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Objective: Many psychiatric diseases have a strong familial aggregation, but it is unknown whether postpartum depression (PPD) without prior psychiatric history aggregates in families. Methods: Based on Danish national registers, we constructed a cohort with information on 848,544 singleton deliveries (1996–2017). Women with an episode of PPD were defined as having used antidepressant medication and/or had a hospital contact for depression within 6 months after delivery. Those with psychiatric history prior to the delivery were excluded. We estimated relative risk (RR) of PPD, comparing women with female relatives with and without PPD history, respectively. Results: Overall, women with a PPD history in female blood relatives had themselves a higher risk of PPD (RR = 1.64, 95% CI 1.16–2.34). Having the first-degree female relative with PPD history was associated with a more than 2.5 times (RR = 2.65, 95% CI 1.79–3.91) increased risk of PPD. However, having the second/third-degree female relative and/or a female non-blood relative with PPD history did not increase the woman's own risk of PPD (RR = 0.58, 95% CI 0.26–1.28, RR = 1.09, 95% CI 0.83–1.44). Conclusion: Postpartum depression aggregates in families with no other psychiatric history, but the findings do not support a strong genetic trait as a major cause. Other possible mechanisms are shared environment and/or health-seeking behavior in close relationships.

Background: Patients with pre-existing severe mental disorders are significantly less likely to receive guideline-recommended cancer treatment and seems to have a significantly lower rate of cancer survival compared to patients with cancer without mental disorders.Aim: To perform a systematic review on barriers at patient-, provider- and system-levels in cancer trajectories of patients with pre-existing severe mental disorders.Method: A systematic review was performed following the PRISMA guidelines (PROSPERO ID: CRD42022316020).Results: Nine eligible studies were identified. Barriers at patient-level included lack of self-care and ability to recognize physical symptoms and signs. Provider-level barriers included stigma from health care professionals on mental disorders, whereas system-level barriers included fragmented health care and consequences of this.Conclusion: This systematic review found that barriers at patient-, provider- and system-levels exist in cancer trajectories for patients with severe mental disorders, causing disparities in cancer care. Further research is needed to improve cancer trajectories for patients with severe mental disorder. Background: Patients with pre-existing severe mental disorders are significantly less likely to receive guideline-recommended cancer treatment and seems to have a significantly lower rate of cancer survival compared to patients with cancer without mental disorders.Aim: To perform a systematic review on barriers at patient-, provider- and system-levels in cancer trajectories of patients with pre-existing severe mental disorders.Method: A systematic review was performed following the PRISMA guidelines (PROSPERO ID: CRD42022316020).Results: Nine eligible studies were identified. Barriers at patient-level included lack of self-care and ability to recognize physical symptoms and signs. Provider-level barriers included stigma from health care professionals on mental disorders, whereas system-level barriers included fragmented health care and consequences of this.Conclusion: This systematic review found that barriers at patient-, provider- and system-levels exist in cancer trajectories for patients with severe mental disorders, causing disparities in cancer care. Further research is needed to improve cancer trajectories for patients with severe mental disorder.

Background Reporting of barriers and successes associated with the implementation and use of patient-reported outcomes (PROs) is limited as a means to ensure enhanced patient involvement, shared decision-making and improved treatment and care. We set out to evaluate the implementation and use of the PRO-Psychiatry initiative on patient-reported outcome measures in Danish mental health care. We aimed to described four specific areas: the quality of the clinical consultations before and after the implementation of PRO-Psychiatry as perceived by the patients (objective A), the motivation for participating in PRO-Psychiatry as perceived by patients and clinicians (objective B), the implementation process as perceived by patients, clinicians and managers (objective C) and suggestions for improvement (objective D). Methods The PRO-Psychiatry initiative was evaluated through a participatory approach, including patients, clinicians and managers. A repeated cross-sectional interview-based survey explored the quality of the clinical consultation before and after the implementation of PRO-Psychiatry. A three-step semi-structured group interview, inspired by the modified mini-Delphi method, was used to establish consensus on the evaluation of the implementation and use of the initiative. Results The evaluation pointed at PRO-Psychiatry as a meaningful initiative, which motivated patients and supported clinicians. The patients emphasised the importance of PROs, but they also found that PROs were not used enough. Clinically relevant improvements were detected after the implementation of the initiative; more patients felt heard and experienced that clinicians took a greater interest in their problems. The clinicians valued the easily accessible real-time graphical display of the PRO responses in the electronic health record (EHR). Clinicians and managers agreed that clinical PRO practices, patient compliance and use of PROs in treatment and care should be supported during implementation. Conclusion The evaluation was overall positive. Patients and clinicians were willing to participate, found the online reporting easy and valued the direct access to PRO responses in the EHR. An essential feature was the integration of well-defined and functional PRO practices into the existing clinical workflow. Using PROs in the clinical sessions in a way that was palpable to the patient was found to be a significant improvement need. At the individual level, PRO-Psychiatry can use patient outcome information to support dialogue, encourage shared decision-making and promote self-management during recovery. At the aggregated patient level, the PROs can be used for monitoring the patient-perceived quality of care and for research.

Objective:S100B is a glial cell protein with bimodal function. In low concentrations, it exerts neurotrophic effects, but higher levels reflect neuronal distress. Recent research suggests that this molecule may be a biomarker of response to electroconvulsive therapy (ECT). We examined the effect of ECT on serum S100B and its utility as 1) a biomarker of a depressive state and 2) a predictor of ECT response. We also wanted to ensure that ECT does not cause a marked serum S100B elevation, indicating neural distress.Methods:We measured serum S100B in 22 in-patients treated with ECT due to depression. Depression severity was assessed using 17-item Hamilton Rating Scale for Depression (HAMD-17). The data were collected before an ECT series, within 1 week after the series (post-ECT), and at a 6-month follow-up. Changes in serum S100B and clinical outcomes were tested using a linear mixed model. A relationship between serum S100B and the clinical outcomes was examined using Spearman’s and partial correlation.Results:Serum S100B did not change significantly immediately after an ECT series or 6 months later. The post-ECT serum S100B change was not associated with the clinical effect (rho = 0.14, n = 22, p = 0.54). The baseline serum S100B did not predict the clinical effect when controlling for age (r = 0.02, n = 22, df = 19, p = 0.92).Conclusion:The study neither supports serum S100B as a state marker of depression nor a predictor of ECT response. No evidence for ECT-related neural distress was found.

Objective The aim of the study is to examine whether electroconvulsive therapy (ECT) was associated with the subsequent risk of being involved in a road traffic accident. Methods A cohort of all 375,435 patients older than 18 years with their first psychiatric hospital contact between 2003 and 2017 in the Danish National Patient Registry was followed for road traffic accidents until December 2018. Associations between ECT and road traffic accidents were examined using Cox regression analyses with multiple adjustments and using propensity score matching on sociodemographic and clinical variables. Results A total of 8486 patients (0.2%) were treated with ECT. During the median follow-up of 5.9 years, 778 of these patients (12.5%) were involved in a road traffic accident and the unadjusted incidence of road traffic accidents was lower among these patients (incidence rate, 15.5 per 1000 patient-years; 95% confidence interval [CI], 14.5-16.7) compared with patients not treated with ECT (incidence rate, 20.0 per 1000 patient-years; 95% CI, 20.0-20.3). Electroconvulsive therapy was not associated with road traffic accidents in the Cox regression models after adjustment for all covariables (hazard ratio, 1.00; 95% CI, 0.92-1.08) or in the propensity score-matched sample (hazard ratio, 0.91; 95% CI, 0.83-1.08). The HRs did not vary materially with follow-up time or when analyses were stratified on sex, age, or type of hospital contact. Conclusions The analysis of Danish National registry data indicates that ECT is not associated with the risk of being involved in major road traffic accidents.

OBJECTIVE: The objective of this review is to identify and synthesize the best available evidence on how adult patients experience living with depression-related insomnia. In particular, the review will examine the experiences related to pharmacological and non-pharmacological interventions to improve sleep.INTRODUCTION: Approximately 80% to 90% of patients with depression have insomnia, which is associated with substantial personal and social costs. Despite these costs, insomnia is often underdiagnosed and viewed as a symptom that disappears when depression abates. However, research indicates that insomnia and depression are overlapping but distinct disorders. Thus, it is important to treat both disorders simultaneously, as improving sleep may, in turn, ease core symptoms of depression. Optimal care and treatment rely on patients' experiences of insomnia and their attitudes toward treatment options. Therefore, it is important to synthesize evidence of patients' experiences of living with insomnia, and the experiences of pharmacological and non-pharmacological sleep interventions, to understand the consequences of insomnia and to optimize sleep interventions.INCLUSION CRITERIA: This systematic review will synthesize qualitative studies exploring how adults with depression experience living with insomnia and how they experience pharmacological or non-pharmacological sleep interventions. Both inpatient and outpatient populations will be considered.METHODS: Databases to be searched include MEDLINE, Embase, CINAHL, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, SveMed+, Scopus, and Web of Science Core Collection. Google Scholar and ProQuest Dissertations and Theses will be searched for unpublished studies. Studies in English, German, Danish, Swedish, and Norwegian will be included. Databases will be searched from their inception to the present date. All studies will be screened against the inclusion criteria and critically appraised for methodological quality. Findings will be pooled using meta-aggregation, and a ConQual Summary of Findings will be presented.SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021276048.

BackgroundPrevious research has suggested that some women are at increased risk of postpartum depression (PPD) because of an extra sensitivity to fluctuating hormones before and after parturition. This may particularly apply to women with endocrine disease, characterised by a less than optimal capability to self-regulate the hormonal feedback system.AimsTo investigate if women with endocrine disease history are at increased risk of developing PPD.MethodBased on information from Danish national registers, this nationwide cohort study included 888 989 deliveries (1995–2018). Endocrine disease history was defined as thyroid disease, pre-pregnancy diabetes, polycystic ovary syndrome and/or previous gestational diabetes within 10 years before pregnancy start. PPD was defined as use of antidepressants and/or hospital contact for depression within 6 months after childbirth.ResultsAmong 888 989 deliveries, 4.1% had a history of endocrine disease and 0.5% had a PPD episode. Overall, women with an endocrine disease history had a 42% (risk ratio 1.42, 95% CI 1.24–1.62) higher risk of PPD when compared with women with no endocrine disease. However, we also found the reverse association, whereby women with a PPD history had a 50% (hazard ratio 1.5, 95% CI 1.4–1.6) higher risk of endocrine disease when compared with women with no PPD history.ConclusionsWomen with endocrine disease history had a 40% higher risk of PPD compared with women with no endocrine disease. More attention should be given to pregnant women with endocrine disease history to increase awareness of early signs of PPD. The bi-directionality of the association points to a common underlying factor.

Autism spectrum disorder (ASD) in adults is exhibiting an increase in prevalence, and a growing rate of referrals is observed from primary health professionals to specialised units. The heterogeneous clinical presentation and high prevalence of comorbidity seen in ASD challenges the case identification, emphasising the need for screening tools with a high validity and reliability. Previously, satisfactory psychometric properties of the Ritvo Autism Asperger Diagnostic Scale - Revised (RAADS-R) have been demonstrated, and it is a widely used screening tool in Denmark. Nevertheless, a validation of a Danish version of the RAADS-R has not been performed in a Danish population. To evaluate its clinical relevance, we aim to test the psychometric properties of a Danish translation of the RAADS-R (RAADS-R-DK) in an adult population.We aim to test 200 ASD patients, 200 non-ASD psychiatric patients and 200 healthy controls. The results from the RAADS-R will be compared with the clinical diagnoses from interdisciplinary teams at specialised outpatient clinics.The aim of the study is to investigate the validity, reliability and clinical features of the RAADS-R-DK.Mental Health Center Glostrup and Trygfonden.gov NCT05213286.

BackgroundPost-acute symptoms are not uncommon after SARS-CoV-2 infection with pre-Omicron variants. How the Omicron variant and COVID-19 booster vaccination influences the risk of post-acute symptoms is less clear.ObjectivesTo evaluate the effects of the Omicron variant and COVID-19 booster vaccination on post-acute symptoms, four months after infection with SARS-CoV-2.MethodsA nationwide Danish questionnaire study comprising 44,004 individuals aged 15 years or older with outcomes on post-acute symptoms and new-onset general health problems, four months after testing. Risk differences (RDs) were estimated by comparing Omicron -cases to controls, Omicron to Delta -cases, and Omicron vaccinated cases with three to -two doses, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation, and vaccination status.ResultsFour months after testing for SARS-CoV-2 during the Omicron period, the largest RD comparing Omicron cases to controls was observed for memory issues (RD=7.2%, 95% CI: 6.4 to 8.1). Compared to cases from the Delta period, Omicron cases reported reduced risks of post-acute dysosmia (RD=-15.5%, 95% CI: -17.5 to -13.4) and dysgeusia (RD=-11.8%, 95% CI: -13.9 to -9.8). Cases vaccinated with three doses prior to Omicron infection reported reduced risk of 13/26 post-acute symptoms and of 4/5 new-onset general health problems, compared to those vaccinated with two doses.ConclusionsCases infected during the Omicron period experienced substantial post-acute symptoms and new-onset health problems, four months after testing, although milder than Delta cases. Booster vaccination was associated with fewer post-acute symptoms and new-onset health problems, four months after Omicron infection, compared to two doses of COVID-19 vaccine.

Purpose To review how patient-reported outcome (PRO) measures in mental health clinical research complement traditional clinician-rated outcome (CRO) measures. Data sources Medline, Embase, PsycInfo and Scopus. Study selection Latest update of the literature search was conducted in August 2019, using a specified set of search terms to identify controlled and uncontrolled studies (published since 1996) of pharmacological or non-pharmacological interventions in adults (≥18 years) in hospital-based mental health care. Data extraction Two authors extracted data independently using a pre-designed extraction form. Results of data synthesis Among the 2962 publications identified, 257 were assessed by full text reading. A total of 24 studies reported in 26 publications were included in this descriptive review. We identified subjective and objective outcome measures, classified these according to the pharmacopsychometric triangle and compared them qualitatively in terms of incremental information added to the clinical study question. The data reviewed here from primarily depression and schizophrenia intervention studies show that results from PRO measures and CRO measures generally point in the same direction. There was a relative lack of PRO measures on functioning and medication side effects compared with PRO measures on symptom burden and health-related quality of life. Conclusion PROs and CROs supplement each other and at most times support identical study conclusions. Future studies would benefit from a more systematic approach toward use of PROs and a clearer rationale of how to weigh and report the results in comparison with CROs.

OBJECTIVE: To examine the hypothesis that PTSD with delayed expression in some cases occurs without subthreshold PTSD symptoms above background levels bridging the gap between the traumatic exposure(s) and the clinical diagnosis.METHODS: We performed systematic searches of peer-reviewed papers in English referenced in Pubmed, Embase, or PsycINFO and ascertained 34 prospective studies of PTSD symptom trajectories identified by latent class growth statistical modeling. Studies with delayed and low-stable trajectories provided appropriate data for this study. We computed the difference between the delayed trajectory PTSD symptom sumscore and the low-stable PTSD sumscore at the observed points in time after the traumatic event(s).RESULTS: In 29 study populations, the latent class growth analyses displayed delayed trajectories, and in these, we identified 110 data points (% PTSD sumscore difference/months since traumatic exposure). The median PTSD symptom sumscore was 25% higher during the initial 6 months among individuals in the delayed trajectory compared to those in low-stable trajectory. From this level, the difference widened and reached a plateau of 40-50% higher. The variation was large, and the baseline participation rate and loss to follow-up were exceeding 25% in the majority of the studies. Heterogeneity of populations, measures, and analyses precluded formal meta-analysis.CONCLUSION: Delayed PTSD is preceded by PTSD symptoms during the first year in most cases. Still, few individuals may experience an asymptomatic delay. The results underpin the rationale for monitoring PTSD symptoms and may inform forensic assessments in that delayed PTSD without symptoms bridging the traumatic event is rare.

Electroconvulsive therapy (ECT) is a highly effective treatment for depression. Continuation ECT (C-ECT) is indicated for patients suffering from severe, recurrent or treatment-resistant forms of depression who have responded to an index course of ECT. This review aims at giving an updated set of guidelines for the use of C-ECT for patients suffering from depression. The guidelines will describe which patients are likely to benefit from the treatment, what to consider before administering the treatments and potential adverse effects.

BACKGROUND: Difficult-to-treat-depression (DTD) is a clinical challenge. The interventions that are well-established for DTD are not suitable or effective for all the patients. Therefore, more treatment options are highly warranted. We formulated an evidence-based guideline concerning six interventions not well-established for DTD in Denmark.METHODS: Selected review questions were formulated according to the PICO principle with specific definitions of the patient population (P), the intervention (I), the comparison (C), and the outcomes of interest (O), and systematic literature searches were performed stepwise for each review question to identify relevant systematic reviews/meta-analyses, and randomized controlled trials. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the methodological quality of the included studies. Clinical recommendations were formulated based on the evidence, the risk-benefit ratio, and perceived patient preferences.RESULTS: We found sufficient evidence for a weak recommendation of repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioural analysis system of psychotherapy (CBASP). The use of bright light therapy in DTD was not sufficiently supported by the evidence, but should be considered as good clinical practice. The interventions should be considered in addition to ongoing antidepressant treatment. We did not find sufficient evidence to recommend intravenous ketamine/esketamine, rumination-focused psychotherapy, or cognitive remediation to patients with DTD.CONCLUSION: The evidence supported two of the six reviewed interventions, however it was generally weak which emphasizes the need for more good quality studies. This guideline does not cover all treatment options and should be regarded as a supplement to relevant DTD-guidelines.

A significant proportion of patients with depression do not respond to classic antidepressants addressing serotonergic or noradrenergic neurotransmission. Certain clinical features of depression seem to involve dopaminergic neurotransmission. Although medications with specific dopaminergic actions are used in the treatment of depression in other countries (e.g. the United States), these drugs are rarely mentioned in Danish treatment guidelines. This review aims at comprehending current dopaminergic treatment strategies and future directions in this field.

In major depressive disorder (MDD), perfusion changes in cortico-limbic pathways are interpreted as altered neuronal activity, but they could also signify changes in neurovascular coupling due to altered capillary function. To examine capillary function in late-onset MDD, 22 patients and 22 age- and gender-matched controls underwent perfusion MRI. We measured normalized cerebral blood flow (nCBF), cerebral blood volume (nCBV), and relative transit-time heterogeneity (RTH). Resulting brain oxygenation was estimated in terms of oxygen tension and normalized metabolic rate of oxygen (nCMRO2). Patients revealed signs of capillary dysfunction (elevated RTH) in the anterior prefrontal cortex and ventral anterior cingulate cortex bilaterally and in the left insulate cortex compared to controls, bilateral hypometabolism (parallel reductions of nCBV, nCBF, and CMRO2) but preserved capillary function in the subthalamic nucleus and globus pallidus bilaterally, and hyperactivity with preserved capillary function (increased nCBF) in the cerebellum and brainstem. Our data support that perfusion changes in deep nuclei and cerebellum reflect abnormally low and high activity, respectively, in MDD patients, but suggest that microvascular pathology affects neurovascular coupling in ventral circuits. We speculate that microvascular pathology is important for our understanding of etiology of late-onset MDD as well as infererences about resulting brain activity changes.

Psychotic depression is a severe and underdiagnosed psychiatric disorder, which differs from non-psychotic depression biologically, clinically, therapeutically and prognostically. Due to the differences in treatment and the higher risk of suicidal behaviour, the correct diagnosis is crucial. Patients with psychotic depression have an increased risk of a new episode and readmission. Treatment of psychotic depression takes place during hospitalisation and is either ECT or a combination of antidepressant treatment and antipsychotics, which is summarised in this review.

Objective Several studies have found an increase in hippocampal volume following electroconvulsive therapy (ECT), but the effect on cortical thickness has been less investigated. We aimed to examine the effects of ECT on cortical thickness and their associations with clinical outcome. Method Using 3 Tesla MRI scanner, we obtained T1-weighted brain images of 18 severely depressed patients at three time points: before, right after and 6 months after a series of ECT. The thickness of 68 cortical regions was extracted using Free Surfer, and Linear Mixed Model was used to analyze the longitudinal changes. Results We found significant increases in cortical thickness of 26 regions right after a series of ECT, mainly within the frontal, temporal and insular cortex. The thickness returned to the baseline values at 6-month follow-up. We detected no significant decreases in cortical thickness. The increase in the thickness of the right lateral orbitofrontal cortex was associated with a greater antidepressant effect, r = 0.75, P = 0.0005. None of the cortical regions showed any associations with cognitive side effects. Conclusion The increases in cortical thickness induced by ECT are transient. Further multimodal MRI studies should examine the neural correlates of these increases and their relationship with the antidepressant effect.

Søren Valgreen Knudsen,1,2 Jan Brink Valentin,1 Poul Videbech,3 Jan Mainz,1,2,4,5 Søren Paaske Johnsen1 1Danish Center for Clinical Health Services Research (DACS), Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 2Psychiatry, Aalborg University Hospital, Aalborg, Denmark; 3Center for Neuropsychiatric Research, Mental Health Center Glostrup, University of Copenhagen, Glostrup, Denmark; 4Department of Community Mental Health, Haifa University, Haifa, Israel; 5Department of Health Economics, University of Southern Denmark, Odense, DenmarkCorrespondence: Søren Valgreen Knudsen, Email soeren.k@rn.dkPurpose: The objective was to examine potential socioeconomic inequities in guideline recommended quality of care as well as several clinical outcomes among first-time inpatients with major depressive disorder (MDD) in a tax-financed universal health care system.Patients and Methods: A nationwide cohort study was performed based on individual-level record linkage of public registers in Denmark. The study included all adult incident inpatients with MDD at Danish psychiatric hospitals in the period 2011– 2017 (n=10,949). Socioeconomic position was assessed according to the level of education and income. Outcomes included quality of depression care for inpatients as reflected by the fulfillment of guideline recommended quality of care measures as well as clinical outcomes in terms of all-cause mortality, suicidal behavior, readmission for depression and all-cause readmission.Results: Patients with low-level education or low-level income were statistically significantly less likely to receive high quality of in-hospital care, defined as fulfillment of at least 70% of relevant performance measures (adjusted relative risk (RR) 0.92 and 0.87, respectively). In addition, the same patients had a higher all-cause mortality (adjusted RR 1.22 and 1.41, respectively). Patients with low education or middle income were associated with a higher risk of suicidal behavior (adjusted RR 1.28 and 1.19, respectively). While no differences were found in the risk of all-cause readmission, low-level education and income was associated with a lower risk of readmission due to MDD (adjusted RR 0.91 and 0.87, respectively).Conclusion: Inequities in quality of care and clinical outcomes were observed among MDD inpatients in a tax-financed universal health care system, indicating that lack of access to care and insurance is not the only explanation for inequity in health.Keywords: quality of care, depression, mental health, health equity, health equality, major depressive disorder

Objectives: Severe depression is associated with an increased risk of developing dementia, however, whether treatment with electroconvulsive therapy (ECT) modify this risk remains unknown. Methods: In this matched cohort study, 1089 consecutive in-patients with affective disorders, receiving ECT during the period 1982 to 2000, were matched with 3011 in-patients with affective disorders not treated with ECT (non-ECT), and 108,867 individuals randomly selected from the background population. The comparison cohorts were matched on sex, age, and the non-ECT cohort was further matched according to diagnoses and admission period and hospital. Dementia diagnoses were retrieved from the national patient health registry. Analyses were adjusted for disease severity, somatic, and psychiatric comorbidities. Results: The cumulative incidence of dementia was 13.45% (10.75-16.46%) in the ECT cohort after 34 years of follow-up, 10.53% (8.5-12.81%) in the non-ECT cohort, and 8.43% (8.17-8.7%) in the background cohort. Using the ECT cohort as reference and age as the underlying time scale, the adjusted hazard ratio of developing dementia was 0.73 (0.52-1.04) in the non-ECT cohort and 0.61 (0.49-0.76) in the background cohort. The stratified analysis based on age at index (80 years) found no age-related difference in the risk of developing dementia between the ECT cohort and non-ECT cohort. Conclusions: The ECT treatment of affective disorders was not associated with an increased long-term risk of developing dementia compared with in-patients with affective disorders not treated with ECT.

Depression is common in pregnant women and is often not treated. It can have major consequences for both mother and child. It is associated with several complications, including miscarriages, vaginal bleeding and preterm birth. It is important, that healthcare professionals, who have contact with pregnant women, have knowledge about dealing with pregnant women with depression and its symptoms, as a large proportion of these depressions continue post-partum. In this review, we describe the aetiology, assessment, potential complication, antenatal care and treatment of pregnant women with depression.

Antidepressants are widely used. All antidepressants are associated with side effects, and in this review we therefore find it reasonable to reassess the indication for long-term use at least once a year. After remission of a depressive episode treatment should be continued for 6-9 months, and treatment should be continued longer for two years or more in the presence of risk factors for new depressive episodes. Antidepressants should be discontinued slowly and with caution in order to reduce the risk of discontinuation symptoms.

Background Depression affects approx. 4% of the global population and is often accompanied by insomnia. Medications used to treat insomnia can have side effects such as development of tolerance and addiction. The Protac Ball Blanket™ (PBB) is a non-pharmacological supplement to sedatives and hypnotics, but evidence for the efficacy of PBB is needed before the treatment is implemented. The objective of this trial is to test the efficacy of PBB on insomnia caused by depression in a randomized controlled design. Methods This study is a multicentre, randomized crossover trial with planned inclusion of 45 patients. The randomization procedure is permuted-block randomization with varying block sizes. Patients are allocated into either a sequence “AB” or “BA” each lasting 4 weeks (28 nights). Patients randomized to the “AB” sequence receive treatment A (Protac Ball Blanket™) in the first 2 weeks and switch to treatment B (treatment as usual) in the second period, whereas patients who are randomized to the BA sequence receive treatment B in the first period and treatment A in the second period. The participants will serve as their own control in this design. The primary outcome is changes in total sleep time. Secondary outcome measures are changes in sleep onset latency, number of awakenings, wake after sleep onset, and use of sedatives and hypnotics. Furthermore, quality of sleep, insomnia severity status, and self-reported symptoms of depression, anxiety, interpersonal sensitivity, and neurasthenia will be measured. A paired, two-sided t test to compare the means of the differences in the outcomes will be performed. Discussion This clinical trial will assess the effect of PBB on depression-related insomnia. The outcomes are of high interest as the PBB is a potential non-pharmacological supplement to medical treatment of patients with insomnia due to depression. Trial registration ClinicalTrials.gov Identifier: NCT03730974. Registered on 5 November 2018.

Objective:Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has been shown to have a statistically and clinically significant anti-depressant effect. The present pilot study was carried out to investigate if right prefrontal low-frequency rTMS as an add-on to electroconvulsive therapy (ECT) accelerates the anti-depressant effect and reduces cognitive side effects.Methods:In this randomised, controlled, double-blind study, thirty-five patients with major depression were allocated to ECT+placebo or ECT+low-frequency right prefrontal rTMS. The severity of depression was evaluated during the course using the Hamilton scale for depression (the 17-item as well as the 6-item scale) and the major depression inventory (MDI). Furthermore, neuropsychological assessment of cognitive function was carried out.Results:The study revealed no significant difference between the two groups for any of the outcomes, but with a visible trend to lower scores for MDI after treatment in the placebo group. The negative impact of ECT on neurocognitive functions was short-lived, and scores on logical memory were significantly improved compared to baseline 4 weeks after last treatment. The ECT-rTMS group revealed generally less impairment of cognitive functions than the ECT-placebo group.Conclusion:The addition of low-frequency rTMS as an add-on to ECT treatment did not result in an accelerated response. On the contrary, the results suggest that low-frequency rTMS could inhibit the anti-depressant effect of ECT.

OBJECTIVE Patients hesitate to consent to electroconvulsive therapy (ECT) because of the fear of memory impairment. The mechanisms underlying this impairment are unclear, but several observations suggest hippocampal alterations may be involved. We investigated whether ECT-induced change in hippocampal volume correlates with memory impairment. METHODS Using a 3 T MRI scanner, we acquired brain images and assessed cognitive performance in 22 severely depressed patients at three time points: (1) before ECT series, (2) within one week after the series, and (3) at six-month follow-up. The hippocampus was segmented into subregions using FreeSurfer. The dentate gyri (DG) were the primary regions of interest (ROIs) and major hippocampal subregions secondary ROIs. Cognitive performance was assessed using the Screen for Cognitive Impairment in Psychiatry and verbal memory using the Verbal Learning subtest. The linear mixed model and the repeated-measures correlation were used for statistical analyses. RESULTS ECT induced an increase in the right and left DG volume with co-occurring worsening in verbal memory, and these changes were within-patients negatively correlated (right DG, rrm = -0.85, df = 18, p = 0.0000002; left DG, rrm = -0.58, df = 18, p = 0.008). At a six-month follow-up, the volume of both DG decreased with a co-occurring improvement in verbal memory, and these changes were negatively correlated in the right DG (rrm = -0.64, df = 15, p = 0.005). Volume increases in 14 secondary ROIs were also negatively correlated with memory impairment. CONCLUSION ECT-related transient increases in the volume of major hippocampal subregions within-patients are associated with memory impairment. Hippocampal alterations following ECT should be the focus in searching for causes of the cognitive side effects.

Objective: The relationship between gender, age and the quality of mental health care among inpatients with depression is unclear. This study examined gender- and age-related differences in the quality of care as reflected by the fulfilment of process performance measures of care among inpatients with unipolar depression in Denmark. Methods: In a nationwide cohort study, 16,858 patients admitted to psychiatric hospital wards for depression between 2011 and 2016 were identified from the Danish Depression Database. Patients were divided according to age (18–39, 40–65, 66–79 and ≥80 years) and stratified by gender. Quality of care was defined as having fulfilled process performance measures of care, reflecting national clinical guideline recommendations. High overall quality of care was defined as having received ≥80% of the processes. The associations were assessed using binomial regressions. Results: With men in the age group 18–39 years serving as the reference, men and women in the age category ≥80 years were more likely to receive higher quality of care with an adjusted relative risk (aRR) of 1.43 [95% confidence interval (CI) = 0.98; 2.10] and 1.30 (95% CI = 0.90; 1.90), respectively. Likewise, for men and women aged 66–79 years, the aRRs as 1.34 (95% CI = 1.07; 1.67) and 1.47 (95% CI = 1.14; 1.90). For men and women aged 40–65, the aRRs was 1.15 (95% CI = 1.00; 1.33) and 1.07 (95% CI = 0.93; 1.24), respectively. Conclusion: Older patients received higher quality of inpatient care for depression, as reflected by a higher proportion of fulfilled guideline supported process measures. In contrast, we found no gender-related differences.

It is thought that the hippocampal neurogenesis is an important mediator of the antidepressant effect of electroconvulsive therapy (ECT). However, most previous studies failed to demonstrate the relationship between the increase in the hippocampal volume and the antidepressant effect. We reinvestigated this relationship by looking at distinct hippocampal subregions and applying repeated measures correlation. Using a 3 Tesla MRI-scanner, we scanned 22 severely depressed in-patients at three time points: before the ECT series, after the series, and at six-month follow-up. The depression severity was assessed by the 17-item Hamilton Rating Scale for Depression (HAMD-17). The hippocampus was segmented into subregions using Freesurfer software. The dentate gyrus (DG) was the primary region of interest (ROI), due to the role of this region in neurogenesis. The other major hippocampal subregions were the secondary ROIs (n = 20). The general linear mixed model and the repeated measures correlation were used for statistical analyses. Immediately after the ECT series, a significant volume increase was present in the right DG (Cohen's d = 1.7) and the left DG (Cohen's d = 1.5), as well as 15 out of 20 secondary ROIs. The clinical improvement, i.e., the decrease in HAMD-17 score, was correlated to the increase in the right DG volume (rrm = −0.77, df = 20, p

Background.The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression.Methods.A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group.Results.In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1;N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years;N = 33) and a chronic current episode (>2 years;N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4.Conclusions.The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.

ObjectivePrior studies suggest that a dysregulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in the pathophysiology of major depression. We aimed to elucidate changes in cortical GABA content in relation to depression and electroconvulsive therapy (ECT) using magnetic resonance spectroscopy (MRS).MethodsIn total, 11 patients with major depression or depressive episode of bipolar disorder (mean pre-ECT Ham-17 of 26) and 11 healthy subjects were recruited. GABA was quantified using short-TE MRS in prefrontal and occipital cortex. Other neurometabolites such as glutathione (GSH), N-acetylaspartate (NAA) and glutamate (Glu) were secondary outcome measures.ResultsNo significant differences in GABA/Cr levels were observed between patients at baseline and healthy subjects in prefrontal cortex, t(20)=0.089, p=0.93 or occipital cortex t(21)=0.37, p=0.72. All patients improved on Ham-17 (mean post-ECT Ham-17 of 9). No significant difference was found in GABA, Glu, glutamine, choline or GSH between pre- and post-ECT values. However, we observed a significant decrease in NAA levels following ECT t(22)=3.89, p=0.0038, and a significant correlation between the NAA decline and the number of ECT sessions p=0.035.ConclusionsOur study does not support prior studies arguing for GABA as a key factor in the treatment effect of ECT on major depression. The reduction in NAA levels following ECT could be due to neuronal loss or a transient dysfunction in prefrontal cortex. As no long-term follow-up scan was performed, it is unknown whether NAA levels will normalise over time.

OBJECTIVE: The relationship between inpatient volume and the quality of mental health care remains unclear. This study examined the association between inpatient volume in psychiatric hospital wards and quality of mental health care among patients with depression admitted to wards in Denmark.METHODS: In a nationwide, population-based cohort study, 17,971 patients (N=21,120 admissions) admitted to psychiatric hospital wards between 2011 and 2016 were identified from the Danish Depression Database. Inpatient volume was categorized into quartiles according to the individual ward's average caseload volume per year during the study period: low volume (quartile 1, 227 inpatients per year). Quality of mental health care was assessed by receipt of process performance measures reflecting national clinical guidelines for care of depression.RESULTS: Compared with patients admitted to low-volume psychiatric hospital wards, patients admitted to very-high-volume wards were more likely to receive a high overall quality of mental health care (≥80% of the recommended process performance measures) (adjusted relative risk [ARR]=1.78, 95% confidence interval [CI]=1.02-3.09) as well as individual processes of care, including a somatic examination (ARR=1.35, CI=1.03-1.78).CONCLUSIONS: Admission to very-high-volume psychiatric hospital wards was associated with a greater chance of receiving guideline-recommended process performance measures for care of depression.

There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had a significant decrease of depressive symptoms during the first 6 days measured by HAM-D6. At Day 6, 41% of the patients responded to the treatment and 19% fulfilled the criteria of remission. Deterioration by the end of wake therapy sessions was however not uncommon. In the short-term phase, mild degree of treatment resistance was associated with remission and low educational level associated with deterioration. Positive diurnal variation (mood best in the evening) was a predictor of both short-term and long-term response to combined wake and light therapy. Furthermore, patients with evening chronotypes (measured with morningness-eveningness score) were more responsive. Our results suggest that targeting the combined chronotherapeutic intervention at patients with positive diurnal variation and evening types is a viable option.

Objective The main purpose of this review was to synthesise evidence on ECT's effects on brain's structure. Method A systematic literature review of longitudinal studies of depressed patients treated with ECT using magnetic resonance imaging (MRI) and meta-analysis of ECT's effect on hippocampal volume. Results Thirty-two studies with 467 patients and 285 controls were included. The MRI studies did not find any evidence of ECT-related brain damage. All but one of the newer MRI volumetric studies found ECT-induced volume increases in certain brain areas, most consistently in hippocampus. Meta-analysis of effect of ECT on hippocampal volume yielded pooled effect size: g = 0.39 (95% CI = 0.18-0.61) for the right hippocampus and g = 0.31 (95% CI = 0.09-0.53) for the left. The DTI studies point to an ECT-induced increase in the integrity of white matter pathways in the frontal and temporal lobes. The results of correlations between volume increases and treatment efficacy were inconsistent. Conclusion The MRI studies do not support the hypothesis that ECT causes brain damage; on the contrary, the treatment induces volume increases in fronto-limbic areas. Further studies should explore the relationship between these increases and treatment effect and cognitive side effects.

Background: Historically, research investigating neural correlates of mentalizing deficits in schizophrenia has focused on patients who have been ill for several years with lengthy exposure to medication. Little is known about the neural and behavioural presentations of theory-of-mind deficits in schizophrenia, shortly after the first episode of psychosis. \ud \ud Methods: We investigated social cognition in seventeen recently diagnosed first-episode schizophrenia (FES) patients with little or no exposure to antipsychotic medication and 1:1 matched healthy controls. We recorded behavioural and neural responses to the Animated Triangles Task (ATT), which is a non-verbal validated mentalizing task that measures the ascription of intentionality to the movements of objects. \ud \ud Results: FES patients under-interpreted social cues and over-interpreted non-social cues. These effects were influenced by current intelligence (IQ). Control group and FES neural responses replicated earlier findings in healthy adults. However, a region of anterior medial prefrontal cortex (amPFC) of FES patients showed a different response pattern to that of controls. Unlike healthy controls, patients increased activity in this social cognition region while studying ‘random’ movements of shapes, as compared to the study of movements normally interpreted as ‘intentional’. \ud \ud Conclusions: Mentalizing deficits in FES consists of hypo- and hyper-mentalizing. The neural pattern of FES patients is consistent with deficits in the ability to switch off mentalizing processes in potentially social contexts, instead increasing them when intentionality is not forthcoming. Overall, results demonstrate complexities of theory of mind deficits in schizophrenia that should be considered when offering social cognitive training programs.