Kim Hinkelmann’s research while affiliated with Charité Universitätsmedizin Berlin and other places

Depression is a common and often very debilitating disease causing a high number of years lost to disability worldwide. Mortality rates are high due to suicide and depression-associated somatic disorders, which seem to have a bidirectional connection. Depression is considered to be stress associated. Adverse life events such as losses, interpersonal conflicts, financial issues, unemployment, and loneliness are often found in the patient history. Also childhood maltreatment is a known risk factor. Chronic stress can cause maladaptive changes in different neurobiological systems and may contribute to the development of depression. Relevant changes have been described in the stress-response and immune systems of persons with depression and those with childhood trauma or abuse. Psychotherapy and antidepressants are both effective, and current treatment guidelines recommend their combination in severe depressive episodes.

Objective Psychogenic non-epileptic seizures (PNES), a common phenomenon in neurological settings, are regarded as a paroxysmal type of functional neurological disorder (FND). In a substantial proportion, PNES are disabling with poor long-term outcomes and high economic costs. Despite the clinical and financial consequences of PNES, there is still a lack of controlled clinical trials on the treatment of this challenging disorder. The study aims to evaluate the feasibility and collect first evidence of the efficacy of a group based-intervention in PNES-patients. Methods A pilot randomized controlled feasibility study with a parallel-group design was performed in adult outpatients with PNES to evaluate a new body-focused group therapy (CORDIS) versus guided self-help groups. Self-assessment of dissociation (Dissociation Experience Scale—DES-20) and seizure severity (Liverpool Seizure Severity Scale—LSSS) were assessed two weeks before and two weeks after the treatment intervention and also six months after treatment as primary outcome parameters. Results A total of 53 patients were recruited from a specialized outpatient clinic, and out of those, 29 patients completed either the body-focused group therapy program ( n = 15) or a guided self-help group (SHG) therapy ( n = 14). When analyzing the ITT sample ( n = 22 CORDIS group, n = 20 SHG), both groups showed an effect on seizure severity and level of dissociation. In the per protocol sample ( n = 13 CORDIS group, n = 12 SHG), CORDIS was superior to the self-help group for reducing seizure severity 6 months after the treatment. Significance CORDIS is a newly developed body-focused group therapy program for adults with PNES. Further studies should include a multicentric design with a higher number of participants.

Objective: Psychogenic non-epileptic seizures (PNES) are considered functional neurological symptoms and are highly prevalent in specialized epilepsy clinics. The underlying mechanisms of PNES are not fully understood. Recent findings point towards possible alterations in attention and executive functions. This study aimed to extend the current knowledge of attention and executive function in patients with PNES and to assess possible relationships between seizures and dissociation, childhood trauma, and cognitive function. Methods: We recruited 40 patients with PNES and 40 sex, age and education matched healthy controls (HC) in this study. Participants completed self-report questionnaires to assess early life stress (Childhood Trauma Questionnaire, CTQ), dissociation (Dissociative Experience Scale; German version FDS-20) and depression (Patient Health Questionnaire, PHQ-9). Executive functions and attention were assessed with the Trail-Making Test (TMT), Digit Span (DS) and Attention Network Task (ANT). Results: Compared to HCs, patients with PNES reported significantly higher levels of childhood trauma, depression and dissociation. Patients with PNES also had reduced performance indices for Digit Span Forward (DSF) (d = 0.62), Digit Span Backward (DSB) (d = 0.62) and TMT (d = 0.67) but not ANT.CTQ scores positively correlated with TMT and DSB performance in patients with PNES. Adjusting for CTQ scores attenuated the observed group difference in TMT performance. Depression and dissociation did not explain the observed findings. Conclusions: These results contribute to the evidence of impaired executive functions in patients with PNES. Furthermore, childhood trauma scores, but not (trait) dissociation or depression scores, seem to drive group differences (HC vs patients with PNES).

In this pilot study, we explored the immune phenotype of patients with severe obesity and comorbid depressive symptoms compared to non‐depressed patients with obesity and normal‐weight controls. Immune cell subsets were analysed by flow cytometry and depressive symptoms assessed using the Patient Health Questionnaire (PHQ‐9). Cell frequencies were correlated with depressive symptom scores and waist‐to‐hip ratio (WHR). Patients with obesity and comorbid depression showed significantly lower numbers of circulating cytotoxic natural killer cells, dendritic cells and CD8⁺ effector memory T cells, compared to normal‐weight controls. Regulatory T cells and CD4⁺ central memory T cells were increased compared to non‐depressed patients with obesity and compared to normal‐weight controls, respectively. Frequencies of cytotoxic natural killer cells and CD4⁺ central memory T cells significantly correlated with PHQ‐9 scores, but not with WHR. Reduced numbers of dendritic cells were observed in both patient groups with obesity and correlated with PHQ‐9 scores and WHR. These findings provide evidence for an altered immune composition in comorbid obesity and depression, supporting a pathobiological overlap between the two disorders.

Introduction Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%–60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity. Methods and analysis This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients’ self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12. Ethics and dissemination This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226—EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences. Trial registration numbers NCT04301271 , DRKS00021119, EudraCT 2018-002947-27.

There is a great amount of research regarding the particular ictal manifestations of psychogenic nonepileptic seizures (PNES) with a focus on the differences to epileptic seizures (Vogrig et al., 2019 [4]; Tyson et al., 2018 [5]; De Paola et al., 2016 [6]). Most of the research aims to define guidelines for diagnosing PNES in differentiation from epilepsy, because this differentiation is clinically relevant for clinical neurological settings. In contrast, very few studies aimed to gain insight about particular ictal manifestations of the different semiological appearances of PNES regarding distinctive psychological processes or prognostic outcomes (Brown, 2016 [7]; Pick et al., 2017 [8]; Brown, 2006 [9]; Cohen, 2013). One study revealed that a higher level of mental dissociation and cognitive impairment was associated with a higher level of traumatization in patients with PNES (Pick et al., 2017 [8]). We analyzed the seizure semiology with a focus on the level of awareness in 60 patients with PNES. Patients were divided into two groups: one with an impaired awareness during their seizures and the other one with preserved awareness during their seizures. We assessed the amount of adverse traumatic experience in childhood with the “Childhood Trauma Questionnaire (CTQ)”. We found that patients with PNES with impaired awareness showed more childhood traumatic experiences in the CTQ, especially on the subscales of sexual and emotional abuse as well as physical neglect. Furthermore, patients with PNES with impaired awareness during seizures were significantly younger, more often female, showed a lower degree on education, and a higher amount of self-harm behavior compared with patients with PNES with preserved awareness during seizures. Our study presents clinical evidence for the potential significance of the level of awareness during PNES for the etiology of PNES. Our results point toward the existence of clinical subgroups of patients with PNES with distinctive etiological mechanisms and indicate that seizure semiology might help to differentiate those potential subgroups.

Objective Evidence suggests that impairments in social cognition are associated with the occurrence of NES. Our aim was to investigate impairments in social cognition in the form of emotional and cognitive empathy in patients with NES compared to healthy controls. Methods For this purpose, we recruited 41 patients with video-EEG secured NES and compared them to 41 healthy controls matched by age, gender and educational level. Emotional and cognitive empathy were assessed using the Multifaceted Empathy Task (MET) and the Read the Mind in the Eye Test (RMET). Self-assessment questionnaires were used to record psychopathology in both groups. Results Patients with NES showed no differences in cognitive empathy compared to the healthy controls. Additionall, they seem to have less emotional empathy specifically towards positive emotions, compared to healthy controls. Discussion Our results are an indication of possible emotional empathy abnormalities in patients with NES. Those deviations, if replicated in large sample sizes, could implicate, that interventions for patients with NES should focus on improving empathy skills.