Subjective Health Perception Moderates the Antidepressant Effects of Home-Based Transcranial Direct Current Stimulation in Perinatal Women: A Real-World Observational Study

Article information

Psychiatry Investig. 2026;23(1):71-78

Publication date (electronic) : 2025 December 18

doi : https://doi.org/10.30773/pi.2025.0259

Sra Jung^1,*, Hyejin Won^1,*, Soojin Back¹, Hyun-Ju Kim², Jae-Seob Park³, Hee Young Cho^,4,5, Min-Kyoung Kim^,1

¹Department of Psychiatry, CHA Ilsan Medical Center, CHA University School of Medicine, Goyang, Republic of Korea

²Department of Psychiatry, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea

³Department of Psychiatry, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea

⁴Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

⁵Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, Republic of Korea

Correspondence: Hee Young Cho, MD, PhD Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea Tel: +82-2-2072-4033, Fax: +82-2-2762-7251, E-mail: hycho.md@gmail.com

Correspondence: Min-Kyoung Kim, MD, PhD Department of Psychiatry, CHA Ilsan Medical Center, CHA University School of Medicine, 1205 Jungang-ro, Ilsandong-gu, Goyang 10414, Republic of Korea Tel: +82-31-782-3157, Fax: +82-31-782-7567, E-mail: mkkim@chamc.co.kr

*These authors contributed equally to this work.

Received 2025 July 29; Revised 2025 September 30; Accepted 2025 October 20.

Abstract

INTRODUCTION

Perinatal depression refers to depressive symptoms that emerge during infertility treatment, pregnancy, or the postpartum period, representing a prevalent and clinically relevant mental health issue. Globally, an estimated 20%–25% of women experience elevated depressive symptoms during the perinatal period, although prevalence rates vary depending on population characteristics, assessment tools, and healthcare access [1,2]. In South Korea, perinatal mood disturbances are common and frequently undertreated, particularly among women undergoing assisted reproductive treatment [3,4]. These depressive symptoms not only cause individual distress but are also associated with impairing in maternal functioning, strained partner relationships, and adverse effects on infant emotional and cognitive development [5,6]. Therefore, early identification and effective management of perinatal depression should be a public health priority.

Despite its high burden, pharmacologic treatment for perinatal depression is often underutilized due to concerns about fetal safety, teratogenic risk, and medication transfer through breast milk [7,8]. Women undergoing infertility treatment may avoid antidepressants due to concerns about treatment efficacy or reproductive outcomes [9,10], while pregnant and postpartum women frequently experience anxiety about fetal development and neonatal medication exposure during lactation [11]. Consequently, many perinatal women remain undertreated during periods of heightened vulnerability. These barriers underscore the urgent need for safe, accessible, and nonpharmacological interventions that can be flexibly applied across the perinatal continuum. Among these strategies, neuromodulation techniques, such as transcranial direct current stimulation (tDCS), have gained attention for their favorable safety profile, portability, and potential antidepressant effects [12-14].

tDCS is a non-invasive neuromodulation method that delivers low-intensity electrical currents to targeted brain regions. Clinical trials in general populations have demonstrated that tDCS can significantly reduce depressive symptoms, often within the first 1 to 2 weeks of treatment [15]. In particular, stimulation of the left dorsolateral prefrontal cortex (DLPFC), a region involved in cognitive control and emotion regulation, leads to mood improvement by modulating cortical excitability and frontolimbic network activity [16]. Open-label studies in pregnant women with depression have also reported reductions in depressive symptoms following repeated tDCS sessions without the pharmacokinetic or teratogenic risks associated with antidepressant use [13,17]. The portability and ease of use of home-based tDCS devices further support their real-world applicability, enabling flexible deployment across different stages of the perinatal period. These features suggest that tDCS may be a promising and scalable intervention to address current gaps in perinatal mental healthcare.

Despite growing evidence of the efficacy and feasibility of tDCS in alleviating depressive symptoms in perinatal populations [13,17], little is known about individual factors that may influence treatment response. Subjective health perception, defined as an individual’s overall evaluation of their health, has gained attention as a potential indicator of depressive symptom severity in various populations [18,19]. Studies suggest that negative subjective health perception is associated with heightened psychological distress, somatic symptom burden, and poor emotion regulation capacity [20,21]. Perinatal concerns about body changes, pregnancy outcomes, or maternal functioning may influence subjective health perceptions and emotional well-being [22,23]. Despite its subjective nature, perceived health status may reflect broader affective and cognitive vulnerabilities relevant to depression, providing a useful lens for understanding individual differences in treatment response.

Although the antidepressant effects of tDCS and the role of subjective health perceptions have been studied independently, their interaction in perinatal populations remains poorly understood. Given the limitations in pharmacological treatment options during pregnancy, postpartum, and infertility care, this study investigated whether baseline subjective health perception moderates the effect of home-based tDCS on depressive symptoms in perinatal women. We proposed the following hypotheses:

• Depressive symptoms would significantly decrease following a 4-week course of home-based tDCS, with effects sustained through week 8.

• Baseline subjective health perception would be associated with the overall severity of depressive symptoms.

• The trajectory of symptom changes over time would differ according to baseline subjective health perception.

METHODS

Clinical assessments

Demographic and clinical characteristics were collected at baseline. Sociodemographic variables included age, educational level (categorized as high school graduate, college graduate, or master’s degree or higher), marital status (married, divorced, or other), and current employment status. Job-related characteristics such as monthly household income were also recorded. Obstetric information included current reproductive status (undergoing fertility treatment, currently pregnant, or postpartum), number of offspring, whether the pregnancy was planned, method of conception (natural, intrauterine insemination, or in vitro fertilization), and number of fetuses (singleton or twin). Participants also reported their subjective perception of current health status using a single question (“How would you describe your current health status?”) rated on a 5-point Likert scale (1=very healthy to 5=very unhealthy). This questionnaire was administered during the screening stage.

Depressive symptoms were assessed using the Korean version of the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). This self-reported instrument evaluated the frequency of depressive symptoms over the past week using a 4-point Likert scale (0=rarely or none of the time to 3= most or all of the time). Total scores ranged from 0 to 60, with higher scores indicating more severe depressive symptoms. The CES-D was administered at four time points: baseline (V1), week 2 (V2), week 4 (V3), and week 8 (V4). All assessments were conducted by trained researchers across the four participating institutions, as illustrated in the study design flowchart (Figure 1).

Figure 1.

Study design flowchart. Flowchart illustrating the timeline of participant visits and clinical assessments. Participants underwent a 4-week home-based tDCS intervention beginning at visit 1 (V1), with depressive symptom evaluations conducted at baseline (V1), 2 weeks (V2), 4 weeks (V3), and 8 weeks (V4). tDCS, transcranial direct current stimulation.

RESULTS

Demographic, employment, and clinical characteristics of the study participants

Baseline characteristics are summarized in Table 1. A total of 38 women treated at four academic hospitals in South Korea were enrolled in this study. The mean ages of participants and their spouses was 36.7±9.4 and 36.5±4.1 years, respectively. Most participants were married (92.1%) and had completed at least a college education (78.9%). Over half (60.5%) were currently employed as were all their spouses. Reproductive status included 21 pregnant women (55.3%), 9 postpartum (23.7%), and 8 undergoing fertility treatment (21.1%). Clinical and obstetric queries indicated that 76.2% of pregnancies were planned and 61.9% were conceived naturally. One participant was carrying twins. Participants’ baseline subjective health perception varied: 10.5% rated themselves as “very healthy” (score=1), 23.7% as “somewhat healthy” (score=2), 18.4% as “neutral” (score=3), 2.6% as “somewhat unhealthy” (score=4), and 5.3% as “very unhealthy” (score=5), while 39.5% did not respond to this item. Mean CES-D scores decreased progressively over the study period: at baseline, 8.79±6.49 at baseline, 5.54±4.53 at week 2, 4.62±4.43 at week 4, and 4.47±4.26 at week 8.

Table 1.

Demographic, employment characteristics and clinical characteristics of the study participants

Change in depressive symptoms over time

Figure 2 shows CES-D score trajectories across timepoints and health perception groups. Overall, CES-D scores decreased significantly over the 8-week period following tDCS treatment. The most marked reduction occurred between baseline (V1) and week 2 (V2), with continued improvement through week 4 (V3) and stabilization by week 8 (V4).

Figure 2.

Changes of CES-D score by subjective health perception group over time. Line graph depicting the change in mean CES-D scores across four timepoints (V1, V2, V3, and V4), stratif ied by participants’ baseline subjective health perception. CES-D, Center for Epidemiologic Studies Depression Scale; V1, visit 1; V2, 2 weeks visit; V3, 4 weeks visit; V4, 8 weeks visit.

Influence of subjective health perception on depressive symptom severity trajectories

Table 2 presents GEE omnibus test results. The GEE model revealed a significant main effect of time (Wald χ²=90.75, degrees of freedom [df]=3, p<0.001) and subjective health perception at baseline (Wald χ²=26.41, df=4, p<0.001), as well as a significant time×health perception interaction (Wald χ²=320.18, df=9, p<0.001). These findings indicate that the trajectory of depressive symptom change was moderated by participants’ self-rated health status at baseline. Additional analyses confirmed the robustness of this effect. When reproductive stage (infertility, pregnant, postpartum) was added as a covariate, time (Wald χ²=89.97, df=3, p<0.001) and the time× subjective health perception interaction (Wald χ²=278.53, df=9, p<0.001) remained significant, whereas the time×reproductive stage interaction was not (Wald χ²=8.65, df=6, p=0.195). When subjective health perception was dichotomized into good (scores 1–2) vs. not good (scores 3–5) with reproductive stage adjustment, the time×subjective health perception interaction also remained significant (Wald χ²=17.49, df=3, p=0.001). Finally, treating nonresponders as a separate subjective health perception category yielded consistent findings (time× subjective health perception: Wald χ²=21.42, df=6, p=0.002).

Table 2.

Summary of GEE model results for CES-D scores

As shown in Table 3 and Figure 2, participants who perceived their health as “very unhealthy” (Group 5) demonstrated the greatest reduction in CES-D scores (ΔCES-D=-10.00). Those reporting “neutral” (Group 3) health also showed substantial improvement (ΔCES-D=-8.43), while those who viewed themselves as “somewhat healthy” (Group 2) showed minimal change (ΔCES-D=-0.33). Supplementary Table 1 provides a detailed summary of the interaction effects and coefficient estimates from the GEE model.

Table 3.

Change in CES-D scores by subjective health perception group

DISCUSSION

This study investigated the effectiveness of home-based tDCS in perinatal women with mild to moderate depression and explored the influence of baseline subjective health perception. Depressive symptoms significantly decreased over the 8-week study period, with the most pronounced reduction occurring during the first 2 weeks of active treatment. Notably, the improvements were maintained at week 8, 4 weeks after the active treatment ended. A significant interaction between time and subjective health perception indicated that individuals who viewed their health more negatively experienced a greater symptom reduction. These results suggest that subjective health perception may serve as a clinically relevant moderator of tDCS treatment outcomes, potentially reflecting differences in emotional processing, or perceived health-related agency.

In the sample, the CES-D scores declined significantly over the 8-week period, with the most marked reduction occurring during the first 2 weeks of active tDCS treatment. Additional improvement was noted through week 4, and symptom reduction was maintained at week 8 and 4 after treatment cessation, indicating both rapid onset and sustained effects. These findings suggest that tDCS is a non-pharmacological option for managing depressive symptoms in perinatal women, a population often with limited options in the use of antidepressants because of concerns related to pregnancy, lactation, or reproductive health. Biologically, tDCS is believed to exert antidepressant effects by modulating cortical excitability and neuroplasticity, particularly through anodal stimulation of the left DLPFC [25], a region involved in the top-down regulation of negative emotions and reward processing [26,27]. Mechanistic studies have suggested that tDCS influences glutamatergic and gamma-aminobutyric acid GABA-ergic neurotransmission, enhances brain-derived neurotrophic factor-dependent synaptic plasticity, and alters connectivity within the frontolimbic circuits associated with depression [28,29]. These neurophysiological effects provide a plausible basis for the antidepressant efficacy of tDCS. Clinical trials have consistently reported early onset symptom improvement with tDCS, often within the first 1 to 2 weeks of treatment [30,31]. Prior open-label studies in pregnant women with depression have demonstrated that repeated tDCS sessions could reduce depressive symptoms without the teratogenic or pharmacokinetic concerns linked to antidepressant medications [13,32]. Building on this evidence, our study demonstrated that a structured 4-week course of home-based tDCS led to rapid improvement with a durable effect lasting up to 4 weeks post-treatment. This sustained response highlights the therapeutic value of tDCS as a practical and scalable intervention in perinatal mental healthcare.

Beyond time effects, our findings demonstrated the role of subjective health perception as a potential moderator of treatment response. Participants who rated their general health poorly consistently reported higher CES-D scores, suggesting that self-perceived health status may have captured their underlying vulnerability to depression. One possible explanation is that negative perceptions of physical health may have reflected broader cognitive-affective schemas such as heightened health-related anxiety, increased somatization, or diminished interoceptive accuracy, all of which have been linked to depressive psychopathology [33,34]. Poor subjective health may have also coincided with more pronounced somatic symptoms such as sleep disturbances, low energy, or physical discomfort, which are frequently embedded in depressive symptom profiles [18,35,36]. In perinatal population, subjective health perception may also be influenced by hormonal fluctuations, altered body image, and concerns about maternal and fetal well-being, which could further intensify emotional distress [37]. Alternatively, viewing health pessimistically may have signaled a broader sense of reduced personal agency or resilience, which, in turn, contributed to feelings of helplessness and hopelessness, which are key features of depression [38]. Although subjective health ratings did not serve as objective clinical indicators, their consistent association with mood suggests that they may offer a modest value for screening and clinical risk stratification. Including a simple self-rated health item in perinatal mental health assessments may offer a pragmatic, low-burden approach for identifying individuals who could benefit from closer monitoring, even in the absence of overt medical illness.

Interestingly, participants who rated their health more negatively exhibited the greatest reduction in CES-D scores over the 8-week period. While this may have partly reflected regression to the mean or higher baseline severity, the magnitude and consistency of the effect suggest moderating role. Even after adjusting for baseline symptom levels, those with negative health perceptions showed greater treatment responsiveness. This indicated that subjective health beliefs may have captured more than symptom burden, reflecting cognitive-affective factors such as interoceptive sensitivity, somatic preoccupation, and health-related anxiety, all of which have been linked to depression and its neural substrates [39,40]. Individuals with poorer perceived health may have exhibited a stronger focus on internal bodily states processed via interoceptive networks such as the insula and anterior cingulate cortex [41,42]. Previous neuroimaging studies have shown that DLPFC-targeted tDCS alters activity in these regions [43,44], potentially restoring the top-down regulation of somatic and emotional reactivity. Therefore, individuals with higher somatic sensitivity may be more responsive to prefrontal neuromodulation. In addition, poorer perceived health may coincide with heightened stress reactivity and dysregulated hypothalamic–pituitary–adrenal axis activity [45,46], which are well-established biological pathways linking vulnerability to depression. Anodal tDCS of the DLPFC has been shown to normalize fronto-limbic connectivity and modulate stress-related circuits, potentially restoring inhibitory control over amygdala and hypothalamic responses. From a psychological perspective, individuals who perceive themselves as less healthy may also hold stronger treatment expectancy and urgency for change, leading to greater engagement and adherence, which in turn enhances neuroplastic effects of neuromodulation. Moreover, heightened emotional salience or motivation to change may enhance therapeutic engagement. Prior research suggests that those with greater perceived vulnerability responded more strongly to interventions involving bodily awareness or self-care routines [47]. Thus, subjective health perception may reflect not only baseline symptom severity but also cognitive and emotional profiles that influence neuromodulatory treatment outcomes.

This study has several limitations. First, given the open-label design without a sham control, natural remission and placebo effects cannot be excluded. The findings should therefore be interpreted as associations rather than causal effects, and randomized controlled trials are warranted to confirm efficacy. Second, modest sample size and clinical heterogeneity across perinatal stages may have introduced variability, although it also enhances real-world clinical settings. Although the main analysis relied on the original five-level SHP scale with uneven cell sizes, additional dichotomized and nonresponse-inclusive analyses confirmed that the moderation effect was consistent. This robustness supports the validity of SHP as a meaningful marker despite sample size limitations in some categories. Third, subjective health perception was measured only once using a single-item scale; repeated assessments and the inclusion of objective health indicators would strengthen future analyses. Finally, depressive symptoms were assessed through self-reporting, without clinician-rated measures or biological markers, highlighting the need for multimodal evaluation in subsequent studies.

In conclusion, this study provides preliminary evidence supporting the feasibility, safety, and sustained antidepressant effects of home-based tDCS in treating depressive symptoms in perinatal women. The observed interaction with subjective health perception suggests that individual differences in self-appraised health may meaningfully shape responsiveness to treatment. Considering the limited pharmacological options available during the perinatal period, these findings highlight that tDCS is a promising, scalable, and non-stigmatizing therapeutic alternative. Incorporating subjective health assessments into clinical screening may also help identify individuals who will benefit the most from neuromodulatory interventions. Future larger-scale controlled studies are warranted to refine targeting strategies and optimize personalized treatment approaches in this vulnerable population.

Supplementary Materials

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