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An Umbrella Review of Effectiveness of Intravenous Ketamine in Treatment-Resistant Depression
- A. M. Klassen, C. Baten, J. H. Shepherd, G. Zamora, E. Johnson-Venegas, S. S. Madugula, E. Woo, J. A. Miller, M. D. Sacchet, D. W. Hedges, C. H. Miller
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- European Psychiatry / Volume 67 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 27 August 2024, pp. S86-S87
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Introduction
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.
ObjectivesThis 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.
MethodsWe 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.
ResultsIn 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.
ConclusionsThis 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.
Disclosure of InterestNone Declared
Neural Abnormalities in Panic Disorder and Agoraphobia: A Meta-Analysis of Functional Activation Studies
- C. Baten, A. M. Klassen, G. Zamora, J. H. Shepherd, A. Badawia, A. Kailay, C. R. Leung, J. Sahota, S. Saravia, J. A. Miller, P. Hamilton, M. D. Sacchet, I. H. Gotlib, E. Woo, D. W. Hedges, C. H. Miller
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- European Psychiatry / Volume 67 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 27 August 2024, p. S41
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Introduction
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.
ObjectivesThis 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.
MethodsWe 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.
ResultsWith 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.
ConclusionsIn 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.
Disclosure of InterestNone Declared
A Meta-Analysis of fMRI Activation Studies of Ketamine in Healthy Participants
- J. H. Shepherd, A. Hickman, C. Baten, A. M. Klassen, G. Zamora, E. Johnson-Venegas, S. S. Madugula, E. Woo, J. A. Miller, M. D. Sacchet, D. W. Hedges, C. H. Miller
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- European Psychiatry / Volume 67 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 27 August 2024, p. S74
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Introduction
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.
ObjectivesThis 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.
MethodsWe 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.
ResultsOur 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).
ConclusionsThese 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.
Disclosure of InterestNone Declared
Neural Abnormalities in Bipolar Disorder: A Meta-Analysis of Functional Neuroimaging Studies
- S. J. Herrera, F. A. Reyes, G. Johnson-Venegas, C. Baten, G. Zamora, A. M. Klassen, J. A. Miller, E. Woo, D. W. Hedges, P. J. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- European Psychiatry / Volume 67 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 27 August 2024, p. S441
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Introduction
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.
ObjectivesThe 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.
MethodsWe 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.
ResultsWe 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.
ConclusionsThis 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.
Disclosure of InterestNone Declared
Abnormal Neural Activation in Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies
- G. Zamora, C. Baten, A. M. Klassen, J. H. Shepherd, A. Catchpole, E. Davis, I. Dillsaver, C. E. Hunt, E. Johnson-Venegas, P. Hamilton, M. D. Sacchet, E. Woo, J. A. Miller, D. W. Hedges, C. H. Miller
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- European Psychiatry / Volume 67 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 27 August 2024, pp. S72-S73
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Introduction
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.
ObjectivesThe 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.
MethodsWe 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.
ResultsParticipants 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.
ConclusionsThis 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.
Disclosure of InterestNone Declared
The effect of LCn-3 PUFA supplementation on body weight, body composition, and muscle function during alternate-day fasting (ADF)
- M. Alblaji, S.R Gray, T. Almesbehi, H. Miller, A. Gonzalo, D. Malkova
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- Proceedings of the Nutrition Society / Volume 83 / Issue OCE2 / June 2024
- Published online by Cambridge University Press:
- 03 July 2024, E216
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During weight loss the loss of body mass is associated not only with body fat reduction but also with a decrease in fat-free mass (FFM), related to the reduction in muscle mass and function(1). Supplementation with long-chain n-3 fatty acids (LCn-3 PUFA), in the absence of caloric restriction, results in a significant decrease in fat mass and an increase in FFM(2) along with improvements in muscle mass and strength(3). However, the impact of supplementation with LCn-3 PUFA during weight loss) remains unknown. Therefore, the aim of this study was to explore the effects of LCn-3 PUFA supplementation, in the form of Krill oil (KO), during alternate day fasting (ADF) on body weight, fat mass loss, FFM and muscle function changes in healthy overweight and obese adults.
A total of 41 men and women (age: 39.35 ± 10.4 years, BMI: 31.05 ± 4.2 kg/m2) completed the study (NCT06001632), in which they were randomised into either a KO or Placebo (PL) groups. Both groups carried out 8-weeks of ADF combined with intake of 4 g/day of the corresponding supplements. ADF involved consuming no more than 500 calories on the 'fast day’ and consuming food ad libitum on each 'feed day’. Data on body weight and body composition (TBF-300, Tanita, Manchester, UK), handgrip strength (Handheld Hydraulic Dynamometer, Vernier Jamar; England, UK), and time to conduct 5 repetition of chair rising test were obtained pre-and post-intervention. Changes from baseline within groups were assessed using paired samples t-test. Mixed analysis of variance (Mixed-ANOVA) was used to measure 2-way interactions between time and group to identify the differences between groups. All statistical analysis were conducted using IBM Statistical Package for the Social Sciences SPSS 28.0.
In both groups, body mass decreased significantly (KO:-4.7 ± 0.4kg, p<0.001; PL:-4.5 ± 0.4kg, p<0.001), along with a significant reduction in fat mass (KO:-2.4 ± 0.5kg p<0.001; PL:-2.3 ± 0.5kg p<0.001), and FFM (KO:-0.6 ± 0.2kg p<0.001; PL:-0.7 ± 0.2kg, p<0.001), with no differences between groups. In the PL group, there was a reduction in handgrip strength (-0.9 ± 0.7 kg, p<0.001), while there was no change in KO group (-0.2 ± 0.5 kg, p=0.1), with a significant difference between groups (p<0.001). In the KO group there was a significant reduction in time to conduct chair rising test (-1.8 ± 0.9s, p<0.05), with no change in the PL group (-0.3 ± 1.3s, p=0.2), with a significant difference between groups (p<0.001).
Supplementation with LCn-3 PUFA (4 g/day) during 8 weeks of ADF, applied to individuals living with overweigh and obesity, does not facilitate body or fat mass loss and does not diminish the reduction in FFM. However, it attenuated the reduction in muscle function in healthy overweight and obese adults.
Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations
- Sarah E. Paul, David A.A. Baranger, Emma C. Johnson, Joshua J. Jackson, Aaron J. Gorelik, Alex P. Miller, Alexander S. Hatoum, Wesley K. Thompson, Michael Strube, Danielle M. Dick, Chella Kamarajan, John R. Kramer, Martin H. Plawecki, Grace Chan, Andrey P. Anokhin, David B. Chorlian, Sivan Kinreich, Jacquelyn L. Meyers, Bernice Porjesz, Howard J. Edenberg, Arpana Agrawal, Kathleen K. Bucholz, Ryan Bogdan
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- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 09 May 2024, pp. 1-14
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Background
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
MethodsData came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
ResultsExternalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
ConclusionsBehavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Supergene Origin of the Lastarria Kaolin Deposit, South-Central Chile, and Paleoclimatic Implications
- H. A. Gilg, S. Hülmeyer, H. Miller, S. M. F. Sheppard
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- Clays and Clay Minerals / Volume 47 / Issue 2 / April 1999
- Published online by Cambridge University Press:
- 28 February 2024, pp. 201-211
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The residual kaolin deposits near Lastarria, South-Central Chile, were formed by weathering of subvolcanic quartz porphyry stocks, which intruded the metamorphic basement of the Coastal Cordillera. The clay fractions (<2 µm) consist mainly of poorly-ordered, very fine-grained kaolinite and lath-shaped illite (17–38 wt. %) with minor amounts of quartz, sanidine, and goethite. A sample from the top of the deposit contains major quantities of gibbsite morphologically indistinguishable from kaolinite flakes. The gibbsite-free clays contain 35.5–36.6 wt. % Al2O3, 0.4–2.6 wt. % Fe2O3, 1.3–3.9 wt. % K2O, and have low TiO2 concentrations (<0.02 wt. %). The absence of quartz veining, the abundance of melt inclusions, and the scarcity of secondary fluid inclusions in quartz phenocrysts from altered rocks imply a lack of significant hydrothermal activity in the quartz porphyries. The δ 18O and δD values of the kaolins indicate formation in a weathering environment at significantly higher annual mean air temperatures (∼12°C) than present mean temperatures of ∼9.4°C. Uplift of the region alone probably cannot account for the change in climate. The stable isotope composition of gibbsite is consistent with an origin of desilication of kaolinite at superficial temperatures. Various criteria proposed to distinguish supergene from hypogene kaolins are discussed.
73 Sex and Race/Ethnicity in Reporting of Lingering Concussion Symptoms by Adolescents
- Stephen C Bunt, Nyaz Didehbani, Cheryl H Silver, Linda S Hynan, Hannah E Wadsworth, Hudaisa Fatima, Cason Hicks, Mathew Stokes, Shane M Miller, Kathleen Bell, C M Cullum
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 176-177
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Objective:
Consideration of individual differences in recovery after concussion has become a focus of concussion research. Sex and racial/ethnic identity as they may affect reporting of concussion symptoms have been studied at single time points but not over time. Our objective was to investigate the factors of self-defined sex and race/ethnicity in reporting of lingering concussion symptoms in a large sample of adolescents.
Participants and Methods:Concussed, symptomatic adolescents (n=849; Female=464, Male=385) aged 13-18 years were evaluated within 30 days of injury at a North Texas Concussion Registry (ConTex) clinic. Participants were grouped by self-defined race/ethnicity into three groups: Non-Hispanic Caucasian (n=570), Hispanic Caucasian (n=157), and African American (n=122). Measures collected at the initial visit included medical history, injury related information, and the Sport Concussion Assessment Tool-5 Symptom Evaluation (SCAT-5SE). At a three-month follow-up, participants completed the SCAT-5SE. Pearson’s Chi-Square analyses examined differences in categorical measures of demographics, medical history, and injury characteristics. Prior to analysis, statistical assumptions were examined, and log base 10 transformations were performed to address issues of unequal group variances and nonnormal distributions. A three-way repeated measures ANOVA (Sex x Race/Ethnicity x Time) was conducted to examine total severity scores on the SCAT-5SE. Bonferroni post-hoc tests were performed to determine specific group differences. SPSS V28 was used for analysis with p<0.05 for significance. Data reported below has been back transformed.
Results:A significant interaction of Time by Race/Ethnicity was found for SCAT-5SE scores reported at initial visit and three-month follow-up (F(2, 843)=7.362, p<0.001). To understand this interaction, at initial visit, Race/Ethnicity groups reported similar levels of severity for concussion symptoms. At three month follow-up, African Americans reported the highest level of severity of lingering symptoms (M= 3.925, 95% CIs [2.938-5.158]) followed by Hispanic Caucasians(M= 2.978, 95% CIs [2.2663.845]) and Non-Hispanic Caucasians who were the lowest(M= 1.915, 95% CIs [1.6262.237]). There were significant main effects for Time, Sex, and Race/Ethnicity. Average symptom levels were higher at initial visit compared to three-month follow-up (F(1, 843)=1531.526, p<0.001). Females had higher average symptom levels compared to males (F(1, 843)=35.58, p<0.001). For Race/Ethnicity (F(2, 843)=9.236, p<0.001), Non-Hispanic Caucasians were significantly different than African Americans (p<0.001) and Hispanic Caucasians (p=0.021) in reported levels of concussion symptom severity.
Conclusions:Data from a large sample of concussed adolescents supported a higher level of reported symptoms by females, but there were no significant differences in symptom reporting between sexes across racial/ethnic groups. Overall, at three-months, the African American and Hispanic Caucasians participants reported a higher level of lingering symptoms than Non-Hispanic Caucasians. In order to improve care, the difference between specific racial/ethnic groups during recovery merits exploration into the factors that may influence symptom reporting.
57 Traumatic Brain Injury and Concussion in Patients with Frontotemporal Dementia Spectrum Diagnoses
- Jessica Bove, Marguerite Knudtson, Michelle You, Michael L Alosco, Jesse Mez, Bruce L Miller, Howie J Rosen, Maria Luisa Gorno-Tempini, William W Seeley, Joel H Kramer, Russell M Bauer, Breton M Asken
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 568-569
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Objective:
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.
MWA rapid follow-up of gravitational wave transients: Prospects for detecting prompt radio counterparts
- J. Tian, G. E. Anderson, A. J. Cooper, K. Gourdji, M. Sokolowski, A. Rowlinson, A. Williams, G. Sleap, D. Dobie, D. L. Kaplan, Tara Murphy, S. J. Tingay, F. H. Panther, P. D. Lasky, A. Bahramian, J. C. A. Miller-Jones, C. W. James, B. W. Meyers, S. J. McSweeney, P. J. Hancock
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 40 / 2023
- Published online by Cambridge University Press:
- 26 October 2023, e050
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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.
Establishing Disorder-Specific and Transdiagnostic Neural Features of Psychiatric Disorders Through Large-Scale Functional Magnetic Resonance Imaging Meta-Analyses
- C. H. Miller, E. Pritchard, S. Saravia, M. Duran, S. L. Santos, J. P. Hamilton, D. W. Hedges, I. H. Gotlib, M. D. Sacchet
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S547-S548
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Introduction
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.
ObjectivesThis 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.
MethodsWe 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.
ResultsWe 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.
ConclusionsThese 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.
Disclosure of InterestNone Declared
Neural Abnormalities Associated with Generalized Anxiety Disorder: A Meta-Analysis of Functional Magnetic Resonance Imaging Activation Studies
- S. K. Kahlon, Z. Ali, E. Pritchard, S. Saravia, C. Baten, A. M. Klassen, J. H. Shepherd, G. Zamora, J. Jordan, M. Duran, S. L. Santos, D. W. Hedges, J. P. Hamilton, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S452
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Introduction
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.
ObjectivesThis meta-analysis seeks to establish the most reliable neural abnormalities observed in individuals with GAD, as reported in the primary fMRI activation literature.
MethodsWe 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.
ResultsPatients 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.
ConclusionsThese 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.
Disclosure of InterestNone Declared
Major Depressive Disorder Across Development and Course of Illness: A Functional Neuroimaging Meta-Analysis
- C. Baten, A. M. Klassen, J. H. Shepherd, G. Zamora, E. Pritchard, S. Saravia, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. Santos, A. F. Nimarko, D. W. Hedges, P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S345-S346
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Introduction
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.
ObjectivesThe 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.
MethodsWe 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.
ResultsAdults 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.
ConclusionsThese 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.
Disclosure of InterestNone Declared
Major Depressive Disorder in Youth: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies
- G. Zamora, C. Baten, A. M. Klassen, J. H. Shepherd, E. Pritchard, S. Saravia, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. L. Santos, A. F. Nimarko, D. W. Hedges, J. P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S219-S220
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Introduction
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.
ObjectivesThe 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.
MethodsWe 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.
ResultsYouth 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.
ConclusionsThis 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.
Disclosure of InterestNone Declared
The Effects of Serotonergic Psychedelics on Neural Activity: A Meta-Analysis of Task-Based Functional Neuroimaging Studies
- J. H. Shepherd, C. Baten, A. Klassen, G. Zamora, S. Saravia, E. Pritchard, Z. Ali, S. K. Kahlon, K. Whitelock, F. A. Reyes, D. W. Hedges, J. P. Hamilton, M. D. Sacchet, C. H. Miller
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S921
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Introduction
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.
ObjectivesThe 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.
MethodsWe 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.
ResultsSerotonergic 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.
ConclusionsThese 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.
Disclosure of InterestNone Declared
The Neural Basis of Major Depressive Disorder in Adults: A Meta-Analysis of Functional Magnetic Resonance Imaging Activation Studies
- A. M. Klassen, C. Baten, J. H. Shepherd, G. Zamora, S. Saravia, E. Pritchard, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. L. Santos, A. F. Nimarko, D. W. Hedges, J. P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S158
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Introduction
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.
ObjectivesThis 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.
MethodsWe 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.
ResultsWe 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.
ConclusionsThis 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.
Disclosure of InterestNone Declared
Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals
- Cecilia A. Hinojosa, Amanda Liew, Xinming An, Jennifer S. Stevens, Archana Basu, Sanne J. H. van Rooij, Stacey L. House, Francesca L. Beaudoin, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Tanja Jovanovic, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Michael C. Kurz, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Anna M. Chang, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Mark W. Miller, Robert H. Pietrzak, Jutta Joormann, Diego A. Pizzagalli, John F. Sheridan, Steven E. Harte, James M. Elliott, Ronald C. Kessler, Karestan C. Koenen, Samuel A. McLean, Kerry J. Ressler, Negar Fani
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 13 June 2023, pp. 338-349
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Background
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.
MethodsIn 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.
ResultsThree 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.
ConclusionsOur 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.
Development of the data registry for the Cardiac Neurodevelopmental Outcome Collaborative
- Anjali Sadhwani, Erica Sood, Andrew H. Van Bergen, Dawn Ilardi, Jacqueline H. Sanz, J. William Gaynor, Michael Seed, Cynthia M. Ortinau, Bradley S. Marino, Thomas A. Miller, Michael Gaies, Adam R. Cassidy, Janet E. Donohue, Amy Ardisana, David Wypij, Caren S. Goldberg
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- Cardiology in the Young / Volume 34 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 19 May 2023, pp. 79-85
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Children with congenital heart disease (CHD) can face neurodevelopmental, psychological, and behavioural difficulties beginning in infancy and continuing through adulthood. Despite overall improvements in medical care and a growing focus on neurodevelopmental screening and evaluation in recent years, neurodevelopmental disabilities, delays, and deficits remain a concern. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with the goal of improving neurodevelopmental outcomes for individuals with CHD and pediatric heart disease. This paper describes the establishment of a centralised clinical data registry to standardize data collection across member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. The goal of this registry is to foster collaboration for large, multi-centre research and quality improvement initiatives that will benefit individuals and families with CHD and improve their quality of life. We describe the components of the registry, initial research projects proposed using data from the registry, and lessons learned in the development of the registry.
Developmental care pathway for hospitalised infants with CHD: on behalf of the Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative
- Amy J. Lisanti, Dorothy J. Vittner, Jennifer Peterson, Andrew H. Van Bergen, Thomas A. Miller, Erin E. Gordon, Karli A. Negrin, Hema Desai, Suzie Willette, Melissa B. Jones, Sherrill D. Caprarola, Anna J. Jones, Stephanie M. Helman, Jodi Smith, Corinne M. Anton, Laurel M. Bear, Lauren Malik, Sarah K. Russell, Dana J. Mieczkowski, Bridy O. Hamilton, Meghan McCoy, Yvette Feldman, Michelle Steltzer, Melanie L. Savoca, Diane L. Spatz, Samantha C. Butler
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- Cardiology in the Young / Volume 33 / Issue 12 / December 2023
- Published online by Cambridge University Press:
- 30 March 2023, pp. 2521-2538
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Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, “Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease,” includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.