Efficacy and Interindividual Variability in Motor-Cortex Plasticity following Anodal tDCS and Paired-Associative Stimulation

Interindividual response variability to various motor-cortex stimulation protocols has been recently reported. Comparative data of stimulation protocols with different modes of action is lacking. We aimed to compare the efficacy and response variability of two LTP-inducing stimulation protocols in the human motor cortex: anodal transcranial direct current stimulation (a-tDCS) and paired-associative stimulation (PAS25). In two experiments 30 subjects received 1mA a-tDCS and PAS25. Data analysis focused on motor-cortex excitability change and response defined as increase in MEP applying different cut-offs. Furthermore, the predictive pattern of baseline characteristics was explored. Both protocols induced a significant increase in motor-cortical excitability. In the PAS25 experiments the likelihood to develop a MEP response was higher compared to a-tDCS, whereas for intracortical facilitation (ICF) the likelihood for a response was higher in the a-tDCS experiments. Baseline ICF (12 ms) correlated positively with an increase in MEPs only following a-tDCS and responders had significantly higher ICF baseline values. Contrary to recent studies, we showed significant group-level efficacy following both stimulation protocols confirming older studies. However, we also observed a remarkable amount of nonresponders. Our findings highlight the need to define sufficient physiological read-outs for a given plasticity protocol and to develop predictive markers for targeted stimulation

How to reduce mental health burden in health care workers during COVID-19? A scoping review of guideline recommendations

The COVID-19 pandemic has posed an unprecedented demand and a huge burden for healthcare workers (HCWs) worldwide, with alarming reports of heightened mental health problems. To counteract these mental health challenges, guidelines and recommendations for the support of HCWs during the COVID-19 pandemic have been published. With this scoping review and guideline evaluation, we aim to provide a critical overview of these guidelines and recommendations and to guide policy makers in establishing respective surveillance and care programs. In summary, 41 articles were included in this review which were published between April 2020 and May 2021. Across all articles, the guidelines and recommendations could be clustered into four main categories: “Social/structural support,” “Work environment,” “Communication/Information,” “Mental health support.” Although there was substantial agreement across articles about the recommendations given, empirical evidence on the effectiveness of these recommendations is still lacking. Moreover, most recommendations were developed without involving different members of the target group (HCWs) or other involved stakeholders. Strategies to detect potential barriers and to implement these guidelines in clinical practice are lacking

Impact of smoking behavior on clozapine blood levels – a systematic review and meta‐analysis

Objective Tobacco smoking significantly impacts clozapine blood levels and has substantial implications on individual efficacy and safety outcomes. By investigating differences in clozapine blood levels in smoking and non‐smoking patients on clozapine, we aim to provide guidance for clinicians how to adjust clozapine levels for patients on clozapine who change their smoking habits. Methods We conducted a meta‐analysis on clozapine blood levels, norclozapine levels, norclozapine/clozapine ratios and concentration to dose (C/D) ratios in smokers and non‐smokers on clozapine. Data were meta‐analysed using a random‐effects model with sensitivity analyses on dose, ethnic origin and study quality. Results Data from 23 studies were included in this meta‐analysis with 21 investigating differences between clozapine blood levels of smokers and non‐smokers. In total, data from 7125 samples were included for the primary outcome (clozapine blood levels in ng/ml) in this meta‐analysis. A meta‐analysis of all between‐subject studies (N=16) found that clozapine blood levels were significantly lower in smokers compared to non‐smokers (Standard Mean Difference (SMD) ‐0.39, 95% confidence interval (CI) ‐0.55 to ‐0.22,

Comparative study of a continuous train of theta-burst stimulation for a duration of 20 s (cTBS 300) versus a duration of 40 s (cTBS 600) in a pre-stimulation relaxed condition in healthy volunteers

As variable after effects have been observed following phasic muscle contraction prior to continuous theta-burst stimulation (cTBS), we here investigated two cTBS protocols (cTBS300 and cTBS600) in 20 healthy participants employing a pre-relaxed muscle condition including visual feedback on idle peripheral surface EMG activity. Furthermore, we assessed corticospinal excitability measures also from a pre-relaxed state to better understand the potential impact of these proposed contributors to TBS. Motor-evoked potential (MEP) magnitude changes were assessed for 30 min. The linear model computed across both experimental paradigms (cTBS300 and cTBS600) revealed a main effect of TIME COURSE (p = 0.044). Separate exploratory analysis for cTBS300 revealed a main effect of TIME COURSE (p = 0.031), which did not maintain significance after Greenhouse–Geisser correction (p = 0.073). For cTBS600, no main effects were observed. An exploratory analysis revealed a correlation between relative SICF at 2.0 ms (p = 0.006) and after effects (relative mean change) of cTBS600, which did not survive correction for multiple testing. Our findings thereby do not support the hypothesis of a specific excitability modulating effect of cTBS applied to the human motor-cortex in setups with pre-relaxed muscle conditions

Comparative study of motor cortical excitability changes following anodal tDCS or high‐frequency tRNS in relation to stimulation duration

Background In this study, we investigate the capacity of two different non‐invasive brain stimulation (NIBS) techniques (anodal transcranial direct current stimulation (anodal tDCS) and high‐frequency transcranial random noise stimulation (hf‐tRNS)) regarding the relationship between stimulation duration and their efficacy in inducing long‐lasting changes in motor cortical excitability. Methods Fifteen healthy subjects attended six experimental sessions (90 experiments in total) and underwent both anodal tDCS of 7, 13, and 20 min duration, as well as high‐frequency 1mA‐tRNS of 7, 13, and 20 min stimulation duration. Sessions were performed in a randomized order and subjects were blinded to the applied methods. Results For anodal tDCS, no significant stable increases of motor cortical excitability were observed for either stimulation duration. In contrast, for hf ‐tRNS a stimulation duration of 7 min resulted in a significant increase of motor cortical excitability lasting from 20 to 60 min poststimulation. While an intermediate duration of 13 min hf‐tRNS failed to induce lasting changes in motor cortical excitability, a longer stimulation duration of 20 min hf‐tRNS led only to significant increases at 50 min poststimulation which did not outlast until 60 min poststimulation. Conclusion Hf‐tRNS for a duration of 7 min induced robust increases of motor cortical excitability, suggesting an indirect proportional relationship between stimulation duration and efficacy. While hf‐tRNS appeared superior to anodal tDCS in this study, further systematic and randomized experiments are necessary to evaluate the generalizability of our observations and to address current intensity as a further modifiable contributor to the variability of transcranial brain stimulation

Lethal lust: suicidal behavior and chemsex — a narrative review of the literature

Chemsex is described as the use of certain drugs—commonly methamphetamine, gamma-butyrolactone (GBL)/gammahydroxybutyrate (GHB), and mephedrone—before or during planned sexual activity primarily among men who have sex with men (MSM). Evidence shows that MSM who engage in chemsex are at increased risk of physical harm, such as sexually transmittable infections (STIs), and are more likely to experience mental health symptoms. To further assess this, we reviewed the recent literature to evaluate whether the psychological impact of chemsex behavior includes suicidal ideation and suicidal attempts. Pubmed/MEDLINE was searched for articles reporting suicidal ideation and behavior among chemsex users with the terms “chemsex”, “sexualized drug use”, “suicide”, and “mental health”. Twelve articles (three case reports and nine cross-sectional studies) were included in the final narrative review. Overall, we retrieved mixed results regarding the relationship between chemsex practice and suicidality outcomes. Considering the inhomogeneous nature of the studies, the findings indicate that suicidality could be an issue of concern among MSM in general but among chemsex users in particular. Possible risk factors for suicidality among chemsex participants may include adversities experienced due to one’s sexual orientation and an increased risk for HIV and other STI infections and the resulting negative impact on mental well-being. These aspects warrant further investigations

Psychiatric medication and physical performance parameters – are there implications for treatment?

Introduction The impact of psychiatric medications and their enhancing or impairing effects on physical performance remains inconclusive. Therefore, with this systematic review we provide a comprehensive overview of frequently used psychotropic drugs and their effects on physical performance for the purpose of providing empirical information and deriving prescription and therapy recommendations for clinical practice. Methods We systematically searched PubMed, PsycInfo, and Cochrane databases and extracted human studies investigating the effect of psychotropic drugs on parameters associated with the level of physical performance, such as exercise time, oxygen consumption, heart rate, muscle contraction or blood lactate concentration in physically healthy participants. 36 studies - comprising a broad range of psychotropic agents, such as antidepressants, antipsychotics, sedatives, and stimulants - were selected for final analyses. Results Most studies (N = 32) were randomized controlled trials (RCT) with a double-blind crossover design. Antidepressants (N = 21) were the most frequently studied drug class, with contradictory results e.g., performance enhancement in warm environment but not in temperate conditions for bupropion or inconsistent findings between studies for other antidepressants. Antipsychotics (N = 3) mainly showed impairing effects on physical performance, while stimulants (N = 4) were often performance-enhancing. Sedatives (N = 9) may cause a hangover effect. Conclusion The examined studies with heterogeneous design showed different effects of psychiatric medications on physical performance. Antipsychotics seemed to be performance impairing, while the findings for antidepressants and sedatives were more inconsistent. Stimulants were the only group with consistent performance-enhancing effects. However, most studies were conducted with a small sample size (N < 10), mostly in well-trained subjects rather than in patients with psychiatric disorders, and most studies used single-dose designs. These issues impede the formulation of generalized conclusions for treatment regimes and should therefore be considered in further longitudinal studies for clinically reliable statements. Nevertheless, answering our research question is quite relevant for clinical practice and therapeutic prescription and should be further investigated especially considering the high drop-out rates in drug treatment. Systematic review registration [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=276103], identifier [CRD42021276103]

Repositioning synthetic glucocorticoids in psychiatric disease associated with neural autoantibodies: a narrative review

Synthetic glucocorticoids (sGCs) are a well-investigated and standard drug therapy for disorders associated with CNS inflammation. Less is known about treating psychiatric disorders associated with neural autoantibodies. Our aim is to elucidate the repositioning of sGCs in psychiatric diseases that co-exist with neural autoantibodies. We used PubMed to identify articles for this narrative review. To our knowledge, no randomized, placebo-controlled trials have yet been conducted on applying sGC to treat neural autoantibody-associated psychiatric disorders. We describe initial results of cohort studies and single cases or case series often associated with autoantibodies against membrane-surface antigens demonstrating a largely beneficial response to sGCs either as monotherapy or polytherapy together with other immunosuppressive agents. However, sGCs may be less efficient in patients with psychiatric diseases associated with autoantibodies directed against intracellular antigens. These results reveal potential benefits of the novel usage of sGCs for the indication of neural autoantibody-associated psychiatric disease. Further large-scale randomized, placebo-controlled trials are needed to discover whether sGCs are safe, well tolerated, and beneficial in subgroups of neural autoantibody-associated psychiatric diseases