Stable neural underpinnings of emotional cognition subgroups in patients newly diagnosed with bipolar disorder: A prospective fMRI study.

OBJECTIVES: This study aimed to investigate the neural underpinnings of emotional cognition subgroups in recently diagnosed patients with bipolar disorder (BD) and change over time over a 15-month follow-up period. METHODS: Patients and healthy controls (HC) underwent emotional and nonemotional cognitive assessments and functional magnetic resonance imaging (fMRI) at the baseline (BD n = 87; HC n = 65) and at 15-month follow-up (BD n = 44; HC n = 38). Neural activity during emotion reactivity and regulation in response to aversive pictures was assessed during fMRI. Patients were clustered into subgroups based on their emotional cognition and, with HC, were compared longitudinally on cognition and neural activity during emotion reactivity and regulation. RESULTS: Patients were optimally clustered into two subgroups: Subgroup 1 (n = 40, 46%) was characterized by heightened emotional reactivity in negative social scenarios, which persisted over time, but were otherwise cognitively intact. This subgroup exhibited stable left amygdala hyper-activity over time during emotion reactivity compared to subgroup 2. Subgroup 2 (n = 47, 54%) was characterized by global emotional cognitive impairments, including stable difficulties with emotion regulation over time. During emotion regulation across both time points, this group exhibited hypo-activity in the left dorsolateral prefrontal cortex. Additionally, patients in subgroup 2 had poorer nonemotional cognition, had more psychiatric hospital admissions and history of psychotic episodes than those in subgroup 1. CONCLUSIONS: Broad impairments in emotional cognition in approximately half of BD patients and associated nonemotional cognitive deficits may originate from insufficient recruitment of prefrontal resources, contributing to poorer clinical outcomes.

Affective cognition in response to infant stimuli in pregnant compared with non-pregnant women.

Physiological, neurocognitive, and psychological changes facilitates adaptation to motherhood. This cross-sectional study aimed to examine differences between pregnant and non-pregnant women in affective cognitive and psychophysiological responses to infant stimuli. We hypothesized that pregnant women would display (I) reduced negative emotional reactivity and perception of distressed infant stimuli, (II) increased attention toward infants compared to adults, and (III) greater psychophysiological response to infant distress. The sample comprised 22 pregnant women (22-38 weeks gestation) and 18 non-pregnant nulliparous women. Four computerized tasks were administered to measure affective cognitive processing of infant stimuli, while recording facial expressions, electrodermal activity, and eye gazes. Results indicated that pregnant women exhibited fewer negative facial expressions, reported less frustration when exposed to distressed infant cries, and showed greater attention to emotional infant faces compared to non-pregnant women, but the differences did not remain statistically significant after correction for multiple comparisons. No differences were observed in psychophysiological responses. The findings indicate a possible pregnancy-mediated effect regarding the cognitive processing of infant stimuli, potentially as preparation for motherhood. Future research with larger samples and longitudinal design is needed to understand the predictors, timing, and plasticity of cognitive changes during pregnancy.

Prediction of postpartum depression with an online neurocognitive risk screening tool for pregnant women.

Postpartum depression (PPD) is a severe mental illness affecting 10-15% of mothers. Emerging evidence indicates that negative neurocognitive bias in response to infant distress during pregnancy marks an increased risk of PPD. This proof-of-concept study aimed to investigate the association between negatively biased neurocognitive processing of infant distress during pregnancy and subsequent PPD and to explore the feasibility of an online risk screening tool. In the second or third trimester of pregnancy, 87 participants underwent two online tests of reactivity to and evaluation of infant distress and completed questionnaires regarding psychosocial risk factors. After birth, participants rated their depressive symptoms online and underwent a diagnostic telephone interview concerning PPD. Irrespective of depressive symptoms during pregnancy, negative reactivity to and evaluation of infant distress predicted PPD (reactivity: Exp(B)=1.33, p = 0.04) and depressive symptoms after birth (reactivity: B = 0.04, p = 0.048; evaluation: B = 0.10, p = 0.04). The negative reactivity toward infant distress showed high sensitivity and moderate specificity (89% and 77%, respectively), while the evaluation of infant distressed cries showed lower sensitivity and specificity (67% and 66%, respectively). The relatively small sample size prevented the inclusion of additional risk variables in the regression models. The replication of an association between negative neurocognitive bias during pregnancy with PPD risk is noteworthy and has clinical implications in terms of early prevention. However, the low response rate indicates that this tool is not feasible in its current form. Future larger-scale studies are needed to further investigate candidate risk factors in a brief online screening tool.

Short-term oestrogen as a strategy to prevent postpartum depression in high-risk women: protocol for the double-blind, randomised, placebo-controlled MAMA clinical trial.

INTRODUCTION: Postpartum depression affects 10%-15% of women and has a recurrence rate of 40% in subsequent pregnancies. Women who develop postpartum depression are suspected to be more sensitive to the rapid and large fluctuations in sex steroid hormones, particularly estradiol, during pregnancy and postpartum. This trial aims to evaluate the preventive effect of 3 weeks transdermal estradiol treatment immediately postpartum on depressive episodes in women at high risk for developing postpartum depression. METHODS AND ANALYSIS: The Maternal Mental Health Trial is a double-blind, randomised and placebo-controlled clinical trial. The trial involves three departments of obstetrics organised under Copenhagen University Hospital in Denmark. Women who are singleton pregnant with a history of perinatal depression are eligible to participate. Participants will be randomised to receive either transdermal estradiol patches (200 µg/day) or placebo patches for 3 weeks immediately postpartum. The primary outcome is clinical depression, according to the Diagnostic and Statistical Manual of Mental Disorders-V criteria of Major Depressive Disorder with onset at any time between 0 and 6 months postpartum. Secondary outcomes include, but are not limited to, symptoms of depression postpartum, exclusive breastfeeding, cortisol dynamics, maternal distress sensitivity and cognitive function. The primary statistical analysis will be performed based on the intention-to-treat principle. With the inclusion of 220 participants and a 20% expected dropout rate, we anticipate 80% power to detect a 50% reduction in postpartum depressive episodes while controlling the type 1 error at 5%. ETHICS AND DISSEMINATION: The study protocol is approved by the Regional Committees on Health Research Ethics in the Capital Region of Denmark, the Danish Medicines Agency and the Centre for Data Protection Compliance in the Capital Region of Denmark. We will present results at scientific meetings and in peer-reviewed journals and in other formats to engage policymakers and the public. TRIAL REGISTRATION NUMBER: NCT04685148.

Screening for cognitive dysfunction in unipolar depression: Validation and evaluation of objective and subjective tools.

BACKGROUND: Persistent cognitive dysfunction in unipolar depression (UD) contributes to socio-occupational impairment, but there are no feasible methods to screen for and monitor cognitive dysfunction in this patient group. The present study investigated the validity of two new instruments to screen for cognitive dysfunction in UD, and their associations with socio-occupational capacity. METHOD: Participants (n=53) with UD in partial or full remission and healthy control persons (n=103) were assessed with two new screening instruments, the Danish translations of the Screen for Cognitive Impairment in Psychiatry (SCIP-D) and Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and with established neuropsychological and self-assessment measures. Depression symptoms and socio-occupational function were rated with the Hamilton Depression Rating Scale and Functional Assessment Short Test respectively. RESULTS: The SCIP-D and COBRA were valid for detection of objective and subjective cognitive impairment, respectively. The three parallel SCIP-D forms were equivalent. A combined SCIP-D-COBRA measure showed high sensitivity and good specificity for objective cognitive impairment (91% and 70%, respectively). There was no correlation between subjective and objective measures of cognition. Subjective cognitive difficulties correlated more with socio-occupational impairment (r=0.7, p<0.01) than did objective cognitive difficulties, for which there was a weak correlation with the executive skills domain only (r =-0.3, p=0.05). LIMITATIONS: A modest sample size. CONCLUSIONS: The SCIP-D and COBRA are valid measures of objective and subjective cognitive impairment, respectively, and should ideally be implemented together in the screening for cognitive dysfunction in UD.