ABSTRACT
OBJECTIVE: To examine the relationship between adrenal androgens and aggression in children with oppositional and antisocial behavior and to compare their levels with those of psychiatric and normal controls. METHOD: Dehydroepiandrosterone sulfate (DHEAS) was measured in 24 children with oppositional defiant disorder (ODD), 42 psychiatric controls (including 20 children with attention-deficit/hyperactivity disorder [ADHD]), and 30 normal controls. The children's parents filled out the Child Behavior Checklist (CBCL). RESULTS: Children with ODD had higher DHEAS levels than either the psychiatric control or normal control groups; DHEAS levels of the latter groups did not differ. Moreover, it was possible to classify children as having either ODD or ADHD on the basis of their DHEAS levels, whereas this was not the case on the basis of the CBCL data. CONCLUSIONS: The results indicate that adrenal androgen functioning is specifically elevated in children with ODD. It is speculated that the mechanism could be a shift in balance of ACTH-beta-endorphin functioning in the hypothalamic-pituitary-adrenal axis due to early stress or genetic factors.
Subject(s)
Adrenal Glands/metabolism , Aggression , Androgens/metabolism , Attention Deficit and Disruptive Behavior Disorders/blood , Attention Deficit and Disruptive Behavior Disorders/psychology , Dehydroepiandrosterone Sulfate/blood , Analysis of Variance , Attention Deficit and Disruptive Behavior Disorders/physiopathology , Case-Control Studies , Child , Conduct Disorder/complications , Dehydroepiandrosterone Sulfate/metabolism , Female , Humans , Hypothalamo-Hypophyseal System , Male , Mental Disorders/blood , Mental Disorders/physiopathology , Mental Disorders/psychology , Pituitary-Adrenal System , Psychiatric Status Rating ScalesABSTRACT
The genome of Pyrococcus furiosus contains the putative mbhABCDEFGHIJKLMN operon for a 14-subunit transmembrane complex associated with a Ni-Fe hydrogenase. Ten ORFs (mbhA-I and mbhM) encode hydrophobic, membrane-spanning subunits. Four ORFs (mbhJKL and mbhN) encode putative soluble proteins. Two of these correspond to the canonical small and large subunit of Ni-Fe hydrogenase, however, the small subunit can coordinate only a single iron-sulfur cluster, corresponding to the proximal [4Fe-4S] cubane. The structural genes for the small and the large subunits, mbhJ and mbhL, are separated in the genome by a third ORF, mbhK, encoding a protein of unknown function without Fe/S binding. The fourth ORF, mbhN, encodes a 2[4Fe-4S] protein. With P. furiosus soluble [4Fe-4S] ferredoxin as the electron donor the membranes produce H2, and this activity is retained in an extracted core complex of the mbh operon when solubilized and partially purified under mild conditions. The properties of this membrane-bound hydrogenase are unique. It is rather resistant to inhibition by carbon monoxide. It also exhibits an extremely high ratio of H2 evolution to H2 uptake activity compared with other hydrogenases. The activity is sensitive to inhibition by dicyclohexylcarbodiimide, an inhibitor of NADH dehydrogenase (complex I). EPR of the reduced core complex is characteristic for interacting iron-sulfur clusters with Em approximately -0.33 V. The genome contains a second putative operon, mbxABCDFGHH'MJKLN, for a multisubunit transmembrane complex with strong homology to the mbh operon, however, with a highly unusual putative binding motif for the Ni-Fe-cluster in the large hydrogenase subunit. Kinetic studies of membrane-bound hydrogenase, soluble hydrogenase and sulfide dehydrogenase activities allow the formulation of a comprehensive working hypothesis of H2 metabolism in P. furiosus in terms of three pools of reducing equivalents (ferredoxin, NADPH, H2) connected by devices for transduction, transfer, recovery and safety-valving of energy.
Subject(s)
Cytochrome c Group/metabolism , Hydrogen/metabolism , Hydrogenase/genetics , Operon , Oxidoreductases/metabolism , Pyrococcus furiosus/enzymology , Pyrococcus furiosus/genetics , Acetates/metabolism , Amino Acid Sequence , Dicyclohexylcarbodiimide/pharmacology , Fermentation , Genome, Bacterial , Hydrogenase/chemistry , Hydrogenase/metabolism , Iron-Sulfur Proteins/chemistry , Iron-Sulfur Proteins/genetics , Iron-Sulfur Proteins/metabolism , Kinetics , Molecular Sequence Data , Open Reading Frames , Protein Subunits , Sequence Alignment , Sequence Homology, Amino Acid , Substrate SpecificityABSTRACT
OBJECTIVE: The primary aim of the study was to ascertain the usefulness and the validity of the set of criteria proposed to define a subgroup within the DSM-III-R category of pervasive developmental disorder-not otherwise specified under the name of multiple complex developmental disorder (MCDD). METHOD: A multivariate analysis (cluster and principal-components analysis) was performed on the characteristics, reliably extracted from the charts of 105 children with MCDD, 32 with autistic disorder, 51 with externalizing disorders, and 56 with internalizing disorders, all with an IQ greater than 70, fully assessed in our department between 1984 and 1991. RESULTS: The main finding was a strong correspondence between the classification of the cases by DSM-III-R categories and the subdivision by means of a multivariate cluster analysis. The cluster analysis did not discriminate between children with emotional and disruptive disorders. Furthermore, children with MCDD and autistic disorder were significantly different both on symptom factors ("psychotic thinking/anxiety," "aggression," "deficient interaction/communication," "stereotyped and rigid behavior," and "suspiciousness/odd interaction") and on factors that reflected developmental and environmental background variables. CONCLUSION: The results of this study add to the nosology of autistic spectrum disorders and lend additional support to the need for a separate subcategory of MCDD within DSM-V. Further corroboration of these results in independent (multicenter) samples will be required.
