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Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

Background Whereas mounting work has begun to document the neural correlates underlying sexual arousal (SA) in humans, the associations between gender identity and the brain correlates of SA as well as their hormonal contributions remain unknown. Aim This study investigated neural activation to sexual arousal in transgender and cisgender persons. Methods 20 transgender men and 19 transgender women (TW) already living in their identified gender were compared to 21 cisgender men (CM) and 19 cisgender women. Participants viewed erotic and neutral video clips while undergoing 3 Tesla magnetic resonance imaging. Outcomes Group-specific brain activation, brain functional connectivity, and brain-hormone associations within the neurophenomenological model of sexual arousal (Stoleru et al, 2012). Results Consistent with the model, participants activated most of its components. However, between-group differences were mostly showing larger activation for CM relative to any of the other 3 groups. Moreover, functional connectivity analyses (psychophysiological interactions) indicated unique patterns for CM, cisgender women, and TW in how different components of SA communicated with one another. Finally, androgens in transgender men and estrogens in TW correlated negatively with parietal cortex and primary (sensori-) motor regions, respectively, while CM showed positive correlations of androgens with parietal cortex, somatosensory regions, and the insula. Clinical Implications Data provide information on neurobiological changes in sexual arousal during treatment with gender-affirming hormone therapy. Strengths & Limitations Although a limitation is the lack of pretreatment data, the present study provides comprehensive information including brain activation, functional connectivity, and hormonal associations in a large sample. Conclusions The results highlight a complex picture of the neural correlates of SA in gender identity and sex assigned at birth.

The number of adolescent refugees around the world has been continuously increasing over the past few years trying to escape war and terror, among other things. Such experience not only increases the risk for mental health problems including anxiety, depression, and post-traumatic stress disorder (PTSD), but also may have implications for socio-cognitive development. This study tested cognitive-affective processing in refugee adolescents who had escaped armed conflict in Syria and now resided in Istanbul, Turkey. Adolescents were split into a high trauma (n = 31, 12 girls, mean age = 11.70 years, SD = 1.15 years) and low trauma (n = 27, 14 girls, mean age = 11.07 years, SD = 1.39 years) symptom group using median split, and performed a working memory task with emotional distraction to assess cognitive control and a surprise faces task to assess emotional interpretation bias. The results indicated that high (vs. low) trauma symptom youth were ~ 20% worse correctly remembering the spatial location of a cue, although both groups performed at very low levels. However, this finding was not modulated by emotion. In addition, although all youths also had a ~ 20% bias toward interpreting ambiguous (surprise) faces as more negative, the high (vs. low) symptom youth were faster when allocating such a face to the positive (vs. negative) emotion category. The findings suggest the impact of war-related trauma on cognitive-affective processes essential to healthy development.

Although the neuroanatomy of transgender persons is slowly being charted, findings are presently discrepant. Moreover, the major body of work has focused on Western populations. One important factor is the issue of power and low signal-to-noise (SNR) ratio in neuroimaging studies of rare study populations including endocrine or neurological patient groups. The present study focused on the structural neuroanatomy of a Non-Western (Iranian) sample of 40 transgender men (TM), 40 transgender women (TW), 30 cisgender men (CM), and 30 cisgender women (CW), while assessing whether the reliability of findings across structural anatomical measures including gray matter volume (GMV), cortical surface area (CSA), and cortical thickness (CTh) could be increased by using two back-to-back within-session structural MRI scans. Overall, findings in transgender persons were more consistent with sex assigned at birth in GMV and CSA, while no group differences emerged for CTh. Repeated measures analysis also indicated that having a second scan increased SNR in all regions of interest, most notably bilateral frontal poles, pre- and postcentral gyri and putamina. The results suggest that a simple time and cost-effective measure to improve SNR in rare clinical populations with low prevalence rates is a second anatomical scan when structural MRI is of interest.

Background:Depressive symptoms are associated with impaired social functioning, arguably because of reduced mentalizing abilities. However, findings in persons with depressive symptoms and/or major depressive disorder (MDD) are presently mixed, finding evidence both for and against the hypothesis of reduced mentalizing abilities.Aims:This study investigated spontaneous cognitive mentalizing in 36 age-, sex- and education-matched students with depressive symptoms and 45 comparisons with minimal depressive symptoms.Method:To assess spontaneous mentalizing, we used the implicit theory of mind (ToM) task, which looks specifically at spontaneous computation of false belief.Results:Bayesian analysis did not support the hypothesis of impaired mentalizing; in fact, it suggested that the results were 3.90 times more likely to have occurred under the null hypothesis. Results remained stable when comparing depressed and non-depressed individuals without maltreatment exposure but were inconclusive in the maltreatment-exposed groups.Conclusion:The findings suggest no effect of spontaneous mentalizing in a high-functioning depressed sample. Moreover, the findings also emphasize the need to control for childhood maltreatment experiences in future ToM and social functioning research, as these may constitute subgroups within depressed samples. Tailored therapy for maltreated depression individuals may be beneficial.

Experience of childhood abuse impairs complex social functioning in children; however, much less is known about its effects on basic socio-cognitive processes and even fewer studies have investigated these in adult survivors. Using two behavioral tasks, this study investigated spontaneous theory of mind (ToM) and imitative behavior in 41 women with childhood abuse (CA) and 26 unaffected comparison women (UC). In the spontaneous ToM task, UCs showed a larger ToM index than CAs, indicating more facilitation by knowledge of another’s false belief. In the imitation-inhibition task, CAs experienced less interference than UCs when observing another’s incongruent movements. After controlling for depression, differences in ToM became marginally significant, yet remained highly significant for inhibiting imitative behavior. The findings suggest childhood abuse survivors have altered perspective-taking, and are less influenced by others’ perspectives, potentially due to changes in self-other distinction. Clinical implications regarding therapeutic practice with survivors of childhood abuse are discussed.

Much research has been conducted on sexual differences of the human brain to determine whether and to what extent a brain gender exists. Consequently, a variety of studies using different neuroimaging techniques attempted to identify the existence of a brain phenotype in people with gender dysphoria (GD). However, to date, brain sexual differences at the metabolite level using magnetic resonance spectroscopy (1H-MRS) have not been explored in transgender people. In this study, 28 cisgender men (CM) and 34 cisgender women (CW) and 29 transgender men with GD (TMGD) underwent 1H-MRS at 3 Tesla MRI to characterize common brain metabolites. Specifically, levels of N–acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate and glutamine (Glx), and myo-inositol + glycine (mI + Gly) were assessed in two brain regions, the amygdala-anterior hippocampus and the lateral parietal cortex. The results indicated a sex-assigned at birth pattern for Cho/Cr in the amygdala of TMGD. In the parietal cortex, a sex-assigned at birth and an intermediate pattern were found. Though assessed post-hoc, exploration of the age of onset of GD in TMGD demonstrated within-group differences in absolute NAA and relative Cho/Cr levels, suggestive for a possible developmental trend. While brain metabolite levels in TMGD resembled those of CW, some interesting findings, such as modulation of metabolite concentrations by age of onset of GD, warrant future inquiry.

Background and objectives Childhood abuse and neglect increase the risk for psychiatric disorders (e.g., depression and anxiety) during adulthood and have been associated with deficits in cognitive control. The specific mechanisms underlying these cognitive control deficits are still unknown. Methods This study examined the expectation for reward to improve inhibitory control in young women (ages 18–35 years) with a history of childhood sexual and/or physical abuse (AG, N = 28), childhood emotional and/or physical neglect (NG, N = 30), or unaffected comparison women (HC, N = 40). They completed a previously validated rewarded (color-word) Stroop task and filled out questionnaires on depression, anxiety, and resilience. Results Surprisingly, a significant group by reward interaction revealed larger performance benefits under reward prospect (relative to no-reward) for the AG group relative to both the NG and HC groups. Limitations A small sample size limiting generalizability. Conclusions These results demonstrate sensitivity of abused subjects to reward in modulating cognitive control and might aid in discussing whether using reward schedules during therapeutic interventions could be effective.

Background In contrast to cisgender persons, transgender persons identify with a different gender than the one assigned at birth. Although research on the underlying neurobiology of transgender persons has been accumulating over the years, neuroimaging studies in this relatively rare population are often based on very small samples resulting in discrepant findings. Aim To examine the neurobiology of transgender persons in a large sample. Methods Using a mega-analytic approach, structural MRI data of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity) were analyzed. Outcomes Structural brain measures, including grey matter volume, cortical surface area, and cortical thickness. RESULTS Transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), we observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined. Clinical Translation The outcomes of this large-scale study may provide a normative framework that may become useful in clinical studies. Strengths and Limitations While this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites. CONCLUSION Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.

Background: Empathy is essential for interpersonal relationships, yet remains difficult to measure. Some evidence suggests that early traumatic experiences leads to alterations in empathic responding. Objective: This study sought to differentiate connections between subtypes of childhood maltreatment, a pictorial test of affective empathy (PET), and self-reported empathy (Interpersonal Reactivity Index; IRI) by using network analysis approach to investigate the structure of relationships between childhood maltreatment and later empathic responding. Method: 301 participants completed the PET, the Early Trauma Inventory Self Report-Short Form (ETISR-SF), the IRI, and questionnaires assessing current mood and perceived stress levels. Results: The PET showed a strong positive association with the IRI subscale empathic concern (EC), after conditioning on all other nodes in the network. EC proved to be a highly central node and was positively related to severity of childhood sexual abuse (CSA), yet not to childhood physical abuse or emotional maltreatment. Pathways between emotional maltreatment and physical abuse and the PET were indirect, passing through self-reported EC and CSA. Conclusions: Our study suggests that CSA more so than other childhood maltreatment experiences is associated with increased self-reported affective empathy, but is not captured directly through a pictorial test of affective empathy.

We provide T2 *-weighted and T1-weighted images acquired on a 3T MRI scanner obtained from 17 transwomen and 29 transmen with gender incongruence; and 22 ciswomen and 19 cismen that identified themselves to the sex assigned at birth. Data from three different techniques that describe global and regional connectivity differences within functional resting-state networks in transwomen and trans men with early-in-life onset gender incongruence are provided: (1) we obtained spatial maps from data-driven independent component analysis using the melodic tool from FSL software; (2) we provide the functional networks interactions of two functional atlases' seeds from a seed to-seed approach; (3) and global graph-theoretical metrics such as the smallworld organization, and the segregation and integration properties of the networks. Interpretations of the present dataset can be found in the original article, doi:10.1016/j.neuroimage.2020.116613 [1] . The original and pro cessed nifti images are available in Mendeley datasets. In addition, correlation matrices for the seed-to-seed and graph theory analyses as well as the graph-theoretical measures were made available in Matlab files. Finally, we present supplementary information for the original article. (C) 2020 The Author(s). Published by Elsevier Inc.

Recent cognitive models suggest that the ability to control emotional information in working memory (WM) may be implicated in the etiology and maintenance of depression. However, few studies have examined the effects of processing relevant and irrelevant emotional stimuli on WM performance in depressed adolescents. In the current study, depressed adolescents (n = 27) and healthy adolescents (n = 49) completed two versions of an emotional n-back task: a low WM load (0-back) task and a high WM load (2-back) task. In the emotion-relevant condition participants were asked to attend to the emotional expression of an angry, happy, or neutral face, whereas in the emotion-irrelevant condition participants were asked to attend to the gender of the face. The results showed a WM improvement for happy faces in the emotion-relevant condition and a WM impairment for happy faces in the emotion-irrelevant condition for healthy adolescents but not for depressed adolescents. No biases toward angry faces were found. These results demonstrate that depressed adolescents do not show a preferential processing of angry faces but rather fail to show a positivity bias as seen in healthy adolescents. This supports the theoretical notion that a depressive disorder is characterized by a blunted reactivity toward positive information and may provide new insights into the underlying mechanisms of youth depression.

International audience; There is a major debate in the theory of mind (ToM) field, concerning whether spontaneous and explicit ToM are based on the same or two distinct cognitive systems. While extensive research on the neural correlates of explicit ToM has demonstrated involvement of the temporo-parietal junction (TPJ) and the medial prefrontal cortex (mPFC), few studies investigated spontaneous ToM, leaving some open questions. Here, we implemented a multistudy approach by pooling data from three fMRI studies to obtain a larger sample to increase power and sensitivity to better define the neurocognitive mechanisms underlying spontaneous ToM. Participants watched videos in which an agent acquires a true or false belief about the location of a ball. Thus, the belief of the agent and that of the participant could either match or differ. Importantly, participants were never asked to consider the belief of the agent and were only instructed to press a button when they detected the presence of the ball after an occluder fell at the end of each video. By analysing the blood-oxygen level dependent signal during the belief formation phase for false versus true beliefs, we found a cluster of activation in the right, and to a lesser extent, left posterior parietal cortex spanning the TPJ, but no mPFC activation. Region of interest (ROI) analysis on bilateral TPJ and mPFC confirmed these results and added evidence to the asymmetry in laterality of the TPJ in spontaneous ToM. Interestingly, the whole brain analysis, supported by an overlap with brain maps, revealed maximum activation in areas involved in visuospatial working memory and attention switching functions, such as the supramarginal gyrus, the middle temporal gyrus, and the inferior frontal gyrus. By contrast, evidence for the presence of brainbehaviour correlations was mixed and there was no evidence for functional connectivity between the TPJ and mPFC. Taken together, these findings help clarifying the brain system supporting spontaneous ToM.

BackgroundPTSD and depression commonly co-occur and have been associated with smaller hippocampal volumes compared to healthy and trauma-exposed controls. However, the hippocampus is heterogeneous, with subregions that may be uniquely affected in individuals with PTSD and depression.MethodsWe used random effects regressions and a harmonized neuroimaging protocol based on FreeSurfer (v6.0) to identify sub-structural hippocampal markers of current PTSD (C-PTSD), depression, and the interaction of these conditions across 31 cohorts worldwide (N=3,115;Mage=38.9±13.9 years). Secondary analyses tested these associations by sex and after modeling the simultaneous effects of remitted PTSD, childhood trauma, mild traumatic brain injury, and alcohol use disorder.ResultsA significant negative main effect of depression (n=800, vs. no depression, n=1456) was observed in the hippocampal tail (ß=−0.13) and CA1 (ß=−0.09) after adjusting for covariates and multiple testing (adjusted p’s (q)=0.028). A main effect of C-PTSD (n=1042 vs. control, n=1359) was not significant, but an interaction between C-PTSD and depression was significant in the CA1 (ß=−0.24, q=0.044). Pairwise comparisons revealed significantly smaller CA1 volumes in individuals with C-PTSD+Depression than controls (ß=−0.12, q=0.012), C-PTSD-only (ß=−0.17, q=0.001), and Depression-only (ß=−0.18, q=0.023). Follow-up analyses revealed sex effects in the hippocampal tail of depressed females, and an interaction effect of C-PTSD and depression in the fimbria of males.ConclusionsCollectively our results suggest that depression is a stronger predictor of hippocampal volumetry than PTSD, particularly in the CA1, and provide compelling evidence of more pronounced hippocampal phenotypes in comorbid PTSD and depression compared to either condition alone.

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.

Background Acute stress leads to a rapid release of noradrenaline and glucocorticoids, which in turn influence cognitive functions such as spatial learning and memory. However, few studies have investigated noradrenergic and glucocorticoid effects on spatial learning and memory in humans. Therefore, we examined the separate and combined effects of noradrenergic and glucocorticoid stimulation on spatial learning and memory. Methods One hundred and four healthy men (mean age = 24.1 years ± SD 3.5) underwent the virtual Morris Water Maze (vMWM) task to test spatial learning and spatial memory retrieval after receiving either 10 mg hydrocortisone or 10 mg yohimbine (an alpha 2-adrenergic receptor antagonist that increases noradrenergic activity), 10 mg hydrocortisone and 10 mg yohimbine combined, or placebo. The vMWM task took place 90 min after yohimbine was administered and 75 min after hydrocortisone was administered. Placebo was given at the same times. Salivary cortisol and alpha amylase levels were measured to check pharmacological stimulation. Results Hydrocortisone and yohimbine increased salivary cortisol and alpha amylase levels. Participants’ task performance improved over time, suggesting successful spatial learning. However, separate and combined noradrenergic and glucocorticoid stimulation had no effect on spatial learning and spatial memory retrieval compared with placebo. Conclusions In healthy young men, hydrocortisone and/or yohimbine did not alter spatial learning or spatial memory retrieval. Importantly, pharmacological stimulation took place prior to learning. Further studies should examine the effects of glucocorticoid and noradrenergic stimulation during encoding, consolidation, and retrieval.

Background: Pain is common and can be debilitating in childhood. Theoretical models propose that attention to pain plays a key role in pain outcomes, however, very little research has investigated this in youth. This study examined how anxiety-related variables and attention control interacted to predict children's attention to pain cues using eye-tracking methodology, and their pain tolerance on the cold pressor test (CPT). Methods: Children aged 8-17 years had their eye-gaze tracked whilst they viewed photographs of other children displaying painful facial expressions during the CPT, before completing the CPT themselves. Children also completed self-report measures of anxiety and attention control. Results: Findings indicated that anxiety and attention control did not impact children's initial fixations on pain or neutral faces, but did impact how long they dwelled on pain versus neutral faces. For children reporting low levels of attention control, higher anxiety was associated with less dwell time on pain faces as opposed to neutral faces, and the opposite pattern was observed for children with high attention control. Anxiety and attention control also interacted to predict pain outcomes. For children with low attention control, increasing anxiety was associated with anticipating more pain and tolerating pain for less time. Conclusions: This is the first study to examine children's attention to pain cues using eye-tracking technology in the context of a salient painful experience. Data suggest that attention control is an important moderator of anxiety on multiple outcomes relevant to young people's pain experiences. Significance: This study uses eye tracking to study attention to pain cues in children. Attention control is an important moderator of anxiety on attention bias to pain and tolerance of cold pressor pain in youth.

Few studies have examined the impact of androgen insensitivity on human spatial learning and memory. In the present study, we tested 11 women with complete androgen insensitivity syndrome (CAIS), a rare genetic disorder characterized by complete absence of AR activity, and compared their performance against 20 comparison males and 19 comparison females on a virtual analog of the Morris Water Maze task. The results replicated a main sex effect showing that men relative to women were faster in finding the hidden platform and had reduced heading error. Furthermore, findings indicated that mean performance of women with CAIS was between control women and control men, though the differences were not statistically significant. Effect size estimates (and corresponding confidence intervals) of spatial learning trials showed little difference between women with CAIS and control women but CAIS women differed from men, but not women, on two variables, latency to find the platform and first-move latency. No differences between groups were present during visible platform trials or the probe trial, a measure of spatial memory. Moreover, groups also did not differ on estimates of IQ and variability of performance. The findings are discussed in relation to androgen insensitivity in human spatial learning and memory.

Functional brain organization in transgender persons remains unclear. Our aims were to investigate global and regional connectivity differences within functional networks in transwomen and transmen with early-in-life onset gender incongruence; and to test the consistency of two available hypotheses that attempted to explain gender variants: (i) a neurodevelopmental cortical hypothesis that suggests the existence of different brain phenotypes based on structural MRI data and genes polymorphisms of sex hormone receptors; (ii) a functional-based hypothesis in relation to regions involved in the own body perception. T2*-weighted images in a 3-T MRI were obtained from 29 transmen and 17 transwomen as well as 22 cisgender women and 19 cisgender men. Resting-state independent component analysis, seed-to-seed functional network and graph theory analyses were performed. Transmen, transwomen, and cisgender women had decreased connectivity compared with cisgender men in superior parietal regions, as part of the salience (SN) and the executive control (ECN) networks. Transmen also had weaker connectivity compared with cisgender men between intra-SN regions and weaker inter-network connectivity between regions of the SN, the default mode network (DMN), the ECN and the sensorimotor network. Transwomen had lower small-worldness, modularity and clustering coefficient than cisgender men. There were no differences among transmen, transwomen, and ciswomen. Together these results underline the importance of the SN interacting with DMN, ECN, and sensorimotor networks in transmen, involving regions of the entire brain with a frontal predominance. Reduced global connectivity graph-theoretical measures were a characteristic of transwomen. It is proposed that the interaction between networks is a keystone in building a gendered self. Finally, our findings suggest that both proposed hypotheses are complementary in explaining brain differences between gender variants.

It has been suggested that altered processing of emotion during cognitive control plays an important role in the etiology of depressive symptoms. The current study investigates the influence of emotional stimuli on working memory (WM) in adolescents with dysphoric symptomatology (DS). Twenty-five adolescents with DS and 40 adolescents with no dysphoric symptomatology (NDS) completed a memory-guided eye movement task. This task assessed the influence of irrelevant affective information on WM processes during high and low cognitive load. Latency analyses showed that, in the high load WM condition, negative distractors disturbed WM performance in adolescents with NDS, but not in adolescents with DS. Accuracy analyses revealed that adolescents with NDS had higher accuracy rates in the presence of positive distractors relative to negative and neutral distractors, and in comparison to adolescents with DS. The findings indicated altered WM performance in the context of emotional distractors in adolescents with DS and may contribute to theoretical knowledge and early prevention of youth depression.

Theories of adolescent behaviour attribute increases in risk-taking and sensation-seeking in this age group to a heightened sensitivity to emotional stimuli on the one hand and a relatively immature cognitive control system on the other hand. However, little research has outlined to what extent relevant and irrelevant emotional stimuli bias the imbalance between affective processing and cognitive control. Thirty-three adolescents (19 females, aged 12-14) and 37 adults (18 females, aged 18-29) completed two attentional conditions of an emotional face working memory (WM) 0-back/2-back task. Participants were asked to attend to the emotional facial expression in the "relevant" emotion condition, and to the gender of the face in the "irrelevant" condition. The results revealed a WM improvement for happy faces in the relevant condition in both age groups, and an impairment for irrelevant happy faces in adolescents, but not adults. Furthermore, the difference between both attentional conditions for happy faces was larger in adolescents than adults. Results are discussed within the framework of theories of adolescent behaviour.

BackgroundStigmatization 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.MethodTwenty 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).ResultsDuring 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.ConclusionThe results bear implications for the role of social exclusion in development of mental health problems in socially marginalized groups.

The current study set out to investigate trait versus state views regarding inhibitory deficits in participants scoring high and low on contamination fear. Furthermore, it was investigated whether inhibitory deficits are specific for contamination-related stimuli. Participants were selected on high (n = 40) vs. low (n = 44) contamination fear and subsequently randomly assigned to receive either a neutral induction or an obsessive-compulsive (OCD) symptom induction. Participants performed a stop-signal task including contamination-specific, general negative, and neutral pictures before and after the induction. In contrast to state views, no change in inhibitory performance after the OCD symptom induction and no differential effect of contamination-related picture valence was found. Moreover, in contrast to the trait view, baseline inhibition capacity did not predict an increase in symptoms after an OCD symptom induction. Finally, contrary to expectations, participants high in contamination fear showed better inhibition than low contamination fear controls. Therefore, the results of the current study are inconclusive regarding the state-trait debate, but are clearly in contrast with the idea of trait inhibitory deficits in contamination fear.

Objectives Sex differences have been found in spatial learning and spatial memory, with several studies indicating that males outperform females. We tested in the virtual Morris Water Maze (vMWM) task, whether sex differences in spatial cognitive processes are attributable to differences in spatial learning or spatial memory retrieval in a large student sample. Methods We tested 90 healthy students (45 women and 45 men) with a mean age of 23.5 years ( SD = 3.5). Spatial learning and spatial memory retrieval were measured by using the vMWM task, during which participants had to search a virtual pool for a hidden platform, facilitated by visual cues surrounding the pool. Several learning trials assessed spatial learning, while a separate probe trial assessed spatial memory retrieval. Results We found a significant sex effect during spatial learning, with males showing shorter latency and shorter path length, as compared to females (all p 0.001). Yet, there was no significant sex effect in spatial memory retrieval ( p = 0.615). Furthermore, post-hoc analyses revealed significant sex differences in spatial search strategies ( p p = 0.375). Conclusion Our results indicate that in healthy young adults, males show faster spatial learning in a virtual environment, as compared to females. Interestingly, we found no significant sex differences during spatial memory retrieval. Our study raises the question, whether men and women use different learning strategies, which nevertheless result in equal performances of spatial memory retrieval.

The incidence of depression is approximately 2-fold greater in women than men but the biological mechanisms underlying this phenomenon remain unclear. One potential mechanism that has been understudied is immune function, which is modulated by sex hormones and differs considerably between males and females. The immune-regulating kynurenine pathway previously has been implicated in the pathogenesis of mood disorders. In particular, a decreased ratio of neuroprotective (kynurenic acid; KynA) to neurotoxic (3-hydroxykynurenine; 3HK and quinolinic acid; QA) kynurenine pathway metabolites has been reported in several mood disorder subtypes. Yet there is a paucity of research investigating sex differences in the kynurenine pathway in the context of depression. Similarly, oral contraceptive (OC) use has been shown to be a risk factor for depression but to our knowledge this epidemiological relationship has not been considered within the framework of immune dysfunction. Here, we compared the concentrations of c-reactive protein (CRP) and kynurenine pathway metabolites in a combined sample of subjects with major depressive disorder (MDD), bipolar disorder (BD), and healthy controls (HC) comprising 130 men and 350 women. CRP was measured in a CLIA-certified hospital laboratory. Kynurenine metabolites were quantified using high performance liquid chromatography with tandem mass spectrometry. Estradiol and progesterone were quantified with the Mesoscale Discovery (MSD) platform. After controlling for diagnosis, age, sex, BMI, analysis batch, and self-reported childhood trauma we found that women had significantly lower KynA/3HK and KynA/QA ratios than men, and that these results were driven by a decrease in KynA. There was no significant difference between males and females in the concentration of CRP. Further, women taking OC showed significantly higher levels of CRP and lower ratios of KynA/3HK and KynA/QA compared with women on no form of contraception. Moreover, among women using OC, progesterone concentrations were positively correlated with KynA, KynA/3HK, and KynA/QA. Although preliminary, our results indicate that on average, healthy women show the same pattern of kynurenine pathway metabolism as that observed in subjects with depression. This finding raises the possibility that a reduction in KynA concentrations in women may constitute a vulnerability factor that partly explains the higher incidence of depression in females. Further, the significant association between OC use and reduced KynA as well as increased CRP, could conceivably partially account for the epidemiological association between OC use and depression. Nonetheless, because of the cross-sectional nature of this study, these hypotheses need to be more rigorously tested with longitudinal designs and/or large epidemiological studies.

Gender dysphoria describes the psychological distress caused by identifying with the sex opposite to the one assigned at birth. In recent years, much progress has been made in characterizing the needs of transgender persons wishing to transition to their preferred gender, thus helping to optimize care. This critical review of the literature examines their common mental health issues, several individual risk factors for psychiatric comorbidity, and current research on the underlying neurobiology. Prevalence rates of persons identifying as transgender and seeking help with transition have been rising steeply since 2000 across Western countries; the current U.S. estimate is 0.6%. Anxiety and depression are frequently observed both before and after transition, although there is some decrease afterward. Recent research has identified autistic traits in some transgender persons. Forty percent of transgender persons endorse suicidality, and the rate of self-injurious behavior and suicide are markedly higher than in the general population. Individual factors contributing to mental health in transgender persons include community attitudes, societal acceptance, and posttransition physical attractiveness. Neurobiologically, whereas structural MRI data are thus far inconsistent, functional MRI evidence in trans persons suggests changes in some brain areas concerned with olfaction and voice perception consistent with sexual identification, but here too, a definitive picture has yet to emerge. Mental health clinicians, together with other health specialists, have an increasing role in the assessment and treatment of gender dysphoria in transgender individuals.

Highlights • Little is known how emotion interacts with cognitive control in adolescents. • Adolescents and adults completed emotional working memory task during 3T fMRI. • Cognitive load interacted with emotion in adults but not adolescents in dlPFC. • Ventral striatum activity to happy faces was larger in adolescents relative to adults. • Under task relevance amygdala activation was stronger to happy faces in adolescents., In adults, cognitive control is supported by several brain regions including the limbic system and the dorsolateral prefrontal cortex (dlPFC) when processing emotional information. However, in adolescents, some theories hypothesize a neurobiological imbalance proposing heightened sensitivity to affective material in the amygdala and striatum within a cognitive control context. Yet, direct neurobiological evidence is scarce. Twenty-four adolescents (12–16) and 28 adults (25–35) completed an emotional n-back working memory task in response to happy, angry, and neutral faces during fMRI. Importantly, participants either paid attention to the emotion (task-relevant condition) or judged the gender (task-irrelevant condition). Behaviorally, for both groups, when happy faces were task-relevant, performance improved relative to when they were task-irrelevant, while performance decrements were seen for angry faces. In the dlPFC, angry faces elicited more activation in adults during low relative to high cognitive load (2-back vs. 0-back). By contrast, happy faces elicited more activation in the amygdala in adolescents when they were task-relevant. Happy faces also generally increased nucleus accumbens activity (regardless of relevance) in adolescents relative to adults. Together, the findings are consistent with neurobiological models of adolescent brain development and identify neurodevelopmental differences in cognitive control emotion interactions.

Background Anxiety disorders are the leading cause of mental illness in adolescence. While anxious adolescents show impairments in emotion processing and deficits in emotion regulation, few studies have attempted to improve emotion regulation within these populations. Method This study used a multi-method design to test a newly developed emotion regulation training aimed at improving insight into emotions and instructing cognitive reappraisal. The efficacy of cognitive reappraisal was investigated in 27 clinically anxious youth (Age: M =12.36, SD =2.59) and 43 healthy controls (Age: M =13.07, SD =2.19) using psychophysiological measures. Specifically, heart rate variability, pupil dilation, and visual fixations were recorded while youth had to up- or downregulate their emotions in response to affective pictures in the Psychophysiological Indicators of Emotion Regulation (PIER) task. Results The novel training effectively improved self-reported emotion regulation and momentary anxiety in both groups. Moreover, initial group differences in emotional reactivity mostly disappeared when participants were instructed to apply emotion regulation in the task. However, pupil dilation data suggested that participants with anxiety disorders required more cognitive resources for the upregulation of negative affect to counteract this effect. Limitations The relatively small sample size and large age range could hamper detection of additional group differences that may exist. Conclusions The current study provides evidence that anxious youth can apply cognitive reappraisal to a similar extent as healthy adolescents after emotion regulation training but may need to exert more effort to do so. This training could be a valuable addition to current treatment programs.

Anxiety and depression are associated with altered communication within global brain networks and between these networks and the amygdala. Functional connectivity studies demonstrate an effect of anxiety and depression on four critical brain networks involved in top-down attentional control (fronto-parietal network; FPN), salience detection and error monitoring (cingulo-opercular network; CON), bottom-up stimulus-driven attention (ventral attention network; VAN), and default mode (default mode network; DMN). However, structural evidence on the white matter (WM) connections within these networks and between these networks and the amygdala is lacking. The current study in a large healthy sample (n = 483) observed that higher trait anxiety-depression predicted lower WM integrity in the connections between amygdala and specific regions of the FPN, CON, VAN, and DMN. We discuss the possible consequences of these anatomical alterations for cognitive-affective functioning and underscore the need for further theory-driven research on individual differences in anxiety and depression on brain structure.

OBJECTIVE: In both children and adults, psychiatric illness is associated with structural brain alterations, particularly in the prefrontal cortex (PFC). However, most studies compare gray matter volume (GMV) in healthy volunteers (HVs) to one psychiatric group. We compared GMV among youth with anxiety disorders, bipolar disorder (BD), disruptive mood dysregulation disorder (DMDD), attention-deficit/hyperactivity disorder (ADHD), and HVs. METHOD: 3-Tesla T1-weighted magnetic resonance imaging (MRI) scans were acquired in 184 youths (39 anxious, 20 BD, 52 DMDD, 20 ADHD, and 53 HV). Voxel-based morphometry analyses were conducted. One-way analysis of variance (ANOVA) tested GMV differences with whole-brain family-wise error (FWE; p

Objectives Stress hormones such as cortisol are known to influence a wide range of cognitive functions, including hippocampal based spatial memory. In the brain, cortisol acts via two different receptors: the glucocorticoid (GR) and the mineralocorticoid receptor (MR). As the MR has a high density in the hippocampus, we examined the effects of pharmacological MR stimulation on spatial memory. Methods Eighty healthy participants (40 women, 40 men, mean age = 23.9 years ± SD = 3.3) completed the virtual Morris Water Maze (vMWM) task to test spatial encoding and spatial memory retrieval after receiving 0.4 mg fludrocortisone, a MR agonist, or placebo. Results There was no effect of MR stimulation on spatial encoding during the vMWM task. However, participants who received fludrocortisone exhibited improved spatial memory retrieval performance. There was neither a main effect of sex nor a sex-by-treatment interaction. Conclusion In young healthy participants, MR stimulation improved hippocampal based spatial memory retrieval in a virtual Morris Water Maze task. Our study not only confirms the importance of MR function in spatial memory, but suggests beneficial effects of acute MR stimulation on spatial memory retrieval in humans.

Despite mounting evidence regarding the underlying neurobiology in transgender persons, information regarding resting-state activity, particularly after hormonal treatment, is lacking. The present study examined differences between transgender persons on long-term cross-sex hormone therapy and comparisons on two measures of local functional connectivity, intensity of spontaneous resting-state activity (low frequency fluctuations, LFF) and local synchronization of specific brain areas (regional homogeneity, ReHo). Nineteen transgender women (TW, male-to-female), 19 transgender men (TM, female-to-male), 21 non-transgender men (NTM) and 20 non-transgender women (NTW) underwent a resting-state MRI scan. The results showed differences between transgender persons and non-transgender comparisons on both LFF and ReHo measures in the frontal cortex, medial temporal lobe, and cerebellum. More interestingly, circulating androgens correlated for TM in the cerebellum and regions of the frontal cortex, an effect that was associated with treatment duration in the cerebellum. By comparison, no associations were found for TW with estrogens. These data provide first evidence for a potential masculinization of local functional connectivity in hormonally-treated transgender men.

Emotion regulation and associated autonomic activation develop throughout childhood and adolescence under the influence of the family environment. Specifically, physiological indicators of autonomic nervous system activity such as interoceptive sensitivity and vagally mediated heart rate variability (HRV) can inform on emotion regulation. Although the effect of parental emotion socialization on emotion regulation appears to be influenced by autonomic processes, research on physiological regulation and the influence of parental factors remains scarce. This study investigated the relationship between self-reported habitual emotion regulation strategies and HRV at rest as well as interoceptive sensitivity in forty-six youngsters (27 female; age: M = 13.00, SD = 2.13). Secondly, the association between these autonomic correlates and parental psychopathology was also studied. Whereas better interoceptive sensitivity was related to reduced maladaptive emotion regulation, specifically rumination, high HRV was related to more use of external emotion regulation strategies (i.e., support seeking). In addition, increased HRV and decreased interoceptive sensitivity were associated with maternal internalizing and there was evidence for a possible mediation effect of HRV in the relationship between maternal internalizing and child external emotion regulation. This study elucidates the link between cognitive emotion regulation strategies and underlying physiological regulation in adolescents but also indicates a putative influence of maternal internalizing symptoms on emotion regulation in their offspring. ispartof: PLOS ONE vol:11 issue:10 ispartof: location:United States status: published

Background: To date, research findings are inconsistent about whether the neuroanatomy in transgender persons resembles that of their natal sex or their gender identity. Moreover, few studies have examined the effects of long-term cross-sex hormonal treatment on neuroanatomy in this cohort. The purpose of the present study was to examine neuroanatomical differences in transgender persons after prolonged cross-sex hormone therapy. Methods: Eighteen transgender men (female-to-male), 17 transgender women (male-to-female), 30 nontransgender men (natal men), and 27 nontransgender women (natal women) completed a high-resolution structural magnetic resonance imaging scan at 3 T. Eligibility criteria for transgender persons were gender-affirming surgery and at least 2 years of cross-sex hormone therapy. Exclusion criteria for nontransgender persons were presence of psychiatric or neurological disorders. Results: The mean neuroanatomical volume for the amygdala, putamen, and corpus callosum differed between transgender women and natal women but not between transgender women and natal men. Differences between transgender men and natal men were found in several brain structures, including the medial temporal lobe structures and cerebellum. Differences between transgender men and natal women were found in the medial temporal lobe, nucleus accumbens, and 3rd ventricle. Sexual dimorphism between nontransgender men and women included larger cerebellar volumes and a smaller anterior corpus callosum in natal men than in natal women. The results remained stable after correcting for additional factors including age, total intracranial volume, anxiety, and depressive symptoms. Conclusions: Neuroanatomical differences were region specific between transgender persons and their natal sex as well as their gender identity, raising the possibility of a localized influence of sex hormones on neuroanatomy.

Controversy revolves around the question of whether psychological factors like attention and emotion can influence the initial feedforward response in primary visual cortex (V1). Although traditionally, the electrophysiological correlate of this response in humans (the C1 component) has been found to be unaltered by psychological influences, a number of recent studies have described attentional and emotional modulations. Yet, research into psychological effects on the feedforward V1 response has neglected possible direct contributions of concomitant pupil-size modulations, which are known to also occur under various conditions of attentional load and emotional state. Here we tested the hypothesis that such pupil-size differences themselves directly affect the feedforward V1 response. We report data from two complementary experiments, in which we used procedures that modulate pupil size without differences in attentional load or emotion while simultaneously recording pupil-size and EEG data. Our results confirm that pupil size indeed directly influences the feedforward V1 response, showing an inverse relationship between pupil size and early V1 activity. While it is unclear in how far this effect represents a functionally-relevant adaptation, it identifies pupil-size differences as an important modulating factor of the feedforward response of V1 and could hence represent a confounding variable in research investigating the neural influence of psychological factors on early visual processing.