Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Electroconvulsive therapy and adiposity-related parameters in treatment-resistant depressed patients.

Obesity is often accompanied by major depressive disorder (MDD), and vice versa. Latest research findings suggest the body mass index (BMI) to play a role in antidepressant treatment response in general. Our study aims to examine whether adiposity-related parameters such as BMI, glucose homeostasis, or serum lipids are associated with remission to electroconvulsive therapy (ECT). A pilot study (PS, n = 9) and a glucose study (GS, n = 29) were conducted. Blood was withdrawn directly before and 15 min (GS) as well as 1 h (PS) after the first ECT and directly before the last one (usually an ECT series comprised up to twelve sessions). BMI was associated with remission in the PS (remitters: M = 28, SD = 2.5; non-remitters: M = 22, SD = 2.08; t(7) = 3.325, p < 0.001, d = 0.24) but not in the GS or when pooled together. Glucose and insulin levels increased significantly after a single ECT session (GS: glucose: F (2,25.66) = 39.04, p < 0.001; insulin: PS: F (2,83) = 25.8, p < 0.001; GS: F (2,25.87) = 3.97, p < 0.05) but no chronic effect was detectable. Serum lipids were neither significantly altered after a single ECT session nor during a whole course of ECT. There was no difference between remitters and non-remitters in insulin, glucose, or serum lipid levels. Our study is lacking the differentiation between abdominal and peripheral fat distribution, and the sample size is small. Unexpectedly, BMI, glucose homeostasis, and lipid serum levels did not differ in patients remitting during ECT. In contrast to recently published studies, we cannot confirm the hypothesis that BMI may have an impact on ECT response.

The impact of post-traumatic stress on the mental state of university hospital physicians - a cross sectional study.

BACKGROUND: Hospital physicians have an increased risk for post-traumatic stress caused by work-related trauma. This study examines the frequency of reported traumatic events (TE), post-traumatic stress (PTS) and its possible consequences for the mental state and work ability of physicians at a university hospital. METHODS: As part of the mandatory psychological risk assessment, n = 145 physicians (n = 56 female; 38.6%) were examined at a university hospital in Germany in a cross sectional study. TE, PTS and symptoms of depression and anxiety were assessed using the self-report questionnaires "Freiburger Screening Fragebogen to identify patients at risk for the development of a post-traumatic stress disorder in the group of severely injured patients" (PTBS-13), the "Patient Health Questionnaire" (PHQ-2) and the "Generalized Anxiety Disorder scale" (GAD-2). Work ability was assessed using a modified version of the questionnaire for workplace analysis (KFZA). The response rate was 52%. RESULTS: Traumatic events were experienced by n = 125 physicians (86.2%) throughout their whole career. Of these, 19 physicians (15.2%) reported PTS. PTS is reported by 12 of 56 female physicians (63.2%), compared to 7 of 89 reports of PTS by male physicians (36.8%). Physicians with PTS symptoms had higher depression scores (p = 0.007) compared to physicians without TE or with TE, but without PTS. Physicians with PTS reported significantly reduced work ability caused by constantly interrupted work (p = 0.03). Female gender was the greatest risk factor for the development of PTS. (p = 0.001). CONCLUSIONS: Physicians - especially females - with PTS may have an increased risk of developing depressive symptoms. Therefore, interventions aimed at reducing trauma-related stress symptoms may be helpful in improving mental health of hospital physicians. Further studies with more physicians from different hospitals are necessary to support the results.

Oscillatory activity in the BNST/ALIC and the frontal cortex in OCD: acute effects of DBS.

Deep brain stimulation (DBS) of the bed nucleus of the stria terminalis/anterior limb of the internal capsule (BNST/ALIC) is successfully used for treatment of patients with obsessive-compulsive disorder (OCD). Clinical and experimental studies have suggested that enhanced network synchronization in the theta band is correlated with severity of symptoms. The mechanisms of action of DBS remain unclear in OCD. We here investigate the effect of acute stimulation of the BNCT/ALIC on oscillatory neuronal activity in patients with OCD implanted with DBS electrodes. We recorded the oscillatory activity of local field potentials (LFPs) from DBS electrodes (contact + 0/- 3; bipolar configuration; both hemispheres) from the BNST/ALIC parallel with frontal cortical electroencephalogram (EEG) one day after DBS surgery in four patients with OCD. BNST/ALIC and frontal EEG oscillatory activities were analysed before stimulation as baseline, and after three periods of stimulation with different voltage amplitudes (1 V, 2 V and 3.5 V) at 130 Hz. Overall, acute high frequency DBS reduced oscillatory theta band (4-8 Hz; p < 0.01) but increased other frequency bands in BNST/ALIC and the frontal cortex (p < 0.01). We show that stimulation of the BNST/ALIC in OCD modulates oscillatory activity in brain regions that are involved in the pathomechanisms of OCD. Our findings confirm and extend the findings that enhanced theta oscillatory activity in neuronal networks may be a biomarker for OCD.

Heart and brain interactions : Pathophysiology and management of cardio-psycho-neurological disorders.

Cardiovascular diseases (CVD) and mental health disorders (MHD; e.g. depression, anxiety and cognitive dysfunction) are highly prevalent and are associated with significant morbidity and mortality and impaired quality of life. Currently, possible interactions between pathophysiological mechanisms in MHD and CVD are rarely considered during the diagnostic work-up, prognostic assessment and treatment planning in patients with CVD, and research addressing bidirectional disease mechanisms in a systematic fashion is scarce. Besides some overarching pathogenetic principles shared by CVD and MHD, there are specific syndromes in which pre-existing neurological or psychiatric illness predisposes and contributes to CVD development (as in Takotsubo syndrome), or in which the distorted interplay between innate immune and central nervous systems and/or pre-existing CVD leads to secondary MHD and brain damage (as in peripartum cardiomyopathy or atrial fibrillation). Clinical manifestations and phenotypes of cardio-psycho-neurological diseases depend on the individual somatic, psychosocial, and genetic risk profile as well as on personal resilience, and differ in many respects between men and women. In this article, we provide arguments on why, in such conditions, multidisciplinary collaborations should be established to allow for more comprehensive understanding of the pathophysiology as well as appropriate and targeted diagnosis and treatment. In addition, we summarize current knowledge on the complex interactions between the cardiovascular and central nervous systems in Takotsubo syndrome and peripartum cardiomyopathy, and on the neurological and psychiatric complications of atrial fibrillation.

Long-Term Deep Brain Stimulation in Treatment-Resistant Obsessive-Compulsive Disorder: Outcome and Quality of Life at Four to Eight Years Follow-Up.

BACKGROUND: Obsessive compulsive disorder (OCD) is a severe disabling disease, and around 10% of patients are considered to be treatment-resistant (tr) in spite of guideline-based therapy. Deep brain stimulation (DBS) has been proposed as a promising treatment for patients with trOCD. However, the optimal site for stimulation is still a matter of debate, and clinical long-term follow-up observations including data on quality of life are sparse. We here present six trOCD patients who underwent DBS with electrodes placed in the bed nucleus of the stria terminalis/anterior limb of the internal capsule (BNST/ALIC), followed for four to eight years after lead implantation. MATERIALS AND METHODS: In this prospective observational study, six patients (four men, two women) aged 32-51 years and suffering from severe to extreme trOCD underwent DBS of the BNST/ALIC. Symptom severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and quality of life using the World Health Organization Quality of Life assessment scale (WHO-QoL BREF). Follow-up was obtained at least for four years in all patients. RESULTS: With chronic DBS for four to eight years, four of the six patients had sustained improvement. Two patients remitted and two patients responded (defined as >35% symptom reduction), while the other two patients were considered nonresponders on long-term. Quality of life markedly improved in remitters and responders. We did not observe peri-interventional side effects or adverse effects of chronic stimulation. CONCLUSIONS: Chronic DBS of ALIC provides long-term benefit up to four to eight years in trOCD, although not all patients take profit. Targeting the BNST was not particularly relevant since no patient appeared to benefit from direct stimulation of the BNST. Quality of life improved in DBS responders, documented by improved QoL scores and, even more important, by regaining of autonomy and improving psychosocial functioning.

Feasibility and outcome of metacognitive therapy for major depressive disorder: a pilot study.

BACKGROUND: Several studies have shown the effectiveness of Metacognitive Therapy (MCT) in treating different mental disorders. Most of these studies were performed in English speaking countries using the original English version of the manual. Our study aimed to examine the feasibility of the translated MCT manual in a sample of German patients with major depressive disorder. METHODS: Twenty outpatients (6 male, 14 female, mean age 42.1y) with major depressive disorder were included. The main outcome was drop-out rate and satisfaction with the treatment; secondary outcomes were changes in metacognitive beliefs assessed with the metacognitive questionnaire 30 (MCQ-30), and symptom reduction measured with the Beck Depression Inventory-2 sum score (BDI-2). RESULTS: No drop-outs during the treatment and the follow-up phase were observed. Patients and therapists were highly satisfied with MCT treatment. The MCQ-30 significantly declined over the treatment course, paralleled by a significant reduction of the BDI-2 sum scores (from 29 ± 8.6 at T0 to 8.4 ± 9.6 at the end of treatment). The average treatment duration was 10 ± 4 sessions. CONCLUSIONS: Applying the German version of the manual for Metacognitive Therapy proved to be feasible in the treatment of depressed patients in an outpatient setting. The treatment was well tolerated by German patients. Outcome in terms of reduction of depressive symptoms was good. Remarkable is the comparably short treatment duration which should be investigated further in future studies. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00023644, 17.11.2020 (retrospectively registered).

Hormone replacement therapy with L-thyroxine promotes working memory and concentration in thyroidectomized female patients after differentiated thyroid carcinoma.

Objective: It is well established that long-term hypothyroidism is associated with cognitive deficits. Based on recent literature, we hypothesized that pharmacologically induced euthyroidism would lead to improved cognitive performance compared to a hypothyroid state. Methods: We analyzed data from 14 nondepressed thyroidectomized female patients after differentiated thyroid carcinoma during hypothyroidism (due to a four-week withdrawal of thyroid hormone, T1) and euthyroidism brought about by substitution with L-thyroxine (T2). At both measurement points, patients completed a cognitive test battery as our dependent measure and Beck's Depression Inventory to control depressive states. Results: A Wilcoxon signed-rank tests revealed a significant improvement in the Rey­Osterrieth complex figure test (cognitive reproduction), Z = −3.183, p = 0.001, and the D2 concentration score, Z = −1.992, p = 0.046 in euthyroidism compared to hypothyroidism. Conclusions: Our results confirm that hormone replacement therapy with L-thyroxine promotes cognitive reproduction and concentration in thyroidectomized female patients after differentiated thyroid carcinoma.

[Addictive disorders in physicians]. / Abhängigkeitserkrankungen bei Ärzten.

Despite their knowledge about the risks and treatment options for substance abuse disorders, physicians are not immune to them. Meanwhile, a number of studies have shown that physicians have an increased risk of depression, addictive diseases and burnout due to the occupation-linked mental and physical burden and in particular an increased prevalence of substance-related disorders, especially alcohol abuse or dependence and drug abuse. Drug dependence among physicians seems to be even higher than in the general population due to the relatively easy access to psychoactive medications, in particular hypnotic drugs, benzodiazepines, ketamine and opioids; however, the prognosis is good. According to data from the medical associations, three quarters of those affected for the first time and every sixth relapsed physician can be helped with preservation of the license and working as physicians.

Attitudes Toward Long-Term Medication Use-A Comparison Between Concerned Populations and a Sample From the German General Population: An Example of Real World Evidence.

PURPOSE/BACKGROUND: The present study was conducted to investigate the difference in attitudes toward psychiatric drugs, long-term medication, and depot formulations between psychiatric patients and patient-related groups and the German general public. METHODS/PROCEDURES: Different groups (n = 50 patients, n = 34 relatives of patients, n = 42 psychiatrists, n = 70 medical students, and n = 58 psychiatric nursing professionals) were surveyed using a questionnaire to investigate their attitude toward depot medication and compared with matched participants from the German general public. FINDINGS/RESULTS: Patients did not differ from their matched controls regarding their attitude toward potential reasons to reject a depot, whereas psychiatrists (P = 0.002) and nursing staff (P = 0.003) were more concerned about patients fearing an injection than their matched controls. IMPLICATIONS/CONCLUSIONS: Psychiatrists and psychiatric nurses were significantly more concerned about giving an (intragluteal) injection because of concerns about patients' fears of this administration method than their matched controls. In contrast, patients' concerns about receiving an injection did not differ from their matched controls. Furthermore, we found that psychiatrists tended to believe that giving an injection might be time-consuming than giving oral medication. These results may emphasize the fact that the low rate of depot medication use is derived from subjective reservations of medical staff rather than actual negative attitudes or fears of patients.

Hypersalivation: update of the German S2k guideline (AWMF) in short form.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes to activate compensation mechanisms as long compliances are given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (Sialanar®) is now indicated for hypersalivation within the EU. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long-lasting saliva reduction. Here, a phase III trial is completed for incobotulinum toxin A and, in the US, is indicated for the treatment of adult patients with chronic hypersalivation. Surgical treatment should be reserved for isolated cases. External radiation is judged as a safe and effective therapy when using modern 3D techniques to minimize tissue damage. Therapy effects and symptom severity have to be followed, especially in cases with underlying neurodegenerative disease.

[Hypersalivation - Update of the S2k guideline (AWMF) in short form]. / Hypersalivation ­ Aktualisierung der S2k-Leitlinie (AWMF) in gekürzter Darstellung.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation.Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes in order to activate compensation mechanisms as long compliances is given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (Sialanar®) is now indicated for hypersalivation within the E. U. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long lasting saliva reduction. Here, a phase III trial is completed for Incobotulinum toxin A and, in the U. S., is indicated for the treatment of adult patients with chronic hypersalivation. Surgical treatment should be reserved for isolated cases. External radiation is judged as a safe and effective therapy when using modern 3 D techniques to minimize tissue damage. Therapy effects and symptom severity has to be followed, especially in cases with underlying neurodegenerative disease.

[Major depression and liver disease: the role of microbiome and inflammation]. / Depressionen und Lebererkrankungen: Die Rolle von Mikrobiom und Inflammation.

Depression and liver disease are closely associated. Every third patient with liver cirrhosis or hepatitis shows depressive symptoms. On the other hand, every third patient with depressive disorder develops an alcohol disorder at some point during his / her life. A crucial link between depression and hepatic disease seems to be inflammatory processes in which the microbiome and increased intestinal permeability of the intestine play a pivotal role. Depression as well as liver disease, alcohol consumption, stress, and aging processes disturb the delicate balance of intestinal microbiota resulting in increased intestinal permeability. Therefore, bacteria or their metabolites such as the endotoxine lipopolysaccharide are able to reach the blood circulation resulting in inflammation in the liver as well as in the brain via a cytokine cascade, which in turn can lead to liver changes, depression, obesity, and metabolic syndrome. Therefore, liver values, blood glucose levels, and metabolic parameters should be closely monitored in patients with depressive disorders, and in the case of patients with hepatic diseases, increased attention should be given to depressive symptoms, diabetes and obesity.

Attitudes Concerning Antipsychotic Depot Medication in the German General Population: A Representative Telephone Survey.

BACKGROUND: Treatment of schizophrenia with depot medication has advantages compared with oral medication, and among these include an improved compliance. Despite such advantages, prescription rates in many European countries are lower than 20%. The aim of this survey was to study the attitudes toward depot medication among the German general population. To the best of our knowledge, only selective samples have been investigated up until now. METHODS: A representative sample of 754 people were interviewed via telephone by a professional market research and polling organization. The questionnaire queried demographic characteristics, experience with medication, and the treatment of mental disorders. Subjects' attitudes toward medication in general, long-term medication, and depot medication were surveyed. RESULTS: Most (66.7%) of the subjects stated that they would be willing to receive depot medication. Subjects who experienced the treatment of mental disorders were more likely to be willing to receive depot medication. Among the reasons for not using depot medication, "fear of injection" (66.3%) and "more self-control when taking medication as tablets" (48.9%) were stated as the most frequent reasons. CONCLUSIONS: This study found a good acceptance of antipsychotic depot medication among the German general population in terms of willingness to receive such treatment. We argue that the clinical practitioners' assumptions that depot formulations would be refused by many patients are unsubstantiated.

Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women: A Laboratory Paradigm.

PURPOSE: The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual function in women. METHODS: In a double-blind, placebo-controlled, crossover laboratory setting, the acute effects of intranasal administered OXT (24 international units) on sexual drive, arousal, orgasm, and refractory aspects of sexual behavior were analyzed in 27 healthy females (mean age ± SD, 27.52 ± 8.04) together with physiological parameters using vaginal photoplethysmography. FINDINGS: Oxytocin administration showed no effect on subjective sexual parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters (vaginal photoplethysmography amplitude and vaginal blood volume) showed a response pattern towards sexual arousal but were not affected by OXT. IMPLICATIONS: Using a well-established laboratory paradigm, we did not find that intranasal OXT influences female sexual parameters. Also, sexual drive and other functions were not affected by OXT. These findings indicate that OXT is not able to significantly increase subjective and objective parameters of sexual function in a setting with high internal validity; however, this might be different in a more naturalistic setting.

Lack of Increase in Sexual Drive and Function After Dopaminergic Stimulation in Women.

Human and animal data indicate that the dopaminergic system plays a crucial role in sexual drive and function. Using a double-blind, placebo-controlled crossover design, this prototype study investigated the effect of the D2 dopamine agonist cabergoline on sexual parameters in 13 healthy women. Cardiovascular and genital parameters were monitored continuously. Sexual drive and function were measured using self-report sexual experience scales. In contrast to previous theories and assumptions, we found that cabergoline did not alter objective and subjective sexual parameters in healthy women. This finding suggests that there may be sex differences in the influence of the dopaminergic system on human sexual functioning.

Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum.

The New Hamburg-Hannover Agitation Scale in Clinical Samples: Manifestation and Differences of Agitation in Depression, Anxiety, and Borderline Personality Disorder.

BACKGROUND/AIMS: Agitation is a burdening phenomenon that occurs in a variety of psychiatric disorders. The aim of this study was to give a first direction for agitation occurrence in depression, anxiety disorder, and borderline personality disorder (BPD) as well as in healthy controls with and without psychiatric record. METHODS: Using the Hamburg-Hannover Agitation Scale (H2A), an instrument that allows for the measurement of agitation independently of the presence of a specific disorder, a patient sample (n = 158) and a healthy control group (n = 685) with (n = 94) and without (n = 591) psychiatric record were examined. The data were mainly analysed using ANOVAs and post hoc tests. RESULTS: Patients showed significantly higher H2A agitation levels than healthy controls. Within the clinical sample, BPD patients exhibited the strongest manifestation of agitation, scoring significantly higher than the depression and the anxiety disorder sample, while these two subgroups did not significantly differ from each other. Moreover, healthy subjects with a psychiatric record experienced a significantly stronger agitation than subjects without a psychiatric record. CONCLUSION: Further studies are needed with larger, more balanced, and differentiated sample sizes including a wider range of clinical pictures. The results demonstrate that agitation occurs and differs in psychiatric patients as well as in healthy controls.

BDNF serum levels and promoter methylation of BDNF exon I, IV and VI in depressed patients receiving electroconvulsive therapy.

We examined potential changes in brain-derived neurotrophic factor (BDNF) serum levels and promoter methylation of the BDNF gene in 11 patients with treatment-resistant major depressive disorder during a series of electroconvulsive therapy (ECT). Blood samples were taken before, 1 and 24 h after ECT treatment sessions 1, 4, 7 and 10. Patients remitting under ECT had significantly lower mean promoter methylation rates, especially concerning the exon I promoter, compared to non-remitters (both p < 0.002). These findings may point to a depression subtype in which ECT is particularly beneficial.