BACKGROUND Changes in platelet bioactivity and aggregation are of interest when studying patients with depression as this could help to explain the statistically observed association of depression and chronic somatic, especially cardiovascular disease. This link could potentially be mediated through serotonergic signaling or immunological changes. METHODS 38 medicated patients with major depressive disorder (MDD) and 30 mentally healthy controls, both without a diagnosis of cardiovascular disease, were included in this naturalistic study. Demographic and psychometric data were obtained. Platelet aggregability was measured by PFA-100 and bioactive compounds and serotonin levels were quantified in platelet sonicate. RESULTS The comparison of patients with controls revealed no changes in platelet aggregability, but significant differences in platelet content of several bioactive compounds. In a second analysis, patients were grouped according to the receptors and transporters influenced by their medication and again compared to controls. A significant effect of MDD was found for platelet content of serotonin, CD40L, interleukin-1β, and platelet factor-4, independent of medication. These markers can thus be classified as sensitive to MDD. The effect of medication on platelet parameters was also evaluated. Platelet content of matrix metalloproteinase-2 and β-thromboglobulin was normalized in MDD patients by medication acting on the serotonin transporter. LIMITATIONS Owing to the naturalistic study design, patients were on a variety of different medications and combination therapies. This was accounted for by a novel analysis method. CONCLUSION Platelet serotonin levels and content of immunomodulatory compounds are significantly altered in patients with MDD, even if treatment effects are taken into account.

Bone mineral density and bone metabolism in patients with major depressive disorder without somatic comorbidities

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Differential changes in platelet reactivity induced by acute physical compared to persistent mental stress

Platelets are important in hemostasis, but also contain adhesion molecules, pro-inflammatory and immune-modulatory compounds, as well as most of the serotonin outside the central nervous system. Dysbalance in the serotonin pathways is involved in the pathogenesis of depressive symptoms. Thus, changes in platelet aggregation and content of bioactive compounds are of interest when investigating physiological stress-related mental processes as well as stress-related psychiatric diseases such as depression. In the present study, a characterization of platelet reactivity in acute physical and persistent mental stress was performed (aggregation, serotonin and serotonin 2A-receptor, P-selectin, CD40 ligand, matrix metalloproteinase-2 and -9 (MMP-2 and -9), platelet/endothelial adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), β-thromboglobulin (β-TG) and platelet factor 4 (PF-4). Acute physical stress increased platelet aggregability while leaving platelet content of bioactive compounds unchanged. Persistent mental stress led to changes in platelet content of bioactive compounds and serotonin 2A-receptor only. The values of most bioactive compounds correlated with each other. Acute physical and persistent mental stress influences platelets through distinct pathways, leading to differential changes in aggregability and content of bioactive compounds.