Association Between Medication Adherence and Oxidative Stress in Patients With First-Episode Mania

Poor adherence is a major problem in patients with manic episodes that impairs functionality and has unknown effects on oxidative stress. The objective of this study was to analyze the relationship between adherence to medication, severity of symptoms and oxidative stress in a sample of patients with a first episode of mania. A longitudinal, 6-month study was performed in 60 patients, who were classified as adherent and non-adherent to medication (mainly antipsychotics). Blood levels of oxidative stress parameters and expression of the antioxidant nuclear transcription factor NRF2 in mononuclear cells of peripheral blood were assessed at baseline and at the end of follow-up. In addition, clinical symptoms and functioning were evaluated. Linear multivariate regression was used to determine the relationship between adherence, oxidative stress, and clinical symptoms. Finally, 44 patients completed follow-up. The results of this study showed that at 6-month follow-up, adherence was significantly associated with better functioning and reduced clinical symptoms. Additionally, more severe symptoms were associated with increased levels of oxidative stress and antioxidant parameters. At study completion, non-adherents exhibited greater levels of antioxidants than adherent patients. In conclusion, poor adherence to medication is associated with a poorer prognosis in the medium term and causes increased antioxidant response

Association Between Medication Adherence and Oxidative Stress in Patients With First-Episode Mania

Poor adherence is a major problem in patients with manic episodes that impairs functionality and has unknown effects on oxidative stress. The objective of this study was to analyze the relationship between adherence to medication, severity of symptoms and oxidative stress in a sample of patients with a first episode of mania. A longitudinal, 6-month study was performed in 60 patients, who were classified as adherent and non-adherent to medication (mainly antipsychotics). Blood levels of oxidative stress parameters and expression of the antioxidant nuclear transcription factor NRF2 in mononuclear cells of peripheral blood were assessed at baseline and at the end of follow-up. In addition, clinical symptoms and functioning were evaluated. Linear multivariate regression was used to determine the relationship between adherence, oxidative stress, and clinical symptoms. Finally, 44 patients completed follow-up. The results of this study showed that at 6-month follow-up, adherence was significantly associated with better functioning and reduced clinical symptoms. Additionally, more severe symptoms were associated with increased levels of oxidative stress and antioxidant parameters. At study completion, non-adherents exhibited greater levels of antioxidants than adherent patients. In conclusion, poor adherence to medication is associated with a poorer prognosis in the medium term and causes increased antioxidant response.This study has been funded by Instituto de Salud Carlos III through the projects PI12/02077, PI16/01164, PI14/01900 (Co-funded by European Regional Development Fund/European Social Fund. Investing in your future); the Basque Foundation for Health Innovation and Research (BIOEF); Networking Center for Biomedical Research in Mental Health (CIBERSAM) and the University of the Basque Country (GIC12/84). The psychiatric research department in University Hospital Araba is supported by the Stanley Research Foundation (03-RC-003). SG has a PhD fellowship from the University of the Basque Country

Psychosis and Smoking Cessation: Difficulties in Quitting Associated with Sex and Substance Abuse

No prospective studies of first psychotic episodes have explored sex differences in smoking cessation. The aim of this study was to determine the influence of sex and substance abuse on smoking cessation during an 8-year follow-up of patients after a first psychotic episode. Logistic regression modeling was used to identify factors associated with smoking cessation by sex. To examine for sex variable interactions, the following two methods were used: 1) for other clinical variables, mixed analyses were calculated; and 2) for use of other substances, logistic regression models were performed only in the substance users. At baseline, 79% of men and 84% of women were current smokers. Lower smoking cessation after 8 years was associated with female sex (odds ratio, OR = 0.30; 95% confidence intervals, CIs = 0.12–0.75) and treatment with typical antipsychotics (OR = 0.30, CIs = 0.10–0.93). In a logistic regression model of alcohol users, those who used alcohol continuously were less likely to stop smoking (adjusted OR = 0.22, CI = 0.05–1.0). Among patients who continued using cannabis, female sex was associated with significant lower smoking cessation (adjusted OR = 0.03, CI = 0.001–0.77). Sex may act as a moderator in smoking cessation after a first psychotic episode. Smoking cessation interventions in these patients should consider sex differences and comorbidity with alcohol and cannabis use

Evolution of bdnf full-length/truncated receptor ratio and cognitive/general functioning after a first episode of psychosis

Brain plasticity has demonstrated to play a role in the pathophysiology of schizophrenia. Cognitive deterioration in these patients can be prevented by ensuring the adequate functioning of signaling pathways associated with brain plasticity. As BDNF exerts its action through receptors, in this study, we hypothesized that levels of some BDNF receptors during a first episode of psychosis (FEP) would correlate with the cognitive and global functioning of patients in the long term. We also hypothesized that the improvement of the ratio of full-length (TrKB-FL) and truncated (TrKB-T) TrKB receptors, and the predominance of the full-length isoform would be associated with better cognition and functioning. Peripheral levels of full-length (TrKB-FL) and truncated (TrKB-T) TrKB receptors were assessed in a sample of 97 FEP patients and 97 matched healthy controls. TrKB-FL/TrKB-T ratio(hereinafter, FL/T) was calculated for each patient. Cognitive and global functioning was measured at inclusion and at two years. A high baseline FL/T ratio was found to be related to a better cognitive function (global cognition, verbal memory, working memory and premorbid IQ). Cognitive performance at disease onset and at two years improved when the levels of the ratio were higher than one, with functional BDNF receptor (TrKB-FL) exceeding the value of the truncated isoform (TrKB-T). In addition the increase in the FL/T ratio during the two years of follow-up had positive effects on global functioning. This may be due either to a reduction in TrKB-T or to an increase in TrKB-FL, or both. In conclusion FL / T ratio was related to general functioning and cognition in the long-term

Cannabis use and involuntary admission may mediate long-term adherence in first-episode psychosis patients: a prospective longitudinal study

Background: This study aimed to examine factors associated with treatment adherence in first-episode psychosis (FEP) patients followed up over 8 years, especially involuntary first admission and stopping cannabis use. Methods: This prospective, longitudinal study of FEP patients collected data on symptoms, adherence, functioning,and substance use. Adherence to treatment was the main outcome variable and was categorized as ‘good’ or ‘bad’. Cannabis use during follow-up was stratified as continued use, stopped use, and never used. Bivariate and logistic regression models identified factors significantly associated with adherence and changes in adherence over the 8-year follow-up period. Results: Of the 98 FEP patients analyzed at baseline, 57.1% had involuntary first admission, 74.4% bad adherence,and 52% cannabis use. Good adherence at baseline was associated with Global Assessment of Functioning score (p = 0.019), Hamilton Depression Rating Scale score (p = 0.017) and voluntary admission (p < 0.001). Adherence patterns over 8 years included: 43.4% patients always bad, 26.1% always good, 25% improved from bad to good. Among the improved adherence group, 95.7% had involuntary first admission and 38.9% stopped cannabis use. In the subgroup of patients with bad adherence at baseline, involuntary first admission and quitting cannabis use during follow up were associated with improved adherence. Conclusions: The long-term association between treatment adherence and type of first admission and cannabis use in FEP patients suggest targets for intervention to improve clinical outcomes

The complex association between the antioxidant defense system and clinical status in early psychosis

Oxidative stress is a pathophysiological mechanism potentially involved in psychiatric disorders. The objective of this study was to assess the relationship between total antioxidant status (TAS) and the functional status of patients with a first episode of psychosis at the onset of the disease. For this purpose, a sample of 70 patients aged between 9 and 17 years with a first episode of psychosis were followed up for a period of two years. Blood samples were drawn to measure TAS levels at three time points: at baseline, at one year, and at two years. Clinical symptoms and functioning were also assessed at the same time points using various scales. Linear regression analysis was performed to investigate the relationship between TAS and clinical status at each assessment, adjusting for potential confounding factors. The distribution of clinical variables was grouped in different percentiles to assess the dose-response in the relation between clinical variables and TAS. At baseline, patient's score on Children's Global Assessment Scale (CGAS) was directly and significantly associated with TAS with a monotonic increase in percentiles, and surprising this association was reversed after one and two years of follow-up with a monotonic decrease. In summary at the onset of the illness, TAS is positively related to clinical status, whereas as the illness progresses this correlation is reversed and becomes negative. This may be the result of an adaptive response.This study has been funded by Instituto de Salud Carlos III through the projects PI14/01900, PI16/01164 (Co-funded by European Regional Development Fund/European Social Fund, "Investing in your future"); the Basque Foundation for Health Innovation and Research (BIOEF); Networking Center for Biomedical Research in Mental Health (CIBERSAM) and the University of the Basque Country (GIC12/84). The psychiatric research department in University Hospital Araba is supported by the Stanley Research Foundation (03-RC-003). Sainza Garcia has a PhD fellowship from the University of the Basque Country. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

The complex association between the antioxidant defense system and clinical status in early psychosis

Oxidative stress is a pathophysiological mechanism potentially involved in psychiatric disorders. The objective of this study was to assess the relationship between total antioxidant status (TAS) and the functional status of patients with a first episode of psychosis at the onset of the disease. For this purpose, a sample of 70 patients aged between 9 and 17 years with a first episode of psychosis were followed up for a period of two years. Blood samples were drawn to measure TAS levels at three time points: at baseline, at one year, and at two years. Clinical symptoms and functioning were also assessed at the same time points using various scales. Linear regression analysis was performed to investigate the relationship between TAS and clinical status at each assessment, adjusting for potential confounding factors. The distribution of clinical variables was grouped in different percentiles to assess the dose-response in the relation between clinical variables and TAS. At baseline, patient's score on Children's Global Assessment Scale (CGAS) was directly and significantly associated with TAS with a monotonic increase in percentiles, and surprising this association was reversed after one and two years of follow-up with a monotonic decrease. In summary at the onset of the illness, TAS is positively related to clinical status, whereas as the illness progresses this correlation is reversed and becomes negative. This may be the result of an adaptive response

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

Background:Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Methods: Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. Results: A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Conclusions: Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology

Peripheral Inflammatory Parameters in Late-Life Depression: A Systematic Review

Depressive disorders appear relatively frequently in older patients, and therefore represent an important disease burden worldwide. Given the high levels of inflammatory parameters found in depressed elderly patients, the “inflammaging” hypothesis is gaining strength. In this systematic review, we summarize current evidence regarding the relationship between inflammatory parameters and late-life depression, with a unique focus on longitudinal studies to guarantee temporality. According to the data summarized in this review, the levels of some proinflammatory parameters—especially interleukin (IL)-8, IL-6, and tumor necrosis factor (TNF)-α—could serve as biomarkers for the future development of depressive symptoms in elderly patients. Proinflammatory cytokines seem to be associated with the future development of clinically significant depression, irrespective of baseline scores, thus indicating that inflammation temporally precedes and increases depression risk. As insufficient research has been conducted in this field, further prospective studies are clearly warranted

Neurotrophin signaling in first episode psychosis: relation to response to antipsychotics after 1 year of follow-up

Congress of the European-College-of-Neuropsychopharmacology (ECNP) (29th. 2017. Viena