Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and use normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1,985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision making.
Anxiety and stress disorders are among the most prevalent neuropsychiatric disorders. In recent years, multiple studies have examined brain regions and networks involved in anxiety symptomatology in an effort to better understand the mechanisms involved and to develop more effective treatments. However, much remains unknown regarding the specific abnormalities and interactions between networks of regions underlying anxiety disorder presentations. We examined recent neuroimaging literature that aims to identify neural mechanisms underlying anxiety, searching for patterns of neural dysfunction that might be specific to different anxiety disorder categories. Across different anxiety and stress disorders, patterns of hyperactivation in emotion-generating regions and hypoactivation in prefrontal/regulatory regions are common in the literature. Interestingly, evidence of differential patterns is also emerging, such that within a spectrum of disorders ranging from more fear-based to more anxiety-based, greater involvement of emotion-generating regions is reported in panic disorder and specific phobia, and greater involvement of prefrontal regions is reported in generalized anxiety disorder and posttraumatic stress disorder. We summarize the pertinent literature and suggest areas for continued investigation.
Post‐traumatic stress disorder (PTSD) is often characterized by deficits in memory encoding and retrieval and aberrant fear and extinction learning. The hippocampus plays a critical role in memory and contextual processing and has been implicated in intrinsic functional connectivity networks involved in self‐referential thought and memory‐related processes. This review focuses on hippocampal activation findings during memory and fear and extinction learning tasks, as well as resting state hippocampal connectivity in individuals with PTSD. A preponderance of functional neuroimaging studies to date, using memory, fear learning, and extinction tasks, report decreased or “controls comparable” hippocampal activation in individuals with PTSD, which is usually associated with poorer performance on the task imaged. Existing evidence thus raises the possibility that greater hippocampal recruitment in PTSD participants may be required for similar performance levels. Studies of resting state functional connectivity in PTSD predominantly report reduced within‐network connectivity in the default mode network (DMN), as well as greater coupling between the DMN and salience network (SN) via the hippocampus. Together, these findings suggest that deficient hippocampal activation in PTSD may be associated with poorer performance during memory, extinction recall, and fear renewal tasks. Furthermore, studies of resting state connectivity implicate the hippocampus in decreased within‐network DMN connectivity and greater coupling with SN regions characteristic of PTSD.
Background: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre-and posttreatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. Methods: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN). Results: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pretreatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042).
Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain. Other treatment options include fixed-dose combination products of oxycodone analgesic together with naloxone.
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