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Exploring Predictive Models of Postpartum Depression and Anxiety Using Non-Invasive Neurophysiological Measures During Pregnancy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Medical psychology and care science. Uppsala University, WoMHeR (Centre for Women's Mental Health during the Reproductive Lifespan).ORCID iD: 0000-0003-3094-5497
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Postpartum depression and anxiety are pervasive and debilitating conditions, yet current risk identification is limited to self-report measures. This thesis examines whether noninvasive physiological measures collected during pregnancy improve prediction of postpartum depression (PPD) and anxiety beyond psychosocial screening. Across two prospective Uppsala cohorts (BASIC; 3PAD), heart rate variability (HRV), prepulse inhibition (PPI) of the acoustic startle response, and task-evoked pupil dilation (PD) were assessed in late pregnancy (BASIC) and at both early and late pregnancy (3PAD). Outcome measures were symptoms of depression and anxiety at six weeks postpartum. In Study I, elastic net models combining HRV with psychosocial variables discriminated PPD (AUC 0.93) and anxiety (AUC 0.83), but inclusion of HRV did not significantly improve accuracy beyond psychosocial predictors. In Study II, logistic regression analyses indicated that reduced PPI at 86 dB predicted de novo PPD among women without antenatal depression (AUC 0.81), with slight gains when covariates were added (AUC 0.91), suggesting potential utility for identifying cases missed by symptom-based screening. In Study III, random-forest models showed HRV from two gestational timepoints provided modest but reliable improvements in predicting PPD and state anxiety, with low frequency/high frequency ratio the most informative index. HRV indices added no incremental value for trait anxiety. In Study IV, elastic-net models including PD achieved good discrimination (AUCs 0.88-0.91) but did not outperform psychosocial predictors. Nevertheless, outcome-specific profiles were observed: PPD was linked to blunted early engagement and reduced sustained effort, state anxiety showed heightened early engagement followed by dampened responses across multiple indices, and trait anxiety involved opposing changes in mobilization speed across pregnancy. These patterns suggest that pupil-linked arousal dynamics may differentiate depression and anxiety outcomes, even if they add little predictive power. Overall, antenatal physiological measures were shown to complement psychosocial screening and provide mechanistic insight into perinatal mood vulnerability. While certain indices showed promise, predictive gains were modest and inconsistent, indicating that these measures are not yet ready for clinical application. Larger, externally validated studies are needed to establish their robustness and to determine whether they can be integrated into multiparametric, tiered risk algorithms to support prevention in perinatal care.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. , p. 74
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2182
Keywords [en]
Postpartum depression, Postpartum anxiety, Perinatal mental health, Pregnancy, Heart rate variability, Prepulse inhibition, Pupil dilation, Neurophysiology, Biomarkers, Predictive modeling
National Category
Psychiatry Gynaecology, Obstetrics and Reproductive Medicine
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-567459ISBN: 978-91-513-2598-9 (print)OAI: oai:DiVA.org:uu-567459DiVA, id: diva2:1999303
Public defence
2025-11-07, Universitetshuset Sal IV, Biskopsgatan 3, 753 10, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2025-10-17 Created: 2025-09-19 Last updated: 2025-10-17
List of papers
1. Investigating heart rate variability measures during pregnancy as predictors of postpartum depression and anxiety: an exploratory study
Open this publication in new window or tab >>Investigating heart rate variability measures during pregnancy as predictors of postpartum depression and anxiety: an exploratory study
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2024 (English)In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 14, no 1, article id 203Article in journal (Refereed) Published
Abstract [en]

Perinatal affective disorders are common, but standard screening measures reliant on subjective self-reports might not be sufficient to identify pregnant women at-risk for developing postpartum depression and anxiety. Lower heart rate variability (HRV) has been shown to be associated with affective disorders. The current exploratory study aimed to evaluate the predictive utility of late pregnancy HRV measurements of postpartum affective symptoms. A subset of participants from the BASIC study (Uppsala, Sweden) took part in a sub-study at pregnancy week 38 where HRV was measured before and after a mild stressor (n = 122). Outcome measures were 6-week postpartum depression and anxiety symptoms as quantified by the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Anxiety Inventory (BAI). In total, 112 women were included in a depression outcome analysis and 106 women were included in an anxiety outcome analysis. Group comparisons indicated that lower pregnancy HRV was associated with depressive or anxious symptomatology at 6 weeks postpartum. Elastic net logistic regression analyses indicated that HRV indices alone were not predictive of postpartum depression or anxiety outcomes, but HRV indices were selected as predictors in a combined model with background and pregnancy variables. ROC curves for the combined models gave an area under the curve (AUC) of 0.93 for the depression outcome and an AUC of 0.83 for the anxiety outcome. HRV indices predictive of postpartum depression generally differed from those predictive of postpartum anxiety. HRV indices did not significantly improve prediction models comprised of psychological measures only in women with pregnancy depression or anxiety.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-528440 (URN)10.1038/s41398-024-02909-9 (DOI)001222549700001 ()38744808 (PubMedID)2-s2.0-85193207486 (Scopus ID)
Funder
Swedish Research Council, 523 – 2014 – 2342 and 523 – 2014 – 0765Magnus Bergvall Foundation, 2017-02165
Available from: 2024-05-22 Created: 2024-05-22 Last updated: 2025-09-19Bibliographically approved
2. The role of prepulse inhibition in predicting new-onset postpartum depression
Open this publication in new window or tab >>The role of prepulse inhibition in predicting new-onset postpartum depression
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2024 (English)In: Nature Mental Health, E-ISSN 2731-6076, Vol. 2, no 8, p. 901-908Article in journal (Refereed) Published
Abstract [en]

Predictive measures for postpartum depression (PPD), which affects around 12% of childbearing women, would enable early, targeted support. Here we explore prepulse inhibition (PPI), a measure of sensorimotor processing, as a biological tool for prediction of women at risk for PPD. Using data from the longitudinal BASIC study in Uppsala, Sweden, we used PPI measures from late pregnancy and reports on depressive symptoms assessed 6 weeks postpartum with the Edinburgh Postnatal Depression Scale to determine the association between pregnancy PPI and PPD. Lower PPI was associated with PPD onset in women who were not depressed during pregnancy. Further studies are encouraged to validate these promising results suggesting PPI as a predictive marker of new-onset PPD.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Gynaecology, Obstetrics and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-546046 (URN)10.1038/s44220-024-00279-1 (DOI)001390111400014 ()
Funder
The Swedish Brain Foundation, FO2022-0098The Swedish Medical Association, SLS-250581
Note

These authors contributed equally: Emma Fransson, Alkistis Skalkidou.

Available from: 2025-01-05 Created: 2025-01-05 Last updated: 2025-09-19Bibliographically approved
3. Exploring Early and Late Pregnancy Heart Rate Variability as Predictors of Postpartum Depression and Anxiety Symptoms
Open this publication in new window or tab >>Exploring Early and Late Pregnancy Heart Rate Variability as Predictors of Postpartum Depression and Anxiety Symptoms
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(English)Manuscript (preprint) (Other academic)
National Category
Psychiatry Gynaecology, Obstetrics and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-567451 (URN)
Available from: 2025-09-17 Created: 2025-09-17 Last updated: 2025-09-19
4. Exploring Pupil Dilation During Pregnancy as a Neurophysiological Predictor of Postpartum Depression and Anxiety Symptoms
Open this publication in new window or tab >>Exploring Pupil Dilation During Pregnancy as a Neurophysiological Predictor of Postpartum Depression and Anxiety Symptoms
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(English)Manuscript (preprint) (Other academic)
National Category
Psychiatry Gynaecology, Obstetrics and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-567453 (URN)
Available from: 2025-09-17 Created: 2025-09-17 Last updated: 2025-09-19

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