ABSTRACT Sotatercept has recently expanded treatment options for pulmonary arterial hypertension (PAH), but its mental health and quality‐of‐life impact is not well characterized. We assessed psychiatric diagnoses and patient‐reported outcomes in PAH patients treated with sotatercept within the clinical trial program. PAH Patients previously assessed for psychiatric disorders and quality of life were re‐evaluated after ≥ 6 months of sotatercept exposure. A senior psychiatrist performed a Structured Clinical Interview for DSM‐5, and participants completed validated questionnaires assessing anxiety/depression (HADS), metacognitive beliefs (MCQ‐30), quality of life (WHOQOL‐BREF), and PAH‐related symptoms/impacts (PAH‐SYMPACT™), alongside items capturing patient experiences during therapy. Twenty patients (85% female; median age 46 years) were included. Hemodynamics, biomarkers, and 6‐min walk distance improved. The prevalence of at least one current psychiatric disorder remained high and largely unchanged from baseline to follow‐up (50% to 45%). Major depressive disorder remained stable (25%), whereas adjustment disorder newly occurred in 25% of patients. HADS and MCQ‐30 scores did not change. WHOQOL‐BREF global scores increased modestly, but the mental health domain declined substantially (69.6 ± 13.3 to 48.1 ± 15.5, p = 0.001). PAH‐SYMPACT™ indicated low symptom burden at follow‐up. Many patients reported increased optimism and plans to travel or return to work, while some expressed concerns about finances and social security. While sotatercept treatment led to clinical improvements in PAH patients, the prevalence of mental disorders remained high with an increased prevalence in adjustment disorder. These findings support routine mental health assessment and targeted psychosocial support when initiating life‐changing PAH therapies.

Short sleep duration has been linked to an increased risk of cardiometabolic disorders and adverse outcomes, including hospitalization and mortality, in patients with cardiovascular disease (CVD). We assessed the association between sleep duration and cardiovascular parameters in adults with congenital heart disease (ACHD). Data were derived from the ongoing PSYConHEART study on morbidity and mortality factors in ACHD. Sleep duration, sociodemographic variables, and symptoms of anxiety and depression were measured using self-report questionnaires. Epicardial adipose tissue (EAT) was measured by echocardiography, and clinical parameters regarding the underlying heart condition, including serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), were assessed. Patients with a score < 3 on the Hospital Anxiety and Depression Scale depression subscale were included (N = 194). Short sleep duration (≤ 6 h/night) was present in 48 patients (25%). Two-way multivariate analysis with sleep duration (≤ 6 h/night vs. > 6 h/night) and age (≥ 35 vs. < 35 years) as independent variables, corrected for BMI, sex, and NYHA class, revealed a significant effect of sleep duration and age on prognostic CVD markers, namely EAT and NT-proBNP. Sleep duration was associated with CVD markers in older patients only. Sleep duration was associated with CVD markers only in older patients. In particular, EAT, which has prognostic value in cardiac diseases, was negatively impacted by short sleep duration. Sleep problems/disorders are amenable to psychological and pharmacological interventions. Therefore, assessment of sleep problems/disorders may be recommended as part of the multimodal treatment of ACHD patients.

IntroductionThe Attention Training Technique (ATT) is a psychotherapeutic intervention in Metacogntive Therapy (MCT) and aims at reducing maladaptive processes by strengthening attentional flexibility. ATT has demonstrated efficacy in treating depression on a clinical level. Here, we evaluated ATT at the neural level. We examined functional connectivity (FC) of the default mode network (DMN).Method48 individuals diagnosed with Major Depressive Disorder (MDD) and 51 healthy controls (HC) participated in a resting-state (rs) functional magnetic resonance imaging (fMRI) experiment. The participants received either one week of ATT or a sham intervention. Rs-fMRI scans before and after treatment were compared using seed-to-voxel analysis.ResultsThe 2x2x2 analysis did not reach significance. Nevertheless, a resting-state connectivity effect was found on the basis of a posttest at the second measurement time point in MDD. After one week, MDD patients who had received ATT intervention presented lower functional connectivity between the left posterior cingulate cortex (PCC) and the bilateral middle frontal gyrus (MFG) as well as between the right PCC and the left MFG compared to the MDD patients in the sham group. In HC we observed higher rsFC in spatially close but not the same brain regions under the same experimental condition.ConclusionWe found a first hint of a change at the neural level on the basis of ATT. Whether the changes in rsFC found here indicate an improvement in the flexible shift of attentional focus due to ATT needs to be investigated in further research paradigms. Further experiments have to show whether this change in functional connectivity can be used as a specific outcome measure of ATT treatment.

AIMS:Adults with congenital heart disease (ACHD) constitute an ever-growing patient population characterized by high risks for cardiovascular- and mental disorders. Personality disorders (PDs) are associated with adverse physical and mental health. Studies assessing PD prevalence in ACHD are lacking. METHODS AND RESULTS:Personality disorder point prevalence was assessed in 210 ACHD by Structured Clinical Interview for Axis-II Personality Disorders (SCID-II) and compared to meta-analytical data from the general population (GP). Depression and anxiety were measured by self-report (Hospital Anxiety and Depression Scale, HADS) and clinician rating (Montgomery-Åsberg depression rating scale, MADRS). Childhood maltreatment was assessed with the Childhood Trauma Questionnaire and quality-of-life (QOL) with the World Health Organization QOL Scale. PD prevalence was markedly higher in ACHD compared to GP (28.1 vs. 7.7%). Particularly borderline (4.8 vs. 0.9%) and cluster C (i.e. anxious or fearful; 17.1 vs. 3.0%) PDs were overrepresented. PD diagnosis was associated with a surgery age ≤12 years (χ²(1) = 7.861, ϕ = 0.195, P = 0.005) and higher childhood trauma levels (U = 2583.5, Z = -3.585, P < 0.001). ACHD with PD reported higher anxiety (HADS-A: U = 2116.0, Z = -5.723, P < 0.001) and depression (HADS-D: U = 2254.5, Z = -5.392, P < 0.001; MADRS: U = 2645.0, Z = -4.554, P < 0.001) levels and lower QOL (U = 2538.5, Z = -4.723, P < 0.001). CONCLUSION:Personality disorders, particularly borderline- and cluster C, are significantly more frequent in ACHD compared to GP and associated with depression, anxiety, and decreased QOL. Data from the GP suggest an association with adverse cardiometabolic and mental health. To ensure guideline-based treatment, clinicians should be aware of the increased PD risk in ACHD.

The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 +/- 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 +/- 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus - ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.

Before the turn of the century, pregnancy in women with pulmonary arterial hypertension (PAH) was associated with maternal mortality rates of 30% and neonatal mortality rates of 11%.1Weiss BM Zemp L Seifert B Hess OM. Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996.J Am Coll Cardiol. 1998; 31: 1650-1657Crossref PubMed Scopus (444) Google Scholar In more recent series, despite improved management of PAH, pregnancy-associated maternal mortality remained high, ranging from 11% to 25%.2Luo J Shi H Xu L Su W Li J. Pregnancy outcomes in patients with pulmonary arterial hypertension: a retrospective study.Medicine (Baltimore). 2020; 99: e20285Crossref PubMed Scopus (5) Google Scholar, 3Duarte AG Thomas S Safdar Z et al.Management of pulmonary arterial hypertension during pregnancy: a retrospective, multicenter experience.Chest. 2013; 143: 1330-1336Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 4Jaïs X Olsson KM Barbera JA et al.Pregnancy outcomes in pulmonary arterial hypertension in the modern management era.Eur Respir J. 2012; 40: 881-885Crossref PubMed Scopus (151) Google Scholar, 5Bédard E Dimopoulos K Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension?.Eur Heart J. 2009; 30: 256-265Crossref PubMed Scopus (359) Google Scholar, 6Kiely DG Condliffe R Webster V et al.Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach.BJOG. 2010; 117: 565-574Crossref PubMed Scopus (116) Google Scholar As of today, there is no cure for PAH, and case reports have suggested that pregnancy may accelerate disease progression.7Bostock S Sheares K Cannon J Taboada D Pepke-Zaba J Toshner M. The potential effects of pregnancy in a patient with idiopathic pulmonary arterial hypertension responding to calcium channel blockade.Eur Respir J. 2017; 501701141Crossref PubMed Scopus (3) Google Scholar Hence, current pulmonary hypertension guidelines continue to recommend that all patients with PAH avoid pregnancy.8Galiè N Humbert M Vachiery JL et al.2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46: 903-975Crossref PubMed Scopus (1516) Google Scholar However, with recent therapeutic advances, an increasing number of young women with PAH have well-controlled disease and are able to lead a near-normal life.9Hjalmarsson C Rådegran G Kylhammar D et al.Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension.Eur Respir J. 2018; 511702310Crossref PubMed Scopus (32) Google Scholar This is particularly true for women who are responders to calcium channel blockers but also for women who respond well to other PAH treatments. Despite the known risks of becoming pregnant with PAH, some women are willing to accept these risks and actively plan pregnancy. At our institution, since 2007, we have been offering individualized advice to women with PAH who consider becoming pregnant. As a basic rule, we never encourage patients to become pregnant. However, in patients with well-controlled disease indicated by a low-risk profile and a pulmonary vascular resistance < 500 dyn × s × cm–5 on therapy, we take a neutral position, share our experience together with published data, and indicate that we support any decision made by the patient and their families. In patients with less well-controlled disease, we strongly advise against pregnancy but still signal our full support in case the patient decides to become pregnant. In addition, in 2007, we initiated prospective documentation of pregnancies in patients with PAH and formed a multidisciplinary team consisting of pulmonary hypertension specialists, obstetricians, anesthesiologists, and cardiothoracic surgeons for standardized management of these patients. Our strategy includes planned delivery by cesarean section under peridural or spinal anesthesia during the 38th gestational week with post-partum intensive care monitoring. Extracorporeal membrane oxygenation (ECMO) standby is ascertained in patients considered at high risk of developing post-partum right heart failure. PAH medications are maintained during pregnancy except for endothelin receptor antagonists, which are discontinued when pregnancy is detected and reintroduced after delivery (all patients are discouraged from breastfeeding). A more detailed description of our management of pregnant patients with PAH can be found in the Supplementary Material available online at ww.jhltonline.org. All patients of the present series were regularly followed after pregnancy. Their offspring underwent the legally required regular infant checks. Between August 2020 and October 2020, we reviewed the reports of these checks and performed a standardized developmental questionnaire for infants and adolescents (Child Behavior Checklist 1.5–5 or 6–18R).10Chen WJ Faraone SV Biederman J Tsuang MT. Diagnostic accuracy of the Child Behavior Checklist scales for attention-deficit hyperactivity disorder: a receiver-operating characteristic analysis.J Consult Clin Psychol. 1994; 62: 1017-1025Crossref PubMed Scopus (242) Google Scholar These studies were approved by the local institutional review board, and all patients as well as all children aged ≥6 years provided written informed consent. In this report, we present the outcomes of all women with PAH whom we attended to during pregnancy between January 2007 and November 2019. Follow-up ended in October 2020. As summarized in Figure 1, there were 25 pregnancies in 16 patients. The characteristics of these patients at the time of pregnancy are depicted in Table 1. A total of 5 patients had a total of 5 spontaneous abortions and 3 terminations of pregnancies. This included 1 patient (Number 9 in the tables) who became pregnant during an accelerated phase of PAH progression. On gestational Week 10, she developed hyperemesis and subsequent right heart failure. She required awake ECMO support during which pregnancy was terminated. After 17 days on ECMO, bilateral lung transplantation was performed. She did well for some time after transplantation but died 2.5 years later from chronic lung allograft dysfunction.Table 1Characteristics of Patients at the Onset of Their Respective PregnanciesPt numberAge (years)TypeFC6MWDNT-pro BNP (ng/liter)RAP (mm Hg)mPAP (mm Hg)CI (liter/ min/m2)PVR (dyn)SvO2 (%)PAH medication11staHemodynamics were obtained while on treatment except for measurements marked, which represent hemodynamics at the time of the PAH diagnosis. In these patients, no follow-up hemodynamics were available before they became pregnant.2nd2132IPAHVRT‒224014954219010480382.32.71,5013797574SIL‒ BOSbEndothelin receptor antagonists were discontinued when pregnancy was detected.SIL + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected.229IPAH, VRT+1379793232.436665NIF31staHemodynamics were obtained while on treatment except for measurements marked, which represent hemodynamics at the time of the PAH diagnosis. In these patients, no follow-up hemodynamics were available before they became pregnant.2nd3rd263134IPAH, VRT+32336354747073661532340182.03.67101737181AMLOAMLOAMLO432IPAH, VRT+25891475373.330778NIF51st2nd3rd4th28293031IPAH, VRT+2112520600587129771383313.129173AMLOAMLOAMLOAMLO + TAD632IPAH VRT‒33668479413.142072TAD + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected.7 1staHemodynamics were obtained while on treatment except for measurements marked, which represent hemodynamics at the time of the PAH diagnosis. In these patients, no follow-up hemodynamics were available before they became pregnant. 2nd2530IPAH, VRT+2251452854610855262.52.37833057369NIFNIF8 1st 2nd3439APAH (SLE) VRT‒21492600309499634362.72.94934005769TADTAD + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected.9 1st 2nd2526HPAHVRT‒3352343229814481238573.52.25397636564TAD + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected.TAD + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected. + IV TRE10aHemodynamics were obtained while on treatment except for measurements marked, which represent hemodynamics at the time of the PAH diagnosis. In these patients, no follow-up hemodynamics were available before they became pregnant.28APAH (SLE) VRT‒154216619601.41,59834TADMACbEndothelin receptor antagonists were discontinued when pregnancy was detected.1132IPAH VRT‒1657742313.830377TAD + AMBbEndothelin receptor antagonists were discontinued when pregnancy was detected.12aHemodynamics were obtained while on treatment except for measurements marked, which represent hemodynamics at the time of the PAH diagnosis. In these patients, no follow-up hemodynamics were available before they became pregnant.37IPAH, VRT+27201032563.762179DIL + TAD + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected.1329IPAH VRT‒1624966474.238475TAD + AMBbEndothelin receptor antagonists were discontinued when pregnancy was detected.14aHemodynamics were obtained while on treatment except for measurements marked, which represent hemodynamics at the time of the PAH diagnosis. In these patients, no follow-up hemodynamics were available before they became pregnant.27APAH(CHD) VRT‒2NA784101022.81,82995TAD + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected.15aHemodynamics were obtained while on treatment except for measurements marked, which represent hemodynamics at the time of the PAH diagnosis. In these patients, no follow-up hemodynamics were available before they became pregnant.32APAH VRT‒25861045753.21,056NATAD + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected.1625APAH (CHD) VRT‒33361426484.249782TAD + MACbEndothelin receptor antagonists were discontinued when pregnancy was detected.Abbreviations: 6MWD, 6-minute walking distance; AMB, ambrisentan; AMLO, amlodipine; APAH, associated pulmonary arterial hypertension; BOS, bosentan; CHD, congenital heart disease; CI, cardiac index; DIL, diltiazem; FC, World Health Organization functional class; HPAH, heritable pulmonary arterial hypertension; IPAH, idiopathic pulmonary arterial hypertension; MAC, macitentan; mPAP, mean pulmonary arterial pressure; NIF, nifedipine; NT-proBNP, N-terminal fragment of probrain natriuretic peptide; PAH, pulmonary arterial hypertension; Pt, patient; PVR, pulmonary vascular resistance; RAP, right atrial pressure; SIL, sildenafil; SLE, systemic lupus erythematosus; SvO2, mixed venous oxygen saturation; TAD, tadalafil; TRE, treprostinil; VRT, vasoreactivity test.Data are from the respective last measurement before pregnancy.a Hemodynamics were obtained while on treatment except for measurements marked, which represent hemodynamics at the time of the PAH diagnosis. In these patients, no follow-up hemodynamics were available before they became pregnant.b Endothelin receptor antagonists were discontinued when pregnancy was detected. Open table in a new tab Abbreviations: 6MWD, 6-minute walking distance; AMB, ambrisentan; AMLO, amlodipine; APAH, associated pulmonary arterial hypertension; BOS, bosentan; CHD, congenital heart disease; CI, cardiac index; DIL, diltiazem; FC, World Health Organization functional class; HPAH, heritable pulmonary arterial hypertension; IPAH, idiopathic pulmonary arterial hypertension; MAC, macitentan; mPAP, mean pulmonary arterial pressure; NIF, nifedipine; NT-proBNP, N-terminal fragment of probrain natriuretic peptide; PAH, pulmonary arterial hypertension; Pt, patient; PVR, pulmonary vascular resistance; RAP, right atrial pressure; SIL, sildenafil; SLE, systemic lupus erythematosus; SvO2, mixed venous oxygen saturation; TAD, tadalafil; TRE, treprostinil; VRT, vasoreactivity test. Data are from the respective last measurement before pregnancy. A total of 13 patients had a total of 17 successful pregnancies—1 with twins—and delivered 18 newborns who all were healthy at the time of birth. The clinical courses are shown in Table 2. During pregnancy, all patients remained stable except 1. This patient (Number 1 in the tables) initially had an uneventful course of her pregnancy. However, at gestational Week 36, she developed a febrile respiratory tract infection followed by rapidly progressive right heart failure. She underwent an emergency cesarean section but required ECMO support within a few hours after delivery. No recovery was seen despite maximized medical therapy, including IV treprostinil, and she underwent lung transplantation 31 days after delivery. Both mother and offspring were alive and well at the last follow-up, which was 2 years after transplantation.Table 2Pregnancy Outcome and Clinical Course After PregnancyPt numberPregnancy outcomeFollow-up durationaFollow-up duration from first abortion or first delivery. (years)FC last visit6MWD last visitClinical worseningPAH medication at last visitLuTxStatus (alive/dead)12 pregnancies;(1) TOP at Week 5;(2) C-section11(1) (after Tx)NAYes, right after deliveryNA (after LuTx)yesAlive2C-section, full-term inf;122446noNIFnoAlive33 pregnancies;(1) C-section(2) C-section(3) C-section82457noAMLOnoAlive4C-section111611Yes,12 months after deliveryNIF + SIL + MACnoAlive54 pregnancies; (1) spont. abortion at Week 7(2) C-section(3) spont. abortion at Week 8;(4) C-section92566Yes, 21 months after the 4th pregnancyAMLO + TAD + MACnoAlive6C-section72NAYes, 17 months after pregnancyTAD + MAC + IV TREnoAlive72 pregnancies;(1) C-section(2) C-section63486Yes, 13 months after 2nd pregnancyNIF + TAD + MACnoAlive82 pregnancies;(1) intrauterine fetal death at Week 20(2) spont abortion at Week 862541noTAD + MACnoAlive92 pregnancies;(1) spont abortion at Week 6;(2) TOP at Week 10;13442Yes, right after 2nd abortionTAD + IV TRE + ECMOyesDead (2.5 years after Tx)10C-section61609noTAD + MACnoAlive11C-section41660noTAD + AMBnoAlive12C-section11716Yes, 22 months after deliveryDIL + RIO + MACnoAlive13C-section11604Yes, 9 months after deliveryTAD + AMB + IV TREnoAlive14C-section12545noTAD + MACnoAlive15C-section12NAnoTAD + MACnoAlive16TOP at Week 1512451noTAD + MACnoAliveAbbreviations: 6MWD, 6-minute walking distance; AMB, ambrisentan; AMLO, amlodipine; C-section, cesarean section; DIL, diltiazem; ECMO, extracorporeal membrane oxygenation; FC, World Health Organization functional class; Inf, infusion; LuTx, lung transplantation; MAC, macitentan; NA, not applicable; NIF, nifedipine; PAH, pulmonary arterial hypertension; Pt, patient; RIO, riociguat; SIL, sildenafil; spont, spontaneous; TAD, tadalafil; TOP, termination of pregnancy; TRE, treprostinil; Tx, transplantation.a Follow-up duration from first abortion or first delivery. Open table in a new tab Abbreviations: 6MWD, 6-minute walking distance; AMB, ambrisentan; AMLO, amlodipine; C-section, cesarean section; DIL, diltiazem; ECMO, extracorporeal membrane oxygenation; FC, World Health Organization functional class; Inf, infusion; LuTx, lung transplantation; MAC, macitentan; NA, not applicable; NIF, nifedipine; PAH, pulmonary arterial hypertension; Pt, patient; RIO, riociguat; SIL, sildenafil; spont, spontaneous; TAD, tadalafil; TOP, termination of pregnancy; TRE, treprostinil; Tx, transplantation. The post-partum follow-up of the remaining patients ranged from 1 to 12 years (median, 6 years). A total of 6 patients (Numbers 4, 5, 6, 7, 12, and 13 in the tables) showed signs of clinical worsening within 9 to 22 months after delivery. All of these patients responded favorably to treatment escalation and were alive at the end of the observation period. At the last follow-up, all but 1 patient presented in the World Health Organization Functional Class I or II, and 6-minute walking distances ranging from 442 m to 716 m. The offspring of our patients (age ranging from 1 to 12 years) were invariably doing well at the end of the observation period. All of them had normal findings at the legally required infant checks, and all children aged ≥18 months had normal results on the Child Behavior Checklist tests. Taken together, our data reinforce the notion that pregnancy in patients with PAH is a risky and complex undertaking. Still, our data suggest that good midterm outcomes are achievable, especially in patients with well-controlled disease when treated by a multiprofessional team experienced in the management of PAH and pregnancy. In this series, all mothers who delivered a baby were alive at the end of the observation period, and their infants were healthy and normally developed. During follow-up, several patients showed signs of clinical worsening, but the relatively long intervals between delivery and clinical worsening did not suggest that pregnancy was a triggering factor. Although our data are limited by the small number of patients, we believe that today, an individualized risk-based approach with shared decision making may be a more appropriate approach to pregnancy in PAH than the current guideline recommendation to avoid pregnancy in all of these patients. L.W. has received fees for lectures from Servier, outside the present work. M.M.H. has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, and Pfizer, all outside the present work. K.M.O. has received fees for lectures and/or consultations from Actelion, Bayer, United Therapeutics, GlaxoSmithKline, and Pfizer, all outside the present work. The remaining authors have no conflicts of interest to disclose. 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Deep brain stimulation (DBS) of the bed nucleus of the stria terminalis/anterior limb of the internal capsule (BNST/ALIC) is successfully used for treatment of patients with obsessive-compulsive disorder (OCD). Clinical and experimental studies have suggested that enhanced network synchronization in the theta band is correlated with severity of symptoms. The mechanisms of action of DBS remain unclear in OCD. We here investigate the effect of acute stimulation of the BNCT/ALIC on oscillatory neuronal activity in patients with OCD implanted with DBS electrodes. We recorded the oscillatory activity of local field potentials (LFPs) from DBS electrodes (contact + 0/− 3; bipolar configuration; both hemispheres) from the BNST/ALIC parallel with frontal cortical electroencephalogram (EEG) one day after DBS surgery in four patients with OCD. BNST/ALIC and frontal EEG oscillatory activities were analysed before stimulation as baseline, and after three periods of stimulation with different voltage amplitudes (1 V, 2 V and 3.5 V) at 130 Hz. Overall, acute high frequency DBS reduced oscillatory theta band (4-8 Hz; p < 0.01) but increased other frequency bands in BNST/ALIC and the frontal cortex (p < 0.01). We show that stimulation of the BNST/ALIC in OCD modulates oscillatory activity in brain regions that are involved in the pathomechanisms of OCD. Our findings confirm and extend the findings that enhanced theta oscillatory activity in neuronal networks may be a biomarker for OCD.

Ärzte sind trotz ihres Wissensvorsprungs gegenüber der Bevölkerung über die Risiken und Behandlungsmöglichkeiten von Substanzkonsumstörungen nicht vor diesen gefeit. Mittlerweile belegt eine Reihe von Studien, dass Ärzte aufgrund berufsbedingter psychischer und physischer Belastungen ein erhöhtes Risiko für Burn-out, Depression und Abhängigkeitserkrankungen aufweisen, hierbei vor allem Missbrauch und Abhängigkeit von Alkohol und Medikamenten. Darüber hinaus bedingt der relativ unkomplizierte Zugang zu psychoaktiv wirksamen Medikamenten, vor allem Hypnotika, Analgetika und Benzodiazepinen, einen höheren Anteil an suchtgefährdeten und abhängigen Ärzten im Vergleich zur Allgemeinbevölkerung. Dabei ist die Prognose gut. Nach Zahlen der Ärztekammern kann drei Viertel der erstmalig Betroffenen unter Erhalt der Approbation und des Arbeitsplatzes geholfen werden.

Objective The purpose of this study was the diagnostic evaluation of the hospital anxiety and depression scale total score, its depression subscale and the Beck depression inventory II in adults with congenital heart disease. Methods This cross-sectional study evaluated 206 patients with congenital heart disease (mean age 35.3 ± 11.7 years; 58.3% men). Major depressive disorder was diagnosed by a structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders IV and disease severity with the Montgomery–Åsberg depression rating scale. Receiver operating characteristics provided assessment of diagnostic accuracy. Youden’s J statistic identified optimal cut-off points. Results Fifty-three participants (25.7%) presented with major depressive disorder. Of these, 28 (52.8%) had mild and 25 (47.2%) had moderate to severe symptoms. In the total cohort, the optimal cut-off of values was >11 in the Beck depression inventory II, >11 in the hospital anxiety and depression scale and >5 in the depression subscale. Optimal cut-off points for moderate to severe major depressive disorder were similar. The cut-offs for mild major depressive disorder were lower (Beck depression inventory II >4; hospital anxiety and depression scale >8; >2 in its depression subscale). In the total cohort the calculated area under the curve varied between 0.906 (hospital anxiety and depression scale) and 0.93 (Beck depression inventory II). Detection of moderate to severe major depressive disorder (area under the curve 0.965–0.98) was excellent; detection of mild major depressive disorder (area under the curve 0.851–0.885) was limited. Patients with major depressive disorder had a significantly lower quality of life, even when they had mild symptoms. Conclusion All scales were excellent for detecting moderate to severe major depressive disorder. Classification of mild major depressive disorder, representing 50% of cases, was limited. Therapy necessitating loss of quality of life is already present in major depressive disorder with mild symptoms. Established cut-off points may still be too high to identify patients with major depressive disorder requiring therapy. External validation is needed to confirm our data.

Ärzte sind trotz ihres Wissensvorsprungs gegenüber der Bevölkerung über die Risiken und Behandlungsmöglichkeiten von Substanzkonsumstörungen nicht vor diesen gefeit. Mittlerweile belegt eine Reihe von Studien, dass Ärzte aufgrund berufsbedingter psychischer und physischer Belastungen ein erhöhtes Risiko für Burn-out, Depression und Abhängigkeitserkrankungen aufweisen, hierbei vor allem Missbrauch und Abhängigkeit von Alkohol und Medikamenten. Darüber hinaus bedingt der relativ unkomplizierte Zugang zu psychoaktiv wirksamen Medikamenten, vor allem Hypnotika, Analgetika und Benzodiazepinen, einen höheren Anteil an suchtgefährdeten und abhängigen Ärzten im Vergleich zur Allgemeinbevölkerung. Dabei ist die Prognose gut. Nach Zahlen der Ärztekammern kann drei Viertel der erstmalig Betroffenen unter Erhalt der Approbation und des Arbeitsplatzes geholfen werden.

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

Objective Major depressive disorder (MDD) has a negative impact on individuals ability to work, and is often associated with long phases of sick leave. Consequently, interventions facilitating return to work in patients with MDD gained increased attention during last decades. We here report results of a feasibility study where a “return-to-work” (RTW) module published by Lagerveld and colleagues in the Netherlands was integrated in cognitive behavioral therapy in depressed patients with long-term sick leaves in Germany. Our study aimed to answer the following questions: Is RTW accepted by patients and therapists? Do RTW interventions lead to return-to-work? Do depressive symptoms improve? Methods Twenty patients with MDD (15 female; mean age, 45 ± 9 years) were included. Patients received cognitive-behavioral therapy with an integrated, standardized return-to-work module (W-CBT). Psychometric measurements included Beck Depression Inventory (BDI-2) and work ability index (WAI). Further, time until return-to-work was measured, and acceptability of W-CBT was assessed using visual analog scales and open questions. Results Mean sick leave days in depressed patients were 127 ± 97, and 75% of patients were sick leave for more than 6 weeks. After treatment, 11/20 patients had returned to their former occupation (55%), 5/20 were in occupational re-deployment or started a new job (25%), and 3/20 patients were still on sick leave (2/20; 10%) or received a pension (1/20; 5%). One patient dropped out. BDI-2 sum score improved from 23 ± 8 to 8 ± 5 (p < 0.001), and WAI improved from 28 ± 6 to 39 ± 7 (p < 0.001). Acceptability of W-CBT in patients and therapists was high. Conclusion We here demonstrate feasibility and acceptability of an RTW module integrated in standard cognitive behavioral therapy. W-CBT leads to improvement of work ability, paralleled by improvement of depressive symptoms. Despite the limitations of this uncontrolled study, the results propose that W-CBT may be feasible in the treatment of depressed patients with long sick leaves and justify a controlled trial evaluating the efficacy of W-CBT.

Adjustment disorders (ADs) belong to the worldwide most diagnosed mental disorders and are particularly frequent in patients with an underlying physical illness. Pulmonary arterial hypertension (PAH) is a severe and disabling disease, which significantly impacts on quality of life and has high mortality rates. The authors here present the case of a young female who developed a severe adjustment disorder with both anxious and depressive symptoms after a diagnosis of PAH requiring intensive care treatment due to right heart failure. Psychosocial functioning was severely impaired, and physical health reduced. Following hemodynamic stabilization and the establishment of PAH treatment, the patient was admitted to the Department of Psychiatry, Social Psychiatry and Psychotherapy and received metacognitive therapy (MCT). AD with mixed anxiety and depressed mood was diagnosed according to DSM-V criteria. At the start of treatment, she reported significant mental distress, indicated by a total sum score of the Hospital Anxiety and Depression Scale (HADS) of 20 points. The 6-min walking distance was only 358 m before the patient was exhausted. She then was treated with MCT without further psychopharmacological drugs. After only four MCT sessions, she fully remitted from AD which was accompanied by an 11-point reduction in the HADS (to 9 points). MCT specific scores also improved (MCQ-30 sum score decreased from 77 to 35). Notably, physical capacity improved as well, documented by an improved walking distance (439 m; +22%). This is the first case of a patient with AD in the context of PAH treated with MCT. The case report suggests that MCT is a possible psychotherapeutic treatment option for AD in the context of a potentially life-threatening disease. The study design does not permit an attribution of outcome to MCT but it suggests MCT is a potentially viable and acceptable treatment option.

AbstractAimsPeripartum cardiomyopathy (PPCM) is a heart disease affecting women during the last month of pregnancy or in the first months after delivery. The impact of the disease on mental health is largely unknown.Methods and resultsMajor mental disorders were assessed by a structured clinical interview in 40 patients with a confirmed PPCM diagnosis, and the data were compared with published prevalence in postpartum women. Circulating biomarkers associated with mental health, such as kynurenine, serotonin, and microRNA (miR)‐30e, were evaluated in PPCM and compared with matched healthy pregnancy‐matched postpartum controls (PP‐Ctrl). Major mental disorders were diagnosed in 65% (26/40) of the PPCM cohort. The prevalence for major depressive disorders was 4‐fold, for post‐traumatic stress disorder 14‐fold, and for panic disorder 6‐fold higher in PPCM patients compared with postpartum women without a PPCM diagnosis. Compared with PP‐Ctrl, PPCM patients displayed elevated levels of serum kynurenine (P < 0.01), reduced levels of serum serotonin (P < 0.05), and elevated levels of plasma miR‐30e (P < 0.05).ConclusionsThe majority of PPCM patients in the present cohort displayed mental disorders with a higher prevalence of major depressive disorders, post‐traumatic stress disorder (PTBS), and panic disorder, compared with postpartum women without a PPCM diagnosis. This higher prevalence was associated with an impaired tryptophan metabolism and elevated levels of the depression‐associated miR‐30e, suggesting a potential predisposition for mental disorders at the time of PPCM diagnosis. Consequently, physicians should be aware of the increased risk for mental disorders in PPCM patients, and psychiatric assessment should be included in the diagnosis and management of PPCM patients.

Psychological risk assessment is a legal obligation for companies and part of occupational safety and employment protection in Germany. However, data from psychological risk assessments in nursing staff are scarce, although this population is at increased risk for secondary traumatic stress by patient experienced trauma. Therefore, our study aimed at examining the frequency of reported secondary trauma events, secondary traumatic stress, and its possible consequences for psychological well-being and work ability in nurses. N = 320 nurses (n = 280 female) were assessed at a University Hospital in Germany as part of the psychological risk assessment. Secondary traumatic events, secondary traumatic stress, and symptoms of depression and anxiety were measured using self-report questionnaires (PHQ-2, GAD-2), and work ability was assessed using a modified version of the questionnaire for workplace analysis (KFZA). Of 320 nurses, 292 (91.2%) experienced secondary trauma, and 74 nurses (25.3%) reported secondary traumatic symptoms. Nurses with secondary traumatic symptoms reported higher depression (p < 0.001) and anxiety scores (p < 0.001) compared to nurses without secondary trauma experience, and to nurses with secondary trauma experience but without secondary traumatic stress (both p < 0.001). Further, nurses with secondary traumatic stress reported significantly reduced work ability, social support and control over work, and increased emotional strain and labor time. Nurses with secondary traumatic stress may be at increased risk of developing major depression and anxiety disorders, and particularly need support in overcoming secondary traumatic experiences. Psychological risk assessment is a useful tool to identify groups at risk, and pave the way to implement strategies to improve mental well-being and prevent work ability in high risk groups.

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

BackgroundAttentional control has been observed to play an important role in affective disorders by impacting information processing, the ability to exert top–down control in response to distracting stimuli, and by affecting emotional regulation. Prior studies demonstrated an association between attentional control and response to psychotherapy, thereby identifying attentional control as an interesting prognostic pre-treatment factor. Improving attentional control and flexibility is a cornerstone in metacognitive therapy (MCT), which is trained by the use of the Attentional Training Technique (ATT). However, as of yet, it remains unclear if pre-treatment attentional control is related to the effect of ATT.MethodsAn aggregated sample of 139 healthy participants [study 1: 85 participants, mean age 23.7 years, previously published (Barth et al., 2019); study 2: 54 participants, mean age 33.7 years, not previously published] performed an attentional performance test battery before and after applying ATT. Before ATT was administered, attentional control was measured using a well-established self-report instrument, i.e., the Attentional Control Scale (ACS; Derryberry and Reed, 2002). ATT was given in 2, 4, or 15 doses and compared to sham ATT. The test battery comprised a selection of established neurocognitive tasks: emotional dot probe, Stroop, 2-back, and dichotic listening.ResultsSham ATT showed no interaction with ACS score on performance outcome in all tests. At four doses of ATT, ACS score was associated with training response, i.e., subjects with high self-reported attentional control before training showed the largest improvements post-training (all P-values <0.05; see Figure 3). At 2 and 15 doses of ATT, the ACS score was unrelated to training response.ConclusionThis is a first attempt in understanding the optimal dosage in which ATT should be administered dependent on the individual characteristics of each subject pre-training. The current data suggest self-reported attentional control pre-training as a marker to determine an optimal individual ATT training profile. Future studies should investigate if other domains of metacognitions also interact with training outcome and evaluate the extent to which this relationship transfers to clinical samples. If successful, assessing attentional control prior to treatment in clinical samples could be of use regarding personalized therapy plans and treatment outcome.

Objective: Congenital heart disease is the most common congenital malformation. In adult congenital heart disease (ACHD), the prevalence of major depressive disorder (MDD) is increased. Beyond its immanent health risks, increased epi- and paracardial adipose tissue has been described in MDD. Epicardial adipose tissue (EAT) is a fat depot surrounding the heart, and it is hypothesized to be associated with coronary artery disease, left-ventricular dysfunction and atrial fibrillation, being frequent problems in ACHD long-term management. We here examined whether EAT is increased in depressed patients with ACHD. Methods: Two-hundred and ten ACHD outpatients (mean age 35.5y, 43% female) were included. MDD was diagnosed according to DSM-IV criteria using expert interviews. EAT was measured using echocardiography. Further assessments comprised NT-proBNP, left and right ventricular end-diastolic diameter, left-ventricular ejection fraction, smoking behavior and physical activity. Results: Of 210 patients, 53 (25.2%) were diagnosed with MDD. EAT was increased in depressed ACHD (F = 5.04; df = 1; p = 0.026). Depressed male patients were less physically active (p < 0.05) and smoked more cigarettes (p < 0.05). EAT was positively predicted by depression severity (p = 0.039), body mass index (p < 0.001), and negatively predicted by physical activity (p = 0.019). Conclusions: The presence of MDD is associated with an increased amount of EAT in ACHD, and is dependent on depression severity. Further, the amount of EAT is at least in part mediated by a more sedentary lifestyle. Given the long-term health risks associated with increased EAT, interventions aiming at increased physical activity, smoking cessation and early identification of comorbid MDD may be recommended in ACHD.

Background: The Attention Training Technique (ATT) as part of Metacognitive Therapy (MCT) has shown to be a promising treatment element for several psychiatric disorders such as depression and anxiety. ATT predicts improvements of the ability to shift attention away from internal and non-relevant stimuli (e.g., ruminative thoughts) toward the relevant stimuli and aims to increase attentional flexibility and control. The current study investigated the impact of the Attention Training Technique on attentional performance. Methods: Eighty-five healthy participants (29 in two doses ATT, 28 in four doses ATT and 28 in the control group; 18-37 years of age) were administered a test battery for attentional performance before and after an intervention of two doses ATT (23 min duration) vs. four doses of ATT (46 min duration) vs. a control condition (non-intervention audio file via headphones. The test battery measured selective attention, inhibition, working memory, and attentional disengagement and comprised the following tasks: dichotic listening, attentional bias, attentional network, stroop, 2-back and a 3-back. Results: After ATT (both two and four doses), reaction time during dichotic listening was significantly faster compared to the control condition. Furthermore, reaction time to neutral stimuli in the attentional bias task was faster after four-doses ATT compared to two doses ATT and the control condition. We found a trend toward a reduced stroop effect for both ATT conditions compared to control group. There were no effects of ATT with regard to the attentional network task, the 2-back or the 3-back task. Conclusion: This first empirical evidence suggests that ATT promotes specific attentional flexibility in healthy participants. Based on the same mechanism, ATT may have beneficial effects on attentional performance in clinical populations and might be a promising tool in both healthy and clinical participants.

Introduction The neurobiological mechanisms underlying the clinical effects of psychotherapy are scarcely understood. In particular, the modifying effects of psychotherapy on neuronal activity are largely unknown. We here present data from an innovative experimental paradigm using the example of a patient with treatment resistant obsessive-compulsive disorder (trOCD) who underwent implantation of bilateral electrodes for deep brain stimulation (DBS). The aim of the paradigm was to examine the short term effect of metacognitive therapy (MCT) on neuronal local field potentials (LFP) before and after 5 MCT sessions. Methods DBS electrodes were implanted bilaterally with stereotactic guidance in the bed nucleus of the stria terminalis/ internal capsule (BNST/IC). The period between implantation of the electrodes and the pacemaker was used for the experimental paradigm. DBS electrodes were externalized via extension cables, yielding the opportunity to record LFP directly from the BNST/IC. The experimental paradigm was designed as follows: (a) baseline recording of LFP from the BNST/IC, (b) application of 5 MCT sessions over 3 days, (c) post-MCT recording from the BNST/IC. The Obsessive-Compulsive Disorder- scale (OCD-S) was used to evaluate OCD symptoms. Results OCD symptoms decreased after MCT. These reductions were accompanied by a decrease of the relative power of theta band activity, while alpha, beta, and gamma band activity was significantly increased after MCT. Further, analysis of BNST/IC LFP and frontal cortex EEG coherence showed that MCT decreased theta frequency band synchronization. Discussion Implantation of DBS electrodes for treating psychiatric disorders offers the opportunity to gather data from neuronal circuits, and to compare effects of therapeutic interventions. Here, we demonstrate direct effects of MCT on neuronal oscillatory behavior, which may give possible cues for the neurobiological changes associated with psychotherapy.