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Objective The objective of this study was to evaluate brain lithium levels using 7Li magnetic resonance spectroscopy after 6 weeks of lithium therapy in bipolar depression to test the hypothesis that brain and plasma lithium are correlated. It was also tested whether responders and remitters have different pharmacokinetics, blood and brain lithium levels (ratio) compared with those presenting suboptimal antidepressant improvement. Method Twenty-three patients with bipolar disorder (I and II) during depressive episodes were included and followed up for 6 weeks at the University of Sao Paulo using flexible dose of lithium (450-900 mg/day). Sixteen patients were drug-naïve. At endpoint, patients underwent a 7Li- MRS scan and brain lithium concentrations were calculated. Results A significant association between central and peripheral lithium levels was found only in remitters ( r = 0.7, P = 0.004) but not in non-remitters ( r = −0.12, P = 0.76). Also, brain lithium (but not plasma) was inversely correlated with age ( r = −0.46, P = 0.025). Plasma lithium did not correlate with any clinical outcome, lithium dosage or adverse effects. Conclusion These findings suggest that non-remitters may not transport lithium properly to the brain, which may underlie treatment resistance to lithium in BD. Future studies with 7Li- MRS integrated with the evaluation of blood-brain barrier transport mechanisms and longitudinal clinical outcomes in BD and aging are warranted. [ABSTRACT FROM AUTHOR]

Phospholipase A2 (PLA2) is a key enzyme in cerebral phospholipid metabolism. Preliminary post-mortem studies have shown that PLA2 activity is decreased in frontal and parietal areas of the AD brain, which is in accordance with recent 31P-Magnetic Resonance Spectroscopy evidence of reduced phospholipid turnover in the pre-frontal cortex of moderately demented AD patients. Such abnormality may also be observed in peripheral cells, and reduced PLA2 activity in platelet membranes of AD patients, and correlates with the severity of dementia. In rat hippocampal slices, PLA2 has been implicated in mechanisms of synaptic plasticity. In adult rats, the stereotaxic injection of PLA2 inhibitors in the CA1 area of hippocampus impaired, in a dose-dependent manner, the formation of short- and long-term memory. Additionally, such inhibition resulted in a reduction of the fluidity of hippocampal membranes. In primary cultures of cortical and hippocampal neurons, the inhibition of PLA2 precluded neurite outgrowth, and the sustained inhibition of the enzyme in mature cultures lead to loss of viability. Taken together, these findings reinforce the involvement of PLA2 enzymes in neurodevelopment and neurodegeneration processes, and further suggest that reduced PLA2 activity, probably reducing membrane phospholipids breakdown, may contribute to the memory impairment in AD. [ABSTRACT FROM AUTHOR]

In neurons, phospholipase A2 (PLA2) plays a central role in the regulation of membrane phospholipid metabolism. We have addressed the pharmacological modulation of PLA2 in primary cultures of rat cortical neurons. Inhibition curves were obtained in 4 day-in-culture neurons treated for 30 minutes with either the dual PLA2 inhibitor methyl arachidonyl fluorophosphonate (MAFP), or the iPLA2 inhibitor bromoenol lactone (BEL). Full inhibition was achieved with 100 and 250 µM of MAFP, or 10 and 20 µM of BEL. Conversely, a dose-dependent activation of PLA2 was obtained with 10–20 µg/ml of melitin. PLA2 inhibition with MAFP or BEL was not acutely toxic for cultured neurons. However, sustained inhibition of the enzyme precluded the development of neurites, and resulted in long-term loss of neuronal viability. We present a model of pharmacological challenge of PLA2 in vitro, which can be further used to address the involvement of the enzyme in neurodevelopment and neurodegeneration models. [ABSTRACT FROM AUTHOR]

Summary. Phospholipase A2 (PLA2) controls the metabolism of phospholipids in cell membranes. In the brain, PLA2 influences the processing of the amyloid precursor protein (APP) and thus the production of the amyloid-beta peptides (Aβ), which are the major components of the senile plaques in Alzheimer’s disease (AD). Reduced PLA2 activity has been reported in brain and in platelets of AD patients. In the present study we investigated PLA2 activity in platelets from 21 AD patients as compared to 17 healthy elderly controls and 11 individuals with mild cognitive impairment (MCI). Subjects were cognitively assessed by the Mini-Mental State Examination (MMSE) and the CAMDEX schedule. Platelet PLA2 activity was determined by radio-enzymatic assay, which mainly detected a calcium-independent form of the enzyme present also in the brain (iPLA2). PLA2 activity was significantly lower in AD than in controls (p < 0.001). Mean PLA2 activity in MCI individuals was between the values of AD patients and controls, with a subgroup showing PLA as low as the lowest AD patients, but the differences from MCI were not significant from AD and control groups. Lower PLA2 activity was significantly correlated with a worse cognitive performance both at the MMSE (p = 0.001) and the cognitive sub-scale of the CAMDEX inventory (p = 0.002). Our data replicate previous findings of reduced platelet PLA2 activity in AD. Both reduced PLA2 activity and the correlation with impaired cognition were also reported in brain tissue of AD patients, suggesting thus that the present determinations in platelets may be related to a reduction in the brain. In the brain the inhibition of PLA2 inhibits the physiological secretion of the APP, a mechanism that increases Aβ formation. Further longitudinal studies should investigate whether those MCI individuals with the lowest PLA2 values in platelets would be at a higher risk to develop AD during a longitudinal follow up. [ABSTRACT FROM AUTHOR]

Brazil has been experiencing a steady increase in the elderly population during the past few years, and as a result old age health-related problems are increasing continuously in number. Psychiatric symptoms are among the most prevalent health problems of the elderly and are an important source of distress for patients and carers, being also associated with significant growth in the costs and demand for the provision of health care services. This study aimed to investigate the prevalence of mental health problems among the elderly attending a regional primary care unit in the city of Sao Paulo, Brazil. A total of 351 patients older than 60 were assessed during a 6-month period with the SRQ-20 (a scale for the detection of minor psychiatric problems), four questions on psychotic symptoms. AMTS (a scale for the assessment of cognitive functioning) and CAGE (a scale for the assessment of alcoholism); demographic variables were also recorded. Subjects' mean age was 71.22 (CI = 70.51-71.92) and 83.5% were female. Thirty-two per cent of subjects were considered 'cases' as they scored more than 7 on the SRQ-20 (26.8% of total), or more than 1 on the CAGE (1.4% of total), or at least 1 on the questions assessing psychotic symptoms (12.2% of total). There was a significant excess of women among those found to suffer from psychiatric problems (90.1% vs 80.4%). Cases were also more likely to be illiterate (23.4% vs 12.1%) and to have a lower income (2.21 vs 4.01 minimum wages). Depressive symptoms and tension were highly prevalent (72.9% of subjects). Somatic complaints and signs of inefficient functioning were also common (50.4% and 45.9% respectively). Only five patients answered affirmatively two or more CAGE questions and 12.2% scored at least 1 on the questions assessing psychotic symptoms. Cognitive deficit, as determined by the AMTS, was observed in 13.4% of the sample and was associated with ageing, being illiterate and having higher total SRQ-20 scores. We suggest, that the organization of health care services should take into account the needs of this population, and should also emphasize professional training for the correct assessment and treatment of the most frequent mental health problems in old age. [ABSTRACT FROM AUTHOR]

Context: Most double-blind studies of efficacy and tolerability of sertraline as compared to tricyclics in the treatment of late-life major depression have used amitriptyline as a standard, leading to the inevitable conclusion that the former drug is better tolerated than the latter, with both being equally efficacious., Objective: To compare the antidepressant efficacy and tolerability of sertraline (50 mg/day) and imipramine (150 mg/day) in the first 6 weeks of the treatment of major depression in the elderly., Design: A randomized double-blind parallel study with 6 weeks of follow-up., Setting: The psychogeriatric clinic at the Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine of the University of São Paulo., Participants: 55 severe and moderately depressed non-demented outpatients aged 60 years or more., Intervention: Patients were assigned to sertraline 50 mg/day or imipramine 150 mg/day., Main Measurements: CAMDEX interview. Psychiatric diagnosis followed the guidelines for "Major Depressive Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental State Examination. Side effects were assessed using the "Safetee-Up" schedule., Results: Both groups had a significant decrease in depressive symptoms according to the MADRS scores after 6 weeks of treatment (P = 0.01). No significant differences between groups were detected regarding treatment outcome (t = 0.4; P = 0.7). Although the dropout rate was greater in the imipramine group, the overall tolerability among patients who completed the 6-week trial was similar in both test groups., Conclusions: Both sertraline and imipramine exhibited good efficacy and an acceptable side-effect profile for elderly depressed patients after 6 weeks of antidepressant treatment.

Laminin (LN) plays a major role in neuronal differentiation, migration and survival. Here, we show that the cellular prion protein (PrPc) is a saturable, specific, high-affinity receptor for LN. The PrPc-LN interaction is involved in the neuritogenesis induced by NGF plus LN in the PC-12 cell line and the binding site resides in a carboxy-terminal decapeptide from the gamma-1 LN chain. Neuritogenesis induced by LN or its gamma-1-derived peptide in primary cultures from rat or either wild type or PrP null mice hippocampal neurons, indicated that PrPc is the main cellular receptor for that particular LN domain. These results point out to the importance of the PrPc-LN interaction for the neuronal plasticity mechanism.

Objective: To determine the frequency and features of psychiatric morbidity in a cross-section of 38 outpatients with neurocysticercosis., Methods: Diagnosis of neurocysticercosis was established by CT scan, MRI and CSF analysis. Psychiatric diagnoses were made by using the Present State Examination and the Schedule for Affective Disorders and Schizophrenia. Lifetime version; cognitive state was assessed by Mini-Mental State Examination and Strub & Black's Mental Status Examination., Results: Depression was the most frequent psychiatric diagnosis (52.6%) as shown by PSE. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression., Conclusions: Depression syndromes are frequent in patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the observed mental changes is yet unclear, though the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the role played by organic factors in the cause of these syndromes. The results of this study are discussed in the light of the data available for other organic psychiatric disorders.