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Abstract

Introduction Major depressive disorder (MDD) is the most common comorbidity among individuals with borderline personality disorder (BPD), affecting over 85% of patients and leading to high recurrence rates and resistance to treatment. Traditional pharmacological and psychotherapeutic interventions often show limited efficacy in this population, highlighting the need for innovative treatment strategies. Emerging evidence suggests that the dorsolateral prefrontal cortex (DLPFC) plays a crucial role in the pathophysiology of both MDD and BPD. In addition, non-invasive brain stimulation, particularly transcranial Direct Current Stimulation (tDCS), has shown promising results in alleviating depression and improving BPD symptoms when targeting the DLPFC. The development of home-based tDCS presents new opportunities for accessible and cost-effective interventions. However, no study has specifically investigated its effects on MDD in the context of BPD.

Methods and analysis This double-blind randomised controlled trial will assess the feasibility and explore the efficacy of home-based tDCS in reducing depressive symptoms in BPD patients who are experiencing moderate to severe depressive episodes. A total of 60 participants will be randomised, following a 2-week online psychoeducation, to receive either active or sham tDCS in 14 sessions over 1 week. The primary outcome is the feasibility of home-based tDCS in remote and urban areas. The secondary aim is to obtain a preliminary assessment of the efficacy of 14 home-based tDCS sessions in reducing depressive symptoms in BPD patients with moderate to severe depressive episodes and BPD symptoms. Exploratory analyses will evaluate the impact of tDCS on neuropsychological functioning, physical activity and substance use. Sociodemographic variables will be considered in predicting treatment response. All assessments will be conducted at baseline, post-treatment and during follow-ups through 3 months after treatment ends.

Ethics and dissemination This study has received approval from the Research Ethics Committee of the Centre intégré universitaire de santé et de services sociaux de l’Est-de-l’Île-de-Montréal (CIUSSS-EMTL) (approval number: MP-12-2025-4050). All participants will provide informed consent prior to inclusion. Findings will be disseminated through peer-reviewed publications, conference presentations and knowledge translation activities targeting clinicians, researchers and mental health stakeholders.

Trial registration number NCT06972368.

https://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.

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by Lionel Cailhol 1,2,3,4,5,6,*ORCID,Kamilia Soltani 1,Cécilia Neige 5,6,Marine Mondino 5,6ORCID,Jérôme Brunelin 5,6ORCID andMartin Blay 7,8ORCID

Faculté de Médecine, Département de Psychiatrie et D’addictologie, Pavillon Roger-Gaudry, C.P. 6128, Succursale Centre-Ville, Montréal, QC H3T 1J4, Canada

2
Centre de Recherche de L’Institut Universitaire de Santé Mentale de Montréal, 7401 Rue Hochelaga, Montréal, QC H1N 3M5, Canada
3
CERVO Brain Research Center, 2301 Av. D’Estimauville, Québec City, QC G1E 1T2, Canada
4
CIUSSS de L’Est de L’île de Montréal, Montréal, QC H1A 1T5, Canada
5
PsyR2 Team, U1028 UMR5292, Centre de Recherche en Neurosciences de Lyon CRNL, CNRS, INSERM, Université Claude Bernard Lyon 1, 69500 Bron, France
6
PsyR2, Le Vinatier Psychiatrie Universitaire Lyon Métropole, 95 Boulevard Pinel, 69500 Bron, France
7
ADDIPSY, Santé Basque Développement Group, Addictology and Psychiatry Oupatient Center, 69007 Lyon, France
8
Centre de Recherche en Epidémiologie et Santé des Populations Team “DevPsy”, INSERM, UVSQ, Université Paris-Saclay, 94807 Villejuif, France
*
Author to whom correspondence should be addressed.
Brain Sci. 2025, 15(6), 547; https://doi.org/10.3390/brainsci15060547
Submission received: 8 May 2025 / Revised: 19 May 2025 / Accepted: 20 May 2025 / Published: 23 May 2025

Abstract

Background: Borderline Personality Disorder (BPD) is a severe psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and unstable interpersonal relationships. Affecting over 1% of the general population, BPD carries significant morbidity, frequent hospitalizations, and an increased risk of suicide. Although specialized psychotherapeutic approaches have shown efficacy, their impact is often constrained by availability, lengthy treatment durations, moderate effect sizes, and high dropout rates. Pharmacological treatments for BPD remain inadequate and are usually accompanied by adverse side effects. Objective: This narrative review seeks to explore the potential of transcranial direct current stimulation (tDCS) as a safe, cost-effective, and accessible neuromodulation intervention aimed at alleviating core BPD symptoms—namely, emotional dysregulation and impulsivity—while also addressing common comorbidities and opportunities for integration with existing therapeutic modalities. Methods: We conducted a narrative literature synthesis in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. A PubMed/MEDLINE search was performed using keywords related to transcranial direct current stimulation (tDCS) and BPD, identifying five published randomized controlled trials on the topic. To provide a broader perspective, we also included studies from related fields examining mechanisms of action, safety and tolerability, cost-effectiveness, stimulation parameters, and clinical outcomes relevant to BPD. Results: Conventional tDCS protocols—typically involving 1–2 mA currents for 20–30 min—have demonstrated an excellent safety profile, resulting in only minimal and transient side effects without any risk of overdose or misuse, which is a key advantage for populations at high risk of suicidality. With moderately priced devices and the feasibility of home-based administration, tDCS provides a substantially more affordable alternative to both long-term pharmacotherapy and intensive psychotherapy. Neurobiologically, tDCS modulates the excitability of the dorsolateral and ventrolateral prefrontal cortex and enhances fronto-limbic connectivity, thereby strengthening top-down regulatory control over emotion and behavior. Pilot randomized controlled trials report moderate effect sizes for improvements in emotional regulation, inhibitory control, and rejection sensitivity, along with ancillary gains in executive functioning and reductions in depressive and substance-use symptoms when stimulating the left dorsolateral prefrontal cortex. Conclusions: tDCS stimulation emerges as a safe and scalable adjunctive treatment for BPD, leveraging targeted neuromodulation to address core features and common comorbidities like depression. However, variability in current protocols and the scarcity of well-powered randomized trials underscore the pressing need for standardized methodologies, longer-term follow-up, and individualized stimulation strategies to establish enduring clinical benefits.

 

1. Introduction

Borderline Personality Disorder (BPD) is a severe and complex psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and interpersonal dysfunction [1]. It affects more than 1% of the general population [2] and is associated with high rates of psychiatric comorbidities, particularly mood disorders, anxiety disorders, and substance use disorders [3]. Beyond its clinical features, BPD is among the most impairing psychiatric disorders, leading to significant functional impairment [4], frequent hospitalizations [5], and an elevated risk of suicide [6,7]. Individuals with BPD experience a mortality rate substantially higher than that of the general population, primarily due to suicide and related health complications [6,8]. Given its prevalence and severity, developing effective and accessible treatment strategies remains a critical challenge in psychiatry.
Specialized psychotherapy is currently the gold standard for BPD treatment [9,10,11]. Approaches such as Dialectical Behavior Therapy (DBT), Mentalization-Based Therapy (MBT), and Schema Therapy have demonstrated efficacy in reducing emotional instability, impulsive behaviors, and self-harm [12]. Despite their effectiveness, these treatments face considerable limitations. The demand for specialized therapy far exceeds the availability of trained clinicians, resulting in limited access to care and prolonged wait times [13]. Even when accessible, psychotherapy requires long-term engagement; while many patients benefit from these interventions, the effect sizes remain moderate [12], with improvements often occurring gradually over months or years. A further challenge is that individuals with BPD frequently struggle with treatment adherence [14], resulting in high dropout rates and diminished therapeutic benefits. In parallel, pharmacotherapy for BPD remains unsatisfactory. Although antidepressants, mood stabilizers, and antipsychotics are widely prescribed, no pharmacological treatment has been explicitly approved for BPD [15]. Available medications offer only partial symptom relief and frequently come with significant side effects, complicating treatment decisions. These challenges underscore the urgent need for innovative, alternative, or adjunctive approaches to improve treatment strategies and patient outcomes.
Neuromodulation has emerged as a promising avenue for psychiatric disorders, especially BPD, offering novel mechanisms to modulate brain activity and alleviate symptoms [16,17]. Transcranial direct current stimulation (tDCS) has gained attention among available techniques due to its safety, accessibility, and potential therapeutic effects. Notably, it is more cost-effective than repetitive transcranial magnetic stimulation (rTMS), and its potential for home-based administration makes it an attractive option for patients who face barriers to accessing traditional in-clinic treatments [18]. In the context of BPD, tDCS may be particularly relevant given its potential capacity to modulate neural networks implicated in emotion regulation and impulsivity. One of the most common hypotheses is the fronto-limbic hypothesis [19], positing that emotional dysregulation arises from heightened amygdala activity, reduced activation in prefrontal regions such as the dorsal anterior cingulate cortex, and weakened fronto-limbic connectivity [20,21], although the validity of this hypothesis remains debated by some authors [22]. By targeting these neural mechanisms, tDCS has the potential to address core symptoms of BPD in a biologically plausible and clinically meaningful manner.
In this context, this narrative review aims to explore the potential role of tDCS in the treatment of BPD. Specifically, it will examine the rationale for integrating tDCS into BPD care—focusing on its safety, affordability, and capacity to target key symptom domains such as emotional dysregulation and impulsivity—and will discuss optimal stimulation protocols (electrode placement, intensity, session duration, and frequency) as well as its potential to complement or enhance psychotherapy. We ask whether tDCS can safely, affordably, and effectively modulate core BPD features, and we hypothesize that (1) specific tDCS parameters (e.g., electrode montage and stimulation intensity) will differentially influence symptomatic targets, from core BPD symptoms to executive functions and common comorbidities, and (2) tDCS will provide additional benefits in terms of cost-effectiveness and synergistic gains when combined with psychotherapeutic interventions. Finally, we will address clinical applications and feasibility, evaluate tDCS as both a standalone and adjunctive treatment, highlight current gaps in the literature, and outline future research directions.

2. Materials and Methods

A comprehensive narrative review was conducted to synthesize preclinical and clinical evidence on tDCS for BPD. This narrative review was conducted in accordance with the guidelines of the SANRA (Scale for the Assessment of Narrative Review Articles), which outlines quality criteria for narrative reviews. The manuscript adheres to SANRA’s six domains: justification of the article’s importance, clear statement of objectives, description of the literature search, appropriate referencing, sound scientific reasoning, and proper presentation of data [23]. We searched PubMed/MEDLINE from database inception through 30 March 2025, using combinations of the keywords “borderline personality disorder”, “BPD”, “transcranial direct current stimulation”, “tDCS”, “neuromodulation”, “prefrontal”, “emotion regulation”, and “impulsivity.” No language restrictions were applied. Reference lists of included articles and pertinent review papers were hand-searched for additional studies. The review process was carried out in two steps. First, we focused on identifying RCTs investigating tDCS in individuals with BPD. Data extraction was conducted independently by two reviewers (MB, LC), based on a prior unpublished systematic review conducted by our team. Second, we performed targeted searches to complement this initial synthesis by including studies addressing (1) the efficacy of tDCS in treating common BPD comorbidities (identified through recent meta-analyses), (2) the safety profile of tDCS (via meta-analyses and clinical guidelines), and (3) cost-related aspects (medico-economic evaluations). Finally, we incorporated selected studies to enrich our understanding of the neurobiological mechanisms underlying tDCS and its potential synergies with psychotherapeutic interventions.
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Transcranial Direct Current Stimulation (tDCS) for Borderline Personality Disorder (BPD): Why and How?

1 Faculté de Médecine, Département de Psychiatrie et D’addictologie, Pavillon Roger-Gaudry, C.P. 6128, Succursale Centre-Ville, Montréal, QC H3T 1J4, Canada
2 Centre de Recherche de L’Institut Universitaire de Santé Mentale de Montréal, 7401 Rue Hochelaga, Montréal, QC H1N 3M5, Canada
3 CERVO Brain Research Center, 2301 Av. D’Estimauville, Québec City, QC G1E 1T2, Canada
4 CIUSSS de L’Est de L’île de Montréal, Montréal, QC H1A 1T5, Canada
5 PsyR2 Team, U1028 UMR5292, Centre de Recherche en Neurosciences de Lyon CRNL, CNRS, INSERM, Université Claude Bernard Lyon 1, 69500 Bron, France
6 PsyR2, Le Vinatier Psychiatrie Universitaire Lyon Métropole, 95 Boulevard Pinel, 69500 Bron, France
7ADDIPSY, Santé Basque Développement Group, Addictology and Psychiatry Oupatient Center, 69007 Lyon, France
8Centre de Recherche en Epidémiologie et Santé des Populations Team “DevPsy”, INSERM, UVSQ, Université Paris-Saclay, 94807 Villejuif, France
*Author to whom correspondence should be addressed.

Abstract

Background: Borderline Personality Disorder (BPD) is a severe psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and unstable interpersonal relationships. Affecting over 1% of the general population, BPD carries significant morbidity, frequent hospitalizations, and an increased risk of suicide. Although specialized psychotherapeutic approaches have shown efficacy, their impact is often constrained by availability, lengthy treatment durations, moderate effect sizes, and high dropout rates. Pharmacological treatments for BPD remain inadequate and are usually accompanied by adverse side effects. Objective: This narrative review seeks to explore the potential of transcranial direct current stimulation (tDCS) as a safe, cost-effective, and accessible neuromodulation intervention aimed at alleviating core BPD symptoms—namely, emotional dysregulation and impulsivity—while also addressing common comorbidities and opportunities for integration with existing therapeutic modalities. 

Methods: We conducted a narrative literature synthesis in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. A PubMed/MEDLINE search was performed using keywords related to transcranial direct current stimulation (tDCS) and BPD, identifying five published randomized controlled trials on the topic. To provide a broader perspective, we also included studies from related fields examining mechanisms of action, safety and tolerability, cost-effectiveness, stimulation parameters, and clinical outcomes relevant to BPD. Results: Conventional tDCS protocols—typically involving 1–2 mA currents for 20–30 min—have demonstrated an excellent safety profile, resulting in only minimal and transient side effects without any risk of overdose or misuse, which is a key advantage for populations at high risk of suicidality. With moderately priced devices and the feasibility of home-based administration, tDCS provides a substantially more affordable alternative to both long-term pharmacotherapy and intensive psychotherapy. Neurobiologically, tDCS modulates the excitability of the dorsolateral and ventrolateral prefrontal cortex and enhances fronto-limbic connectivity, thereby strengthening top-down regulatory control over emotion and behavior. Pilot randomized controlled trials report moderate effect sizes for improvements in emotional regulation, inhibitory control, and rejection sensitivity, along with ancillary gains in executive functioning and reductions in depressive and substance-use symptoms when stimulating the left dorsolateral prefrontal cortex. Conclusions: tDCS stimulation emerges as a safe and scalable adjunctive treatment for BPD, leveraging targeted neuromodulation to address core features and common comorbidities like depression. However, variability in current protocols and the scarcity of well-powered randomized trials underscore the pressing need for standardized methodologies, longer-term follow-up, and individualized stimulation strategies to establish enduring clinical benefits.

1. Introduction

Borderline Personality Disorder (BPD) is a severe and complex psychiatric condition characterized by pervasive emotional dysregulation, impulsivity, and interpersonal dysfunction [1]. It affects more than 1% of the general population [2] and is associated with high rates of psychiatric comorbidities, particularly mood disorders, anxiety disorders, and substance use disorders [3]. Beyond its clinical features, BPD is among the most impairing psychiatric disorders, leading to significant functional impairment [4], frequent hospitalizations [5], and an elevated risk of suicide [6,7]. Individuals with BPD experience a mortality rate substantially higher than that of the general population, primarily due to suicide and related health complications [6,8]. Given its prevalence and severity, developing effective and accessible treatment strategies remains a critical challenge in psychiatry.
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