The noradrenergic system is involved in the etiology and progression of Alzheimer’s disease (AD) but its role is still unclear. Dopamine beta-hydroxylase (DBH) as a catecholamine-synthesizing enzyme plays a central role in noradrenaline (NA) synthesis and turnover. Plasma DBH (pDBH) activity shows wide inheritable interindividual variability that is under genetic control. The aim of this study was to determine pDBH activity, DBH (C-970T; rs1611115) and DBH (C1603T; rs6271) gene polymorphisms in 207 patients with AD and in 90 healthy age-matched controls. Plasma DBH activity was lower, particularly in the early stage of AD, compared to values in middle and late stages of the disease, as well as to control values. Two-way ANOVA revealed significant effect of both diagnosis and DBH (C-970T) or DBH (C1603T) genotypes on pDBH activity, but without significant diagnosis×genotype interaction. No association was found between AD and DBH C-970T (OR=1.08, 95% CI 1.13–4.37; p=0.779) and C1603T (OR=0.89; 95% CI 0.36–2.20; p=0.814) genotypes controlled for age, gender, and ApoE4 allele. The decrease in pDBH activity, found in early phase of AD suggests that alterations in DBH activity represent a compensatory mechanism for the loss of noradrenergic neurons, and that treatment with selective NA reuptake inhibitors may be indicated in early stages of AD to compensate for loss of noradrenergic activity in the locus coeruleus.
BackgroundIncreased physical morbidity in patients with schizophrenia (SCH) is well established. However, our knowledge on the role of gender in chronic physical multimorbidities (CPM) remains limited, and the evidence about the effect of CPM on SCH treatment outcome is sparse. The present study explored the gender-dependent differences in the prevalence, and age of onset of CPM between SCH and the general population (GEP), as well as the effect of CPM on hospital readmission in patients with SCH.MethodsThis cross-sectional study was nested within the larger frame of a prospective cohort study conducted at Psychiatric Hospital ‘‘Sveti Ivan’’, Croatia. Data were collected for a consecutive sample of 136 (49 female and 87 male) patients diagnosed with SCH (ICD-10) and 861 (467 female and 394 male) participants from the general population. The primary outcome was the prevalence of CPM. A secondary outcome was the number of psychiatric readmissions since diagnosis.ResultsIn the total sample we observed the significant difference in CPM prevalence between SCH and GEP in the youngest age group, <35 years old (p=0.006). Among the male participants <35 years old, there were no significant differences in the prevalence of CPM between SCH (25%) and GEP (15%) (p=0.216). However, among the female participants <35 years old, the difference was significant and clinically relevant (p=0.002). Prevalence of CPM was 50% in SCH patients, and 14% in GEP. After the adjustment for age, sex, a number of psychiatric comorbidities and duration of SCH, the number of physical illness comorbidities was significantly associated with the number of previous psychiatric hospital readmission. (multivariate, robust regression; B=0.98; β=0.24; p=0.022). Approximately, the number of rehospitalizations increases for one with each chronic physical illness.DiscussionThis study identified gender differences in the prevalence of CPM in SCH patients, and the significant association of CPM with psychiatric hospital readmission. Higher physical morbidity points to a substantial disadvantage of female patients early in the course of illness. Understanding the nature and biological basis of gender-determined differences in risk and outcome of CPM might help to identify new therapeutic targets, allow more individualized treatment, and facilitate better risk prediction and application of healthcare resources.
IntroductionAlzheimer’ disease (AD) is a complex and progressive neurodegenerative disorder with unclear aetiology. Cognitive impairment and the behavioral disturbances in patients with AD might be associated with altered serotonergic system.ObjectivesPlatelet serotonin (5-HT) levels and platelet monoamine oxidase type B (MAO-B) activity might be the biological markers for the progress of AD.AimsTo determine platelet 5-HT concentrations and MAO-B activity in female patients with mild, moderate or severe stage of AD and sex and age matched healthy controls.MethodsThe study included 106 female patients with the diagnosis of probable AD (DSM-IV-TR and NINCDS-ADRDA criteria), subdivided according to the Mini Mental State Examination (MMSE) score in early (MMSE 26-18), middle (MMSE 17-10) and late (MMSE 9-0) phase of AD. Control group consisted of 102 healthy elderly women (MMSE 30-27). Platelet 5-HT concentrations and MAO-B activity were determined using spectrofluorimetric methods.ResultsPlatelet 5-HT concentrations and MAO-B activity were similar between all patients with AD and healthy controls. Patients in the late phase of AD had significantly (p < 0.05) lower platelet 5-HT concentrations and MAO-B activity than patients in other phases of AD and healthy controls. The significant correlations were found between MMSE scores and platelet 5-HT concentrations, MAO-B activity and age.ConclusionThe results suggest that platelet 5-HT concentration and MAO-B activity might be the peripheral biological markers for the severity and/or clinical progress of AD.
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