Clinical precursors of adolescent conduct disorder in children with attention-deficit/hyperactivity disorder

OBJECTIVE: To examine precursors of adolescent conduct disorder (CD) in children with attention-deficit/hyperactivity disorder (ADHD), investigating the significance of childhood oppositional defiant disorder (ODD) and ADHD. METHOD: A total of 151 children with ADHD recruited from child psychiatric and pediatric clinics were assessed through standardized diagnostic interviews at ages 6 to 13 years and in adolescence 5 years later. Using multiple regression analysis, we assessed baseline ODD diagnosis and ODD, CD, and ADHD symptom scores as clinical predictors of adolescent CD diagnosis and symptom scores. RESULTS: Childhood ODD (diagnosis and severity) was significantly associated with adolescent CD (diagnosis and severity), independent of childhood ADHD severity and childhood CD. Children with a diagnosis of ODD were almost three times more likely to develop CD in adolescence (odds ratio = 2.79, 95% CI 1.16-6.70, p = .02). Childhood ADHD severity predicted adolescent CD scores but not diagnosis of CD (although there was a trend toward association). The presence of at least one CD symptom in childhood predicted adolescent CD severity. CONCLUSIONS: ODD is a significant precursor of adolescent CD in children with ADHD independent of ADHD severity. Considering the negative prognosis of ADHD with comorbid CD, it is imperative that clinicians pay specific attention to the presence of childhood ODD behaviors.     

Impairment in childhood anxiety disorders: preliminary examination of the child anxiety impact scale-parent version

Although anxiety disorders are prevalent among children and adolescents, with a chronic and often disabling course, there is a paucity of research examining the specific ways in which anxiety interferes with various domains of functioning in childhood. The purpose of the current investigation was to examine the initial reliability and construct validity of the Child Anxiety Impact Scale-Parent version (CAIS-P). The CAIS-P is a parent-report measure consisting of School, Social, and Home/Family subscales. In a clinical sample (N = 92), the internal reliability and the convergent and divergent validity were evaluated. Internal consistency was good for the total score as well as each subscale (Cronbach's alpha ranged from 0.73-0.87). The CAIS-P total score demonstrated good construct validity, showing predicted significant correlations with the Child Behavior Checklist Internalizing Scale and the Child Depression Inventory but not the Externalizing Scale of the Child Behavior Checklist. The Social subscale of the CAIS-P was also significantly correlated with measures of social anxiety. The results provide initial support that the CAIS-P is a reliable and valid measure for the assessment of the impact of anxiety on child and adolescent functioning.     

Oxidative stress‐induced death in the nervous system: Cell cycle dependent or independent?

Neuronal death, attributable to perturbed redox homeostasis, is the underlying factor in many acute and chronic neurological disorders. The mechanisms employed by oxidatively stressed neurons to commit to cell death pathways are beginning to be characterized, but this is hampered by a lack of good models that extrapolate readily to redox-dependent neuronal death paradigms. In this Mini-Review, we discuss mechanisms by which oxidative stress can result in neurodegeneration. We examine evidence on which terminally differentiated neurons might commit to death under conditions of oxidative stress. In some cases, death may be linked to an aberrant and uncoordinated reentry into the cell cycle and mitotic catastrophe. Other evidence suggests that cell cycle reentry is not mandatory for death execution. Rather, the reexpression of cell cycle proteins may induce apoptotic pathways in a cell cycle-independent manner. In contrast to these models, there is also evidence that oxidative neuronal death is independent of cell cycle proteins. We conclude that oxidative stress-induced neuronal death may be promoted via several pathways, which may be cycle protein dependent or independent. The determining factor for which or how many pathways are induced appears to be context dependent and determined by the level and duration of oxidative stress.     

Spectrin Nice (beta 220/216): a shortened beta-chain variant associated with an increase of the alpha I/74 fragment in a case of elliptocytosis

We describe a new spectrin variant with a truncated beta-chain. It was discovered in a 17-year-old white boy presenting with intermittent jaundice and spleen enlargement. He also displayed numerous smooth elliptocytes. On sodium dodecyl sulfate-polyacrylamide gel, the truncated beta-chain (beta'-chain) appeared as an additional band of approximately 216 kilodaltons, migrating between spectrin beta-chain and ankyrin. It represented 30% of total beta-chain. The beta'-chain reacted with an antispectrin beta-chain monoclonal antibody. It failed to become phosphorylated when ghosts were incubated in the presence of [gamma-32P] adenosine triphosphate. Whole spectrin tetramerization was defective since the amount of spectrin dimer was increased in spectrin crude extract and the association constant of the spectrin dimer self- association was decreased. Spectrin whole tetramer isolated from spectrin crude extracts contained small quantities of beta'-chain. Spectrin tryptic peptides showed an increase of the 74,000-dalton fragment at the expense of the 80,000-dalton fragment. So far, the latter abnormality has been used to characterize a number of cases of hereditary elliptocytosis or pyropoikilocytosis with no other apparent change. In the present case, we consider that the abnormality is a consequence of the beta-chain alteration. The parents seemed asymptomatic. As a result, we regard this new spectrin variant as deriving from a de novo mutation.