Efficacy of Augmentation of Cognitive Behavioral Therapy With Transcranial Direct Current Stimulation for Depression: A Randomized Clinical Trial.

Importance: Major depressive disorder (MDD) affects approximately 10% of the population globally. Approximately 20% to 30% of patients with MDD do not sufficiently respond to standard treatment. Therefore, there is a need to develop more effective treatment strategies. Objective: To investigate whether the efficacy of cognitive behavioral therapy (CBT) for the treatment of MDD can be enhanced by concurrent transcranial direct current stimulation (tDCS). Design, Setting, and Participants: The double-blind, placebo-controlled randomized clinical trial PsychotherapyPlus was conducted at 6 university hospitals across Germany. Enrollment took place between June 2, 2016, and March 10, 2020; follow-up was completed August 27, 2020. Adults aged 20 to 65 years with a single or recurrent depressive episode were eligible. They were either not receiving medication or were receiving a stable regimen of antidepressant medication (selective serotonin reuptake inhibitor and/or mirtazapine). A total of 148 women and men underwent randomization: 53 individuals were assigned to CBT alone (group 0), 48 to CBT plus tDCS (group 1), and 47 to CBT plus sham-tDCS (group 2). Interventions: Participants attended a 6-week group intervention comprising 12 sessions of CBT. If assigned, tDCS was applied simultaneously. Active tDCS included stimulation with an intensity of 2 mA for 30 minutes (anode over F3, cathode over F4). Main Outcomes and Measures: The primary outcome was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to posttreatment in the intention-to-treat sample. Scores of 0 to 6 indicate no depression; 7 to 19, mild depression; 20 to 34, moderate depression; and 34 and higher, severe depression. Results: A total of 148 patients (89 women, 59 men; mean [SD] age, 41.1 [13.7] years; MADRS score at baseline, 23.0 [6.4]) were randomized. Of these, 126 patients (mean [SD] age, 41.5 [14.0] years; MADRS score at baseline, 23.0 [6.3]) completed the study. In each of the intervention groups, intervention was able to reduce MADRS scores by a mean of 6.5 points (95% CI, 3.82-9.14 points). The Cohen d value was -0.90 (95% CI, -1.43 to -0.50), indicating a significant effect over time. However, there was no significant effect of group and no significant interaction of group × time, indicating the estimated additive effects were not statistically significant. There were no severe adverse events throughout the whole trial, and there were no significant differences of self-reported adverse effects during and after stimulation between groups 1 and 2. Conclusions and Relevance: Based on MADRS score changes, this trial did not indicate superior efficacy of tDCS-enhanced CBT compared with 2 CBT control conditions. The study confirmed that concurrent group CBT and tDCS is safe and feasible. However, additional research on mechanisms of neuromodulation to complement CBT and other behavioral interventions is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02633449.

Empathy and altruistic behavior in antisocial violent offenders with psychopathic traits.

Deficiencies in empathic functioning are considered a core characteristic of violent behavior. Enhancing empathy in aggressive populations may thus represent a promising intervention target. Hence, the aims of the present work were two-fold: First, we wanted to thoroughly assess empathic competencies and second, we aimed to investigate effects of an empathy induction on experienced empathy levels and prosocial behavior in a sample of violent offenders relative to matched controls. Empathy was assessed using both self-report as well as objective measures. For the empathy induction, participants were presented with empathy inducing and control videos. To assess the effects of the empathy induction on behavior, participants played a dictator game indicative of prosocial behavior after every video. Violent offenders showed no systematic impairment in empathy measures. Despite lower shares in the dictator game across conditions, the empathy induction led to a substantial increase in prosocial behavior in both groups. Importantly, high psychopathy scores were distinctively associated with lower self-reported empathy levels, an attenuated affective responsiveness to the empathy induction, and less altruistic behavior. Treatment programs aiming to improve empathy should take individual characteristics into account and may be applied to distinctive subgroups rather than to violent offenders per se.

PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with prefrontal transcranial direct current stimulation (tDCS) in major depressive disorder-study design and methodology of a multicenter double-blind randomized placebo-controlled trial.

Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. About 20-30% of patients do not respond to the standard psychopharmacological and/or psychotherapeutic interventions. Mounting evidence from neuroimaging studies in MDD patients reveal altered activation patterns in lateral prefrontal brain areas. Successful cognitive behavioral therapy (CBT) is associated with a recovery of these neural alterations. Moreover, it has been demonstrated that transcranial direct current stimulation (tDCS) is capable of influencing prefrontal cortex activity and cognitive functions such as working memory and emotion regulation. Thus, a clinical trial investigating the effects of an antidepressant intervention combining CBT with tDCS seems promising. The present study investigates the antidepressant efficacy of a combined CBT-tDCS intervention as compared to CBT with sham-tDCS or CBT alone. A total of 192 patients (age range 20-65 years) with MDD (Hamilton Depression Rating Scale Score ≥ 15, 21-item version) will be recruited at four study sites across Germany (Berlin, Munich, Tuebingen, and Freiburg) and randomly assigned to one of the following three treatment arms: (1) CBT + active tDCS; (2) CBT + sham-tDCS; and (3) CBT alone. All participants will attend a 6-week psychotherapeutic intervention comprising 12 sessions of CBT each lasting 100 min in a closed group setting. tDCS will be applied simultaneously with CBT. Active tDCS includes stimulation with an intensity of 2 mA for 30 min with the anode placed over F3 and the cathode over F4 according to the EEG 10-20 system, if assigned. The primary outcome measure is the change in Montgomery-Åsberg Depression Rating Scale scores from baseline to 6, 18, and 30 weeks after the first session. Participants also undergo pre- and post-treatment neuropsychological testing and functional magnetic resonance imaging (fMRI) to assess changes in prefrontal functioning and connectivity. The study investigates whether CBT can be augmented by non-invasive brain stimulation techniques such as tDCS in the treatment of MDD. It is designed as a proof-of-principle trial for the combined tDCS-CBT treatment, but also allows the investigation of the neurobiological underpinnings of the interaction between both interventions in MDD. Trial registration ClinicalTrials.gov Identifier NCT02633449.

Frontal alpha asymmetry and callous-unemotional traits in imprisoned violent offenders: A pilot study.

Based on the approach-withdrawal model of hemispheric asymmetry, anger and aggression have been linked to an approach-related pattern, characterized by stronger relative left-hemispheric anterior cortical activity. Recent work suggests that also in individuals with extremely violent tendencies, such as imprisoned offenders, approach-related asymmetry may be associated with self-reported trait anger and aggression. A putative association between alpha asymmetry and further characteristics relevant for aggression, such as callous-unemotional (CU) traits, remains to be explored. CU traits may increase the probability of aggressive behavior; nevertheless, they may also enable individuals to inhibit and postpone the overt display of aggression until circumstances grant its strongest impact. In the current exploratory study, we measured trait aggression, CU traits, and resting-state EEG asymmetry in the alpha band (8-13 Hz) in imprisoned violent offenders in a German high security prison. Results revealed that particularly trait callousness was associated with stronger relative right-hemispheric anterior cortical activity (i.e., a withdrawal-related pattern). An association between alpha asymmetry and aggression was not replicated. These preliminary findings suggest that, due to the involved emotional and interpersonal detachment, callousness might be withdrawal related, despite its potential to bring about aggressive behavior. They also imply that the identification of putative clinical subtypes in prisoners is required, as varying psychopathology might undermine an association between alpha asymmetry and aggression.

Smooth criminal: convicted rule-breakers show reduced cognitive conflict during deliberate rule violations.

Classic findings on conformity and obedience document a strong and automatic drive of human agents to follow any type of rule or social norm. At the same time, most individuals tend to violate rules on occasion, and such deliberate rule violations have recently been shown to yield cognitive conflict for the rule-breaker. These findings indicate persistent difficulty to suppress the rule representation, even though rule violations were studied in a controlled experimental setting with neither gains nor possible sanctions for violators. In the current study, we validate these findings by showing that convicted criminals, i.e., individuals with a history of habitual and severe forms of rule violations, can free themselves from such cognitive conflict in a similarly controlled laboratory task. These findings support an emerging view that aims at understanding rule violations from the perspective of the violating agent rather than from the perspective of outside observer.

Empathy promotes altruistic behavior in economic interactions.

What are the determinants of altruism? While economists assume that altruism is mainly driven by fairness norms, social psychologists consider empathy to be a key motivator for altruistic behavior. To unite these two theories, we conducted an experiment in which we compared behavior in a standard economic game that assesses altruism (the so-called Dictator Game) with a Dictator Game in which participants' behavioral choices were preceded either by an empathy induction or by a control condition without empathy induction. The results of this within-subject manipulation show that the empathy induction substantially increased altruistic behavior. Moreover, the increase in experienced empathy predicted over 40% of the increase in sharing behavior. These data extend standard economic theories that altruism is based on fairness considerations, by showing that empathic feelings can be a key motivator for altruistic behavior in economic interactions.