Guilt and Shame in Patients with Obsessive-Compulsive Disorders.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a tremendous psychiatric illness with a variety of severe symptoms. Feelings of shame and guilt are universal social emotions that fundamentally shape the way people interact with each other. Mental illness is therefore often related to pronounced feelings of shame and guilt in a maladaptive form. METHODS: A total of 62 participants (38 women and 24 men) were clinically and psychometrically investigated. RESULTS: The OCD patients (n = 31) showed a maladaptive guilt and shame profile, characterized by increased interpersonal feelings of guilt accompanied by a stronger tendency to self-criticism and increased punitive sense of guilt with a simultaneous prevailing tendency to perfectionism, as well as an increased concern for the suffering of others. The proneness to profuse shame in OCD patients seems to be in the context of the violation of inner values and a negative self-image with persistent self-criticism. CONCLUSION: Although there are limitations with a small sample size in this monocentric approach, our study underlines the importance of an individual consideration of the leading obsessive-compulsive symptomatology, especially in the context of very personal feelings of guilt and shame. Further multidimensional studies on guilt and shame could contribute to their implementation more strongly in individualized psychotherapy.

Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice.

Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.

[Virtual reality in teaching using mentally ill patient avatars]. / Virtuelle Realität in der Lehre mit psychisch kranken Patientenavataren.

BACKGROUND: Medical interaction and exploration techniques are the most important tools that medical students have to acquire in the subject of psychiatry and psychotherapy. The new digital technologies currently available, such as virtual reality (VR), as important supplements can contribute to a significant improvement in the teaching of psychiatric-psychopathological learning content as well as, in particular, the technique of ascertaining the psychiatric history and diagnosis. OBJECTIVE: Evaluation of the Bochum Avatar Exploration Project (AVEX) as part of the curricular course in medical studies at the Ruhr University Bochum for its possibilities to convey learning content and techniques of anamnesis and diagnosis in the subject of psychiatry and psychotherapy. METHODS: In AVEX, a total of 87 medical students in the clinical study section have so far been able to enter into a dialogue with "mentally ill" avatars and gain experience with VR technology as a learning and teaching method in the subject of psychiatry and psychotherapy. RESULTS: Despite the limited possibilities for interaction with the digital avatars, it is possible to achieve a substantial transfer of learning content in psychiatry; however, the students must be well supported by the lecturers. CONCLUSION: The AVEX project already shows promising possibilities for supplementing the teaching of medical students, even if the fit of questions and replies in dialogue with the virtual avatars still needs to be improved. As advances in the linguistic communication of emotions and the visual effects of the avatar representation can be predicted, the significance of this technology will continue to increase.

Emotional Context Effects on the Rating of Ambiguous Facial Expressions in Depression and Schizophrenia Spectrum Disorders.

ObjectiveTo investigate the influence of visual contextual information on emotion recognition of ambiguous facial expressions in depression and schizophrenia spectrum disorders. Method: Ambiguous facial expressions and emotional contexts representing anger, disgust, fear, joy, sadness and surprise were validated in a pre-test with healthy independent raters. Afterwards, 20 healthy participants (8 women, 12 men; mean age 24.35 ± 2.85 years), 20 participants with schizophrenia spectrum disorders (9 women, 11 men; mean age 40.25 ± 11.68 years) and 19 participants with depression (11 women, 8 men; mean age 43.74 ± 12.65 years) rated the emotional content of nine different faces in seven different emotion-suggesting contexts. The proportions of context-congruent answers and differences between emotion ratings in each context were analysed using non-parametric Kruskal-Wallis and explorative, paired Wilcoxon tests. Correlational analyses explored the influence of clinical symptoms assessed by clinician-administered scales. Results: The overall proportion of context-congruent answers did not differ between participants with depression and schizophrenia spectrum disorders compared to healthy participants. Participants with schizophrenia spectrum disorders were more susceptible to anger-suggesting contexts and participants with depression were more susceptible to fear-suggesting contexts. Differences in emotion recognition were associated with the severity of depressive, but not psychotic, symptoms. Conclusion: Despite increased susceptibility to anger-suggesting cues in schizophrenia and to fear-suggesting cues in depression, visual contextual influence remains largely consistent with healthy participants. Preserved emotional responsiveness suggests an efficacy of emotion training but emphasizes the need for additional research focusing on other factors contributing to social interaction deficits.

Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features.

BACKGROUND: Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features. METHODS: Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar). RESULTS: For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11-0.361) and a balanced accuracy of 63.1% (95% CI 55.9-70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI -0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6-67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance. CONCLUSIONS: Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.

Treatment of adult attention-deficit hyperactivity disorder (ADHD) with transcranial direct current stimulation (tDCS): study protocol for a parallel, randomized, double-blinded, sham-controlled, multicenter trial (Stim-ADHD).

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects.Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148).

Young people at risk for developing bipolar disorder: Two-year findings from the multicenter prospective, naturalistic Early-BipoLife study.

Early identification and intervention of individuals with an increased risk for bipolar disorder (BD) may improve the course of illness and prevent long­term consequences. Early-BipoLife, a multicenter, prospective, naturalistic study, examined risk factors of BD beyond family history in participants aged 15-35 years. At baseline, positively screened help-seeking participants (screenBD at-risk) were recruited at Early Detection Centers and in- and outpatient depression and attention-deficit/hyperactivity disorder (ADHD) settings, references (Ref) drawn from a representative cohort. Participants reported sociodemographics and medical history and were repeatedly examined regarding psychopathology and the course of risk factors. N = 1,083 screenBD at-risk and n = 172 Ref were eligible for baseline assessment. Within the first two years, n = 31 screenBD at-risk (2.9 %) and none of Ref developed a manifest BD. The cumulative transition risk was 0.0028 at the end of multistep assessment, 0.0169 at 12 and 0.0317 at 24 months (p = 0.021). The transition rate with a BD family history was 6.0 %, 4.7 % in the Early Phase Inventory for bipolar disorders (EPIbipolar), 6.6 % in the Bipolar Prodrome Interview and Symptom Scale-Prospective (BPSS-FP) and 3.2 % with extended Bipolar At-Risk - BARS criteria). In comparison to help-seeking young patients from psychosis detection services, transition rates in screenBD at-risk participants were lower. The findings of Early-BipoLife underscore the importance of considering risk factors beyond family history in order to improved early detection and interventions to prevent/ameliorate related impairment in the course of BD. Large long-term cohort studies are crucial to understand the developmental pathways and long-term course of BD, especially in people at- risk.

[Care trajectories of homeless or precariously housed mentally ill patients from two psychiatric-psychotherapeutic hospitals in North Rhine-Westphalia]. / Versorgungstrajektorien wohnungsloser oder in prekären Wohnverhältnissen lebender psychisch Erkrankter zweier psychiatrisch-psychotherapeutischer Kliniken der Regelversorgung Nordrhein-Westfalens.

OBJECTIVES: Mental illness and homelessness are often associated with each other. The study aim was to describe the care trajectories of psychiatric inpatients admitted from precarious housing or homelessness. METHODS: An anonymized data collection was performed at two psychiatric hospitals in North Rhine-Westphalia. RESULTS: Of 76 identified patients, every other was discharged to unsecured housing or homelessness. An unresolved housing situation delayed discharge in almost every third case. Upon discharge outpatient somatic or psychiatric treatment was not secured in more than 30%, and in more than 40% of cases, resp. CONCLUSION: Improvement of the housing situation is possible in a minority of cases for psychiatric inpatients admitted from unsecured housing. The unresolved housing situation was seen as an obstacle to discharge in every third case.

Understanding suicidal ideation-a network analysis of the Interpersonal Needs Questionnaire.

INTRODUCTION: Identifying various interacting risk factors for suicidality is important to develop preventive measures. The Interpersonal-Psychological Theory of Suicidal Behavior (IPTS) postulates suicidal ideation resulting from the occurrence of Perceived Burdensomeness (PB) and Thwarted Belongingness (TB). Suicidal behavior ultimately occurs if people have a Capability for Suicide. In past studies, the validity of TB was often not empirically confirmed, questioning which of the aspects of TB are central and related to suicidal ideation and whether applied measurement methods adequately capture the construct. METHOD: Using a sample of 3,404 individuals from different clinical and nonclinical settings, 30% (1,023) of whom reported suicidal ideation, two network analyses were conducted on the Interpersonal Needs Questionnaire (INQ) and a variable mapping suicidal ideation. RESULTS: Analyses revealed that some items of the INQ were not related to suicidal ideation and the most central items did not have the strongest associations to suicidal ideation. CONCLUSION: Based on these results, a shortened version of the INQ with the four items that showed the strongest associations with suicidal ideation in the network analyses was suggested.

The significance of nonurgent psychiatric emergencies in an ED: a retrospective study.

BACKGROUND: In emergency departments, patients with mental health conditions are a major concern and make up the third or fourth of the most common diagnosis seen during all consultations. Over the past two decades, there has been a noticeable rise in the number of cases, particularly due to an increase in nonurgent visits for somatic medical issues. The significance of nonurgent visits for psychiatric patients is yet to be determined. This study aims to uncover the significance and identify the characteristics of this group. METHODS: A retrospective analysis of psychiatric emergency visits at an interdisciplinary emergency department of a German general hospital in 2015 was conducted. For this purpose, patient records were reviewed and evaluated. An analysis was conducted based on the German definition of psychiatric emergencies according to the German guidelines for emergency psychiatry. RESULTS: A total of 21,124 emergency patients visited the evaluated Emergency Department. Of this number, 1,735 psychiatric patient records were evaluated, representing 8.21% of the total population. Nearly 30% of these patients did not meet any emergency criteria according to German guidelines. Significant differences were observed between previously treated patients and those presenting for the first time. CONCLUSIONS: The high proportion of nonurgent psychiatric patients in the total volume of psychiatric emergency contacts indicates a possible control and information deficit within the emergency system. Just as prior research has emphasized the importance of investigating nonurgent somatic medical visits, it is equally imperative to delve into studies centered around psychiatric nonurgent presentations.

Death Anxiety in Obsessive-Compulsive Disorders.

Objective: Death anxiety has long been attributed a role as a psychopathologically decisive factor in the development of mental illnesses such as obsessive-compulsive disorder (OCD). For example, patients with washing compulsions associate their behavior with a fear of life-threatening diseases or patients with control compulsions report that the constant checking is driven by the fear of fatal or deadly consequences for the occupants.Method: The Bochum Questionnaire to Assess Death Anxiety and Attitudes Towards Death (BOFRETTA) was administered to 31 patients with OCD and 31 healthy volunteers within a semi-structured interview using broad psychometry.Results: OCD patients showed increased death anxiety and negative attitute to death in comparison to healthy volunteers. A significant correlation was found between BOFRETTA-anxiety and the currently present religious obsessive thoughts.Conclusions: Our investigation provides further findings on the role of death anxiety and the problematic attitude towards death in OCD patients.

Genetic variation of the 5-HT1A rs6295, 5-HT2A rs6311, and CNR1 rs1049353 and an altered endocannabinoid system in depressed patients.

BACKGROUND: The reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives attention. METHOD: In this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5-HT2A rs6311, and 5-HT1A rs6295 by high-resolution melting genotyping. The concentration of arachidonoyl ethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) in the blood was measured by liquid chromatography-tandem mass spectrometry. Additionally, depression and anxiety symptoms were evaluated based on self-questionnaires. Fifty-nine patients participated in a second appointment to measure the concentration of AEA, 2-AG, and symptoms of depression and anxiety. RESULTS: We observed higher AEA and decreased 2-AG concentrations in patients with depression compared to healthy participants. During the treatment, the concentrations of AEA and 2-AG did not change significantly. In patients higher symptoms of anxiety correlated with lower concentrations of 2-AG. Gender differences were found concerning increased 2-AG concentration in male patients and increased anxiety symptoms in female patients. Genotypic variations of 5-HT1A rs6295 and 5-HT2A rs6311 are associated with altered serotonergic activity and serotonin content in patients. CONCLUSION: In conclusion, it seems that the endocannabinoid system, especially the endocannabinoids 2-AG and AEA, and genetic variations of the 5-HT1A and 5-HT2A could play a role in patients with depression and may be involved in a depressive disorder.

Microbiome composition and central serotonergic activity in patients with depression and type 1 diabetes.

The role of gut-brain axis functioning gains growing attention in research on the pathophysiology of major depressive disorders. Here, especially consequences of altered microbiota composition on tryptophan metabolism resulting in altered serotonergic neurotransmission in the central nervous system (CNS) have reached a central position. Previous research, however, mainly focused on either microbiota and peripheral serotonin levels or central serotonergic neurotransmission. The present study aimed to combine the analysis of microbiota composition and central serotonergic activity using a valid neurophysiological indicator. We recruited 19 adult patients with type 1 diabetes and depression (D + D; 7 males), 19 patients with type 1 diabetes (D-; 7 male), and 20 healthy participants (HC; 7 males). Next to the analysis of fecal microbiota regarding α- and ß-diversity, the loudness dependence of auditory evoked potential (LDAEP) was investigated, a non-invasive measurement of central serotonergic activity. High α-diversity was associated with high LDAEP, i.e., low serotonergic activity, in patients with diabetes and additional depression. Furthermore, relative abundances of bacterial families belonging to Bacteroidetes, Proteobacteria and Firmicutes were shown to have an impact on central serotonergic activity. This finding was supported by a tendency indicating an association of central serotonergic activity with the Bacteroidetes-Firmicutes ratio in both patients' groups. Together, this data suggests that the guts' microbiota composition might play an important role in regulating the central serotonergic activity in the brain.

Rodent models for mood disorders - understanding molecular changes by investigating social behavior.

Mood disorders, including depressive and bipolar disorders, are the group of psychiatric disorders with the highest prevalence and disease burden. However, their pathophysiology remains poorly understood. Animal models are an extremely useful tool for the investigation of molecular mechanisms underlying these disorders. For psychiatric symptom assessment in animals, a meaningful behavioral phenotype is needed. Social behaviors constitute naturally occurring complex behaviors in rodents and can therefore serve as such a phenotype, contributing to insights into disorder related molecular changes. In this narrative review, we give a fundamental overview of social behaviors in laboratory rodents, as well as their underlying neuronal mechanisms and their assessment. Relevant behavioral and molecular changes in models for mood disorders are presented and an outlook on promising future directions is given.

Death Anxiety in the Context of Religion, Personality and Life Meanings.

Previous studies on the context between death anxiety and religion do not provide any clear evidence regarding "anxiety buffer" function. In this explorative study, death anxiety and attitude to death were determined in the context of mood, personality and meaning of life among groups of Muslims (n = 60) and Christian Protestants (n = 60). Death anxiety and attitude to death were assessed using the Bochum questionnaire for recording death anxiety and attitudes to death. Death anxiety was mild to moderate in our healthy Participants of Muslim and Christian faith. Attitude towards death was therefore much more pronounced among Muslim members than Christians. The influence of religious beliefs on the fear of death does not appear to be direct and linear. Sources that provide meaning in life and emotional stability can contribute to a reduction in death anxiety and a less problematic attitude towards death.

l-Arginine/nitric oxide pathway and oxidative stress in adults with ADHD: Effects of methylphenidate treatment.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a mental disorder that was once thought to occur only in children. Meanwhile, it is known that adults can also be affected. The first-line drug in children and adults to treat symptoms of inattention, impulsivity, lack of self-regulation, and hyperactivity is methylphenidate (MPH). Known adverse effects of MPH include cardiovascular problems, such as elevated blood pressure and heart rate. Therefore, biomarkers to monitor potential cardiovascular side effects of MPH are needed. The l-Arginine/Nitric oxide (Arg/NO) pathway is involved in noradrenaline and dopamine release as well as in normal cardiovascular functioning and is therefore a prime candidate for the search of biomarkers. The aim of the present study was to investigate the Arg/NO pathway as well as oxidative stress in adult ADHD patients in plasma and urine and the potential influence of MPH medication. METHODS: In plasma and urine samples of 29 adults with ADHD (39.2 ± 10.9 years) and 32 healthy adults serving as controls (CO) (38.0 ± 11.6 years) the major NO metabolites nitrite and nitrate, Arg, the NO synthesis inhibitor asymmetric dimethylarginine (ADMA) and its major urinary metabolite dimethylamine (DMA) as well as malondialdehyde (MDA) were measured by gas chromatography-mass spectrometry. RESULTS: Of the 29 patients with ADHD 14 were currently without MPH treatment (-MPH) and 15 were treated with MPH (+MPH). Plasma nitrate concentrations were significantly higher in patients not treated with MPH vs. CO (-MPH 60.3 µM [46.2-76.0] vs. CO 44.4 µM [35.0-52.7]; p = 0.002), while plasma nitrite tended to be higher in -MPH patients (2.77 µM [2.26-3.27]) vs. CO (2.13 µM [1.50-2.93]; p = 0.053). Additionally, plasma creatinine concentrations were significantly different, with -MPH showing significantly higher concentrations than the other two groups (-MPH 141 µM [128-159]; +MPH 96.2 µM [70.2-140]; Co 75.9 µM [62.0-94.7]; p < 0.001). Urinary creatinine excretion tended to be lowest in -MPH group vs. +MPH and CO (-MPH 11.4 ± 8.88 mM; +MPH 20.7 ± 9.82 mM; 16.6 ± 7.82 mM; p = 0.076). None of the other metabolites, including MDA, a marker of oxidative stress, showed a difference between the groups. CONCLUSION: Adult patients with ADHD, who are not treated with MPH (-MPH), showed varied Arg/NO pathway, but Arg bioavailability seemed to be consistent over the groups. Our findings imply that urinary reabsorption may be increase and/or excretion of nitrite and nitrate may be decreased in ADHD, resulting in an increase in the plasma concentration of nitrite. MPH seems to partially reverse these effects by not yet known mechanisms, and does not affect oxidative stress.

Psychosocial functioning as a mediator between childhood trauma and symptom severity in patients with schizophrenia.

BACKGROUND: There is empirical evidence that childhood trauma is associated with symptom severity and psychosocial functioning in schizophrenia. OBJECTIVE: The present study aimed to further elucidate these associations by examining which subdomains of schizophrenic symptoms and psychosocial functioning are associated with childhood trauma. In addition, it should be tested whether the association between childhood trauma and schizophrenic symptoms is mediated by psychosocial functioning. PARTICIPANTS AND SETTING: Participants of this study were 253 inpatients of five psychiatric hospitals diagnosed with schizophrenia. Clinical interviews were conducted with these patients towards the end of therapy. METHODS: Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ), a retrospective self-report scale. Schizophrenic symptoms were measured with the Positive and Negative Syndrome Scale (PANSS) and psychosocial functioning with the Personal and Social Performance Scale (PSP), two measures for ratings by experts. RESULTS: Most participants were affected by childhood trauma, with 91.7 % reporting at least one trauma. Childhood trauma showed small but significant correlations with positive symptoms and general psychopathology, and also with psychosocial functioning in the occupational and social area and in control over aggressive behavior. Psychosocial functioning was shown to mediate the association between childhood trauma and symptom severity, whereby full mediation was found with regard to positive symptoms and partial mediation with regard to general psychopathology. CONCLUSIONS: The findings suggest that good psychosocial functioning mitigates the negative impact of childhood trauma on illness severity in schizophrenic patients. Therapeutic interventions that promote personal and social resources are therefore useful in the treatment of schizophrenia.