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Major depressive disorder (MDD) is prevalent with a high subjective and socio-economic burden. Despite the effectiveness of classical treatment methods, 20–30% of patients stay treatment-resistant. Deep Brain Stimulation of the superolateral branch of the medial forebrain bundle is emerging as a clinical treatment. The stimulation region (ventral tegmental area, VTA), supported by experimental data, points to the role of dopaminergic (DA) transmission in disease pathology. This work sets out to develop a workflow that will allow the performance of analyses on midbrain DA-ergic neurons and projections in subjects who have committed suicide. Human midbrains were retrieved during autopsy, formalin-fixed, and scanned in a Bruker MRI scanner (7T). Sections were sliced, stained for tyrosine hydroxylase (TH), digitized, and integrated into the Montreal Neurological Institute (MNI) brain space together with a high-resolution fiber tract atlas. Subnuclei of the VTA region were identified. TH-positive neurons and fibers were semi-quantitatively evaluated. The study established a rigorous protocol allowing for parallel histological assessments and fiber tractographic analysis in a common space. Semi-quantitative readings are feasible and allow the detection of cell loss in VTA subnuclei. This work describes the intricate workflow and first results of an investigation of DA anatomy in VTA subnuclei in a growing naturalistic database.

The use of non-prescribed opioid substitution drugs is a serious public health problem, involving general population as well as vulnerable populations such as prisoners. The estimation of the prevalence of opioid substitution drug misuse in prisoners is crucial to suggest strategies to contrast this phenomenon and reduce the associated morbidity and mortality. The present study aimed to provide an objective estimation of the prevalence of illicit use of methadone and buprenorphine in two German prisons. Urine samples were collected from inmates of Freiburg and Offenburg prisons at random times and tested for the detection of methadone, buprenorphine and their metabolites. Analyses were performed by a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. In total 678 inmates participated in this study. The participation rate was about 60% of all permanent inmates. Of the 675 samples suitable for the analysis, 70 samples (10.4%) tested positive for methadone, 70 samples (10.4%) for buprenorphine, and 4 samples (0.6%) for both drugs. At least 100 samples (14.8%) were not associated with reported prescribed-opioid substitution treatment (OST). Buprenorphine was the most common illicitly used drug. In one of the prisons, buprenorphine was brought in from the outside. The present cross-sectional experimental study was able to provide reliable information regarding the illicit use of opioid substitution drugs in prisons.

In many parts of the world, ethanol is a widely consumed substance that displays its effect in the brain, the target organ for desired, but also negative impact. In a previous study, the ethanol concentrations were analyzed in different regions of the brain by magnetic resonance spectroscopy (MRS). In this study, the same method is used to demonstrate the kinetics of the ethanol concentration in the human brain after oral ethanol uptake. A drinking study was performed with 10 healthy participants. After the uptake of ethanol in a calculated amount leading to a plasma ethanol concentration of 0.92 g/L (19.95 mM corresponding to a blood ethanol concentration of 0.7 g/kg), brain ethanol concentrations were continuously measured by means of MRS on a 3 Tesla human magnetic resonance imaging (MRI) system. For the data acquisition a single-voxel sLASER sequence was used, with the volume of interest located in the occipital cortex. Intermittently, blood samples were taken and plasma was analyzed for ethanol using headspace gas chromatography with flame ionization detection (HS-GC-FID). The obtained MRS brain ethanol curves showed distinct inter-individual differences; however, a good intra-individual correlation of plasma and brain ethanol concentrations was observed. The results suggest a rapid equilibration between blood and brain. The ethanol concentrations measured in the brain were substantially lower than the measured plasma ethanol results, suggesting an MRS visibility of about 63% for ethanol in brain tissue. The maximum individual ethanol concentrations in the brain (normalized to water content) ranged between 7.1 and 14.1 mM across the cohort, while the highest measured plasma concentrations were in the range between 0.35 g/L (9.41 mM) and 0.95 g/L (20.52 mM).

Major depressive disorder (MDD) is prevalent with a high subjective and socio-economic burden. Despite the effectiveness of classical treatment methods, 20–30% of patients stay treatment-resistant. Deep Brain Stimulation of the superolateral branch of the medial forebrain bundle is emerging as a clinical treatment. The stimulation region (ventral tegmental area, VTA), supported by experimental data, points to the role of dopaminergic (DA) transmission in disease pathology. This work sets out to develop a workflow that will allow the performance of analyses on midbrain DA-ergic neurons and projections in subjects who have committed suicide. Human midbrains were retrieved during autopsy, formalin-fixed, and scanned in a Bruker MRI scanner (7T). Sections were sliced, stained for tyrosine hydroxylase (TH), digitized, and integrated into the Montreal Neurological Institute (MNI) brain space together with a high-resolution fiber tract atlas. Subnuclei of the VTA region were identified. TH-positive neurons and fibers were semi-quantitatively evaluated. The study established a rigorous protocol allowing for parallel histological assessments and fiber tractographic analysis in a common space. Semi-quantitative readings are feasible and allow the detection of cell loss in VTA subnuclei. This work describes the intricate workflow and first results of an investigation of DA anatomy in VTA subnuclei in a growing naturalistic database. [ABSTRACT FROM AUTHOR]