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BrighT STAR was a diagnostic stewardship collaborative of 14 pediatric intensive care units (PICUs) across the United States designed to standardize and reduce unnecessary blood cultures and study the impact on patient outcomes and broad-spectrum antibiotic use. We now examine the implementation process in detail to understand how sites facilitated this diagnostic stewardship program in their PICUs.
Design:
A multi-center electronic survey of the 14 BrighT STAR sites, based on qualitative data about the implementation process collected during the primary phase of BrighT STAR.
Setting:
14 PICUs enrolled in BrighT STAR.
Participants:
Site leads at each enrolled site.
Methods:
An electronic survey guided by implementation science literature and based on data collected during BrighT STAR was administered to all 14 sites after completion of the primary phase of the collaborative.
Results:
10 specific tasks appear critical to implementing blood culture diagnostic stewardship, with variability in site-level strategies employed to accomplish those tasks. Sites rated certain tasks and strategies as highly important. Strategies used in top-performing sites were distinct from those used in lower-performing sites. Certain strategies may link to drivers of culture overuse and represent key targets for changing clinician behavior.
Conclusions:
BrighT STAR offers important insights into the tasks and strategies used to facilitate successful diagnostic stewardship in the PICU. More work is needed to compare specific strategies and optimize stewardship outcomes in this complex environment.
Major depressive disorder (MDD) is a tremendous global disease burden and the leading cause of disability worldwide. Unfortunately, individuals diagnosed with MDD typically experience a delayed response to traditional antidepressants and many do not adequately respond to pharmacotherapy, even after multiple trials. The critical need for novel antidepressant treatments has led to a recent resurgence in the clinical application of psychedelics, and intravenous ketamine, which has been investigated as a rapid-acting treatment for treatment resistant depression (TRD) as well acute suicidal ideation and behavior. However, variations in the type and quality of experimental design as well as a range of treatment outcomes in clinical trials of ketamine make interpretation of this large body of literature challenging.
Objectives
This umbrella review aims to advance our understanding of the effectiveness of intravenous ketamine as a pharmacotherapy for TRD by providing a systematic, quantitative, large-scale synthesis of the empirical literature.
Methods
We performed a comprehensive PubMed search for peer-reviewed meta-analyses of primary studies of intravenous ketamine used in the treatment of TRD. Meta-analysis and primary studies were then screened by two independent coding teams according to pre-established inclusion criteria as well as PRISMA and METRICS guidelines. We then employed metaumbrella, a statistical package developed in R, to perform effect size calculations and conversions as well as statistical tests.
Results
In a large-scale analysis of 1,182 participants across 51 primary studies, repeated-dose administration of intravenous ketamine demonstrated statistically significant effects (p<0.05) compared to placebo-controlled as well as other experimental conditions in patients with TRD, as measured by standardized clinician-administered and self-report depression symptom severity scales.
Conclusions
This study provides large-scale, quantitative support for the effectiveness of intravenous, repeated-dose ketamine as a therapy for TRD and a report of the relative effectiveness of several treatment parameters across a large and rapidly growing literature. Future investigations should use similar analytic tools to examine evidence-stratified conditions and the comparative effectiveness of other routes of administration and treatment schedules as well as the moderating influence of other clinical and demographic variables on the effectiveness of ketamine on TRD and suicidal ideation and behavior.
Panic disorder (PD) and agoraphobia (AG) are highly comorbid anxiety disorders with an increasing prevalence that have a significant clinical and public health impact but are not adequately recognized and treated. Although the current functional neuroimaging literature has documented a range of neural abnormalities in these disorders, primary studies are often not sufficiently powered and their findings have been inconsistent.
Objectives
This meta-analysis aims to advance our understanding of the neural underpinnings of PD and AG by identifying the most robust patterns of differential neural activation that differentiate individuals diagnosed with one of or both these disorders from age-matched healthy controls.
Methods
We conducted a comprehensive literature search in the PubMed database for all peer-reviewed, whole-brain, task-based functional magnetic resonance imaging (fMRI) activation studies that compared adults diagnosed with PD and/or AG with age-matched healthy controls. Each of these articles was screened by two independent coding teams using formal inclusion criteria and according to current PRISMA guidelines. We then performed a voxelwise, whole-brain, meta-analytic comparison of PD/AG participants with age-matched healthy controls using multilevel kernel density analysis (MKDA) with ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias and 10,000 Monte Carlo simulations to correct for multiple comparisons.
Results
With data from 34 primary studies and a substantial sample size (N=2138), PD/AG participants, relative to age-matched healthy controls, exhibited a reliable pattern of statistically significant, (p<.05-0.0001; FWE-corrected) abnormal neural activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
In this meta-analysis we found robust patterns of differential neural activation in participants diagnosed with PD/AG relative to age-matched healthy controls. These findings advance our understanding of the neural underpinnings of PD and AG and inform the development of brain-based clinical interventions such as non-invasive brain stimulation (NIBS) and treatment prediction and matching algorithms. Future studies should also investigate the neural similarities and differences between PD and AG to increase our understanding of possible differences in their etiology, diagnosis, and treatment.
There has been rapidly growing interest in understanding the pharmaceutical and clinical properties of psychedelic and dissociative drugs, with a particular focus on ketamine. This compound, long known for its anesthetic and dissociative properties, has garnered attention due to its potential to rapidly alleviate symptoms of depression, especially in individuals with treatment-resistant depression (TRD) or acute suicidal ideation or behavior. However, while ketamine’s psychopharmacological effects are increasingly well-documented, the specific patterns of its neural impact remain a subject of exploration and basic questions remain about its effects on functional activation in both clinical and healthy populations.
Objectives
This meta-analysis seeks to contribute to the evolving landscape of neuroscience research on dissociative drugs such as ketamine by comprehensively examining the effects of acute ketamine administration on neural activation, as measured by functional magnetic resonance imaging (fMRI), in healthy participants.
Methods
We conducted a meta-analysis of existing fMRI activation studies of ketamine using multilevel kernel density analysis (MKDA). Following a comprehensive PubMed search, we quantitatively synthesized all published primary fMRI whole-brain activation studies of the effects of ketamine in healthy subjects with no overlapping samples (N=18). This approach also incorporated ensemble thresholding (α=0.05-0.0001) to minimize cluster-size detection bias and Monte Carlo simulations to correct for multiple comparisons.
Results
Our meta-analysis revealed statistically significant (p<0.05-0.0001; FWE-corrected) alterations in neural activation in multiple cortical and subcortical regions following the administration of ketamine to healthy participants (N=306).
Conclusions
These results offer valuable insights into the functional neuroanatomical effects caused by acute ketamine administration. These findings may also inform development of therapeutic applications of ketamine for various psychiatric and neurological conditions. Future studies should investigate the neural effects of ketamine administration, including both short-term and long-term effects, in clinical populations and their relation to clinical and functional improvements.
Bipolar I disorder (BD-I) is a chronic and recurrent mood disorder characterized by alternating episodes of depression and mania; it is also associated with substantial morbidity and mortality and with clinically significant functional impairments. While previous studies have used functional magnetic resonance imaging (fMRI) to examine neural abnormalities associated with BD-I, they have yielded mixed findings, perhaps due to differences in sampling and experimental design, including highly variable mood states at the time of scan.
Objectives
The purpose of this study is to advance our understanding of the neural basis of BD-I and mania, as measured by fMRI activation studies, and to inform the development of more effective brain-based diagnostic systems and clinical treatments.
Methods
We conducted a large-scale meta-analysis of whole-brain fMRI activation studies that compared participants with BD-I, assessed during a manic episode, to age-matched healthy controls. Following PRISMA guidelines, we conducted a comprehensive PubMed literature search using two independent coding teams to evaluate primary studies according to pre-established inclusion criteria. We then used multilevel kernel density analysis (MKDA), a well-established, voxel-wise, whole-brain, meta-analytic approach, to quantitatively synthesize all qualifying primary fMRI activation studies of mania. We used ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias, and 10,000 Monte Carlo simulations to correct for multiple comparisons.
Results
We found that participants with BD-I (N=2,042), during an active episode of mania and relative to age-matched healthy controls (N=1,764), exhibit a pattern of significantly (p<0.05-0.0001; FWE-corrected) different activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
This study supports the formulation of a robust neural basis for BD-I during manic episodes and advances our understanding of the pattern of abnormal activation in this disorder. These results may inform the development of novel brain-based clinical tools for bipolar disorder such as diagnostic biomarkers, non-invasive brain stimulation, and treatment-matching protocols. Future studies should compare the neural signatures of BD-I to other related disorders to facilitate the development of protocols for differential diagnosis and improve treatment outcomes in patients with BD-I.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric condition that frequently originates in early development and is associated with a variety of functional impairments. Despite a large functional neuroimaging literature on ADHD, our understanding of the neural basis of this disorder remains limited, and existing primary studies on the topic include somewhat divergent results.
Objectives
The present meta-analysis aims to advance our understanding of the neural basis of ADHD by identifying the most statistically robust patterns of abnormal neural activation throughout the whole-brain in individuals diagnosed with ADHD compared to age-matched healthy controls.
Methods
We conducted a meta-analysis of task-based functional magnetic resonance imaging (fMRI) activation studies of ADHD. This included, according to PRISMA guidelines, a comprehensive PubMed search and predetermined inclusion criteria as well as two independent coding teams who evaluated studies and included all task-based, whole-brain, fMRI activation studies that compared participants diagnosed with ADHD to age-matched healthy controls. We then performed multilevel kernel density analysis (MKDA) a well-established, whole-brain, voxelwise approach that quantitatively combines existing primary fMRI studies, with ensemble thresholding (p<0.05-0.0001) and multiple comparisons correction.
Results
Participants diagnosed with ADHD (N=1,550), relative to age-matched healthy controls (N=1,340), exhibited statistically significant (p<0.05-0.0001; FWE-corrected) patterns of abnormal activation in multiple brains of the cerebral cortex and basal ganglia across a variety of cognitive control tasks.
Conclusions
This study advances our understanding of the neural basis of ADHD and may aid in the development of new brain-based clinical interventions as well as diagnostic tools and treatment matching protocols for patients with ADHD. Future studies should also investigate the similarities and differences in neural signatures between ADHD and other highly comorbid psychiatric disorders.
Removal and disposal of nonnative trees is expensive and time-consuming. Using these nonnative trees as a substrate to produce edible mushrooms could diversify farming operations and provide additional income to small-scale farmers. This research compared the production of shiitake mushrooms (Lentinula edodes) on nonnative tree logs to shiitake mushroom production on native oak (Quercus L.) logs, which are the traditional substrate. In a 2-yr study, we evaluated nonnative tree species as alternate substrates for growing shiitake mushrooms at farms in northern Florida and southern Georgia. A mix of native Quercus spp. and nonnative trees was targeted for removal on participating farms. Five nonnative tree species were initially tested for their ability to produce edible mushrooms, either shiitake or oyster (Pleurotus ostreatus var. florida). Of the nonnative trees we tested: Chinaberry (Melia azedarach L.), Chinese tallowtree [Triadica sebifera (L.) Small], silktree (Albizia julibrissin Durazz.), earleaf acacia (Acacia auriculiformis A. Cunn. ex Benth.), and paperbark tree [Melaleuca quinquenervia (Cav.) S.F. Blake], only T. sebifera produced shiitake mushrooms, and none produced native Florida oyster mushrooms. In on-farm trials, Quercus spp. logs produced more total mushrooms and more mushrooms per log and had a higher total mushroom yield per log. However, mushrooms produced on T. sebifera logs had higher mean weight per mushroom. Edible fungi can be used to recycle invasive, nonnative T. sebifera and transform their biomass from waste into an income-producing resource.
European chub Leuciscus cephalus collected from five localities in the lowland and subalpine regions of Austria were analysed for oestrogenic effects of endocrine-disrupting chemicals and the presence of the plerocercoid of the tapeworm Ligula intestinalis. Of 1494 chub analysed, only seven (six males, one female) were found to be infected with single, but large plerocercoids up to 15 cm in length. Ligula-infected fish showed comparatively immature gonads, as demonstrated by the gonadosomatic index and gamete developmental stages. Plasma levels of the egg precursor protein vitellogenin also showed concentrations ranging below the detection limit. The present results indicate that chub infected with L. intestinalis and exposed to exogenous oestrogenic compounds can result in reduced gonadal maturation and produce false oestrogen-positive diagnoses in male fish. For plasma vitellogenin levels, L. intestinalis infections can result in false oestrogen-negative diagnoses in male and female fish.
Potentiometric titration analysis was used to examine the hydrolysis behavior of Fe2+ Fe3+, and Al3+ in pure solution and in mixture, in order to evaluate the potential for coprecipitation and mixed solid-phase formation. Mixtures of Fe3+ and Al3+ did not interact during neutralization; base consumed in their respective buffer regions was equivalent to the total metal added. Fe2+-Al3+ solutions, however, showed excess base consumption in the Al3+ buffer region, indicating hydrolysis of Fe2+ at lower than normal pH. Ferric/ferrous iron analyses of systems at the Al endpoint (pH 5.5) showed amounts of oxidized Fe equivalent to the excess base consumption (∼10% of total Fe), with substantial amounts of Fe2+ sorbed to or occluded within Al polymers present. Increased electrolyte levels or the presence of SO42- inhibited oxidation and sorption of Fe2+ on Al surfaces, suggesting that Fe hydrolysis and oxidation was catalyzed at the surfaces. Increasing Al3+: Fe2+ ratios in the titrated solutions also increased the amount of Fe2+ coprecipitation, supporting a surface-mediated reaction mechanism. Ferrous iron oxidation was sensitive to O2 levels, which also affected the amount of coprecipitation. These findings suggest that surface-facilitated oxidation of Fe2+ may be important in the formation of mixed Fe-Al mineral phases in dilute soil solutions.
Traumatic brain injury (TBI) and concussion are associated with increased dementia risk. Accurate TBI/concussion exposure estimates are relatively unknown for less common neurodegenerative conditions like frontotemporal dementia (FTD). We evaluated lifetime TBI and concussion frequency in patients diagnosed with a range of FTD spectrum conditions and related prior head trauma to cavum septum pellucidum (CSP) characteristics observable on MRI.
Participants and Methods:
We administered the Ohio State University TBI Identification and Boston University Head Impact Exposure Assessment to 108 patients (age 69.5 ± 8.0, 35% female, 93% white or unknown race) diagnosed at the UCSF Memory and Aging Center with one of the following FTD or related conditions: behavioral variant frontotemporal dementia (N=39), semantic variant primary progressive aphasia (N=16), nonfluent variant PPA (N=23), corticobasal syndrome (N=14), or progressive supranuclear palsy (N=16). Data were also obtained from 217 controls (“HC”; age 76.8 ± 8.0, 53% female, 91% white or unknown race). CSP characteristics were defined based on width or “grade” (0-1 vs. 2+) and length of anterior-posterior separation (millimeters). We first describe frequency of any and multiple (2+) prior TBI based on different but commonly used definitions: TBI with loss of consciousness (LOC), TBI with LOC or posttraumatic amnesia (LOC/PTA), TBI with LOC/PTA or other symptoms like dizziness, nausea, “seeing stars,” etc. (“concussion”). TBI/concussion frequency was then compared between FTD and HC using chi-square. Associations between TBI/concussion and CSP characteristics were analyzed with chi-square (CSP grade) and Mann-Whitney U tests (CSP length). We explored sex differences due to typically higher rates of TBI among males.
Results:
History of any TBI with LOC (FTD=20.0%, HC=19.2%), TBI with LOC/PTA (FTD:32.2%, HC=31.5%), and concussion (FTD: 50.0%, HC=44.3%) was common but not different between study groups (p’s>.4). In both FTD and HC, prior TBI/concussion was nominally more frequent in males but not significantly greater than females. Frequency of repeat TBI/concussion (2+) also did not differ significantly between FTD and HC (repeat TBI with LOC: 6.7% vs. 3.3%, TBI with LOC/PTA: 12.2% vs. 10.3%, concussion: 30.2% vs. 28.7%; p’s>.2). Prior TBI/concussion was not significantly related to CSP grade or length in the total sample or within the FTD or HC groups.
Conclusions:
TBI/concussion rates depend heavily on the symptom definition used for classifying prior injury. Lifetime symptomatic TBI/concussion is common but has an unclear impact on risk for FTD-related diagnoses. Larger samples are needed to appropriately evaluate sex differences, to evaluate whether TBI/concussion rates differ between specific FTD phenotypes, and to understand the rates and effects of more extensive repetitive head trauma (symptomatic and asymptomatic) in patients with FTD.
We present and evaluate the prospects for detecting coherent radio counterparts to gravitational wave (GW) events using Murchison Widefield Array (MWA) triggered observations. The MWA rapid-response system, combined with its buffering mode ($\sim$4 min negative latency), enables us to catch any radio signals produced from seconds prior to hours after a binary neutron star (BNS) merger. The large field of view of the MWA ($\sim$$1\,000\,\textrm{deg}^2$ at 120 MHz) and its location under the high sensitivity sky region of the LIGO-Virgo-KAGRA (LVK) detector network, forecast a high chance of being on-target for a GW event. We consider three observing configurations for the MWA to follow up GW BNS merger events, including a single dipole per tile, the full array, and four sub-arrays. We then perform a population synthesis of BNS systems to predict the radio detectable fraction of GW events using these configurations. We find that the configuration with four sub-arrays is the best compromise between sky coverage and sensitivity as it is capable of placing meaningful constraints on the radio emission from 12.6% of GW BNS detections. Based on the timescales of four BNS merger coherent radio emission models, we propose an observing strategy that involves triggering the buffering mode to target coherent signals emitted prior to, during or shortly following the merger, which is then followed by continued recording for up to three hours to target later time post-merger emission. We expect MWA to trigger on $\sim$$5-22$ BNS merger events during the LVK O4 observing run, which could potentially result in two detections of predicted coherent emission.
Our institution sought to evaluate our antimicrobial stewardship empiric treatment recommendations for Salmonella. Results from 36 isolates demonstrated reduced susceptibilities to fluoroquinolones with 1 isolate susceptible only to ceftriaxone. Analysis supports the current recommendation of empiric ceftriaxone therapy for severe infection and updated recommendation for sulfamethoxazole-trimethoprim in non-severe infections.
Meta-analyses of functional magnetic resonance imaging (fMRI) studies have been used to elucidate the most reliable neural features associated with various psychiatric disorders. However, it has not been well-established whether each of these neural features is linked to a specific disorder or is transdiagnostic across multiple disorders and disorder categories, including mood, anxiety, and anxiety-related disorders.
Objectives
This project aims to advance our understanding of the disorder-specific and transdiagnostic neural features associated with mood, anxiety, and anxiety-related disorders as well as to refine the methodology used to compare multiple disorders.
Methods
We conducted an exhaustive PubMed literature search followed by double-screening, double-extraction, and cross-checking to identify all whole-brain, case-control fMRI activation studies of mood, anxiety, and anxiety-related disorders in order to construct a large-scale meta-analytic database of primary studies of these disorders. We then employed multilevel kernel density analysis (MKDA) with Monte-Carlo simulations to correct for multiple comparisons as well as ensemble thresholding to reduce cluster size bias to analyze primary fMRI studies of mood, anxiety, and anxiety-related disorders followed by application of triple subtraction techniques and a second-order analysis to elucidate the disorder-specificity of the previously identified neural features.
Results
We found that participants diagnosed with mood, anxiety, and anxiety-related disorders exhibited statistically significant (p < .05 – 0.0001; FWE-corrected) differences in neural activation relative to healthy controls throughout the cerebral cortex, limbic system, and basal ganglia. In addition, each of these psychiatric disorders exhibited a particular profile of neural features that ranged from disorder-specific, to category-specific, to transdiagnostic.
Conclusions
These findings indicate that psychiatric disorders exhibit a complex profile of neural features that vary in their disorder-specificity and can be detected with large-scale fMRI meta-analytic techniques. This approach has potential to fundamentally transform neuroimaging investigations of clinical disorders by providing a novel procedure for establishing disorder-specificity of observed results, which can be then used to advance our understanding of individual disorders as well as broader nosological issues related to diagnosis and classification of psychiatric disorders.
Generalized anxiety disorder (GAD) is a highly prevalent mental illness that is associated with clinically significant distress, functional impairment, and poor emotional regulation. Primary functional magnetic resonance imaging (fMRI) studies of GAD report neural abnormalities in comparison to healthy controls. However, many of these findings in the primary literature are inconsistent, and it is unclear whether they are specific to GAD or shared transdiagnostically across related disorders.
Objectives
This meta-analysis seeks to establish the most reliable neural abnormalities observed in individuals with GAD, as reported in the primary fMRI activation literature.
Methods
We conducted an exhaustive literature search in PubMed to identify primary studies that met our pre-specified inclusion criteria and then extracted relevant data from primary, whole-brain fMRI activation studies of GAD that reported coordinates in Talairach or MNI space. We then used multilevel kernel density analysis (MKDA) with ensemble thresholding to examine the differences between adults with GAD and healthy controls in order to identify brain regions that reached statistical significance across primary studies.
Results
Patients with GAD showed statistically significant (α=0.05–0.0001; family-wise-error-rate corrected) neural activation in various regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
These results inform our understanding of the neural basis of GAD and are interpreted using a frontolimbic model of anxiety as well as specific clinical symptoms of this disorder and its relation to other mood and anxiety disorders. These results also suggest possible novel targets for emerging neurostimulation therapies (e.g., transcranial magnetic stimulation) and may be used to advance our understanding of the effects of current pharmaceutical treatments and ways to improve treatment selection and symptom-targeting for patients diagnosed with GAD.
Functional magnetic resonance imaging (fMRI) has been used to identify the neural activity of both youth and adults diagnosed with major depressive disorder (MDD) in comparison to healthy age-matched controls. Previously reported abnormalities in depressed youth appear to mostly align with those found in depressed adults; however, some of the reported aberrant brain activity in youth has not been consistent with what is observed in adults, and to our knowledge there has not yet been a formal, quantitative comparison of these two groups. In addition, it is not known whether these observed differences between youth and adults with depression are attributable to developmental age or length-of-illness.
Objectives
The aim of this study is to elucidate the similarities and differences in patterns of abnormal neural activity between adults and youth diagnosed with MDD and to then determine whether these observed differences are due to either developmental age or length-of-illness.
Methods
We used multilevel kernel density analysis (MKDA) with ensemble thresholding and triple subtraction to separately determine neural abnormalities throughout the whole brain in primary studies of depressed youth and depressed adults and then directly compare the observed abnormalities between each of those age groups. We then conducted further comparisons between multiple subgroups to control for age and length-of-illness and thereby determine the source of the observed differences between youth and adults with depression.
Results
Adults and youth diagnosed with MDD demonstrated reliable, differential patterns of abnormal activation in various brain regions throughout the cerebral cortex that are statistically significant (p < .05; FWE-corrected). In addition, several of these brain regions that exhibited differential patterns of neural activation between the two age groups can be reliably attributed to either developmental age or length-of-illness.
Conclusions
These findings indicate that there are common and disparate patterns of brain activity between youth and adults with MDD, several of which can be reliably attributed to developmental age or length-of-illness. These results expand our understanding of the neural basis of depression across development and course of illness and may be used to inform the development of new, age-specific clinical treatments as well as prevention strategies for this disorder.
Major depressive disorder (MDD) is a highly prevalent mental illness that frequently originates in early development and is pervasive during adolescence. Despite its high prevalence and early age of onset, our understanding of the potentially unique neural basis of MDD in this age group is still not well understood, and the existing primary literature on the topic includes many new and divergent results. This limited understanding of MDD in youth presents a critical need to further investigate its neural basis in youth and presents an opportunity to also improve clinical treatments that target its neural abnormalities.
Objectives
The present study aims to advance our understanding of the neural basis of MDD in youth by identifying abnormal functional activation in various brain regions compared with healthy controls.
Methods
We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of MDD by using a well-established method, multilevel kernel density analysis (MKDA) with ensemble thresholding, to quantitatively combine all existing whole-brain fMRI studies of MDD in youth compared with healthy controls. This method involves a voxel-wise, whole-brain approach, that compares neural activation of patients with MDD to age-matched healthy controls across variations of task-based conditions, which we subcategorize into affective processing, executive functioning, positive valence, negative valence, and symptom provocation tasks.
Results
Youth with MDD exhibited statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in multiple brain regions compared with age-matched healthy controls. These results include significant effects that are stable across various tasks as well as some that appear to depend on task conditions.
Conclusions
This study strengthens our understanding of the neural basis of MDD in youth and may also be used to help identify possible similarities and differences between youth and adults with depression. It may also help inform the development of new treatment interventions and tools for predicting unique treatment responses in youth with depression.
Curiosity toward the effects of psychedelic drugs on neural activation has increased due to their potential therapeutic benefits, particularly serotonergic psychedelics that act as 5-HT2A receptor agonists such as LSD, psilocybin, and MDMA. However, the pattern of their effects on neural activity in various brain regions in both clinical and healthy populations is still not well understood, and primary studies addressing this issue have sometimes generated inconsistent results.
Objectives
The present meta-analysis aims to advance our understanding of the most widely used serotonergic psychedelics – LSD, psilocybin, and MDMA – by examining their effects on the functional activation throughout the whole brain among both clinical and healthy participants.
Methods
We conducted this meta-analysis by applying multilevel kernel density analysis (MKDA) with ensemble thresholding to quantitatively combine existing functional magnetic resonance imaging (fMRI) studies that examined whole-brain functional activation of clinical or healthy participants who were administered a serotonergic psychedelic.
Results
Serotonergic psychedelics, including LSD, psilocybin, and MDMA, exhibited significant effects (α=0.05) on neural activation in several regions throughout the cerebral cortex and basal ganglia, including effects that may be common across and unique within each drug.
Conclusions
These observed effects of serotonergic psychedelics on neural activity advance our understanding of the functional neuroanatomy associated with their administration and may inform future studies of both their adverse and therapeutic effects, including emerging clinical applications for the treatment of several psychiatric disorders.
Major depressive disorder (MDD) is a highly prevalent mental illness that often first occurs or persists into adulthood and is considered the leading cause of disability and disease burden worldwide. Unfortunately, individuals diagnosed with MDD who seek treatment often experience limited symptom relief and may not achieve long-term remission, which is due in part to our limited understanding of its underlying pathophysiology. Many studies that use task-based functional magnetic resonance imaging (fMRI) have found abnormal activation in brain regions in adults diagnosed with MDD, but those findings are often inconsistent; in addition, previous meta-analyses that quantitatively integrate this large body literature have found conflicting results.
Objectives
This meta-analysis aims to advance our understanding of the neural basis of MDD in adults, as measured by fMRI activation studies, and address inconsistencies and discrepancies in the empirical literature.
Methods
We employed multilevel kernel density analysis (MKDA) with ensemble thresholding, a well-established method for voxel-wise, whole-brain meta-analyses, to conduct a quantitative comparison of all relevant primary fMRI activation studies of adult patients with MDD compared to age-matched healthy controls.
Results
We found that adults with MDD exhibited a reliable pattern of statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in several brain regions compared to age-matched healthy controls across a variety of experimental tasks.
Conclusions
This study supports previous findings that there is reliable neural basis of MDD that can be detected across heterogenous fMRI studies. These results can be used to inform development of promising treatments for MDD, including protocols for personalized interventions. They also provide the opportunity for additional studies to examine the specificity of these effects among various populations-of-interest, including youth vs. adults with depression as well as other related mood and anxiety disorders.
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
Methods
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Results
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Conclusions
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions.
Methods
Data came from n = 999 patients ages 18–75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models.
Results
Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31–1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65–2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43–2.87) and bullying (RR = 1.44; 95% CI = 0.99–2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE.
Conclusions
Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.