End-of-life care for cancer patients with pre-existing severe mental disorders-a systematic review.

BACKGROUND: Cancer patients with pre-existing severe mental disorders (SMDs) less frequently receive guideline recommended cancer treatment and have a higher cancer mortality. However, knowledge is needed concerning end-of-life care in this patient group. The aim of this systematic review was to provide an overview of the literature concerning end-of-life care in cancer patients with pre-existing SMD. METHODS: A systematic search was conducted in the following databases: PubMed, Embase and Science Direct and all results were downloaded to Endnote on 1st of September 2023. The review was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023468571). The quality of the studies was assessed according to the Newcastle-Ottawa Scale. RESULTS: Ten studies fulfilling the inclusion criteria were included. There was a recurring pattern indicating a difference between the end-of-life care received by cancer patients with SMD, compared to those without. Cancer patients with pre-existing SMD received more palliative end-of-life care but less high-intensive-end-of-life (HIEOL) care, e.g., less hospitalisations and chemotherapy at the end of life, and died less frequently at hospital. CONCLUSIONS: The study indicates that patients with pre-existing SMD and cancer more often received palliative end-of-life care and less HIEOL care compared to controls. Further research regarding the difference in end-of-life care is lacking, including the consequences of less intense HIEOL care for this patient group. Thus, further studies are needed to identify reasons for less intense HIEOL among cancer patients with pre-existing SMD.

Psychopharmacological treatment in patients planned for hip or knee replacement.

Psychopharmacological treatment may be an independent risk factor for increased length of stay and readmission after hip and knee replacement. Thus, temporary perioperative discontinuation may be beneficial. However, little is known regarding the treatments, and not all are feasible to discontinue. Therefore, the aim of this study was to describe the treatments in terms of type, dose, duration, indication and initiating physician to assess the feasibility of temporary perioperative discontinuation. We included 482 patients planned for hip or knee replacement in psychopharmacological treatment for psychiatric disorders from 2021 to 2023 at five orthopaedic departments in Denmark. Most patients were treated with antidepressants (89%); most frequently, either selective serotonin reuptake inhibitors (SSRIs; 48%) or serotonin-norepinephrine reuptake inhibitors (SNRIs; 21%). The majority received monotherapy (70%); most frequently, an SSRI (36%) or an SNRI (12%). Most antidepressants were initiated by general practitioners (71%), and the treatments had lasted for more than a year (87%). The doses of SSRIs/SNRIs were moderate, and the most frequent indication for antidepressants was depression (77%). These results imply that temporary perioperative SSRI/SNRI discontinuation may be feasible in hip and knee replacement patients and support a future randomized controlled trial investigating the potential benefits of temporary discontinuation.

Professionals' perspectives on caring for cancer patients with pre-existing severe mental disorders.

INTRODUCTION: Cancer trajectories among patients with pre-existing severe mental disorders (SMD) are challenging and these pateints' prognosis is poor. This study aimed at exploring barriers in cancer trajectories among patients with pre-existing SMD as experienced by Danish healthcare professionals. METHODS: Semi-structured interviews were conducted with healthcare professionals who were sampled by purposive sampling. Data were analysed using inductive qualitative content analysis. RESULTS: The participants wanted to optimise treatment, but several barriers were reported, including lack of knowledge of supportive social systems. Oncological participants experienced a lack of knowledge of psychiatric disorders and a reluctance to deal with patients with SMD among some colleagues. Furthermore, participants expressed a lack of time and continuity. CONCLUSIONS: Concerns about how to create optimal cancer care trajectories for people with pre-existing SMD exist among healthcare professionals. Even so, stigmatisation, lack of knowledge and system barriers such as a lack of time and continuity must be addressed to optimise care for this population. FUNDING: This study was funded by The Danish Cancer Society (R283-A16499). TRIAL REGISTRATION: This study is registered in the internal register of research projects of the Central Denmark Region (R. no. 1-16-02-227-21).

The efficacy of ball blankets on insomnia in depression in outpatient clinics: A randomised crossover multicentre trial.

Many patients with depression report insomnia symptoms that profoundly affect their health and well-being. Non-pharmacological treatments of insomnia may be preferable for some patients. In this randomised crossover trial, we investigated the efficacy of the Protac Ball Blanket® on insomnia among patients with depression. Included patients (n = 45) were diagnosed with unipolar depression, and with subjective insomnia and poor sleep quality (Pittsburgh Sleep Quality Index Score > 5). Each patient slept 2 weeks with a Protac Ball Blanket® and 2 weeks with a control duvet. Randomisation defined the order of the 2-week sleep periods. Patients served as their own control in this design. The primary outcome was changes in total night-time sleep. Secondary outcomes were sleep-onset latency, number of awakenings, wake after sleep onset, daily use of pro necessitate sedatives and hypnotics, subjective sleep quality (Pittsburgh Sleep Quality Index), insomnia severity (Insomnia Severity Index), symptoms of depression (Hamilton Depression Rating Scale, Major Depression Inventory), symptoms of anxiety (Beck Anxiety Index), and patient-reported outcomes concerning interpersonal sensitivity, neurasthenia, anxiety and depression (Self-Reported Symptom State Scale). Paired two-sided t-tests were used to compare the means of the differences of the outcomes. Protac Ball Blanket® increased total night-time sleep by 12.9 min (95% confidence interval: 1.21-24.63, p = 0.031). Among the secondary outcomes, Protac Ball Blanket® decreased Hamilton Depression Rating Scale by 2.78 (95% confidence interval: -5.44; -0.11, p = 0.042) and Insomnia Severity Index by 2.98 (95% confidence interval: -5.45; -0.50, p = 0.020). No changes were observed in sleep-onset latency, number of awakenings, wake after sleep onset, Pittsburgh Sleep Quality Index, Major Depression Inventory, Beck Anxiety Index, Self-Reported Symptom State Scale, and medication use. The results suggest that some patients may benefit from Protac Ball Blanket® as an add-on non-pharmacological treatment to improve sleep in depression.

User Experiences of Ball Blankets in Adults with Depression-Related Insomnia: A Qualitative Content Analysis Study.

Insomnia is prevalent in patients suffering from depression and may itself exacerbate the disability associated with depression and impede the path to recovery. Although crucial in ensuring meaningful interactions and interventions for patients, research on patients' experiences of depression-related insomnia and its treatment is limited. The purpose of this study was therefore to investigate how adult patients with depression-related insomnia experience sleeping with a weighted Protac Ball Blanket®, focusing on how the blanket feels and works and contributes to their subjective sleep quality experience. An inductive content analysis approach was adopted. Semi-structured interviews were conducted with 13 patients. Four categories were identified: 1) Deep and dynamic touch pressure from the plastic balls induced calmness; 2) Changing sensory impressions from the rolling balls distracted attention from distressing thoughts and emotions; 3) The ball blanket improved the quality and quantity of sleep, which increased daily well-being; 4) Sleeping with the ball blanket was associated with positive as well as negative experiences depending on personal preferences for sensory stimulation. This study explains how the Protac Ball Blanket® as a potential non-pharmacological sleep-intervention improved the sleep of adult patients with depression-related insomnia. The blanket was found meaningful for coping with sleeplessness and with mental and physical unrest.

Schema therapy versus treatment as usual for outpatients with difficult-to-treat depression: study protocol for a parallel group randomized clinical trial (DEPRE-ST).

BACKGROUND: About one third of patients with depression are in a condition that can be termed as "difficult-to-treat". Some evidence suggests that difficult-to-treat depression is associated with a higher frequency of childhood trauma and comorbid personality disorders or accentuated features. However, the condition is understudied, and the effects of psychotherapy for difficult-to-treat depression are currently uncertain. The aim of this trial is to investigate the beneficial and harmful effects of 30 sessions of individual schema therapy versus treatment as usual for difficult-to-treat depression in the Danish secondary, public mental health sector. METHODS: In this randomized, multi-centre, parallel-group, superiority clinical trial, 129 outpatients with difficult-to-treat depression will be randomized (1:1) to 30 sessions of individual schema therapy or treatment as usual; in this context mainly group-based, short-term cognitive behaviour or psychodynamic therapy. The primary outcome is the change from baseline in depressive symptoms 12 months after randomization, measured on the observer-rated 6-item Hamilton Rating Scale for Depression. The secondary outcomes are health-related quality of life assessed with the European Quality of Life 5 Dimensions 5 Level Version, functional impairment assessed with the Work and Social Adjustment Scale, psychological wellbeing assessed with the WHO-5 Well-being Index, and negative effects of treatment assessed with the Negative Effects Questionnaire. Exploratory outcomes are improvement on patient self-defined outcomes, personal recovery, anxiety symptoms, anger reactions, metacognitive beliefs about anger, and perseverative negative thinking. Outcomes will be assessed at 6, 12, and 24 months after randomization; the 12-month time-point being the primary time-point of interest. Outcome assessors performing the depression-rating, data managers, statisticians, the data safety and monitoring committee, and conclusion makers for the outcome article will be blinded to treatment allocation and results. To assess cost-effectiveness of the intervention, a health economic analysis will be performed. DISCUSSION: This trial will provide evidence on the beneficial and harmful effects, as well as the cost-effectiveness of schema therapy versus treatment as usual for outpatients with difficult-to-treat depression. The results can potentially improve treatment for a large and understudied patient group. TRIAL REGISTRATION: ClinicalTrials.gov NCT05833087. Registered on 15th April 2023 (approved without prompts for revision on 27th April 2023).

A register and questionnaire study of long-term general health symptoms following SARS-CoV-2 vaccination in Denmark.

Many individuals who refuse COVID-19 vaccination have concerns about long-term side effects. Here, we report findings on self-reported symptoms from a Danish survey- and register study. The study included 34,868 vaccinated primary course recipients, 95.8% of whom received mRNA vaccines, and 1,568 unvaccinated individuals. Participants had no known history of SARS-CoV-2 infection. Using g-computation on logistic regression, risk differences (RDs) for symptoms between vaccinated and unvaccinated persons were estimated with adjustments for possible confounders. Within six weeks after vaccination, higher risks were observed for physical exhaustion (RD 4.9%, 95% CI 1.1% to 8.4%), fever or chills (RD 4.4%, 95% CI 2.1% to 6.7%), and muscle/joint pain (RD 7.0%, 95% CI 3.1% to 10.7%), compared to unvaccinated individuals. Beyond twenty-six weeks, risks were higher among the vaccinated for sleeping problems (RD 3.0, 95% 0.2 to 5.8), fever or chills (RD 2.0, 95% CI 0.4 to 3.6), reduced/altered taste (RD 1.2, 95% CI 0.2 to 2.3) and shortness of breath (RD 2.6, 95% CI 0.9 to 4.0). However, when examining pre-omicron responses only, the difference for reduced/altered taste was significant. As expected, the risk of experiencing physical exhaustion, fever or chills, and muscle/joint pain was higher among persons who responded within six weeks of completing the primary course. No significant differences were observed for the 7-25-week period after vaccination. Associations for the period beyond 26 weeks must be interpreted with caution and in the context of undetected SARS-CoV-2 infection, wide confidence intervals, and multiple testing. Overall, we observe no concerning signs of long-term self-reported physical, cognitive, or fatigue symptoms after vaccination.

Electroconvulsive therapy disrupts functional connectivity between hippocampus and posterior default mode network.

BACKGROUND: The mechanisms underlying memory deficits after electroconvulsive therapy (ECT) remain unclear but altered functional interactions between hippocampus and neocortex may play a role. OBJECTIVES: To test whether ECT reduces functional connectivity between hippocampus and posterior regions of the default mode network (DMN) and to examine whether altered hippocampal-neocortical functional connectivity correlates with memory impairment. A secondary aim was to explore if these connectivity changes are present 6 months after ECT. METHODS: In-patients with severe depression (n = 35) received bitemporal ECT. Functional connectivity of the hippocampus was probed with resting-state fMRI before the first ECT-session, after the end of ECT, and at a six-month follow-up. Memory was assessed with the Verbal Learning Test - Delayed Recall. Seed-based connectivity analyses established connectivity of four hippocampal seeds, covering the anterior and posterior parts of the right and left hippocampus. RESULTS: Compared to baseline, three of four hippocampal seeds became less connected to the core nodes of the posterior DMN in the week after ECT with Cohen's d ranging from -0.9 to -1.1. At the group level, patients showed post-ECT memory impairment, but individual changes in delayed recall were not correlated with the reduction in hippocampus-DMN connectivity. At six-month follow-up, no significant hippocampus-DMN reductions in connectivity were evident relative to pre-ECT, and memory scores had returned to baseline. CONCLUSION: ECT leads to a temporary disruption of functional hippocampus-DMN connectivity in patients with severe depression, but the change in connectivity strength is not related to the individual memory impairment.

SARS-CoV-2 Infection and Risk of Postacute Psychiatric and Neurologic Diagnoses: A Nationwide Danish Cohort Study.

BACKGROUND AND OBJECTIVES: The extent and burden of postacute psychiatric and neurologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not yet fully understood. To evaluate the association between SARS-CoV-2 infection and postacute manifestations of psychiatric and neurologic disorders, we conducted a nationwide cohort study including the entire Danish population aged 12 years or older on March 1, 2020. METHODS: Individuals were followed up for SARS-CoV-2 infection and diagnosis of subsequent psychiatric and neurologic disorders from March 1, 2020, to January 31, 2023, using the Danish nationwide coronavirus disease 2019 (COVID-19) test surveillance database and the Danish National Patient Registry. The main period of interest was 1-12 months after infection. Incidence rate ratios (IRRs) of new onset of 11 psychiatric and 30 neurologic disorders were calculated by comparing incidence rates of disorders between SARS-CoV-2-positive individuals and individuals without a positive test (nonpositive individuals). Stratified analyses were conducted according to COVID-19 vaccination status, variant period, age, sex, and severity of infection. RESULTS: Overall, 1,775,639 individuals in the study cohort (n = 3,239,008) were tested SARS-CoV-2 positive during follow-up. SARS-CoV-2-positive individuals compared with nonpositive individuals were at 24% reduced risk of any psychiatric disease (IRR 0.76, 95% CI 0.74-0.78) in the postacute period. The risk of any neurologic disorder was slightly higher among SARS-CoV-2-positive individuals than among those without a positive test (IRR 1.05, 95% CI 1.04-1.07). IRRs for specific disorders varied considerably from a 3.9-fold increased risk of change in sense of smell or taste (IRR 3.91, 95% CI 2.77-5.53) to a 29% reduced risk of dementia (IRR 0.71, 95% CI 0.65-0.78). The severity of infection and vaccination status, more so than age, sex, and variant, were found to significantly influence the stratified IRRs. Compared with nonpositive individuals, hospitalized patients with COVID-19 were at a 2.1-fold (IRR 2.05, 95% CI 1.78-2.37) increased risk of psychiatric disorders and at a 2.4-fold increased risk of neurologic disorders (IRR 2.44, 95% CI 2.29-2.60). DISCUSSION: Our study does not support previous findings of substantial postacute neurologic and psychiatric morbidities among the general population of SARS-CoV-2-infected individuals, but does corroborate an elevated risk among the most severe cases with COVID-19.

Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression: A randomized, double-blind, placebo-controlled trial.

Electroconvulsive therapy (ECT) is one of the most effective and rapid-acting treatment for severe depression but is associated with cognitive side-effects. Identification of add-on treatments that counteract these side-effects would be very helpful. This randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of four add-on erythropoietin (EPO; 40,000 IU/ml) or saline (placebo) infusions over 2.5 weeks of ECT (eight ECT sessions) in severely depressed patients with unipolar or bipolar depression. Neuropsychological assessments were conducted pre-ECT, three days after the eighth ECT (week 4), and at a 3-month follow-up. Further, functional magnetic resonance imaging (fMRI) was conducted after the eighth ECT. The primary outcome was change from pre- to post-ECT in a 'speed of complex cognitive processing' composite. Secondary outcomes were verbal and autobiographical memory. Of sixty randomized patients, one dropped out before baseline. Data were thus analysed for 59 patients (EPO, n = 33; saline, n = 26), of whom 28 had fMRI data. No ECT-related decline occurred in the primary global cognition measure (ps≥0.1), and no effect of EPO versus saline was observed on this outcome (ps≥0.3). However post-ECT, EPO-treated patients exhibited faster autobiographical memory recall than saline-treated patients (p = 0.02), which was accompanied by lower memory-related parietal cortex activity. The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36.

Post-acute symptoms 4 months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study.

Post-acute symptoms are not uncommon after SARS-CoV-2 infection with pre-Omicron variants. How Omicron and COVID-19 booster vaccination influence the risk of post-acute symptoms is less clear. We analyzed data from the nationwide Danish questionnaire study EFTER-COVID comprising 44,553 individuals ≥15 years old, tested between July 2021 and January 2022, in order to evaluate the association of the Omicron variant and COVID-19 booster vaccination with post-acute symptoms and new-onset general health problems, four months after infection with SARS-CoV-2. 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. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial post-acute symptoms and new-onset health problems compared to controls; the largest RD was observed for memory issues (RD=7.2%, 95%CI: 6.4 to 8.1). However, risks were generally lower than in the Delta period, particularly for dysosmia (RD=-15.0%, 95%CI: -17.0 to -13.2) and dysgeusia (RD=-11.2%, 95%CI: -13.2 to -9.5). Booster vaccination was associated with fewer post-acute symptoms and new-onset health problems, four months after Omicron infection, compared to two COVID-19 vaccine doses.

Blood-brain barrier permeability and electroconvulsive therapy: a systematic review.

OBJECTIVE: The cause of cognitive side effects after electroconvulsive therapy (ECT) is largely unknown. Alterations in the blood-brain barrier (BBB) have been considered in several recent ECT studies. We therefore found it worthwhile to perform a systematic review of the literature to examine if electrically induced seizures affect the permeability of the BBB. METHODS: PubMed/MEDLINE and Embase were searched 16 November 2022. Studies with a direct measurement of BBB permeability in animals treated with modified electroconvulsive stimulation (ECS) and in humans treated with ECT were included. Synthesis of results was narrative due to the low number of studies and differences in study designs. RESULTS: Four animal and two human (31 participants) studies were included. In animals, two studies found increased BBB permeability to some smaller molecules after modified ECS, while the two other studies found marginally increased or unchanged permeability to albumin after treatment. In contrast, the human studies did not find increased BBB permeability to smaller molecules or albumin after ECT. CONCLUSION: Animal but not human studies support increased BBB permeability to some smaller molecules after electrically induced seizures. However, this conclusion is confined by the low number of studies and the lack of studies applying state-of-the-art methods. More studies using modern approaches to measuring of BBB permeability are warranted. FUNDING AND REGISTRATION: The study was founded by Mental Health Services in the Capital Region of Denmark (grant number 61151-05) and was registered on PROSPERO before data extraction was initiated (CRD42022331385).

Postpartum depression and stigmatisation.

Perinatal depression occurs during pregnancy or within the first year of life. It has a negative effect on the quality of life of parents and the relationship with the child. In Denmark perinatal depression affects up to 12% of mothers and 8% of fathers. There is stigmatisation in relation to recognition and referral for symptoms of perinatal depression which may in part be due to insufficient knowledge among professionals. This review presents the main barriers to help-seeking for perinatal depression and the status regarding early detection and possibilities for the reduction of stigmatisation.

Psychedelic drugs in the treatment of psychiatric disorders.

This review aims at RCT's of psychedelics used in the treatment of depression and PTSD. Psilocybin has shown an antidepressant effect in cancer patients that was sustained at 6- and 12-months follow-up. The effect of psilocybin was comparable to escitalopram in one study. Ketamine has shown effect for the treatment of resistant depression. Phase 2 and 3 trials have shown the effect of MDMA on PTSD. No serious adverse events were reported in controlled settings, but larger studies are needed to establish safety and long-term effects.

Barriers in cancer trajectories of patients with pre-existing severe mental disorders-A systematic review.

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.

Protocol for the development and testing of the schiZotypy Autism Questionnaire (ZAQ) in adults: a new screening tool to discriminate autism spectrum disorder from schizotypal disorder.

BACKGROUND: Autism spectrum disorder (ASD) and schizotypal disorder (SD) both have a heterogenous presentation, with significant overlaps in symptoms and behaviour. Due to elevated recognition and knowledge of ASD worldwide, there is a growing rate of referrals from primary health professionals to specialised units. At all levels of assessment, the differential diagnostic considerations between ASD and SD exert major challenges for clinicians. Although several validated screening questionnaires exist for ASD and SD, none have differential diagnostic properties. Accordingly, in this study, we aim to develop a new screening questionnaire, the schiZotypy Autism Questionnaire (ZAQ), which provides a combined screening for both conditions, while also indicating the relative likelihood of each. METHODS: We aim to test 200 autistic patients and 100 schizotypy patients recruited from specialised psychiatric clinics and 200 controls from the general population (Phase 1). The results from ZAQ will be compared to the clinical diagnoses from interdisciplinary teams at specialised psychiatric clinics. After this initial testing phase, the ZAQ will be validated in an independent sample (Phase 2). CONCLUSIONS: The aim of the study is to investigate the discriminative properties (ASD vs. SD), diagnostic accuracy, and validity of the schiZotypy Autism Questionnaire (ZAQ). FUNDING: Funding was provided by Psychiatric Centre Glostrup, Copenhagen Denmark, Sofiefonden (Grant number: FID4107425), Trygfonden (Grant number:153588), Takeda Pharma. TRIAL REGISTRATION: Clinical Trials, NCT05213286, Registered 28 January 2022, clinicaltrials.gov/ct2/show/NCT05213286?cond = RAADS&draw = 2&rank = 1.

Endocrine disease history and the risk of postpartum depression.

BACKGROUND: Previous 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. AIMS: To investigate if women with endocrine disease history are at increased risk of developing PPD. METHOD: Based 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. RESULTS: Among 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. CONCLUSIONS: Women 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.