Deficient vesicular storage: A common theme in catecholaminergic neurodegeneration

Several neurodegenerative diseases involve loss of catecholamine neurons--Parkinson's disease (PD) is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are lost has been mysterious. Accumulating evidence supports the concept of "autotoxicity"--inherent cytotoxicity caused by catecholamine metabolites. Since vesicular sequestration limits the buildup of toxic products of enzymatic and spontaneous oxidation of catecholamines, a vesicular storage defect could play a pathogenic role in the death of catecholaminergic neurons in a variety of neurodegenerative diseases. In putamen, deficient vesicular storage is revealed in vivo by accelerated loss of (18)F-DOPA-derived radioactivity and post-mortem by decreased tissue dopamine (DA):DOPA ratios; in myocardium in vivo by accelerated loss of (18)F-dopamine-derived radioactivity and post-mortem by increased 3,4-dihydroxyphenylglycol:norepinephrine (DHPG:NE) ratios; and in sympathetic noradrenergic nerves overall in vivo by increased plasma F-dihydroxyphenylacetic acid (F-DOPAC):DHPG ratios. We retrospectively analyzed data from 20 conditions with decreased or intact catecholaminergic innervation, involving different etiologies, pathogenetic mechanisms, and lesion locations. All conditions involving parkinsonism had accelerated loss of putamen (18)F-DOPA-derived radioactivity; in those with post-mortem data there were also decreased putamen DA:DOPA ratios. All conditions involving cardiac sympathetic denervation had accelerated loss of myocardial (18)F-dopamine-derived radioactivity; in those with post-mortem data there were increased myocardial DHPG:NE ratios. All conditions involving localized loss of catecholaminergic innervation had evidence of decreased vesicular storage specifically in the denervated regions. Thus, across neurodegenerative diseases, loss of catecholaminergic neurons seems to be associated with decreased vesicular storage in the residual neurons

Juvenile sex offenders: a complex population

Individuals who engage in sexual offending behavior represent a heterogeneous population. Recent research has found some success in categorizing sexual offenders based on a number of variables, particularly the type of victim. For example, differences have been found between those offenders who victimize adults when compared with those who victimize children. However, the research in this area has been conducted predominantly with adult samples. As the adult sex offender literature has progressed, it has become evident that risk assessment, treatment effectiveness, and risk management are dependent on such offender characteristics. Unfortunately, the relevance to juveniles of characteristics deemed to be important with adult sex offenders is limited due to the complexity of developmental processes, particularly with respect to mental disorders and personality formation. As such, the formulation and implementation of treatment and risk management strategies that will be effective with juvenile sex offenders are challenging. The goal of this paper is to review some of the complexities inherent in the juvenile sex offender population by focusing on specific areas of complication, including: classification systems, comorbid paraphilias and other mental illnesses, and maladaptive personality traits