Aggressive intentions after social exclusion and their association with loneliness.

Both social exclusion and loneliness are aversive experiences that can lead to hostile behavioral reactions, including aggressive behavior. This study aimed to assess whether a social exclusion scenario in the subject's imagination elicits aggressive reactions towards an excluding person as measured with the hot sauce paradigm. Furthermore, we studied the effect of loneliness on such reactions. In total, 251 subjects (67.7% female; mean age 27.3 ± 9.3 years) participated in this study which was based on an online survey. After trait loneliness was assessed with the UCLA Loneliness scale at baseline, two imaginary scenarios were presented in randomized order, i.e., an exclusion condition (with one of two working colleagues excluding the participant from a social activity) and an inclusion condition (without exclusion). Following each scenario, participants had the task to allocate the amount of hot sauce to each colleague that they find appropriate. Participants distributed significantly more hot sauce to the excluder than to the includers. The amount of hot sauce was significantly correlated with loneliness for all includer interactions (i.e., after the inclusion as well as the exclusion scenario), but not for the interaction with the excluder. Our results support the hypothesis that social exclusion elicits aggressive behavior. Interestingly, the experience of loneliness seems to be associated with an increase in aggressive behavioral tendencies or a lack of their inhibition. The cognitive and/or emotional processes underlying the interplay between social exclusion, loneliness and aggression should be a focus of future research.

Attachment mediates the link between childhood maltreatment and loneliness in persistent depressive disorder.

BACKGROUND: A central concept of attachment theory is that early experiences with close attachment figures shape the way we interact with and relate to other social partners throughout life. As such, early experiences of childhood maltreatment (CM) have been suggested as a key precursor of adult insecure attachment representations. As CM has been linked to feelings of loneliness in adulthood, this study examines whether insecure attachment could explain the relationship between CM and loneliness. Also, the moderating role of a diagnosis of persistent depressive disorder (PDD) is investigated, a disorder characterized by high levels of CM and loneliness. METHOD: 60 patients with PDD (DSM-5) and 60 gender- and age-matched non-clinical control participants (NC) completed self-report questionnaires measuring attachment, loneliness, and CM. Mediation analyses (PDD as a moderator) were performed. RESULTS: PDD patients reported higher levels of CM, attachment anxiety, attachment avoidance, and loneliness than NC. CM was positively associated with loneliness in both groups. Mediation analyses demonstrated that the relationship between CM and loneliness was mediated by avoidant, but not anxious attachment, regardless of a diagnosis of PDD. LIMITATIONS: Caution when interpreting these results is crucial as the study lacked a clinical control group, relied on self-report measures, and the cross-sectional design limits the ability to draw causal inferences. CONCLUSIONS: All constructs studied were present to a greater degree in PDD. Above, findings provide initial evidence that avoidant attachment may explain the relationship between CM and loneliness. Potentially, adult avoidant attachment may lead to and maintain feelings of loneliness, regardless of PDD.

Transcranial Direct Current Stimulation (tDCS) for major depression - Interim analysis of cloud supervised technical data from the DepressionDC trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) of prefrontal cortex regions has been reported to exert antidepressant effects, though large scale multicenter trials in major depressive disorder (MDD) supporting this notion are still lacking. Application of tDCS in multicenter settings, however, requires measurement, storage and evaluation of technical parameters of tDCS sessions not only for safety reasons but also for quality control. To address this issue, we conducted an interim analysis of supervised technical data across study centers in order to monitor technical quality of tDCS in an ongoing multicenter RCT in MDD (DepressionDC trial). METHODS: Technical data of 818 active tDCS sessions were recorded, stored in a data cloud, and analysed without violating study blinding. Impedance, voltage and current were monitored continuously with one data point recorded every second of stimulation. RESULTS: Variability of impedance was considerable (1,42 kΩ, to 8,23 kΩ), inter-individually and even more intra-individually, but did not significantly differ between the study centre in Munich and all other sites. CONCLUSION: Measurement, centralized data storage via data cloud and remote supervision of technical parameters of tDCS are feasible and proposed for future RCTs on therapeutic tDCS in multiple settings.

Dynamics of the immediate behavioral response to partial social exclusion.

Social rejection and exclusion (ostracism) represent main stressors in daily life and even threaten mental and physical health. Abundant data from subjective measures in social exclusion paradigms are available, but the dynamic behavioral response is largely unexplored. Here, we applied modified variants of the Cyberball paradigm in two consecutive experiments to investigate the adaptive behavioral and emotional reactions to partial social exclusion. In experiment 1, 68 healthy participants (females, mean age 24.76 ± 4.05 years) played 2 min inclusion, 5 min partial exclusion and 2 min total exclusion. In experiment 2, 94 healthy participants (48 females, mean age 34.50 ± 12.08 years) underwent an experimental condition (2 min inclusion, 10 min partial exclusion) and a control condition (12 min inclusion only) in randomized order. In experiment 1, behavioral responses to partial exclusion showed two characteristics: (1) an immediate increase in ball passes to the excluding player followed (2) by a later return of participants' behavior to baseline. This finding was replicated for both genders and in comparison to a control condition in experiment 2. The dynamic behavioral response observed here may point to overlapping principles of cooperation in this ball tossing paradigm and serves as a novel experimental proxy.

[A review of the update of the German S3-guideline on diagnostics and therapy of bipolar disorders 2019]. / Überblick über Neuerungen der überarbeiteten und aktualisierten Leitlinie zur Diagnostik und Therapie bipolarer Störungen 2019.

Since the first publication of the guideline in 2012, which included critically reviewed evidence up to 2010, several hundred articles with new evidence were published and some topics of the clinical consensus needed to be reconsidered. Therefore, it was urgently necessary to revise the guideline to bring them up to date. In this article important revisions and updates are presented and the chances and limitations of the development of the guidelines and their implementation are discussed.

Minor structural modifications of bisphenol A strongly affect physiological responses of HepG2 cells.

Bisphenols represent a large group of structurally similar compounds. In contrast to bisphenol A (BPA) and bisphenol S (BPS), however, toxicological data are usually scarce, thus making bisphenols an ideal candidate for read-across assessments. BPA, bisphenol C (BPC) and a newly synthesized bisphenol A/C (BPA/C) differ only by one methyl group attached to the phenolic ring. Their EC50 values for cytotoxicity and logPOW values are comparable. However, the estrogenic activities of these bisphenols are not comparable and among this group only BPC leads to a decrease of the mitochondrial membrane potential and ATP concentration in HepG2 cells. Conversely, the cell division rate was decreased by BPS, BPA, BPC and BPA/C at 10% toxicity (EC10). At lower concentrations, only BPC significantly affected proliferation. The pro-inflammatory cytokines TGFB1 and TNF were significantly upregulated by BPC only, while SPP1 was upregulated by BPA, BPA/C and BPS. BPC led to the release of cytochrome c from mitochondria, indicating that this compound is capable of inducing apoptosis. In conclusion, the read-across approach revealed non-applicable in the case of the various structurally and physicochemically comparable bisphenols tested in this study, as the presence of one or two additional methyl group(s) attached at the phenol ring profoundly affected cellular physiology.

Oxytocin plasma levels predict the outcome of psychotherapy: A pilot study in chronic depression.

BACKGROUND: Oxytocin is associated with bonding and social deficits in psychiatric disorders and has also been discussed as a potential therapeutic intervention to augment psychotherapy. The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is a specific form of psychotherapy for chronic depression, an illness in which interpersonal deficits play a major role. In this pilot study, we investigated whether Oxytocin plasma levels predict the clinical outcome of chronic depressive patients after CBASP. METHODS: Sixteen patients with chronic depression participated in a 10-week CBASP inpatient program. Oxytocin plasma levels were measured before and after participants played a virtual ball-tossing game (Cyberball) that mimics social exclusion. Clinical outcome after CBASP was evaluated with the Beck Depression Inventory-II (BDI-II) and the 24-item Hamilton Depression Rating Scale (HAMD-24). RESULTS: After CBASP, depressive symptoms decreased significantly: the response rates were 44% (BDI-II) and 50% (HAMD-24); and the remission rates, 38% (BDI-II) and 44% (HAMD-24). Lower oxytocin plasma levels at baseline correlated with smaller changes in BDI-II scores, but not with the change in HAMD-24 scores. LIMITATIONS: The limitations of our study were the small sample size, concomitant and non-standardized pharmacotherapy, and lack of a controlled design and a follow-up period. CONCLUSIONS: Our study provides first evidence that oxytocin plasma levels may predict the outcome of psychotherapy in chronic depression. These findings need to be replicated in larger randomized, controlled trials.

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.

Attachment representations, patterns of emotion regulation, and social exclusion in patients with chronic and episodic depression and healthy controls.

BACKGROUND: The experience of social exclusion (ostracism) is linked to the etiology and maintenance of depression. Most individuals experience emotional stress in states of social exclusion. Insecurely attached individuals, especially with an unresolved trauma, show maladaptive coping in response to social stress. The present study examines (a) the differences with regards to attachment representations in episodic (ED) and chronic depressive (CD) inpatients and (b) how ostracism affects their emotional reactions. METHODS: Patients with CD (n=29) and ED (n=23) and healthy control subjects (n=29) were interviewed using the Adult Attachment Projective Picture System (AAP), a valid measure to assess attachment representation; and played a virtual ball tossing game simulating social exclusion (Cyberball). Multiple depression-related risk and protective factors were considered. We hypothesized that CD patients show the most severe attachment disorganization and are emotionally most affected by the social exclusion situation. Moreover, we explored the interaction between ostracism and attachment. RESULTS: Contradicting our hypotheses, ED and CD individuals were almost akin with regards to their attachment insecurity/disorganization and reactions to Cyberball. An emotionally altered reaction to social exclusion was identified in the insecure-disorganized depressive subgroup. LIMITATIONS: Small sample size hampering further subgroup analyses. The ED sample may include single CD subjects with recent manifestation. CONCLUSIONS: The pattern of emotion regulation in the depressive groups matches with findings from clinical studies, including attachment research. The relationship between attachment representations and ostracism should be further investigated in larger samples of depressive individuals.

[The German research network for mental disorders]. / Das deutsche Forschungsnetz zu psychischen Erkrankungen.

Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28 % of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50 %. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained support for a German center for mental disorders.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe.

PURPOSE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.

[Transcranial direct current stimulation (tDCS) for depression: Results of nearly a decade of clinical research]. / La stimulation transcrânienne à courant continu (tDCS) dans la dépression : bilan de près d'une décennie de recherche clinique.

OBJECTIVE: Since 2006 transcranial direct current stimulation (tDCS) has been investigated in the treatment of depression. In this review, we discuss the implications and clinical perspectives that tDCS may have as a therapeutic tool in depression from the results reported in this domain. METHODS: A comprehensive literature review has found nearly thirty articles - all in English - on this topic, corresponding to clinical studies, placebo-controlled or not, case reports and reviews. RESULTS: Several meta-analyses showed that the antidepressant effects of active tDCS are significant against placebo, but variable, mainly due to the heterogeneity of the patients included in the studies, for example regarding the resistance to antidepressant treatment. CONCLUSIONS: Specific recommendations for the use of tDCS in treating depression may not yet be available, but some elements of good practice can be highlighted. Of particular note is that anodal tDCS of the left prefrontal cortex at 2mA for 20 minutes per day has a potential therapeutic value without risk of significant side effects: tDCS offers safe conditions for clinical use in the treatment of depression.

[Transcranial direct current stimulation for depressive disorders]. / Transkranielle Gleichstromstimulation bei depressiven Störungen.

Major depressive disorders are one of the most prevalent psychiatric disorders worldwide but approximately 20-30 % of patients do not respond to standard guideline conform treatment. Recent neuroimaging studies in depressive patients revealed altered activation patterns in prefrontal brain areas and that successful cognitive behavioral therapy and psychopharmacological interventions are associated with a reversal of these neural alterations. Therefore, a direct modulation of prefrontal brain activation by non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) seems to be a promising and innovative approach for the treatment of depressive disorders. In addition, recent neuropsychological findings indicated an augmentation of positive tDCS effects by simultaneous external activation of the stimulated brain area, for example by cognitive training tasks. Based on these findings, the possibility to augment cognitive-emotional learning processes during cognitive behavioral therapy by simultaneous tDCS to increase antidepressive therapeutic effects is discussed in this article.

Transcranial Direct Current Stimulation (tDCS) in a Patient with PRES and Bipolar Depression.

Transcranial direct current stimulation (tDCS) is a non-invasive tool for brain stimulation and has proven efficacy in depressive disorders. Here, we report the case of a patient with recurrent bipolar depressive disorder and neurologic complications due to posterior reversible encephalopathy syndrome (PRES) due to parathyroid adenoma. During a long-term hospital stay, multiple drug regimens did not resolve depressive symptoms. Finally, an add-on therapy with tDCS brought improvement of symptoms. This case highlights the feasibility of tDCS in treatment-resistant depression and concomitant neurologic disorder.

[Non-invasive brain stimulation for treatment of schizophrenic psychoses]. / Hirnstimulationsverfahren zur Behandlung schizophrener Psychosen.

Despite many different available pharmacological and psychosocial treatment options, an optimal control of symptoms is only partly possible for most schizophrenia patients. Especially, persistent auditory hallucinations, negative symptoms and cognitive impairment are difficult to treat symptoms. Several non-invasive brain stimulation techniques are increasingly being considered as new therapeutic add on options for the management of schizophrenia, targeting these symptom domains. The technique which has been available for the longest time and that is best established in clinical care is electroconvulsive therapy (ECT). New stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) allow a more pathophysiological-based approach. This review article introduces various non-invasive brain stimulation techniques and discusses recent treatment studies on schizophrenia. In total, the novel brain stimulation techniques discussed here can be considered relevant add on therapeutic approaches for schizophrenia. In this context, the best evidence is available for the application of rTMS for the treatment of negative symptoms and persistent auditory hallucinations; however, negative studies have also been published for both indications. Studies using other non-invasive brain stimulation techniques showed promising results but further research is needed to establish the clinical efficacy. Based on a growing pathophysiological knowledge, non-invasive brain stimulation techniques provide new treatment perspectives for patients with schizophrenia.