Oxytocin and Prader-Willi Syndrome.

In the chapter, we explore the relationship between the peptide hormone, oxytocin (OT), and behavioral and metabolic disturbances observed in the genetic disorder Prader-Willi Syndrome (PWS). Phenotypic and genotypic characteristics of PWS are described, as are the potential implications of an abnormal OT system with respect to neural development including the possible effects of OT dysfunction on interactions with other regulatory mediators, including neurotransmitters, neuromodulators, and hormones. The major behavioral characteristics are explored in the context of OT dysfunction, including hyperphagia, impulsivity, anxiety and emotion dysregulation, sensory processing and interoception, repetitive and restrictive behaviors, and dysfunctional social cognition. Behavioral overlaps with autistic spectrum disorders are discussed. The implications of OT dysfunction on the mechanisms of reward and satiety and their possible role in informing behavioral characteristics are also discussed. Treatment implications and future directions for investigation are considered.

Behavioral phenotype in a child with Prader-Willi syndrome and comorbid 47, XYY.

We report a 12-year-old male with Prader-Willi syndrome (PWS) and 47, XYY syndrome. Genetic work up revealed 47, XYY karyotype. PWS diagnosis was made by polymerase chain reaction methylation and maternal uniparental disomy (mUPD) was determined to be the etiology. Review of distinct behavioral features, possible interplay between the two syndromes and considerations for diagnoses are presented. To our knowledge, this is the first report of behavioral features in PWS with comorbid 47, XYY.

Hypometric allocentric and egocentric distance estimates in Parkinson disease.

OBJECTIVE AND BACKGROUND: Persons with Parkinson disease (PD) show hypometric movements and make hypometric estimates of imagined actions. These deficits may be related to misestimates of the length of body parts. Our objective was to learn whether patients with PD are impaired in their estimations of their arm's length and standard units of distance. METHODS: We tested 20 patients with PD, all on therapeutic doses of dopaminergic medications, and 13 healthy controls. In half of the trials, the participants stood so that either their right or left shoulder was adjacent to a wall; in the other half, their right or left shoulder was 5 feet from the wall. In the egocentric testing condition, they were asked to move their body toward or away from the wall to what they considered was an arm's length from the wall. In the allocentric testing condition, they were to move toward or away from the wall so that their proximal shoulder was a standard unit distance of 1, 2, or 3 feet from the wall. RESULTS: The patients with PD made much greater hypometric (too close to the wall) errors. Since at 5 feet from the wall they had to move farther to underestimate distances, their errors cannot be explained by hypometric movements. The results did not differ significantly by egocentric or allocentric estimation, side of shoulder proximity, or side of PD onset. CONCLUSIONS: Our findings support the idea that the egocentric and allocentric hypometria associated with PD is a perceptual rather than motor disorder.

Dysexecutive functioning in mild cognitive impairment: derailment in temporal gradients.

Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fuster's (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI.

Verbal serial list learning in mild cognitive impairment: a profile analysis of interference, forgetting, and errors.

Using cluster analysis Libon et al. (2010) found three verbal serial list-learning profiles involving delay memory test performance in patients with mild cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored higher on recognition compared to delay free recall tests; and dysexecutive MCI (dMCI) patients generated relatively intact scores on both delay test conditions. The aim of the current research was to further characterize memory impairment in MCI by examining forgetting/savings, interference from a competing word list, intrusion errors/perseverations, intrusion word frequency, and recognition foils in these three statistically determined MCI groups compared to normal control (NC) participants. The aMCI patients exhibited little savings, generated more highly prototypic intrusion errors, and displayed indiscriminate responding to delayed recognition foils. The mxMCI patients exhibited higher saving scores, fewer and less prototypic intrusion errors, and selectively endorsed recognition foils from the interference list. dMCI patients also selectively endorsed recognition foils from the interference list but performed similarly compared to NC participants. These data suggest the existence of distinct memory impairments in MCI and caution against the routine use of a single memory test score to operationally define MCI.

Reversible dementias.

The causes of potentially reversible dementia syndromes are legion, as many perturbations of body chemistry can lead to dysfunction of higher cortical function, including the chemical interventions we call medication. It is vital for the cautious clinician to take a painstaking history to develop a differential diagnosis of potential causally related reversible phenomena. This, coupled with an extensive examination and a widecast net of serological, and when appropriate, cerebrospinal, electrophysiologic, and neuroimaging studies can increase the potential for discovering these mimics of the primary neurodegenerative dementias. While some cases of reversible dementia will be obvious from history and physical and only require a few confirmatory tests or even just a trial of treatment (or often, discontinuation of a suspect treatment), it is worthwhile to perform more extensive work-up in cases of dementia, as the costs to allowing our patients to remain in an incapacitated, possibly progressive, state of disability far outweigh the costs of ruling out reversible causes. This chapter provides a lengthy, though by no means exhaustive, review of etiologies and work-up for the currently recognized reversible dementias.