Summary:
A large prospective study of 2,435 pregnant women in Japan found that developing restless legs syndrome (RLS) during pregnancy is associated with about a threefold higher risk of perinatal depression. The risk was strongest when RLS emerged in the third trimester, when evening leg discomfort and sleep disruption are most likely to worsen mood and impair restorative sleep. These findings emphasize the value of targeted late-pregnancy screening for RLS as a practical step to identify women at elevated risk for perinatal depression.
Key Facts:
- Increased depression risk: Pregnant women who developed RLS had approximately three times the risk of a major perinatal depressive episode and about twice the risk of clinically relevant depressive symptoms compared with those without RLS.
- Third-trimester onset matters: The association with perinatal depression was driven by RLS that appeared in the third trimester; RLS limited to the second trimester did not show the same increased risk.
- Association independent of sociodemographic factors: The relationship remained statistically significant after adjusting for maternal age, education, partner status, occupation, parity, and pregnancy intention.
Source: American Academy of Sleep Medicine (AASM) / University of Tokyo
Perinatal depression, which includes major depressive episodes during pregnancy and the months following childbirth, affects many new mothers worldwide and can harm maternal well-being and early mother–infant bonding. While hormonal changes, biological vulnerability, and psychosocial stressors are established contributors, sleep-related movement disorders such as restless legs syndrome have received less clinical attention as potential early warning signs.
Researchers at the University of Tokyo Graduate School of Medicine conducted a prospective cohort study, published in the Journal of Clinical Sleep Medicine, to examine how changes in RLS status across pregnancy relate to the onset of perinatal depression. They followed 2,435 expectant mothers through pregnancy and for three months after delivery, assessing RLS symptoms and depressive outcomes with validated diagnostic questionnaires.
Sleep disruption as a neurological trigger
Restless legs syndrome is a sensorimotor neurological condition characterized by an uncontrollable urge to move the legs, typically prompted by uncomfortable sensations described as creeping, crawling, or pulling deep inside the limbs. Symptoms worsen at rest, peak in the evening, and ease only with movement, producing pronounced sleep fragmentation and loss of restorative slow-wave sleep.
In general adult populations, RLS is linked to higher rates of depression and anxiety. Pregnancy-related physiological changes—shifts in dopamine signaling, rising estrogen levels, and temporary iron deficiency—can trigger or reveal RLS symptoms. In the Tokyo cohort, 1.6% (40 women) screened positive for RLS in the second trimester and 3.5% (60 women) in the third trimester. Across the entire sample, 69 participants developed full clinical perinatal depression during follow-up.
Statistical analyses showed that time-varying RLS status was associated with a threefold increased hazard of incident perinatal depression (hazard ratio 3.04) and a twofold increased hazard for elevated depressive symptoms as measured by the Edinburgh Postnatal Depression Scale (EPDS ≥ 13). These associations persisted after controlling for a range of potential confounders.
“We found that pregnant women with restless legs syndrome had about three times the risk of developing perinatal depression,” said lead author Kazuhide Tezuka, MD, PhD. He noted that this effect was specifically linked to RLS emerging in late pregnancy rather than earlier in the second trimester.
The crucial window of late-stage screening
The concentration of risk in the third trimester likely reflects the growing physical and neurobiological burden of late pregnancy: increasing fetal growth, escalating physical discomfort, and already disrupted sleep. The onset of persistent nighttime leg agitation can further fragment sleep and overload stress-response systems, tipping vulnerable individuals into mood disorders.
Routine prenatal assessments often ask about sleep and movement problems only at initial visits or not at all. Because RLS commonly appears later in pregnancy, brief reassessment in the third trimester could capture new-onset RLS and identify women who may benefit from closer mental health monitoring or early intervention.
Moving toward targeted preventive care
The authors acknowledge limitations: the observed RLS prevalence was lower than reported in some Western studies, the absolute number of depressive episodes among women with RLS was modest, and measures relied on validated self-report instruments rather than clinician-administered interviews for every outcome. Despite these caveats, the study points to RLS as a measurable clinical marker that could guide preventive strategies.
Future trials should test whether treating RLS during pregnancy—using nonpharmacological approaches such as iron repletion when appropriate, targeted exercise or stretching programs, and sleep hygiene interventions—can reduce the subsequent risk of perinatal depression. If effective, such interventions would provide a low-cost, actionable pathway to protect maternal mental health and newborn outcomes.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by editorial staff.
- Additional context was added by the editorial team.
About this RLS and depression research:
- Media Contact: Taylor Spanbauer
- Source: AASM
- Image Credit: Image credited to Neuroscience News
- Original Research: Journal of Clinical Sleep Medicine (Oct 1, 2026). Title: “Time-varying restless legs syndrome and risk of incident perinatal depression.” Authors: Kazuhide Tezuka, Yuka Ito, Natsu Sasaki & Daisuke Nishi.
- DOI: 10.1007/s44470-026-00168-7
Abstract
Time-varying restless legs syndrome and risk of incident perinatal depression
Purpose
Although cross-sectional studies have linked restless legs syndrome to depressive symptoms during pregnancy, longitudinal research using diagnostic instruments to track changes in RLS across gestation has been limited. This study aimed to determine whether time-varying RLS status is associated with increased risk of incident perinatal depression.
Methods
In this prospective cohort analysis, researchers used data from 2,435 pregnant Japanese women enrolled as the control arm of a randomized trial on perinatal depression. RLS status was assessed in the second and third trimesters with the short form of the Cambridge–Hopkins diagnostic questionnaire. Incident major depressive episodes and depressive symptoms from the second trimester to three months postpartum were evaluated using the World Health Organization Composite International Diagnostic Interview 3.0 and the Edinburgh Postnatal Depression Scale (EPDS). Cox proportional hazards models with time-varying covariates were used to analyze associations.
Results
RLS prevalence was 1.6% (40 women) in the second trimester and 3.5% (60 women) in the third trimester. Over an average follow-up of 6.5 months, 69 participants developed perinatal depression. Time-varying RLS was associated with a higher risk of incident perinatal depression (HR 3.04; 95% CI, 1.22–7.58) and elevated depressive symptoms (EPDS ≥ 13; HR 2.12; 95% CI, 1.28–3.51). These relationships remained after adjusting for potential confounders.
Conclusion
Modeling RLS as a time-varying condition revealed an association with increased risk of incident perinatal depression. The findings support routine screening for RLS during pregnancy—especially in the third trimester—as a strategy to identify women at higher risk and enable timely preventive care.
Brief summary
Current knowledge and study rationale
RLS is relatively common in pregnancy and has been associated with depressive symptoms, potentially through mechanisms such as disrupted sleep and iron deficiency. Longitudinal evidence using diagnostic tools to examine how changes in RLS relate to perinatal depression has been scarce; this study addresses that gap by evaluating time-varying RLS status.
Study impact
Women who developed RLS during pregnancy—particularly in the third trimester—had higher rates of perinatal depression, underscoring the clinical value of routine RLS screening late in pregnancy. Greater awareness among pregnant people and health care providers could prompt earlier identification and supportive measures. Whether treating RLS can lower perinatal depression risk remains an important question for future research.