Association of postpartum maternal mood with infant speech perception at 2 and 6.5 months of age

Importance: Language development builds on speech perception, with early disruptions increasing the risk for later language difficulties. Although a major postpartum depressive episode is associated with language development, this association has not been investigated among infants of mothers experiencing a depressed mood at subclinical levels after birth, even though such a mood is frequently present in the first weeks after birth. Understanding whether subclinical depressed maternal mood after birth is associated with early language development is important given opportunities of coping strategies for subclinical depressed mood.Objective: To examine whether depressed maternal mood at subclinical levels 2 months after birth is associated with infant speech perception trajectories from ages 2 to 6.5 months.Design, setting, and participants: In this longitudinal cohort study conducted between January 1, 2018, and October 31, 2019, 46 healthy, monolingual German mother-infant dyads were tested. The sample was recruited from the infants database of the Max Planck Institute for Human Cognitive and Brain Sciences. Initial statistical analysis was performed between January 1 and March 31, 2021; the moderation analysis (results reported herein) was conducted between July 1 and July 31, 2022.Exposures: Mothers reported postpartum mood via the German version of the Edinburgh Postnatal Depression Scale (higher scores indicated higher levels of depressed mood, with a cutoff of 13 points indicating a high probability of clinical depression) when their infants were 2 months old.Main outcomes and measures: Electrophysiological correlates of infant speech perception (mismatch response to speech stimuli) were tested when the infants were aged 2 months (initial assessment) and 6.5 months (follow-up).Results: A total of 46 mothers (mean [SD] age, 32.1 [3.8] years) and their 2-month-old children (mean [SD] age, 9.6 [1.2] weeks; 23 girls and 23 boys) participated at the initial assessment, and 36 mothers (mean [SD] age, 32.2 [4.1] years) and their then 6.5-month-old children (mean [SD] age, 28.4 [1.5 weeks; 18 girls and 18 boys) participated at follow-up. Moderation analyses revealed that more depressed maternal subclinical postpartum mood (mean [SD] Edinburgh Postnatal Depression Scale score, 4.8 [3.6]) was associated with weaker longitudinal changes of infants' electrophysiological brain responses to syllable pitch speech information from ages 2 to 6.5 months (coefficient: 0.68; 95% CI, 0.03-1.33; P = .04).Conclusions and relevance: The results of this cohort study suggest that infant speech perception trajectories are correlated with subclinical depressed mood in postpartum mothers. This finding lays the groundwork for future research on early support for caregivers experiencing depressed mood to have a positive association with children's language development

Longitudinal 7T MRI reveals volumetric changes in subregions of human medial temporal lobe to sex hormone fluctuations

The hippocampus and surrounding medial temporal lobe (MTL) are critical for memory processes, with local atrophy linked to memory deficits. Animal work shows that MTL subregions densely express sex hormone receptors and exhibit rapid structural changes synchronized with hormone fluctuations. Such transient effects in humans have thus far not been shown. By combining a dense-sampling protocol, ultra-high field neuroimaging and individually-derived segmentation analysis, we demonstrate how estradiol and progesterone fluctuations affect MTL subregion volumes across the human menstrual cycle. Twenty-seven healthy women (19-34 years) underwent 7T MRI at six timepoints to acquire T1-weighted and T2-weighted images. Linear mixed-effects modeling showed positive associations between estradiol and parahippocampal cortex volume, progesterone and subiculum and perirhinal Area 35 volumes, and an estradiol*progesterone interaction with CA1 volume. We confirmed volumetric changes were not driven by hormone-related water (cerebral spinal fluid) or blood-flow (pulsed arterial spin labeling) changes. These findings suggest that sex hormones alter structural brain plasticity in subregions that are differentially sensitive to hormones. Mapping how endogenous endocrine factors shape adult brain structure has critical implications for women’s health during the reproductive years as well as later in life, such as increased dementia risk following perimenopause, a period of pronounced sex hormone fluctuations

A single dose of escitalopram blunts the neural response in the thalamus and caudate during monetary loss

Background: Selective serotonin reuptake inhibitors (SSRIs) show acute effects on the neural processes associated with negative affective bias in healthy people and people with depression. However, whether and how SSRIs also affect reward and punishment processing on a similarly rapid time scale remains unclear. Methods: We investigated the effects of an acute and clinically relevant dose (20 mg) of the SSRI escitalopram on brain response during reward and punishment processing in 19 healthy participants. In a doubleblind, placebo-controlled study using functional MRI, participants performed a well-established monetary reward task at 3 time points: at baseline; after receiving placebo or escitalopram; and after receiving placebo or escitalopram following an 8-week washout period. Results: Acute escitalopram administration reduced blood-oxygen-level-dependent (BOLD) response during punishment feedback in the right thalamus (family-wise error corrected [FWE] p = 0.013 at peak level) and the right caudate head (pFWE = 0.011 at peak level) compared to placebo. We did not detect any significant BOLD changes during reward feedback. Limitations: We included only healthy participants, so interpretation of findings are limited to the healthy human brain and require future testing in patient populations. The paradigm we used was based on monetary stimuli, and results may not be generalizable to other forms of reward. Conclusion: Our findings extend theories of rapid SSRI action on the neural processing of rewarding and aversive stimuli and suggest a specific and acute effect of escitalopram in the punishment neurocircuitry

One‐week escitalopram intake alters the excitation–inhibition balance in the healthy female brain

Neural health relies on cortical excitation-inhibition balance (EIB). Previous research suggests a link between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear. Thus, in a randomized double-blind study, we administered a clinically relevant dose of 20 mg escitalopram for 7 days (time when steady state is achieved) in 59 healthy women (28 escitalopram, 31 placebo) on oral contraceptives. We acquired resting-state electroencephalography data at baseline, after a single dose, and at steady state. We assessed 1/f slope of the power spectrum as a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Escitalopram-intake was associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after a single dose of escitalopram was associated with 1/f slope at steady state. Higher plasma escitalopram levels at a single dose were associated with better maintenance of these EIB changes throughout the drug administration week. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the lens through which we map the human brain by testing an interventional psychopharmacological design in a clearly defined endocrinological state

The attention-emotion interaction in healthy female participants on oral contraceptives during 1-week escitalopram intake

Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebo-controlled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment

Testosterone imbalance may link depression and increased body weight in premenopausal women

Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m2), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance

Decreased thalamo-cortico connectivity during an implicit sequence motor learning task and 7 days escitalopram intake

Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. While previous findings support an effect of SSRIs on intrinsic functional connectivity, little is known regarding the influence of SSRI-administration on connectivity during sequence motor learning. To investigate this, we administered 20 mg escitalopram or placebo for 1-week to 60 healthy female participants undergoing concurrent functional magnetic resonance imaging and sequence motor training in a double-blind randomized controlled design. We assessed task-modulated functional connectivity with a psycho-physiological interaction (PPI) analysis in the thalamus, putamen, cerebellum, dorsal premotor, primary motor, supplementary motor, and dorsolateral prefrontal cortices. Comparing an implicit sequence learning condition to a control learning condition, we observed decreased connectivity between the thalamus and bilateral motor regions after 7 days of escitalopram intake. Additionally, we observed a negative correlation between plasma escitalopram levels and PPI connectivity changes, with higher escitalopram levels being associated with greater thalamo-cortico decreases. Our results suggest that escitalopram enhances network-level processing efficiency during sequence motor learning, despite no changes in behaviour. Future studies in more diverse samples, however, with quantitative imaging of neurochemical markers of excitation and inhibition, are necessary to further assess neural responses to escitalopram

Association of estradiol and visceral fat with structural brain networks and memory performance in adults

Importance Changes in estradiol during aging are associated with increased dementia risk. It remains unclear how estradiol supports cognitive health and whether risk factors, such as midlife obesity, are exacerbated by estrogen loss. Objectives To assess whether visceral adipose tissue (VAT) moderates the association between age and brain network structure and to investigate whether estradiol moderates the association between VAT and brain network structure. Design, Setting, and Participants Cross-sectional study of data from 974 cognitively healthy adults in Germany who participated in the Health Study of the Leipzig Research Centre for Civilization Diseases, a previously described population-based cohort study. Two moderation analyses were performed, including VAT as the moderator variable between age and brain network structure and estradiol as the moderator variable between VAT and brain network structure. The study was conducted from August 1, 2011, to November 23, 2014. Analyses were conducted from August 2017 to September 201