Cariprazine in the acute treatment of unipolar and bipolar depression: A systematic review and meta-analysis.

BACKGROUND: Cariprazine has emerged as a promising augmenting treatment agent for unipolar depression and as a monotherapy option for bipolar depression. We evaluated cariprazine's efficacy in treating acute major depressive episodes in individuals with major depressive disorder (MDD) or bipolar disorder. METHODS: A systematic review was conducted on MEDLINE, Embase, PyscInfo, Scopus and Web of Science, ClinicalTrials.gov and ScanMedicine. Study quality was assessed using the RoB 2 tool. Pairwise and dose-response meta-analyses were conducted with RStudio. Evidence quality was assessed with GRADE. RESULTS: Nine RCTs meeting inclusion criteria encompassed 4877 participants. Cariprazine, compared to placebo, significantly reduced the MADRS score (MD = -1.49, 95 % CI: -2.22 to -0.76) and demonstrated significantly higher response (RR = 1.21, 95 % CI: 1.12 to 1.30) and remission (RR = 1.19, 95 % CI: 1.06 to 1.34) rates. Subgroup analysis unveiled statistically significant reductions in MADRS score in MDD (MD = -1.15, 95 % CI: -2.04 to -0.26) and bipolar I disorder (BDI) (MD = -2.53, 95 % CI: -3.61 to -1.45), higher response rates for both MDD (RR = 1.19, 95 % CI: 1.08 to 1.31) and BDI (RR = 1.27, 95 % CI: 1.10 to 1.46), and higher remission rates only for BDI (RR = 1.41, 95 % CI: 1.24 to 1.60). A higher rate of treatment discontinuation due to adverse events was observed. LIMITATIONS: Reliance solely on RCTs limits generalisability; strict criteria might not reflect real-world diversity. CONCLUSIONS: Cariprazine demonstrates efficacy in treating major depressive episodes, although variations exist between MDD and BDI and tolerability may be an issue.

The role of lack of grandparental support in perinatal depression.

BACKGROUND: Low social support has been identified as a risk factor for perinatal mental health problems. However, previous studies mainly focused on partner support or general social support and neglected the roles of grandparents. Here, we examine whether a lack of grandparental support is related to increased risk of a diagnosis of perinatal depression. In addition, we examine whether poor grandparental support is related to more depressive symptoms in mothers with and without previously diagnosed perinatal depression and whether perceived grandparental support buffers against parenting difficulties in mothers with perinatal depression. METHODS: The sample was drawn from an Australian pregnancy cohort study and consisted of 725 women, including 230 women who met criteria for Major Depression. At 12 months postpartum, women reported on grandparental geographical proximity and hours of grandparental childcare support. Perceived grandparental support was assessed with the Postpartum Social Support Questionnaire and parenting difficulties and depressive symptoms with the Parenting Stress Index and the Edinburgh Postnatal Depression Scale. RESULTS: Perceived grandparental support was related to fewer depressive symptoms among mothers with perinatal depression. In addition, higher levels of perceived grandparental support were related to lower parenting stress in mothers with and without perinatal depression. LIMITATIONS: Intergenerational conflicts and quality of grandparenting were not assessed. CONCLUSIONS: Our findings indicate that supportive grandparents may prevent the development of more severe perinatal depression in mothers experiencing perinatal mental health problems. Future studies should examine whether involving grandparents in treatment may add to the effectiveness of existing perinatal mental health interventions.

Airway and Anaesthetic Management of Adult Patients with Mucopolysaccharidoses Undergoing Cardiac Surgery.

Background: Mucopolysaccharidoses (MPSs) are rare congenital lysosomal storage disorders due to a deficiency of enzymes metabolising glycosaminoglycans, leading to their accumulation in tissues. This multisystem disease often requires surgical intervention, including valvular cardiac surgery. Adult MPSs have complex airways making anaesthesia risky. Methods: We report novel three-dimensional (3D) modelling airway assessments and multidisciplinary peri-operative airway management. Results: Five MPS adults underwent cardiac surgery at the national MPS cardiac centre (type I = 4, type II = 1; ages 20, 24, 33, 35, 37 years; two males, three females). All had complex airway abnormalities. Assessments involved examination, nasendoscopy, imaging, functional studies, 3D reconstruction, virtual endoscopy, virtual reality and simulation using computerised, physical modelling. Awake oral fibre-optic intubation was achieved via airway conduit. Staged extubation was performed on the first post-operative day under laryngo-tracheoscopic guidance. The post-operative period involved chest physiotherapy and occupational therapy. All patients had safe intubation, ventilation and extubation. Four had good cardiac surgical outcomes, one (MPS type I; age 35 years) was inoperable due to endocarditis. None had post-operative airway complications. Conclusions: Expertise from cardiovascular-heart team, multidisciplinary airway management, use of novel techniques is vital. Traditional airway assessments are insufficient, so ENT input, radiology and computerised methods to assess and simulate the airway in 3D by collaboration with clinical engineering is essential.

Intimate partner violence across pregnancy and the postpartum and the relationship to depression and perinatal wellbeing: findings from a pregnancy cohort study.

PURPOSE: To compare the prevalence of emotional and physical intimate partner violence (IPV) across pregnancy and the first year postpartum in those with and without clinical depression and assess the association between maternal childhood trauma, current stressful life events and depression and IPV over the perinatal period. METHODS: Data were obtained from 505 pregnant women from the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a cohort study with data collected across pregnancy until 12 months postpartum. Maternal antenatal depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) with repeat measurement of perinatal depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS). Trauma was measured using the Childhood Trauma Questionnaire, and experiences of physical and emotional intimate partner violence using items in the Stressful Life Events Scale. RESULTS: Women experiencing IPV across the perinatal period were significantly more likely to score over 13 on the EPDS (p < .001) at each timepoint in pregnancy and the postpartum and physical IPV was associated with clinical depression. Further, a history of childhood trauma and current additional stressful life events were significantly associated with reporting current IPV in the perinatal period. CONCLUSIONS: This study confirmed the risk factors of childhood trauma and current stressful life events for reporting experiences of IPV in the perinatal period. Furthermore, women experiencing IPV reported higher depressive symptoms, providing evidence supporting the value of assessing those women who screen higher on the EPDS for IPV. Together these findings also support trauma informed care across pregnancy and the postpartum.

The role of parental divorce in the later vulnerability to perinatal depression and early parenting stress.

OBJECTIVE: This study will examine the role of childhood experience of parental divorce on later perinatal depression and parenting stress. METHODS: 546 women were recruited at less than 20 weeks pregnancy into an ongoing pregnancy cohort study and followed up in pregnancy and the postpartum. Depression at recruitment was measured using the Structured Clinical Interview for the DSM and the Edinburgh Postnatal Depression Scale repeated in pregnancy and the postpartum. Parenting stress was measured at 12 months postpartum using Parenting Stress Index. RESULTS: This study found 33% of women had experienced parental divorce. While we did not find a statistically significant relationship between the experience of parental divorce and perinatal depression, there was a higher rate of perinatal depression when parental divorce occured at a younger age. There was no association with parental divorce and parenting stress. Childhood divorce was significantly associated with other adverse childhood experiences. CONCLUSIONS: Our findings did not support an impact of parental divorce on either maternal perinatal depression or on parenting stress, suggesting the experience of parental divorce for children may not inevitably impact their later experiences as parents. Further research on the association with age of parental divorce and later perinatal mental health is warranted.

The Relationship Between Early Term Birth and the Risk of Later Childhood Mental Disorders Within a Pregnancy Cohort.

This study examines whether gestational age, birth weight, and early term birth is associated with childhood mental disorders in 342 pregnant women recruited at less than 20 weeks gestation and were then followed up until 4 years postpartum, including 93 children born at early term. Women were assessed at recruitment using the Structured Clinical Interview for DSM. At 4 years of age their children were assessed using the Preschool Age Psychiatric Assessment (PAPA) and the Child Behavior Checklist (CBCL). This study found earlier birth predicted an increased risk for anxiety disorders and demonstrated a significant interaction between gestational age and lower birthweight. The risk for ADHD increased with lower gestational age independent of birthweight. In contrast, gestational age was not associated with Oppositional Defiant Disorder, Conduct Disorder, internalizing or externalizing symptoms. These findings highlight the important differences in the association of early term birth and vulnerability for specific mental disorders.

Perinatal depression: The use of the Edinburgh Postnatal Depression Scale to derive clinical subtypes.

BACKGROUND: Predicting the course and complications of perinatal depression through the identification of clinical subtypes has been previously undertaken using the Edinburgh Postnatal Depression Scale and has the potential to improve the precision of care and improve outcomes for women and their children. METHODS: Edinburgh Postnatal Depression Scale scores were collected twice in pregnancy and twice in the postpartum in a sample of 360 women who met diagnostic criteria for perinatal depression using the Structured Clinical Interview for DSM disorder. These data were used to compare with previous, though conflicting, evidence from cross-sectional studies and extend this by undertaking longitudinal measurement invariance modelling to test the structural validity across the perinatal period. Latent profile and transition modelling was used to identify distinct subtypes of women and assess the utility of these subtypes and transition profiles to predict clinically meaningful outcomes. RESULTS: Although our data supported one of the previously reported three-factor Edinburgh Postnatal Depression Scale structures used to compute subfactor totals for depressed mood, anxiety and anhedonia at both early pregnancy and 6 months postpartum, there was little value in using these Edinburgh Postnatal Depression Scale subfactor scores to identify subtypes predictive of clinically meaningful postpartum symptom subtypes, or of general health, pregnancy and neonatal outcomes. CONCLUSION: Our study does not support the use of the Edinburgh Postnatal Depression Scale to distinguish perinatal depressive subtypes for the purposes of predicting course and complications associated with perinatal depression. However, the results give guidance on alternative ways to study the value of personalised management in improved outcomes for women living with or at risk for perinatal depression.

Ghana 3D Telemedicine International MDT: A proof-of-concept study.

A real-time 3D Telemedicine system - leveraging Microsoft's Holoportation™ communication technology - enabled an international multidisciplinary team meeting (MDT) to consult with complex reconstructive patients before, during, and after an overseas surgical collaboration. METHODS: A proof-of-concept international 3D MDT clinic took place in November 2022, between the Canniesburn Plastic Surgery Unit, UK, and the National Reconstructive Plastic Surgery and Burns Centre, Korle Bu Teaching Hospital, Ghana. The 3D system was utilised 1) previsit to assess patients and enable logistical planning, 2) on-site in Ghana to further allow patients to see themselves and proposed operations in 3D, and 3) post visit to debrief the team and patients. RESULTS: Four Ghana patients were followed through their patient journey (mandibular ameloblastoma, sarcoma thigh, maxillary tumour, sarcoma back). Thirteen participants (four patients, four Ghana clinicians, and five UK clinicians) completed feedback on the 3D MDT. Outcome measures were rated highly with satisfaction 84.31/100, perceived benefit 4.54/5, overall quality 127.3/147 (Telehealth Usability Questionnaire), and usability 83.2/100 (System Usability Scale). These data show close alignment with that previously published on high-income countries. CONCLUSIONS: This novel technology has the potential to enhance the delivery of overseas surgical visits to low-to-middle-income countries, by improving planning, informed discussion with patients, expert consensus on complex cases, and fostering engagement with professionals who may be thousands of miles away. This is the first demonstration that real-time 3D Telemedicine can both work, and enhance care within an international MDT clinic, and may thus enable change in the approach to overseas surgical collaborations.

Patient evaluation of gynaecological information provision and preferences.

AIM: To evaluate gynaecological patients' preferences and satisfaction regarding information provision, exploring enablers and barriers to information access. DESIGN: A descriptive cross-sectional survey design was used. METHODS: A total of 293 women accessing gynaecological services responded to the survey. Quantitative analysis included descriptive and inferential statistics. Content analysis was conducted on qualitative data. RESULTS: Health professionals were the most common and preferred sources of gynaecological health information. Enablers to information provision included positive communication strategies by health professionals, participants having prior knowledge and doing their own research. Despite its widespread availability, only 24.2% of women preferred the internet as an information source. Poor communication and inadequate information provision were identified as barriers to information access. Statistically significant associations were identified between location of residence, education level, year of birth, diagnostic group and health information preferences. Recommendations from women included improved communication strategies, system changes and provision of individualized information. CONCLUSION: Health professionals are central to women accessing information about gynaecological diagnoses. Areas for improvement include communication strategies, facilitating access to internet-based resources for information and consideration of women's preferences when providing health information. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Consumer co-design of gynaecological health information and communication training for health professionals is recommended. Improved communication and facilitated use of internet-based resources may improve women's understanding of information. IMPACT: This study explored gynaecological patients' preferences and satisfaction regarding information provision, exploring enablers and barriers to information access. It was found that gynaecological patients preferred individualized information provided to them directly by health professionals and despite its widespread availability, the internet is an underutilized health information resource. These findings are applicable to health professionals and patients utilizing tertiary gynaecological health services in Australia but may be generalized if demographic data aligns with other jurisdictions. REPORTING METHOD: The STROBE reporting method was used in the preparation of the manuscript. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Outcomes for pregnant women with Borderline Personality Disorder who attended a specialist antenatal service.

OBJECTIVE: Our study focussed on the obstetric and psychosocial outcomes of pregnant women with Borderline Personality Disorder (BPD) who received care via a specialist antenatal clinic in Western Australia. METHOD: This study is a retrospective examination of outcomes for 80 women with a confirmed diagnosis of BPD, with findings compared with published population outcome data for the state. RESULTS: Pregnant women with BPD appeared to be at a risk of complications including pre-eclampsia and special care nursery admission for their newborns when compared to population data. Furthermore, the studied women had elevated rates of psychiatric admissions during pregnancy, child protection involvement, and domestic violence. Polypharmacy exposure was frequent, with the likely impact on obstetric and neonatal outcomes requiring further study. CONCLUSION: The findings reinforced the notion that pregnant women with BPD experience complex multifaceted vulnerabilities and require enhanced multidisciplinary care. Our study further calls for the development of clinical practice guidelines for managing BPD in the perinatal period.

The trajectory of maternal perinatal depressive symptoms predicts executive function in early childhood.

BACKGROUND: Perinatal maternal depression may affect fetal neurodevelopment directly or indirectly via exposures such as smoking, alcohol, or antidepressant use. The relative contribution of these risk factors on child executive function (EF) has not been explored systematically. METHODS: A prospective pregnancy cohort of 197 women and their children was studied to determine whether maternal depression diagnosis and the trajectory of maternal depressive symptoms (MDSs) from early pregnancy to 12 months postpartum predicts child EF at age 4 (measured using the preschool age psychiatric assessment, NEPSY-II, and Shape School task) using latent growth curve modeling. Indirect effects of smoking, alcohol, and antidepressant use were also formally tested. RESULTS: Increasing maternal perinatal depressive symptoms over time predicted more inattentive symptoms, poorer switching, and motor inhibition, but not cognitive inhibition. When adjusted for multiple comparison, and after accounting for maternal cognition and education, the association with child inattentive symptoms remained significant. However, diagnosed depression did not predict child EF outcomes. Prenatal exposure to smoking, alcohol, and antidepressants also did not mediate pathways from depressive symptoms to EF outcomes. Our findings were limited by sample size and statistical power to detect outcome effects of smaller effect size. CONCLUSIONS: This study suggests that increasing MDSs over the perinatal period is associated with poorer EF outcomes in children at age 4 - independent of prenatal smoking, drinking, or antidepressant use. Depressive chronicity, severity, and postpartum influences may play crucial roles in determining childhood outcomes of EF.

Depression in Sjögren's syndrome mediates the relationship between pain, fatigue, sleepiness, and overall quality of life.

Objectives: Sjögren's syndrome (SS) includes many extra-glandular symptoms such as fatigue, pain, sleepiness and depression, which impact on quality of life (QoL). These symptoms also influence each other and could be linked by autonomic nervous system (ANS) dysregulation. Our aim was to model the role of putative predictive variables, including depression in the relationships between ANS function, fatigue, and QoL in SS. Methods: Cross-sectional analysis of self-reported data from the multicentre UK primary SS registry. The Composite Autonomic Symptom Scale (COMPASS) was used to assess autonomic function, the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression and the EuroQol-5 Dimension (EQ-5D) to assess QoL. Validated scales were used for other clinical variables. Using multiple regression analysis and structural equation modelling (SEM), we investigated how the QoL of people with SS is impacted by the direct and indirect effects of fatigue, sleepiness, depression, symptom burden and ANS function, and their interactions. Results: Data was obtained for 1046 people with SS, 56% COMPASS completers. Symptoms of ANS dysregulation were common. Participants with ANS dysregulation had more severe depression, anxiety, dryness, fatigue, pain, sleepiness and QoL (P < 0.01 for all). Depression, anxiety, dryness, and pain were independent predictors of ANS function in the multiple regression model (P < 0.05 for all). ANS function could not be included in the SEM. The SEM model had good fit to the data (comparative fit index = 0.998) and showed that, in people with SS, depression mediates the effects of pain, fatigue and sleepiness on QoL. Conclusion: Our results show that diagnosing and treating depression in people with SS could have direct positive impact on QoL, and significantly ameliorate the impact of fatigue and pain.

Effect of differing flap reconstruction strategies in perineal closure following advanced pelvic oncological resection: a retrospective cohort study.

INTRODUCTION: Advancing approaches to locally invasive pelvic malignancy creates a large tissue defect resulting in perineal wound complications, dehiscence, and perineal hernia. Use of reconstructive flaps such as vertical rectus abdominus myocutaneous (VRAM) flap, gracilis, anterolateral thigh and gluteal flaps have been utilised in our institution to address perineal closure. The authors compared outcomes using different flap techniques along with primary perineal closure in advanced pelvic oncological resection. METHODS: A prospectively maintained database of patients undergoing advanced pelvic oncological resection in a single tertiary hospital was retrospectively analysed. This study included consecutive patients between 2014 and 2021 according to the Strengthening The Reporting of Cohort Studies in Surgery (STROCSS) criteria. Primary outcome measures were the frequency of postoperative perineal complications between primary closure, VRAM, gluteal and thigh (anterolateral thigh and gracilis) reconstruction. RESULTS: One hundred twenty-two patients underwent advanced pelvic resection with perineal closure. Of these, 40 patients underwent extra-levator abdominoperineal resection, and 70 patients underwent pelvic exenteration. Sixty-four patients received reconstructive flap closure, which included VRAM (22), gluteal (21) and thigh flaps (19). Perineal infection and dehiscence rates were low. Infection rates were lower in the flap group despite a higher rate of radiotherapy ( P <0.050). Reoperation rates were infrequent (<10%) but specific for each flap, such as donor-site hernia following VRAM and flap dehiscence after thigh flap reconstruction. CONCLUSIONS: In patients who are at high risk of postoperative perineal infections, reconstructive flap closure offers acceptable outcomes. VRAM, gluteal and thigh flaps offer comparable outcomes and can be tailored to the individual patient.

Fetal SSRI antidepressant exposure and infant sleep: Findings from the MPEWS pregnancy cohort study.

This longitudinal study examines the association between fetal Selective Serotonergic Reuptake Inhibitor antidepressant exposure and infant sleep behaviours at six and 12 months of age and focus on three of the most commonly prescribed antidepressants in pregnancy. This study utilises data on 698 women recruited at less than 20 weeks of pregnancy and are followed up at six and 12 months postpartum. Women were recruited into one of three groups: those taking either sertraline, citalopram or escitalopram antidepressants in pregnancy (n = 85); women with a depressive disorder who were not taking antidepressants (non-medicated depressed, NMD; n = 82); and, and a control group of women (n = 531). At six and 12 months, data were collected on breastfeeding and sleep location and infant sleep was measured using the Brief Infant Sleep Questionnaire. Antidepressants sertraline, escitalopram and citalopram were not associated with increased infant waking or time awake. However, sertraline was associated with longer time for an infant to go to sleep. This study provides reassurance that SSRI antidepressants and, in particular, sertraline, escitalopram and citalopram are not associated with infant sleep behaviours that are commonly regarded as problematic including night waking. Further replication of these findings, including with direct measures of infant sleep, are recommended.

Cognitive constraints on vocal combinatoriality in a social bird.

A critical component of language is the ability to recombine sounds into larger structures. Although animals also reuse sound elements across call combinations to generate meaning, examples are generally limited to pairs of distinct elements, even when repertoires contain sufficient sounds to generate hundreds of combinations. This combinatoriality might be constrained by the perceptual-cognitive demands of disambiguating between complex sound sequences that share elements. We test this hypothesis by probing the capacity of chestnut-crowned babblers to process combinations of two versus three distinct acoustic elements. We found babblers responded quicker and for longer toward playbacks of recombined versus familiar bi-element sequences, but no evidence of differential responses toward playbacks of recombined versus familiar tri-element sequences, suggesting a cognitively prohibitive jump in processing demands. We propose that overcoming constraints in the ability to process increasingly complex combinatorial signals was necessary for the productive combinatoriality that is characteristic of language to emerge.

A survey of Australian midwives: Experts in nitrous oxide administration within the peripartum setting.

PROBLEM: There is little documented evidence of midwives' perspectives regarding the use of nitrous oxide in the peripartum period. BACKGROUND: Nitrous oxide is an inhaled gas used widely in the peripartum period; usually offered and managed by midwives. AIM: Explore midwives' knowledge, perceptions, and practices of facilitating women's use of nitrous oxide in the peripartum period. METHODS: An exploratory cross-sectional survey design was used. Quantitative data were analysed using descriptive and inferential statistics; open-ended responses underwent template analysis. FINDINGS: Midwives (n = 121) working in three Australian settings reported regularly recommending the use of nitrous oxide and high levels of knowledge and confidence supporting its use. There was a significant association between midwifery experience, and perspectives on women's capacity to use nitrous effectively (p = 0.004); and desire for refresher education (p < 0.001). Midwives working in continuity models were more likely to support women using nitrous oxide in any situation (p = 0.039). DISCUSSION: Midwives demonstrated expertise in facilitating nitrous oxide use, citing utility to relieve anxiety and distract women from pain or discomfort. Nitrous oxide was identified as an important adjunct to the provision of supportive care requiring midwifery therapeutic presence. CONCLUSION: This study provides novel insight into midwives' support of nitrous oxide use in the peripartum setting revealing high levels of knowledge and confidence. Recognition of this unique expertise held by midwives is important to ensure transfer and development of professional knowledge and skills and emphasises the need for midwifery leadership in clinical service provision, planning and policy.

Autonomic dysregulation, cognition and fatigue in people with depression and in active and healthy controls: observational cohort study.

BACKGROUND: Autonomic nervous system (ANS) dysregulation might be relevant to the pathophysiology of fatigue and cognitive impairment in depression and perhaps should be considered when making prescribing decisions. AIMS: To determine the relationship of self-reported ANS symptoms with fatigue, cognition and prescribed medication in people with a diagnosis of depression, in comparators without depression but with other mental health, neurodevelopmental or neurodegenerative disorders (active controls) and in healthy controls. METHOD: Cross-sectional analysis of an opportunistic sample from England. Self-reported data were collected on demographics, diagnosis, medication, ANS symptoms (Composite Autonomic Symptom Scale-31, COMPASS-31) and fatigue (Visual Analogue Scale for Fatigue, VAS-F). A subsample completed cognitive tests (THINC-it), including the subjective Perceived Deficits Questionnaire five-item version (PDQ-5). Spearman's correlation and mediation models were used to explore the relationship between COMPASS-31, VAS-F and PDQ-5 scores. RESULTS: Data were obtained for 3345 participants, 22% with depression. The depression group had significantly (P < 0.01) more severe autonomic dysregulation as measured by COMPASS-31 scores (median 30) than active (median 23) and healthy controls (median 10). The depression group had significantly higher symptom severity (P < 0.01) than both control groups on the VAS-F and PDQ-5. Overall, there was a significantly positive correlation (P < 0.01) between COMPASS-31, VAS-F scores (Spearman's rho rs = 0.44) and PDQ-5 scores (rs = 0.56). COMPASS-31 scores mediated greater symptom severity on the VAS-F and PDQ-5 for those with depression. COMPASS-31 scores remained significantly different between the depression group and both control groups independently of medication. CONCLUSIONS: People with a diagnosis of depression report worse fatigue and cognition than active and healthy comparators; this appears to be mediated by ANS dysregulation.

The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome.

OBJECTIVES: Fatigue is one of the most important symptoms needing improvement in Primary Sjögren's syndrome (PSS). Previous data from our group suggest that noninvasive stimulation of the vagus nerve (nVNS) may improve symptoms of fatigue. This experimental medicine study uses the gammaCore device (electroCore) and a sham device to investigate the relationship between nVNS and fatigue in PSS, and to explore potential mechanisms involved. MATERIALS AND METHODS: Forty participants with PSS were randomly assigned to use active (n = 20) or sham (n = 20) nVNS devices twice daily for 54 days in a double-blind manner. Patient-reported measures of fatigue were collected at baseline and day 56: Profile of Fatigue (PRO-F)-Physical, PRO-F-Mental and Visual Analogue Scale of abnormal fatigue (fVAS). Neurocognitive tests, immunologic responses, electroencephalography alpha reactivity, muscle acidosis, and heart rate variability were compared between devices from baseline to day 56 using analysis of covariance. RESULTS: PRO-F-Physical, PRO-F-Mental, and fVAS scores were significantly reduced at day 56 in the active group only (p = 0.02, 0.02, and 0.04, respectively). Muscle bioenergetics and heart rate variability showed no change between arms. There were significant improvements in digit span and a neurocognitive test (p = 0.03), and upon acute nVNS stimulation, frontal region alpha reactivity showed a significant negative relationship with fatigue scores in the active group (p < 0.01). CONCLUSIONS: We observed significant improvements in three measures of fatigue at day 56 with the active device but not the sham device. Directly after device use, fatigue levels correlate with measures of alpha reactivity, suggesting modulation of cholinergic system integrity as a mechanism of action for nVNS.

Maternal attachment state of mind and perinatal emotional wellbeing: Findings from a pregnancy cohort study.

OBJECTIVES: Maternal attachment state of mind is an important potential predictor of risk and resilience to perinatal emotional wellbeing and early parenting. To explore maternal attachment in relation to perinatal depression and emotional wellbeing. METHODS: This study drew on data collected within an ongoing cohort from 170 women recruited in early pregnancy, including 67 who met criteria for Major Depression. Maternal attachment state of mind was assessed with the Adult Attachment Interview (AAI) in pregnancy. Additional measures included the Structured Clinical Interview for the DSM (SCID), at 12 months the Strange Situation Procedure (SSP), Child Trauma Questionnaire (CTQ), Parenting Stress Index, and antenatal maternal hair cortisol concentrations (HCC). LIMITATIONS: Sample size to be able to undertake all analyses using the 4 way classifications, cortisol measurement is limited to hair only and there is no prospectively collected measure of childhood trauma in mothers. CONCLUSIONS: This study found that maternal attachment, specifically the Non-Autonomous states of mind, adjusted for clinical depression, was associated with higher cortisol in pregnancy and higher depressive symptoms across pregnancy and the postpartum. Furthermore, separately those with depression and Non-Autonomous states of mind also had higher postpartum parenting stress. There was no significant intergenerational concordance between AAI and SSP attachment classifications. Our findings support future research exploring the role of maternal attachment state of mind in understanding perinatal depression and emotional wellbeing.