Neuronal response to high negative affective stimuli in major depressive disorder: An fMRI study.

BACKGROUND: Disturbed emotion processing underlies depression. We examined the neuronal underpinnings of emotional processing in patients (PAT) with major depressive disorder (MDD) compared to healthy volunteers (HV) using functional magnetic resonance (fMRI) scan. METHODS: Thirty-six MDD patients and 30 HV underwent T2-weighted fMRI assessments during the presentation of an implicit affective processing task in three conditions. They differed regarding their affective quality (=valence, high negative, low negative and neutral stimuli) and regarding the arousal based on stimuli from the International Affective Picture System. RESULTS: Group contrasts showed lower left-sided activation in dorsolateral prefrontal cortex (DLPFC), anterior PFC, precentral and premotor cortex in PAT compared with HV (Cluster-level threshold, 5000 iterations, p<0.01). We found a significant interaction effect of valence and group, a significant effect of emotional valence and a significant effect of group. All effects were shown in brain regions within the emotional network (Cluster-level threshold, 5000 iterations, p<0.01). Higher arousal (rho=-0.33, p<0.01) and higher valence (rho=-0.33, p<0.01) during high negative stimuli presentation as well as more severe depression (Beck Depression Inventory II [BDI II]; r = 0.39, p = 0.01) were significantly negatively associated with left DLFPC activity in patients. LIMITATIONS: Potential influence of psychopharmacological drugs on functional activation is one of the most discussed source of bias in studies with medicated psychiatric patients. CONCLUSIONS: The results highlight the importance of left DLPFC during the processing of negative emotional stimuli in MDD. The integration of a neurophysiological model of emotional processing in MDD may help to clarify and improve therapeutic options.

Age-related changes in capillaries of rat oral mucosa. A quantitative electron microscopic study.

Ultrastructural age changes in capillaries of the buccal mucosa were examined in montages of cross sections made from electron micrographs at 37,500 x. Six rats aged 6 months and 6 aged 30 months were perfused with glutaraldehyde and conventional thin sections obtained. Two capillaries located within a connective tissue papilla were studied from each rat. Capillaries of the old group differed from those of the young group by statistically significant increases in several parameters. The endothelial cell was increased in thickness, especially in the vicinity of junctions. The frequency of pinocytotic vesicles/unit length of the cell circumference was nearly doubled. Junctions were of nearly double length and took a more oblique course. All parts of the basement membranes were thickened, though perhaps less than seems true in skin. In striking contrast to epidermis, the epithelium of oral mucosa undergoes no appreciable thinning with age. We suggest that the observed age increases in frequency of pinocytotic vesicles and in the length of junctions may facilitate blood/tissue exchange, thus compensating for impaired exchange due to the thickened basement membranes. These compensatory changes in conjunction with the unchanged size of the mucosal capillary bed in the aged rat (demonstrated previously) could explain the unchanged thickness of the oral epithelium.

Comparative analysis of biopsy specimens from gingiva and alveolar mucosa.

A total of 834 consecutive biopsy specimens from the gingiva and 448 from the alveolar mucosa were examined to see if differences in structure and function are reflected in categories and frequency of diagnoses. In both regions, inflammatory/reactive hyperplasia accounted for about 85% of the lesions and neoplasia for most of the remainder. Pyogenic granuloma was the most common lesion in the gingiva (23.6%) and fibrous hyperplasia in the alveolar mucosa (23.2%). The ratio of benign to malignant neoplasms was greater in the gingiva (10:1) than in the alveolar mucosa (almost 1:1). Benign tumors of the gingiva and malignant tumors of the alveolar mucosa occurred more often in males than one would expect from their proportion in the survey (keeping in mind that the numbers in alveolar mucosa were small). Lesions in these two regions were similar, but differed greatly in their frequency and in sex and age distribution.

Age-related changes in the epithelial dimensions and capillaries of the oral mucosa of the rat.

Seven homologous regions of the oral mucosa were compared in rats 6, 18 and 30 months of age. Capillaries were visualized by their alkaline-phosphatase activity revealed by an azo-dye. Measurements on tracings of densely-spaced histological sections in two planes perpendicular to the epithelial surface showed epithelial thickness in masticatory mucosa decreased by 18 months, but increased by 30 months. In regions of lining mucosa, thickness increased by 18 months, but decreased by up to 13 per cent at 30 months. The size of the capillary bed increased substantially by 18 months and further increased by 30 months. Variability in the epithelial dimensions increased up to 18 months but not beyond; variability in the capillary measurements showed no change with age. The quantitative relationship between epithelial thickness and the size of the epithelial-connective tissue interface and the capillary bed remained unchanged with age.

Epithelial dimensions and capillary supply in the oral mucosa of the rat.

Subdividing the cheek, palate and ventral tongue into seven anatomically identifiable regions enabled us to assess relationships that were previously obscured by the great heterogeneity of rat oral epithelium. Capillaries were visualized by an alkaline phosphatase azo dye method in oral mucosa of four 3-month old male rats. Basal layer length per unit surface length showed a statistically significant relationship with the thickness of the epithelial cell layer in all seven regions. Linear regression of mean regional length of basal layer on mean thickness of the cellular layer in the seven regions was statistically highly significant. This was true also for mean capillary length. Thickness of the cellular layer, length of the basal layer and capillary length were similar in a palatal ruga and a thick region of cheek, suggesting that epithelial thickness rather than the type of mucosa influences the magnitude of these values. Proportional reductions in all three variables were observed in a second region of cheek and a region of ventral tongue, supporting this suggestion.

Gingival hyperplasia: a side effect of nifedipine and diltiazem.

Currently, calcium channel blockers are being used increasingly for the treatment of hypertension in the elderly. Several case reports in the dental literature suggest that patients treated with the calcium channel blockers manifest gingival hyperplasia similar to that seen in patients taking phenytoin (Dilantin, Parke-Davis). A small study of 89 patients undertaken at the Westside Veterans Administration Medical Center, Chicago seems to indicate that nifedipine and diltiazem do indeed cause gingival hyperplasia. A total of 83% of the patients studied receiving nifedipine showed evidence of hyperplastic tissue and 74% of those on diltiazem were found to have hyperplastic tissue.

Abnormal functional and structural asymmetry as biomarker for schizophrenia.

The hemispheres of the human brain are anatomically and functionally asymmetric. Many cognitive and motor functions such as language and handedness are lateralized. In this review, we discuss the principles of laterality and brain asymmetry in relation to schizophrenia. Schizophrenia is one of the most disabling forms of mental illness. One important challenge is to develop and set up biological markers, which can accurately identify at-risk individuals in preclinical stages and thus improve the effects of early intervention strategies. The concept of hemispheric laterality plays a central role in current neuropsychological and pathophysiological models of schizophrenia. Recent research reflects an increasing interest in the molecular and population genetics of laterality and its potential use as biological marker for the illness. The review is an overview of literature from the 1990's on cerebral asymmetry in schizophrenia. We critically discuss the use of cerebral asymmetry for biomarker research, regarding diagnosis improvements, the improvement of psychopharmacology and the prediction of conversion in at-risk individuals. We propose that abnormal cerebral asymmetry is an attractive biomarker candidate for schizophrenia that could index changes in a range of pathophysiological pathways.

Correlation of changes in capillary supply and epithelial in the hyperplastic buccal mucosa of zinc-deficient rats.

Lengths of capillaries and epithelial dimensions were measured on tracings of sections of buccal mucosa stained for the alkaline phosphatase from rats on a zinc-deficient diet. The diet-deficient animals showed the following increases over controls; length of capillaries X 2.67; thickness of cell layer, X1.47; thickness of keratin layer. X2.82; basal layer length: surface length ratio, X1.41. Lengthening of the basal layer and the capillaries showed high positive correlations with thickening of the basal layer cell layer. Lengthening of the capillaries exceeded the lengthening of the basal layer cell layer amd the thickening of the epithelium but fell short of the increased anabolic performance of the epithelium as quantitated in previous investigations.

Endogenous alkaloids in man. XXVI. Determination of the dopaminergic neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) in biological samples using gas chromatography with selected ion monitoring.

Highly chlorinated beta-carbolines have a potential in vivo relevance to Parkinson's disease. In this paper, a gas chromatographic method for the determination of the neurotoxic 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), the condensation product of tryptamine and chloral hydrate, is described. The specific and sensitive assay involves purification of the biological samples by solid-phase extraction with C18 cartridges, derivatization with heptafluorobutyric anhydride, and chromatography on a non-polar fused-silica capillary column. Detection of TaClo was achieved by the registration of characteristic mass fragments of the TaClo heptafluorobutyric amide derivative using selected ion monitoring. The method was utilized to detect and quantify TaClo in blood, urine, bile, faeces, and brain tissue of rats treated with this alkaloid-type heterocycle. Four-fold deuterium-labelled TaClo was used as an internal standard.