Dopamine genes and migraine

Migraine is a common chronic disorder with an etiology still mostly unknown. Several neurotransmitters such as dopamine and serotonin are considered to be involved in the pathogenesis of the disease and the study of their systems is crucial in the understanding of migraine. Dopaminergic receptors are variously represented in human CNS and periphery. The hypothesis that a hypersensitivity of the dopaminergic system may have a role in migraine is based on clinical and genetic data. Genetic data are represented by association studies using dopaminergic genes as candidate genes which show that the D2 receptor gene appears to be involved in the pathogenesis of migraine

Analysis on in vitro effect of lithium on telomere length in lymphoblastoid cell lines from bipolar disorder patients with different clinical response to long-term lithium treatment

Background It has been suggested that bipolar disorder (BD) is associated with clinical and biological features of accelerated aging. In our previous studies, we showed that long-term lithium treatment was correlated with longer leukocyte telomere length (LTL) in BD patients. A recent study explored the role of TL in BD using patients-derived lymphoblastoid cell lines (LCLs), showing that baseline TL was shorter in BD compared to controls and that lithium in vitro increased TL but only in BD. Here, we used the same cell system (LCLs) to explore if a 7-day treatment protocol with lithium chloride (LiCl) 1 mM was able to highlight differences in TL between BD patients clinically responders (Li-R; n = 15) or non-responders (Li-NR; n = 15) to lithium, and if BD differed from non-psychiatric controls (HC; n = 15). Results There was no difference in TL between BD patients and HC. Moreover, LiCl did not influence TL in the overall sample, and there was no difference between diagnostic or clinical response groups. Likewise, LiCl did not affect TL in neural precursor cells from healthy donors. Conclusions Our findings suggest that a 7-day lithium treatment protocol and the use of LCLs might not represent a suitable approach to deepen our understanding on the role of altered telomere dynamics in BD as previously suggested by studies in vivo

Investigation of Genetic Variants Associated with Tryptophan Metabolite Levels via Serotonin and Kynurenine Pathways in Patients with Bipolar Disorder

The kynurenine pathway (KP) may play a role in the pathophysiology of bipolar disorder (BD). We conducted a genome-wide association study (GWAS) to identify genetic variants associated with the plasma levels of the metabolites of tryptophan (TRP) via the serotonin (5-HT) and kynurenine (KYN) pathways in 44 patients with BD and 45 healthy controls. We assessed whether variants that were differentially associated with metabolite levels based on the diagnostic status improved the prediction accuracy of BD using penalized regression approaches. We identified several genetic variants that were significantly associated with metabolites (5-HT, 5-hydroxytryptophan (5-HTP), TRP, and quinolinic acid (QA) or metabolite ratios (5-HTP/TRP and KYN/TRP) and for which the diagnostic status exerted a significant effect. The inclusion of genetic variants led to increased accuracy in the prediction of the BD diagnostic status. Specifically, we obtained an accuracy of 0.77 using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The predictors retained as informative in this model included body mass index (BMI), the levels of TRP, QA, and 5-HT, the 5-HTP/TRP ratio, and genetic variants associated with the levels of QA (rs6827515, rs715692, rs425094, rs4645874, and rs77048355) and TRP (rs292212) or the 5-HTP/TRP ratio (rs7902231). In conclusion, our study identified statistically significant associations between metabolites of TRP via the 5-HT and KYN pathways and genetic variants at the genome-wide level. The discriminative performance of penalized regression models incorporating clinical, genetic, and metabolic predictors warrants a follow-up analysis of this panel of determinants

Exploring the association between brain-derived neurotrophic factor (BDNF) levels and longitudinal psychopathological and cognitive changes in Sardinian psychotic patients

Background and Hypothesis: Schizophrenia is among the most debilitating mental disorders and has complex pathophysiological underpinnings. There is growing evidence that brain-derived neurotrophic factor (BDNF) can play a role in its pathogenesis. The present study investigated the longitudinal variation of serum BDNF levels in a 24-month observational prospective cohort study of Sardinian psychotic patients and its relationship with psychopathological and cognitive changes. Further, we examined whether genetic variation within the BDNF gene could moderate these relationships. Study design: Every six months 105 patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and social measures. We performed a targeted analysis of four tag single nucleotide polymorphisms (SNPs) within the BDNF gene that were selected and analyzed using Polymerase Chain Reaction (PCR). Longitudinal data were analyzed using mixed-effects linear regression models (MLRM). Study results: We observed a declining longitudinal trajectory of BDNF levels in psychotic patients in general, and in relation to the severity of depressive and negative symptoms. BDNF serum levels also declined in patients scoring lower in cognitive measures such as attention and speed of information processing and verbal fluency. The rs7934165 polymorphism moderated the significant association between verbal fluency and BDNF levels. Conclusions: These findings in patients from real-world settings suggest a plausible role of peripheral BDNF levels as a marker of illness burden in schizophrenia spectrum disorders

Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders

Brain-derived neurotrophic factor (BDNF) is a key modulator of neuroplasticity and has an important role in determining the susceptibility to severe psychiatric disorder with a significant neurodevelopmental component such as major psychoses. Indeed, a potential association between BDNF serum levels and schizophrenia (SCZ) and schizoaffective disorder (SAD) has been tested in diverse studies and a considerable amount of them found reduced BDNF levels in these disorders. Here, we aimed at testing the association of BDNF serum levels with several demographic, clinical, and psychometric measures in 105 patients with SCZ and SAD, assessing the moderating effect of genetic variants within the BDNF gene. We also verified whether peripheral BDNF levels differed between patients with SCZ and SAD. Our findings revealed that BDNF serum levels are significantly lower in patients affected by SCZ and SAD presenting more severe depressive symptomatology. This finding awaits replication in future independent studies and points to BDNF as a possible prognostic indicator in major psychoses

Correlation between \u3b3-globulins and Encephalitozoon cuniculi immunoglobulins in suspected infected rabbits

Abstract Encephalitozoon cuniculi is a parasite that can infect a variety of animals, including immune-compromised humans. Rabbits are prone to encephalitozoonosis but the subclinical course and high serum prevalence make it difficult to diagnose with certainty in live animals. Different approaches have been used to support the presence of an active infection in symptomatic rabbits: antibodies titers, IgM and IgG serum evaluation, electrophoresis, PCR in urine, and cerebrospinal fluid analysis. In this study, 76 symptomatic rabbits were divided in three groups based on their Ig results: IgM+ IgG+, IgM-IgG+ and IgM-IgG-. By statistical analysis total serum protein was proved not to be effective in predicting an antibody response, in contrast the ?-globulin ranges from serum electrophoresis can predict whether the patient is positive for IgM and/or IgG. In fact, a significant quantitative correlation between percentage of ?-globulins and positive IgM and IgG serum for E. cuniculi was established in symptomatic rabbit. These values can be useful to perform a screening both for symptomatic and asymptomatic rabbits

Association study between the phenotype migraine without aura-panic disorder and dopaminergic receptor genes

Clinical and epidemiological evidence suggests that migraine often co-occurs with psychopathological conditions. Several longitudinal and population-based studies have suggested that migraine and panic disorder might share a common predisposition. An abnormal dopaminergic function has been hypothesized to be involved as etiological factor in panic disorder as well as in migraine. Epidemiological and molecular data suggest the role of genetic factors in the pathogenesis of both migraine and panic attack disorder. We assessed the presence of panic disorder in 100 probands suffering from migraine without aura and the present study was designed to analyse the possible association of the migraine-panic phenotype with dopaminergic genes. In our sample, 17 out of 100 migraineurs were affected by panic disorder and were thus considered for the genetic association study. The allele frequencies of DRD1, DRD3, DRD5, DRD2 in probands did not differ from that of parental non-transmitted chromosomes. This result does not seem to support, in our limited sample, a common pathological basis, with regard to the dopaminergic system, between migraine and panic. Should migraine and panic disorder share some common mechanisms, these could be sought in neuro-chemical systems other than the dopaminergic one

Oxidation of kynuramine by Lentil seedling copper amine oxidase: demonstrtion of a single turnover mechanismin the apoenzyme

Copper amine oxidase was shown to be able to oxidize kynuramine to the corresponding aldehyde, which spontaneously rearranged to 4-hydroxyquinoline. Under anaerobic conditions, the native enzyme oxidized one equivalent of kynuramine and released one equivalent of aldehyde per enzyme subunit. The apoenzyme gave exactly the same 1:1:1 stoichiometry under anaerobic as well as aerobic conditions. These findings demonstrate unequivocally that copper-free amine oxidase can oxidize substrates with a single incomplete turnover

The effect of Leptomastix dactylopii parasitism and venom injection on host Planococcus citri

10One of the major alterations observed in mealybug Planococcus citri parasitized by Leptomastix dactylopii is a strong reduction of laid eggs, which is evident soon after parasitization. Venom injection in unparasitized hosts determines a drastic reduction of fecundity indicating that this female secretion injected at the oviposition plays a key-role in host regulation. In order to assess the impact of parasitism and venom injection on host reproductive tissues, ovaries were dissected at different time intervals after these treatments and observed by light and transmission electron microscopy. The developing eggs showed clear symptoms of degeneration, already half an hour after parasitization or venom injection. Heat and protease treatments of venom nearly suppressed its effects on host reproduction, indicating that proteins are likely responsible for the observed alterations. The electrophoretic profile of venom proteins covers a wide range of molecular masses between 15 to 200 kDa but five major bands having a molecular mass of about 27, 30, 40, 90 and 120 kDa respectively were more evident. Moreover, to establish any parasitoid preference in host selection, among the adult female mealybugs at different stages of maturation and a possible relation with fecundity reduction in the host, the parasitoid behavior was observed.openBattaglia, D.; Colella, T.; Laurino, S.; Grossi, G.; Salvia, R.; Riviello, L.; Grimaldi, A.; Congiu, T.; de Eguileor, M.; Falabella, P.Battaglia, D.; Colella, T.; Laurino, S.; Grossi, G.; Salvia, R.; Riviello, L.; Grimaldi, Annalisa; Congiu, Terenzio; DE EGUILEOR, MAGDA ANNA; Falabella, P