Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. METHODS: The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18-65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164). FINDINGS: Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; -8·2, SD 7·2) and the sham tDCS group (n=73; -8·0, 9·3; difference 0·3 [95% CI -2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028). INTERPRETATION: Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD. FUNDING: German Federal Ministry of Education and Research.

Loneliness in Personality Disorders.

PURPOSE OF REVIEW: Loneliness is a common experience in patients with personality disorders (PDs) that are characterized by impairment in self (identity, self-direction) and interpersonal functioning (empathy, intimacy). Here, we review studies assessing the association of loneliness with PD or PD traits including DSM-5's Alternative Model of PD (AMPD). RECENT FINDINGS: The number of loneliness studies varied greatly among different PDs with most studies conducted in borderline PD. Across PDs, loneliness was associated with the severity of psychopathological symptoms and with several AMPD trait domains. Consequently, loneliness may contribute to PD severity and further impair personality functioning. Loneliness and PD share intra- and interpersonal factors (i.e., increased rejection sensitivity, information processing biases, social withdrawal) and common origins in childhood maltreatment that may explain their close association. Future research needs to investigate mechanisms on how loneliness and core characteristics of PD mutually reinforce each other in order to therapeutically address loneliness in PD.

Association of loneliness and social network size in adulthood with childhood maltreatment: Analyses of a population-based and a clinical sample.

BACKGROUND: Perceived loneliness and objective social network size are related but distinct factors, which negatively affect mental health and are prevalent in patients who have experienced childhood maltreatment (CM), for example, patients with persistent depressive disorder (PDD) and borderline personality disorder (BPD). This cross-diagnostic study investigated whether loneliness, social network size, or both are associated with self-reported CM. METHODS: Loneliness and social network size were assessed in a population-based sample at two time points (Study 1, N = 509), and a clinical group of patients with PDD or BPD (Study 2, N = 190) using the UCLA Loneliness Scale and the Social Network Index. Further measures were the Childhood Trauma Questionnaire, and standard depression rating scales. Linear regression analyses were applied to compare associations of loneliness or social network size with CM. Multiple mediation analyses were used to test the relative importance of loneliness and social network size in the relationship between CM and depressive symptoms. RESULTS: In both studies, loneliness showed a stronger association than social network size with CM. This was particularly marked for emotional neglect and emotional abuse. Loneliness but not social network size mediated the relationship between CM and depressive symptoms. CONCLUSIONS: Loneliness is particularly associated with self-reported CM, and in this respect distinct from the social network size. Our results underline the importance of differentiating both psychosocial constructs and suggest focusing on perceived loneliness and its etiological underpinnings by mechanism-based psychosocial interventions.

Suicidal behaviors are associated with loneliness and decrease during inpatient CBASP treatment for persistent depressive disorder.

Suicidal ideation and behavior (SIB) are common in persistent depressive disorder (PDD) and may be related to interpersonal dysfunction. While SIB has been extensively analyzed in other high-risk disorders (e.g., borderline personality disorder, BPD), data on interpersonal risk factors and effects of specific psychotherapy on SIB in PDD are limited. This study aimed at investigating loneliness versus social network size as interpersonal risk factors for SIB in PDD and assess effects of cognitive behavioral analysis system of psychotherapy (CBASP) on this domain. In a prospective naturalistic study, 64 PDD patients were assessed, who underwent a 10-weeks inpatient CBASP program. Our clinical comparison group consisted of 34 BPD patients, who underwent a 10-weeks inpatient dialectical behavioral therapy (DBT) program. SIB was measured with the Columbia-Suicide Severity Rating Scale (C-SSRS), loneliness and social network size with the UCLA Loneliness Scale (UCLA) and the Social Network Index (SNI). Twenty-six PDD patients (40.6% of the PDD sample) showed current SIB at baseline in comparison with 26 BPD patients (76.5% of the BPD sample). While in suicidal PDD patients, SIB was associated with perceived social isolation (UCLA), but not with reduced social network size (SNI), this association was not observed in suicidal BPD patients. In PDD, SIB significantly decreased during CBASP. In conclusion, SIB appears to be associated with interpersonal factors related to loneliness in PDD, but not in BPD. CBASP showed first positive evidence in reducing SIB in PDD, but our pilot data need replication studies.

Loneliness is associated with maladaptive schema modes in patients with persistent depressive disorder.

OBJECTIVES: Though loneliness represents a public health concern, this complex unpleasant feeling is commonly neglected in psychiatric care and may constitute a new treatment target in clinical groups particularly prone to feeling lonely and socially isolated, e.g., persistent depressive disorder (PDD). Schema modes encompass a set of distinct cognitive-affective patterns that may contribute to loneliness and social isolation. Aim of this study was to examine the interplay between subjective loneliness and objective social network size with schema modes in patients with PDD as well as healthy controls (HC). METHOD: Sixty-two PDD patients (DSM-5; 35 female, Mage = 40.5, SD = 12.4) and 71 HC (60 female, Mage = 28.1, SD = 10.1) were assessed cross-sectionally using the following self-report measures: UCLA Loneliness Scale, Social Network Index (SNI), and Schema-Mode-Inventory, revised version (SMI-r). Correlational and multiple linear regression analyses were performed. RESULTS: PDD patients reported significantly higher scores of loneliness and maladaptive schema modes and a smaller social network than HC. Loneliness was significantly positively associated with the modes Vulnerable Child, Detached Protector, Bully and Attack, and Punitive Parent, and negatively with Contented Child and Healthy Adult in both groups. In contrast, social network size was only positively associated with the Contented Child mode. CONCLUSION: Loneliness is highly prevalent in PDD and in contrast to social network size associated with maladaptive schema modes. Therapeutically addressing these schema modes with specific techniques may represent a mechanism-based intervention for patients suffering from loneliness and should be investigated in clinical trials.

Transcranial Direct Current Stimulation (tDCS) for Depression during Pregnancy: Results from an Open-Label Pilot Study.

INTRODUCTION: Depression is the most common morbidity during pregnancy. Available first-line therapy options are limited and depressive disorders in pregnant women are often untreated, leading to negative effects on maternal and fetal health. OBJECTIVES: The aim of this open-label pilot study is to extend evidence on the use of transcranial direct current stimulation (tDCS) as a treatment of antenatal depression and to point out options for the use of tDCS in this population. METHODS: Six drug-free female patients with major depressive disorder during pregnancy (later than 10th gestational week) were included in this pilot study. Patients were treated with twice-daily tDCS (2 mA, 30 min, anode: F3, cathode: F4) over ten days during inpatient stay (Phase 1) and with once-daily tDCS over 10 days during an optional outpatient stay (Phase 2). Clinical (HAMD-21, BDI) and neuropsychological ratings (Trail Making Test A/B) were performed at baseline, after two and four weeks as well as an obstetric examination. RESULTS: Six right-handed females (23-43 years, 12-33. gestational week) completed Phase 1; four patients additionally joined in Phase 2. tDCS was well tolerated and no adverse effects occurred. Clinical ratings showed an improvement of mean baseline HAMD-21 from 22.50 ± 7.56 to 13.67 ± 3.93 after week 2, and to 8.75 ± 4.99 after week 4. The mean baseline BDI was 26.00 ± 13.90 and declined to 11.17 ± 5.46 after week 2, and to 9.25 ± 3.30 after week 4. CONCLUSIONS: Statistically significant changes in HAMD-21 and BDI were observed after Phase 1. One patient achieved remission in terms of HAMD in Phase 1. Although this small-scale study lacks sham control, it shows clinical improvement and absence of adverse events in this critical population.

Borderline Personality Features in Patients With Persistent Depressive Disorder and Their Effect on CBASP Outcome.

Introduction: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) was developed for the treatment of persistent depressive disorder (PDD), where comorbid personality disorders (PD) are common. In contrast to other PD, comorbid borderline personality disorder (BPD) is often regarded as an exclusion criterion for CBASP. In clinical settings, however, subthreshold BPD symptoms are prevalent in PDD and may not be obvious at an initial assessment prior to therapy. As data on their impact on CBASP outcome are very limited, this naturalistic study investigates BPD features in PDD and their relevance for the therapeutic outcome of a multimodal CBASP inpatient program. Method: Sixty patients (37 female, mean age 38.3, SD 11.9 years) meeting DSM-5 criteria for PDD underwent a 10 weeks CBASP inpatient program. BPD features (i.e., number of fulfilled DSM-5 criteria) together with childhood maltreatment and rejection sensitivity were assessed on admission. Before and after treatment, severity of depressive symptoms was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI-II). BPD symptoms were assessed using the Borderline Personality Disorder Severity Index (BPDSI-IV) and the Borderline Symptom List (BSL-23). Intercorrelations of baseline characteristics and symptom change during treatment were analyzed. Results: Patients with PDD met a mean of 1.5 (SD 1.6) BPD criteria with 4 patients fulfilling ≥5 criteria. BPD symptoms and depressive symptoms showed a strong correlation, and BPD symptoms were additionally correlated with emotional abuse and rejection sensitivity. There was no association between BPD features at baseline and improvement on the MADRS, however, BPD features tended to be associated with a lower response according to the BDI-II score after 10 weeks of treatment. Furthermore, BPD symptoms (i.e., abandonment, impulsivity and affective instability) were reduced after 10 weeks of CBASP treatment. Discussion: BPD symptoms are prevalent in patients with PDD and highly intertwined with the experience of depressive symptoms. In this naturalistic study in PDD, BPD features at baseline did not limit the clinical response to CBASP. Future studies may extend the spectrum of PDD to comorbid subsyndromal or even syndromal BPD in order to develop tailored psychotherapeutic treatment for these complex affective disorders.

Loneliness, Social Isolation and Their Difference: A Cross-Diagnostic Study in Persistent Depressive Disorder and Borderline Personality Disorder.

Background: Interpersonal difficulties are a key feature of persistent depressive disorder (PDD) and borderline personality disorder (BPD). Caught in a vicious circle of dysfunctional interpersonal transaction, PDD and BPD patients are at great risk of experiencing prolonged loneliness. Loneliness, in turn, has been associated with the development of mental disorders and chronic illness trajectories. Besides, several factors may contribute to the experience of loneliness across the lifespan, such as social network characteristics, a history of childhood maltreatment (CM), and cognitive-affective biases such as rejection sensitivity (RS). This cross-diagnostic study approached the topic of perceived loneliness by comparing PDD and BPD patients with healthy controls (HC) in its interplay with symptom burden, social network characteristics, RS as well as CM. Method: Thirty-four PDD patients (DSM-5; 15 female, Mage = 38.2, SD = 12.3), 36 BPD patients (DSM-5; 19 female, Mage = 28.8, SD = 9.2), and 70 age- and gender-matched HC were assessed cross-sectionally using the following self-report measures: UCLA Loneliness Scale, Social Network Index (SNI; size, diversity, and embeddedness), Beck Depression Inventory (BDI-II), Borderline Symptom List (BSL-23), Childhood Trauma Questionnaire (CTQ), and Rejection Sensitivity Questionnaire (RSQ). Results: Both patient groups reported significantly higher levels of perceived loneliness, symptom severity, and smaller social network characteristics compared to HC. Loneliness was significantly correlated with severity of self-reported clinical symptoms in PDD and at trend level in BPD. Besides, loneliness tended to be related to social network characteristics for all groups except PDD patients. Both PDD and BPD patients showed higher RS as well as CTQ scores than HC. A history of emotional abuse and emotional neglect was associated with loneliness, and this association was mediated by RS as demonstrated by an exploratory mediation analysis. Discussion: Loneliness is highly prevalent in PDD and BPD patients and contributes to the overall symptom burden. Interestingly, loneliness showed an association with prior experiences of CM as well as current RS. We therefore propose a comprehensive model on how intra- und interpersonal aspects may interplay in the dynamics of loneliness in light of CM. Finally, this model may have further implications for psychotherapeutic interventions.