Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany.

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study's aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as "probable psychiatric AE (pAE)," if well-characterized neuronal IgG autoantibodies were detected or "possible pAE" (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.

Behavioral evidence for an impairment of affective theory of mind capabilities in chronic depression.

BACKGROUND: The only treatment specifically developed for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), is based amongst others on the hypothesis that chronically depressed patients (CD) show considerable deficits of affective theory of mind (ToM) capabilities. Data are scarce, however, and it remains unclear if ToM deficits are specific or if they arise from global cognitive deficits associated with depression. This study investigates the specific deficits of affective ToM abilities in CD. SAMPLING AND METHODS: ToM abilities were assessed in 26 medication-free CD and 26 matched healthy controls (HC) by means of a previously established false-belief ToM cartoon task. Since the task allowed an intern control for cognitive factors - operationalized in a visuospatial ToM task - it was possible to investigate specific affective ToM deficits. RESULTS: As hypothesized, the CD showed a significant specific slowdown of affective ToM compared to cognitive ToM (3rd person perspective) when compared to HC. Simultaneously, we observed a general deterioration of all ToM functions in CD. CONCLUSIONS: This study provides evidence that CD have a mentalization deficit, specifically for affective ToM functions. This deficit is combined with a general deterioration of ToM functions, most likely attributable to frequently described cognitive deficits in depression.

Development and Pilot Testing of an Algorithm-Based Approach to Anticholinergic Deprescribing in Older Patients.

BACKGROUND: Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is still scant. This study proposes an algorithm-based approach to evaluate and reduce anticholinergic load, and reports the results of its pilot testing. METHODS: Based on published evidence and expert opinion, a list of 85 anticholinergic drugs and 21 algorithms for reducing anticholinergic load, e.g., by recommending alternative drugs with lower risk, were developed. An accompanying test battery was assembled by focusing on instruments that sensitively reflect anticholinergic load and may be sensitive to depict changes (Neuropsychological Assessment Battery to measure memory and attention, validated assessments for constipation, urinary symptoms, and xerostomia, as well as blood biomarkers). The approach was pilot-tested in a geriatric rehabilitation unit, with clinician feedback as the primary outcome and characterization of anticholinergic symptoms as the secondary outcome. The intervention was delivered by a pharmacist and a clinical pharmacologist who used the algorithms to generate personalized recommendation letters. RESULTS: We included a total of 20 patients, 13 with anticholinergic drugs and 7 without. Recommendations were made for 22 drugs in nine patients from the intervention group, of which seven letters (78%) were considered helpful and 8/22 (36%) anticholinergic drugs were discontinued, reducing anticholinergic load in seven patients. In contrast to patients without drug change, memory assessment in patients with reduced anticholinergic load improved significantly after 2 weeks (6 ± 3 vs. -1 ± 6 points). CONCLUSIONS: The approach was well received by the participating physicians and might support standardized anticholinergic deprescribing.

[Childhood Experiences of Care and Abuse (CECA) - validation of the German version of the questionnaire and interview, and results of an investigation of correlations between adverse childhood experiences and suicidal behaviour]. / Validierung der deutschen Version von Fragebogen und korrespondierendem Interview sowie Ergebnisse einer Untersuchung von Zusammenhangen belastender Kindheitserlebnisse mit suizidalen Verhaltensweisen.

OBJECTIVES: Validation of the German translation of a questionnaire and the corresponding interview for the assessment of adverse childhood experiences within the family environment and investigation of an association of these experiences with suicidal behaviour. METHOD: The questionnaire was tested in a consecutively recruited sample of 125 psychiatric inpatients (aged 13 to 25 years) at the University Hospital Heidelberg. Retests and corresponding interviews were also performed. Suicidal behaviour was measured by the Paykel Suicide Scale. RESULTS: The questionnaire and interview showed very good internal consistency and retest reliability; the interrater reliability of the interview was good, and there was a significant correlation between the questionnaire and the interview. Suicidal behaviour was significantly associated to all adverse childhood experiences, but maternal neglect and antipathy proved to be the best predictors of suicidal behaviour. CONCLUSIONS: The CECA instruments are reliable and valid instruments for the assessment of adverse childhood experiences. They assess a broad spectrum of adverse childhood experiences including negative bonding experiences. The association of these experiences to higher levels of suicidal behaviour shows the importance of assessing such experiences in research and therapy.

Let the team fix it?-Performance and mood of depressed workers and coworkers in different work contexts.

Depression in the workplace is a significant factor for reduced personal well-being and productivity. Consequently, this has negative effects on the economic success of the companies in which depressed people are employed. In addition, the economy has to deal with the significant burden of this illness on the health system. In this paper, we investigated how different working contexts-working in a group or individually-influenced depressed individuals towards higher or lower well-being and productivity. We examined this using a laboratory experiment. In this setting, we were also able to analyze how, in turn, a depressive individual impacted the productivity and affective situation of their workgroup, reflecting the company perspective. The experimental design mimicked the very basic processes of a workplace in a stylized way. We used two distinct samples: subclinically and clinically depressed, both working in a group with healthy controls. As expected, we found generally lower performance in the clinically depressed sample, but in the subclinically depressed sample, we only found this in the individual work context. In contrast to our expectations, the performance of subclinically depressed individuals working in groups with healthy controls was even higher than that of healthy controls in homogenously healthy groups. The performance of the entire group with a depressed member was lower for the sample with clinically manifested depression, while the performance of groups with a subclinically depressed participant was significantly higher than the performance of homogeneously non-depressed control groups. We discuss our results with a focus on the design of workplaces to both re-integrate clinically depressed employees and prevent subclinically depressed employees from developing major depression.

[Medicinal Complex Therapy - Drug Interaction of Valproate and Dipyrone]. / Medikamentöse Komplextherapie ­ Arzneimittelinteraktionen von Valproat und Metamizol.

The clinical relevance of the drug interaction between valproic acid and dipyrone is presented in the context of a gerontopsychiatric case. It is assumed that dipyrone at a dose of 4 g/d has a relevant influence on the valproate level and the associated clinical outcome. This may be due to a possible induction of CYP2B6 and increased valproate metabolism. In the case of a treatment of valproate combined with dipyrone, a close monitoring of the valproate level is recommended.

Self-injury: Treatment, Assessment, Recovery (STAR): online intervention for adolescent non-suicidal self-injury - study protocol for a randomized controlled trial.

BACKGROUND: Non-suicidal self-injury (NSSI) is a clinically significant behavior affecting approximately 18% of adolescents and young adults worldwide. The importance of NSSI is supported by its association with a broad spectrum of mental disorders. Despite its high relevance, evidence-based, specific, time-, and cost-effective treatment approaches are scarce. Cognitive behavioral therapy (CBT) seems effective in reducing the frequency of NSSI in adolescents and young adults. However, young people are often reluctant to seek professional help and effective interventions adressing NSSI are not sufficiently available across all regions of Germany. Research indicates that the majority of youth with risk behavior (including NSSI) prefer technology-based interventions. To date, effective interventions for adolescents and young adults with NSSI that are deliverd online are not available. METHODS: The present project aims to develop and evaluate an online intervention for adolescents and young adults with NSSI based on the content of a recently evaluated face-to-face short-term program that includes elements of CBT and dialectical behavior therapy (DBT): "The Cutting Down Programme" (CDP). The efficacy of the new online CDP intervention will be tested in a randomized controlled trial (RCT) in which n = 700 youths engaging in repetitive NSSI will participate in either an online psychoeducation (n = 350) or online CDP (n = 350). Within a postline assessment four months after baseline (end of treatment; T1), and follow-up evaluations 12 and 18 months after baseline (follow-ups; T2 and T3), NSSI and comorbid symptoms as well as quality of life will be assessed. It is hypothesized that participants receiving online CDP report a greater reduction in the frequency of NSSI within the last three months at T2 (primary endpoint) compared to those receiving online psychoeducation. Exploratory analyses will focus on predictors of treatment outcome. DISCUSSION: We report on the development and evaluation of an online intervention for adolescents and young adults engaging in NSSI based on the CDP. If supported by empirical evidence, an online-based intervention for NSSI might help to overcome the limited availability of adequate interventions for youth. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00014623 . Registered on 22 May 2018.

Cochlear Implant in Severe Impaired Psychiatric Patients: A Case Series.

OBJECTIVE: Psychotic disorders and intelligence deficiencies are no longer contraindications for cochlear implantation regarding the revised German guidelines from May 2012. This article aims to evaluate the outcome of patients with severe psychiatric comorbidities. Therefore the database of the Cochlear Implant Center of the University Hospital of Heidelberg was investigated. STUDY DESIGN: Retrospective case review. METHODS: We present three patients who received a cochlear implant (CI) despite a serious psychiatric disorder. Two were sent from psychiatrists asking if a CI was possible for their profound hearing loss. One patient had acoustic hallucinations and a recurrent depressive disorder, the other had a schizophrenic psychosis and a minor impairment of intelligence. The third patient had a recurrent depressive disorder, a posttraumatic stress disorder, a chronic pain disorder, and paranoid personality traits. We discuss the preoperative diagnosis, course of diseases, and psychosocial situation. RESULTS: All three patients received a CI and rehabilitation in the Cochlear Implant Center of the University Hospital of Heidelberg. All three of them opted for a second implant and developed a good hearing outcome. Free field understanding of words in quite is for all three of them over 60% in the Freiburger monosyllable test with two implants, similar to nonpsychiatric patients' results. No patient has acceptance problems. In the long run, no aggravation of the psychiatric diseases occurred. CONCLUSION: With interdisciplinary evaluation, a cochlear implantation is possible in severely impaired psychiatric patients. For a good result the indication is to be discussed interdisciplinary.

Functional Correlates of childhood maltreatment and symptom severity during affective theory of mind tasks in chronic depression.

Among multiple etiological factors of depressive disorders, childhood maltreatment (CM) gains increasing attention as it confers susceptibility for depression and predisposes to chronicity. CM assumedly inhibits social-cognitive development, entailing interactional problems as observed in chronic depression (CD), especially in affective theory of mind (ToM). However, the extent of CM among CD patients varies notably as does the severity of depressive symptoms. We tested whether the extent of CM or depressive symptoms correlates with affective ToM functions in CD patients. Regional brain activation measured by functional magnetic resonance imaging during an affective ToM task was tested for correlation with CM, assessed by the Childhood Trauma Questionnaire (CTQ), and symptom severity, assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS), in 25 unmedicated CD patients (mean age 41.52, SD 11.13). Amygdala activation during affective ToM correlated positively with CTQ total scores, while (para)hippocampal response correlated negatively with MADRS scores. Our findings suggest that differential amygdala activation in affective ToM in CD is substantially modulated by previous CM and not by the pathophysiological equivalents of current depressive symptoms. This illustrates the amygdala's role in the mediation of CM effects. The negative correlation of differential (para)hippocampal activation and depressive symptom severity indicates reduced integration of interactional experiences during depressive states.

Adverse childhood experiences and their impact on frequency, severity, and the individual function of nonsuicidal self-injury in youth.

This study aimed to investigate a specific relationship between nonsuicidal self-injury (NSSI) and a variety of adverse childhood experiences (ACEs) over and above childhood abuse and their impact on frequency, severity, and functions of NSSI. A sample of 125 inpatients (aged 13 to 26) was consecutively recruited within a psychiatric university hospital. Frequency, methods and functions of NSSI were assessed by the Functional Assessment of Self-Mutilation (FASM), ACEs were assessed by the Childhood Experiences of Care and Abuse Questionnaire (CECA.Q). The 12 month prevalence of NSSI in this representative, clinical sample was 60.0%. Engagement in NSSI was significantly related to ACEs with highest associations for maternal antipathy and neglect. Whilst ACEs were not associated with frequency or severity of NSSI, some ACEs were significantly related to the automatic functions of NSSI (e.g., affect regulation, anti-dissociative function or self-punishment) as well as to a peer identification function. NSSI represents a frequent phenomenon among young clinical populations and seems to be specifically related to ACEs with maternal antipathy or neglect commonly featured over and above experiences of abuse. Since ACEs also influence the functions of NSSI such factors need to be examined as part of clinical care planning.

Effects of subtotal fasting on plasmatic coagulation, fibrinolytic status and platelet activation: a controlled pilot study in healthy subjects.

BACKGROUND AND AIM: There is considerable controversy as to whether fasting can be recommended to patients with cardiovascular disease. The objective of this study was to determine whether a well-known method of 1-week subtotal fasting affects hemostasis in healthy subjects. METHODS AND RESULTS: Analyses were carried out before, four times during and 3 days after fasting in 12 fasting subjects (< 300 kcal/day, only from carbohydrates) (group 1), and 8 control subjects (group 2). Plasmatic coagulation (prothrombin time, partial thromboplastin time, p < or = 0.001) and fibrinolysis (plasminogen, plasmin-antiplasmin-complex, p < 0.05) increased during fasting but remained within the normal limits. While the platelet count was similar in both groups, platelet sensitivity to stimulators was reduced in group 1 (P-selectin and activated GP IIb/IIIa on ADP-stimulated platelets, p < or = 0.01). Furthermore, soluble P-selectin (p < or = 0.01) and C-reactive protein were decreased in comparison to group 2 (p < or = 0.05). CONCLUSIONS: Hemostasis and inflammation parameters during 1-week subtotal fasting do not imply an increase in cardiovascular risk.