ABSTRACT
Alzheimer's disease (AD) is a common cause of functional decline in Down syndrome (DS) adults. Acquired cognitive deficits may be difficult to evaluate in the context of baseline impairments. Behavioral symptoms are also common and may represent the effects of depression, AD, or both. Therefore, the objective of this study was to report a clinical case series of selected adults with DS and behavioral change who responded to treatment with selective serotonin-reuptake inhibitor (SSRI) medication. Six patients, aged 23 to 63 years, 5 women and 1 man, with the clinical diagnosis of DS presented for diagnosis and treatment of functional decline in adult life. Noncognitive symptoms were prominent and included aggression, social withdrawal, and compulsive behaviors. Memory dysfunction was reported in varying degrees. Treatment with SSRI antidepressants was instituted for depressive, apathetic, and compulsive behaviors. Treated patients showed improvement in behaviors as reported by caregivers, and on objective measures, such as workplace productivity. Noncognitive symptoms are a cardinal feature of functional decline in adults with DS and may represent either depression or AD. In some patients, the symptoms respond well to SSRI agents with concomitant improvement in daily function. Treatment trials with SSRIs may, therefore, be warranted in such cases.
Subject(s)
Alzheimer Disease/drug therapy , Behavioral Symptoms/drug therapy , Depression/drug therapy , Down Syndrome/drug therapy , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Alzheimer Disease/diagnosis , Alzheimer Disease/etiology , Behavioral Symptoms/etiology , Depression/diagnosis , Depression/etiology , Disease Progression , Down Syndrome/complications , Female , Humans , Male , Middle AgedABSTRACT
The expression of novel TrkB receptor transcripts has been characterized to understand the potentially diverse roles of brain-derived neurotrophic factor (BDNF) in the developing avian visual system. In situ localization with an extracellular domain probe common to all TrkB transcripts labeled a sub-population of large retinal ganglion cells as well as many associated visual nuclei, including the neuronal layers within the tectum that receive retinal innervation. Because of the potential for structurally and functionally distinct receptors derived from the TrkB gene locus, cDNA cloning and reverse transcription-PCR analysis were used to further analyze receptor isoform expression in the retina and tectum. Receptor isoforms were sequenced that contained a deletion of the N terminus, a deletion in the putative ligand-binding domain, or a deletion in the cytoplasmic juxtamembrane (JM) domain. Two novel JM insertion sequences also were identified, one of which exhibits weak homology to beta-actin and was found in both kinase-containing (TK+) and kinase deletion (KD) receptor isoforms. In the developing retina, TK+ receptor mRNA is upregulated during the period of retinal ganglion cell (RGC) death, consistent with the proposed role of BDNF as a tectal-derived survival factor for RGCs. However, the expression of TK+ transcripts in the tectum indicates that this structure also contains cells responsive to BDNF throughout development. Because BDNF is expressed in both the retina and tectum, it is conceivable that TrkB also mediates autocrine/paracrine signaling within these structures or anterograde retinotectal trophic support.
