International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Oct. 8, 2019

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct genome-wide association study PTSD. We demonstrate SNP-based heritability estimates 5-20%, varying by sex. Three significant loci are identified, 2 in European 1 African-ancestry analyses. Analyses stratified sex implicate 3 additional men. Along with other novel genes non-coding RNAs, Parkinson's disease gene involved dopamine regulation, PARK2, associated Finally, that polygenic for significantly predictive re-experiencing symptoms the Million Veteran Program dataset, although specific did not replicate. These results role genetic variation biology highlight necessity conducting sex-stratified analyses expanding GWAS beyond ancestry populations.

Language: Английский

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Behavioral and neurobiological mechanisms of pavlovian and instrumental extinction learning

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(2), P. 611 - 681

Published: Sept. 24, 2020

This article reviews the behavioral neuroscience of extinction, phenomenon in which a behavior that has been acquired through Pavlovian or instrumental (operant) learning decreases strength when outcome reinforced it is removed. Behavioral research indicates neither nor operant extinction depends substantially on erasure original but instead new inhibitory primarily expressed context learned, as exemplified by renewal effect. Although nature inhibition may differ and either case decline responding depend both generalization decrement correction prediction error. At neural level, requires tripartite circuit involving amygdala, prefrontal cortex, hippocampus. Synaptic plasticity amygdala essential for learning, cortical neurons encoding fear memories involved retrieval. Hippocampal-prefrontal circuits mediate relapse phenomena, including renewal. Instrumental involves distinct ensembles corticostriatal, striatopallidal, striatohypothalamic well their thalamic returns (extinction) excitatory (renewal other phenomena) control over responding. The field made significant progress recent decades, although fully integrated biobehavioral understanding still awaits.

Language: Английский

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Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders

Pharmacology & Therapeutics, Journal Year: 2019, Volume and Issue: 204, P. 107402 - 107402

Published: Aug. 27, 2019

Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need improved drug treatments. In this review an overview drugs being studied different phases clinical trials their potential treatment fear-, anxiety- trauma-related presented. One strategy followed development refining improving compounds interacting with existing anxiolytic targets, such as serotonergic prototypical GABAergic benzodiazepines. A more innovative approach involves search novel mechanisms action using growing knowledge base concerning relevant neurocircuitries neurobiological underlying pathological fear anxiety. The target systems evaluated include glutamate, endocannabinoid neuropeptide systems, well ion channels targets derived from phytochemicals. Examples promising candidates currently generalised disorder, social panic obsessive compulsive disorder or post-traumatic stress ketamine, riluzole, xenon one common pharmacological modulation glutamatergic neurotransmission, neurosteroid aloradine. Finally, D-cycloserine, MDMA, L-DOPA cannabinoids have shown efficacy enhancing fear-extinction learning humans. They are thus investigated augmentative speeding up long-term effectiveness exposure-based psychotherapy, which could render chronic dispensable many patients. These efforts indicative a rekindled interest renewed optimism discovery field, after decades relative stagnation.

Language: Английский

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Cognitive Network Science: A Review of Research on Cognition through the Lens of Network Representations, Processes, and Dynamics

Complexity, Journal Year: 2019, Volume and Issue: 2019(1)

Published: Jan. 1, 2019

Network science provides a set of quantitative methods to investigate complex systems, including human cognition. Although cognitive theories in different domains are strongly based on network perspective, the application methodologies quantitatively study cognition has so far been limited scope. This review demonstrates how approaches have applied and can uniquely address provide novel insight important questions related complexity systems processes that occur within those systems. Drawing literature science, with focus semantic lexical networks, we argue three key points. (i) powerful approach represent (ii) The enables scientists achieve deeper understanding by capturing structure, i.e., underlying network, operating structure interact produce behavioral phenomena. (iii) framework model dynamics operationalized as structural changes timescales resolutions. Finally, highlight milestones field needs it matures order continued insights into nature structures processes.

Language: Английский

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Amygdala Reward Neurons Form and Store Fear Extinction Memory

Neuron, Journal Year: 2020, Volume and Issue: 105(6), P. 1077 - 1093.e7

Published: Jan. 14, 2020

Language: Английский

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Optimizing exposure therapy with an inhibitory retrieval approach and the OptEx Nexus

Behaviour Research and Therapy, Journal Year: 2022, Volume and Issue: 152, P. 104069 - 104069

Published: March 14, 2022

Language: Английский

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The neurobiology of human fear generalization: meta-analysis and working neural model

Neuroscience & Biobehavioral Reviews, Journal Year: 2021, Volume and Issue: 128, P. 421 - 436

Published: July 6, 2021

Language: Английский

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Neuropharmacological Modulation of N-methyl-D-aspartate, Noradrenaline and Endocannabinoid Receptors in Fear Extinction Learning: Synaptic Transmission and Plasticity

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5926 - 5926

Published: March 21, 2023

Learning to recognize and respond potential threats is crucial for survival. Pavlovian threat conditioning represents a key paradigm investigating the neurobiological mechanisms of fear learning. In this review, we address role specific neuropharmacological adjuvants that act on neurochemical synaptic transmission, as well brain plasticity processes implicated in memory. We focus novel manipulations targeting glutamatergic, noradrenergic, endocannabinoid systems, how modulation these systems affects extinction learning humans. show administration N-methyl-D-aspartate (NMDA) agonists system by fatty acid amide hydrolase (FAAH) inhibition can boost through stabilization regulation receptor concentration. On other hand, elevated noradrenaline levels dynamically modulate learning, hindering long-term processes. These pharmacological interventions could provide targeted treatments prevention strategies fear-based anxiety-related disorders.

Language: Английский

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Neurobiology and systems biology of stress resilience

Physiological Reviews, Journal Year: 2024, Volume and Issue: 104(3), P. 1205 - 1263

Published: March 14, 2024

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts unravel factors and mechanisms make possible harness its insights for development of preventative interventions in individuals at risk acquiring stress-related dysfunctions. Biological has been lagging behind psychological social sciences but seen a massive surge recent years. At same time, progress this field hampered methodological challenges related finding suitable operationalizations study designs, replicating findings, modeling animals. We embed review behavioral, neuroimaging, neurobiological, systems biological findings adults critical methods discussion. find preliminary evidence hippocampus-based pattern separation prefrontal-based cognitive control functions protect against pathological fears aftermath singular, event-type stressors [as found fear-related disorders, including simpler forms posttraumatic stress disorder (PTSD)] facilitating perception safety. Reward system-based pursuit savoring positive reinforcers appear more generalized dysfunctions anxious-depressive spectrum resulting from severe longer-lasting (as depression, comorbid anxiety, PTSD). Links between preserved functioning these neural under neuroplasticity, immunoregulation, gut microbiome composition, integrity barrier blood-brain are beginning emerge. On basis, avenues pointed out.

Language: Английский

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New Perspectives on the Aging Lexicon

Trends in Cognitive Sciences, Journal Year: 2019, Volume and Issue: 23(8), P. 686 - 698

Published: July 6, 2019

The field of cognitive aging has seen considerable advances in describing the linguistic and semantic changes that happen during adult life span to uncover structure mental lexicon (i.e., repository lexical conceptual representations). Nevertheless, there is still debate concerning sources these changes, including role environmental exposure several mechanisms associated with learning, representation, retrieval information. We review current status research this outline a framework promises assess contribution both ecological psychological aspects lexicon.

Language: Английский

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