Bernhard J. Connemann

Background: Only few studies so far have investigated the molecular underpinnings of Internet Use Disorders (IUD), which can shed light on the neurochemical basis of excessive online behaviors. There are even less epigenetic studies in this research field, and longitudinal evidence is even more scarce. Methods: The present study investigated in n = 83 depressed patients and n = 83 healthy controls potential links between DNA-methylation of three candidate genes (serotonin transporter gene SLC6A4, glucocorticoid receptor gene NR3C1 and gene coding for oxytocin OXT) known to play a role in affective disorders and self-reported excessive Internet and problematic social media use over a two-week period. Results: In depressed patients, we found a significant positive association between problematic social media use, IUD tendencies in general, craving and methylation of a CpG site in NR3C1. In healthy controls, we found a significant positive association between social support and methylation of a CpG site in OXT. Further we found that higher social media addiction tendencies were associated with decreasing differences in methylation of OXT over a two-week period in both the group of depressed patients and healthy controls. However, this effect was small and the confidence interval contained zero. Conclusions: Our findings might provide first preliminary indications that NR3C1 and OXT might be involved in overuse of social media. However, small effect sizes and complex interaction effects require replication in larger samples with longitudinal measurements over a longer time period.

Sexual dysfunction is a common side effect of antidepressants, significantly impacting patients’ quality of life and treatment adherence. This study investigates the relationship between sexual dysfunction and antidepressants by analyzing data from VigiBase™, the World Health Organization’s global database of individual case safety reports. In this study, we examined, for the first time, reports related to sexual response—desire, arousal, and orgasm—by grouping appropriate side effect terms and calculated the reporting odds ratios (RORs) for various antidepressants. The findings of this study highlight a high disproportional reporting of sexual dysfunction, particularly with selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors. In contrast, agents such as agomelatine, bupropion, and mirtazapine showed a lower association. Furthermore, we investigated the correlation between reporting odds ratios and the binding affinities of antidepressants to specific neurotransmitter receptors and transporters, unveiling significant relationships that provide insights into the pharmacodynamic pathways underlying these adverse effects. For instance, a positive correlation was observed between the serotonin transporter and side effects in the category desire: r (19) = 0.67, p = 0.001 These insights underscore the necessity for clinicians to consider sexual side effects when prescribing antidepressants and to monitor and address these issues to improve patient outcomes.

Relationship dysfunction—marked by frequent conflicts—is one of the hallmark features of borderline personality disorder (BPD). However, the BPD couple as a dyad and partner-related features have rarely been taken into account. The aim of the present study was to investigate hormonal, personality, and relationship relevant factors, such as relationship satisfaction, attachment, and trauma in both partners within a dyad where one partner is diagnosed with BPD. The total sample consisted of 26 heterosexual couples. All studies were conducted at 2 p.m. Primary outcomes: Neo-Five-Factor-Inventory, Childhood Trauma Questionnaire, Experiences in Close Relationships Scale. Secondary outcomes: Problem List, Partnership Questionnaire, Questionnaire for Assessing Dyadic Coping. Upon questionnaire completion, one saliva sample was taken via passive drool to assess baseline cortisol and testosterone levels. Results showed that females with BPD have higher scores on childhood maltreatment, dysfunctional attachment styles, and neuroticism than mentally healthy females. Furthermore, they have more relationship-related problems and are less satisfied in their romantic relationship. Male partners of women with BPD showed lower testosterone levels, higher levels of childhood maltreatment, dysfunctional attachment styles, neuroticism, and openness compared with the healthy control partners. Furthermore, childhood trauma, neuroticism as well as dysfunctional attachment styles displayed a significant positive correlation with relationship-related problems. Traumatic childhood experiences, insecure attachment styles as well as neurotic personality characteristics contribute to increased relationship disruptions in couples. Relevant hormonal and psychosocial parameters in BPD partners should be taken into account when treating females with BPD.

Purpose: In aut-idem or generic substitution, discrepancies between summaries of product characteristics (SmPCs) referring to the same active substance (AS) may cause difficulties regarding informed consent and medical liability. The qualitative and quantitative characteristics of such discrepancies are insufficiently studied, impeding harmonization of same-substance SmPCs and compromising safe drug treatment. Methods: SmPCs of the one hundred most frequently prescribed ASs in Germany were analyzed for discrepancies in the presentation of indications (Inds) and contraindications (CInds). Inclusion and exclusion criteria of drugs/SmPCs were chosen according to the standards of the aut-idem substitution in Germany. Results: According to the study protocol, we identified 1486 drugs, of which 1426 SmPCs could be obtained. 41% respectively 65% of the ASs had same-substance SmPCs that differed from the respective reference SmPC in the number of listed Inds respectively CInds. The number of listed Inds/CInds varied considerably between same-substance SmPCs with maximum ranges in Inds of 7 in amoxicillin, and in CInds of 11 in lisinopril. Many ASs had large proportions (> 50%) of associated same-substance SmPCs that differed from the respective reference SmPC. A considerable proportion of ASs had same-substance SmPCs with formal and content-related differences other than the discrepancy in the number of Inds/CInds. Conclusion: This evaluation of same-substance SmPCs shows a clear lack of harmonization of same-substance SmPCs. Considering that generic substitution has become the rule and that physicians usually do not know which drug the patient receives in the pharmacy, these discrepancies raise several questions, that require a separate legal evaluation.

Background: Current research on borderline personality disorder report an association between emotionally dysregulated behaviors and intrusive mental imagery depicting similar scenes. Imagery rescripting techniques have proven effective in reducing intrusive mental imagery in numerous contexts. We developed a two session-short intervention in which intrusive mental images are identified, analyzed, and modified for daily rehearsal at home. This study aimed to reduce the negative emotions and cognitions associated with self-injurious behaviors by replacing unhealthy imagery with more adaptive content. Methods: Seven females diagnosed with borderline personality disorder who reported intrusive mental imagery of dysregulated behaviors were recruited for participation. Each participant engaged in two individualized treatment sessions and daily homework requiring the rehearsal of modified imagery. Emotion regulation strategies, borderline symptom severity, and depressiveness were assessed before and after treatment. Results: Acceptance was positive, as no patient dropped out from treatment. Symptom exacerbation was not observed. Borderline symptom reduction was noted and indicia of emotional dysregulation and negative affect declined. Limitations: The generalizability of results is limited by the small sample size and the absence of a control group. Conclusions: This new two-session short intervention was shown to decrease the emotionally dysregulated behaviors that accompany negative feelings in females with borderline personality disorder.

Background: It is repeatedly reported that pregabalin (PRG) and gabapentin feature a potential for abuse/misuse, predominantly in patients with former or active substance use disorder. The most common route of use is oral, though reports of sublingual, intravenous, rectal, and smoking administration also exist. A narrative review was performed to provide an overview of current knowledge about nasal PRG use. Methods: A narrative review of the currently available literature of nasal PRG use was performed by searching the MEDLINE, EMBASE, and Web of Science databases. The abstracts and articles identified were reviewed and examined for relevance. Secondly, a request regarding reports of cases of nasal PRG administration was performed in the worldwide spontaneous reporting system of adverse drug reactions of the European Medicines Agency (EMA, EudraVigilance database). Results: The literature search resulted in two reported cases of nasal PRG use. In the analysis of the EMA-database, 13 reported cases of nasal PRG use (11 male (two not specified), mean age of users = 34.2 years (four not specified)) were found. In two cases fatalities occurred related to PRG nasal use. Conclusions: Even if only little evidence can be found in current literature, the potential for misuse/abuse of PRG via nasal route might be of particular importance in the near future in PRG users who misuse it. Physicians should be aware of these alternative routes of administration.

Deficits in inhibitory function are assumed to underlie psychopathology in bipolar disorder (BD), especially in states of mania. A subdomain of inhibition, semantic inhibition (SI), referring to the suppression of irrelevant word meanings, may underlie formal thought disorder, such as flights of ideas. In the present study, we investigated SI in patients with BD during semantic ambiguity resolution using behavioral and event-related potential (ERP) measures. We presented 14 patients with BD with current manic, hypomanic, or mixed clinical states and 28 healthy controls sequentially with word triplets containing either a homonym (e.g., “organ”) or a comparable unambiguous word (e.g., “piano”). Participants were instructed to make a decision whether or not the target word was related to the meaning field of the first two words. The inappropriate homonym meaning had to be inhibited to correctly perform the target decision. In addition to reaction times (RT) and error rates (ER), the N400 ERP component to the target, an electrophysiological index of semantic processing, was analyzed as measure of the amount of SI that had taken place. Analyses of the behavioral data revealed that BD patients exhibited an overall worse performance in terms of RT and ER. In the ERP data, we found differences in N400 amplitude to ambiguous and unambiguous conditions over the right hemisphere in patients with BD depending on target congruence: In incongruent trials, N400 amplitude was smaller in ambiguous than in unambiguous words. In congruent trials, in contrast, N400 amplitude was larger in ambiguous than in unambiguous words. Such ERP differences between ambiguous and unambiguous words were absent in controls. We conclude that N400 amplitude differences in the ambiguous and unambiguous conditions of the BD group may reflect insufficient suppression of irrelevant homonym meanings in the right hemisphere. Disturbed SI processes might contribute to formal thought disorder in BD.

Gegenstand und Ziel Psychopharmakotherapie hat bei der Behandlung zahlreicher psychischer Störungen einen großen Stellenwert. Unerwünschte Arzneimittelwirkungen (UAW) beeinflussen dabei die Compliance und Verträglichkeit. Auch Beeinträchtigungen des Schlafs können als UAW einer Psychopharmakotherapie auftreten. Schlafstörungen sind mit einem erhöhten Risiko für körperliche und psychische Erkrankungen assoziiert und beeinträchtigen Kognition, Impulskontrolle, Emotionsregulation und Stimmung. Ziel der vorliegenden Arbeit ist die systematische Darstellung der Art und des Risikos für Schlafstörungen/Beeinträchtigungen des Schlafs durch häufig verordnete Psychopharmaka. Methodik Auf der Basis des Arzneiverordnungs-Reports 2016 wurden die in Deutschland verordnungsstärksten Psychopharmaka identifiziert. Die Fachinformationen (FI) der zugehörigen Originalpräparate wurden im Hinblick auf Nennung und Häufigkeitsangaben von Schlafstörungen/Beeinträchtigungen des Schlafs gemäß der International Classification of Sleep Disorders 3 (ICSD-3) untersucht. Ergebnisse Es wurden n = 64 FI untersucht. Bei der überwiegenden Zahl wurde mindestens eine Schlafstörung aufgeführt (50/64; 78 %). In den Kategorien Insomnien (52 %), Parasomnien (33 %) und schlafbezogene Bewegungsstörungen (20 %) wurde am häufigsten mindestens eine FI mit entsprechender UAW gefunden; schlafbezogene Atmungsstörungen (6 %) und Hypersomnien zentralnervösen Ursprungs (5 %) waren selten aufgeführt; zirkadiane Schlaf-Wach-Rhythmusstörungen wurden nicht gefunden. In den FI der vier verordnungsstärksten Wirkstoffe (Citalopram > Venlafaxin > Mirtazapin > Sertralin) war Insomnie aufgeführt. Nahezu alle untersuchten Hypnotika (Ausnahme: Chlorahlydrat) waren mit Albträumen assoziiert. Schlussfolgerung(en) Die meisten der in Deutschland häufig verordneten Psychopharmaka können Schlafstörungen/Beeinträchtigungen des Schlafs induzieren. Bei den vier verordnungsstärksten Wirkstoffen handelte es sich um Antidepressiva und in den zugehörigen FI war jeweils Insomnie aufgeführt. Bei der Behandlung mit Psychopharmaka sollte auf das Auftreten von Schlafstörungen als eine mögliche Nebenwirkung geachtet werden. Objective Psychopharmacotherapy is essential in the treatment of many mental disorders. Adverse drug reactions (ADR) have impact on compliance and tolerability. Sleep disorders or impaired sleep may occur as ADRs of psychopharmacotherapy. Sleep disorders are associated with an increased risk for physical and mental illness and may impair cognition, impulse control, emotion regulation and mood. Objective of the following study was the systematic presentation of type and risk of sleep disorders/impairments of sleep of frequently prescribed psychotropic drugs. Methods Psychotropic agents that are most frequently prescribed in Germany were identified by using the Arzneiverordnungs-Report 2016. Summaries of product characteristics (SmPC) of corresponding original products were analyzed regarding presence and frequency of sleep disorders/impairments of sleep according to the International Classification of Sleep Disorders 3 (ICSD-3). Results N = 64 SmPCs were analyzed. In most of the analyzed SmPCs, at least one sleep disorder (50/64; 78 %) was listed. At least one SmPC with a corresponding ADR was found in the categories insomnia (52 %), parasomnias (33 %), and sleep-related movement disorders (20 %); sleep-related breathing disorders (6 %) and central disorders of hypersomnolence (5 %) were rarely listed; circadian rhythm sleep-wake disorder was not found. The SmPCs of the four most frequently prescribed agents (citalopram > venlafaxine > mirtazapine > sertraline) listed insomnia as an ADR. Nearly all analysed hypnotics (except chloral hydrate) were associated with nightmares. Conclusion(s) Most of the psychotropic agents frequently prescribed in Germany may induce sleep disorders/impairments of sleep. The four most frequently prescribed agents were antidepressants and all of the corresponding SmPCs listed insomnia as a possible ADR. Sleep disorders should be taken seriously as possible ADRs of psychopharmacotherapy.