Andrada D. Neacsiu

Beginning at puberty and throughout the lifespan, women experience greater rates of depression, anxiety disorders, eating disorders, post-traumatic stress disorder, and hormone-linked mood disorders relative to men. How these disorders relate to hormonal fluctuations and associated changes in physiology and brain circuitry in women during the reproductive years is only partially understood. In this review, the molecular, structural, and functional brain changes during the reproductive years are discussed, with a specific focus on transitional changes during the perinatal period. Preclinical and clinical models of neuroplastic change are also discussed, along with neuromodulatory approaches that account for the contextual, spatial, and temporal parameters of interventions delivered during the postpartum period. Future directions may consider how hormonal fluctuations during reproductive years may improve preclinical and clinical models for womens mental health while acknowledging that greater work is needed to understand the role of a broader range of hormonal and environmental factors linked to mental health including lactation, trauma, contraceptive use, menstruation, and perimenopause.

Misophonia is a poorly understood clinical condition characterized by reduced tolerance to select trigger sounds. Whether misophonic distress and its regulation involve unique neural mechanisms compared to other forms of emotion dysregulation remains unclear. We used functional magnetic resonance imaging (fMRI) to identify putative neural signatures of misophonic reactivity and regulation compared to a transdiagnostic clinical control group. Twenty-nine adults with misophonia and 30 with high emotional dysregulation and a DSM-5 psychiatric disorder underwent an fMRI session. After the presentation of misophonic, aversive, or neutral sound cues, they either experienced emotions naturally or reduced negative affect through cognitive reappraisal. Compared to controls, participants with misophonia showed greater distress after listening to or downregulating misophonic sounds and lower distress when listening to non-misophonic aversive sounds. Listening to misophonic sounds elicited lower functional connectivity between the right insula and the left dorsomedial prefrontal cortex (dmPFC), and between the left insula and the right superior temporal sulcus, in the misophonia group compared with controls. During the regulation of misophonic sounds, the misophonia group showed increased left insula connectivity with the anterior cingulate cortex and increased right insula connectivity with the bilateral dmPFC and other sensorimotor regions compared to controls. In the misophonia group only, higher emotion dysregulation and lower habitual use of reappraisal were respectively associated with increased insula-dmPFC connectivity and with increased insula connectivity with the dorsolateral prefrontal cortex. Prefrontal cortex activation during regulation of misophonic distress was not significantly different between the two groups. Insula activity and connectivity may be key features that distinguish misophonia from other forms of emotional dysregulation. These novel findings identify candidate neural processes that may be selectively associated with misophonia, as well as processes that may be shared between misophonia and other forms of emotion dysregulation.

This pilot study evaluated the feasibility and acceptability of a five-session version of the transdiagnostic Unified Protocol adapted for older adults with emotional distress and impaired functional activity. In Phase 1, the therapist-delivered treatment was adapted for this population. In Phase 2, 16 older adults with emotional distress and impairments in functioning were randomly assigned to either a Self-Guided or Therapist-Delivered version of the 5-session protocol. Assessments were conducted after one week and one month. The intervention was feasible, with participants in the therapist-delivered group expressing significantly higher treatment satisfaction (Cohen’s d_{1_week} = 2.08; d_{1_month} =2.00). Both groups showed improvement in functioning (d = 3.11), with no significant differences between conditions. Emotional distress decreased significantly (d_anxiety =1.14; d_depression =0.81) with no condition differences. Physical activity showed modest gains (ds = 0.17–0.18). These findings support the feasibility and preliminary efficacy of the adapted intervention. The UP-ST-5 may be a promising intervention for older adults, with the self-guided version offering a scalable option.

Background: People living longer with metastatic non‐small cell lung cancer (mNSCLC) experience heightened psychological distress and decrements in quality of life. Therefore, we developed LiveWell, an 8‐session adapted dialectical behavioral therapy skills training (DBT‐ST) protocol delivered one‐on‐one via telehealth to reduce psychological distress. Aim: To conduct a single‐arm pilot trial examining the feasibility and acceptability of LiveWell and explore change in outcome variables. Methods: Patients receiving systemic therapy for mNSCLC with at least mild distress participated. Outcomes were feasibility (accrual N = 30 in 18 months, > 80% sessions attended, < 25% attrition) and acceptability (> 80% participant satisfaction). Distress (depression and anxiety symptoms; primary outcomes), intolerance of uncertainty, emotion regulation, illness acceptance, symptoms (e.g., fatigue, dyspnea, pain), skill use, and quality of life (secondary outcomes) were assessed at baseline, post‐intervention (primary endpoint), and 1‐month post‐intervention and examined with paired sample t ‐tests. Results: Thirty participants ( M _age = 63 years, 77% female) consented and completed the baseline assessment. LiveWell met feasibility (accrual N = 30 in 8 months, 93% sessions attended, 87% retention at post‐intervention) and acceptability (96% satisfaction) benchmarks. Participants demonstrated reductions in distress (depression d = 0.35, anxiety d = 0.22) from baseline to post‐treatment. Intolerance of uncertainty ( d = 0.71), emotion regulation ( d = 0.49), and illness acceptance ( d = 0.45) improved. Fatigue and pain remained stable or improved ( d 's 0.07–0.38). Skill use increased ( d = 0.65) and quality of life improved ( d = 0.21). Improvements were maintained or enhanced at 1‐month follow‐up. Conclusions: LiveWell was feasible and acceptable, and participants demonstrated promising improvement in primary and secondary outcomes. Findings support a larger randomized efficacy trial. Trial registration: ClinicalTrials.gov Identifier: NCT04973436

Background: The motor threshold (MT) plays a central role in probing brain excitability and individualizing transcranial magnetic stimulation (TMS). Previously, we proposed stochastic approximation (SA) as a new method for determining TMS MT and demonstrated its excellent speed and accuracy via simulations. SA also has low computational requirements and is robust to potential model flaws. Objective: This project aimed to develop a practical SA thresholding method and assess its performance in clinical studies. Methods: The SA thresholding method was implemented as an online software application—SAMT (Stochastic Approximator of MT)—that incorporated features for detection of inaccurate MT estimation. Two ongoing clinical studies use SAMT and have collected 281 finger muscle MTs from 124 participants to date. SAMT’s misestimation detection method marked MTs of 7 thresholding trials as inaccurate, and SAMT’s performance in the remaining 274 trials was assessed by comparing the MT at each step to the threshold estimated by fitting a sigmoidal probability distribution to the complete muscle response data from the session. Results: By the 25 ^th TMS pulse, 99% of the SAMT MTs deviated by less than 3.0% (relative) and 1.3% of maximum stimulator output (absolute) from the corresponding fitted sigmoid thresholds and were within their 95% confidence intervals. Conclusions: We provide the TMS community with a new motor thresholding tool, SAMT. Combined with the prior simulation results, the experimental assessment presented here supports the practicality and accuracy of the SA thresholding method and the SAMT software.

Emotion dysregulation (ED) is a key target for change among empirically supported treatments for emotional disorders, including dialectical behaviour therapy skills training (DBT‐ST), yet how treatments improve ED is poorly understood. Using data from a randomised trial of DBT‐ST versus supportive group therapy for transdiagnostic ED, we tested whether three mechanistic variables—behavioural skills use, mindfulness, and perceived control—explain variability in ED within people over time. We additionally explored the mediating roles of these variables between conditions. Adults with transdiagnostic ED (N = 44) participated in weekly groups for 4 months, with assessments at pre‐, mid‐ and post‐treatment and at 2‐month follow‐up. As hypothesised, multilevel models disaggregating within‐ and between‐person effects indicated that skills use, mindfulness, and perceived control each had significant total and unique within‐person associations with ED at concurrent time points, net the effect of time. Unexpectedly, these within‐person relations were not significant for mechanistic variables predicting ED 2 months later. Further, unique between‐person variability in skills use, mindfulness, and perceived control did not significantly mediate the relationship between condition and ED improvements. The present study is an important step in clarifying ED mechanisms of change, both within and between persons.