Jan Malte Bumb

New evidence for seizure quality improvement by hyperoxia and mild hypocapnia.

Introduction Preoxygenation and hyperventilation (with oxygen) in electroconvulsive therapy (ECT) may improve not only safety but also seizure quality. Methods We retrospectively examined transcutaneous tissue partial pressure of oxygen (tcpO2) and carbon dioxide (tcpCO2) in 441 ECT sessions of 37 consecutive patients. All patients received standard face mask airway management. In parallel, seizure quality markers such as seizure duration, seizure amplitude, central inhibition, interhemispheric coherence, and sympathetic activation were documented and used to build up a seizure quality sum score. Results Mean (SD) tcpO2 was 289 (123) mm Hg and for tcpCO2 41 (11) mm Hg. A multivariate repeated measurement regression analysis revealed that the ratio of tcpO2/tcpCO2 had a significant influence on the seizure quality sum score (P = 0.033). Furthermore, a corresponding regression analysis with charge (“stimulation energy”) as a dependent variable showed a significant influence of tcpO2 (P = 0.019) and of tcpO2/tcpCO2 (P = 0.03), too. Conclusions We observed, in our typical clinical ECT sample of 37 patients, a significant and synergistic influence of tcpO2/tcpCO2 on seizure quality. Partial pressure of oxygen covaried with lower stimulation energy. The ratio tcpO2/tcpCO2 was associated with lower stimulation energy and still better seizure quality.

Pineal gland volume in primary insomnia and healthy controls: a magnetic resonance imaging study.

Little is known about the relation between pineal volume and insomnia. Melatonin promotes sleep processes and, administered as a drug, it is suitable to improve primary and secondary sleep disorders in humans. Recent magnetic resonance imaging studies suggest that human plasma and saliva melatonin levels are partially determined by the pineal gland volume. This study compares the pineal volume in a group of patients with primary insomnia to a group of healthy people without sleep disturbance. Pineal gland volume (PGV) was measured on the basis of high‐resolution 3 Tesla MRI (T1‐magnetization prepared rapid gradient echo) in 23 patients and 27 controls, matched for age, gender and educational status. Volume measurements were performed conventionally by manual delineation of the pineal borders in multi‐planar reconstructed images. Pineal gland volume was significantly smaller (P < 0.001) in patients (48.9 ± 26.6 mm3) than in controls (79 ± 30.2 mm3). In patients PGV correlated negatively with age (r = −0.532; P = 0.026). Adjusting for the effect of age, PGV and rapid eye movement (REM) latency showed a significant positive correlation (rS = 0.711, P < 0.001) in patients. Pineal volume appears to be reduced in patients with primary insomnia compared to healthy controls. Further studies are needed to clarify whether low pineal volume is the basis or the consequence of functional sleep changes to elucidate the molecular pathology for the pineal volume loss in primary insomnia.

Oleoylethanolamide and Human Neural Responses to Food Stimuli in Obesity

IMPORTANCE Obesity has emerged as a leading health threat but its biological basis remains insufficiently known, hampering the search for novel treatments. Here, we study oleoylethanolamide, a naturally occurring lipid that has been clearly implicated in weight regulation in animals. However, its role for weight regulation and obesity in humans is still unclear. OBJECTIVE To investigate associations between plasma oleoylethanolamide levels and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and functional magnetic resonance imaging response to food stimuli in obese patients and matched control participants. DESIGN, SETTING, AND PARTICIPANTS Case-control study of 21 obese patients and 24 matched control participants. Obesity was defined as having a BMI of at least 30. The mean age of participants was 40.8 years and BMIs ranged from 18.2 to 47.5. MAIN OUTCOMES AND MEASURES Interactions between plasma oleoylethanolamide levels and obesity on BMI and functional magnetic resonance imaging response to food stimuli. RESULTS Associations between oleoylethanolamide and BMI differed significantly depending on whether individuals were obese or not (P = .02). In obese individuals, oleoylethanolamide showed a trend toward a positive correlation with BMI (P = .06, ρ = 0.42), while this relationship was inverse for nonobese control participants (P = .07, ρ = -0.34). Similarly, we found significant interactions between oleoylethanolamide levels and obesity on food-related brain activation in cortical areas associated with reward processing and interoceptive signaling (P = .009). Specifically, nonobese individuals with higher oleoylethanolamide levels had higher insular brain activity (P < .001, ρ = 0.70); again, the relationship trended to be inverse for obese patients (P = .11, ρ = -0.36). These effects were not associated with plasma levels of leptin and anandamide, suggesting an independent role of oleoylethanolamide in hunger-associated interoceptive signaling. Analysis of food craving during the functional magnetic resonance imaging task suggested that the identified brain areas may be involved in suppressing food-liking reactions in nonobese individuals. CONCLUSIONS AND RELEVANCE This study suggests that oleoylethanolamide-mediated signaling plays an important role for hedonic regulation of food craving and obesity in humans and thus may be a valuable target for developing novel antiobesity drugs.

Morphology and function: MR pineal volume and melatonin level in human saliva are correlated

To investigate the relation between circadian saliva melatonin levels and pineal volume as determined by MRI. Plasma melatonin levels follow a circadian rhythm with a high interindividual variability.

Drug repurposing and emerging adjunctive treatments for schizophrenia

Introduction: Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial. Nevertheless, the understanding of the pathophysiology of this syndrome, concise diagnostic methods and more effective and tolerable treatments are still lacking. Thus, innovative approaches and the exploration of new territories are required. Areas covered: An overview of repurposed drugs and emerging treatments for schizophrenia is presented, focusing on randomized, controlled trials and meta-analyses. Expert opinion: Despite many years of drug research, several needs in the treatment of schizophrenia including the safety and tolerability, stage-dependent and personalized approaches, as well as drug delivery and sustainability have not been addressed sufficiently. Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs (e.g., acetylsalicylic acid, celecoxib and minocycline), as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones (e.g., estrogen, raloxifene and oxytocin), glutamatergic (e.g., glycine and d-serine) and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoidmodulator, represent promising agents in this field.

Microstructural analysis of pineal volume using trueFISP imaging

AIM To determine the spectrum of pineal microstructures (solid/cystic parts) in a large clinical population using a high-resolution 3D-T2-weighted sequence. METHODS A total of 347 patients enrolled for cranial magnetic resonance imaging were randomly included in this study. Written informed consent was obtained from all patients. The exclusion criteria were artifacts or mass lesions prohibiting evaluation of the pineal gland in any of the sequences. True-FISP-3D-imaging (1.5-T, isotropic voxel 0.9 mm) was performed in 347 adults (55.4 ± 18.1 years). Pineal gland volume (PGV), cystic volume, and parenchyma volume (cysts excluded) were measured manually. RESULTS Overall, 40.3% of pineal glands were cystic. The median PGV was 54.6 mm(3) (78.33 ± 89.0 mm(3)), the median cystic volume was 5.4 mm(3) (15.8 ± 37.2 mm(3)), and the median parenchyma volume was 53.6 mm(3) (71.9 ± 66.7 mm(3)). In cystic glands, the standard deviation of the PGV was substantially higher than in solid glands (98% vs 58% of the mean). PGV declined with age (r = -0.130, P = 0.016). CONCLUSION The high interindividual volume variation is mainly related to cysts. Pineal parenchyma volume decreased slightly with age, whereas gender-related effects appear to be negligible.

Electroconvulsive therapy selectively enhances amyloid β 1–42 in the cerebrospinal fluid of patients with major depression: A prospective pilot study

A complex interplay between β-amyloid (Aβ), Alzheimer׳s disease (AD) and major depression disorder (MDD) suggests that patients with MDD have an altered cerebral Aβ metabolism and an increased risk of developing AD. In order to elucidate the relationship between antidepressant treatment and Aβ metabolism in humans, we performed a study on Aβ peptides in the cerebrospinal fluid (CSF) in patients with MDD during electroconvulsive therapy (ECT) as an effective antidepressant treatment. We measured the levels of Aβ1-42, Aβ1-40 and of tau proteins in the CSF in 12 patients with MDD before and after a course of ECT. Aβ1-42 was significantly elevated after the ECT treatment compared to baseline, whereas no difference was found for other peptides and proteins such as Aβ1-40, Aβ ratio, total tau protein or its phosphorylated form. The most salient finding was, that the increase of Aβ1-42 after ECT was found in all patients with clinical response to the treatment, but not in those who did not respond. The number of ECT sessions of each responding patient correlated with the increase of Aβ1-42 in the CSF. Our data point towards to a specific antidepressant mechanism which is not based on a general increase of Aβ, but seems to involve merely Aβ1-42, the isoform with highest amyloidogenic potential. We present the first study in humans demonstrating an isolated mobilization of Aβ1-42 in the CSF of patients with depression who respond to an ECT treatment.

Improvement in verbal memory performance in depressed in-patients after treatment with electroconvulsive therapy.

Electroconvulsive therapy (ECT) is a highly effective and well‐tolerated therapy for severe and treatment‐resistant depression. Cognitive side‐effects are still feared by some patients and clinicians. Importantly, cognitive impairments are among the most disabling symptoms of depression itself.

ECT seizure quality and serum BDNF, revisited

expected since seizures with lower adequacy (and lower antidepressive effect) are still seizures producing a lower (or less effective) but still present BDNF rise.To cope with this problem (not to “control” for covari-ates), we added an ANCOVA (as Molendijk and Polyakova suggested), including an interaction term for the delay of blood sampling and high versus low seizure quality. ANCOVA (STATA, StataCorp, Texas 77845, USA, version 11) then reveals a significant model (

Ketamin als Anästhetikum bei der Elektrokrampftherapie

BACKGROUND Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment for severe psychiatric disorders. Ketamine is known as a core medication in anesthesiology and has recently gained interest in ECT practice as there are three potential advantages: (1) ketamine has no anticonvulsive actions, (2) according to recent studies ketamine could possess a unique intrinsic antidepressive potential and (3) ketamine may exhibit neuroprotective properties, which again might reduce the risk of cognitive side effects associated with ECT. OBJECTIVES The use of ketamine in psychiatric patients has been controversially discussed due to its dose-dependent psychotropic and psychotomimetic effects. This study was carried out to test if the occurrence of side effects is comparable and if seizure quality is better with ketamine when compared to thiopental. MATERIAL AND METHODS This retrospective study analyzed a total of 199 patients who received ketamine anesthesia for a total of 2178 ECT sessions. This cohort was compared to patients who were treated with thiopental for 1004 ECT sessions. RESULTS AND DISCUSSION A repeated measurement multiple logistic regression analysis revealed significant advantages in the ketamine group for seizure concordance and postictal suppression (both are surrogates for central inhibition). S-ketamin also necessitated the use of a higher dose of urapidil and a higher maximum postictal heart frequency. Clinically relevant psychiatric side effects were rare in both groups. No psychiatric side effects occurred in the subgroup of patients with schizophrenia (ketamine: n = 30). The mean dose of S-ketamine used increased in the first years but stabilized at 63 mg per patient in 2014. From these experiences it can be concluded that S-ketamine can be recommended at least as a safe alternative to barbiturates.