ABSTRACT
BACKGROUND: Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. METHOD: A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. RESULTS: We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. CONCLUSIONS: Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.
Subject(s)
Catechol O-Methyltransferase/genetics , Emotions/physiology , Prefrontal Cortex/physiopathology , Schizophrenia/genetics , Adult , Amygdala/metabolism , Amygdala/physiopathology , Analysis of Variance , Brain Mapping , Case-Control Studies , Catechol O-Methyltransferase/metabolism , Dopamine/metabolism , Facial Expression , Female , Functional Laterality , Genetic Predisposition to Disease , Genotype , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/methods , Male , Photic Stimulation , Polymorphism, Single Nucleotide/physiology , Prefrontal Cortex/metabolism , Psychiatric Status Rating Scales , Schizophrenia/metabolism , Schizophrenia/physiopathology , SiblingsABSTRACT
To find a better method for predicting the biological behavior of certain oral cavity lesions, the expression of nucleolar protein p120 and nucleolar organizer region counts (AgNOR) was compared with that of nuclear proliferation markers MIB-1 and PCNA in 10 cases of keratotic epithelial hyperplasia (KEH), 10 cases of epithelial dysplasia (ED), and 15 cases of squamous cell carcinoma (SCC). Significant differences in p120 and AgNOR mean area values and PCNA labeling index (LI) were recorded between KEH and ED, as well as ED and SCC (Student-Neumann-Keuls test). All markers significantly differed between SCC grades I and III. Significant differences were also noted in AgNOR mean area values between grade I and II SCC and in p120 mean area values. MIB-1 and PCNA LI differed significantly when grade II and III SCC were compared (SNK test). There were significant correlations between p120 and AgNOR (Pearson correlation coefficients) and between both of them and the proliferative indexes. AgNOR correlated with tumor grade, stage, and lymph node status (Spearman correlation coefficients), suggesting a prognostic role for that marker.
Subject(s)
Biomarkers, Tumor/analysis , Mouth Diseases/immunology , Mouth Neoplasms/immunology , Nucleolus Organizer Region/pathology , Analysis of Variance , Antigens, Neoplasm/analysis , Antigens, Nuclear , Humans , Hyperplasia/immunology , Ki-67 Antigen , Nuclear Proteins/analysis , Nucleolus Organizer Region/chemistry , Prognosis , Proliferating Cell Nuclear Antigen/analysis , Retrospective Studies , Silver Staining , Statistics, Nonparametric , tRNA MethyltransferasesABSTRACT
A study was carried out on Met- and Leu-enkephalin, Gastrin/CCK-, SP-, CGRP-, NPY-immunoreactive fibers using paraffin sections of dental pulp taken from 8 apparently normal teeth (wisdom teeth or teeth extracted for orthodontic reasons). Within the limitations of the samples studied, dental pulp is characterized by the presence of sensory (Enkephalin-, Gastrin/CCK-immunoreactive) and pain fibers (SP-immunoreactive) and of fibers with a potent vasodilatory action (CGRP-immunoreactive) and by the absence of fibers with a vasoconstrictor action (NPY-immunoreactive).
