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Levonorgestrel (LNG)-intrauterine devices (IUDs) are an effective method of contraception; however, there is growing evidence regarding potential psychiatric side effects such as depressive symptoms, anxiety, and suicidal thoughts. Therefore, we conducted this systematic review to summarise the psychiatric effects of using LNG-IUDs. We searched six databases (MEDLINE, Web of Science, Scopus, Science Direct, Cochrane Library, and PsycInfo), and we included all study designs. The included studies were extracted, quality assessed, and qualitatively summarised. Out of the screened studies, only 22 were finally included. While ten studies showed increased depressive symptoms, two studies showed reduced symptoms. Moreover, one study showed increased anxiety, another one reported an increased risk of suicide, four studies concluded no association with depressive symptoms, and four other studies showed uncertainty about a potential association but mentioned other psychiatric symptoms. Despite unreliable data, many studies report psychiatric symptoms associated with LNG-IUDs, predominantly depression. Gynaecologists, general practitioners, and psychiatrists should therefore be aware of these potential risks, especially depressive symptoms and suicidality. Counselling patients about these risks should be mandatory. Further studies should investigate the absolute risk of mental disorders associated with LNG-IUDs and other hormonal contraceptives. Many researchers are reporting adverse psychiatric events associated with levonorgestrel intrauterine devices (LNG-IUDs). Despite their effectiveness, a proper psychiatric assessment should be done before inserting LNG-IUDs. Proper counselling regarding the depressive symptoms and suicidality should be done by the treating obstetrician. Further studies should investigate the absolute risk of mental disorders associated with LNG-IUDs and other hormonal contraceptives. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its development. Previous studies have reported elevated plasminogen activator inhibitor-1 (PAI-1) levels in patients with depression, suggesting that PAI-1 levels might be linked to the etiology of MDD. Methods: We systematically searched the following online databases: MEDLINE, Scopus, and Web of Science up to September 10, 2020, to identify studies in which PAI-1 levels were reported in subjects with MDD. Subsequently we used RevMan 5.3 to perform a meta-analysis of data extracted from the included studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO criteria for the search and analysis. Results: Six studies that reported mean ± standard deviation (SD) were included in the analysis, with a total of 507 MDD patients and 3,453 controls. The overall standardized mean difference (SMD) was 0.27 (95% confidence interval [95% CI] 0.01-0.53). PAI-1 serum levels were 0.27 SDs higher in MDD patients than in controls. The test for overall effect was significant (z = 2.04, p = 0.04). Substantial heterogeneity was detected among the studies, demonstrated by the inconsistency test (I² = 72%) and the chi-square test (χ² = 18.32; p = 0.003). Conclusion: This systematic review and meta-analysis showed that MDD might be related to elevated PAI-1 levels. We propose larger prospective clinical studies to further investigate this clinical correlation and validate the clinical significance of these observations. [ABSTRACT FROM AUTHOR]

Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field. The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations. Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects. [ABSTRACT FROM AUTHOR]

Background: An early onset of depression is associated with higher chronicity and disability, more stressful life events (SLEs), higher negative emotionality as described by the primary emotion SADNESS and more severe depressive symptomatology compared to depression onset later in life. Additionally, methylation of the serotonin transporter gene (SLC6A4) is associated with SLEs and depressive symptoms. Methods: We investigated the relation of SLEs, SLC6A4 methylation in peripheral blood, the primary emotions SADNESS and SEEKING (measured by the Affective Neuroscience Personality Scales) as well as depressive symptom severity to age at depression onset in a sample of N = 146 inpatients suffering from major depression. Results: Depressed women showed higher SADNESS (t (91.05) = − 3.17, p = 0.028, d = − 0.57) and higher SLC6A4 methylation (t (88.79) = − 2.95, p = 0.02, d = − 0.55) compared to men. There were associations between SLEs, primary emotions and depression severity, which partly differed between women and men. The Akaike information criterion (AIC) indicated the selection of a model including sex, SLEs, SEEKING and SADNESS for the prediction of age at depression onset. SLC6A4 methylation was not related to depression severity, age at depression onset or SLEs in the entire group, but positively related to depression severity in women. Conclusions: Taken together, we provide further evidence that age at depression onset is associated with SLEs, personality and depression severity. However, we found no associations between age at onset and SLC6A4 methylation. The joint investigation of variables originating in biology, psychology and psychiatry could make an important contribution to understanding the development of depressive disorders by elucidating potential subtypes of depression. [ABSTRACT FROM AUTHOR]

The levonorgestrel-releasing intrauterine system (LNG-IUS) is used as hormonal contraception by millions of women worldwide. It is considered as a safe device with low rates of systemic adverse drug reactions (ADRs). However, an emerging evidence suggest mood changes as ADRs. Whereas most of these studies report psychiatric ADRs after the first implantation of the LNG-IUS, it has to be considered that these may also occur after replacement, even when psychiatric symptoms were not evident at the time of the initial insertion. A potential explanation for the development of psychiatric ADRs in subsequent LNG-IUS may rely on fluctuations of sex hormones throughout the female life cycle with changing windows of vulnerabilities for developing mood disorders. Thus, the reliable contraception for women remains a continual challenge. We present the case of a 41-year-old woman that used the LNG-IUS (Mirena®) for contraception over 5 years without any complaints. Within the first weeks after insertion of the second LNG-IUS, she developed a depressive syndrome and anxieties. An extensive somatic, including gynecological examination revealed no pathological findings and a mental disorder was suggested. Due to the patient´s request and the recommendation of her psychiatrist, the device was removed and led to a remission of her mental complaints up to a 6- and 12-months follow-up. Beyond the mood changes considerably affecting her quality of life, the patient raised the concerns that she has never been informed about potential ADRs on mental health and her remarks regarding the potential association between psychiatric symptoms and the LNG-IUS were considered as groundless. With this case, we strengthen previous observations regarding mood changes under LNG-IUS. Moreover, we illustrate that psychiatric symptoms may also occur as ADRs during the subsequent insertion. Thus, we emphasize that psychiatric symptoms have to be clearly communicated as ADRs to patients with LNG-IUS within a written informed consent and should be routinely examined by gynecologists. [ABSTRACT FROM AUTHOR]

Background: Psychotherapeutic interventions share common factors, which might contribute to treatment success independent of the type of psychotherapy. Previous research on common factors of psychotherapy was mostly conducted in outpatients and covered the development of common factors throughout a therapy over months or years. However, the role of common factors for the psychotherapeutic treatment success in inpatients during their hospital stay has not been addressed so far. The present research therefore aimed to explore changes of the common factors within a short-term stay at the psychiatric hospital for inpatients with major depressive disorder (MDD) and their relation to treatment outcome. Method: We developed a standardized manualized individual cognitive–behavioral psychotherapy (SMiCBT) for depression. The SMiCBT treatment lasted 4 weeks with eight therapy sessions. Following each treatment session, patients and therapists separately completed the questionnaire of "Stundenbogen für die Allgemeine und Differentielle Einzel-Psychotherapie" (STEP) to assess common factors from the perspective of the patient and the therapist. Severity of depression was also measured by the German version of the "Beck Depression Inventory" (BDI-II) before and after the treatment (SMiCBT). We conducted multilevel analysis for the longitudinal data for each scale of the STEP. Results: We found an improvement in the severity of depressive symptoms across the treatment period according to BDI-II scores. Regarding the STEP scales, motivational clarification and problem-solving scores increased over the treatment period for both patient and therapist perspectives. This was not the case for the scale therapeutic relationship. Furthermore, baseline levels of motivational clarification and problem solving were related to the treatment response. Limitations: The results have to be interpreted with care because of the small sample with MDD and the lack of a control group for comparison of treatment outcome. Conclusion: Our data demonstrate that common factors improve within a short-term psychotherapy in inpatients with MDD. Most importantly, our research highlights the distinguished role of motivational clarification and problem solving for the improvement of depressive symptoms during short-term psychotherapy in inpatient settings. [ABSTRACT FROM AUTHOR]

Background: Recent studies on the pathophysiology of major depression (MD) indicate that degenerative and inflammatory processes may play a role. This finding is supported by magnetic resonance imaging (MRI)-based meta-analysis that show volume reductions in circumscribed areas of the brain in patients with MD. Using optical coherence tomography (OCT), retinal changes have been demonstrated in neurodegenerative disorders. In light of this inflammatory/degenerative hypothesis, we tested whether patients with MD exhibit retinal alterations that might correlate with the severity and duration of the disease.Methods: Patients with MD and age- and gender-matched healthy controls were recruited for the measurement of the total volume and thickness of their retina as well as the thicknesses and volumes of five different retinal layers using single-layer-analysis provided by the spectral-domain-OCT.Results: OCT data from 28 patients with MD and 20 healthy controls were available for evaluation. The exploratory intra-individual group comparison of the two eyes showed a small but significant difference in the retinal total volume (right = 8.69mm3; left = 8.72mm3; p = 0.03) only in patients with MD. There were no other significant differences between the patients with MD and the healthy controls with respect to the OCT measurements.Limitations: The small group size as well as the absence of correction for multiple testing due to the exploratory design should be considered as limitations of our study.Conclusion: While retinal total volume differs between the eyes of patients with MD, the comparison of retinal parameters between these patients and age- and gender-matched healthy volunteers did not show any differences. [ABSTRACT FROM AUTHOR]

Abstract: Though electroconvulsive therapy (ECT) requires a close cooperation between anesthesiology and psychiatry, literature lacks of approaches that consider both disciplines in parallel. Special problems might be posed by patients with complicated features or ECT-indications other than treatment-refractory depression (TRD). Considering these patients there is a particular paucity of data, especially regarding anesthesiological aspects. Therefore, we sought (1) to discuss special issues of the peri-interventional management of non-TRD-cases from a combined psychiatric–anesthesiological point of view and (2) to assess the efficacy of ECT in the classical indication of TRD as compared to cases undergoing ECT for other indications or under difficult conditions (non-TRD) by means of Clinical Global Impression-Improvement (CGI-I) scale scores. A retrospective chart analysis of patients treated with ECT between the years 2009 and 2011 at the University of Ulm, Department of Psychiatry, was conducted. Special anesthesiological efforts were necessary in cohort non-TRD. There was no difference in the clinical outcome between cohort non-TRD (n=7) and TRD (n=22) with a median CGI-I score of 2 (“much improved”) in both groups. Close cooperation between psychiatry and anesthesiology is indispensable in non-TRD patients. Our results provide preliminary evidence that ECT is equally effective in the standard indication of TRD compared to other indications. [Copyright &y& Elsevier]

Abstract: Tranylcypromine (TCP) is a non-selective and irreversible monoamine oxidase inhibitor and an effective agent in the treatment of major depression. It features a complex pharmacologic profile and overdoses might induce severe intoxications. To identify typical clinical presentations of TCP-intoxications, range of associated TCP-dosages and possible differences between fatal and non-fatal intoxications a systematic review of all previously published cases of TCP-intoxications was conducted. We detected n=20 reports of TCP-intoxications in the literature (fatalities n=10). Mean age was 36.7 years (median 37); the majority of patients were female (60%). Frequent findings in patients with TCP-intoxications were disturbance of consciousness/cognitive dysfunction (90%), cardio-vascular symptoms (55%), hyperthermia (50%), respiratory distress (45%), delirium (45%), muscular rigidity (30%) and renal failure (20%). Suicidal intent was present in n=18 (90%) patients. First clinical symptoms related to TCP-intoxication developed on average in less than 1 day. The average dosage related to TCP-intoxication was 677mg. The highest survived TCP-dosage was 4000mg and the lowest fatal dosage was 170mg. Patients with fatal intoxications were on average older (40.5 vs. 32.8 years) and developed a more rapid onset of symptoms (0.2 vs. 0.8 days). Death occurred after a mean time of 0.6 days; symptom relief in patients with non-fatal intoxications developed on average after 3.2 days. Considering the large dose spectrum between survived and lethal TCP-dosages individual susceptibility factors might play a role regarding the severity of clinical symptoms independently of the ingested dosage. [Copyright &y& Elsevier]

Summary: Repetitive transcranial magnetic stimulation (rTMS) has been increasingly evaluated as a therapeutic tool for the treatment of depression, using various stimulation parameters and protocols. Heterogeneous results have been reported with regard to clinical outcome, at least partly due to the variety of procedures for coil placement above the desired site of stimulation. This article reviews the strategies for coil positioning in the treatment of depression. Considering preliminary clinical evidence, neuronavigated rTMS appears desirable to treat depression, compared to the standard targeting procedure (5cm anterior to the motor cortex). Coil positioning strategy might improve in the future by taking into consideration the individual abnormalities revealed by functional neuroimaging data. [Copyright &y& Elsevier]

Summary We report the case of a German male with a major depressive episode who also suffered from the terrifying perception that his penis was shrinking. These so-called koro-like symptoms (KLS) had also been present in earlier depressive episodes and subsided in the symptom-free interval of the recurrent depressive disorder. Under sufficient antidepressant medication with venlafaxine and lithium not only KLS but also the depressive symptoms remitted. The course of illness provides further evidence that KLS are not a distinct clinical entity in Western countries, but represent a concomitant syndrome that requires treatment of the underlying illness. [ABSTRACT FROM AUTHOR]

Depression in former ecstasy users may not respond to selective serotonin reuptake inhibitors (SSRIs) possibly due to damaged serotonergic synapses following tong-term heavy ecstasy use. We report findings in a patient suffering from MDMA-induced depression which was refractory to several antidepressive medications including selective noradrenergic reuptake inhibitor (SNRI) and SSRI. An add-on repeated bilateral electroconvulsive therapy (ECT) was able to achieve a stable remission of affective and cognitive symptoms with a follow-up of more than 1.5 years. Add-on ECT could be a treatment option in former ecstasy users with severe depressive disorders that fail to respond to SSRI and/or SNRI. Clinical trials are needed to evaluate further the usefulness of ECT in this patient group. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18–65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164). Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; –8·2, SD 7·2) and the sham tDCS group (n=73; –8·0, 9·3; difference 0·3 [95% CI –2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028). Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD. German Federal Ministry of Education and Research. [ABSTRACT FROM AUTHOR]

Background: Depression, as major depressive disorder (MDD) or as bipolar depression, is frequent among pregnant women (Evans et al., 2001) and an efficient treatment is fundamental. If left untreated, there are specific risks such as preterm delivery, low birth weight, and potentially death due to acute suicidality. Treatment of depression during pregnancy supposes a great challenge for pregnant women, their partner and for physicians involved. Despite psychopharmacotherapy and psychotherapy, electroconvulsive therapy (ECT) and other brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) or vagus nerve stimulation (VNS) are current available treatment strategies to treat depressive symptoms. ECT is recommended by the American Psychiatric Association Task Force on ECT as a safe and effective treatment of depression throughout pregnancy. However, ECT during pregnancy often involves concerns by both the patient and the physician due to unsolved questions regarding safety and tolerability as well as efficacy. Method: In order to retrieve insights into the frequency of reports, safety and efficacy of ECT for the treatment of MDD and bipolar depression during pregnancy we performed a systematic review of the existing literature. All publications between 1942 and the 1th December 2012 in the Medline, Embase and Scopus databases, that deal with ECT in MDD and bipolar depression during pregnancy were considered. Results: N=87 cases of ECT during pregnancy (MDD n =78; bipolar depression n =9) published in n =41 articles were detected. Of these 30 were case reports and 11 case series (with reported cases between n =2 and n =16). Furthermore, we evaluated the number of reported cases between the first report in 1942 and 2012 and divided the results in 4 time periods (1942–1959 n =46, 1960–1977 n =0, 1978–1995 n =14, and 1996–2012 n =18) in order to compare reported frequency. The results of our preliminary analysis suggest that ECT is efficacious and well tolerated in mother and offspring in the majority of analysed cases. In terms of safety, the comparison of the 4 time periods revealed that in the last analyzed time period a lower complication rate was observed. Most reported adverse effects were transient confusion, memory loss, headache and very rare premature contractions (mother) and fetal bradyarrhythmias. Further parameters (e.g. outcome of follow-up investigations, applied, narcotics, gestation age at the time of ECT, mean number of ECT sessions, detailed efficacy parameters as measured by psychometric scales, changes of the frequencies of reported ECTs during pregnancy) will be presented at the congress. Conclusions: Considering the results of our systematic review, ECT seems feasible in pregnant patients with MDD or bipolar depression. Our data support ECT to be more safe in the last decades for mother and offspring; however, the registered reported frequency does not support an increasingly use of this method with regard to the mentioned indication. [Copyright &y& Elsevier]

Psychiatric disorders are widely underreported diseases, especially in their early stages. So far, there is no fluid biomarker to confirm the diagnosis of these disorders. Proteomics data suggest the synaptic protein glutamate receptor 4 (GluR4), part of the AMPA receptor, as a potential diagnostic biomarker of major depressive disorder (MDD). A novel sandwich ELISA was established and analytically validated to detect GluR4 in cerebrospinal fluid (CSF) samples. A total of 85 subjects diagnosed with MDD (n = 36), bipolar disorder (BD, n = 12), schizophrenia (SCZ, n = 12) and neurological controls (CON, n = 25) were analysed. The data exhibited a significant correlation (r = 0.74; CI:0.62 to 0.82; p < 0.0001) with the antibody-free multiple reaction monitoring (MRM) mass spectrometry (MS) data. CSF GluR4 levels were lower in MDD (p < 0.002) and BD (p = 0.012) than in CON. Moreover, subjects with SCZ described a trend towards lower levels than CON (p = 0.13). The novel GluR4 ELISA may favour the clinical application of this protein as a potential diagnostic biomarker of psychiatric disorders and may facilitate the understanding of the pathophysiological mechanisms behind these disorders. • Glutamate receptor 4 as a novel CSF biomarker in the diagnosis of psychiatric disorders. • The sample comprised major depressive disorder, bipolar disorder and schizophrenia. • A novel sandwich ELISA to detect GluR4 in CSF samples was developed and validated. • Patients with MDD and BD presented lower GluR4 levels in CSF than controls. • The data correlated with the published targeted mass spectrometry findings. [ABSTRACT FROM AUTHOR]

Neuroinflammation has been connected to the pathophysiology of major depressive disorder (MDD) and neurochemical biomarkers of glial pathology could aid the diagnosis and might support patient stratification and monitoring in clinical trials. Our study aimed to determine the utility of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, for the differential diagnosis and monitoring of MDD. Employing Simoa technology we measured levels of GFAP in prospectively collected serum samples from 81 age-matched patients with MDD, schizophrenia (SZ), bipolar disorder (BP), and healthy controls (HC). Highest GFAP levels were determined for MDD. At a cut-off of 130 pg/ml, MDD could be discriminated with 87% sensitivity from SZ and BP (specificity 70%) and from HC (specificity 56%). GFAP levels increased with age (r = 0.5236, p = 0.0002) and with MDD severity quantified based on the Montgomery-Åsberg Depression Rating Scale (r = 0.4308, p = 0.0221). Neurofilament light chain serum levels were not different in the diagnostic groups and not associated with GFAP levels (r = 0.0911, p = 0.576) pointing to an independence of astrocyte activation on neurodegeneration. Our study provides first evidence that serum GFAP levels could improve the differential diagnosis of MDD and that depression severity could be objectively quantified using serum GFAP levels. Furthermore, serum GFAP might represent a marker to monitor astroglial pathology in the course of MDD. [ABSTRACT FROM AUTHOR]

Abstract When treating older adults, a main factor to consider is physical frailty. Because specific assessments in clinical trials are frequently lacking, critical appraisal of treatment evidence with respect to functional status is challenging. Our aim was to identify and categorize assessments for functional status given in clinical trials in older adults to allow for a retrospective characterization and indirect comparison of treatment evidence from these cohorts. We conducted 4 separate systematic reviews of randomized and nonrandomized controlled clinical trials in older people with hypertension, diabetes, depression, and dementia. All assessments identified that reflected functional status were analyzed. Assessments were categorized across 4 different functional status levels. These levels span from functionally not impaired, slightly impaired, significantly impaired, to severely impaired/disabled. If available from the literature, cut-offs for these 4 functioning levels were extracted. If not, or if the existing cut-offs did not match the predefined functional levels, cut-off points were defined by an expert group composed of geriatricians, pharmacists, pharmacologists, neurologists, psychiatrists, and epidemiologists using a patient-centered approach. We identified 51 instruments that included measures of functional status. Although some of the assessments had clearly defined cut-offs across our predefined categories, many others did not. In most cases, no cut-offs existed for slightly impaired or severely impaired older adults. Missing cut-offs or values to adjust were determined by the expert group and are presented as described. The functional status assessments that were identified and operationalized across 4 functional levels could now be used for a retrospective characterization of functional status in randomized controlled trials and observational studies. Allocated categories only serve as approximations and should be validated head-to-head in future studies. Moreover, as general standard, upcoming studies involving older adults should include and explicitly report functional impairment as a baseline characteristic of all participants enrolled. [ABSTRACT FROM AUTHOR]

Allogeneous hematogenic stem cell transplantation (HSCT) is a curative therapeutic strategy for numerous benign and malignant hematologic diseases. The transplantation procedure is characterized by significant physical, social and psychological stressors, especially for the graft recipient. This can lead to depression and anxiety. Every HSCT represents a potential risk for transmission of known and unknown diseases. Hematologically transmissible diseases of the donor therefore are considered a contraindication. Recent animal experiments have demonstrated that psychiatric diseases can transmitted via HSCT from donor to recipient. So far there are no such observations in human patients. Here we report the case of a 33 year old male patient who, because of a rare chronic hypoplastic congenital aenemia, underwent HSCT. The BM donor was the brother of the patient and suffered from recurrent depressive disorder. Because of the short stature resulting from his underlying hematologic disease the patient had been in psychotherapy form several years. Depressive episodes had not been observed during this time. 10 weeks post HSCT the patient experienced a depressed mood and recurring anxiety attacs. The initiation of antidpressant medication was considered but not started due to the mild symptomatology. While depressive symptoms after HSCT are not infrequent because of the multiple stressors outlined above, we argue that in the light of the recent animals studies on the transmission of psychiatric disease via hematopoeitic stem cells in the present constellation a hematologic transmission of the mood disorder can also be condsidered. Acknowledment: To the colleagues of the Department of Pediatrics. [ABSTRACT FROM AUTHOR]

Objective: Repetitive transcranial magnetic stimulation (rTMS) is regarded as a potentially new tool to treat depression. In a double-blind, randomized, sham-controlled pilot study we investigated the efficacy of neuronavigated rTMS, guided according to the prefrontal metabolic state determined by positron emission tomography (PET). Methods: 25 patients with major depression were included. Prior to rTMS, PET scans were obtained. For the real stimulation condition, the dorsolateral prefrontal cortex (DLPFC) with lower metabolic activity compared to the contralateral hemisphere was selected, if detected by prior PET. Stimulation parameters were 15 Hz, 110% motor threshold (MT), 3000 stimuli/day, for 10 days. A neuronavigational system was used to place the magnetic coil above each individuals’ selected cortical region (real condition: DLPFC, sham: midline parieto-occipital, intensity 90% of MT). RTMS was administered add-on to medication. Depression-related symptoms were rated with Beck''s, Hamilton''s (HAM-D), and Montgomery–Asberg''s (MADRS) depression rating scales. Results: Real stimulation improved depression according to HAM-D and MADRS moderately but significantly better compared to sham at the end of the stimulation sessions. In the real condition, four out of 13 patients responded with a mean improvement in HAM-D and/or MADRS of at least 50%, whereas none responded to sham. Antidepressant effects of stimulation of the relatively hypometabolic DLPFC were comparable to stimulation in absence of metabolic differences. Conclusions: A moderate improvement of depressive symptoms after rTMS was observed. Our preliminary data show that stimulation of prefrontal hypometabolism may not be advantageous to stimulation irrespective of the metabolic state. [Copyright &y& Elsevier]

Current understanding of the molecular mechanisms underlying ketamine's antidepressant effect remains largely incomplete. Recent imaging studies provide evidence for ketamine effects on amygdalo-hippocampal. This study in mice aimed to investigate acute proteomic changes after ketamine administration in various brain regions including amygdala and hippocampus. One hour after administration of s-ketamine, the brain-region tissues of interest were dissected out and analyzed using label-free shotgun proteomics. The deep proteomic analysis of amygdala and hippocampus identified 89,526 peptides corresponding to 8000 proteins. The analysis revealed a pronounced proteomic signature of the acute ketamine effect in the amygdala. We anticipate that this proteomic dataset will improve understanding of the mechanism of action of ketamine and identification of new drug targets. Major depressive disorder (MDD) is the leading cause of global disability and it presents a significant challenge to human health. S-ketamine has been proposed as a rapid acting antidepressant and, indeed, the FDA recently approved it for treatment of resistant MDD. However, the mechanism of action of s-ketamine as an antidepressant is still elusive. In this context, we investigated the short-term proteomic changes after ketamine administration in mouse brain regions previously related to ketamine effects such as amygdala and hippocampus. We anticipate that this proteomic dataset will provide highly useful information to improve our understanding of the mechanism of action of ketamine and identification of new drug targets. Unlabelled Image • The study investigates s-ketamine induced acute proteomic changes in the murine brain. • It presents a comprehenisve coverage of amygdala and hippocampus proteomes. • It reports on a pronounced rapid effect of s-ketamine on amygdala. • It reveals altered levels of Grm5 and GABA α 1 and ß3. • S-ketamine may affect the balance between excitatory and inhibatory signals. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Female sexual hormones (estrogens and gestagens) may affect neurocognitive functioning and mood. Thus, the use of oral hormonal contraceptives (OHC) bears the risk of psychiatric adverse drug reactions such as depression and psychosis. However, the available empiric evidence regarding this connection is conflicting, and, moreover, female sex hormones seem to feature also mood-stabilizing and antidepressive effects. Hence, individual susceptibility factors and preparation-specific pharmacologic properties might play a pivotal role in the development of mood disturbances related to OHC. Single case reports provide empiric data for further systematic approaches. Methods: A clinical case is presented and discussed. Results: A 36-year-old female patient with recurrent major depressive disorder developed rapid relapse in depression after initialization of OHC with ethinyl estradiol 30 μg/chlormadinone acetate 2 mg. This OHC combination was described to particularly feature positive effects on depressive mood. Conclusions: OHC may induce serious mood disturbances and should be administered with care, particularly in patients with affective disorders. [Copyright &y& Elsevier]

Question: Little is known regarding the risks of electroconvulsive therapy (ECT) in patients with clippings of intracerebral aneurysms. Currently, literature merely provides few anecdotal reports (Najiar and Guttmacher, 1998) and manufacturers of such clipping systems (usually made of titanium) refrain from any suggestions concerning the safety during the performance of ECT. Thus, clinicians facing the coincidence of therapy-refractory depression (suggesting performance of ECT) and presence of intracerebral clips have to trade of possible benefits of ECT against theoretical risks in the complete absence of any guidelines or recommendations. Indeed, titanium is principally inert and the application of electric current should therefore not result in significant warming (with the risk of damaging surrounding brain tissue). However, the indication of ECT under these conditions must be confirmed meticulously. Methods: A case report is presented in order to to contribute to the available experience concerning this clinical situation. Results: We present the case of a 55-year old female patient who successfully underwent clipping (Yasargil Titanium Clip, Aesculap®) of the left middle cerebral artery (MCA) due to MCA-aneurysm three years prior. The patient suffered from treatment-refractory major depressive disorder (recurrent type). Taking into account that various pharmacologic treatment attempts failed, ECT was considered. The patient was comprehensively informed about possible risks of the procedure related to the titanium clip. Before ECT CT-angiography was performed showing no re-development of the surgically treated aneurysm or development of new aneurysms. 12 cycles of right-unilateral ECT were performed without any complications despite ECT-related tachycardia. During ECT the patient was treated with esmolol. Subsequently, the patient’s clinical situation significantly improved. Conclusions: Though clear guidelines or suggestions of manufacturers of neurosurgical clips regarding safety during ECT are absent we did not observe any major complications during ECT in a patient with an intracerebral Yasargil titanium clip. However, the material behaviour of titanium during application of electric current remains to be studied systematically in order to rule out problematic warming with the risk of tissue damage. [ABSTRACT FROM AUTHOR]

The treatment of psychiatric disorders during pregnancy poses a challenge particularly regarding limited pharmacological possibilities. Repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) have been described to be successful in few single cases but, however, literature lacks of guidelines. In order to contribute to the pool of empirical data that is necessary to create evidenced based recommendations we present a case of successful treatment of major depression with ECT in a 35.year old pregnant patient with non-response to rTMS. [ABSTRACT FROM AUTHOR]