Background: The present study was designed to evaluate the efficacy of a therapist-guided internet-based cognitive-behavioral therapy (iCBT) intervention for service members of the German Armed Forces with posttraumatic stress disorder (PTSD). The iCBT was adapted from Interapy, a trauma-focused evidence-based treatment based on prolonged exposure and cognitive restructuring. It lasted for 5 weeks and included 10 writing assignments (twice a week). The program included a reminder function if assignments were overdue, but no multimedia elements. Therapeutic written feedback was provided asynchronously within one working day. Methods: Male active and former military service members were recruited from the German Armed Forces. Diagnoses were assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Mini-International Neuropsychiatric Interview. Psychopathology was assessed at pre-treatment, post-treatment, and 3-month followup. Severity of PTSD was the primary outcome and anxiety was the secondary outcome. Participants were randomly allocated to a treatment group that received iCBT immediately or to a waitlist group that received iCBT after 6 weeks. Due to the overall small sample size (n = 37), the two groups were collapsed for the statistical analyses. Change during the intervention period was investigated using latent-change score models. Results: Improvements in the CAPS-5 were small and not statistically significant. For anxiety, small significant improvements were observed from pre-to follow-up assessment. The dropout rate was 32.3%. Conclusions: The low treatment utilization and the high dropout rate are in line with previous findings on treatment of service members. The interpretation of the current null results for the efficacy of iCBT is limited due to the small sample size, however for military samples effect estimates were also smaller in other recent studies. Our results demonstrate the need to identify factors influencing treatment engagement and efficacy in veterans. Trial registration: Australian Clinical Trials Registry ACTRN12616000956404.

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.

Across species, sleep is characterized by a complex architecture. Sleep deprivation is a classic method to study the consequences of sleep loss, which include alterations in the activity of sleep circuits and detrimental consequences on well being. Automating the observation and manipulation of sleep is advantageous to study its regulation and functions. Caenorhabditis elegans shows sleep behavior similar to other animals that have a nervous system. However, a method for real-time automatic sleep detection that allows sleep-specific manipulations has not been established for this model animal. Also, our understanding of how sleep deprivation affects sleep neurons in this system is incomplete. Here we describe a system for real-time automatic sleep detection of C. elegans grown in microfluidic devices based on a frame-subtraction algorithm using a dynamic threshold. As proof of principle for this setup, we used automated mechanical stimulation to perturb sleep behavior and followed the activity of the sleep-active RIS neuron. We show that our system can automatically detect sleep bouts and deprive worms of sleep. We found that mechanical stimulation generally leads to the activation of the sleep-active RIS neuron, and this stimulation-induced RIS depolarization is most prominent during sleep deprivation.

IMPORTANCEMajor 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 PARTICIPANTSThe 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 MEASURESThe 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 RELEVANCEBased 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.