Women with early maltreatment experience show increased resting-state functional connectivity in the theory of mind (ToM) network

Background: Experience of childhood maltreatment significantly increases the risk for the development of psychopathology and is associated with impairments in socio-cognitive skills including theory-of-mind (ToM). In turn, neural alterations in ToM processing might then influence future interpersonal interaction and social-emotional understanding. Objective: To assess resting-state activity in the theory-of-mind network in traumatized and non-traumatized persons. Methods: Thirty-five women with a history of childhood maltreatment and 31 unaffected women completed a resting-state scan and a ToM localizer task. The peak coordinates from the localizer were used as the seed regions for the resting-state functional connectivity (RSFC) analyses (temporo-parietal junction, dorsomedial prefrontal cortex, middle temporal gyrus and precuneus). Results: Child abuse was associated with increased RSFC between various ToM regions including the precuneus and the brainstem suggesting altered hierarchical processing in ToM regions. Number of types of abuse was driving the effect for the temporo-parietal junction and the brainstem, while the severity of abuse was linked to increased RSFC between the middle temporal gyrus and the frontal cortex. Post-hoc analyses of brainstem regions indicated the involvement of the serotonergic system (dorsal raphe). Conclusions: The data indicate a lasting impact of childhood maltreatment on the neural networks involved in social information processing that are integral to understanding others' emotional states. Indeed, such altered neural networks may account for some of the interpersonal difficulties victims of childhood maltreatment experience

Neural correlates of ostracism in transgender persons living according to their gender identity : a potential risk marker for psychopathology?

Background. Stigmatization in society carries a high risk for development of psychopathology. Transgender persons are at particularly high risk for such stigmatization and social rejection by others. However, the neural correlates of ostracism in this group have not been captured. Method. Twenty transgender men (TM, female-to-male) and 19 transgender women (TW, male-to-female) already living in their gender identity and 20 cisgender men (CM) and 20 cisgender women (CW) completed a cyberball task assessing both exclusion and re-inclusion during functional magnetic resonance imaging (fMRI). Results. During psychosocial stress between-group differences were found in the dorsal and ventral anterior cingulate cortex (ACC) and the inferior frontal gyrus (IFG). Patterns were consistent with sex assigned at birth, i.e. CW showed greater activation in dorsal ACC and IFG relative to CM and TW. During re-inclusion, transgender persons showed greater ventral ACC activity relative to CW, possibly indicating persistent feelings of exclusion. Functional connectivity analyses supported these findings but showed a particularly altered functional connectivity between ACC and lateral prefrontal cortex in TM, which may suggest reduced emotional regulation to the ostracism experience in this group. Depressive symptoms or hormonal levels were not associated with these findings. Conclusion. The results bear implications for the role of social exclusion in development of mental health problems in socially marginalized groups

Women with early maltreatment experience show increased resting-state functional connectivity in the theory of mind (ToM) network.

Background: Experience of childhood maltreatment significantly increases the risk for the development of psychopathology and is associated with impairments in socio-cognitive skills including theory-of-mind (ToM). In turn, neural alterations in ToM processing might then influence future interpersonal interaction and social-emotional understanding. Objective: To assess resting-state activity in the theory-of-mind network in traumatized and non-traumatized persons. Methods: Thirty-five women with a history of childhood maltreatment and 31 unaffected women completed a resting-state scan and a ToM localizer task. The peak coordinates from the localizer were used as the seed regions for the resting-state functional connectivity (RSFC) analyses (temporo-parietal junction, dorsomedial prefrontal cortex, middle temporal gyrus and precuneus). Results: Child abuse was associated with increased RSFC between various ToM regions including the precuneus and the brainstem suggesting altered hierarchical processing in ToM regions. Number of types of abuse was driving the effect for the temporo-parietal junction and the brainstem, while the severity of abuse was linked to increased RSFC between the middle temporal gyrus and the frontal cortex. Post-hoc analyses of brainstem regions indicated the involvement of the serotonergic system (dorsal raphe). Conclusions: The data indicate a lasting impact of childhood maltreatment on the neural networks involved in social information processing that are integral to understanding others' emotional states. Indeed, such altered neural networks may account for some of the interpersonal difficulties victims of childhood maltreatment experience

Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial

In the EMN01 trial, the addition of an alkylator (melphalan or cyclophosphamide) to lenalidomide-steroid induction has been prospectively evaluated in transplant-ineligible multiple myeloma patients. After induction, patients were randomly assigned to maintenance treatment with lenalidomide alone or with prednisone continuously. This analysis (median follow-up of 71 months) focused on maintenance treatment and on subgroup analyses according to the International Myeloma Working Group Frailty Score. 217 patients in lenalidomide-dexamethasone, 217 in melphalan-prednisone-lenalidomide and 220 in cyclophosphamide-prednisone-lenalidomide arms were evaluable. 284 (43%) patients were fit, 205 (31%) intermediate-fit and 165 (25%) frail. After induction, 402 patients were eligible for maintenance, (lenalidomide arm: 204; lenalidomide-prednisone: 198). After a median duration of maintenance of 22.0 months, progression-free survival from start of maintenance was 22.2 months with lenalidomide-prednisone vs 18.6 months with lenalidomide (HR 0.85,p=0.14), with no differences across frailty subgroups. The most frequent grade ≥3 toxicity was neutropenia (10% of lenalidomide-prednisone and 21% of lenalidomide patients; p=0.001). Grade ≥3 non-hematologic adverse events were rare (<15%). In fit patients, melphalan-prednisone-lenalidomide significantly prolonged progression-free survival compared to cyclophosphamide-prednisone-lenalidomide (HR 0.72,p=0.05) and lenalidomide-dexamethasone (HR 0.72, p=0.04). Likewise, a trend towards a better overall survival was noted for melphalan-prednisone-lenalidomide and cyclophosphamide-prednisone-lenalidomide, as compared to lenalidomide-dexamethasone. No differences were observed in intermediate-fit and frail patients. This analysis showed positive outcomes of maintenance with lenalidomide-based regimens, with a good safety profile. For the first time, we showed that fit patients benefit from a triplet full-dose regimen, while intermediate-fit and frail patients from gentler regimens. ClinicalTrials.gov registration number: NCT01093196