Positive rumination can (also) interfere with sleep: A study in a non-clinical sample.

It is postulated that negative ruminations perpetuate insomnia symptoms by increasing arousal. Less is known about the role of positive rumination. In this study, we set out to test the association between positive and negative ruminations and insomnia symptoms in a non-clinical sample, asking whether reappraisal and suppression moderate the relationship between rumination types and symptoms of insomnia. Methods: A convenience sample of 354 participants (59% women), ages 18-50, responded to online questionnaires regarding symptoms of insomnia (Insomnia Severity Index [ISI]), Emotion Regulation Questionnaire that provides separate scales for Reappraisal and Suppression, Negative Rumination (Ruminative Response Scale), Positive Rumination and Dampening (Responses to Positive Affect questionnaire), and general health and demographics. Results: About 30% of respondents had moderate to severe symptoms of insomnia according to the ISI. The primary hypothesis was tested using three moderation models, where rumination type, emotion regulation styles, and interaction terms were predictors, and ISI scores were the outcome variable. Negative rumination positively predicted ISI (ß = 0.56, p < 0.001), while the interaction terms with Reappraisal (ß = 0.02, p = 0.575) and Suppression (ß = 0.07, p = 0.092) were not significant. Dampening also positively predicted ISI (ß = 0.56, p < 0.001), with the interaction term with Reappraisal nearly significant (ß = -0.09, p = 0.060), but not with Suppression (ß = 0.08, p =0.098). Positive rumination negatively predicted ISI (ß = -0.12, p = 0.021), this relationship was reversed with emotion regulation factors in the model (ß = 0.11, p = 0.094), where the interaction with Reappraisal (ß = 0.13, p = 0.020) and Suppression (ß = -0.13, p = 0.024) were both significant. Discussion: Positive Rumination weakly and negatively correlated with ISI, but the combination with Reappraisal was associated with more insomnia symptoms. By contrast, Dampening was associated with more insomnia symptoms, with minimal to no moderating effects. These observations are interpreted in the context of the role of emotion regulation strategies and sleep, and their potential clinical implications.

COVID-19 related worry moderates the association between postpartum depression and mother-infant bonding.

The aim of this study was to ask whether a substantial external stressor, such as the COVID-19 pandemic, affects the association between postpartum depression (PPD) and mother-infant bonding. Specifically, we aimed to determine whether worry regarding such an external threat differentially affected PPD and bonding by analyzing a longitudinal sample of postpartum women assessed before and during the pandemic. One-hundred forty women responded to online questionnaires at (T1) Pre-COVID-19: Six months postpartum (February 2018 to December 2019), and (T2) During COVID-19: Twenty-one months postpartum (April 2020 to January 2021). The strength of correlation between mother-infant bonding and PPD significantly declined from before (T1: R = 0.64, p < 0.00) to during the pandemic (T2: R = 0.44, p < 0.001; Difference = 0.20, p = 0.05). Furthermore, only PPD correlated with the worry due to the pandemic; thus the PPD-bonding association was weaker among women who were less concerned about the pandemic (F(3, 136) = 15.4, R2 = 0.25). The study suggests that emotions and cognitions related to motherhood, such as mother-infant bonding, may be more resilient to external pressures such as a pandemic than affective states such as PPD. (174 words).

A paradoxical role of childbirth-related posttraumatic stress disorder (PTSD) symptoms in the association between personality factors and mother-infant bonding: A cross-sectional study.

OBJECTIVE: As mother-infant bonding difficulties are potentially detrimental to child development, it is of importance to study its etiology and associated factors. Only a minority of studies have focused on the role of personality and postpartum depression and posttraumatic stress disorder (PTSD) in the etiology of bonding difficulties. The present article attempted to ascertain the association of vulnerability (Neuroticism) and resilience (Dispositional Optimism) with bonding, wherein postpartum depression and PTSD symptoms were possible mediators. METHOD: There were 504 mothers of infants, 0-13 months, who were sampled cross-sectionally using social media. Respondents completed an online survey consisting of the following questionnaires: demographic details, Neuroticism (subscale of the Big Five Inventory, BFI), Dispositional Optimism (Life Orientation Test-Revised), postpartum PTSD symptoms (City Birth Trauma Scale, BiTS), postpartum depression symptoms (Edinburgh Postpartum Depression Scale, EPDS), and mother-infant bonding difficulties (Postpartum Bonding Questionnaire, PBQ). RESULTS: Path analysis revealed 5 significant indirect paths: Dispositional Optimism affected bonding through EPDS (ß = -0.04, p = .010) and through BiTS general symptoms (ß = -.02, p = .019), and BFI-Neuroticism affected bonding through EPDS (ß = 0.14, p = .001), BiTS birth-related symptoms (ß = -0.03, p = .013), and BiTS general symptoms (ß = 0.11, p = .001). CONCLUSIONS: Both Dispositional Optimism and Neuroticism correlated with bonding difficulties, mediated by postpartum depression and PTSD symptoms. When all variables were measured in a single model, postpartum PTSD birth-related symptoms predicted fewer bonding difficulties while general postpartum PTSD symptoms were associated with more bonding difficulties. Taken together, these results can promote better understanding of postpartum psychopathology and mother-infant bonding to allow for better treatments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sleep restriction alters physiological and emotional responses to emotion induction.

NEW FINDINGS: What is the central question of this study? The aim of the present study was to assess the effects of sleep restriction on self-report and autonomic responses to neutral and sad film clips. What is the main finding and its importance? Ratings of sadness and heart rate deceleration were greater while watching the sad clip, with no effect of sleep restriction, whereas heart rate variability and skin conductance were impacted by sleep restriction and, to a lesser extent, by film clips. The results suggest that autonomic function was adaptively altered by sleep restriction, in order to maintain a 'normal' response to emotional cues, despite mounting fatigue. ABSTRACT: Habitual insufficient sleep has long-term health consequences via its impact on autonomic nervous system (ANS) function and on regulation of emotion. To our knowledge, the effects of insufficient sleep on emotion-induced ANS function have not been tested. The present study aimed to address this lacuna. Using an emotion induction procedure, the effects of sleep restriction on physiological responses to validated neutral and sad film clips were assessed in a two-by-two, pseudo-randomized, cross-over design. Thirty-one participants, aged 20-33 years, were assessed after sleeping for either 5 h (sleep restricted, SR) or 8 h (well rested, WR) per night, for three consecutive nights. Physiological measures included heart rate, heart rate variability, skin conductance response (SCR) and participants' ratings of affect and fatigue. There was no effect of sleep conditions on self-reported negative affect, but watching the sad clip reduced self-reported fatigue in the SR condition. There was greater heart rate deceleration while watching sad relative to neutral clips, independent of the sleep condition. Sleep restriction increased heart rate variability measures, with no effect of emotion induction. There was an interaction of emotion induction with sleep condition for SCR, with more SCRs to sad relative to neutral clips in the WR condition, and the opposite effect in the SR condition. Combined, the results suggest that the ANS response to an emotional cue was altered by sleep restriction. The results suggest an adaptive ANS response to mild, chronic sleep restriction, resulting in constant heart rate response and self-reported experience across WR and SR conditions, despite mounting fatigue.

Mother-infant bonding is not associated with feeding type: a community study sample.

BACKGROUND: Bonding refers to emotions and cognitions towards one's infant. Breastfeeding is believed to facilitate bonding, yet only a handful of studies have empirically tested this assertion. This study aimed to confirm whether a positive association between breastfeeding and bonding exists and whether breastfeeding may be protective against the negative consequences of mood and sleep disturbances on bonding. METHOD: A cross-sectional survey was administered to a convenience sample of Israeli mothers of infants ages 1-9 months. The main outcome measures were breastfeeding history, bonding (Postpartum Bonding Questionnaire, PBQ), mood (Edinburgh Postnatal Depression Scale, EPDS) and sleep (Pittsburgh Sleep Quality Index, PSQI). RESULTS: Two hundred seventy-one mothers (21-46 years) completed the survey. 65.7% reported current breastfeeding, 22.1% past breastfeeding, 12.2% never nursed. The PBQ correlated with both the EPDS and PSQI. Breastfeeding was associated with greater daytime fatigue, but not with any other sleep problem, and was not associated with bonding. This negative result was confirmed with Bayesian analysis demonstrating that the probability for the null hypothesis was 4.5 times greater than the hypothesized effect. Further, hierarchical regression revealed a positive relationship between bonding, daytime fatigue and depression symptoms only among women who were currently breastfeeding. CONCLUSIONS: These findings suggest that among healthy mothers, breastfeeding may not be a central factor in mother-infant bonding, nor is it protective against the negative impact of mood symptoms and bonding difficulties. Theoretical and methodological bases of these findings are discussed.

Construct Validity and Psychometric Properties of the Hebrew Version of the City Birth Trauma Scale.

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.

Maternal depressed mood moderates the impact of infant sleep on mother-infant bonding.

Parent-infant bonding has long-term consequences for the psychological wellbeing of the child. Considering the centrality of infant sleep patterns in infant-caregiver interactions in the first year of life, we propose that infant sleep patterns act as a catalyst or disruptor for mother-infant relationship, such that infant sleep patterns contribute to maternal mood, maternal sleep quality, perception of infant temperament, and her bonding experience. One hundred fifty-two Israeli mothers, of 5-8-month-old infants, responded to Internet-based questionnaires regarding their sleep, their mood, their infant's sleep, the infant's temperament, and their bonding experience. Eight percent of the mothers reported clinically significant depression, while 67 % reported significant sleep difficulties. Infant sleep difficulties correlated with maternal mood and sleep quality, infant fussiness, and bonding. Structural equation modeling demonstrated that maternal sleep partially mediated the relationship between infant sleep and maternal mood. Additionally, 22 % of the variance in bonding was explained by infant sleep problems and temperament. Notably, maternal depression moderated this effect such that infant sleep problems correlated with bonding only in those mothers who were depressed. The results suggest that infant sleep is a vector by which maternal cognitions and mood are transmitted to her child, with long-term implications for psychological development.

Sleep mediates the link between resiliency and behavioural problems in children at high and low risk for alcoholism.

Children of alcoholic parents are at greater risk for developing substance use problems. Having a parent with any mental illness increases the risk for sleep disorders in children. Using actigraphy, this study characterized sleep in children of alcoholics and community controls over a period of 1 week. This study further examined whether sleep characteristics of the children mediated the relationship between self-regulation indices (i.e. undercontrol and resiliency) and outcome measures of function (e.g. problem behaviours and perceived conflict at home). Eighty-two children (53 boys, 29 girls, 7.2-13.0 years old) were recruited from the ongoing Michigan Longitudinal Study. Seventeen participants had no parental history of alcohol abuse or dependence family history negative (FH-), 43 had at least one parent who was a recovered alcoholic, and 22 had at least one parent who met diagnostic criteria within the past 3 years. Sleep was assessed with actigraphy and sleep diaries for 1 week, and combined with secondary analysis of data collected for the longitudinal study. FH- children had more objectively measured total sleep time. More total sleep time was associated with greater resiliency and behavioural control, fewer teacher-reported behavioural problems, and less child-reported conflict at home. Further, total sleep time partially mediated the relationship between resiliency and perceived conflict, and between resiliency and externalizing problems. These findings suggest that in high-risk homes, the opportunity to obtain sufficient sleep is reduced, and that insufficient sleep further exacerbates the effects of impaired dispositional self-regulatory capacity on behavioural and emotional regulation.

Odors enhance slow-wave activity in non-rapid eye movement sleep.

Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9-15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5-4 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations.

Humans can learn new information during sleep.

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.

Dim light melatonin onset in alcohol-dependent men and women compared with healthy controls.

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean ± SD age: 36.0 ± 11.0 yrs of age, 10 women) who were 3-12 wks since their last drink (abstinence: 57.9 ± 19.3 d) and 19 age- and sex-matched HCs (34.4 ± 10.6 yrs, 5 women). Following a 23:00-06:00 h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00 h bedtime) during which salivary melatonin samples were collected every 30 min beginning at 19:30 h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02 ± 00:41 h, than in HC, 20:44 ± 00:21 h (t = -2.4, p = .02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18 min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats.

A test of the bidirectional association between sleep and mood in bipolar disorder and insomnia.

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.

The role of infant sleep in intergenerational transmission of trauma.

INTRODUCTION: Children of parents who experienced trauma often present emotional and behavioral problems, a phenomenon named inter-generational transmission of trauma (IGTT). Combined with antenatal factors, parenting and the home environment contribute to the development and maintenance of sleep problems in children. In turn, infant sleep difficulty predicts behavioral and emotional problems later in life. The aim of this study was to investigate whether infant sleep problems predict early behavioral problems indicative of IGTT. METHODS: 184 first-time mothers (ages 18-47) participated. N=83 had a history of childhood abuse and posttraumatic stress disorder (PTSD+); 38 women reported childhood abuse but did not meet diagnostic criteria for PTSD (PTSD-); and the control group (N=63) had neither a history of abuse nor psychopathology (CON). Depression, anxiety, and sleep difficulty were assessed in the mothers at 4 months postpartum. Infant sleep was assessed using the Child Behavior Sleep Questionnaire (CSHQ). Outcome measures included the Parent Bonding Questionnaire (PBQ) at 4 months and the Child Behavior Check List (CBCL) at 18 months. RESULTS: Infants of PTSD+ mothers scored higher on the CSHQ and had more separation anxiety around bedtime than PTSD- and CON, and the severity of their symptoms was correlated with the degree of sleep disturbance. Maternal postpartum depression symptoms mediated impaired mother-infant bonding, while infant sleep disturbance contributed independently to impaired bonding. Mother-infant bonding at 4 months predicted more behavioral problems at 18 months. CONCLUSIONS: Infant sleep difficulties and maternal mood play independent roles in infant-mother bonding disturbance, which in turn predicts behavioral problems at 18 months.

Sensory gating in primary insomnia.

Although previous research indicates that sleep architecture is largely intact in primary insomnia (PI), the spectral content of the sleeping electroencephalographic trace and measures of brain metabolism suggest that individuals with PI are physiologically more aroused than good sleepers. Such observations imply that individuals with PI may not experience the full deactivation of sensory and cognitive processing, resulting in reduced filtering of external sensory information during sleep. To test this hypothesis, gating of sensory information during sleep was tested in participants with primary insomnia (n = 18) and good sleepers (n = 20). Sensory gating was operationally defined as (i) the difference in magnitude of evoked response potentials elicited by pairs of clicks presented during Wake and Stage II sleep, and (ii) the number of K complexes evoked by the same auditory stimulus. During wake the groups did not differ in magnitude of sensory gating. During sleep, sensory gating of the N350 component was attenuated and completely diminished in participants with insomnia. P450, which occurred only during sleep, was strongly gated in good sleepers, and less so in participants with insomnia. Additionally, participants with insomnia showed no stimulus-related increase in K complexes. Thus, PI is potentially associated with impaired capacity to filter out external sensory information, especially during sleep. The potential of using stimulus-evoked K complexes as a biomarker for primary insomnia is discussed.

The effect of mood on sleep onset latency and REM sleep in interepisode bipolar disorder.

The present study investigates whether interepisode mood regulation impairment contributes to disturbances in sleep onset latency (SOL) and rapid eye movement (REM) sleep. Individuals with interepisode bipolar disorder (n = 28) and healthy controls (n = 28) slept in the laboratory for 2 baseline nights, a happy mood induction night, and a sad mood induction night. There was a significant interaction whereby on the happy mood induction night the bipolar group exhibited significantly longer SOL than did the control group, while there was no difference on the baseline nights. In addition, control participants exhibited shorter SOL on the happy mood induction night compared to the baseline nights, a finding that was not observed in the bipolar group. On the sad mood induction night, participants in both groups had shorter SOL and increased REM density when compared to the baseline nights. Bipolar participants exhibited heightened REM density compared to control participants on both nights. These results raise the possibility that regulation of positive stimuli may be a contributor to difficulties with SOL, while hyperactivity may be characteristic of REM sleep.

Neural mechanisms of the time-order error: an MEG study.

The time-order error (TOE) refers to the influence of presentation order on performance accuracy in a discrimination task. Despite it being a well-documented perceptual bias, the underlying mechanisms have not been studied. In this study, observers were trained on a two-interval forced-choice procedure. The stimuli presented for discrimination were a standard, consisting of four tones presented at a 5-Hz rate, and targets, consisting of various rates higher than 5 Hz. Psychometric functions were measured for discrimination of the trained standard and targets, a novel standard of 13 Hz with higher target rates; and the trained 5 Hz standard with novel targets with rates below 5 Hz. Discrimination did not improve with training; in fact, accuracy declined when standard was presented in the first interval during the session, resulting in a TOE. The TOE was specific to the 5-Hz standard generalizing to the novel targets slower than 5 Hz, but not to the 13-Hz STANDARD. Analysis of the event-related magnetic field responses (ERFs) revealed a waveform to the whole stimulus, rather than to each tone in the train. Although ERFs in the second interval were attenuated independent of stimulus type, the M300 component in the second interval was attenuated only when the standard was first, but remained of equivalent magnitude when the standard was second. This was observed only in the two 5-Hz conditions. Combined, these results suggest that the TOE reflects the emergence of an internal representation of the standard, and that the M300 is potentially a neural correlate of plasticity.

Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning.

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.

Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice.

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.