Summary:
A prospective study of more than 2,400 pregnant women reveals that developing restless legs syndrome (RLS) during pregnancy is tied to a threefold increase in the risk of perinatal depression. The vulnerability peaks during the third trimester, when severe evening leg discomfort and sleep disruption compound emotional strain, highlighting late-pregnancy RLS screening as a vital opportunity for early maternal mental health intervention.
Key Facts:
- Threefold Depression Risk: Expectant mothers who developed restless legs syndrome faced roughly three times the risk of major perinatal depression and twice the likelihood of elevated depressive symptoms compared to unaffected peers.
- Third-Trimester Timing: The heightened depression risk was specifically associated with RLS identified during the third trimester, with no significant elevation observed when symptoms appeared solely in the second trimester.
- Controlled Confounders: The robust association remained significant even after controlling for maternal age, education, partner status, occupation, parity, and whether the pregnancy was planned.
Source: American Academy of Sleep Medicine (AASM) / University of Tokyo
Perinatal depression, encompassing major depressive episodes occurring during pregnancy or across the vulnerable first months postpartum, affects millions of new mothers worldwide, impairing maternal health and early infant bonding. While biological, hormonal, and psychosocial stressors are well-known contributors, sleep-related movement disorders have largely flown under the diagnostic radar.
Now, a prospective investigation led by researchers from the University of Tokyo Graduate School of Medicine points to restless legs syndrome (RLS) as a substantial clinical warning sign for perinatal mental health decline.
Publishing in the Journal of Clinical Sleep Medicine, the official publication of the American Academy of Sleep Medicine, the team followed 2,435 pregnant women in Japan to trace the connection between gestational RLS onset and subsequent depressive episodes through three months after childbirth.
Sleep Disruption as a Neurological Trigger
Restless legs syndrome is a sensorimotor neurological disorder defined by an irresistible urge to move the legs, typically driven by unpleasant creeping, crawling, or pulling sensations deep within the limbs. Because these symptoms emerge during rest, peak late in the evening, and temporarily resolve only with active movement, RLS causes severe sleep fragmentation, prolonging the time it takes to fall asleep and destroying restorative slow-wave rest.
In the general adult population, individuals with RLS experience depression and anxiety at approximately four times the national average. During pregnancy, physiological shifts, including fluctuating dopamine levels, surging estrogen, and transient maternal iron deficiency, frequently trigger or unmask dormant RLS symptoms.
The Tokyo study tracked women across gestation: 1.6% (40 participants) screened positive for RLS during their second trimester, while prevalence climbed to 3.5% (60 participants) by the third trimester. Following delivery, 69 women across the broader cohort developed full clinical perinatal depression.
The statistical modeling delivered a stark correlation: pregnant women with RLS were three times more likely to experience perinatal depression and twice as likely to report clinically meaningful depressive symptoms.
“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, a visiting researcher in the Department of Mental Health at the University of Tokyo Graduate School of Medicine. “This association was seen for restless legs syndrome identified in the third trimester, but not in the second.”
Crucially, this vulnerability held firm after adjusting for confounding variables including maternal age, education level, socioeconomic indicators, partner support, number of prior children, and pregnancy intention.
The Crucial Window of Late-Stage Screening
The finding that risk concentrates in the third trimester reflects the cumulative biological strain of late pregnancy. As fetal growth peaks, physical discomfort and insomnia are already pronounced; the sudden onset of persistent nocturnal leg agitation can push an already strained neurobiological system into severe affective distress.
Currently, routine prenatal intake forms assess sleep and movement complaints predominantly in the first trimester, if at all. Because gestational RLS predominantly manifests as the third trimester approaches, standard clinical evaluations frequently miss the disorder entirely.
“Because restless legs syndrome often develops later in pregnancy, asking about its symptoms again in the third trimester, not just at early prenatal visits, may help healthcare providers identify women at higher risk of perinatal depression,” emphasized Tezuka.
Moving Toward Targeted Preventative Care
The researchers noted several study caveats: the observed RLS prevalence in this cohort was lower than typical Western cohorts, the overall count of depressive episodes among RLS-affected mothers was modest, and measures relied on validated self-reported instruments.
Nevertheless, recognizing RLS as an early biomarker provides clinicians with a concrete, actionable intervention point. Future research will explore whether non-pharmacological RLS treatments, such as targeted iron supplementation, stretching regimens, and specialized sleep hygiene, can directly lower subsequent rates of postpartum and perinatal depression, protecting both mother and child during the transition into parenthood.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this RSL and depression Research:
- Media Contact: Taylor Spanbauer
- Source: AASM
- Image Credit: Image credited to Neuroscience News
- Original Research is Open Access: Journal of Clinical Sleep Medicine (Oct 1, 2026). “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
Previous studies have reported associations between restless legs syndrome (RLS) and perinatal depressive symptoms. However, no study has used diagnostic instruments to examine changes in RLS status during pregnancy in relation to the incidence of perinatal depression. This study aimed to investigate whether time-varying RLS status is associated with an increased risk of incident perinatal depression.
Methods
This prospective cohort study analyzed data from 2435 Japanese pregnant women in the control group of a randomized controlled trial on perinatal depression. Time-varying RLS status was assessed using data obtained 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 3 months postpartum were assessed using the self-administered World Health Organization Composite International Diagnostic Interview 3.0 and the Edinburgh Postnatal Depression Scale (EPDS), respectively. Associations were examined using Cox proportional hazards models with time-varying covariates.
Results
The prevalence of RLS was 40 (1.6%) in the second trimester and 60 (3.5%) in the third trimester. During a mean follow-up of 6.5 months (SD, 3.2), 69 participants developed perinatal depression. Time-varying RLS status was significantly associated with an increased risk of incident perinatal depression (hazard ratio [HR], 3.04; 95% CI, 1.22–7.58) and depressive symptoms (EPDS ≥ 13; HR, 2.12; 95% CI, 1.28–3.51). These associations remained robust after adjustment for potential confounders.
Conclusion
RLS, modeled as a time-varying condition, was associated with an increased risk of incident perinatal depression, suggesting the importance of screening for RLS during pregnancy for the prevention of perinatal depression.
Brief summary
Current knowledge/study rationale
RLS is common during pregnancy and has been linked to depressive symptoms, possibly through shared pathophysiological mechanisms such as sleep disturbances and iron deficiency; however, longitudinal evidence using diagnostic instruments remains limited. This study examined whether time-varying RLS status is associated with incident perinatal depression.
Study impact
Pregnant women with RLS, particularly in the third trimester, had an increased risk of perinatal depression, suggesting the clinical importance of routine RLS screening to support timely treatment and potentially prevent perinatal depression. Increased awareness of RLS among pregnant women and healthcare providers may promote early identification of individuals at higher risk. However, whether RLS treatment can reduce perinatal depression risk requires further investigation.
