Improving mental health in Multiple Sclerosis with an interpersonal emotion regulation intervention: A prospective, randomized controlled trial.

BACKGROUND: Over a third of people with Multiple Sclerosis (PwMS) struggle with poor mental health, which exacerbates physical symptoms and complicates clinical treatment. To address this, we tested the efficacy of an interpersonal emotion regulation intervention: this intervention seeks to improve mental health by teaching participants to use emotion regulation strategies which leverage social support (e.g., reaching out to others for comfort when experiencing a stressful event). METHOD: Nineteen PwMS completed this prospective, blinded randomized controlled trial (intervention n = 10; control n = 9). Intervention participants met with an interventionist over six weeks to discuss their emotional challenges and develop goals to use interpersonal emotion regulation strategies. Participants in the control condition met with the interventionist on the same schedule but their emotion regulation strategies were only measured and not manipulated. Pre-registered primary outcomes were self-reported depression, stress, and quality of life (QoL). The pre-registered secondary outcome was self-reported social support. RESULTS: Intervention participants' depression scores improved from time 1 to time 2 (mean difference=3.60, 95% CI [0.44-6.76]), yet remained unchanged for the control group (mean difference=-1.67, 95% CI [-5.00-1.67], overall interaction, F(1,17)=5.84, p=.027, ηp2=.256). The remaining primary (stress and QoL) and secondary (social support) outcomes did not show a significant effect of the intervention (stress: p=.601, ηp2=.016; QoL: p=.179, ηp2=.104; social support: p=.140, ηp2=.124). CONCLUSION: Interpersonal emotion regulation is beneficial in improving depression in PwMS. Consequently, these strategies can be implemented in conjunction with existing mental health treatments in a holistic approach to improving well-being.

Emotional processing intervention (EMOPRINT): A blinded randomized control trial to treat facial affect recognition deficits in multiple sclerosis.

OBJECTIVE: Facial affect recognition deficits have been noted in persons with MS, however there is no treatment for these impairments. We investigated the efficacy of the Emotional Processing Intervention (EMOPRINT), a 12-session behavioral intervention teaching facial affect recognition skills and mimicry to improve facial affect recognition abilities in persons with MS. METHODS: This double blind, placebo-controlled, randomized clinical trial with two time points (pre-treatment; post-treatment) included 36 participants with clinically definite MS, 21 in the treatment group and 15 in the placebo control group. Participants completed a pre-test and post-test neuropsychological assessment, which consisted of tasks of facial affect recognition (primary outcome measure) and questionnaires to assess quality of life and emotional functioning (secondary outcome measures). We hypothesized that improvements in facial affect recognition skills would be observed following treatment. We also examined changes to quality of life and social functioning. Changes in outcome measures were analyzed using a mixed-method analysis of variance. RESULTS: The treatment group showed significantly improved facial affect recognition skills relative to the placebo group post-treatment, F(1,34)=5.91, p=.022, partial ꞃ2=0.146. No significant change was noted on secondary outcomes. The majority of the participants in the intervention group reported that the intervention was helpful and that they used the skills learned in their daily interactions. CONCLUSION: EMOPRINT is effective for improving facial affect recognition skills in MS.

Immediate vaginal and perineal reconstruction after abdominoperineal excision using the Inferior Gluteal Artery Perforator Flap (V-IGAP).

BACKGROUND: The fasciocutaneous inferior gluteal artery perforator (IGAP) has been previously demonstrated to be a robust reconstructive choice after abdominoperineal excision (APE), with comparably low morbidity relative to other flaps. In patients who undergo concurrent vaginectomy, we demonstrate in this retrospective cohort study how IGAP modification allows simultaneous vaginal reconstruction with a favourable complication profile and long-term return to sexual activity. METHODS: Oncological resection was completed with the patient prone. Unilateral or bilateral IGAP flaps may be used based on vaginal defect size and surgeon preference. In this study, important features of flap design, mobilisation and inset are presented, together with a retrospective cohort study of all cases who underwent vaginal reconstruction. Clinical outcomes were determined by the length of stay, early to late complications, and quality of life assessment including a return to sexual function. RESULTS: Over a 10-year period, 207 patients underwent abdominoperineal resection (APE) in our cross-centre study (86% subject to neoadjuvant chemoradiotherapy), with 22/84 female patients electing for vaginal reconstruction (19 partial, 3 total vaginectomies). Minor complications were observed in 6/22 cases, with two patients progressing to healing after-theatre debridement (major). The median follow-up time was 410 days. Quality of life questionnaires reported high patient satisfaction, with 70% of patients returning to sexual activity. CONCLUSIONS: For patients undergoing APE with concurrent vaginectomy, the IGAP flap can be used alone for both perineal dead space management and neovaginal reconstruction, negating the need for an alternative second flap and avoiding significant donor morbidity. This study shows excellent long-term clinical outcomes, including a return to sexual activity.

Independent contributions of social cognition and depression to functional status after moderate or severe traumatic brain injury.

Impairments in cognitive processing related to social understanding and communication (i.e., "social cognition") are well documented after moderate or severe traumatic brain injury (TBI) and can contribute to negative functional outcome. Depression is also a common feature of TBI with detrimental functional consequences. We evaluated relationships between social cognition, depression symptom severity, and functional status in individuals with chronic TBI (>1 year post injury; n = 25) and healthy controls (n = 30) using objective tests of social cognition as well as self-reported depression (Beck Depression Inventory-II) and functional status (Functional Behavior Profile). Results revealed significant relationships between depression and functional status across the sample, and relationships between social cognition and functional status specific to TBI. In the TBI group only, social cognition significantly predicted both overall and social functional status above and beyond depression. Group differences in functional status were independently mediated by social cognition and, especially, depression. Our findings suggest that social cognitive impairments and depression are distinct, functionally relevant TBI sequelae. Interventions to improve social functioning in this population may be most effective when contextualized within treatments for emotional disturbances.

Perioral pressure ulcers in patients with COVID-19 requiring invasive mechanical ventilation.

BACKGROUND: Facial pressure ulcers are a rare yet significant complication. National Institute for Health and Care Excellence (NICE) guidelines recommend that patients should be risk-assessed for pressure ulcers and measures instated to prevent such complication. In this study, we report case series of perioral pressure ulcers developed following the use of two devices to secure endotracheal tubes in COVID-19 positive patients managed in the intensive care setting. METHODS: A retrospective analysis was conducted on sixteen patients identified to have perioral pressure ulcers by using the institutional risk management system. Data parameters included patient demographics (age, gender, comorbidities, smoking history and body mass index (BMI)). Data collection included the indication of admission to ITU, duration of intubation, types of medical devices utilised to secure the endotracheal tube, requirement of vasopressor agents and renal replacement therapy, presence of other associated ulcers, duration of proning and mortality. RESULTS: Sixteen patients developed different patterns of perioral pressure ulcers related to the use of two medical devices (Insight, AnchorFast). The mean age was 58.6 years. The average length of intubation was 18.8 days. Fourteen patients required proning, with an average duration of 5.2 days. CONCLUSIONS: The two devices utilised to secure endotracheal tubes are associated with unique patterns of facial pressure ulcers. Measures should be taken to assess the skin regularly and avoid utilising devices that are associated with a high risk of facial pressure ulcers. Awareness and training should be provided to prevent such significant complication.Level of evidence: Level IV, risk/prognostic study.

Relationship between social cognition and fatigue, depressive symptoms, and anxiety in multiple sclerosis.

Emerging research indicates that in addition to physical and cognitive deficits, individuals with multiple sclerosis (MS) may also have impairments in social cognition, such as facial affect recognition and Theory of Mind (ToM). However, there is little research into how social cognition impairments relate to other domains in MS, such as mood and fatigue levels. The current study investigated whether social cognitive ability is associated with fatigue, depressive symptoms and anxiety in MS. Twenty-eight individuals with MS completed questionnaires assessing fatigue (Modified Fatigue Impact Scale), depression (Beck Depression Inventory) and anxiety (State-Trait Anxiety Inventory), as well as tasks of facial affect recognition and ToM (Reading the Mind in the Eyes; Strange Stories). Bivariate correlations were run to examine relationships between variables; partial correlations were subsequently used to ascertain whether these relationships persisted after controlling for cognitive ability (measured with the Symbol Digit Modalities Test). The results indicated that worse performance in both facial affect recognition and ToM were associated with higher rates of psychosocial fatigue, depressive symptoms, and anxiety levels; furthermore, these relationships were not explained by participants' cognitive ability. These preliminary results help us better understand the association between social cognitive abilities and other symptoms in MS, including depressive symptomatology, anxiety and fatigue.

Default Mode Network Connectivity Predicts Emotion Recognition and Social Integration After Traumatic Brain Injury.

Moderate-severe traumatic brain injury (TBI) may result in difficulty with emotion recognition, which has negative implications for social functioning. As aspects of social cognition have been linked to resting-state functional connectivity (RSFC) in the default mode network (DMN), we sought to determine whether DMN connectivity strength predicts emotion recognition and level of social integration in TBI. To this end, we examined emotion recognition ability of 21 individuals with TBI and 27 healthy controls in relation to RSFC between DMN regions. Across all participants, decreased emotion recognition ability was related to increased connectivity between dorsomedial prefrontal cortex (dmPFC) and temporal regions (temporal pole and parahippocampal gyrus). Furthermore, within the TBI group, connectivity between dmPFC and parahippocampal gyrus predicted level of social integration on the Community Integration Questionnaire, an important index of post-injury social functioning in TBI. This finding was not explained by emotion recognition ability, indicating that DMN connectivity predicts social functioning independent of emotion recognition. These results advance our understanding of the neural underpinnings of emotional and social processes in both healthy and injured brains, and suggest that RSFC may be an important marker of social outcomes in individuals with TBI.

Cognitive but Not Affective Theory of Mind Deficits in Progressive MS.

OBJECTIVE: Social cognitive deficits are an important consequence of multiple sclerosis (MS), yet our understanding of how these deficits manifest in progressive MS is currently limited. To this end, we examined theory of mind (ToM) ability in a sample of individuals with progressive MS using an ecologically valid virtual assessment tool that allows for delineation of cognitive ToM (inferring thoughts and intentions of others) from affective ToM (inferring emotions of others). METHODS & RESULTS: We compared 15 individuals with progressive MS and 15 healthy controls on their ToM ability using the Virtual Assessment of Mentalising Ability. We found that, relative to healthy controls, participants with progressive MS were impaired in cognitive ToM, but not in affective ToM. Furthermore, we found that the MS participants' deficits in cognitive ToM were mediated by their general cognitive ability such that poor cognitive ToM ability in MS was explained by poor performance on tests of memory and processing speed. CONCLUSIONS: Our findings demonstrate that ToM deficits in progressive MS may be limited to cognitive ToM, while affective ToM is conserved. This could be attributable to the MS-related deficits in general cognitive ability, which appear to negatively affect only the cognitive component of ToM.

Community Integration in Traumatic Brain Injury: The Contributing Factor of Affect Recognition Deficits.

OBJECTIVE: Individuals with traumatic brain injury (TBI) can experience social isolation, which is damaging to well-being and counterproductive to successful rehabilitation. It has been proposed that social cognitive deficits that commonly result from TBI may contribute to weakened social integration. However, the consequences of specific social cognitive deficits in TBI are still being delineated. The current work sought to better characterize the relationship between community integration and facial affect recognition (FAR) in TBI. PARTICIPANTS AND METHODS: A total of 27 participants with moderate to severe TBI and 30 healthy controls (HCs) completed two tests of FAR, which employed either static photographic stimuli or dynamic video stimuli (The Awareness of Social Inference Test). The Community Integration Questionnaire was also administered to participants. RESULTS: Participants with TBI were significantly impaired on both the static and dynamic FAR measures, yet the deficits were most pronounced within the dynamic task. Furthermore, participants with TBI reported lower community integration compared with HCs. FAR was positively associated with community integration in both groups, such that participants with proficient affect recognition skills were better integrated into their communities. CONCLUSIONS: FAR deficits may contribute to the lack of community integration often observed in TBI; thus, interventions designed to improve FAR may be beneficial to this population's ability to successfully reintegrate into society.

DNA methylation of OXTR is associated with parasympathetic nervous system activity and amygdala morphology.

Oxytocin has anxiolytic properties whose mechanisms of action are still being identified. DNA methylation in the promoter region of the oxytocin receptor gene (OXTR), an epigenetic modification that putatively reflects a downtuning of the oxytocin system, has previously been implicated in the regulation of fear-related responses through the amygdala. In this study, we attempted to characterize the relationship between methylation of OXTR and anxiogenesis using two distinct endophenotypes: autonomic nervous system activity and subcortical brain structure. In 79 participants, we found that increased OXTR methylation is associated with attenuated resting parasympathetic tone, measured using high-frequency heart rate variability. Further, we found that this relationship is mediated by brain morphology, such that OXTR methylation is associated with increased gray matter of the central amygdala which is, in turn, associated with decreased parasympathetic tone. These results further our understanding of epigenetic regulation of the human oxytocin system and its role in anxiogenesis.

The Role of Endogenous Oxytocin in Anxiolysis: Structural and Functional Correlates.

BACKGROUND: Oxytocin is anxiolytic, and administration of synthetic oxytocin in humans reduces amygdala reactivity to negative stimuli. However, it is unknown whether endogenous oxytocin levels-which are heritable and stable across time-attenuate anxiety via similar mechanisms. METHODS: In this study, we used plasma assays and structural and functional neuroimaging to examine potential anxiolytic effects of endogenous oxytocin in 73 participants. RESULTS: We found that higher endogenous oxytocin levels are associated with reduced central amygdala volume and blood oxygen level-dependent activity in response to aversive stimuli. In contrast to previous reports, we found that oxytocin was not related to patterns of functional connectivity between the amygdala and other brain regions. CONCLUSIONS: Together, our results underscore the importance of considering individual differences in participants' endogenous oxytocin with respect to anxiety-related neural activity and neuromorphology.

Neuroimaging Epigenetics: Challenges and Recommendations for Best Practices.

Neuroimaging epigenetics is an interdisciplinary application of epigenetics to cognitive neuroscience that seeks to identify molecular and neural predictors of human behavior. This approach can be sensitive to the dynamic interaction between biological predisposition and environmental influences, and is potentially more informative than an approach using static genetic code. Recent work in this field has generated considerable enthusiasm, yet caution is warranted since any novel cross-disciplinary approach lacks a set of established conventions or standards. In this paper we review existing research in the field of imaging epigenetics, outline important caveats and considerations, and suggest a set of guidelines for researchers conducting this work.

Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex.

Plasma oxytocin explains individual differences in neural substrates of social perception.

The neuropeptide oxytocin plays a critical role in social cognition and behavior. A number of studies using intranasal administration have demonstrated that oxytocin improves social perception. However, little is known about the relationship between individual differences in endogenous levels of oxytocin and social cognition. In the current study, we assessed the relationship between endogenous oxytocin and brain activity during an animacy perception paradigm. Thirty-seven male participants underwent scanning and provided a blood sample for oxytocin analysis. In line with previous research, perception of animacy was associated with activations in superior temporal sulcus, inferior frontal gyrus, and medial prefrontal cortex (mPFC). Notably, participants' levels of plasma oxytocin robustly predicted activation in areas critical for social cognitive processes, such that higher oxytocin levels were related to increased activity in dorsal mPFC, ventral mPFC, dorsolateral PFC, superior temporal gyrus, and temporoparietal junction (TPJ), suggesting differential processing of social stimuli. Together these results show that stable variations in endogenous oxytocin levels explain individual differences in social perception.

17ß-estradiol differentially regulates stress circuitry activity in healthy and depressed women.

Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17ß-estradiol (E2) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E2 during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E2 conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E2 modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E2 conditions were attenuated under high E2 conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex difference in MDD risk.

Combining explicit and implicit measures of racial discrimination in health research.

OBJECTIVES: To improve measurement of discrimination for health research, we sought to address the concern that explicit self-reports of racial discrimination may not capture unconscious cognition. METHODS: We used 2 assessment tools in our Web-based study: a new application of the Implicit Association Test, a computer-based reaction-time test that measures the strength of association between an individual's self or group and being a victim or perpetrator of racial discrimination, and a validated explicit self-report measure of racial discrimination. RESULTS: Among the 442 US-born non-Hispanic Black participants, the explicit and implicit measures, as hypothesized, were weakly correlated and tended to be independently associated with risk of hypertension among persons with less than a college degree. Adjustments for both measures eliminated the significantly greater risk for Blacks than for Whites (odds ratio = 1.4), reducing it to 1.1 (95% confidence interval = 0.7, 1.7). CONCLUSIONS: Our results suggest that the scientific rigor of research on racism and health will be improved by investigating how both unconscious and conscious mental awareness of having experienced discrimination matter for somatic and mental health.