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ZusammenfassungDiabetes mellitus ist häufig mit psychischen Erkrankungen assoziiert. Depressive Störungen kommen bei diabetischen Patient:innen doppelt so häufig vor wie in der nicht-diabetischen Population. Andere psychische Erkrankungen, die gehäuft mit Prädiabetes und Diabetes mellitus vorkommen, sind kognitive Dysfunktionen bis zur Demenz, auffälliges Essverhalten, Angststörungen, Schizophrenie, bipolare Störungen und Borderline-Persönlichkeitsstörungen. Die ungünstigen Auswirkungen dieser Koinzidenz auf den Stoffwechsel sind nachhaltig und manifestieren als schlechtere metabolische Kontrolle und vermehrte mikro- und makroangiopathische Komplikationen. Ziel dieses Positionspapieres ist die Sensibilisierung aller involvierten medizinischen Fachkolleg:innen sowie aller anderen mit dem Thema Diabetes befassten Berufsgruppen und Organisationen, um eine Intensivierung der komplexen therapeutischen Interventionen bei Patient:innen zu erreichen.Positive Auswirkungen wären die Verringerung der Inzidenz von Diabetes mellitus bei Patient:innen mit psychischen Erkrankungen, sowie die Reduktion von Spätfolgen des Diabetes mellitus, insbesondere der kardiovaskulären Morbidität und Mortalität und eine verbesserte Lebensqualität der Betroffenen.

Introduction Due to favorable antidepressant (AD) efficacy and tolerability, selective-serotonin reuptake inhibitors (SSRIs) are consistently recommended as substances of first choice for the treatment of major depressive disorder (MDD) in international guidelines. However, little is known about the real-world clinical correlates of patients primarily prescribed SSRIs in contrast to those receiving alternative first-line ADs. Methods These secondary analyses are based on a naturalistic, multinational cross-sectional study conducted by the European Group for the Study of Resistant Depression at ten research sites. We compared the socio-demographic and clinical characteristics of 1410 patients with primary MDD, who were either prescribed SSRIs or alternative substances as first-line AD treatment, using chi-squared tests, analyses of covariance, and logistic regression analyses. Results SSRIs were prescribed in 52.1% of MDD patients who showed lower odds for unemployment, current severity of depressive symptoms, melancholic features, suicidality, as well as current inpatient treatment compared to patients receiving alternative first-line ADs. Furthermore, patients prescribed SSRIs less likely received add-on therapies including AD combination and augmentation with antipsychotics, and exhibited a trend towards higher response rates. Conclusion A more favorable socio-demographic and clinical profile associated with SSRIs in contrast to alternative first-line ADs may have guided European psychiatrists’ treatment choice for SSRIs, rather than any relevant pharmacological differences in mechanisms of action of the investigated ADs. Our results must be cautiously interpreted in light of predictable biases resulting from the open treatment selection, the possible allocation of less severely ill patients to SSRIs as well as the cross-sectional study design that does not allow to ascertain any causal conclusions.

Purpose Bariatric surgery reduces mortality in patients with severe obesity and is predominantly performed in women. Therefore, an analysis of sex-specific differences after bariatric surgery in a population-based dataset from Austria was performed. The focus was on deceased patients after bariatric surgery. Materials and Methods The Austrian health insurance funds cover about 98% of the Austrian population. Medical health claims data of all Austrians who underwent bariatric surgery from 01/2010 to 12/2018 were analyzed. In total, 19,901 patients with 107,806 observed years postoperative were eligible for this analysis. Comorbidities based on International Classification of Diseases (ICD)-codes and drug intake documented by Anatomical Therapeutical Chemical (ATC)-codes were analyzed in patients deceased and grouped according to clinically relevant obesity-associated comorbidities: diabetes mellitus (DM), cardiovascular disease (CV), psychiatric disorder (PSY), and malignancy (M). Results In total, 367 deaths were observed (1.8%) within the observation period from 01/2010 to 04/2020. The overall mortality rate was 0.34% per year of observation and significantly higher in men compared to women (0.64 vs. 0.24%; p p p = 0.034), whereas malignant diseases (36%) were more frequent in women (30 vs. 41%; p = 0.025). Conclusion After bariatric surgery, short-term mortality as well as long-term mortality was higher in men compared to women. In deceased patients, diabetes was more common in men, whereas malignant diseases were more common in women. Graphical abstract

Contains fulltext : 292377.pdf (Publisher’s version ) (Open Access) BACKGROUND: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are among the most frequently prescribed antidepressants (ADs) for major depressive disorder (MDD), with an increasing trend in the last decade. Given the relative dearth of information regarding rationales for their preferred use as first-line ADs in the broad clinical routine, the present study systematically investigated real-world characteristics of MDD patients prescribed either SNRIs or other AD substances across different countries and treatment settings. METHODS: In the present secondary analyses based on a large European, multi-site, naturalistic and cross-sectional investigation with a retrospective assessment of treatment outcome, we firstly defined the proportion of MDD patients receiving SNRIs as first-line AD psychopharmacotherapy and secondly compared their sociodemographic and clinical characteristics to those patients prescribed alternative first-line ADs during their current major depressive episode (MDE). RESULTS: Within the total sample of 1410 MDD patients, 336 (23.8 %) received first-line SNRIs. Compared to other ADs, SNRIs were significantly associated with inpatient care, suicidality and treatment resistance during the current MDE, and a longer lifetime duration of psychiatric hospitalizations. Moreover, greater severity of depressive symptoms at study entry, higher daily doses of the administered ADs, as well as more frequent prescriptions of psychopharmacotherapeutic add-on strategies in general and antipsychotic augmentation in particular, were significantly related to first-line SNRIs. CONCLUSIONS: Considering the limitations of a cross-sectional and retrospective study design, our data point towards a preferred use of first-line SNRIs in a generally more severely ill MDD patients, although they did not lead to superior treatment outcomes compared to alternative ADs.

ZusammenfassungAktive Sterbehilfe ist aktuell in Österreich noch gesetzlich verboten. Aufgrund einer Entscheidung des Verfassungsgerichtshofs wäre assistierter Suizid ab dem Jahr 2022 gänzlich legal. Eine gesetzliche Regelung, die Grenzen zwischen legalen Formen einer Assistenz sowie deren Voraussetzungen und weiterhin unerlaubten Assistenzleistungen zieht, ist derzeit noch nicht in Sicht. Ein Suizid, der auf Verlangen des Suizidenten von fremder Hand herbeigeführt wird, bleibt jedenfalls weiterhin strafbar; dies auch dann, wenn der Suizident physisch nicht mehr in der Lage ist, bei seiner Tötung mitzuwirken. In mehreren europäischen Ländern wurde aktive Sterbehilfe bereits legalisiert und in manchen Ländern, wie zum Beispiel der Schweiz, kann assistierter Suizid auch ohne lebenszeitlimitierende Grunderkrankung, bei unerträglichem Leid und insuffizient vorhandenen weitere Behandlungsmöglichkeiten in Anspruch genommen werden. In diesem Fallbericht wird die Kasuistik einer Patientin geschildert welche, als Grunderkrankung an einer Persönlichkeitsstörung leidend, einen assistierten Suizid in der Schweiz geplant hatte. Es werden die ethischen und juristischen Hintergründe dieses Fallberichts diskutiert.Das zur Verfügung stellen assistierter Suizidmöglichkeiten birgt die große Gefahr, dass Menschen mit psychischer Erkrankung, insbesondere bei schweren depressiven Episoden, Behandlungsangebote ablehnen und anstelle Suizid durch einen professionellen Sterbehilfeanbieter wählen könnten. Insbesondere gewarnt werden muss vor der Tatsache, dass Menschen in aktuell schwer depressivem Zustandsbild aufgrund dessen zumeist unter eingeschränkter Entscheidungsfähigkeit leiden und nur bedingt über die Möglichkeit der freien Willensentscheidung verfügen.

Objective Major depressive disorder (MDD) and anxiety disorders are both common and especially challenging during pregnancy. Considering possible risks of intrauterine drug exposure of the child, the role of psychopharmacological treatment is ambiguous and various negative obstetric outcomes were inconsistently associated with medication. Consequently, a critical examination of peri- and postnatal phenomena associated with intrauterine exposure to antidepressants based on serotonin-reuptake inhibition (SRI) and subsumed under the term "poor neonatal adaptation syndrome" (PNAS) is urgently called for. Methods A comprehensive literature search was conducted, revealing a total number of 33 relevant studies and 69 individual outcomes among 3025 screened studies. Seventeen outcomes allowed meta-analytic evaluation (random effects model). Measures for heterogeneity (I2 ) and contour-enhanced funnel plots were generated. Results Single studies showed increased risks for deficits in neurological functioning and autonomous adaptation in SRI exposed infants. Meta-analytical evaluation showed increased symptom occurrence or severity in exposed neonates for low APGAR scores, birth weight, size for gestational age, preterm delivery, neuromuscular and autonomous regulation, and higher rates of admission to specialized care. Mostly, increased risk after SRI exposure was supported by comparison to unexposed infants born to mothers diagnosed with depression. Conclusion Whereas statistically significant evidence for various effects of intrauterine exposure to SRI was found, the clinical relevance remains unresolved due to inherently low data quality in this research domain and insufficiently defined samples and outcomes. More systematic research under ethical considerations is required to improve multiprofessional counselling in the many women dealing with MDD during pregnancy and the peripartum.

Combining mouse experiments with big data analysis of the Austrian population, we investigated the association between high-dose statin treatment and bone quality.The bone microarchitecture of the femur and vertebral body L4 was measured in male and ovariectomized female mice on a high-fat diet containing simvastatin (1.2 g/kg). A sex-specific matched big data analysis of Austrian health insurance claims using multiple logistic regression models was conducted (simvastatin 60-80 mg/day vs. controls; males: n = 138,666; females: n = 155,055).High-dose simvastatin impaired bone quality in male and ovariectomized mice. In the trabecular femur, simvastatin reduced bone volume (µmHigh-dose simvastatin dramatically reduces bone quality in obese male and ovariectomized female mice, suggesting that direct drug action accounts for the association between high dosage and increased risk of osteoporosis as observed in comparable human cohorts. The underlying pathophysiological mechanisms behind this relationship are presently unknown and require further investigation.

Background: Sex-related effects on the evolution and phenotype of major depressive disorder (MDD) were reported previously. Methods: This European multicenter cross-sectional study compared sociodemographic, clinical, and treatment patterns between males and females in a real-world sample of 1410 in- and outpatients with current MDD. Results: Male MDD patients (33.1%) were rather inpatients, suffered from moderate to high suicidality levels, received noradrenergicand specific serotonergic antidepressants (ADs) as first-line AD treatment, generally higher mean AD daily doses, and showed a trend towards a more frequent administration of add-on treatments. Female MDD patients (66.9%) were rather outpatients, experienced lower suicidality levels, comorbid thyroid dysfunction, migraine, asthma, and a trend towards earlier disease onset. Conclusions: The identified divergencies may contribute to the concept of maleand female depressive syndromes and serve as predictors of disease severity and course, as they reflect phenomena that were repeatedly related to treatment-resistant depression (TRD). Especially the greater necessity of inpatient treatment and more complex psychopharmacotherapy in men may reflect increased therapeutic efforts undertaken to treat suicidality and to avoid TRD. Hence, considering sex may guide the diagnostic and treatment processes towards targeting challenging clinical manifestations including comorbidities and suicidality, and prevention of TRD and chronicity.

Background While the association between relationship status and the development of depressive symptoms in the general population were reported previously, its relation to the severity and the course of major depressive disorder (MDD) as well as the treatment patterns and response rates needs to be elucidated. Methods The present international multicenter cross-sectional study performed by the European Group for the Study of Resistant Depression (GSRD) investigated socio-demographic and clinical patterns of relationship status in a real-world sample of 1410 adult in- and outpatients with MDD as primary diagnosis. Results While 49.9% of all MDD patients were partnered, 25.4% were separated, and 24.8% were single. Single relationship status was linked to younger mean age, earlier mean age of onset, and current suicidal risk. Being separated was related to older mean age, unemployment, greater symptom severity, current suicidal risk, and add-on treatment strategies. Partnered relationship status was associated with less frequent current suicidal risk. Limitations The retrospective assessment of treatment response that was exclusively based on psychopharmacotherapeutic strategies should be critically considered and weighed while interpreting the present results providing novel insights into the complex interaction of relationship status with the clinical phenotype of MDD. Conclusions Although MDD patients living in relationships do not seem to be omitted from the evolution of MDD, they may be spared from chronicity and suicidality. Hence, being aware of the current relationship status might support clinicians in the diagnostic and therapeutic process towards optimized management of such challenging clinical phenomena and their negative consequences.

Objectives Predictors for unfavorable treatment outcome in major depressive disorder (MDD) applicable for treatment selection are still lacking. The database of a longitudinal multicenter study on 1079 acutely depressed patients, performed by the German research network on depression (GRND), allows supervised and unsupervised learning to further elucidate the interplay of clinical and psycho‐sociodemographic variables and their predictive impact on treatment outcome phenotypes. Experimental Procedures Treatment response was defined by a change of HAM‐D 17‐item baseline score ≥50% and remission by the established threshold of ≤7, respectively, after up to eight weeks of inpatient treatment. After hierarchical symptom clustering and stratification by treatment subtypes (serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotic, and lithium augmentation), prediction models for different outcome phenotypes were computed with random forest in a cross‐center validation design. In total, 88 predictors were implemented. Results Clustering revealed four distinct HAM‐D subscores related to emotional, anxious, sleep, and appetite symptoms, respectively. After feature selection, classification models reached moderate to high accuracies up to 0.85. Highest accuracies were observed for the SSRI and TCA subgroups and for sleep and appetite symptoms, while anxious symptoms showed poor predictability. Conclusion Our results support a decisive role for machine learning in the management of antidepressant treatment. Treatment‐ and symptom‐specific algorithms may increase accuracies by reducing heterogeneity. Especially, predictors related to duration of illness, baseline depression severity, anxiety and somatic symptoms, and personality traits moderate treatment success. However, prospectives application of machine learning models will be necessary to prove their value for the clinic.

Context A substantial number of patients undergoing bariatric surgery are prescribed psychopharmacological medication. However, the impact of concomitant psychopharmacological medication on the frequency of relevant vitamin deficiencies in postoperative follow-up is not known. Methods Five hundred twenty-four patients with obesity who underwent bariatric surgery (January 2004 to September 2018) with follow-up of at least 12 months, were included in retrospective analysis. Postoperative follow-up visits between January 2015 and September 2019 were analyzed. Anthropometric and laboratory data were analyzed at the first documented follow-up visit after on average 39.5 ± 37.3 months and at every following visit during the observation period. Patients with prescribed psychopharmacological drugs (PD) were compared with patients without (control group, CON). Results Psychopharmacological medication was documented in 25% (132) of patients. In 59 patients documented prescription of more than one psychiatric drug was found, whereas psychopharmacological monotherapy was found in 73 patients. Frequencies of vitamin deficiencies were comparable between PD and CON (vitamin A: p = 0.852; vitamin D: p = 0.622; vitamin E: p = 0.901; folic acid: p = 0.941). Prevalence of vitamin B12 deficiency was rare (6% CON, 1% PD) but was significantly higher in CON (p = 0.023). A comparison of CON and POLY also showed no significant differences between the groups concerning prevalence of vitamin deficiencies. Conclusions Intake of psychopharmacological medication is highly prevalent in patients after bariatric surgery. Patients with psychopharmacological medication, who participate in structured follow-up care after bariatric surgery, are not at higher risk for vitamin deficiencies compared with controls.

About two thirds of the patients with major depressive disorder (MDD) do not sufficiently respond to monotherapy with antidepressants (ADs) which makes them reliant on further treatment approaches. Hereby, combination of different ADs and augmentation with second-generation antipsychotics (SGAs) are widely used and recommended psychopharmacotherapeutic strategies. The present secondary analyses are based on an international, naturalistic, cross-sectional multicenter study conducted by the European Group for the Study of Resistant Depression. Comparing socio-demographic and clinical characteristics of 436 adult MDD patients receiving either SGAs (N = 191, 43.8%) or ADs (N = 245, 56.2%), that were additionally administered to their first-line AD psychopharmacotherapy, we aimed to identify possible trajectories of decision-making for clinicians regarding which treatment option to prefer in individual patients. Our most robust findings represent an association of SGA augmentation with the presence of psychotic symptoms, longer mean duration of lifetime psychiatric hospitalizations, employment of further augmentation strategies with mood-stabilizers and benzodiazepines, and a trend towards higher mean daily dosages of their first-line ADs and current suicidal risk. Treatment outcome was not significantly different between patients receiving either SGA augmentation or AD combination. Being aware of limitations inherent to the cross-sectional study design and the lack of randomization, more severe and rather chronic conditions in MDD seemed to encourage clinicians to choose SGA augmentation over AD combination. The fact that mood-stabilizers and/or benzodiazepines were more frequently co-administered with SGAs may represent a requirement of an overall refined psychopharmacotherapy including additional fast-acting agents with potent AD, tranquilizing and anti-suicidal effects in MDD patients experiencing challenging clinical manifestations. New glutamatergic substances seem to be promising in this regard.

Background Augmentation with second-generation antipsychotics (SGAs) represents an evidence-based psychopharmacotherapeutic strategy recommended in case of insufficient response to the first-line antidepressant (AD) treatment in major depressive disorder (MDD). Comparative evidence regarding efficacy and prescription preferences of the individual SGAs is scarce. Methods In the scope of this European, multi-site, naturalistic cross-sectional investigation with retrospective assessment of treatment outcome, we compared sociodemographic and clinical characteristics of 187 MDD patients receiving either quetiapine (n = 150) or aripiprazole (n = 37) as augmentation of their first-line AD psychopharmacotherapy. Results Comorbid posttraumatic stress disorder and diabetes were significantly associated with aripiprazole augmentation in our primary and post-hoc binary logistic regression analyses. Furthermore, we identified an association between aripiprazole co-administration and the presence of additional psychotic features, higher rates of AD combination treatment, and a longer duration of psychiatric hospitalizations during the lifetime, which, however, lost significance after correcting for multiple comparisons. Regarding treatment outcome, we found a trend of higher response rates and greater reductions in severity of depressive symptoms in MDD patients dispensed quetiapine. Conclusions Factors associated with a more chronic and severe profile of MDD seem to encourage clinicians to choose aripiprazole over quetiapine, that was, however, administered in the majority of our MDD patients, which might reflect the current approval situation allowing to prescribe exclusively quetiapine as on-label augmentation in MDD in Europe. Given the retrospective assessment of treatment response, the markedly smaller proportion of patients receiving aripiprazole augmentation generally showing an unfavorable disease profile, and the partially heterogeneous statistical robustness of our findings, further studies are required to elaborate on our observation and to generate unambiguous recommendations regarding the choice of first-line SGA augmentation in MDD.

Since selective serotonin reuptake inhibitors, that are recommended as first-line antidepressant psychopharmacotherapy for major depressive disorder (MDD), may not be the optimal choice for every patient, antidepressants with different modes of action exerting a distinct set of expectant effects, represent a valuable alternative. Despite the previously observed increased prescription rates of noradrenergic and specific serotonergic antidepressants (NaSSAs) particularly mirtazapine in Europe, the individual profiles of patients primarily prescribed NaSSAs in real-world settings have not been systematically investigated yet. In this secondary analysis based on a European, cross-sectional, naturalistic, multicenter study involving 1410 adult males and females with primary MDD, sociodemographic and clinical variables were compared between patients dispensed NaSSAs and those with alternative first-line antidepressants. Hereby, NaSSAs were administered in 8.6 % of the sample (mirtazapine: n = 114, mianserin: n = 7). We detected associations with older mean age, male sex, unemployment, as well as additional melancholic and catatonic features, inpatient treatment, lower mean daily dosages of the administered antidepressants but higher rates of augmentation with low-potency antipsychotics, and greater mean reductions of depressive symptoms during their current major depressive episodes. Although the study design is unsuitable to draw any causal conclusions, our findings provide a realistic picture of patients eligible for first-line antidepressant treatment with NaSSAs, especially mirtazapine, and underscore the role of this AD substance class in severe MDD. Further, they may represent a promising basis for future systematic research focusing on precision diagnostics and treatment in MDD, that would ideally result in faster responses and better outcomes, especially in the so-called difficult-to-treat conditions including treatment resistant depression.

Objective: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing infectious diseases such as pneumonia. Hitherto, there has been uncertainty as to whether there is a relationship between different antidiabetic drug combinations and development of pneumonia in this specific cohort. Research Design and Methods: In this longitudinal retrospective study we used multiple logistic regression analysis to assess the odds ratios (ORs) of pneumonia during an observational period of 2 years in 31,397 patients with T2DM under previously prescribed stable antidiabetic drug combinations over a duration of 4 years in comparison to 6568 T2DM patients without drug therapy over 4 years adjusted for age, sex and hospitalization duration. Results: Of the 37,965 patients with T2DM, 3720 patients underwent stable monotherapy treatment with insulin (mean age: 66.57 ± 9.72 years), 2939 individuals (mean age: 70.62 ± 8.95 y) received stable statin and insulin therapy, and 1596 patients were treated with a stable combination therapy of metformin, insulin and statins (mean age: 68.27 ± 8.86 y). In comparison to the control group without antidiabetic drugs (mean age: 72.83 ± 9.96 y), individuals undergoing insulin monotherapy (OR: 2.07, CI: 1.54–2.79, p &lt, 0.001), insulin and statin combination therapy (OR: 2.24, CI: 1.68–3.00, p &lt, metformin, insulin and statin combination therapy (OR: 2.27, CI: 1.55–3.31, p &lt, statin, insulin and dipeptidyl peptidase-4 inhibitor (DPP-IV inhibitor) combination therapy (OR: 4.31, CI: 1.80–10.33, p = 0.001), as well as individuals treated with metformin and sulfonylureas (OR: 1.70, CI: 1.08–2.69, p = 0.02) were at increased risk of receiving a diagnosis of pneumonia. Conclusions: Stable monotherapy with insulin, but also in combination with other antidiabetic drugs, is related to an increased risk of being diagnosed with pneumonia during hospital stays in patients with type 2 diabetes mellitus compared to untreated controls.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a robust genetic influence. The norepinephrine transporter (NET) is of particular interest as it is one of the main targets in treatment of the disorder. As ADHD is a complex and polygenetic condition, the possible regulation by epigenetic processes has received increased attention. We sought to determine possible differences in NET promoter DNA methylation between patients with ADHD and healthy controls. DNA methylation levels in the promoter region of the NET were determined in 23 adult patients with ADHD and 23 healthy controls. A subgroup of 18 patients with ADHD and 18 healthy controls underwent positron emission tomography (PET) with the radioligand (S,S)-[18F]FMeNER-D2 to quantify the NET in several brain areas in vivo. Analyses revealed significant differences in NET methylation levels at several cytosine–phosphate–guanine (CpG) sites between groups. A defined segment of the NET promoter (“region 1”) was hypermethylated in patients in comparison with controls. In ADHD patients, a negative correlation between methylation of a CpG site in this region and NET distribution in the thalamus, locus coeruleus, and the raphe nuclei was detected. Furthermore, methylation of several sites in region 1 was negatively associated with the severity of hyperactivity–impulsivity symptoms. Our results point to an epigenetic dysregulation in ADHD, possibly due to a compensatory mechanisms or additional factors involved in transcriptional processing.

Pharmacological imaging of the effects of selective serotonin reuptake inhibitors (SSRI) may aid the clarification of their mechanism of action and influence treatment of highly prevalent neuropsychiatric conditions if the detected effects could be related to patient outcomes. In a randomized double-blind design, 38 healthy participants received a constant infusion of 8 mg citalopram or saline during either their first or second of two PET/MR scans. Resting-state functional MRI (fMRI) was acquired simultaneously with PET data on the binding of serotonin transporters (5-HTT) using [11C]DASB. Three different approaches for modeling of pharmacological fMRI response were tested separately. These relied on the use of regressors corresponding to (1) the drug infusion paradigm, (2) time courses of citalopram plasma concentrations and (3) changes in 5-HTT binding measured in each individual, respectively. Furthermore, the replication of results of a widely used model-free analysis method was attempted which assesses the deviation of signal in discrete time bins of fMRI data acquired after start of drug infusion. Following drug challenge, average 5-HTT occupancy was 69±7% and peak citalopram plasma levels were 111.8 ± 21.1 ng/ml. None of the applied methods could detect significant differences in the pharmacological response between SSRI and placebo scans. The failed replication of SSRI effects reported in the literature despite a threefold larger sample size highlights the importance of appropriate correction for family-wise error in order to avoid spurious results in pharmacological imaging. This calls for the development of analysis methods which take regional specialization and the dynamics of brain activity into account.

The objective of the present multicenter study was to elucidate relevant associations between major depressive disorder (MDD) and comorbid hypertension that are known for their frequent co-occurrence and interaction with regard to functional disability. Demographic and clinical information of altogether 1410 patients were retrieved cross-sectionally. Consecutively, a comparison of patient characteristics between MDD subjects with and without comorbid hypertension were conducted by descriptive statistics, analyses of covariance (ANCOVA) and binary logistic regression analyses. The point prevalence rate for comorbid hypertension was 18.9%. Patients with MDD+comorbid hypertension were significantly older, heavier, more likely to be in a relationship, inpatient and diagnosed with further comorbid chronic somatic diseases including heart disease, diabetes and thyroid dysfunction. In addition, individuals with MDD and comorbid hypertension exhibited a higher score at the Montgomery and Åsberg Depression Rating Scale (MADRS) at onset of the current depressive episode. Melancholic features of depression showed a higher probability. The first line antidepressant treatment did not differ significantly between MDD subjects with versus without comorbid hypertension. Augmentation with pregabalin and combination with one additional antidepressant, however, were more common in the MDD+hypertension group. In conclusion, high blood pressure may influence illness severity and is associated with a distinct psychopathology in MDD patients. Patients with MDD and comorbid hypertension, that seems to be underdiagnosed in MDD patients compared to the general population, are subject to additional somatic diseases in almost 100 percent of the cases and hence, need to be screened and treated accordingly.

Diabetes mellitus ist haufig mit psychischen Erkrankungen assoziiert. Depressive Storungen kommen bei diabetischen PatientInnen doppelt so haufig vor wie in der nicht-diabetischen Population. Andere psychische Erkrankungen, die gehauft mit Pradiabetes und Diabetes mellitus vorkommen, sind kognitive Dysfunktionen bis zur Demenz, auffalliges Essverhalten, Angststorungen, Schizophrenie, bipolare Storungen und Borderline-Personlichkeitsstorungen. Die ungunstigen Auswirkungen dieser Koinzidenz auf den Stoffwechsel sind nachhaltig und manifestieren als schlechtere metabolische Kontrolle und vermehrte mikro- und makroangiopathische Komplikationen. Ziel dieses Positionspapieres ist sowohl die Sensibilisierung aller involvierten medizinischen FachkollegInnen sowie sonstiger mit dem Thema befasster Berufsgruppen und Organisationen als auch die Intensivierung der komplexen therapeutischen Interventionen bei PatientInnen. Positive Auswirkungen waren die Verringerung der Inzidenz von Diabetes mellitus bei PatientInnen mit psychischen Erkrankungen, die konsekutive Reduktion von Spatfolgen, insbesondere der kardiovaskularen Morbiditat und Mortalitat sowie eine verbesserte Lebensqualitat der Betroffenen.

Assisted suicide is currently still prohibited in Austria. However, following a finding of the Austrian Constitutional Court it would be completely legal from 2022. A statutory regulation defining the limits between legal ways of assistance and the conditions therefor on the one hand and, on the other hand, assistive actions that shall remain prohibited is currently not in sight. However, a suicidal action performed upon the request of the person willing to die solely by someone else will remain illegal; this also applies if the person willing to commit suicide is physically unable to participate in her or his killing. In several European countries euthanasia and/or assisted suicide has already been legalized and in some countries, Switzerland for example, assisted suicide is a legal option even for patients without suffering from a life-limiting disease, unbearable suffering and insufficient treatment options are the only criteria. In this case report the clinical case of an Austrian patient will be presented, suffering from a personality disorder, who planed an assisted suicide in Switzerland. Ethic and legal backgrounds are discussed.The possibility of assisted suicide bears the danger that people suffering from psychiatric disorders, especially current major depressive episode, could refuse treatment options and choose suicide trough a commercial provider of assisted suicide.In particular it must be considered that currently severely depressed people usually suffer from limited insight and judgement as well as from limited freedom of choice.Aktive Sterbehilfe ist aktuell in Österreich noch gesetzlich verboten. Aufgrund einer Entscheidung des Verfassungsgerichtshofs wäre assistierter Suizid ab dem Jahr 2022 gänzlich legal. Eine gesetzliche Regelung, die Grenzen zwischen legalen Formen einer Assistenz sowie deren Voraussetzungen und weiterhin unerlaubten Assistenzleistungen zieht, ist derzeit noch nicht in Sicht. Ein Suizid, der auf Verlangen des Suizidenten von fremder Hand herbeigeführt wird, bleibt jedenfalls weiterhin strafbar; dies auch dann, wenn der Suizident physisch nicht mehr in der Lage ist, bei seiner Tötung mitzuwirken. In mehreren europäischen Ländern wurde aktive Sterbehilfe bereits legalisiert und in manchen Ländern, wie zum Beispiel der Schweiz, kann assistierter Suizid auch ohne lebenszeitlimitierende Grunderkrankung, bei unerträglichem Leid und insuffizient vorhandenen weitere Behandlungsmöglichkeiten in Anspruch genommen werden. In diesem Fallbericht wird die Kasuistik einer Patientin geschildert welche, als Grunderkrankung an einer Persönlichkeitsstörung leidend, einen assistierten Suizid in der Schweiz geplant hatte. Es werden die ethischen und juristischen Hintergründe dieses Fallberichts diskutiert.Das zur Verfügung stellen assistierter Suizidmöglichkeiten birgt die große Gefahr, dass Menschen mit psychischer Erkrankung, insbesondere bei schweren depressiven Episoden, Behandlungsangebote ablehnen und anstelle Suizid durch einen professionellen Sterbehilfeanbieter wählen könnten. Insbesondere gewarnt werden muss vor der Tatsache, dass Menschen in aktuell schwer depressivem Zustandsbild aufgrund dessen zumeist unter eingeschränkter Entscheidungsfähigkeit leiden und nur bedingt über die Möglichkeit der freien Willensentscheidung verfügen.

Objectives: Diabetic patients are often diagnosed with several comorbidities. The aim of the present study was to investigate the relationship between different combinations of risk factors and complications in diabetic patients. Research design and methods: We used a longitudinal, population-wide dataset of patients with hospital diagnoses and identified all patients (n = 195,575) receiving a diagnosis of diabetes in the observation period from 2003–2014. We defined nine ICD-10-codes as risk factors and 16 ICD-10 codes as complications. Using a computational algorithm, cohort patients were assigned to clusters based on the risk factors they were diagnosed with. The clusters were defined so that the patients assigned to them developed similar complications. Complication risk was quantified in terms of relative risk (RR) compared with healthy control patients. Results: We identified five clusters associated with an increased risk of complications. A combined diagnosis of arterial hypertension (aHTN) and dyslipidemia was shared by all clusters and expressed a baseline of increased risk. Additional diagnosis of (1) smoking, (2) depression, (3) liver disease, or (4) obesity made up the other four clusters and further increased the risk of complications. Cluster 9 (aHTN, dyslipidemia and depression) represented diabetic patients at high risk of angina pectoris “AP” (RR: 7.35, CI: 6.74–8.01), kidney disease (RR: 3.18, CI: 3.04–3.32), polyneuropathy (RR: 4.80, CI: 4.23–5.45), and stroke (RR: 4.32, CI: 3.95–4.71), whereas cluster 10 (aHTN, dyslipidemia and smoking) identified patients with the highest risk of AP (RR: 10.10, CI: 9.28–10.98), atherosclerosis (RR: 4.07, CI: 3.84–4.31), and loss of extremities (RR: 4.21, CI: 1.5–11.84) compared to the controls. Conclusions: A comorbidity of aHTN and dyslipidemia was shown to be associated with diabetic complications across all risk-clusters. This effect was amplified by a combination with either depression, smoking, obesity, or non-specific liver disease.

Background Accumulating evidence suggests beneficial effects of media stories featuring individuals mastering their suicidal crises, but effects have not been assessed for psychiatric patients. Methods We randomized n = 172 adult psychiatric patients (n = 172, 97.1% inpatients) to read an educative article featuring a person mastering a suicidal crisis (n = 92) or an unrelated article (n = 80) in a single-blind randomized controlled trial. Questionnaire data were collected before (T1) and after exposure (T2) as well as 1 week later (study end-point, T3). The primary outcome was suicidal ideation as assessed with the Reasons for Living Inventory; secondary outcomes were help-seeking intentions, mood, hopelessness, and stigmatization. Differences between patients with affective versus other diagnoses were explored based on interaction tests. Results We found that patients with affective disorders (n = 99) experienced a small-sized reduction of suicidal ideation at 1-week follow up (mean difference to control group [MD] at T3 = −0.17 [95% CI −0.33, −0.03], d = −0.15), whereas patients with nonaffective diagnoses (n = 73) experienced a small-sized increase (T2: MD = 0.24 [95% CI 0.06, 0.42], d = 0.19). Intervention group participants further experienced a nonsustained increase of help-seeking intentions (T2: MD = 0.53 [95% CI 0.11, 0.95], d = 0.19) and a nonsustained deterioration of mood (T2: MD = −0.14 [95% CI −0.27, −0.02], d = −0.17). Conclusions This study suggests that patients with affective disorders appear to benefit from media materials featuring mastery of suicidal crises. More research is needed to better understand which patient groups are at possible risk of unintended effects.

Treatment-resistant depression (TRD) occurs in ~30% of patients with major depressive disorder (MDD) but the genetics of TRD was previously poorly investigated. Whole exome sequencing and genome-wide genotyping were available in 1209 MDD patients after quality control. Antidepressant response was compared to non-response to one treatment and non-response to two or more treatments (TRD). Differences in the risk of carrying damaging variants were tested. A score expressing the burden of variants in genes and pathways was calculated weighting each variant for its functional (Eigen) score and frequency. Gene-based and pathway-based scores were used to develop predictive models of TRD and non-response using gradient boosting in 70% of the sample (training) which were tested in the remaining 30% (testing), evaluating also the addition of clinical predictors. Independent replication was tested in STAR*D and GENDEP using exome array-based data. TRD and non-responders did not show higher risk to carry damaging variants compared to responders. Genes/pathways associated with TRD included those modulating cell survival and proliferation, neurodegeneration, and immune response. Genetic models showed significant prediction of TRD vs. response and they were improved by the addition of clinical predictors, but they were not significantly better than clinical predictors alone. Replication results were driven by clinical factors, except for a model developed in subjects treated with serotonergic antidepressants, which showed a clear improvement in prediction at the extremes of the genetic score distribution in STAR*D. These results suggested relevant biological mechanisms implicated in TRD and a new methodological approach to the prediction of TRD., SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives: Psychological stress affects central as well as peripheral metabolism and hormone trafficking via the hypothalamic-pituitary-adrenal axis. Stress thereby plays a decisive role in the etiology and progression of overweight and obesity, leading to several chronic diseases, such as diabetes, and mental health disorders. The interplay of biological and psychometric correlates of stress, anthropometric, immunological, and metabolic parameters and psychosocial factors such as gender roles, however, remains poorly understood. Methods: In this exploratory study, 43 healthy women were assessed for glucose metabolism by an oral glucose tolerance test and computation of functional parameters for insulin secretion, sensitivity, and resistance. Further, the fatty liver index (FLI) and anthropometric parameters body mass index (BMI), waist-to-hip ratio, body fat, and lean mass were assessed. Psychological stress assessment included the “Brief Symptom Inventory” (BSI), the “Burnout Dimensions Inventory” (BODI), and Perceived Stress Scale (PSS). Biological stress response was evaluated with heart rate variability and cortisol levels. Finally, gender role self-identification was assessed with the “Bem Sex-Role Inventory” (BSRI). Generalized linear models were computed for exploratory association with psychometric outcome. Uncorrected p values are reported. Results: Burnout and PSS scores were associated with insulin secretion, sputum cortisol, thyroid-stimulating hormone, anthropometric measures, and gender role. BSI ratings for psychiatric symptom dimensions were associated with insulin resistance, sex hormones, anthropometric measures, and gender role. Female self-identification was associated with higher BMI as well as body fat and a higher FLI. Conclusions: Considering the increased risk of unfavorable metabolic, cardiovascular, and also mental health outcome in obese women, a higher BMI in women with predominant female gender self-identification may be relevant for clinical risk assessment. The broad range of interacting biological, psychological, and gender-related parameters calls for an integrative management of both mental and endocrinological health. However, the exploratory nature of the study requires replication in larger samples before definite conclusion can be drawn.

There is still a debate, if melancholic symptoms can be seen rather as a more severe subtype of major depressive disorder (MDD) or as a separate diagnostic entity. The present European multicenter study comprising altogether 1410 MDD in- and outpatients sought to investigate the influence of the presence of melancholic features in MDD patients. Analyses of covariance, chi-squared tests, and binary logistic regression analyses were accomplished to determine differences in socio-demographic and clinical variables between MDD patients with and without melancholia. We found a prevalence rate of 60.71% for melancholic features in MDD. Compared to non-melancholic MDD patients, they were characterized by a significantly higher likelihood for higher weight, unemployment, psychotic features, suicide risk, inpatient treatment, severe depressive symptoms, receiving add-on medication strategies in general, and adjunctive treatment with antidepressants, antipsychotics, benzodiazepine (BZD)/BZD-like drugs, low-potency antipsychotics, and pregabalin in particular. With regard to the antidepressant pharmacotherapy, we found a less frequent prescription of selective serotonin reuptake inhibitors (SSRIs) in melancholic MDD. No significant between-group differences were found for treatment response, non-response, and resistance. In summary, we explored primarily variables to be associated with melancholia which can be regarded as parameters for the presence of severe/difficult-to treat MDD conditions. Even if there is no evidence to realize any specific treatment strategy in melancholic MDD patients, their prescribed medication strategies were different from those for patients without melancholia.

Background Selective serotonin reuptake inhibitors (SSRIs) are predominantly prescribed for people suffering from major depressive disorder. These antidepressants exert their effects by blocking the serotonin transporter (SERT), leading to increased levels of serotonin in the synaptic cleft and subsequently to an attenuation of depressive symptoms and elevation in mood. Although long-term studies investigating white matter (WM) alterations after exposure to antidepressant treatment exist, results on the acute effects on the brain’s WM microstructure are lacking. Methods In this interventional longitudinal study, 81 participants were included (33 patients and 48 healthy controls). All participants underwent diffusion weighted imaging on 2 separate days, receiving either citalopram or placebo using a randomized, double-blind, cross-over design. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated within the FMRIB software library and analyzed using tract-based spatial statistics. Results The repeated-measures ANOVA model revealed significant decreases after SSRI administration in mean diffusivity, axial diffusivity, and radial diffusivity regardless of the group (P Conclusions Our investigation provides the first evidence, to our knowledge, that fast WM microstructure adaptations within 1 hour after i.v. SSRI administration precede elevations in mood due to SSRI treatment. These results add a new facet to the complex mode of action of antidepressant therapy. This study was registered at clinicaltrials.gov with the identifier NCT02711215.

This cross-sectional European multicenter study with retrospective assessment of treatment response sought to determine variables associated with the administration of augmentation strategies with second-generation antipsychotics (SGAs) and lithium in the pharmacotherapy of major depressive disorder (MDD). In 349 DSM-IV-TR MDD patients, differences in socio-demographic, clinical, treatment, and pharmacological features between participants receiving add-on treatment of their antidepressants with either SGAs (n = 318) or lithium (n = 31) were investigated using analyses of covariance, chi-squared tests, and binary logistic regression analyses. As only significant between-group difference, we found SGA augmentation (compared with lithium augmentation) to be associated with high depressive symptom severity expressed by a higher mean Montgomery and Åsberg Depression Rating (MADRS) total score (27.19 ± 11.35 vs 18.87 ± 12.88, F = 14.82, p = .0001) and a higher mean 21-item Hamilton Rating Scale for Depression (HAM-D) total score (21.27 ± 9.30 vs 13.74 ± 9.11, F = 18.60, p = .0001). No significant differences for socio-demographic features, psychotic symptoms, suicidality, psychiatric and somatic comorbidities, antidepressant pharmacotherapy, and other add-on medications could be seen. Even if there was no significant superiority of one augmentation strategy with regard to treatment response pattern, a trend whereupon adjunctive SGAs were more likely dispensed in treatment-resistant and difficult-to-treat MDD conditions could be observed. In terms of the prescription pattern, we could demonstrate that lithium is less frequently used than SGAs in the clinical routine care which may reflect the need of continuous plasma level determinations and the anticipation of adverse effects.

Objectives: Clinical variables were investigated in the ‘treatment resistant depression (TRD)- III’ sample to replicate earlier findings by the European research consortium ‘Group for the Study of Resistant Depression’ (GSRD) and enable cross-sample prediction of treatment outcome in TRD. Experimental procedures: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. Results: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD-I. Conclusion: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD-III enabled robust prediction of treatment outcome in TRD-I., SCOPUS: ar.j, info:eu-repo/semantics/published

Increased cerebral monoamine oxidase A (MAO-A) levels have been shown in non-seasonal depression using positron emission tomography (PET). Seasonal affective disorder (SAD) is a sub-form of major depressive disorder and is typically treated with bright light therapy (BLT). The serotonergic system is affected by season and light. Hence, this study aims to assess the relevance of brain MAO-A levels to the pathophysiology and treatment of SAD. Changes to cerebral MAO-A distribution (1) in SAD in comparison to healthy controls (HC), (2) after treatment with BLT and (3) between the seasons, were investigated in 24 patients with SAD and 27 HC using [11C]harmine PET. PET scans were performed in fall/winter before and after 3 weeks of placebo-controlled BLT, as well as in spring/summer. Cerebral MAO-A distribution volume (VT, an index of MAO-A density) did not differ between patients and HC at any of the three time-points. However, MAO-A VT decreased from fall/winter to spring/summer in the HC group (F 1, 187.84 = 4.79, p

Background: This European multicenter study aimed to elucidate suicidality in major depressive disorder. Previous surveys suggest a prevalence of suicidality in major depressive disorder of ≥50%, but little is known about the association of different degrees of suicidality with socio-demographic, psychosocial, and clinical characteristics. Methods: We stratified 1410 major depressive disorder patients into 3 categories of suicidality based on the Hamilton Rating Scale for Depression item 3 (suicidality) ratings (0 = no suicidality; 1–2 = mild/moderate suicidality; 3–4 = severe suicidality). Chi-squared tests, analyses of covariance, and Spearman correlation analyses were applied for the data analyses. Results: The prevalence rate of suicidality in major depressive disorder amounted to 46.67% (Hamilton Rating Scale for Depression item 3 score ≥1). 53.33% were allocated into the no, 38.44% into the mild/moderate, and 8.23% into the severe suicidality patient group. Due to the stratification of our major depressive disorder patient sample according to different levels of suicidality, we identified some socio-demographic, psychosocial, and clinical variables differentiating from the patient group without suicidality already in presence of mild/moderate suicidality (depressive symptom severity, treatment resistance, psychotic features, add-on medications in general), whereas others separated only when severe suicidality was manifest (inpatient treatment, augmentation with antipsychotics and benzodiazepines, melancholic features, somatic comorbidities). Conclusions: As even mild/moderate suicidality is associated with a failure of achieving treatment response, adequate recognition of this condition should be ensured in the clinical practice., SCOPUS: ar.j, info:eu-repo/semantics/published

Obesity is highly prevalent, causing substantial cardiovascular and mental health morbidity. Women show increased risk for mental health disorders, that is multiplied in obesity and related to cellular and psychological stress that can be targeted by non-pharmacological interventions. A total of 43 women underwent two weeks of caloric restriction, half of which also received 7 h of individualized clinical psychological intervention including psychoeducation, mindfulness, and heart-rate-variability biofeedback. Effects on body mass index (BMI), fatty liver index (FLI), bioimpedance measures, serum parameters, perceived stress (PSS), burn-out susceptibility (burn out diagnostic inventory) and dimensional psychiatric symptom load (brief symptom inventory, BSI) were analyzed with linear mixed effects models. Caloric restriction led to a reduction in BMI, body fat and FLI, decreased serum concentrations of leptin, PSS score, BSI dimensions and global severity index (all p ≤ 0.0001, withstanding Bonferroni–Holm correction). Benefits of add-on biofeedback were observed for BMI reduction (p = 0.041). Caloric restriction was effective in ameliorating both psychological wellbeing and metabolic functions following a BMI reduction. Biofeedback boosted effects on BMI reduction and the combinative therapy may be protective against common progression to mental health and cardiovascular disorders in overweight women while comparing favorably to pharmacological interventions in terms of side-effects and acceptability.

This international, multicenter, cross-sectional study comprising 1346 adult in- and outpatients with major depressive disorder (MDD) investigated the association between MDD as primary diagnosis and comorbid post-traumatic stress disorder (PTSD). In a cross-sectional data collection process, the presence of comorbid PTSD was determined by the Mini International Neuropsychiatric Interview (MINI) and the patients’ socio-demographic, clinical, psychopharmacological, and response information were obtained. Clinical features between MDD with and without concurrent PTSD were compared using descriptive statistics, analyses of covariance (ANCOVA), and binary logistic regression analyses. 1.49% of the MDD patients suffered from comorbid PTSD. Significantly more MDD + comorbid PTSD patients exhibited atypical features, comorbid anxiety disorders (any comorbid anxiety disorder, panic disorder, agoraphobia, and social phobia), comorbid bulimia nervosa, current suicide risk, and augmentation treatment with low-dose antipsychotic drugs. In the binary logistic regression analyses, the presence of atypical features (odds ratio (OR) = 4.49, 95%CI:1.01–20.12; p≤.05), any comorbid anxiety disorder (OR = 3.89, 95%CI:1.60-9.44; p = .003), comorbid panic disorder (OR = 6.45, 95%CI:2.52–16.51; p = .001), comorbid agoraphobia (OR = 6.51, 95%CI:2.54-16.68; p≤.001), comorbid social phobia (OR = 6.16, 95%CI:1.71–22.17; p≤.001), comorbid bulimia nervosa (OR = 10.39, 95%CI:1.21–88.64; p = .03), current suicide risk (OR = 3.58, 95%CI:1.30–9.91; p = .01), and augmentation with low-potency antipsychotics (OR = 6.66, 95%CI:2.50–17.77; p

Introduction In-vivo quantification of serotonin transporters (SERT) in human brain has been a mainstay of molecular imaging in the field of neuropsychiatric disorders and helped to explore the underpinnings of several medical conditions, therapeutic and environmental influences. The emergence of PET/MR hybrid systems and the heterogeneity of SERT binding call for the development of efficient methods making the investigation of larger or vulnerable populations with limited scanner time and simultaneous changes in molecular and functional measures possible. We propose [11C]DASB bolus plus constant infusion for these applications and validate it against standard analyses of dynamic PET data. Methods [11C]DASB bolus/infusion optimization was performed on data acquired after [11C]DASB bolus in 8 healthy subjects. Subsequently, 16 subjects underwent one scan using [11C]DASB bolus plus constant infusion with Kbol 160–179 min and one scan after [11C]DASB bolus for inter-method reliability analysis. Arterial blood sampling and metabolite analysis were performed for all scans. Distribution volumes (VT) were obtained using Logan plots for bolus scans and ratios between tissue and plasma parent activity for bolus plus infusion scans for different time spans of the scan (VT-70 for 60–70 min after start of tracer infusion, VT-90 for 75–90 min, VT-120 for 100–120 min) in 9 subjects. Omitting blood data, binding potentials (BPND) obtained using multilinear reference tissue modeling (MRTM2) and cerebellar gray matter as reference region were compared in 11 subjects. Results A Kbol of 160 min was observed to be optimal for rapid equilibration in thalamus and striatum. VT-70 showed good intraclass correlation coefficients (ICCs) of 0.61–0.70 for thalamus, striatal regions and olfactory cortex with bias ≤5.1% compared to bolus scans. ICCs increased to 0.72–0.78 for VT-90 and 0.77–0.93 for VT-120 in these regions. BPND-90 had negligible bias ≤2.5%, low variability ≤7.9% and ICCs of 0.74–0.87; BPND-120 had ICCs of 0.73–0.90. Low-binding cortical regions and cerebellar gray matter showed a positive bias of ~8% and ICCs 0.57–0.68 at VT-90. Cortical BPND suffered from high variability and bias, best results were obtained for olfactory cortex and anterior cingulate cortex with ICC=0.74–0.75 for BPND-90. High-density regions amygdala and midbrain had a negative bias of −5.5% and −22.5% at VT-90 with ICC 0.70 and 0.63, respectively. Conclusions We have optimized the equilibrium method with [11C]DASB bolus plus constant infusion and demonstrated good inter-method reliability with accepted standard methods and for SERT quantification using both VT and BPND in a range of different brain regions. With as little as 10–15 min of scanning valid estimates of SERT VT and BPND in thalamus, amygdala, striatal and high-binding cortical regions could be obtained. Blood sampling seems vital for valid quantification of SERT in low-binding cortical regions. These methods allow the investigation of up to three subjects with a single radiosynthesis.

Since many patients with major depressive disorder (MDD) do not satisfactorily respond to initial antidepressant monotherapy, add-on treatment strategies with other psychiatric compounds are often established. The present European multicenter cross-sectional study comprising 1410 MDD in- and outpatients investigated the prescription pattern of benzodiazepines as add-on treatment in the psychopharmacotherapy of MDD. Analyses of variance, chi-squared tests, and logistic regression analyses were conducted to examine differences in socio-demographic, clinical, and treatment characteristics between benzodiazepine users and non-users. The prescription rate for adjunctive benzodiazepine treatment amounted to 31.35%. The most often administered benzodiazepines were lorazepam (11.13%), clonazepam (6.74%), and alprazolam (6.60%). Benzodiazepine users exhibited more severe depressive symptoms expressed by a higher mean Montgomery and Åsberg Depression Rating Scale total score at study entry (26.92 ± 11.07 vs 23.55 ± 11.23, p

BackgroundUp to 60% of patients with major depressive disorder (MDD) do not respond to the first treatment with antidepressants. Response to antidepressants is a polygenic trait, although its underpinning genetics has not been fully clarified. This study aimed to investigate if Polygenic Risk Scores (PRSs) for major psychiatric disorders and neuroticism were associated with non-response or resistance to antidepressants in MDD.MethodsPRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) were computed in 1148 MDD patients recruited by the European Group for the Study of Resistant Depression. Summary statistics from largest meta-analyses of genome-wide association studies were used as base data. Patients were classified as responders, non-responders to one treatment, non-responders to two or more treatments (treatment-resistant depression or TRD). Regression analyses were adjusted for population stratification and recruitment sites.ResultsPRSs did not predict either non-response or TRD after Bonferroni correction. However, SCZ-PRS was nominally associated with non-response (p=0.003). Patients in the highest SCZ-PRS quintile were more likely to be non-responders than those in the lowest quintile (OR=2.23, 95% CI=1.21-4.10, p=0.02). Patients in the lowest SCZ-PRS quintile showed higher response rates when they did not receive augmentation with second-generation antipsychotics (SGAs), while those in the highest SCZ-PRS quintile had a poor response independently from the treatment strategy (p=0.009).ConclusionsA higher genetic liability to SCZ may reduce responsiveness to pharmacological treatment in MDD. From a clinical point of view, our results suggest that MDD patients with low SCZ-PRS do not benefit from augmentation with SGAs.

In the original Article, co-author Professor Andreas Hahn was not included in the author list. This has been corrected in the XML, PDF and HTML versions of this Article.

Objectives: The overview outlines two decades of research from the European Group for the Study of Resistant Depression (GSRD) that fundamentally impacted evidence-based algorithms for diagnostics and psychopharmacotherapy of treatment-resistant depression (TRD). Methods: The GSRD staging model characterising response, non-response and resistance to antidepressant (AD) treatment was applied to 2762 patients in eight European countries. Results: In case of non-response, dose escalation and switching between different AD classes did not show superiority over continuation of original AD treatment. Predictors for TRD were symptom severity, duration of the current major depressive episode (MDE), suicidality, psychotic and melancholic features, comorbid anxiety and personality disorders, add-on treatment, non-response to the first AD, adverse effects, high occupational level, recurrent disease course, previous hospitalisations, positive family history of MDD, early age of onset and novel associations of single nucleoid polymorphisms (SNPs) within the PPP3CC, ST8SIA2, CHL1, GAP43 and ITGB3 genes and gene pathways associated with neuroplasticity, intracellular signalling and chromatin silencing. A prediction model reaching accuracy of above 0.7 highlighted symptom severity, suicidality, comorbid anxiety and lifetime MDEs as the most informative predictors for TRD. Applying machine-learning algorithms, a signature of three SNPs of the BDNF, PPP3CC and HTR2A genes and lacking melancholia predicted treatment response. Conclusions: The GSRD findings offer a unique and balanced perspective on TRD representing foundation for further research elaborating on specific clinical and genetic hypotheses and treatment strategies within appropriate study-designs, especially interaction-based models and randomized controlled trials.