In this study, we explored to what extent brain abnormalities can be identified in specific brain structures of patients suffering from late onset depression. We examined the structural difference in regional gray and white matter volume between 14 community-dwelling patients suffering from geriatric depression and 20 age-matched non-depressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging. All subjects also underwent an extensive neuropsychological assessment. Compared with control subjects, patients with depression were impaired in measures of verbal and visual memory, construction, executive ability, and information-processing speed. VBM of gray matter revealed a significant decrease of volume in the right rostral hippocampus, in the right amygdala and in the medial orbito-frontal cortex (gyrus rectus) bilaterally. In the correlation analysis of gray matter volume with the score of the geriatric depression scale, we observed a negative correlation with the medial orbito-frontal cortex (gyrus rectus) bilaterally. There were no differences in white matter volumes between patients with depression and healthy control subjects. The most important limitation of this study was sample size. A larger sample size may have improved detection of changes not reaching significance. Furthermore, our results may not be generalizable across depression severity or to hospitalized patients. The findings are consistent with our hypothesis that depression in the elderly is associated with local gray matter dysfunction.

BACKGROUND Risperidone and olanzapine are second-generation antipsychotics that are increasingly used in child and adolescent psychiatry. So far, little is known about plasma concentrations and concentration-to-dose (C/D) ratios of these agents in children and adolescents compared to adults. METHOD This study investigated whether age and gender influence risperidone and olanzapine plasma concentration by determining risperidone and olanzapine plasma levels by tandem mass spectrometry in 162 Caucasian patients (98 risperidone and 64 olanzapine). RESULTS For risperidone and 9-hydroxyrisperidone, the C(total)/D ratio was almost identical in both age groups (10-18 and 19-45 years, respectively). In the younger age group, females exhibited significantly higher total plasma levels than males while receiving similar doses of risperidone. For olanzapine, in adolescents significantly higher C/D ratios were detected by an average of 43% (after adjustment for weight: 34%) compared to adults. CONCLUSION This study demonstrates an age effect for olanzapine but not for risperidone resulting in higher olanzapine plasma levels in younger patients. For risperidone, we found a gender effect as female adolescent patients had significantly higher risperidone plasma concentrations than male adolescent patients. Future prospective studies are necessary to clarify whether the prescribed dosage should be different in young and older patients.

Cerebrospinal fluid (CSF) biological markers may be of valuable help in the diagnosis of dementia. The aim of the present study was to evaluate CSF levels of 13 potential biomarkers in patients with Alzheimer's disease (AD), frontotemporal lobe dementia, alcohol dementia, major depression and control patients without any neuropsychiatric disease. The study was performed using beta-amyloid 1-42 (Abeta42), total tau and phosphorylated tau-181 (P-tau181) as core markers. The ratio P-tau181/Abeta42 could significantly distinguish AD patients from all other diagnostic subgroups. CSF levels of 5 growth factors (HGF, GDNF, VEGF, BDNF, FGF-2) and 3 cytokines/chemokines (TNF-alpha, TGF-beta1, MIP-1alpha) did not significantly differentiate between the studied groups. However, depending on the degree of neurodegeneration (as expressed by the ratio P-tau181/Abeta42), patients with AD displayed significantly increased CSF levels of nerve growth factor (NGF) as compared to healthy controls. CSF levels of monocyte chemoattractant protein 1 (MCP-1) were found to be significantly increased with age in all groups but did not distinguish AD patients from healthy controls. The results confirmed the suitability of the ratio P-tau181/Abeta42 for the diagnosis of AD, while CSF levels of NGF and MCP-1 are less specific and reliable for AD. It is suggested that the increase in NGF depends on the extent of neurodegeneration of the AD type and the increase in MCP-1 on age.