Does the Augmentation of Trauma Informed Hatha Yoga Increase the Effect of Dialectical Behavior Therapy for Substance Use Disorders on Psychopathological Strain of Patients with Borderline Personality Disorder and Comorbid Substance Use Disorder? Results of a Quasi-Experimental Study.

BACKGROUND: Borderline personality disorder (BPD) is one of the most common personality disorders among persons with substance use disorders (SUDs) and is characterized by severe clinical symptoms. The aim of this study was to investigate if the effect of dialectical behavior therapy for substance use disorders (DBT-S) inpatient treatment on psychopathological symptom load in patients suffering from both BPD and SUD can be augmented by weekly 60-min "Trauma Informed Hatha Yoga" sessions. MATERIALS AND METHODS: Thirty-nine patients suffering from comorbid BPD and SUD were consecutively in time included in this quasi-experimental pilot study (first intervention then control group). In the intervention group, weekly Trauma Informed Hatha Yoga sessions were added to standard DBT-S for 8 weeks. The participants of the control group received standard DBT-S. All participants completed several self-report questionnaires to assess symptoms of depression, anxiety, symptoms of BPD, and their subjective stress perception at three points in time during the study course. RESULTS: A repeated measures analysis of variance with patients' psychopharmacological medication as covariate revealed a significant main effect of time for each of the psychometric scales (State and Trait Anxiety Inventory subscale for state anxiety [STAI-S] p = 0.001, Beck Depression Inventory [BDI] p < 0.001; Borderline Symptom List 23 [BSL] p = 0.036) indicating that the psychopathological symptom load of the patients was significantly lower at the end of the DBT-S therapy compared to the beginning in both study groups. Moreover, there was a significant interaction effect of group*time on the psychometric scales STAI-T (subscale for trait anxiety) sum score (p = 0.010) and the sum score of the Perceived Stress Scale (PSS) (p = 0.043). This was expressed by the fact that the participants of the intervention group showed a significant reduction of the STAI-T sum score as well as the sum score of the Perceived Stress Scale (PSS), while the control group did not. Due to the exploratory nature of this study, correction for multiple testing was omitted. CONCLUSION: Although they are very preliminary, our results suggest that practicing Trauma Informed Hatha Yoga on a regular basis in addition to DBT-S inpatient treatment seems to reduce the level of trait anxiety and perceived stress significantly more than DBT-S inpatient treatment alone. Nevertheless, the effectiveness of Trauma Informed Hatha Yoga in reducing trait anxiety and perceived stress in patients suffering from SUD und BPD must be tested in large randomized controlled trials.

G-CuP: the effect of a forced oral glucose intake on alcohol craving and mesolimbic cue reactivity in alcohol dependence-study protocol of a randomized, double-blind, placebo-controlled crossover study.

BACKGROUND: Multiple studies indicate that a lower plasma level of the acetylated form of the appetite-regulating hormone ghrelin and higher plasma levels of insulin lead to a reduction in subjective alcohol craving and a reduced mesolimbic cue reactivity in functional magnetic resonance imaging (fMRI) when being exposed to alcohol-associated stimuli. The ghrelin level can physiologically be reduced by the induction of stomach distension and the ingestion of glucose or lipids. METHODS: A total of 108 alcohol-dependent patients aged between 18 and 65 years are examined in the randomized, double-blind, placebo-controlled crossover study. After collecting demographic and psychometric data, participants take part in an alcohol exposure session. Afterwards, the participants go through the intervention condition (oral glucose intake) and the control condition (placebo intake) in a randomized order on two examination days. Blood samples are taken repeatedly (every 10 min) during the study course on both measuring days to determine changes in acetylated and total ghrelin and insulin plasma levels. In parallel, subjective alcohol craving after the glucose or placebo intake as the primary outcome is assessed using the Alcohol Urge Questionnaire (AUQ) and a visual analog scale (VAS). To examine the mesolimbic cue reactivity as the secondary outcome, a fMRI measurement is conducted while being exposed to alcohol-related stimuli. Appropriate statistical analysis will be used for the evaluation of the outcomes. DISCUSSION: If successful, the results of this study could offer alcohol-dependent patients a new potential option for acute short-term reduction of alcohol craving and thus prevent relapses and prolong periods of abstinence in the long term. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022419 (UTN: U1111-1278-9428). Retrospectively registered on September 15, 2020.

Characterization and quantification of alcohol-related polyneuropathy by magnetic resonance neurography.

BACKGROUND: We characterized and quantified peripheral nerve damage in alcohol-dependent patients (ADP) by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. METHODS: Thirty-one adult patients with a history of excessive alcohol consumption and age-/sex-matched healthy controls were prospectively examined. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into ADP with alcohol-related polyneuropathy (ALN) and without ALN (Non-ALN). 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was performed using dual-echo 2-dimensional relaxometry sequences with spectral fat saturation. Detailed quantification of nerve injury by morphometric (cross-sectional area [CSA]) and microstructural MRN markers (proton spin density [ρ], apparent T2-relaxation-time [T2app ]) was conducted in all study participants. RESULTS: MRN detected nerve damage in ADP with and without ALN. A proximal-to-distal gradient was identified for nerve T2-weighted (T2w)-signal and T2app in ADP, indicating a proximal predominance of nerve lesions. While all MRN markers differentiated significantly between ADP and controls, microstructural markers were able to additionally differentiate between subgroups: tibial nerve ρ at thigh level was increased in ALN (p < 0.0001) and in Non-ALN (p = 0.0052) versus controls, and T2app was higher in ALN versus controls (p < 0.0001) and also in ALN versus Non-ALN (p = 0.0214). T2w-signal and CSA were only higher in ALN versus controls. CONCLUSIONS: MRN detects and quantifies peripheral nerve damage in ADP in vivo even in the absence of clinically overt ALN. Microstructural markers (T2app , ρ) are most suitable for differentiating between ADP with and without manifest ALN, and may help to elucidate the underlying pathomechanism in ALN.

Duration of Electroconvulsive Therapy Postictal Burst Suppression Is Associated With Time to Reorientation.

INTRODUCTION: A burst suppression pattern in the electroencephalogram represents a down-regulated brain state, which also occurs in the postictal phase of electroconvulsive therapy (ECT). Suppressive actions of the brain to terminate the seizure are thought to be necessary for the efficacy of ECT. On the other hand, recent studies showed an association of burst suppression in general anesthesia or sedation with (postprocedural) cognitive complications. METHODS: We retrospectively examined the length of postictal burst suppression and reorientation time in 49 ECT sessions of 25 consecutive patients. Burst suppression duration was determined by bispectral index monitoring and defined as the time with a bispectral index value of less than 20%. The association between duration of burst suppression and reorientation time was analyzed with multivariate logistic and linear regression analysis controlling for several covariates. RESULTS: The reorientation time showed a statistically significant association with the duration of burst suppression, but with no other variable. Longer phase of postictal burst suppression predicted longer reorientation time in the recovery room (P = 0.046). CONCLUSIONS: The association between the duration of postictal burst suppression and reorientation time after ECT in this sample suggests that (not only the efficacy but also the) cognitive adverse effects of ECT might be related to the extent of postictal central inhibition after the termination of the seizure.

Evaluation of the German biographic screening interview for fetal alcohol spectrum disorder (BSI-FASD).

Alcohol consumption during pregnancy may lead to permanent damage in the offspring, including fetal alcohol spectrum disorders (FASD), which have an estimated prevalence of 1-8% worldwide. In adulthood, diagnosing FASD is time-consuming and costly. This study aimed to evaluate the discriminatory power of a German screening instrument for FASD in adults-the biographic screening interview (BSI-FASD). In an open-label comparative cohort study wherein a one-time survey was administered per participant, we compared 22 subjects with confirmed FASD with control groups of 15 subjects diagnosed with attention deficit hyperactivity disorder (ADHD), 20 subjects with alcohol or opiate dependence, 18 subjects with depression, and 31 controls without prenatal alcohol exposure. The BSI-FASD was found to be resource-efficient, user-friendly, comprehensible, and easily applicable. It provided an overall good convergent and discriminant validity with a sensitivity of 0.77 (adapted 0.86) and specificities between 0.70 and 1.00. The BSI-FASD subdomains differed in their power to differentiate FASD from the groups. This study established that the BSI-FASD is an efficient instrument to screen adults with suspected FASD. The BSI-FASD may facilitate future diagnostic evaluation and thereby contribute to improved treatment of affected individuals.

Oxytocin attenuates neural response to emotional faces in social drinkers: an fMRI study.

INTRODUCTION: Oxytocin is a key mediator of emotional and social behavior that seems to be of relevance for the development and maintenance of addictive behaviors. We thus investigated the effect of oxytocin on neural response and behavior during a face-matching task in a sample of social drinkers. METHODS: Thirteen social drinkers underwent a randomized double-blind placebo-controlled cross-over functional magnetic resonance imaging face-matching task with and without prior intranasal application of 24 international units oxytocin. Effects of oxytocin and task condition (faces, shapes) on brain activation and individual task performance were assessed. RESULTS: Face-matching compared to shape-matching trials resulted in higher brain activation in the bilateral amygdala, hippocampus and parts of the occipital gyri. Oxytocin application vs. placebo reduced activation in bilateral amygdala, parts of the frontal gyri, and the parietal lobe. Region of interest analyses indicated that the oxytocin-induced attenuation of amygdala response was specific to face-stimuli and associated with lower subjective alcohol craving, and a lower percentage of heavy-drinking days (defined as ≥ 5 standard drinks/day). CONCLUSION: For the first time, we could show that a larger oxytocin-induced attenuation of amygdala response to fearful faces is associated with lower subjective craving for alcohol and percentage of heavy drinking days in social drinkers. Modulation of amygdala activation, induced by emotional stimuli, might represent a neurobiological substrate of oxytocin's protective effects on drug seeking behavior.

Empirical ratio of the combined use of S-ketamine and propofol in electroconvulsive therapy and its impact on seizure quality.

Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders. In certain cases, ECT-associated anaesthesia can be improved by the use of ketofol (i.e., S-ketamine + propofol). We aimed to evaluate the empirical mixing ratio of ketofol in these cases for better clinical implementation. We retrospectively investigated n = 52 patients who received 919 ECT sessions with S-ketamine plus propofol as anaesthetic agents. Several anaesthesia and ECT-related parameters including doses of S-ketamine and propofol were analysed. The mean empirically determined S-ketamine/propofol ratio was 1.38 (SD ± 0.57) for 919 individual ECT sessions and 1.52 (SD ± 0.62) for 52 patients, respectively. The mean relative dose was 0.72 (± 0.18) mg/kg S-ketamine and 0.54 (± 0.21) mg/kg propofol. Higher propofol dose was associated with poorer seizure quality. Seizure quality and time in recovery room were significantly influenced by age. Ketofol could be an option to exploit the advantageous qualities of S-ketamine and propofol, if both doses are reduced compared with single use of S-ketamine or propofol. Patients with poor seizure quality may benefit from lower propofol doses, which are applicable by the addition of ketamine. An empirically determined mixing ratio in favour of ketamine turned out to be preferable in a clinical setting. Recovery time was primarily prolonged by higher age rather than by ketamine dose, which had previously often been associated with a prolonged monitoring time in the recovery room. These new findings could improve electroconvulsive therapy and should be replicated in a prospective manner.

BDNF influences neural cue-reactivity to food stimuli and food craving in obesity.

There is increasing evidence that brain-derived neurotrophic factor (BDNF) impacts on the development of obesity. We are the first to test the hypothesis that BDNF levels might be associated with neural reactivity to food cues in patients suffering from obesity and healthy controls. We assessed visual food cue-induced neural response in 19 obese patients and 20 matched controls using functional magnetic resonance imaging and analyzed the associations between BDNF levels, food cue-reactivity and food craving. Whole-brain analysis in both groups revealed that food cues elicited higher neural activation in clusters of mesolimbic brain areas including the insula (food > neutral). Patients suffering from obesity showed a significant positive correlation between plasma BDNF levels and visual food cue-reactivity in the bilateral insulae. In addition, patients suffering from obesity with positive food cue-induced insula activation also reported significantly higher food craving than those with low cue-reactivity-an effect that was absent in normal weight participants. The present findings implicate that BDNF levels in patients suffering from obesity might be involved in food craving and obesity in humans. This highlights the importance to consider BDNF pathways when investigating obesity and obesity treatment.

The training game SALIENCE for the therapy of alcohol use disorder.

The feasibility study was aimed to develop a web-based gaming tool for the therapy of alcohol use disorder to offer patients a cue-exposure-based extinction and decision training, enhanced with virtual reality. To increase the training effect, patients playfully experience situations that resemble critical real-life situations. For implementing the game, a combination of HTML5 and JavaScript was used. The application comes with an administrator interface, to allow editing the game content. Initially, we included 21 patients (Group 1), 18 suffering from alcohol use disorder and 3 using cannabis (18/3 male/female, mean age 39 ± 13 years). Considering the iterative process of a feasibility study, we developed the game design as suggested by participants of Group 1 and additionally included 11 novel participants (Group 2) (11 suffering from an alcohol use disorder, 7/4 male/female, mean age 46 ± 14 years). Basically, the game was very well received. Usability ratings were generally high, even in patients with little computer experience. Both groups rated the application as realistic, and would generally be willing to play it on a daily basis. Given that SALIENCE is inexpensive, easily available, and engaging, it might be a reasonable add-on intervention to the standard treatment of alcohol use disorder.

Ghrelin modulates mesolimbic reactivity to alcohol cues in alcohol-addicted subjects: a functional imaging study.

Ghrelin has been shown to be involved in the pathophysiology of alcohol dependence, affecting alcohol self-administration and craving. However, the mechanism of action in alcohol dependence still has to be determined. We thus investigated whether ghrelin is associated with mesolimbic cue reactivity to alcohol cues and alcohol craving in recently detoxified alcohol-addicted subjects. We included 41 recently detoxified alcohol-dependent individuals. Functional magnetic resonance imaging (fMRI) was used to study mesolimbic cue reactivity during the presentation of alcohol-related pictures. Additionally, we assessed patients' alcohol craving using the Alcohol Urge Questionnaire and a visual analogue scale. Plasma concentrations of total and acylated (activated) ghrelin were measured in parallel to the fMRI session. The association between ghrelin plasma concentrations, mesolimbic cue reactivity and alcohol craving was assessed by performing correlation and mediation analyses. Alcohol-induced brain response in a network of brain clusters, including the right and left ventral striatum, showed a significant positive association with acylated ghrelin plasma concentration. Additionally, acylated ghrelin was significantly associated with craving. Mediation analyses showed that the association between acylated ghrelin plasma concentration and alcohol craving is mediated by a cue-induced brain response in the ventral striatum. Based on the finding that ghrelin modulates mesolimbic reactivity to alcohol cues, the following should be considered: If alcohol craving and the appetitive status were interrelated, this has to be taken into account when implementing fMRI studies for addictive disorders. Moreover, appetite regulation seems to represent a valid treatment target for reducing cue reactivity in addictive disorders.

Evaluation of Myocardial Damage After Electroconvulsive Therapy: Analyses of High-Sensitive Cardiac Troponin I and N-Terminal pro-B-type Natriuretic Peptide.

Electroconvulsive therapy (ECT) is a remarkably safe procedure. However, there might exist a subgroup of patients with an increased risk for cardiovascular events. The cardiac-specific enzymes high-sensitive cardiac troponin I (hscTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured before and after ECT in 23 patients. No relevant increase of hscTnI after ECT was found. Mean NT-proBNP levels were higher after ECT and in three patients a new NT-proBNP elevation after ECT was identified. In conclusion, our small study did not find any evidence for myocardial damage due to ECT by measuring hsTnI, but an increase of NT-proBNP, whose clinical relevance could only be speculated, yet.

Effects of leptin and ghrelin on neural cue-reactivity in alcohol addiction: Two streams merge to one river?

Leptin and ghrelin and a "cross-talk" between both hormones were implicated in the pathophysiology of alcohol dependence, both modulating alcohol craving and drug-seeking. To date, the neurobiological mechanisms underlying those effects are still little-known. We thus investigated the effect of leptin and ghrelin on alcohol cue-induced brain response, alcohol craving and relapse risk in alcohol-dependent subjects. Seventy abstinent alcohol dependent individuals underwent a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task and patients` alcohol craving was assessed. Plasma levels of leptin, total and acylated, active ghrelin were measured prior to the fMRI session. Additionally, relapse data was collected during a three-month follow-up. Associations between hormone levels, mesolimbic cue-reactivity, alcohol craving and relapse risk were tested. Leptin levels showed a significant negative association to alcohol cue-induced brain response in the striatum and alcohol craving. In addition, there was a significant effect of leptin on time to first heavy relapse in which higher leptin levels predicted longer times to first heavy relapse. Moreover, positive associations between acylated ghrelin and increased cue-reactivity in bilateral insulae as well as increased craving for alcohol during the fMRI task were revealed. Leptin and acylated ghrelin show opposing effects on mesolimbic cue-reactivity and alcohol craving. We suspect that the reduced striatal cue-reactivity might be the neurobiological correlate of leptin's effect on relapse-risk. The reported results further support the relevance of appetite regulating hormones in the pathophysiology of addiction and their potential role as future treatment targets.

Electroconvulsive therapy induced gray matter increase is not necessarily correlated with clinical data in depressed patients.

BACKGROUND: Electroconvulsive therapy (ECT) and depression have been associated with brain volume changes, especially in the hippocampus and the amygdala. METHODS: In this retrospective study we collected data from individual pre-post ECT whole brain magnetic resonance imaging scans of depressed patients from six German university hospitals. Gray matter volume (GMV) changes were quantified via voxel-based morphometry in a total sample of 92 patients with major depressive episodes (MDE). Additionally, 43 healthy controls were scanned twice within a similar time interval. RESULTS: Most prominently longitudinal GMV increases occurred in temporal lobe regions. Within specific region of interests we detected significant increases of GMV in the hippocampus and the amygdala. These results were more pronounced in the right hemisphere. Decreases in GMV were not observed. GMV changes did not correlate with psychopathology, age, gender or number of ECT sessions. We ruled out white matter reductions as a possible indirect cause of the detected GMV increase. CONCLUSION: The present findings support the notion of hippocampus and amygdala modulation following an acute ECT series in patients with MDE. These results corroborate the hypothesis that ECT enables primarily unspecific and regionally dependent neuroplasticity effects to the brain.

A novel Seizure Quality Index based on ictal parameters for optimizing clinical decision making in electroconvulsive therapy. Part 1: development.

Early identification of patients at high risk for an unfavorable outcome to ECT during the course might be beneficial because it provides an opportunity for timely intensification or optimization of stimulus conditions. We aimed to develop a new Seizure Quality Index (SQI) that delivers a clinical relevant outcome prediction early in the treatment course and can be used within common clinical setting. An observational study was conducted. Patients (n = 86) with a depressive episode and the clinical decision for ECT (right unilateral, brief pulse) were included, and several ictal parameters derived from the second ECT session and the clinical outcome of the patients were documented. Optimal cut-off points for five different domains of ictal adequacy for younger and older patients for the prediction of "non-response" and "non-remission" based on seizure quality was determined by the Youden Index and a sum score was built. Logistic regression analyses tested the predictive power of derived models. For both outcome variables "non-response" and "non-remission", the logistic regression models were statistically significant, albeit for remission only for subjects below the age of 65 years (χ2 = 17.9, p = 0.001) and (χ2 = 6.4, p = 0.020), respectively. The models correctly classified 87.2% (non-response) and 50.0% (non-remission) of the cases. ROC curve analysis showed an AUC of 0.87 (non-response) and 0.70 (non-remission). In elderly patients (> 65), no such model could be established due to a response rate of 100%. Our data provide promising, clinically relevant results about the prediction of response to ECT at an early stage for patients with depression.

Antidepressant efficacy of electroconvulsive therapy is associated with a reduction of the innate cellular immune activity in the cerebrospinal fluid in patients with depression.

OBJECTIVES: A bidirectional link between the antidepressant effects of electroconvulsive therapy (ECT) and the modulation of the immune system has been proposed. To elucidate the interplay between antidepressant treatment and macrophage/microglia activation in humans, we performed a study on the effects of the antidepressant treatment by ECT on markers of macrophage/microglia activation in patients with depression. METHODS: We measured six different markers (IL-6, neopterin, sCD14, sCD163 MIF and MCP1) of macrophage/microglia activation in the cerebrospinal fluid (CSF) and blood of 12 patients with a severe, treatment-resistant depressive episode before and after a course of ECT. RESULTS: Some markers in the CSF of remitters were reduced after the ECT course and differed from non-remitters, but no differences were found before and after ECT independently from the antidepressant efficacy. CSF baseline levels of some markers could predict the reduction of depressive psychopathology during ECT. Higher CSF levels indicating increased macrophage/microglia activation at baseline predicted a better treatment response to ECT. CONCLUSIONS: Although the sample size was small, our data suggest that macrophages/microglia are involved in the pathophysiology of major depression and that antidepressant efficacy by ECT might be partly explained by the modulation of the innate immune system within the brain.

Electroconvulsive therapy enhances the anti-ageing hormone Klotho in the cerebrospinal fluid of geriatric patients with major depression.

Klotho is a humoral factor with pleiotropic effects. Most notably, Klotho deficiency is associated with a phenotype comprising organ manifestations accompanying aging including atherosclerosis and cognitive impairment. Research on the role of Klotho in affective disorder is scarce, which is surprising in light of the fact that depression is associated with accelerated cellular aging as well as aging-related phenotypes and comorbidity observed in Klotho deficiency. On these grounds we investigated Klotho levels in the cerebrospinal fluid (CSF) and serum of eight geriatric patients undergoing electroconvulsive therapy (ECT) for severe depression. We hypothesize that ECT as a highly effective antidepressant treatment leads enhances Klotho levels. We found a significant difference between pre- and post-ECT CSF Klotho (792.5pg/ml vs. 991.3pg/ml, p=0.0020), but no difference in serum Klotho (602.5 vs. 594.3, p=0.32). Moreover, CSF Klotho increase positively correlated with the number of single ECT sessions that were performed in each patient (F1, 6)=7.84, p=0.031). Conjointly, the results of our exploratory study with a small sample size suggest a central nervous system-specific impact of ECT on Klotho, which may in turn partake in mediating the antidepressant effect of ECT. We suggest the modulation of neuroinflammatory processes, which have been ascribed pathophysiological relevance within the conceptual framework of the neuroinflammation hypothesis of depression, through ECT as a potential mechanism by which Klotho is enhanced in response to treatment. Further preclinical and clinical investigation should aim for a precise identification of the role of Klotho in depressive disorder.

The "Forgotten" Treatment of Alcohol Withdrawal Delirium With Electroconvulsive Therapy: Successful Use in a Very Prolonged and Severe Case.

OBJECTIVE: Alcohol withdrawal delirium (AWD) is a notorious complication in alcohol withdrawal. Usually, the symptomatic treatment is efficacious; however, some patients show treatment resistance or a prolonged course of AWD. METHOD: We report the case of a patient with a prolonged and severest form of AWD. Even 11 weeks after admission, he received approximately 100 mg diazepam per week to manage the symptoms of withdrawal delirium. RESULTS: A treatment course of electroconvulsive therapy was initiated, which allowed a complete tapering off of benzodiazepines during electroconvulsive therapy without adverse effects. CONCLUSIONS: The reported case might contribute to alternative approaches reserved for severest forms of prolonged AWD.