[Show abstract][Hide abstract] ABSTRACT: Background:
Cholesterol is reduced in depressed patients, however, these patients have a higher risk for cardiovascular diseases. Electroconvulsive therapy (ECT) is a highly effective treatment option for specific forms of depression. Like for other non-pharmacological therapies targeting depression such as psychotherapy or sleep deprivation, there is a lack of evidence about the effects on peripheral lipid parameters. Our objective was to study the impact of ECT as a non-pharmacological treatment on the peripheral lipid pattern in depressive patients.
Peripheral lipid profile composition before and after a course of ECT was analysed in 27 non-fasting inpatients at a university psychiatric hospital with DSM-IV major depressive episode. For the impact of ECT treatment on each lipid parameter a multivariate repeated measurement regression analysis was performed and computed separately for every dependent variable.
Total Cholesterol and the cholesterol subtypes HDL and LDL were increased after the treatment compared to baseline. Apolipoprotein A1 was also increased after ECT, whereas apolipoprotein B was not. Indices for the prediction of cardiovascular diseases were unchanged after successful treatment by ECT. The reduction of depressive psychopathology negatively correlated with increases of HDL cholesterol and apolipoprotein A1.
Subjects received several antidepressants and other psychotropic medication before and during the ECT.
In our preliminary pilot study ECT as a non-pharmacological, effective treatment of depression led to distinct effects on the peripheral lipid pattern.
[Show abstract][Hide abstract] ABSTRACT: Defining the markers corresponding to a high risk of developing depression in humans would have major clinical significance; however, few studies have been conducted since they are not only complex but also require homogeneous groups. This study compared congenital learned helpless (cLH) rats, selectively bred for high stress sensitivity and learned helplessness (LH) behavior, to congenital non-learned helpless (cNLH) rats that were bred for resistance to uncontrollable stress. Naïve cLH rats show some depression-like behavior but full learned helplessness behavior need additional stress, making this model ideal for studying vulnerability to depression. Resting-state functional connectivity obtained from seed correlation analysis was calculated for multiple regions that were selected by anatomy AND by a data-driven approach, independently. Significance was determined by t-statistic AND by permutation analysis, independently. A significant reduction in functional connectivity was observed by both analyses in the cLH rats in the sensory, motor, cingulate, infralimbic, accumbens and the raphe nucleus. These reductions corresponded primarily to reduced inter-hemispheric connectivity. The main reduction however was in the sensory system. It is argued that reduced connectivity and inter-hemispheric connectivity of the sensory system reflects an internal convergence state which may precede other depressive symptomatology and therefore could be used as markers for vulnerability to the development of depression.
[Show abstract][Hide abstract] ABSTRACT: Aberrant prefrontal-hippocampal (PFC-HC) connectivity is disrupted in several psychiatric and at-risk conditions. Advances in rodent functional imaging have opened the possibility that this phenotype could serve as a translational imaging marker for psychiatric research. Recent evidence from functional magnetic resonance imaging (fMRI) studies has indicated an increase in PFC-HC coupling during working-memory tasks in both schizophrenic patients and at-risk populations, in contrast to a decrease in resting-state PFC-HC connectivity. Acute ketamine challenge is widely used in both humans and rats as a pharmacological model to study the mechanisms of N-methyl-D-aspartate (NMDA) receptor hypofunction in the context of psychiatric disorders.
We aimed to establish whether acute ketamine challenge has consistent effects in rats and humans by investigating resting-state fMRI PFC-HC connectivity and thus to corroborate its potential utility as a translational probe.
Twenty-four healthy human subjects (12 females, mean age 25 years) received intravenous doses of either saline (placebo) or ketamine (0.5 mg/kg body weight). Eighteen Sprague-Dawley male rats received either saline or ketamine (25 mg/kg). Resting-state fMRI measurements took place after injections, and the data were analyzed for PFC-HC functional connectivity.
In both species, ketamine induced a robust increase in PFC-HC coupling, in contrast to findings in chronic schizophrenia.
This translational comparison demonstrates a cross-species consistency in pharmacological effect and elucidates ketamine-induced alterations in PFC-HC coupling, a phenotype often disrupted in pathological conditions, which may give clue to understanding of psychiatric disorders and their onset, and help in the development of new treatments.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Der Anaesthesist 05/2015; 64(5). DOI:10.1007/s00101-015-0027-5 · 0.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obsessive-compulsive disorder represents one of the most disabling psychiatric disorders. The underlying pathophysiology is not fully understood. In a recent Science article, Ahmari and colleagues enlighten fundamental aspects of obsessive-compulsive disorder by means of optogenetic stimulation, thereby also elucidating the usefulness of SSRI in the treatment for OCD.
European Archives of Psychiatry and Clinical Neuroscience 02/2015; 265(8). DOI:10.1007/s00406-015-0584-2 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dear Editor,We are grateful to answer the questions arising from the fruitful comments of Marc Molendijk and Maryna Polyakova . We absolutely agree on their general criticism on statistical approaches in neuroscience, especially with regard to the literature they cited [2, 3].We are aware of the fact that a t test approach per se is statistically not absolutely correct, and we agree with Nieuwenhuis et al. that its use is not justifiable by the fact that it is commonly used in high-ranking journals. But as Nieuwenhuis et al. also stated, we think that this does not mean that results are meaningless or even not present in all cases.The idea of presenting data just from a subsample of patients with sufficient seizures  comes from our extensive clinical impression that such seizures are necessary to induce a significant antidepressive effect and that many circumstances may influence seizure quality [5-8].In our study, the t test of BDNF level increase (pre-post ECT) of patients in w ...
European Archives of Psychiatry and Clinical Neuroscience 02/2015; 265(4). DOI:10.1007/s00406-015-0580-6 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dementia-related behavioral disturbances are mostly treated with antipsychotics; however, the observed beneficial effects are modest and the risk of serious adverse effects high. We report the case of a 57-year-old woman with severe early-onset Alzheimer's disease and severe agitation, whom we treated with electroconvulsive therapy (ECT). A significant clinical improvement was achieved over eight ECT sessions, which were tolerated well without cognitive worsening, and lasted approximately 3 months. Our case demonstrates the safe and effective use of ECT in pharmacotherapy-resistant severe agitation in Alzheimer's disease. The risk-benefit profile of ECT for dementia-related agitation should be further investigated in clinical trials.
[Show abstract][Hide abstract] ABSTRACT: Background
Learned helplessness has excellent validity as an animal model for depression, but problems in reproducibility limit its use and the high degree of stress involved in the paradigm raises ethical concerns. We therefore aimed to identify which and how many trials of the learned helplessness paradigm are necessary to distinguish between helpless and non-helpless rats.
A trial-by-trial reanalysis of tests from 163 rats with congenital learned helplessness or congenital non-learned helplessness and comparison of 82 rats exposed to inescapable shock with 38 shock-controls revealed that neither the first test trials, when rats showed unspecific hyperlocomotion, nor trials of the last third of the test, when almost all animals responded quickly to the stressor, contributed to sensitivity and specificity of the test. Considering only trials 3–10 improved the classification of helpless and non-helpless rats.
The refined analysis allows abbreviation of the test for learned helplessness from 15 trials to 10 trials thereby reducing pain and stress of the experimental animals without losing statistical power.
[Show abstract][Hide abstract] ABSTRACT: Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.
European Archives of Psychiatry and Clinical Neuroscience 09/2014; 265(3). DOI:10.1007/s00406-014-0543-3 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mechanism of the reversible cognitive deficits that might occur within an electroconvulsive therapy (ECT) treatment has not been clarified in a substantial way yet. Although the data available so far do not point towards a cause due to any structural or diffuse damage, further clarification, especially of the role of S-100 seems to be necessary before robust conclusions can be drawn. Serum levels of protein S-100 and neuron-specific enolase (NSE) were analysed in 19 patients with depression, who received ECT. The sampling was adjusted for the short half-life of protein S-100. Several outcome parameters such as Hamilton Depression Rating Scale and Mini-mental state examination before and after the ECT, response and remission to the treatment were recorded. S-100 and NSE levels at baseline, 30 and 60 min after the third session and after the end of the ECT remained stable. S-100 and NSE levels were neither associated with antidepressant response or remission nor with alterations in the cognitive performance. Although aiming for detecting potential rise in these established brain damage markers, an increase due to ECT was not observed, which is in line with the previous studies concerning the safety of ECT on a cellular basis.
[Show abstract][Hide abstract] ABSTRACT: Preoxygenation and hyperventilation (with oxygen) in electroconvulsive therapy (ECT) may improve not only safety but also seizure quality.
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.
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.
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.
The journal of ECT 03/2014; 30(4). DOI:10.1097/YCT.0000000000000109 · 1.39 Impact Factor