Publications by authors named "Krystal J"

Background: Auditory steady-state response (ASSR) abnormalities in the 40-Hz (gamma band) frequency have been observed in schizophrenia and rodent studies of N-methyl D-aspartate glutamate receptor (NMDAR) hypofunction. However, the extent to which 40-Hz ASSR abnormalities in schizophrenia resemble deficits in 40-Hz ASSR induced by acute administration of ketamine, an NMDAR antagonist, is not yet known.

Methods: To address this knowledge gap, we conducted parallel EEG studies: a crossover, placebo-controlled ketamine drug challenge study in healthy subjects (Study 1) and a comparison of patients with schizophrenia and healthy controls subjects (Study 2).

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Article Synopsis
  • MDMA, also known as Ecstasy or Molly, has been used since the 1970s for both recreational and therapeutic purposes, with the FDA recognizing its potential for treating PTSD as a Breakthrough Therapy in 2017.
  • The effects of MDMA in therapeutic settings are distinct, promoting trust and self-compassion while allowing cognitive clarity, which differentiates it from other psychedelics.
  • Preliminary evidence indicates that MDMA-Assisted Therapy is effective, with 67%-71% of PTSD patients no longer meeting diagnostic criteria after treatment, significantly more than those receiving placebo therapy.
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Objective: The authors critically examine the evidence base for psilocybin administered with psychological support/therapy (PST) in the treatment of psychiatric disorders and offer practical recommendations to guide future research endeavors.

Methods: PubMed was searched for English-language articles from January 1998 to November 2023, using the search term "psilocybin." A total of 1,449 articles were identified and screened through titles and abstracts.

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  • The review explores the role of various omics-based biomarkers in understanding alcohol and alcohol use disorder (AUD), providing definitions and background on key concepts.
  • It highlights four types of omics information: genetic, epigenetic, transcriptomic, and metabolomic, detailing their use as risk and diagnostic biomarkers for AUD and related alcohol consumption.
  • Finally, the review discusses the clinical implications of these findings and suggests directions for future research in the field of alcohol studies.
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Psychological trauma has profound effects on brain function and precipitates psychiatric disorders in vulnerable individuals, however, the molecular mechanisms linking trauma with psychiatric risk remain incompletely understood. Using RNA-seq data postmortem brain tissue of a cohort of 304 donors (N=136 with trauma exposure), we investigated transcriptional signatures of trauma exposures in two cortical regions (dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex) and two amygdala regions (medial amygdala and basolateral amygdala) associated with stress processing and regulation. We focused on dissecting heterogeneity of traumatic experiences in these transcriptional signatures by investigating exposure to several trauma types (childhood, adulthood, complex, single acute, combat, and interpersonal traumas) and interactions with sex.

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The study conducted a comprehensive genome-wide analysis of differential 5mC and 5hmC modifications at both CpG and non-CpG sites in postmortem orbitofrontal neurons from 25 PTSD cases and 13 healthy controls. It was observed that PTSD patients exhibit a greater number of differential 5hmC sites compared to 5mC sites. Specifically, individuals with PTSD tend to show hyper-5mC/5hmC at CpG sites, particularly within CpG islands and promoter regions, and hypo-5mC/5hmC at non-CpG sites, especially within intragenic regions.

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Slow waves are a distinguishing feature of non-rapid-eye-movement (NREM) sleep, an evolutionarily conserved process critical for brain function. Non-human studies suggest that the claustrum, a small subcortical nucleus, coordinates slow waves. We show that, in contrast to neurons from other brain regions, claustrum neurons in the human brain increase their spiking activity and track slow waves during NREM sleep, suggesting that the claustrum plays a role in coordinating human sleep architecture.

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Chordomas are rare sarcomas arising from notochordal tissue and occur most commonly in the spine. The standard of care for chordomas without evidence of metastatic disease generally consists of en bloc resection followed by adjuvant radiotherapy. However, long-term (20-year) survival rates are approximately 30%.

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Article Synopsis
  • Our brains can change how they work from day to day (state) and also differ from person to person (trait), but scientists don’t fully understand how this affects our behavior.
  • Researchers studied brain activity using special scans and found that each person's brain has unique patterns that can change over time.
  • They discovered that these brain patterns relate to how we think, feel, and behave, suggesting that understanding our brain could help us learn more about ourselves and improve our lives.
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Neuroimaging plays a crucial role in understanding brain structure and function, but the lack of transparency, reproducibility, and reliability of findings is a significant obstacle for the field. To address these challenges, there are ongoing efforts to develop reporting checklists for neuroimaging studies to improve the reporting of fundamental aspects of study design and execution. In this review, we first define what we mean by a neuroimaging reporting checklist and then discuss how a reporting checklist can be developed and implemented.

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  • - Post-traumatic stress disorder (PTSD) is a serious mental health condition where individuals repeatedly relive traumatic experiences, and the role of the cerebellum in this process is still under investigation.
  • - In a study with 28 chronic PTSD patients, researchers used fMRI to examine brain activity while participants listened to their own traumatic and sad memories, finding specific activation in cerebellar lobule VI during trauma recall linked to symptom severity.
  • - Results indicate that while lobule VI is particularly engaged with traumatic memories, another cerebellar area, Crus II, is also active during sad memories, suggesting its broader role in managing negative emotions.
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Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls.

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Background And Objectives: Noradrenergic dysregulation is important in the pathophysiology of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD); pharmacotherapies targeting adrenergic function have potential as treatment for comorbidity. Dexmedetomidine (sublingual film formulation-BXCL501; IGALMI) is a highly potent, selective ⍺2-adrenergic receptor agonist and may be superior to other pharmacotherapeutic approaches. A within subjects, phase 1b safety laboratory study was conducted to evaluate adverse effects of BXCL501 when combined with alcohol; BXCL501's potential efficacy was also explored.

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Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition that follows exposure to a traumatic stressor. Though previous in vivo proton (H) MRS) research conducted at 4 T or lower has identified alterations in glutamate metabolism associated with PTSD predisposition and/or progression, no prior investigations have been conducted at higher field strength. In addition, earlier studies have not extensively addressed the impact of psychiatric comorbidities such as major depressive disorder (MDD) on PTSD-associated H-MRS-visible brain metabolite abnormalities.

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Reductions in default mode (DMN) connectivity strength have been reported in posttraumatic stress disorder (PTSD). However, the specificity of DMN connectivity deficits in PTSD compared to major depressive disorder (MDD), and the sensitivity of these alterations to acute stressors are not yet known. 52 participants with a primary diagnosis of PTSD ( = 28) or MDD ( = 24) completed resting-state functional magnetic resonance imaging immediately before and after a mild affective stressor.

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Background: Chronic pain affects one fifth of American adults, contributing significant public health burden. Chronic pain mechanisms can be further understood through investigating brain gene expression.

Methods: We tested differentially expressed genes (DEGs) in chronic pain, migraine, lifetime fentanyl and oxymorphone use, and with chronic pain genetic risk in four brain regions (dACC, DLPFC, MeA, BLA) and imputed cell type expression data from 304 postmortem donors.

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In recent history, the world has witnessed a trend towards liberalization of abortion laws driven by an increasing understanding of the negative personal and public health consequences of criminalizing abortion. By contrast, several countries have recently implemented restrictive reproductive laws, joining the 112 countries where access to abortion care is banned completely or with narrow exceptions. On June 24, 2022, the US Supreme Court ruling in Dobbs v Jackson Women's Health Organization overturned its landmark decisions in Roe v Wade that established abortion until the point of viability of the fetus as a constitutional right.

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Background: Instrumented spinal fusions can be used in the treatment of vertebral fractures, spinal instability, and scoliosis or kyphosis. Construct-level selection has notable implications on postoperative recovery, alignment, and mobility. This study sought to project future trends in the implementation rates and associated costs of single-level versus multilevel instrumentation procedures in US Medicare patients aged older than 65 years in the United States.

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Background: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects.

Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition.

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Background: Increasing evidence demonstrates disparities among patients with differing insurance statuses in the field of spine surgery. However, no pooled analyses have performed a robust review characterizing differences in postoperative outcomes among patients with varying insurance types.

Methods: A comprehensive literature search of the PUBMED, MEDLINE(R), ERIC, and EMBASE was performed for studies comparing postoperative outcomes in patients with private insurance versus government insurance.

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Objective: Problem opioid use (POU) is a serious public health crisis in the United States. However, little research has examined the prevalence, correlates, and psychiatric characteristics of POU in vulnerable segments of the population, such as US military veterans.

Methods: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 2441 US veterans.

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Purpose Of Review: We review recent advances in the treatment of treatment-resistant depression (TRD), a disorder with very limited treatment options until recently. We examine advances in psychotherapeutic, psychopharmacologic, and interventional psychiatry approaches to treatment of TRD. We also highlight various definitions of TRD in recent scientific literature.

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Slow waves are a distinguishing feature of non-rapid-eye-movement (NREM) sleep, an evolutionarily conserved process critical for brain function. Non-human studies posit that the claustrum, a small subcortical nucleus, coordinates slow waves. We recorded claustrum neurons in humans during sleep.

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Background: To adapt to threats in the environment, animals must predict them and engage in defensive behavior. While the representation of a prediction error signal for reward has been linked to dopamine, a neuromodulatory prediction error for aversive learning has not been identified.

Methods: We measured and manipulated norepinephrine release during threat learning using optogenetics and a novel fluorescent norepinephrine sensor.

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