Long-term health-related quality of life and mental health in patients with immune thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially life-threatening disorder. Treatment advances have lowered morbidity rates, but past acute events can still cause long-term consequences, reducing health-related quality of life (HRQoL) and determining cognitive impairment, anxiety, and depression. We aimed to investigate these aspects and the role of caplacizumab and rituximab: 39 patients were evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the FACIT-Fatigue, the Hospital Anxiety and Depression Scale, and the Functional Assessment in Cancer Therapy-Cognitive Function questionnaires. The median age at study inclusion was 50 years (IQR 38-60), and the median follow-up from diagnosis was 97 months (IQR 14-182); 82% of patients were female, and 36% had one or more recurrences. Caplacizumab was administered in 16 patients (41%), as well as rituximab. ITTP patients reported lower physical and mental HRQoL scores than the general population. No differences in physical or mental domains were observed between patients treated or not with caplacizumab, while those who received rituximab reported lower scores in mental health. Neurological impairment at diagnosis correlated with worse fatigue. The majority of patients (72%) reported anxiety or depression (82%). ITTP had a significant impact on the long-term cognitive function, fatigue, depression, and anxiety levels of patients, with a negative effect on their HRQoL. Our findings underscore the need to pay special attention to patients' long-term physical and mental health, regardless of the medical treatments received.

How attachment style, mentalization and preparedness for death are associated with pre-loss grief symptoms' severity: A network analysis study in caregivers of terminally ill cancer patients.

Several psychological dimensions influence the psychological adjustment of terminally ill cancer patients' caregivers, during the end-of-life phase. The present study explored the associations between attachment styles, mentalization, preparedness for death, and the severity of pre-loss grief symptoms in 102 caregivers of terminal cancer patients. The results of the network analysis showed that insecure attachment dimensions were positively associated with several central pre-loss grief symptoms. Mentalization and preparedness for death showed negative associations with several pre-loss grief symptoms. Interestingly, bitterness showed a negative association with need for approval and a positive association with mentalization. The results provided insight into the grieving process for palliative care providers to implement effective caregiver support interventions.

Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study.

(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation (ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse < 12 months from upfront therapy (15%), ≥2 lines of salvage therapy (73%), extranodal disease (65%). Nineteen patients (73%) had ≥3 of these factors. In addition, 16 patients (61%) also displayed PET-positive (Deauville ≥ 4) disease before ASCT. Treatment-related adverse events (TRAEs), never graded > 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6−30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients' subsets more likely to benefit from this approach.

Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab.

BACKGROUND: Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade. METHODS: Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015-December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan-Meier method, landmark-analyses and Cox regressions. RESULTS: Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15-82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1-9), received a median of 18 nivolumab doses (range, 1-57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI. CONCLUSIONS: In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic 'equalizers' counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.

Real-life evidence of low-dose mepolizumab efficacy in EGPA: a case series.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, small vessel, necrotizing vasculitis. The disease is mainly characterized by hypereosinophilia and asthma with frequent sinonasal involvement, although multiple organs can be affected, including the heart, lungs, skin, gastrointestinal tract, kidneys, and nervous system. IL-5 production is pathogenetically central for the development of the disease by promoting proliferation, transvascular migration and functional activation of eosinophils. The degree of blood and tissue eosinophilia appears to be associated with disease pathogenesis and eosinophil depletion represents a promising treatment approach for EGPA. We prospectively evaluated the efficacy and safety of a low dose (100 mg q4w), 12-month course of mepolizumab, an anti-IL-5 monoclonal antibody, in eight patients with severe asthma and active EGPA. Patients were recruited by the tertiary care center of Clinical Immunology and Allergy, University of Naples Federico II. The following outcomes were assessed before (T0), and after 6 (T6) and 12 months (T12) of mepolizumab treatment: Birmingham Vasculitis Activity Score (BVAS), prednisone intake, Sino-Nasal Outcome Test (SNOT-22), Total Endoscopic Polyp Score (TENPS), Asthma Control Test (ACT), Forced Expiratory Volume one second (FEV1)%, blood eosinophilia. BVAS score significantly decreased showing a sharp reduction in disease activity score. Clinical improvements in terms of sinonasal scores and asthma symptoms were observed, in parallel with a drastic drop in eosinophil blood count. Prednisone intake was significantly reduced. In two patients, asthma exacerbations led to discontinuation in mepolizumab therapy after 6 and 12 months despite BVAS reduction. Mepolizumab treatment was well tolerated, and no severe adverse drug effects were registered. In conclusion, our 12-month real-life study suggests that mepolizumab may be beneficial and safe in active EGPA patients by improving disease activity score, sinonasal and asthma outcomes while reducing the burden of prednisone intake.

The association between Major Depressive Disorder and premature death risk in hematologic and solid cancer: a longitudinal cohort study.

BACKGROUND: the aim was to verify the association between Major Depressive Disorders (MDD) and the risk of premature death in people with oncological diseases, and to collect evidence about the causality of a possible association from a longitudinal perspective. DESIGN AND METHODS: it is a cohort study lasting 9 months, involving people with solid or hematologic cancers. The assessment was conducted by an ad hoc form to collect socio-demographic and clinical-oncological data, the PHQ-9 to screen MDD (cut-off ≥10) and the SF-12 to evaluate HRQoL. Relative Risk (RR) of early death between MDD exposed and not-exposed and Kaplan-Meier survival were carried out. RESULTS: people exposed to MDD during the follow-up were 107/263 (40.7%). Among them, 36 deceased during the observation period. Overtime, having MDD and death' occurrence showed a strong association (RR=2.15; 95% CI (1.10-4.20); χ²=5.224, p=0.0022), confirmed by Kaplan-Meier survival analysis (χ²=4.357, p=0.037). Among people who died, there was not any association between MDD, age, gender, HRQoL, cancer stage and site. CONCLUSIONS: the study confirms the association between MDD and early death in people with cancer. The absence of any association between the onset of MDD and advanced stage of cancer may suggest that it could be due to the consequences of MDD in worsening the clinical conditions related to cancer. The findings point out the relevance of MDD' early detention among people with cancer.

Patient-Physician Communication in Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Introduction: An effective communication is an integral part of the patient-physician relationship. Lack of a healthy patient-physician relationship leads to a lower level of patient satisfaction, scarce understanding of interventions and poor adherence to treatment regimes. Patients need to be involved in the therapeutic process and the assessment of risks and perspectives of the illness in order to better evaluate their options. Physicians, in turn, must convey and communicate information clearly in order to avoid misunderstandings and consequently poor medical care. The patient-physician relationship in cancer care is extremely delicate due to the complexity of the disease. In cancer diagnosis, the physician must adopt a communicative approach that considers the psychosocial factors, needs and patient's preferences for information,which in turn all contribute to affect clinical outcomes. Search Strategy and Methods: This review was conducted using the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) statement. We included studies on the importance of physician-patient communication in Acute Myeloid Leukaemia and Myelodysplastic Syndrome care. We searched PubMed, Web of Sciences, Scopus, Google scholar for studies published from December 1 st , 2020 up to March 1 st , 2021. Using MeSH headings, we search for the terms "Physician and patient communication AND Acute Myeloid leukemia" or "Myelodysplastic syndrome" or "Doctor" or "Clinician", as well as variations thereof . Purpose of the Review: This review examines the progress in communication research between patient and physician and focuses on the impact of communication styles on patient-physician relationshipin hematologic cancers, including Acute Myeloid Leukaemia and Myelodysplastic Syndromes.

Health-Related Quality of Life Assessment in Patients with Myelodysplastic Syndromes: Evidence from Randomized Clinical Trials.

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and blood cytopenia with a variable risk of progression to acute myeloid leukemia. The main goal of therapy for the large majority of patients is to improve health-related quality of life (HRQoL). Its rigorous assessment is now recommended in international MDS guidelines. Our review provides an overview of HRQoL results from randomized controlled trials (RCTs) in MDS patients. The literature search undertaken in PubMed identified 10 RCTs with HRQoL endpoints (all secondary) published between August 2008 and September 2020. These RCTs have helped to better understand the impact of therapies from the patient perspective and have generated valuable information that can be used to further support clinical decisions. However, the number of RCTs in MDS patients, including HRQoL endpoints, is still low. Given the importance of symptom relief and HRQoL improvement in the treatment of MDS patients, the assessment of the patient perspective in future RCTs is highly recommended to keep expanding the knowledge of the impact of new MDS therapies.

Health Related Quality of Life in Patients with Onco-hematological Diseases.

BACKGROUND: HRQoL is generally conceptualized as a broad multidimensional construct that refers to patients' perceptions of the impact of disease and its treatment on their physical, psychological, and social functioning and well-being. Little is known in patients with onco-hematological cancer in comparison with the general population and other chronic diseases. OBJECTIVE: We assessed HRQoL in patients diagnosed with haematological cancers in comparison with the general population and other chronic diseases. METHODS: The questionnaire Short Form (SF)-12 was administered to 62 patients with onco-hematological disease and results were compared with 702 controls (184 healthy people, 37 Major Depression, 201 Multiple Sclerosis; 23 Wilson disease; 46 Carotidal Atherosclerosis; 60 Celiac disease; 151 solid tumours). RESULTS: HRQoL in patients diagnosed with a haematological cancer was significantly worse in comparison with the general population (F= 43.853, p <0.00001) but similar when compared with solid tumour and other chronic diseases such as Major Depression and Carotid Atherosclerosis. In addition, HRQoL in patients diagnosed with a haematological cancer was significantly higher than that due to Celiac disease (p <0.00001) and Wilson's disease (p= 0.02), and lower than that due to Multiple Sclerosis (p= 0.032). CONCLUSION: This study confirmed that haematological cancers negatively affects overall HRQoL. The results showed an impact of haematological cancers on HRQoL that is similar to what found in patients with solid tumors, Major Depression and Carotid Atherosclerosis. Current successful therapeutic strategy achieved in the treatment of haematological cancers not only positively impact on survival rate but also could improve the overall HRQoL.

5-HT2C receptor blockade reverses SSRI-associated basal ganglia dysfunction and potentiates therapeutic efficacy.

Serotonin (5-HT) selective reuptake inhibitors (SSRIs) are widely used in the treatment of depression and anxiety disorders, but responsiveness is uncertain and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs reduce dopaminergic (DAergic) activity, but specific mechanistic insight is missing. Here we show in mice that SSRIs impair motor function by acting on 5-HT2C receptors in the substantia nigra pars reticulata (SNr), which in turn inhibits nigra pars compacta (SNc) DAergic neurons. SSRI-induced motor deficits can be reversed by systemic or SNr-localized 5-HT2C receptor antagonism. SSRIs induce SNr hyperactivity and SNc hypoactivity that can also be reversed by systemic 5-HT2C receptor antagonism. Optogenetic inhibition of SNc DAergic neurons mimics the motor deficits due to chronic SSRI treatment, whereas local SNr 5-HT2C receptor antagonism or optogenetic activation of SNc DAergic neurons reverse SSRI-induced motor deficits. Lastly, we find that 5-HT2C receptor antagonism potentiates the antidepressant and anxiolytic effects of SSRIs. Together our findings demonstrate opposing roles for 5-HT2C receptors in the effects of SSRIs on motor function and affective behavior, highlighting the potential benefits of 5-HT2C receptor antagonists for both reduction of motor side effects of SSRIs and augmentation of therapeutic antidepressant and anxiolytic effects.

The Microbiota-Gut-Brain Axis.

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.

[Acute kidney failure in differentiation syndrome: a possible complication during therapy with differentiating agents for acute promyelocytic leukemia. A case report].

Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis.

Circulating dendritic cells deficiencies as a new biomarker in classical Hodgkin lymphoma.

No robust biomarkers have been yet validated to identify the recurrence of disease in classical Hodgkin Lymphoma (cHL) patients upon induction treatment. The relevance of the inflammatory microenvironment in cHL prompted us to investigate the key immunomodulator myeloid dendritic cells type-1 (mDC1), type-2 (mDC2) and plasmacytoid dendritic cells (pDC). Blood DC levels were assessed in 52 newly diagnosed patients through multiparametric flow-cytometry. All but two patients received ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). The median counts of all DC subsets were lower in cHL patients than in healthy controls (P < 0·001). Median mDC counts were inferior for the advanced vs early stage patients for both mDC1s and mDC2s (P = 0·008; P = 0·0007 respectively). Also, median mDC2 counts were reduced in case of bulky (P = 0·0004) and extra-nodal (P = 0·046) disease. Patients with B symptoms had lower levels for mDC1s (P = 0·046), mDC2s (P = 0·009) and pDCs (P = 0·040). All the DC subtypes increased at the end of treatment in 26 patients (P < 0·001): 4·6-fold for mDC1, 2·4-fold for mDC2, 4·5-fold for pDC and aligned DCs subsets with the reference frequencies and the interquartile ranges of the controls. In conclusion, DCs may contribute to the disturbed immunological interplay typical of cHL, prompting a further evaluation of their value as a potential new biomarker.

Spirituality and Awareness of Diagnoses in Terminally Ill Patients With Cancer.

OBJECTIVE: Aims of the present study were to investigate the association between awareness of own illness condition and psychological outcome in end-of-life phase and to test the association between the spirituality and the awareness of own illness condition. METHODS: Three hundred and ninety-nine terminally ill patients with cancer were enrolled in a hospice in central Italy. One hundred patients satisfied the inclusion criteria. The Systems of Belief Inventory, the Hospital Anxiety and Depression Scale, and a psychological interview to determine the level of awareness of the illness diagnosis (aware; partially aware; and not aware) were administered to terminally ill patients. RESULTS: The main finding was that the awareness of one's own illness condition was positively associated with the extrinsic spirituality and negatively associated with intrinsic spirituality (regression model R = .26; R2 = .07; adjusted R2 = .05; F2, 97 = 3.45; P = .036). The aware group showed lower anxiety and depression ( F2, 97 = 1.9; P = . 075; F2, 97 = 2.6; P = .04) scores than partially aware and not aware groups. The psychological outcome was not associated with the spirituality level. CONCLUSION: In terminally ill patients with cancer, the levels of depression and anxiety were lower in patients aware of their own illness state. Moreover, higher levels of extrinsic and lower levels of intrinsic spirituality predicted the awareness of one's own illness state.

Persistent complex bereavement disorder in caregivers of terminally ill patients undergoing supportive-expressive treatment: a pilot study.

BACKGROUND: The proposal of persistent complex bereavement disorder (PCBD) in the DSM-V increased the interest on the impact of grief on the psychological health. AIMS: Investigating the time course of psychological symptoms, emotional and social abilities in caregivers (undergoing or not to supportive-expressive treatment) of terminally ill cancer patients from 1 months before loss to 14 months after it. METHOD: Thirty-three of 60 caregivers were assessed by PG-12, HAM-A, HAM-D, TAS-20 and ASQ, at the admission in Hospice, and after 3, 10 and 14 months from the loss. Twelve caregivers adhered to follow a supportive-expressive treatment and 21 caregivers did not. RESULTS: PG-12, anxiety, and depression scores decreased in both groups over time. The score of difficulty in identifying emotions and confidence with closeness decreased significantly only in the treated-group. PG-12 score at T0 was able to predict the DSM V diagnosis of PCBD at T3. CONCLUSIONS: Findings showed a decrease of the anxiety, depression, security in the attachment style and an increase of the ability to identify emotions during the first year after loss in caregivers of terminally ill cancer patients. Pre-loss assessment of prolonged grief risk seems useful to predict the diagnosis of PCBD 1 year after loss.

Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.

Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.

Multidisciplinary approach and anesthetic management of a surgical cancer patient with methylene tetrahydrofolate reductase deficiency: a case report and review of the literature.

INTRODUCTION: Hyperhomocysteinemia is a known risk factor for myocardial infarction, stroke, peripheral vascular disease, and thrombosis. Elevated plasma homocysteine levels have been demonstrated in patients with recurrent episodes or a single episode of thrombosis. Here we describe the development of cardiovascular disease as a complication of a surgical intervention in a patient with colorectal cancer and hyperhomocysteinemia. CASE PRESENTATION: A 65-year-old Caucasian man complained of pain and constipation, attributed to previously diagnosed adenocarcinoma (stage IIB) of the hepatic flexure. An anamnestic investigation showed that he had undergone two surgical interventions. During both, he suffered thrombotic postoperative complications, a deep vein thrombosis of the upper extremity after the first operation and retinal vein occlusion after the second. He was diagnosed with hyperhomocysteinemia associated with a homozygous C677T mutation of the gene encoding the enzyme methylenetetrahydrofolate reductase. Our patient was initially treated with folic acid and high-dose B vitamins. On day 7 he underwent a right hemicolectomy. Anesthesia was performed with sevoflurane in 40% O2 and without the use of nitrous oxide. Postoperatively, our patient remained on folic acid and B vitamins and was without immediate or subsequent complications. CONCLUSIONS: Neoplastic disease and related surgery followed by the administration of chemotherapeutic drugs alter the hemostatic balance in cancer patients. Those suspected of also having a thrombophilic disease require a thorough laboratory diagnostic workup, including a molecular analysis aimed at identifying the genetic mutation responsible for the hyperhomocysteinemia, as indicated. The case described in this report highlights the importance of a multidisciplinary approach that includes expertise in peri-operative anesthesia, surgery, oncology, and hematology.

Attachment style dimensions can affect prolonged grief risk in caregivers of terminally ill patients with cancer.

OBJECTIVE: The aim of the present study was to evaluate the predictive role of attachment dimensions on the risk of prolonged grief. Sixty caregivers of 51 terminally ill patients with cancer who had been admitted in a hospice were selected. METHODS: Caregivers were interviewed using Attachment Scale Questionnaire, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Prolonged Grief Disorder 12 (PG-12). RESULTS: The consort caregivers showed higher PG-12 level compared to the sibling caregivers. Anxiety, depression, need for approval, and preoccupation with relationships levels were significantly correlated with PG-12 scores. CONCLUSION: Female gender, high levels of depression, and preoccupation with relationships significantly predicted higher levels of prolonged grief risk.

Postnatal day 2 to 11 constitutes a 5-HT-sensitive period impacting adult mPFC function.

Early-life serotonin [5-hydroxytryptamine (5-HT)] signaling modulates brain development, which impacts adult behavior, but 5-HT-sensitive periods, neural substrates, and behavioral consequences remain poorly understood. Here we identify the period ranging from postnatal day 2 (P2) to P11 as 5-HT sensitive, with 5-HT transporter (5-HTT) blockade increasing anxiety- and depression-like behavior, and impairing fear extinction learning and memory in adult mice. Concomitantly, P2-P11 5-HTT blockade causes dendritic hypotrophy and reduced excitability of infralimbic (IL) cortex pyramidal neurons that normally promote fear extinction. By contrast, the neighboring prelimbic (PL) pyramidal neurons, which normally inhibit fear extinction, become more excitable. Excitotoxic IL but not PL lesions in adult control mice reproduce the anxiety-related phenotypes. These findings suggest that increased 5-HT signaling during P2-P11 alters adult mPFC function to increase anxiety and impair fear extinction, and imply a differential role for IL and PL neurons in regulating affective behaviors. Together, our results support a developmental mechanism for the etiology and pathophysiology of affective disorders and fear-related behaviors.