Adult-Onset ADHD: A Critical Analysis and Alternative Explanations.

Attention deficit/hyperactivity disorder (ADHD) is characterized as a neurodevelopmental disorder. However, data from several recent studies suggest that there may be adults who meet current criteria for ADHD, yet did not experience symptoms until adulthood (i.e., "adult-onset ADHD"). This systematic review evaluated and synthesized the empirical evidence on adult-onset ADHD to answer the question: Is the extant literature strong enough to evaluate adult-onset ADHD? Nine studies met strict inclusion/exclusion criteria. Results suggest that the methodologies of the extant studies were not strong enough to evaluate adult-onset ADHD. Insufficient methodologies provide presently unclear information about the nature of late-onset symptoms. These symptoms seem to exist but their source could be (1) adult-emergent symptoms that were previously surpassed due to lower environmental demands/supportive facilitators, (2) mimics that were not properly assessed, or (3) childhood-onset symptoms that were not detected earlier due to failure to come to clinical attention. Future directions, clinical recommendations, and limitations of the literature and the current review are discussed.

Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion independent hexamer.

BACKGROUND: The enzyme porphobilinogen synthase (PBGS), which is central to the biosynthesis of heme, chlorophyll and cobalamins, has long been known to use a variety of metal ions and has recently been shown able to exist in two very different quaternary forms that are related to metal ion usage. This paper reports new information on the metal ion independence and quaternary structure of PBGS from the photosynthetic bacterium Rhodobacter capsulatus. RESULTS: The gene for R. capsulatus PBGS was amplified from genomic DNA and sequencing revealed errors in the sequence database. R. capsulatus PBGS was heterologously expressed in E. coli and purified to homogeneity. Analysis of an unusual phylogenetic variation in metal ion usage by PBGS enzymes predicts that R. capsulatus PBGS does not utilize metal ions such as Zn2+, or Mg2+, which have been shown to act in other PBGS at either catalytic or allosteric sites. Studies with these ions and chelators confirm the predictions. A broad pH optimum was determined to be independent of monovalent cations, approximately 8.5, and the Km value shows an acidic pKa of approximately 6. Because the metal ions of other PBGS affect the quaternary structure, gel permeation chromatography and analytical ultracentrifugation experiments were performed to examine the quaternary structure of metal ion independent R. capsulatus PBGS. The enzyme was found to be predominantly hexameric, in contrast with most other PBGS, which are octameric. A protein concentration dependence to the specific activity suggests that the hexameric R. capsulatus PBGS is very active and can dissociate to smaller, less active, species. A homology model of hexameric R. capsulatus PBGS is presented and discussed. CONCLUSION: The evidence presented in this paper supports the unusual position of the R. capsulatus PBGS as not requiring any metal ions for function. Unlike other wild-type PBGS, the R. capsulatus protein is a hexamer with an unusually high specific activity when compared to other octameric PBGS proteins.