Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(5), P. 273 - 288

Published: March 29, 2022

Language: Английский

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Candidate biomarkers in psychiatric disorders: state of the field

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(2), P. 236 - 262

Published: May 9, 2023

The field of psychiatry is hampered by a lack robust, reliable and valid biomarkers that can aid in objectively diagnosing patients providing individualized treatment recommendations. Here we review critically evaluate the evidence for most promising psychiatric neuroscience literature autism spectrum disorder, schizophrenia, anxiety disorders post‐traumatic stress major depression bipolar substance use disorders. Candidate reviewed include various neuroimaging, genetic, molecular peripheral assays, purposes determining susceptibility or presence illness, predicting response safety. This highlights critical gap biomarker validation process. An enormous societal investment over past 50 years has identified numerous candidate biomarkers. However, to date, overwhelming majority these measures have not been proven sufficiently reliable, useful be adopted clinically. It time consider whether strategic investments might break this impasse, focusing on limited number candidates advance through process definitive testing specific indication. Some N170 signal, an event‐related brain potential measured using electroencephalography, subgroup identification within disorder; striatal resting‐state functional magnetic resonance imaging (fMRI) measures, such as connectivity index (SCI) abnormalities (FSA) index, prediction schizophrenia; error‐related negativity (ERN), electrophysiological first onset generalized structural connectomic social disorder. Alternate forms classification may conceptualizing Collaborative efforts allowing inclusion biosystems beyond genetics neuroimaging are needed, online remote acquisition selected naturalistic setting mobile health tools significantly field. Setting benchmarks well‐defined target application, along with development appropriate funding partnership mechanisms, would also crucial. Finally, it should never forgotten that, actionable, will need clinically predictive at individual level viable clinical settings.

Language: Английский

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New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(1), P. 4 - 24

Published: Jan. 14, 2023

Psychiatric genetics has made substantial progress in the last decade, providing new insights into genetic etiology of psychiatric disorders, and paving way for precision psychiatry, which individual profiles may be used to personalize risk assessment inform clinical decision‐making. Long recognized heritable, recent evidence shows that disorders are influenced by thousands variants acting together. Most these commonly occurring, meaning every a each disorder, from low high. A series large‐scale studies have discovered an increasing number common rare robustly associated with major disorders. The most convincing biological interpretation findings implicates altered synaptic function autism spectrum disorder schizophrenia. However, mechanistic understanding is still incomplete. In line their extensive epidemiological overlap, appear exist on continua share large degree one another. This provides further support notion current diagnoses do not represent distinct pathogenic entities, ongoing attempts reconceptualize nosology. also influences range behavioral somatic traits diseases, including brain structures, cognitive function, immunological phenotypes cardiovascular disease, suggesting shared potential importance. Current polygenic score tools, predict susceptibility illness, yet provide clinically actionable information. likely improve coming years, they eventually become part practice, stressing need educate clinicians patients about use misuse. review discusses key possible applications, suggests future directions.

Language: Английский

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Shared mechanisms across the major psychiatric and neurodegenerative diseases

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 26, 2022

Several common psychiatric and neurodegenerative diseases share epidemiologic risk; however, whether they pathophysiology is unclear the focus of our investigation. Using 25 GWAS results LD score regression, we find eight significant genetic correlations between diseases. We integrate with human brain transcriptomes (n = 888) proteomes 722) to identify cis- trans- transcripts proteins that are consistent a pleiotropic or causal role in each disease, referred as for brevity. Within disease group, many distinct shared proteins. Remarkably, 30% (13 42) disorders. Furthermore, 2.6-fold more protein-protein interactions among than expected by chance. Together, findings suggest these have molecular pathophysiology, which has important ramifications early treatment therapeutic development.

Language: Английский

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Exploring the genetic overlap between twelve psychiatric disorders

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(12), P. 1795 - 1802

Published: Dec. 1, 2022

Language: Английский

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Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(5), P. 792 - 808

Published: April 18, 2024

Language: Английский

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Multi-omics data integration methods and their applications in psychiatric disorders

European Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 69, P. 26 - 46

Published: Jan. 26, 2023

Language: Английский

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A Gpr35-tuned gut microbe-brain metabolic axis regulates depressive-like behavior

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(2), P. 227 - 243.e6

Published: Jan. 9, 2024

Language: Английский

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Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood

Science, Journal Year: 2024, Volume and Issue: 384(6698)

Published: May 23, 2024

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study posttraumatic stress disorder (PTSD) and major depressive (MDD) included the central nucleus amygdala, hippocampal dentate gyrus, medial prefrontal cortex (mPFC). Genes exons within mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal synaptic regulation, hormones. Multiomic factor gene network analyses provided underlying genomic structure. Single RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) non-neuronal cell types. Analyses brain-blood intersections >50,000 UK Biobank participants were conducted along with fine-mapping results PTSD MDD genome-wide association studies distinguish risk from processes. data suggest shared distinct both propose potential therapeutic targets biomarkers.

Language: Английский

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Mendelian randomization analyses reveal causal relationships between brain functional networks and risk of psychiatric disorders

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: 8(7), P. 1417 - 1428

Published: May 9, 2024

Language: Английский

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