Multivariate analyses provide a more accurate characterization of the association between brain alterations and psychosis because they enable the modeling of other key factors that influence neuroimaging phenotypes.

Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother–child interactions. Following a mental health assessment, 45 mothers and their children (ages 12–42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother–child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother–child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD.

This study tested whether mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) vs healthy controls (HC) would show greater limbic and less frontocortical activity when viewing young children during separation compared to quiet play. Mothers of 20 children (12-42 months) participated: 11 IPV-PTSD mothers and 9 HC with no PTSD. During fMRI, mothers watched epochs of play and separation from their own and unfamiliar children. The study focused on comparison of PTSD mothers vs HC viewing children in separation vs play, and viewing own vs unfamiliar children in separation. Both groups showed distinct patterns of brain activation in response to viewing children in separation vs play. PTSD mothers showed greater limbic and less frontocortical activity (BA10) than HC. PTSD mothers also reported feeling more stressed than HC when watching own and unfamiliar children during separation. Their self-reported stress was associated with greater limbic and less frontocortical activity. Both groups also showed distinct patterns of brain activation in response to viewing their own vs unfamiliar children during separation. PTSD mothers' may not have access to frontocortical regulation of limbic response upon seeing own and unfamiliar children in separation. This converges with previously reported associations of maternal IPV-PTSD and atypical caregiving behavior following separation.

Background. The pandemic caused by coronavirus disease 2019 (COVID-19) has forced governments to implement strict social mitigation strategies to reduce the morbidity and mortality from acute infections. These strategies, however, carry a significant risk for mental health, which can lead to increased short-term and long-term mortality and is currently not included in modeling the impact of the pandemic. Methods. We used years of life lost (YLL) as the main outcome measure, applied to Switzerland as an example. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status, and social isolation, as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans. Results. The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average of 9.79 YLL. Conclusions. The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

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Maternal interpersonal violence-related post-traumatic stress disorder (IPV-PTSD) is known to be associated with impairment of a mother's capacity to participate in mutual emotion regulation during her child's first years of life. This study tested the hypothesis that maternal difficulty in identifying feelings in self and other, as an important dimension of the construct of alexithymia, together with maternal IPV-PTSD, would be negatively associated with maternal sensitivity. Maternal sensitivity to child emotional communication is a marker of maternal capacity to engage in mutual regulation of emotion and arousal. Following diagnostic interviews and administration of the Toronto Alexithymia Scale, 56 mothers and their toddlers (ages 12-42 months) were filmed during free-play and separation/novelty-exposure. Observed maternal sensitivity was coded via the CARE-Index. Maternal IPV-PTSD severity, difficulty in identifying emotions, and lower socio-economic status were all associated with less maternal sensitivity, and also with more maternal controlling and unresponsive behavior on the CARE-Index.

IMPORTANCE Major depressive disorder, bipolar disorder, posttraumatic stress disorder, and anxiety disorders are highly comorbid and have shared clinical features. It is not yet known whether their clinical overlap is reflected at the neurobiological level. OBJECTIVE To detect transdiagnostic convergence in abnormalities in task-related brain activation. DATA SOURCE Task-related functional magnetic resonance imaging articles published in PubMed, Web of Science, and Google Scholar during the last decade comparing control individuals with patients with mood, posttraumatic stress, and anxiety disorders were examined. STUDY SELECTION Following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines, articles were selected if they reported stereotactic coordinates of whole-brain-based activation differences between adult patients and control individuals. DATA EXTRACTION AND SYNTHESIS Coordinates of case-control differences coded by diagnosis and by cognitive domain based on the research domain criteria were analyzed using activation likelihood estimation. MAIN OUTCOMES AND MEASURES Identification of transdiagnostic clusters of aberrant activation and quantification of the contribution of diagnosis and cognitive domain to each cluster. RESULTS A total of 367 experiments (major depressive disorder, 149; bipolar disorder, 103; posttraumatic stress disorder, 55; and anxiety disorders, 60) were included comprising observations from 4507 patients and 4755 control individuals. Three right-sided clusters of hypoactivation were identified centered in the inferior prefrontal cortex/insula (volume, 2120 mm 3), the inferior parietal lobule (volume, 1224 mm 3), and the putamen (volume, 888 mm 3); diagnostic differences were noted only in the putamen (χ 2 3 = 8.66; P = .03), where hypoactivation was more likely in bipolar disorder (percentage contribution = 72.17%). Tasks associated with cognitive systems made the largest contribution to each cluster (percentage contributions >29%). Clusters of hyperactivation could only be detected using a less stringent threshold. These were centered in the perigenual/dorsal anterior cingulate cortex (volume, 2208 mm 3), the left amygdala/parahippocampal gyrus (volume, 2008 mm 3), and the left thalamus (volume, 1904 mm 3). No diagnostic differences were observed (χ 2 3 < 3.06; P > .38), while tasks associated with negative valence systems made the largest contribution to each cluster (percentage contributions >49%). All findings were robust to the moderator effects of age, sex, and magnetic field strength of the scanner and medication. CONCLUSIONS AND RELEVANCE In mood disorders, posttraumatic stress disorder, and anxiety disorders, the most consistent transdiagnostic abnormalities in task-related brain activity converge in regions that are primarily associated with inhibitory control and salience processing. Targeting these shared neural phenotypes could potentially mitigate the risk of affective morbidity in the general population and improve outcomes in clinical...

Abstract-In young individuals, caffeine-mediated blockade of adenosine receptors and vasoconstriction has direct repercussions on task-related activations, changes in functional connectivity, as well as global vascular effects. To date, no study has explored the effect of caffeine on brain activation patterns during highly demanding cognitive tasks in the elderly. This prospective, placebo-controlled crossover design comprises 24 healthy elderly individuals (mean age 68.8 ± 4.0 years, 17 females) performing a 2-back working memory (WM) task in functional magnetic resonance imaging (fMRI). Analyses include complimentary assessment of task-related activations (general linear model, GLM), functional connectivity (tensorial independent component analysis, TICA), and baseline perfusion (arterial spin labeling). Despite a reduction in whole-brain global perfusion (À22.7%), caffeine-enhanced task-related GLM activation in a local and distributed network is most pronounced in the bilateral striatum and to a lesser degree in the right middle and inferior frontal gyrus, bilateral insula, left superior and inferior parietal lobule as well as in the cerebellum bilaterally. TICA was significantly enhanced (+8.2%) in caffeine versus placebo in a distributed and task-relevant network including the pre-frontal cortex, the supplementary motor area, the ventral premotor cortex and the parietal cortex as well as the occipital cortex (visual stimuli) and basal ganglia. The inverse comparison of placebo versus caffeine had no significant difference. Activation strength of the task-relevant-network component correlated with response accuracy for caffeine yet not for placebo, indicating a selective cognitive effect of caffeine. The present findings suggest that acute caffeine intake enhances WM-related brain activation as well as functional connectivity of blood oxygen level-dependent fMRI in elderly individuals. Ó