Cerebral deposition of beta-amyloid (Abeta) peptides is an invariant pathological hallmark in brains of patients with Alzheimer's disease (AD) and transgenic mice coexpressing familial AD-linked APP and PS1 variants. We now report that exposure of transgenic mice to an "enriched environment" results in pronounced reductions in cerebral Abeta levels and amyloid deposits, compared to animals raised under "standard housing" conditions. The enzymatic activity of an Abeta-degrading endopeptidase, neprilysin, is elevated in the brains of "enriched" mice and inversely correlated with amyloid burden. Moreover, DNA microarray analysis revealed selective upregulation in levels of transcripts encoded by genes associated with learning and memory, vasculogenesis, neurogenesis, cell survival pathways, Abeta sequestration, and prostaglandin synthesis. These studies provide evidence that environmental enrichment leads to reductions in steady-state levels of cerebral Abeta peptides and amyloid deposition and selective upregulation in levels of specific transcripts in brains of transgenic mice.

During sleep, humans can strengthen previously acquired memories, but whether they can acquire entirely new information remains unknown. The nonverbal nature of the olfactory sniff response, in which pleasant odors drive stronger sniffs and unpleasant odors drive weaker sniffs, allowed us to test learning in humans during sleep. Using partial-reinforcement trace conditioning, we paired pleasant and unpleasant odors with different tones during sleep and then measured the sniff response to tones alone during the same nights' sleep and during ensuing wake. We found that sleeping subjects learned novel associations between tones and odors such that they then sniffed in response to tones alone. Moreover, these newly learned tone-induced sniffs differed according to the odor pleasantness that was previously associated with the tone during sleep. This acquired behavior persisted throughout the night and into ensuing wake, without later awareness of the learning process. Thus, humans learned new information during sleep.

Sleep deprivation impairs hippocampal-dependent learning, which, in turn, is associated with increased survival of newborn cells in the hippocampus. We tested whether the deleterious effects of sleep restriction on hippocampus-dependent memory were associated with reduced cell survival in the hippocampus. We show that sleep restriction impaired hippocampus-dependent learning and abolished learning-induced neurogenesis. Animals were trained in a water maze on either a spatial learning (hippocampus-dependent) task or a nonspatial (hippocampus-independent) task for 4 days. Sleep-restricted animals were kept awake for one-half of their rest phase on each of the training days. Consistent with previous reports, animals trained on the hippocampus-dependent task expressed increased survival of newborn cells in comparison with animals trained on the hippocampus-independent task. This increase was abolished by sleep restriction that caused overall reduced cell survival in all animals. Sleep restriction also selectively impaired spatial learning while performance in the nonspatial task was, surprisingly, improved. Further analysis showed that in both training groups fully rested animals applied a spatial strategy irrespective of task requirements; this strategy interfered with performance in the nonspatial task. Conversely, in sleep-restricted animals, this preferred spatial strategy was eliminated, favoring the use of nonspatial information, and hence improving performance in the nonspatial task. These findings suggest that sleep loss altered behavioral strategies to those that do not depend on the hippocampus, concomitantly reversing the neurogenic effects of hippocampus-dependent learning.

As many as third of the women perceive their childbirth as traumatic and although prevalence rates vary between studies, around 2–5% of women in community samples may develop childbirth-related postpartum post-traumatic stress disorder (PPTSD). The City Birth Trauma Scale (BiTS) was developed to address the need for a DSM-5-based instrument that assesses PPTSD. The BiTS is a self-report questionnaire, which covers all DSM-5 PTSD criteria, including the four symptom clusters – re-experiencing, avoidance, negative mood and cognitions and hyperarousal symptoms. The present study aimed to describe the psychometric properties and validate the Hebrew version of the BiTS. Five hundred and four mothers of 0- to 12-month-old infants were sampled using social media and the snowball method. Respondents completed an online survey consisting of a demographic questionnaire and the Hebrew versions of the BiTS, the impact of event scale-revised (IES-R), the Edinburgh postpartum depression scale (EPDS), and the Pittsburgh Sleep Quality Index (PSQI). The Hebrew BiTS demonstrated high internal consistency for the total scale (Cronbach α = 0.90) and good internal consistency (Cronbach’s α = 0.75–0.85) for the subscales. An exploratory factor (EFA) analysis yielded a two-factors solution, accounting for 45% of variance, with general symptoms loaded on Factor 1, and childbirth-related symptoms loaded on Factor 2, with both factors demonstrating high internal consistency (Cronbach’s α = 0.90, 0.85, respectively). High convergent validity for the symptom cluster subscales was demonstrated with the parallel IES-R subscales, EPDS and PSQI. A two-step cluster analysis indicated that dysphoric and hyperarousal symptoms best differentiated the severity of symptoms of respondents across measures. In sum, the Hebrew BiTS was psychometrically sound, indicating its utility for clinical and non-clinical research. The EFA and cluster analyses support the differentiation between symptoms of dysphoria and hyperarousal from trauma (i.e., childbirth) specific symptoms, suggesting that symptoms relating to specific aspects of the trauma differ qualitatively from general symptom in the phenomenology of PPTSD. Further research using clinical samples and comparing the BiTS to DSM-5 diagnosis using clinical interview is needed.

The present study investigates sleep, mood, and the proposed bidirectional relationship between the two in psychiatric disorders. Participants with interepisode bipolar disorder (n = 49), insomnia (n = 34), and no psychiatric history (n = 52) completed seven consecutive days of sleep diaries and mood measures. The interepisode bipolar and insomnia participants exhibited greater sleep disturbance than the healthy control individuals. Negative mood was equally heightened in both interepisode bipolar disorder and insomnia, and there were no differences between the three groups in positive mood. Total wake time was associated with next morning negative mood in bipolar disorder, whereas evening negative mood was associated with subsequent total wake time in both bipolar disorder and insomnia. Additionally, positive mood was associated with subsequent total wake time for the insomnia group. Results support the theory that disruptions in nighttime sleep and daytime mood may be mutually maintaining and suggest the potential importance of transdiagnostic or universal processes.