Dentate gyrus-cornu ammonis (CA) 4 volume is decreased and associated with depressive episodes and lipid peroxidation in bipolar II disorder: Longitudinal and cross-sectional analyses.

OBJECTIVES: Reduced dentate gyrus volume and increased oxidative stress have emerged as potential pathophysiological mechanisms in bipolar disorder. However, the relationship between dentate gyrus volume and peripheral oxidative stress markers remains unknown. Here, we examined dentate gyrus-cornu ammonis (CA) 4 volume longitudinally in patients with bipolar II disorder (BD-II) and healthy controls and investigated whether BD-II is associated with elevated peripheral levels of oxidative stress. METHODS: We acquired high-resolution structural 3T-magnetic resonance imaging (MRI) images and quantified hippocampal subfield volumes using an automated segmentation algorithm in individuals with BD-II (n=29) and controls (n=33). The participants were scanned twice, at study inclusion and on average 2.4 years later. In addition, we measured peripheral levels of two lipid peroxidation markers (4-hydroxy-2-nonenal [4-HNE] and lipid hydroperoxides [LPH]). RESULTS: First, we demonstrated that the automated hippocampal subfield segmentation technique employed in this work reliably measured dentate gyrus-CA4 volume. Second, we found a decreased left dentate gyrus-CA4 volume in patients and that a larger number of depressive episodes between T1 and T2 predicted greater volume decline. Finally, we showed that 4-HNE was elevated in BD-II and that 4-HNE was negatively associated with left and right dentate gyrus-CA4 volumes in patients. CONCLUSIONS: These results are consistent with a role for the dentate gyrus in the pathophysiology of bipolar disorder and suggest that depressive episodes and elevated oxidative stress might contribute to hippocampal volume decreases. In addition, these findings provide further support for the hypothesis that peripheral lipid peroxidation markers may reflect brain alterations in bipolar disorders.

Oxidative stress in older patients with bipolar disorder.

OBJECTIVE: Increases in oxidative stress have been consistently reported in younger patients with bipolar disorder (BD) in postmortem brain and blood samples studies. Changes in oxidative stress are also associated with the natural aging process. Thus, the investigation of oxidative stress across the life span of patients with BD is crucial. METHODS: We compared the levels of oxidative damage to proteins and lipids in plasma from 110 euthymic older patients with BD I or II (mean±SD age: 63.9±9.7 years) and 75 older healthy individuals (66.0±9.6 years). To assess protein oxidation, we measured the plasma levels of protein carbonyl (PC) and 3-nitrotyrosine (3-NT) using the ELISA technique. To assess lipid peroxidation, we measured plasma levels of lipid hydroperoxide (LPH) and 4-hydroxynonenal (4-HNE) using spectrophotometric assays. RESULTS: LPH levels were higher in patients than in the comparison healthy individuals, whereas there were no significant differences for PC, 3-NT, and 4-HNE between the two groups. CONCLUSIONS: The increased levels of an early component of the peroxidation chain (LPH) in euthymic older patients with BD support the hypothesis of a persistent effect of reactive species of oxygen in patients with BD into late life.

The Portuguese version of the Personal and Social Performance Scale (PSP): reliability, validity, and relationship with cognitive measures in hospitalized and community schizophrenia patients.

PURPOSE: Deficits in social functioning are a core feature of schizophrenia and are influenced by both symptomatic and neurocognitive variables. In the present study we aimed to determine the reliability and validity of the Portuguese version of the Personal and Social Performance (PSP) scale, and possible correlations with measures of cognitive functioning. METHODS: One-hundred and four community and inpatients with schizophrenia were assessed using measures of social functioning and symptom severity alongside measures of executive function, processing speed, and verbal memory. RESULTS: Convergent validity with the GAF in the four domains of the PSP varied from 0.357 to 0.899. Reliability was found to be satisfactory, with a Cronbach's alpha coefficient of 0.789. Inter-rater reliability in the four domains of the PSP varied from 0.430 to 0.954. Low-functioning patients (PSP < 70) were older, had longer duration of illness, were more symptomatic and had worse cognitive performances, as compared with high-functioning patients (PSP ≥ 70). In a regression model, deficits in social functioning were strongly predicted both by symptomatic and neurocognitive variables; these together accounted for up to 62% of the variance. CONCLUSIONS: The present study supports the reliability and validity of the Portuguese language version of the PSP and further supports the original measure. The co-administration of brief cognitive assessments with measures of functioning may lead to more focused interventions, possibly improving outcomes in this group.

Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease and Depression.

Emerging evidence is showing nutrition as a crucial factor in the high prevalence and incidence of neurodegenerative mental disorders. Preventive interventions on neuroinflammation seem to be able to interfere with neurodegeneration. Supplementation of essential nutrients, such as long-chain-polyunsaturated fatty acids, vitamin E and mineral elements, may minimize inflammation, enhancing antioxidative defense, and lowering the risk and incidence of age-related diseases, such as cardiovascular diseases and neurodegenerative diseases. This manuscript reviews the current evidence on the role of neuroinflammation in the pathophysiology of neurodegenerative and mental disorders, and preventive strategies for food supplementation in these neuropsychiatric diseases. Dietary supplementation-based strategies have been demonstrated to be effective in subjects with mild cognitive impairment, while weaker results have been obtained in patients with advance neurodegenerative disease. Adjunctive supplementation has also been demonstrated to improve depression, this being of marked benefit considering the comorbidity between cognitive impairment/dementia and depression. Further research is needed to improve the prescriptive precision of supplementation in patients, and to better understand potential interactions with clinical and pharmacokinetic factors.

Current Therapeutic Approaches for Targeting Inflammation in Depression and Cardiovascular Disease.

BACKGROUND: Cardiovascular disease (CVD) and depression are extremely prevalent and debilitating conditions. Evidence suggest that there is a two-way relationship between depression and CVD. Inflammation is implicated in the pathophysiology of both conditions, thus representing a central candidate mediating the link between these disorders. Depression is consistently associated with increased inflammation and increased blood levels of inflammatory molecules. In recent years, studies have shown that depression significantly increases the risk of developing inflammatory-related diseases such as CVD, precipitated by the same inflammatory pathways involved in the pathophysiology of CVD. OBJECTIVE AND METHOD: The aim of this work is to discuss the role of inflammation in depression and CVD and review the evidence of the benefits and side effects of anti-inflammatory drugs in both the diseases. RESULTS: Drugs with anti-inflammatory properties have shown benefit in alleviating signs and symptoms in CVD and in depression. This was shown to be particularly true for the following classes of drugs: non-steroidal antiinflammatory drugs (NSAIDS), polyunsaturated fatty acids (PUFAs) statins and cytokine inhibitors. Finally, antidepressant drugs initially used exclusively to treat depression also lead to improvement in CVD indicators, while lowering inflammation markers in patients at the same time. This evidence further strengthens the suggestion of the biological link between depression and CVD through inflammation. CONCLUSION: Strategies that can mitigate this risk profile are highly needed in the clinical setting, and these particular groups of drugs have the possibility of becoming increasingly important in treatment strategies aiming to improve both the conditions.

NT-proBNP is a potential mediator between reduced ejection fraction and depression in patients with heart failure.

Depression and anxiety are prevalent in patients with heart failure (HF). Reduced ejection fraction (EF) and increased N-terminal-prohormone B-type natriuretic peptide (NT-proBNP) have been shown to be independently associated with depressive symptoms and may therefore increase HF disease progression and mortality. This study evaluated whether NT-proBNP mediated the impact of reduced EF on depressive and anxiety symptoms in patients with HF. Participants (n = 124) were patients with a diagnosis of chronic HF enrolled in the Heart Failure Disease Management Program at Health Sciences North. Subjects were assessed for depressive and anxiety symptoms according to the Hospital Anxiety and Depression Scale questionnaire at enrolment. Ejection fraction, measured through Multigated Acquisition Technique and NT-proBNP, measured through chemiluminescent immunoassay, were obtained at baseline. Patient outcomes were monitored for 12-months after enrollment. Associations were determined using regression and multivariate models. Indirect effects were assessed using mediation analysis. EF and NT-proBNP were highly correlated. Mediation analysis showed no significant direct effect of EF on the levels of depressive and anxiety symptoms, however, there was a significant indirect effect of EF on depression that was mediated by the levels of NT-proBNP, but not for EF and anxiety. Our results suggest that NT-proBNP is a potential mechanism linking reduced EF and depressive symptoms in patients with HF. While results are still preliminary, this study suggests that NT-proBNP may be a potential biomarker in identifying HF patients with reduced EF at high risk for depression, disease progression and mortality.

[Psychopharmacology in medical illness: cardiology, nephrology, hepatology]. / Psicofármacos na doença médica: cardiologia, nefrologia, hepatología.

The high prevalence of psychiatric disturbances in the context of medical illness and its association with worse prognostic of the last one, are the reasons for which it becomes essential that the doctor, not psychiatrist, has the skills in the use of psychopharmaceuticals. A systematic review of the literature published until January of 2006 was done, through MEDLINE, using as key-words psychiatric illness, renal illness, hepatic illness, cardiovascular illness, psychopharmacology. The reviewed studies include original articles, reviews and observational studies. 39 articles were selected for its adequacy and acquired for the accomplishment of this revision. The authors intend to review the use of the several classes of psychopharmaceuticals, its risks and benefits, according to the different medical illnesses. The first part of this article will have is focus in the area of cardiology, nephrology and hepatology.