Integration of Prior Expectations and Suppression of Prediction Errors During Expectancy-Induced Pain Modulation: The Influence of Anxiety and Pleasantness.

Pain perception arises from the integration of prior expectations with sensory information. Although recent work has demonstrated that treatment expectancy effects (e.g., placebo hypoalgesia) can be explained by a Bayesian integration framework incorporating the precision level of expectations and sensory inputs, the key factor modulating this integration in stimulus expectancy-induced pain modulation remains unclear. In a stimulus expectancy paradigm combining emotion regulation in healthy male and female adults, we found that participants' voluntary reduction in anticipatory anxiety and pleasantness monotonically reduced the magnitude of pain modulation by negative and positive expectations, respectively, indicating a role of emotion. For both types of expectations, Bayesian model comparisons confirmed that an integration model using the respective emotion of expectations and sensory inputs explained stimulus expectancy effects on pain better than using their respective precision. For negative expectations, the role of anxiety is further supported by our fMRI findings that (1) functional coupling within anxiety-processing brain regions (amygdala and anterior cingulate) reflected the integration of expectations with sensory inputs and (2) anxiety appeared to impair the updating of expectations via suppressed prediction error signals in the anterior cingulate, thus perpetuating negative expectancy effects. Regarding positive expectations, their integration with sensory inputs relied on the functional coupling within brain structures processing positive emotion and inhibiting threat responding (medial orbitofrontal cortex and hippocampus). In summary, different from treatment expectancy, pain modulation by stimulus expectancy emanates from emotion-modulated integration of beliefs with sensory evidence and inadequate belief updating.

Understanding the heterogeneity of anxiety using a translational neuroscience approach.

Anxiety disorders affect millions of people worldwide and present a challenge in neuroscience research because of their substantial heterogeneity in clinical presentation. While a great deal of progress has been made in understanding the neurobiology of fear and anxiety, these insights have not led to effective treatments. Understanding the relationship between phenotypic heterogeneity and the underlying biology is a critical first step in solving this problem. We show translation, reverse translation, and computational modeling can contribute to a refined, cross-species understanding of fear and anxiety as well as anxiety disorders. More specifically, we outline how animal models can be leveraged to develop testable hypotheses in humans by using targeted, cross-species approaches and ethologically informed behavioral paradigms. We discuss reverse translational approaches that can guide and prioritize animal research in nontraditional research species. Finally, we advocate for the use of computational models to harmonize cross-species and cross-methodology research into anxiety. Together, this translational neuroscience approach will help to bridge the widening gap between how we currently conceptualize and diagnose anxiety disorders, as well as aid in the discovery of better treatments for these conditions.

Sleep loss and emotion: A systematic review and meta-analysis of over 50 years of experimental research.

In a largely sleep-deprived society, quantifying the effects of sleep loss on emotion is critical for promoting psychological health. This preregistered systematic review and meta-analysis quantified the effects of various forms of sleep loss on multiple aspects of emotional experiences. Eligible studies used experimental reductions of sleep via total sleep deprivation, partial sleep restriction, or sleep fragmentation in healthy populations to examine effects on positive affect, negative affect, general mood disturbances, emotional reactivity, anxiety symptoms, and/or depressive symptoms. In total, 1,338 effect sizes across 154 studies were included (N = 5,717; participant age range = 7-79 years). Random effects models were conducted, and all forms of sleep loss resulted in reduced positive affect (standardized mean difference [SMD] = -0.27 to -1.14), increased anxiety symptoms (SMD = 0.57-0.63), and blunted arousal in response to emotional stimuli (SMD = -0.20 to -0.53). Findings for negative affect, reports of emotional valence in response to emotional stimuli, and depressive symptoms were mixed and depended on the type of sleep loss. Nonlinear effects for the amount of sleep loss as well as differences based on the stage of sleep restricted (i.e., rapid eye movement sleep or slow-wave sleep) were also detected. This study represents the most comprehensive quantitative synthesis of experimental sleep and emotion research to date and provides strong evidence that periods of extended wakefulness, shortened sleep duration, and/or nighttime awakenings adversely influence human emotional functioning. Findings provide an integrative foundation for future research on sleep and emotion and elucidate the precise ways that inadequate sleep may impact our daytime emotional lives. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The VLPFC-Engaged Voluntary Emotion Regulation: Combined TMS-fMRI Evidence for the Neural Circuit of Cognitive Reappraisal.

A clear understanding of the neural circuit underlying emotion regulation (ER) is important for both basic and translational research. However, a lack of evidence based on combined neuroimaging and neuromodulation techniques calls into question (1) whether the change of prefrontal-subcortical activity intrinsically and causally contributes to the ER effect; and (2) whether the prefrontal control system directly modulates the subcortical affective system. Accordingly, we combined fMRI recordings with transcranial magnetic stimulation (TMS) to map the causal connections between the PFC and subcortical affective structures (amygdala and insula). A total of 117 human adult participants (57 males and 60 females) were included in the study. The results revealed that TMS-induced ventrolateral PFC (VLPFC) facilitation led to enhanced activity in the VLPFC and ventromedial PFC (VMPFC) as well as attenuated activity in the amygdala and insula during reappraisal but not during nonreappraisal (i.e., baseline). Moreover, the activated VLPFC intensified the prefrontal-subcortical couplings via the VMPFC during reappraisal only. This study provides combined TMS-fMRI evidence that downregulating negative emotion involves the prefrontal control system suppressing the subcortical affective system, with the VMPFC serving as a crucial hub within the VLPFC-subcortical network, suggesting an indirect pathway model of the ER circuit. Our findings outline potential protocols for improving ER ability by intensifying the VLPFC-VMPFC coupling in patients with mood and anxiety disorders.SIGNIFICANCE STATEMENT Using fMRI to examine the TMS effect, we uncovered that the opposite neural changes in prefrontal (enhanced) and subcortical (attenuated) regions are not a byproduct of emotion regulation (ER); instead, this prefrontal-subcortical activity per se causally contributes to the ER effect. Furthermore, using TMS to amplify the neural changes within the ER circuit, the "bridge" role of the VMPFC is highlighted under the reappraisal versus nonreappraisal contrast. This "perturb-and-measure" approach overcomes the correlational nature of fMRI data, helping us to identify brain regions that causally support reappraisal (the VLPFC and VMPFC) and those that are modulated by reappraisal (the amygdala and insula). The uncovered ER circuit is important for understanding the neural systems underlying reappraisal and valuable for translational research.

Gut enterochromaffin cells drive visceral pain and anxiety.

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain1. For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved2. Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men1. Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium3-5. EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings3,6 but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation7,8. Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell-mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell-mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain.

Cardiogenic control of affective behavioural state.

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1-3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3-8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.

The effect of inherently threatening contexts on visuocortical engagement to conditioned threat.

Fear and anxiety are crucial for adaptive responding in life-threatening situations. Whereas fear is a phasic response to an acute threat accompanied by selective attention, anxiety is characterized by a sustained feeling of apprehension and hypervigilance during situations of potential threat. In the current literature, fear and anxiety are usually considered mutually exclusive, with partially separated neural underpinnings. However, there is accumulating evidence that challenges this distinction between fear and anxiety, and simultaneous activation of fear and anxiety networks has been reported. Therefore, the current study experimentally tested potential interactions between fear and anxiety. Fifty-two healthy participants completed a differential fear conditioning paradigm followed by a test phase in which the conditioned stimuli were presented in front of threatening or neutral contextual images. To capture defense system activation, we recorded subjective (threat, US-expectancy), physiological (skin conductance, heart rate) and visuocortical (steady-state visual evoked potentials) responses to the conditioned stimuli as a function of contextual threat. Results demonstrated successful fear conditioning in all measures. In addition, threat and US-expectancy ratings, cardiac deceleration, and visuocortical activity were enhanced for fear cues presented in threatening compared with neutral contexts. These results are in line with an additive or interactive rather than an exclusive model of fear and anxiety, indicating facilitated defensive behavior to imminent danger in situations of potential threat.

Effects of wheel-running on anxiety and depression-relevant behaviours in the MCAO mouse model of stroke: moderation of brain-derived neurotrophic factor and serotonin receptor gene expression.

Stroke continues to be a major cause of mortality globally. Post-stroke treatment is complicated by the heterogenous nature of pathology and the emergence of secondary psychological symptoms are an additional challenge to the recovery process. Poststroke depression (PSD) is a common co-morbidity and is a major impediment to recovery. While selective serotonin reuptake inhibitors (SSRIs) have proven to be clinically efficacious in treating PSD, the pathogenic processes that underlie the manifestation of depressive mood post-stroke remains unclear. Furthermore, the use of SSRIs is associated with risks of intracerebral haemorrhage, so alternative treatment options need to be continuously explored. Exercise has been demonstrated to be beneficial for improving mood in humans and preclinical models of neurological conditions. Little is known of the mood-related benefits of physical exercise post-stroke. Using the middle cerebral artery occlusion (MCAO) mouse model of cerebral ischaemia, we investigated whether behavioural deficits emerge post-MCAO and could be rescued by voluntary wheel-running. We report that MCAO induced hypo-locomotion and anhedonia-related behaviours, with some improvements conferred by wheel-running. Serotonin transporter gene expression was increased in the MCAO hippocampus and frontal cortex, but this increase remained despite wheel-running. Wheel-running associated up-regulation of BDNF gene expression was unaffected in MCAO mice, reflecting conservation of key neuroplasticity molecular pathways. Taken together, our results highlight the need for further research into serotonergic modulation of the affective symptoms of stroke.

Sleeping off stress.

Social defeat activates midbrain cells, promoting sleep and reducing anxiety in mice.

Maternal age and maternal environment affect egg composition, yolk testosterone, offspring growth and behaviour in laying hens.

Maternal effects have been reported to alter offspring phenotype in laying hens. In this study, we investigated the effects of maternal environment and maternal age on egg traits and offspring development and behaviour. For this, we ran two experiments. First (E1), commercial hybrid hens were reared either in aviary or barren brooding cages, then housed in aviary, conventional cages or furnished (enriched) cages, thus forming different maternal housing treatments. Hens from each treatment were inseminated at three ages, and measures of egg composition, yolk testosterone concentration and offspring's development, anxiety and fearfulness were assessed. In experiment 2 (E2), maternal age effects on offspring's growth and behaviour were further investigated using fertile eggs from commercial breeder flocks at three different ages. Results from E1 showed that Old hens laid heavier eggs with less yolk testosterone and produced offspring with fewer indicators of anxiety and fearfulness. Maternal rearing and housing affected egg traits, offspring weight and behaviour, but not in a consistent way. Effects of maternal age were not replicated in E2, possibly due to differences in management or higher tolerance to maternal effects in commercial breeders. Overall, our research confirms that maternal age and maternal environment affects egg composition, with maternal age specifically affecting yolk testosterone concentration, which may mediate physical and behavioural effects in offspring.

NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model.

Emotional stress is considered a severe pathogenetic factor of psychiatric disorders. However, the circuit mechanisms remain largely unclear. Using a three-chamber vicarious social defeat stress (3C-VSDS) model in mice, we here show that chronic emotional stress (CES) induces anxiety-like behavior and transient social interaction changes. Dopaminergic neurons of ventral tegmental area (VTA) are required to control this behavioral deficit. VTA dopaminergic neuron hyperactivity induced by CES is involved in the anxiety-like behavior in the innate anxiogenic environment. Chemogenetic activation of VTA dopaminergic neurons directly triggers anxiety-like behavior, while chemogenetic inhibition of these neurons promotes resilience to the CES-induced anxiety-like behavior. Moreover, VTA dopaminergic neurons receiving nucleus accumbens (NAc) projections are activated in CES mice. Bidirectional modulation of the NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior. In conclusion, we propose that a NAc-VTA circuit critically establishes and regulates the CES-induced anxiety-like behavior. This study not only characterizes a preclinical model that is representative of the nuanced aspect of CES, but also provides insight to the circuit-level neuronal processes that underlie empathy-like behavior.

Beneficial effects of voluntary wheel running on activity rhythms, metabolic state, and affect in a diurnal model of circadian disruption.

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). Voluntary exercise strengthened general activity rhythms, improved memory and lowered anxiety- and depressive-like behaviors, enhanced oral glucose tolerance, and decreased plasma insulin levels and liver weight. Animals with access to a running wheel had larger heart weight and heart/body weight ratio, and thicker left ventricular wall. Our results demonstrate that exercising ameliorates pathological-like daily rhythms in activity and blood glucose levels, glucose tolerance and depressive- and anxiety-like behaviors in the sand rat model, supporting the important role of physical activity in modulating the "circadian syndrome" and circadian rhythm-related diseases. We suggest that the utilization of a diurnal rodent animal model may offer an effective way to further explore metabolic, cardiovascular, and affective-like behavioral changes related to chronodisruption and their underlying mechanisms.

Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice.

Psoriasis is a common inflammatory skin disorder, which can be associated with psychological disorders, such as anxiety and depression. This study investigated the efficacy and the mechanism of action of a natural compound coptisine using imiquimod (IMQ)-induced psoriasis mice. Coptisine reduced the severity of psoriasis-like skin lesions, decreased epidermal hyperplasia and the levels of inflammatory cytokines TNF-α, IL-17, and IL-22. Furthermore, coptisine improved IMQ-induced anxiety in mice by increasing the number of entries and time in open arms in the elevated plus maze (EPM) test. Coptisine also lowered the levels of inflammatory cytokines TNF-α and IL-1ß in the prefrontal cortex of psoriasis mice. HaCaT keratinocytes and BV2 microglial cells were used to investigate the effects of coptisine in vitro. In M5-treated HaCaT cells, coptisine decreased the production of IL-6, MIP-3α/CCL20, IP-10/CXCL10, and ICAM-1 and suppressed the NF-κB signaling pathway. In LPS-stimulated BV2 cells, coptisine reduced the secretion of TNF-α and IL-1ß. These findings suggest that coptisine might be a potential candidate for psoriasis treatment by improving both disease severity and psychological comorbidities.

Assessing cardiovascular links to depression and anxiety in Australian professional drivers.

Train and truck drivers experience a myriad of unique occupational factors, which have been postulated to contribute to a high incidence of health conditions such as depression anxiety and cardiovascular disease amongst this population. The present study aimed to identify associations between heart rate variability and negative mood states such as depression and anxiety in a cohort of Australian truck and train drivers. 120 professional drivers (60 truck drivers, 60 train drivers) were recruited from the local community. Participants complete a battery of psychometric questionnaires to assess levels of negative mood states such as depression and anxiety. Participants then completed a baseline (resting) and active (driving) task while concurrent electrocardiography data was collected to obtain heart rate variability parameters. Anxiety and depression were found to be associated with increases in low frequency heart rate variability and sympathovagal balance, and a reduction in total power. The present study identified associations between negative mood states and heart rate variability parameters that are unique to this cohort.

Dietary rescue of adult behavioral deficits in the Fmr1 knockout mouse.

The current study aimed to further address important questions regarding the therapeutic efficacy of omega-3 fatty acids for various behavioral and neuroimmune aspects of the Fmr1 phenotype. To address these questions, our experimental design utilized two different omega-3 fatty acid administration timepoints, compared to both standard laboratory chow controls ("Standard") and a diet controlling for the increase in fat content ("Control Fat"). In the first paradigm, post-weaning supplementation (after postnatal day 21) with the omega-3 fatty acid diet ("Omega-3") reversed deficits in startle threshold, but not deficits in prepulse inhibition, and the effect on startle threshold was not specific to the Omega-3 diet. However, post-weaning supplementation with both experimental diets also impaired acquisition of a fear response, recall of the fear memory and contextual fear conditioning compared to the Standard diet. The post-weaning Omega-3 diet reduced hippocampal expression of IL-6 and this reduction of IL-6 was significantly associated with diminished performance in the fear conditioning task. In the perinatal experimental paradigm, the Omega-3 diet attenuated hyperactivity and acquisition of a fear response. Additionally, perinatal exposure to the Control Fat diet (similar to a "Western" diet) further diminished nonsocial anxiety in the Fmr1 knockout. This study provides significant evidence that dietary fatty acids throughout the lifespan can significantly impact the behavioral and neuroimmune phenotype of the Fmr1 knockout model.

Anxiety-like behavior induced by allergen is associated with decreased irregularity of breathing pattern in rats.

Allergic rhinitis (AR) is a chronic inflammatory disorder associated with a high prevalence of anxiety symptoms and respiratory disorders that adversely affect the quality of life. Studies have shown that allergen exposure induces anxiety-like behaviors. On the other hand, stress impairs the breathing pattern. However, the effect of stress on respiration and the relationship between anxiety-like behavior and stress-induced changes in breathing pattern has not been evaluated in AR. We assessed the impact of ovalbumin (OVA)-induced anxiety-like behaviors on stress-induced breathing pattern changes. Our findings showed that the allergic rhinitis induced by OVA challenge in sensitized rats induces anxiety-like behavior. Also, we found that stress decreases respiratory irregularity and increases respiratory variability, as well as the synchronization between IBI and RV time-series in AR animals. Moreover, in AR animals, we found a significant positive correlation between anxiety-like behavior and respiratory irregularity under non-stress conditions. Besides, a significant negative correlation was observed under stress conditions. The findings showed that anxiety-related behaviors may contribute to respiratory impairments under stress conditions in AR.

State anxiety alters the neural oscillatory correlates of predictions and prediction errors during reward-based learning.

Anxiety influences how the brain estimates and responds to uncertainty. The consequences of these processes on behaviour have been described in theoretical and empirical studies, yet the associated neural correlates remain unclear. Rhythm-based accounts of Bayesian predictive coding propose that predictions in generative models of perception are represented in alpha (8-12 Hz) and beta oscillations (13-30 Hz). Updates to predictions are driven by prediction errors weighted by precision (inverse variance) encoded in gamma oscillations (>30 Hz) and associated with the suppression of beta activity. We tested whether state anxiety alters the neural oscillatory activity associated with predictions and precision-weighted prediction errors (pwPE) during learning. Healthy human participants performed a probabilistic reward-based learning task in a volatile environment. In our previous work, we described learning behaviour in this task using a hierarchical Bayesian model, revealing more precise (biased) beliefs about the tendency of the reward contingency in state anxiety, consistent with reduced learning in this group. The model provided trajectories of predictions and pwPEs for the current study, allowing us to assess their parametric effects on the time-frequency representations of EEG data. Using convolution modelling for oscillatory responses, we found that, relative to a control group, state anxiety increased beta activity in frontal and sensorimotor regions during processing of pwPE, and in fronto-parietal regions during encoding of predictions. No effects of state anxiety on gamma modulation were found. Our findings expand prior evidence on the oscillatory representations of predictions and pwPEs into the reward-based learning domain. The results suggest that state anxiety modulates beta-band oscillatory correlates of pwPE and predictions in generative models, providing insights into the neural processes associated with biased belief updating and poorer learning.

mGlu2/3 receptors within the ventral part of the lateral septal nuclei modulate stress resilience and vulnerability in mice.

Resilience refers to the ability to withstand or recover quickly from difficult conditions. Identification of the neurobiological mechanisms underlying resilience offers a novel way to the prevention and treatment of stress-induced psychiatric disorders such as depression. The septal nuclei have been described as an important node in emotional regulations. Metabotropic glutamate receptors (mGluRs) are abundantly expressed within the septum and play important regulatory roles in its neural activity. In this study, we assessed the functional roles of the mGlu2/3Rs and mGlu5Rs within different subregions of the septum in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in C57BL/6J male mice. Our results showed that approximately 47.9% of subjects exhibited anxiety- or depression-like behaviors after exposure to CSDS. The susceptible mice showed higher c-Fos expression in the lateral septal nucleus after confronted with an attacker. Compared with the resilient and control groups, the expression of mGlu2/3Rs was significantly down-regulated in the ventral part of lateral septal nucleus (LSv), but the expression of mGlu5Rs showed no significant difference among the three groups in the whole septum. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LSv injection of LY379268, an mGlu2/3Rs' agonist. Our findings point to an important role for mGlu2/3Rs in the LSv in promoting stress resilience and may provide potential new therapeutic targets for stress-induced psychiatric disorders, such as anxiety and depression.

Longitudinal Changes in Sleep, Biological Rhythms, and Light Exposure From Late Pregnancy to Postpartum and Their Impact on Peripartum Mood and Anxiety.

Objective: In one of the largest and most comprehensive studies investigating the link between objective parameters of sleep and biological rhythms with peripartum mood and anxiety to date, we prospectively investigated the trajectory of subjective and objective sleep and biological rhythms, levels of melatonin, and light exposure from late pregnancy to postpartum and their relationship with depressive and anxiety symptoms across the peripartum period.Methods: One hundred women were assessed during the third trimester of pregnancy, of whom 73 returned for follow-ups at 1-3 weeks and 6-12 weeks postpartum. Participants were recruited from an outpatient clinic and from the community from November 2015 to May 2018. Subjective and objective measures of sleep and biological rhythms were obtained, including 2 weeks of actigraphy at each visit. Questionnaires validated in the peripartum period were used to assess mood and anxiety.Results: Discrete patterns of longitudinal changes in sleep and biological rhythm variables were observed, such as fewer awakenings (F = 23.46, P < .001) and increased mean nighttime activity (F = 55.41, P < .001) during postpartum compared to late pregnancy. Specific longitudinal changes in biological rhythm parameters, most notably circadian quotient, activity during rest at night, and probability of transitioning from rest to activity at night, were most strongly linked to higher depressive and anxiety symptoms across the peripartum period.Conclusions: Biological rhythm variables beyond sleep were most closely associated with severity of depressive and anxiety symptoms across the peripartum period. Findings from this study emphasize the importance of biological rhythms and activity beyond sleep to peripartum mood and anxiety.