Findings of PTSD-specific deficits in default mode network strength following a mild experimental stressor.

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.

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA.

Background: Post-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Available pharmacotherapies are limited, take weeks to show modest benefit and remain ineffective for up to 40% of patients. Methylone is currently in clinical development for the treatment of PTSD.

Neural differentiation of emotional faces as a function of interpersonal violence among adolescent girls.

Interpersonal violence (IV) is associated with altered neural threat processing and risk for psychiatric disorder. Representational similarity analysis (RSA) is a multivariate approach examining the extent to which differences between stimuli correspond to differences in multivoxel activation patterns to these stimuli within each ROI. Using RSA, we examine overlap in neural patterns between threat and neutral faces in youth with IV.

Biological embedding of early trauma: the role of higher prefrontal synaptic strength.

Early trauma predicts poor psychological and physical health. Glutamatergic synaptic processes offer one avenue for understanding this relationship, given glutamate's abundance and involvement in reward and stress sensitivity, emotion, and learning. Trauma-induced glutamatergic excitotoxicity may alter neuroplasticity and approach/avoidance tendencies, increasing risk for psychiatric disorders.

Nicotine Use and Metabotropic Glutamate Receptor 5 in Individuals With Major Depressive and Posttraumatic Stress Disorders.

Metabotropic glutamate receptor 5 (mGluR5) dysregulation has been implicated in the pathophysiology of many psychiatric disorders, as well as nicotine use and dependence. We used positron emission tomography with [F]FPEB to measure mGluR5 availability in vivo in 6 groups: (1) nicotine users (NUs) without other psychiatric comorbidities (=23); (2) comparison controls (CCs) without nicotine use or psychiatric comorbidities (=38); (3) major depressive disorder subjects with concurrent nicotine use (MDD-NU; =19); (4) MDD subjects without concurrent nicotine use (MDD-CC; =20); (5) posttraumatic stress disorder subjects with concurrent nicotine use (PTSD-NU; =17); and (6) PTSD subjects without concurrent nicotine use (PTSD-CC; =16). The goal of the study was to test the hypothesis that mGluR5 availability in key corticolimbic regions of interest (ROIs) is different in NU with versus without comorbid psychiatric disorders (ROI: dorsolateral prefrontal cortex [dlPFC], orbitofrontal cortex [OFC], ventromedial prefrontal cortex [vmPFC], anterior cingulate cortex [ACC], amygdala, hippocampus).

Policy considerations that support equitable access to responsible, accountable, safe, and ethical uses of psychedelic medicines.

There is mounting evidence suggesting psychedelic and entactogen medicines (namely psilocybin and 3,4-methylenedioxymethamphetamine [MDMA]), in conjunction with proper psychosocial support, hold the potential to provide safe, rapid acting, and robust clinical improvements with durable effects. In the US, both psilocybin and MDMA have been granted Breakthrough Therapy designations by the US Food and Drug Administration and may potentially receive full FDA approval with similar regulatory considerations occurring in multiple countries. At the same time, regulatory changes are poised to increase access to legal or decriminalized psychedelic use in various non-medical settings.

Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans.

Background: Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC).

Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions.

Major depressive disorder is the most common neuropsychiatric disorder, affecting 11% of veterans. Here we report results of a large meta-analysis of depression using data from the Million Veteran Program, 23andMe, UK Biobank and FinnGen, including individuals of European ancestry (n = 1,154,267; 340,591 cases) and African ancestry (n = 59,600; 25,843 cases). Transcriptome-wide association study analyses revealed significant associations with expression of NEGR1 in the hypothalamus and DRD2 in the nucleus accumbens, among others.

Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin.

Twenty-four hours after administration, ketamine exerts rapid and robust antidepressant effects that are thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. Twenty patients suffering a major depressive episode were randomized to pretreatment with oral rapamycin (6 mg) or placebo 2 h prior to the intravenous administration of ketamine 0.

White matter microstructural alterations in posttraumatic stress disorder: An ROI and whole-brain based meta-analysis.

Background: Posttraumatic stress disorder (PTSD) is a debilitating mental illness that is thought to be associated with brain white matter (WM) alterations. Individual diffusion tensor imaging (DTI) studies to date have reported inconsistent alterations in FA across different brain regions in patients with PTSD. Here, we aimed to investigate FA in PTSD using both region-of-interest (ROI)-based and whole-brain-based meta-analytic approaches.

Heterogeneity of posttraumatic stress symptomatology and social connectedness in treatment-seeking military veterans: a longitudinal examination.

Elucidating whether PTSD symptoms predict poorer social connectedness over time (i.e. social erosion) and/or that poor social connectedness contributes to maintenance of PTSD (i.

Salience Network Disruption in U.S. Army Soldiers With Posttraumatic Stress Disorder.

Background: Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graph-based topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty US Army soldiers with PTSD compared to controls.

Methods: 102 participants with (n=50) or without PTSD (n=52) completed functional magnetic resonance imaging (MRI) at rest and during symptom provocation using subject-specific script imagery.

Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment.

Background: In soldiers with posttraumatic stress disorder (PTSD), symptom provocation was found to induce increased connectivity within the salience network, as measured by functional magnetic resonance imaging (MRI) and global brain connectivity with global signal regression (GBCr). However, it is unknown whether these GBCr disturbances would normalize following effective PTSD treatment.

Methods: 69 US Army soldiers with (n = 42) and without PTSD (n = 27) completed MRI at rest and during symptom provocation using subject-specific script imagery.

Topology of brain functional connectivity networks in posttraumatic stress disorder.

Here we present functional neuroimaging-based network data (focused on the default mode network) collected from a cohort of US Veterans with history of combat exposure, combined with clinical assessments for PTSD and other psychiatric comorbidities. The data has been processed and analyzed using several network construction methods (signed, thresholded, normalized to phase-randomized and rewired surrogates, functional and multimodal parcellation). An interpretation and discussion of the data can be found in the main NeuroImage article by Akiki et al.

Ketamine, but Not the NMDAR Antagonist Lanicemine, Increases Prefrontal Global Connectivity in Depressed Patients.

Background: Identifying the neural correlates of ketamine treatment may facilitate and expedite the development of novel, robust, and safe rapid-acting antidepressants. Prefrontal cortex (PFC) global brain connectivity with global signal regression (GBCr) was recently identified as a putative biomarker of major depressive disorder (MDD). Accumulating evidence have repeatedly shown reduced PFC GBCr in MDD, an abnormality which appears to normalize following ketamine treatment.

Locus of control in US combat veterans: Unique associations with posttraumatic stress disorder 5-factor model symptom clusters.

Given elevated rates of posttraumatic stress disorder (PTSD) among US military veterans, identifying correlates of PTSD and specific PTSD symptom clusters that best represent PTSD in veterans (i.e., the five-factor Dysphoric Arousal model) is critical to prevention and intervention efforts.

Default mode network abnormalities in posttraumatic stress disorder: A novel network-restricted topology approach.

Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, studies have largely been limited to seed-based methods and involved inconsistent definitions of the DMN. Recent advances in neuroimaging and graph theory now permit the systematic exploration of intrinsic brain networks.

Stress Response Modulation Underlying the Psychobiology of Resilience.

Purpose Of Review: This review focuses on the relationship between resilience and the ability to effectively modulate the stress response. Neurobiological and behavioral responses to stress are highly variable. Exposure to a similar stressor can lead to heterogeneous outcomes-manifesting psychopathology in one individual, but having minimal effect, or even enhancing resilience, in another.

Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment.

Background: Prefrontal global brain connectivity with global signal regression (GBCr) was proposed as a robust biomarker of depression, and was associated with ketamine's mechanism of action. Here, we investigated prefrontal GBCr in treatment-resistant depression (TRD) at baseline and following treatment. Then, we conducted a set of pharmacological challenges in healthy subjects to investigate the glutamate neurotransmission correlates of GBCr.

The Association of PTSD Symptom Severity with Localized Hippocampus and Amygdala Abnormalities.

Background: The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have made it possible to identify specific locations of subtle morphometric changes within a structure of interest.