The DiSCoVeR Project: ‘Examining the synergistic effects of a cognitive control videogame and a self-administered non-invasive brain stimulation on alleviating depression’ is a double-blind, sham controlled, randomized controlled trial investigating the feasibility and efficacy of an innovative, self-applied treatment approach for patients diagnosed with major depressive disorder. The trial is conducted at three clinical trial sites (Hadassah, Israel; Riga Stradiņš University, Latvia; Ludwig-Maximilian-University, Germany). The treatment approach combines prefrontal transcranial direct current stimulation with a videogame designed to enhance cognitive and emotional control. This treatment is self-applied at home and remotely monitored. At the beginning of the intervention the patients are randomized in an active group receiving both active stimulation and videogame and the other group receiving sham stimulation and visually similar but not active videogame.

The present interims analysis after half of the patients included examines patients’ intrinsic motivation after completing the first five sessions (of 30) of the treatment. We also examine patients’ interest/enjoyment, perceived competence, effort, felt pressure/tension, and perceived choice following the first week of treatment. Intrinsic motivation has been associated with enhanced learning and performance, so it can be used as one of the predictors for patient compliance.

At the end of the 5th session, the patients filled in the Intrinsic Motivation Inventory (IMI) including the following subscales: interest/enjoyment, perceived choice, perceived competence, effort/importance and felt pressure/tension (scored on a 7-point Likert scale, ranging from 1 “not at all true” to 7 “very true”).

This report includes the first 55 patients randomized (27 patients in the active group and 28 patients in placebo group) for the DiSCoVeR trial. Patients rated their overall interest/enjoyment at 4.50 out of 7 (SD±0.17 95% CI 4.16 to 4.84), their perceived choice at 5.55 (SD±0.16; 95% CI 5.23 to 5.87), their perceived competence at 4.52 (SD±0.15; 95%CI 4.22 to 4.82), their effort/importance at 5.07 (SD±0.16; 95%CI 4.74 to 5.40) and their pressure/tension at 3.00 (SD±0.13; 95% CI 2.73 to 3.26).

We conclude that overall patients were quite interested in the treatment and had inherent pleasure while doing the sessions, felt that it was their choice to do them, felt that they performed the task quite effectively, were invested in doing the sessions and the experienced pressure and tension were low. The perceived choice and competence are positive predictors of intrinsic motivation. This aligns with the previous published data of a smaller patient subset (L. Konosonoka et al Medicina (Kaunas) 2022;58(Supplement 1):72) with the standard deviations being smaller in our larger patient sample.

None Declared

The DiSCoVeR trial is a multi-site, double-blind, sham controlled, randomized controlled trial (RCT) investigating the feasibility and efficacy of an innovative, self-applied treatment approach for patients suffering from major depressive disorder (MDD). The treatment approach incorporates non-invasive brain stimulation, i.e. prefrontal transcranial direct current stimulation (tDCS), and a videogame designed to enhance emotional cognitive control. This treatment is aimed to be applied at home and monitored remotely.

In this study we are looking at the first 10 single-site patients and comparing expected in person visits (according to the study protocol) versus actual in person visits as well as looking at the patients initial view of the therapy using the therapy evaluation form (CEQ) submitted after the 5th session.

Before continuing to self-administer the treatment at home patients undergo supervised training, during clinic visits, for up to 5 sessions. At the end of the 5th session, they are asked to fill out a therapy evaluation form (CEQ).

Patients needed on average 2.3 in person training sessions before continuing the intervention remotely. Nine patients completed CEQ. Results show that on average patients thought that this course will be 4.78 (with probability 95% CI 4.74 to 4.82) points successful at raising their level of functioning and thought that their functioning will have increased on average by 37.8% (CI 37.2% to 38.4%) by the end of the study.

Patients needed less than half of planned in person training visits. Most patients felt like they will gain some improvement from this intervention.

No significant relationships.

New insights into the pathophysiology of mental disorders and innovations in psychiatric care depend on the availability of representative, longitudinal and multidimensional datasets across diverse, transdiagnostic populations. Biobanks usually attempt to collect such data in parallel to clinical routine, which is resource-intensive, puts additional burden on health-care providers, and may reduce the generalizability of the results. Despite containing rich phenotypic and biological information, data generated in routine clinical care is seldomly used for research purposes, because it is usually unstructured and locked in data silos. To truly link clinical practice and research, solutions that optimize the generation and scientific utilization of real-world clinical data are needed.

Evaluation of a new digital infrastructure which warrants the efficient, automatized, and structured collection of real-world data in psychiatric care, and integrates the generated data into existing biobanking efforts.

We have developed a new documentation system which augments the existing IT-structures, enables the collection of routine clinical data in a structured format and involves patients in the data generation process. In an implementation science approach, to replicate and extend the findings of Blitz et al. (JMIR Ment Health 2021), we are investigating the acceptance, efficacy, and safety of the system in our outpatient clinic for affective disorders.

First results describing the technical safety, usage metrics, and acceptance of the system, and the quality of the collected data will be presented.

Challenges of collecting real-world data for biobanking and research purposes and perspectives on future digital solutions will be discussed.

No significant relationships.

Obesity and its related disorders are growing epidemic across the world. As some forms of abnormal temperament are considered as subtype of the soft bipolar spectrum, we aimed to evaluate abnormal temperaments in morbid obese patients.

Using a short version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego, we investigated abnormal depressive, cyclothymic, hyperthymic, irritable or anxious temperament in 213 patients with morbid obesity compared to a control group of 90 patients admitted prior to transplantation. Additionally, the Beck-Depression Inventory (BDI) and the Self-Report Manic Inventory (SRMI) were applied to assess the current mood states.

The obese group showed statistically significant more psychiatric comorbidities compared to the control group. Abnormal temperaments were significantly more often observed in patients with morbid obesity rather than in controls. Cyclothymic, irritable and anxious temperaments showed specificity to obesity. Obese patients had significantly higher scores in BDI, while no difference for SRMI scores was registered among the whole groups. All temperaments were positively correlated with BDI and SRMI in the obese group.

Our results need replication but indicate an affective overlap in form of abnormal temperament and depressive symptoms in obese patients, whereas mood swings should be evaluated and early mood stabilization considered for patients with significant weight gain to prevent obesity or to reduce already existing overweight. Studies of mood stabilizers and prospective observations would shed further insight on this complex interface of a major clinical and public health issue.

TDCS for modulating neurophysiology is known since the 1960s. tDCS trials in patients with depression showed promising results.

22 patients with therapy resistant major depression (DSM-IV criteria) were included in a four week cross-over trial, 10 received 1 mA tDCS, 12 received 2 mA tDCS, 2 dropped out. Patients received add-on tDCS under a stable antidepressant treatment over 3 weeks and were randomized to active or sham tDCS treatment. The sham condition was evaluated in 10 healthy volunteers and was indistinguishable.Both, active (1 mA resp. 2 mA) and placebo tDCS were applied for 20 min per day and for two weeks and then switched to the other condition. The anode was positioned over F3 and the cathode over the contralateral supraorbital region. For placebo tDCS a novel sham device (neuroConn, llmenau, Germany) was used which is indistinguishable for the applying person. Severity of depression was assessed by HAMD, BDI, CGI and CORE scales and raters were blind to treatment conditions.

Mean HAMD decreased by 25% in the whole population after four weeks of tDCS. Active tDCS performed significantly better (p = 0.0492) than the control treatment. However this positive association was restricted to the first study phase as there was also a significant (p = 0.0271) influence of the study phase in the cross-over design and an almost significant (p = 0.0864) interaction between treatment and study phase.

Though active tDCS was not superior to sham treatment, we observed hangover effects in weeks 3 and 4 depending on the first condition.

Transcranial direct current stimulation (tDCS) is currently investigated for the treatmentof various neuropsychiatric disorders. Neuroplastic effects may be achieved by prolonged neuronal depolarization/hyperpolarization.

Schizophrenia studies revealed a neuroplasticity deficit of cortical areas. Promising results of anodal/cathodal tDCS for acute and chronic symptoms were shown in one randomized clinical trial and several case reports.

To improve negative symptoms, anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) and cathodal tDCS above the supraorbital region was used. Clinical scores were assessed with Positive and Negative Symptoms Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS).

20 patients with predominant negative symptoms and stable medication (>3 weeks) were randomized to active or sham group. Anode was placed over the left DLPFC, cathode over right orbit. 2 mA tDCS was delivered 10 times within weeks 1 and 2. Concomitant medication was continued. Functional connectivity MRI (fcMRI) was performed before and after tDCS.

Post-hoc test (least significant difference, factor ‘group’) showed significant PANSS amelioration in the active group (p = 0.014) for the follow-up, two weeks after the end of stimulation. SANS revealed significant improvement in the active group in week 1 (p = 0.047), week 2 (p = 0.005), and follow-up (p = 0.011). In the active group, fcMRI showed a significant deactivated cluster (corrected p< 0.05) in the anatomical regions of ncl. accumbens, subgenual cortex and striatum.

tDCS is a promising tool to improve various schizophrenic symptoms that are otherwise often difficult to treat.

Attachment and companionship are fundamental basic needs of human beings and contribute the feeling of security and social affiliation. It is assumed that dysfunctional attachment behaviour in people with Borderline Personality Disorder leads to difficulties in the interpersonal contact. Unsecure and especially disorganized manners of attachment seem to be frequently represented by mentally ill people. In this study the release of oxytocin according to attachment relevant situations was investigated and attachment representations of people with BPD have been analysed.

In order to determine attachment representations of healthy people and of people with BPD we used the validated ‘Adult Attachment Projective’/ ‘AAP’ by George, West and Pettem (1999). The projective contains eight contour drawings of attachment relevant situations. The participant should make up a story of each picture, which was evaluated by its coherence, its content and the used defence mechanisms. Attachment representations of 30 patients with BPD were surveyed. Furthermore we measured the release of oxytocin evoked by an activation of the attachment system via the ‘AAP’ in 10 healthy people. Therefor blood drawings were performed at four different points of time.

Here, we present pilot data on oxytocin measures induced via the ‘AAP’. We could detect a decrease of oxytocin in healthy people caused by an activation of the attachment system. Moreover attachment representations of patients with BPD will be presented and discussed. These preliminary data could lead to further studies on a possible dysregulation of the attachment- and the oxytocin system of people with BPD.

Ear acupuncture based on the NADA-Protocol combines the use of five standardized ear points in an open group setting. The NADA-Protocol has shown some positive effects in patients with different psychiatric diseases. To assess the practicality and effectiveness of NADA ear acupuncture we conducted a prospective observational trial on a psychosomatic ward.

During the 6 months investigation period the CGI, SCL-90R, SF-36 and ‘Cohen’s Perceived Stress Scale’ (PSS) were applied at baseline, every six weeks before and every four weeks after introduction of the NADA-Protocoll. The current level of ‘stress’, ‘sensation of pain’, ‘agitation’ and ‘fatigue’ were assessed using visual analog scales (VAS). We applied regression models with NADA group intervention and time or their interaction as factors.

We included a total of 31 patients, (22 females (71%); mean age 42,6 years), mainly diagnosed with a Major Depressive Episode. We found an increase in SF-36 total scores in linear regression (p = 0.04, t = 2.17). The VAS scores for’stress’ (before 4,1 (SD 3,2); after 2,5 (SD 2,3); linear regression p < 0.0001), and’agitation’ (before 4,6 (SD 3,2); after 3,0 (SD 2,5); linear regression p < 0.0001) dropped significantly. In all models the intervention, the time and their interaction were significant factors.

The NADA-Protocol seemed to have some impact on increase in overall health-related quality of life and ‘stress’ and ‘agitation’ levels. As for now the NADA-Protocol appears to be a useful additional treatment option in the context of patients on a psychosomatic ward.

Besides affective instability and identity diffusion, disturbances in social interactions are a core symptom of borderline personality disorder (BPD). Interpersonal problems in BPD have been suggested to be associated with oxytocin dysregulation. To directly address this hypothesis, we investigated oxytocin plasma levels during a social exclusion (ostracism) paradigm in female BPD patients.

Twenty-two female BPD patients (diagnosed according to DSM-IV) and twenty-one healthy controls matched for gender, age, and education underwent repeated neuroendocrine measurements in a standardized laboratory setting during the Cyberball paradigm, a virtual balltossing game that evokes a social exclusion situation. Emotional reactions were assessed and oxytocin and cortisol levels measured at baseline and 5, 15, and 40 min after Cyberball.

After social exclusion, oxytocin plasma levels were lower in BPD patients than in healthy controls, whereas cortisol levels did not differ between groups. BPD patients showed distinct differences in emotion regulation compared to healthy participants and reacted to social exclusion with an increase of other-focused negative emotions, particularly anger and contempt.

Our pilot study suggests that the oxytocin system shows a differential response to social exclusion in BPD patients compared to healthy controls. This difference may be related to the high rejection sensitivity of BPD patients and their difficulties in resolving social conflict.

Transcranial direct current stimulation (tDCS) is currently discussed as a therapeutic intervention in various psychiatric disorders. Based on the report about the effectiveness of tDCS in a patient with catatonic schizophrenia, we applied bilateral prefrontal tDCS in a patient with corpus callosum aplasia (CCA) and severe catatonia instead of maintenance electroconvulsive therapy (ECT).

To investigate whether tDCS can replace ECT in a largely treatment-resistant patient.

The 41 year-old male patient showed severe catatonic symptoms since adolescence and was treated by weekly ECT for almost 6 years. Due to cardiac complications and increasing cognitive deficits caused by long-term ECT and weekly anesthesia, tDCS was suggested. The anode was positioned over the left dorsolateral prefrontal cortex (DLPFC), the cathode over the right DLPFC. 2mA tDCS was delivered for 2x 20 minutes (90 minutes break in between), three times a week for the first two weeks, thereafter once to twice weekly. Concomitant medication (clozapine 600 mg/d, aripiprazole 10 mg/d, pirenzepine 50 mg/d, lorazepam 3 mg/d) was continued.

So far, more than 20 double sessions of tDCS were applied. ECT was needed once after a period of hospitalisation for 10 days due to pneumonia. Since then the patient has solely received tDCS for more than 13 weeks. Catatonic symptoms resolved further under tDCS compared to ECT (Bush-Francis Catatonia Rating Scale: 27/69 points during ECT, 5/69 during tDCS).

tDCS in combination with neuroleptic treatment could be an alternative to ECT in organic catatonia. Further studies are needed to support our hypothesis.

Ostracism (social exclusion) has been found to be a remarkable stress factor to mentally ill people with difficulties in situations of social interaction. In an earlier study it was found that patients with borderline personality disorder (BPD) showed differences in oxytocin dysregulation by having lower oxytocin plasma levels during a social exclusion paradigm (Jobst et al., 2013, submitted). To our knowledge, this is the first study investigating neuroendocrinological changes of social exclusion in chronically depressed patients. Chronic depression (CD) is associated with poor social functioning and behavioral interpersonal problems which are considered to be based on the non-responsiveness of CD patients to environmental consequences.

To manipulate a situation of social exclusion we used the Cyberball Paradigm, a virtual ball tossing game which has been well validated and applied in numerous previous studies on the effects of social exclusion. 19 CD patients (according to DSM-IV) and 19 healthy controls matched for gender, age and education underwent repeated neuroendocrine measurements in a standardized laboratory setting during the Cyberball Paradigm. Assessments of psychological variables as well as measurements of oxytocin plasma levels were performed at baseline, 5 min, 15 min and 40 min after Cyberball.

As an association of interpersonal problems in BPD with oxytocin dysregulation has been found, we suggest differences in changes of oxytocin levels in a social exclusion situation in CD patients versus healthy subjects. The data will be presented and discussed in relation to specific interpersonal problems of patients suffering from CD.

Chronically depressed patients show considerably impaired interpersonal features, which could be explained by a reduced Theory of Mind (ToM) ability.

The aim of this study was to examine whether chronically depressed patients are impaired in their ToM performance compared to a healthy control group in three different components of ToM: the social cognitive and social perceptual component as well as the ability to take someone else's visual perspective.

32 chronically depressed patients (DSM-IV) were compared to 32 matched healthy controls. ToM abilities were assessed by a cartoon picture story test (CT), the ‘Perspective task’ (PT) and the ‘Reading the mind in the Eyes’ test (RMET). In addition, information about depression severity, childhood trauma and executive functioning (working and logical memory) was assessed for both groups.

Patients mentalized significantly less frequently than healthy controls in the CT (Mann-Whitney-U=340,50, p<0,05). Furthermore, the CT was significantly correlated with the RMET (patients: r=0,46, p<0,05; controls: r=0,57, p<0,01). We didn’t find any significant difference between both groups in the RMET (p>0,05). In the PT, patients showed significantly lower scores than controls (t(35,68)=2,10, p<0,05). There wasn’t any significant correlation between the three ToM tests and severity of depression, duration of illness or childhood trauma (p>0,05).

Our results suggest that chronically depressed patients show deficits in their social cognitive ToM ability compared to controls, whereas their social perceptual ToM ability seems to be unimpaired. As to the capacity to take someone else's perspective, our results suggest that chronically depressed patients present significant deficits.

Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given.

We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders.

We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences.

The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD.

Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

Epinephrine enhances emotional memory whereas β-adrenoceptor antagonists (β-blockers, BBs) impair it. However, the effects of BB administration on memory are sex dependent. Therefore, we predicted differential effects of epinephrine and the BB metoprolol given to male and female patients after cardiac surgery (CS) on traumatic memories and post-traumatic stress disorder (PTSD) symptoms.

We performed a prospective observational study and determined the number of standardized traumatic memories (NTRM) and PTSD symptom intensity in cardiac surgical patients at 1 day before surgery, and at 1 week and 6 months after the procedure. PTSD symptoms and NTRM were quantified using validated questionnaires. Metoprolol could be administered any time post-operatively.

Baseline NTRM was not significantly different between male (n=95) and female patients (n=33). One week after CS, the NTRM in male patients was significantly higher. Metoprolol had no significant effect in either sex. At 6 months, females with metoprolol (n=18) showed a significantly lower NTRM and significantly lower PTSD symptom scores than females without BBs (n=15, p=0.02). By contrast, the totally administered dosage of epinephrine correlated with NTRM in males (r=0.33, p<0.01) but not in females (r=0.21, p=0.29).

β-Adrenergic stimulation with epinephrine enhances memory for adverse experiences in males but not in females whereas β-blockade selectively reduces memory for post-operative adverse events and PTSD symptoms in females.

Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression.

An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically.

The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (⩾50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%).

VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.