Improvements in mental health associated with increased electronic communication and deterioration in physical health in adults aged 50+ during the COVID-19 pandemic.

Background: Previous studies have documented changes in physical health, mental health and social parameters during COVID-19. At the same time, there are no comprehensive analyses of these parameters designed as longitudinal studies on large-scale older populations before and during the pandemic. Objective: This longitudinal study aims to provide a quantitative analysis of the COVID-19 impact on the physical, mental, and social parameters in adults aged 50 and older before, in the early stages, and during the COVID-19 pandemic. Methods: The data for this study were collected from three waves of the Survey of Health, Ageing and Retirement in Europe (SHARE), a supranational longitudinal database: pre-COVID (October 2019-March 2020), early-COVID (June-September 2020), and during-COVID (June-August 2021). The sample included 31,526 individuals, compared across the three-time points through nonparametric group comparison tests. Results: Physical health was subjectively rated as poorer in the during-COVID wave compared to the pre-COVID wave. Additionally, the number of illnesses or health conditions reported in the during-COVID wave was significantly higher than in the pre-COVID wave, with the biggest increases registered for cardiovascular diseases. The results also show that employment and overall social contact decreased while loneliness increased over time. Unexpectedly, mental health issues, such as sadness or depression and trouble sleeping, decreased significantly in the COVID waves compared to the pre-COVID wave. The analysis of two additional pre-COVID waves (2015, 2017) revealed that poorer pre-COVID mental health reflected in high values of sadness or depression and trouble sleeping was not an isolated peak but represented a typical baseline. The positive influence on the individuals' mental health during COVID-19 was found to be electronic communication, which showed higher values than face-to-face communication and lowered the odds of sadness or depression. Conclusion: Future policies should thus consider the positive impact of electronic contacts on mental health to promote overall health in adults aged 50 and older.

Utilization of psychiatry services in the emergency department following a terror event in Israel.

In October 2023, Israel sustained a massive terror attack, with 1,300 people murdered, over 240 kidnapped, and millions exposed to the horrors. This study's aim is to examine the profile of patients arriving to the emergency department (ED) for psychiatric services during the month following the attack, compared to a similar period the year prior. In this cohort study, we compared patients arriving to the ED of a large general hospital in the center of Tel Aviv for psychiatric services during the month post-attack with the previous year using t-tests and chi-square exams. In 2023, 256 patients arrived in the ED for psychiatric evaluation and/or treatment, 46 % more than in 2022. Of these, 64 % were examined due to symptoms related to the terror attack. In 2023, significantly fewer patients had a prior psychiatric diagnosis (68% vs. 89 %). Significantly more patients were diagnosed with acute stress reaction or acute stress disorder in the ED, compared to almost no such diagnoses in 2022 (14 % and 43% vs. 0 % and 1 %). Major terror incidents profoundly influence psychiatric ED visits. Planning efforts for major emergencies should be adapted accordingly.

Prenatal Cannabis Exposure and The Risk for Neuropsychiatric Anomalies in the Offspring: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the association between cannabis use during pregnancy and the risk for long-term neuropsychiatric pathology in the offspring. DATA SOURCES: MEDLINE, EMBASE, and Cochrane library databases were systematically searched until January 22, 2024, with no language or date restrictions. STUDY ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they reported quantitative data on any long-term neuropsychiatric outcome in offspring whose mothers used cannabis during pregnancy for medical or recreational use, by any route and at any trimester, in comparison to offspring of women who abstained from cannabis use during pregnancy. All observational study designs were included in the analysis. STUDY APPRAISAL AND SYNTHESIS METHODS: A systematic review and meta-analysis were performed according to the PRISMA and MOOSE guidelines. The data was extracted independently by two reviewers. The following offspring outcomes were of interest: attention-deficit/ hyperactivity disorder (ADHD), autism spectrum disorder (ASD), depression, anxiety, psychotic disorders, as well as cannabis and other substance use. Odds ratios (OR) and 95% confidence intervals (CI) were pooled for each neuropsychiatric outcome in the offspring of women exposed to cannabis during pregnancy compared with non-exposed. Data were pooled using random-effects models. RESULTS: Eighteen eligible observational studies were included in the systematic review, and seventeen were included in the final quantitative analysis, representing 534,445 participants. After adjusting for confounders, the pooled OR for ADHD was 1.13 (95% CI 1.01-1.26); for ASD, the pooled OR was 1.04 (95% CI 0.74-1.46); for psychotic symptoms, the pooled OR was 1.29 (95% CI 0.97-1.72); for anxiety, the pooled OR was 1.34 (95% CI 0.79-2.29); for depression, the pooled OR was 0.72 (95% CI 0.11-4.57); and for offspring's cannabis use the pooled OR was 1.20 (95% CI 1.01-1.42). CONCLUSIONS: Prenatal cannabis exposure is not associated with an increased risk of ASD, psychotic symptoms, anxiety, or depression in offspring. However, it may slightly elevate the risk of ADHD and predispose offspring to cannabis consumption. Despite these findings, caution is warranted regarding cannabis use during pregnancy. Further research is imperative, especially given the increasing potency of cannabis in recent years.

Social networks as a protective factor for worsened self-perceived health status related to self-perceived changes in loneliness and health conditions in adults aged 50+ during the COVID-19 outbreak.

The coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, leading millions of people to change their lifestyles, especially older individuals who are the most at-risk population. Social isolation, the main preventive action to slow the pandemic's spread, reduced and drastically limited social connections, increasing older individuals' loneliness and stress, and worsening their health. We examined the connection between self-perceived changes in loneliness, the existence and type of social contact (face-to-face/electronic), and health conditions on self-perceived changes in health status during the outbreak, analyzing 51,778 individuals aged 50 plus from the Survey of Health, Ageing and Retirement in Europe (SHARE) database Wave 8 beta (June-August 2020). We found that the odds for worsened self-perceived health status were 249% higher among individuals who reported increased loneliness compared to the non-increase group and were lower in individuals with face-to-face contact (31%) or electronic contact (54%) during the outbreak. In addition, the odds for worsened self-perceived health status were higher for individuals with hypertension (17%), cancer (19%), chronic lung disease (25%), heart problems (27%), and other illnesses (32%). Based on the results obtained, electronic contact has shown a stronger connection as a protective factor for worsened self-perceived health since the outbreak compared to face-to-face interactions. Thus, adopting a policy that encourages the usage of electronic communications could reduce the burden on the healthcare system, particularly during pandemics, while improving patient health outcomes and minimizing pandemic-related health risks. This approach is especially important for older individuals, for whom any departure from home can cause an additional risk of exposure to the virus.

The association between emotion regulation and pain during the immediate postpartum period.

PURPOSE: The present study aims to investigate the association between emotion regulation difficulties and pain perception during the immediate postpartum period. METHODS: A cross-sectional study was performed in women during the immediate postpartum period. Women completed the Difficulties in Emotion Regulation Scale (DERS) questionnaire to measure difficulties in emotion regulation. A second analysis was conducted for the six subdomains of the DERS questionnaire. The visual analog scale (VAS) was used to measure pain intensity. The association between DERS scores and VAS score was assessed. Multivariable logistic regression models were constructed to control for potential confounders. RESULTS: A total of 150 women were included in the final analysis, of whom 112 (74.6%) delivered vaginally and 38 (25.4%) had a cesarean delivery. Higher DERS scores, indicating more difficulties in emotion regulation, were significantly associated with higher VAS scores regardless of mode of delivery. Likewise, higher emotion regulation scores in 5 of 6 subdomains were associated with higher VAS scores (p < 0.001). Using multivariate logistic regression models higher DERS scores were independently associated with higher VAS scores. CONCLUSION: Difficulties in emotion regulation are associated with higher pain perception during the immediate postpartum period. Interventions designed to improve emotion regulation may improve maternal well-being in the immediate postpartum period and possibly reduce use of pain medication.

Patterns of psychiatric hospitalizations of Arab and Jewish adults with chronic psychotic disorders, before and after national mental health reforms, Israel, 1991-2016.

BACKGROUND: Members of the Arab minority in Israel are at increased risk of developing mental illness, although less likely to seek care and have accessible treatment. This study compares trends in psychiatric hospitalizations between Arabs and Jews with chronic psychotic disorders, before and after introduction of the Community Rehabilitation of Persons with Mental Disability Law in 2000, and governmental recognition of the need to allocate resources for patients with co-occurring substance use disorder and mental illness in 2010. METHODS: The National Psychiatric Case Registry provided data on 18,684 adults with schizophrenia/schizoaffective disorder, hospitalized in 1991-2016 (at least once in 2010-2015). Repeated-measures ANOVA was used to measure the effect (and interactions) of population-group (Arabs and Jews), time-period (Period1: 1991-2000, Period2: 2001-2009, Period3: 2010-2016) and sex, on average length of stay (LOS), annual number of hospitalizations and hospitalization days. RESULTS: The proportion of Arab patients hospitalized with a diagnosis of chronic psychotic disorder (14.4%) was significantly lower than their proportion in the general population (21%), and their average age at first hospitalization (28.4 years) was older than that of Jewish inpatients (27.0 years). The average number of hospitalization days and LOS of Jewish patients were double that of Arab patients in Period1. Following implementation of the Rehabilitation Law, hospitalization days increased among Arab patients and decreased slightly among Jewish patients, such that by Period3 the average number of hospitalization days was similar among Jewish (41) and Arab (37) patients. The increase in hospitalization days among Arab patients was limited to men with no change noted among women. The number of hospitalization days among Arab women was about half that of Jewish women (p < 0.0001). CONCLUSIONS: The findings reveal a narrowing of disparities in psychiatric hospitalizations between Arab and Jewish patients in Israel over time. However, among Arab women the number of hospitalization days remains considerably lower than that of Jewish women, raising concerns that Arab women may be receiving insufficient care. Further study is needed to fully understand the underpinnings of these disparities, although increasing the number of Arabic-language mental health services and providing psycho-education, will help further close the gap.

Ethnic inequalities in community rehabilitation use and psychiatric hospitalizations among people with chronic psychotic disorder.

PURPOSE: Community rehabilitation is crucial for the long-term treatment of people with chronic psychotic disorder. Ethnic minorities are less likely to seek care and have accessible treatment. This study examines whether the use of rehabilitation services and the relationship between rehabilitation and number of hospitalization days differ between Arabs and Jews. METHODS: Data from the Israel National Psychiatric Case Register on 18,684 adults with schizophrenia/schizoaffective disorders hospitalized in 1963-2016 were merged with data from the national Mental Rehabilitation Register. Associations between the use of rehabilitation services and demographic and clinical characteristics were assessed through logistic regression modeling. Associations between ethnicity and duration of rehabilitation (housing or vocational) and annual hospitalization days during Period1: 2001-2009 and Period2: 2010-2016 were analyzed using ANOVA. RESULTS: Among Jewish patients (N = 2556), 37% and 57% used rehabilitation services during Period1 and Period2, respectively, compared with 18% and 40% among Arab patients (N = 15,145) (p < 0.0001). The use of rehabilitation services was significantly higher among Jews (adjusted OR = 2.26, 95% CI 2.07-2.47). Average duration of housing and vocational rehabilitation services did not differ between Arab and Jewish patients. In both groups, duration of rehabilitation was inversely associated with annual hospitalization days. CONCLUSIONS: The ethnic disparity in the use of rehabilitation services has narrowed over time, yet remains. Although fewer Arab patients use rehabilitation, Jewish and Arab benefit similarly from the services with regard to reduced hospitalization days. To further close the ethnic gap, greater efforts must be made to expand the availability of culturally appropriate rehabilitation services for the Arab minority.

Psychiatric referrals to the general hospital emergency department: are we being effective?

Introduction: General hospital emergency departments (GHEDs) are notoriously overcrowded. This is caused, in part, by ineffective referrals, that is to say referrals that do not require medical examination or other interventions in the context of a general hospital. This study aims to investigate the contribution of psychiatric referrals to this issue, to identify potential determinants of these referrals and offer means to reduce them. Materials and methods: Retrospective data were collected from psychiatric admission files within a GHED of a tertiary-care city hospital over a 1 year period. Two experienced clinicians separately reviewed each file to determine rationale of referrals according to predetermined criteria. Results: A total of 2,136 visits included a psychiatric examination, 900 (42.1%) were determined "effective," and 1,227 (57.4%) were deemed "potentially ineffective." The leading causes for potentially ineffective referrals to a GHED were psychiatric illness exacerbation (43.4%), and suicidal ideations (22%). Most referrals (66.9%) were initiated by the patient or their family, and not by a primary care physician or psychiatrist. Conclusion: More than half of the psychiatric referrals did not necessarily require the services of a general hospital, and may be more suitable for referral to a dedicated psychiatric facility. Ineffective referrals to the GHED pose a burden on general hospital resources, and may be less effective for the psychiatric patients. This calls for clear guidelines for the provision of optimal emergency treatment for mental-health patients.

Aberrant Intrinsic Brain Network Functional Connectivity During a Face-Matching Task in Women Diagnosed With Premenstrual Dysphoric Disorder.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is characterized by affective, cognitive, and physical symptoms, suggesting alterations at the brain network level. Women with PMDD demonstrate aberrant discrimination of facial emotions during the luteal phase of the menstrual cycle and altered reactivity to emotional stimuli. However, previous studies assessing emotional task-related brain reactivity using region-of-interest or whole-brain analysis have reported conflicting findings. Therefore, we utilized both region-of-interest task-reactivity and seed-voxel functional connectivity (FC) approaches to test for differences in the default mode network, salience network, and central executive network between women with PMDD and control participants during an emotional-processing task that yields an optimal setup for investigating brain network changes in PMDD. METHODS: Twenty-four women with PMDD and 27 control participants were classified according to the Daily Record of Severity of Problems. Participants underwent functional magnetic resonance imaging scans while completing the emotional face-matching task during the midfollicular and late-luteal phases of their menstrual cycle. RESULTS: No significant between-group differences in brain reactivity were found using region-of-interest analysis. In the FC analysis, a main effect of diagnosis was found showing decreased default mode network connectivity, increased salience network connectivity, and decreased central executive network connectivity in women with PMDD compared with control participants. A significant interaction between menstrual cycle phase and diagnosis was found in the central executive network for right posterior parietal cortex and left inferior lateral occipital cortex connectivity. A post hoc analysis revealed stronger FC during the midfollicular than the late-luteal phase of PMDD. CONCLUSIONS: Aberrant FC in the 3 brain networks involved in PMDD may indicate vulnerability to experience affective and cognitive symptoms of the disorder.

Schizophrenia or schizoaffective disorder? A 50-year assessment of diagnostic stability based on a national case registry.

BACKGROUND: Schizoaffective disorder (SAD) remains a controversial diagnosis in terms of necessity and reliability. OBJECTIVES: We assessed diagnostic patterns of SAD and schizophrenia (SZ) among hospitalized psychiatric patients over a fifty-year period. METHOD: Data from the Israeli National Psychiatric Registry on 16,341 adults diagnosed with SZ or SAD, hospitalized at least twice in 1963-2017, were analyzed. Stability between most-frequent, first and last diagnosis, and diagnostic-constancy (the same diagnosis in >75 % of a person's hospitalizations) were calculated. Three groups were compared: People with both SAD and SZ diagnoses over the years (SZ-SAD), and people with only one of these diagnoses (SZ-only; SAD-only). The incidence of SAD and SZ before and after DSM-5 publication was compared. RESULTS: Reliability between last and first diagnosis was 60 % for SAD and 94 % for SZ. Agreement between first and most-frequent diagnosis was 86 % for SAD and 92 % for SZ. Diagnostic shifts differ between persons with SAD and with SZ. Diagnostic-constancy was observed for 50 % of SAD-only patients. In the SZ-SAD group, 9 % had a constant SAD diagnosis. Compared to the other groups, the SZ-SAD group exhibited a higher substance use prevalence, younger age at first-hospitalization, and more hospitalizations/person (p < 0.0001). The incidence of a first-hospitalization SAD diagnosis increased by 2.2 % in the 4-years after vs. prior to DSM-5. CONCLUSIONS: A SAD diagnosis is less stable than SZ. The incidence of a SAD diagnosis increased after DSM-5, despite stricter diagnostic criteria. The SZ-SAD group exhibited the poorest outcomes. SAD may evolve over time necessitating periodic re-evaluation.

Common model of stress, anxiety, and depressive symptoms in pregnant women from seven high-income Western countries at the COVID-19 pandemic onset.

OBJECTIVE: Increases in stress, anxiety, and depression among women pregnant during the COVID-19 pandemic have been reported internationally. Yet rigorous comparison of the prevalence of maternal mental health problems across countries is lacking. Moreover, whether stress is a common predictor of maternal mental health during the pandemic across countries is unknown. METHODS: 8148 pregnant women from Germany, Israel, Italy, Poland, Spain, Switzerland, and the United States were enrolled in the International COVID-19 Pregnancy Experiences (I-COPE) Study between April 17 and May 31, 2020. Sociodemographic characteristics, pandemic-related stress, pregnancy-specific stress, anxiety, and depression were assessed with well-validated instruments. The magnitude of stress and mood disturbances was compared across countries. A path model predicting clinically significant levels of anxiety and depression from maternal characteristics and stress was tested for all study participants and then examined separately in each country with >200 participants. RESULTS: Countries differed significantly in magnitude of pandemic-related pregnancy stress and pandemic-unrelated pregnancy-specific stress, and in prevalence of clinically significant anxiety and depression levels. A well-fitting common path model for the entire sample indicated that mood and anxiety disturbances were strongly predicted by pandemic-related and pregnancy-specific stress after accounting for maternal characteristics. The model was replicated in individual countries. CONCLUSIONS: Although pregnant women in high-income Western countries experienced different levels of stress resulting from the COVID-19 pandemic, stress is a strong, common predictor of anxiety and depressive symptoms in these individuals. The common model can be used to inform research and clinical interventions to protect against adverse consequences of prenatal maternal stress, anxiety, and depression for mothers and infants.

In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice.

Transplantation of B cells engineered ex vivo to secrete broadly neutralizing antibodies (bNAbs) has shown efficacy in disease models. However, clinical translation of this approach would require specialized medical centers, technically demanding protocols and major histocompatibility complex compatibility of donor cells and recipients. Here we report in vivo B cell engineering using two adeno-associated viral vectors, with one coding for Staphylococcus aureus Cas9 (saCas9) and the other for 3BNC117, an anti-HIV bNAb. After intravenously injecting the vectors into mice, we observe successful editing of B cells leading to memory retention and bNAb secretion at neutralizing titers of up to 6.8 µg ml-1. We observed minimal clustered regularly interspaced palindromic repeats (CRISPR)-Cas9 off-target cleavage as detected by unbiased CHANGE-sequencing analysis, whereas on-target cleavage in undesired tissues is reduced by expressing saCas9 from a B cell-specific promoter. In vivo B cell engineering to express therapeutic antibodies is a safe, potent and scalable method, which may be applicable not only to infectious diseases but also in the treatment of noncommunicable conditions, such as cancer and autoimmune disease.

Neural oscillations while remembering traumatic memories in post-traumatic stress disorder.

OBJECTIVE: The current study investigated the oscillatory brain activity of PTSD patients during directed and imaginal exposure to the traumatic memory using magnetoencephalography (MEG), in a paradigm resembling exposure therapy. METHODS: Brain activity of healthy trauma-exposed controls and PTSD participants was measured with MEG as they listened to individualized trauma narratives as well as to a neutral narrative and as they imagined the narrative in detail. Source localization analysis by frequency bands was conducted in order to map neural generators of oscillatory activity. RESULTS: Elicitation of traumatic memories resulted in a distinct neural pattern in PTSD patients compared to healthy trauma-exposed individuals. In response to trauma scripts PTSD patients showed increases in high-gamma band power in visual areas, increased frontal and temporal theta as well as prefrontal alpha and medial temporal beta power relative to neutral scripts. CONCLUSIONS: Results suggest that when recollecting and imagining traumatic memories PTSD patients attempt to engage control or inhibition mechanisms. However, these are either not successfully recruited or inefficient leading to heightened responses and recollection. SIGNIFICANCE: Investigating the oscillatory neural dynamics of PTSD patients can help us better understand the processes underlying trauma re-experiencing.

The association between epidural analgesia during labor and mother-infant bonding.

STUDY OBJECTIVE: This study was aimed to assess the association between the use of epidural analgesia during labor and mother-infant bonding. DESIGN: A cross-sectional study. SETTING: Maternity ward at Soroka University Medical Center during 2020. PATIENTS: Women who delivered a singleton live-born infant vaginally in their immediate post-partum period. INTERVENTIONS: Women completed questionnaires. 25 items post-partum bonding questionnaire (PBQ) to assess mother-infant bonding (A high score on the PBQ indicates impaired mother-infant bonding) and the Edinburgh postnatal depression scale (EPDS) questionnaire to assess risk for post-partum depression. MEASUREMENTS: The study used PBQ questionnaire and four sub-scales to assess mother-infant bonding and the EPDS questionnaire to assess risk for post- partum depression. Generalized linear regression models (gamma) were constructed to examine the association between epidural analgesia and mother-infant bonding total score and impaired bonding sub- scale, while adjusting for confounders Additional information such as pregnancy complications and sociodemographic data was drawn from women's medical records. MAIN RESULTS: A total of 234 women were included in the final analysis, of them 126 (53.8%) delivered with epidural analgesia. The total PBQ score was significantly lower among women who received epidural analgesia compared to women without epidural analgesia (7.6 vs. 10.2, p = 0.024), demonstrating a better mother -infant bonding. Using two multivariable linear regression models, controlling for confounders such as maternal age and educational status, epidural analgesia during labor was independently associated with a better mother -infant bonding total score and better impaired bonding sub-scale score (Beta coefficient-0.252, 95% CI -0.5; -0.006, p = 0.045 and Beta coefficient - 0.34, 95% CI -0.52; -0.08, p = 0.01 for mother-infant bonding total score and sub-scale score, respectively). No differences in post-partum depression risks were found between the groups (EDPS≥13, 5.7% vs. 13%, p = 0.058). CONCLUSION: Our study demonstrated better mother -infant bonding among women delivering with epidural analgesia.

Seizure phobia: A distinct psychiatric disorder among people with epilepsy.

OBJECTIVE: Epilepsy is characterized by unpredictable attacks. Hence, people with epilepsy (PWE) may develop anxious anticipation of upcoming seizures. Seizure phobia is an anxiety disorder wherein seizure anticipatory situations trigger fear, accompanied by avoidance behaviors. Research on seizure phobia among PWE is scarce. Therefore, we aimed to describe the diagnosis of seizure phobia and its association with demographic, psychiatric and neurological variables. METHODS: This is a cross-sectional study of adult PWE in a tertiary epilepsy outpatient clinic. Data were collected from semi-structured interviews, demographic questionnaires and medical records. Patients with and without seizure phobia were compared in terms of sociodemographic, psychiatric, and neurological variables. A logistic regression analysis was performed to identify variables that predicted seizure phobia. RESULTS: Among 69 PWE included in the study, 19 (27.5%) were diagnosed with seizure phobia. In comparison with PWE without seizure phobia, PWE with seizure phobia were predominantly female (84.2% vs 44.2%, p = 0.005), and had more comorbid anxiety disorders (84.2% vs 34.9%, p = 0.01), past major depressive episode (MDE) (63.2% vs 20.9%, p = 0.003), and post-traumatic stress disorder (26.3% vs 7%, p = 0.05). There was a significant association between seizure phobia and comorbid psychogenic non-epileptic seizures (36.8% vs 11.6%, p = 0.034). However, no significant association was found with epilepsy-related variables. A multivariate logistic regression model indicated anxiety and a past MDE as predictive factors for seizure phobia (R2 = 0.43). CONCLUSION: Seizure phobia is a distinct psychiatric entity among PWE. Further research is required to understand its etiology, risk factors, and potential interventions for these patients.

A Transgenic Model Reveals the Role of Klotho in Pancreatic Cancer Development and Paves the Way for New Klotho-Based Therapy.

Klotho is an anti-aging transmembrane protein, which can be shed and can function as a hormone. Accumulating data indicate that klotho is a tumor suppressor in a wide array of malignancies, and designate the subdomain KL1 as the active region of the protein towards this activity. We aimed to study the role of klotho as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Bioinformatics analyses of The Cancer Genome Atlas (TCGA) datasets revealed a correlation between the survival of PDAC patients, levels of klotho expression, and DNA methylation, and demonstrated a unique hypermethylation pattern of klotho in pancreatic tumors. The in vivo effects of klotho and KL1 were examined using three mouse models. Employing a novel genetic model, combining pancreatic klotho knockdown with a mutation in Kras, the lack of klotho contributed to PDAC generation and decreased mousece survival. In a xenograft model, administration of viral particles carrying sKL, a spliced klotho isoform containing the KL1 domain, inhibited pancreatic tumors. Lastly, treatment with soluble sKL prolonged survival of Pdx1-Cre; KrasG12D/+;Trp53R172H/+ (KPC) mice, a model known to recapitulate human PDAC. In conclusion, this study provides evidence that klotho is a tumor suppressor in PDAC. Furthermore, these data suggest that the levels of klotho expression and DNA methylation could have prognostic value in PDAC patients, and that administration of exogenous sKL may serve as a novel therapeutic strategy to treat PDAC.

Women's Depressive Symptoms during the COVID-19 Pandemic: The Role of Pregnancy.

The Coronavirus Disease 2019 (COVID-19) pandemic has multiple ramifications for pregnant women. Untreated depression during pregnancy may have long-term effects on the mother and offspring. Therefore, delineating the effects of pregnancy on the mental health of reproductive-age women is crucial. This study aims to determine the risk for depressive symptoms in pregnant and non-pregnant women during COVID-19, and to identify its bio-psycho-social contributors. A total of 1114 pregnant and 256 non-pregnant women were recruited via social media in May 2020 to complete an online survey that included depression and anxiety questionnaires, as well as demographic, obstetric and COVID-19-related questionnaires. Pregnant women also completed the Pandemic-Related Pregnancy Stress Scale (PREPS). Pregnant women reported fewer depressive symptoms and were less concerned that they had COVID-19 than non-pregnant women. Among pregnant women, risk factors for depression included lower income, fewer children, unemployment, thinking that one has COVID-19, high-risk pregnancy, earlier gestational age, and increased pregnancy-related stress. Protective factors included increased partner support, healthy behaviors, and positive appraisal of the pregnancy. Thus, being pregnant is associated with reduced risk for depressive symptoms during the pandemic. Increased social support, engaging in health behaviors and positive appraisal may enhance resilience. Future studies of pregnant versus non-pregnant women could clarify the role of pregnancy during stressful events, and clarify aspects of susceptibility and resilience during pregnancy.

The impact of childhood trauma on psychological interventions for depression during pregnancy and postpartum: a systematic review.

Women who have experienced childhood trauma (CT) are at increased risk for depression during pregnancy and postpartum, pregnancy complications, and adverse child outcomes. There are effective psychotherapeutic interventions to treat depression during pregnancy and postpartum, yet there is a paucity of literature on the impact of CT on treatment outcomes. This review aims to determine whether and how maternal CT history affects the outcomes of psychological interventions for depression during pregnancy and postpartum. PubMed, PsycINFO, and Cochrane Library searches were conducted to identify papers on psychological interventions designed to treat depression during pregnancy and postpartum in women with CT. Seven manuscripts, describing six studies, met the inclusion criteria (N = 1234). Three studies utilized core principles of interpersonal psychotherapy (IPT). Two studies investigated interventions based on cognitive behavioral therapy (CBT). One study was based on a psychoeducation component. Results suggest that IPT-based interventions are beneficial for women with CT. The evidence regarding CBT-based interventions is less conclusive. This review is written in light of the paucity of research addressing the question systematically. The Childhood Trauma Questionnaire (CTQ) was the main measure used to assess CT. Trauma related to accidents, illness, and political violence was not included. The results are only applicable to interventions based on either IPT or CBT and cannot be generalized to other forms of psychotherapy. Psychotherapeutic interventions are beneficial for depressed women with history of CT during pregnancy and postpartum; however, further systematic research is needed.

Trait-related changes in brain network topology in premenstrual dysphoric disorder.

The female predominance in the prevalence of depression is partially accounted by reactivity to hormonal fluctuations. Premenstrual dysphoric disorder (PMDD) is a reproductive subtype of depression characterized by cyclic emotional and somatic symptoms that recur before menstruation. Despite the growing understanding that most psychiatric disorders arise from dysfunctions in distributed brain circuits, the brain's functional connectome and its network properties of segregation and integration were not investigated in PMDD. To this end, we examined the brain's functional network organization in PMDD using graph theoretical analysis. 24 drug naïve women with PMDD and 27 controls without premenstrual symptoms underwent 2 resting-state fMRI scans, during the mid-follicular and late-luteal menstrual cycle phases. Functional connectivity MRI, graph theory metrics, and levels of sex hormones were computed during each menstrual phase. Altered network topology was found in PMDD across symptomatic and remitted stages in major graph metrics (characteristic path length, clustering coefficient, transitivity, local and global efficiency, centrality), indicating decreased functional network segregation and increased functional network integration. In addition, PMDD patients exhibited hypoconnectivity of the anterior temporal lobe and hyperconnectivity of the basal ganglia and thalamus, across menstrual phases. Furthermore, the relationship between difficulties in emotion regulation and PMDD was mediated by specific patterns of functional connectivity, including connections of the striatum, thalamus, and prefrontal cortex. The shifts in the functional connectome and its topology in PMDD may suggest trait vulnerability markers of the disorder.

Sex differences during emotion processing are dependent on the menstrual cycle phase.

Sex differences in the neural processing of emotion are of special interest considering that mood and anxiety disorders predominant in females. However, these sex-related differences were typically studied without considering the hormonal status of female subjects, although emotion processing in the brain was shown to differ between phases of the menstrual cycle. In this functional MRI study, we demonstrated the influence of the menstrual cycle phase on sex differences in brain activity and functional connectivity during negative and positive emotions, using two different paradigms: emotion perception and emotion experience. Twenty naturally cycling healthy women without premenstrual symptoms were scanned twice: during the mid-follicular and late-luteal menstrual phases, and compared to a matched group of twenty healthy men. During negative emotion perception, men showed increased neural activity in the right hippocampal formation relative to women in the mid-follicular phase, and increased activity in the right cerebellum relative to women in the late-luteal phase. During experience of amusement, reduced putamen-ventrolateral prefrontal cortex and putamen-dorsomedial prefrontal cortex functional connectivity were observed for women in the late-luteal phase relative to men and associated with levels of sex hormones. These neural and hormonal findings were complemented by behavioral reports of reduced amusement and increased sadness in late-luteal women. Our results demonstrate menstrual phase-dependent sex differences in emotion perception and experience and may suggest a biological tendency for a deficient experience of pleasure and reward during the late-luteal phase. These findings may further shed light on the underlying pathophysiology of premenstrual dysphoric disorder.