Candidate biomarkers in psychiatric disorders: state of the field

World Psychiatry, Год журнала: 2023, Номер 22(2), С. 236 - 262

Опубликована: Май 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.

Язык: Английский

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Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders

Nature Mental Health, Год журнала: 2023, Номер 1(3), С. 210 - 223

Опубликована: Март 22, 2023

Язык: Английский

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Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci

Molecular Psychiatry, Год журнала: 2022, Номер 27(10), С. 3970 - 3979

Опубликована: Июль 25, 2022

Abstract Despite the large toll of opioid use disorder (OUD), genome-wide association studies (GWAS) OUD to date have yielded few susceptibility loci. We performed a large-scale GWAS in individuals European (EUR) and African (AFR) ancestry, optimizing genetic informativeness by performing MTAG (Multi-trait analysis GWAS) with genetically correlated substance disorders (SUDs). Meta-analysis included seven cohorts: Million Veteran Program, Psychiatric Genomics Consortium, iPSYCH, FinnGen, Partners Biobank, BioVU, Yale-Penn 3, resulting total N = 639,063 ( cases 20,686;N effective 77,026) across ancestries. were defined as having lifetime diagnosis, controls anyone not known meet criteria. estimated SNP-heritability (h 2 SNP ) correlations (r g ). Based on correlation, we OUD, alcohol (AUD), cannabis (CanUD). A leave-one-out polygenic risk score (PRS) was compare OUD-MTAG PRS predictors case status 3. The EUR meta-analysis identified three significant (GWS; p ≤ 5 × 10 − 8 lead SNPs—one at FURIN (rs11372849; 9.54 two OPRM1 variants (rs1799971, 4.92 09 ; rs79704991, 1.11 08 r 0.02). Rs1799971 (p 4.91 another variant (rs9478500; 1.95 0.03) cross-ancestry meta-analysis. Estimated h 12.75%, strong CanUD 0.82; 1.14 47 AUD 0.77; 6.36 78 resulted equivalent 128,748 18 independent GWS loci, some mapping genes or gene regions that previously been associated psychiatric addiction phenotypes. accounted for 3.81% variance (beta 0.61;s.e. 0.066; 2.00 16 compared 2.41% 0.45; s.e. 0.058; 2.90 13 explained PRS. current study associations , single OUD-MTAG. architecture is likely influenced both OUD-specific loci shared SUDs.

Язык: Английский

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Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 31, 2024

Abstract In brain, the striatum is a heterogenous region involved in reward and goal-directed behaviors. Striatal dysfunction linked to psychiatric disorders, including opioid use disorder (OUD). subregions are divided based on neuroanatomy, each with unique roles OUD. OUD, dorsal altered processing, formation of habits, development negative affect during withdrawal. Using single nuclei RNA-sequencing, we identified both canonical (e.g., dopamine receptor subtype) less abundant cell populations interneurons) human striatum. Pathways related neurodegeneration, interferon response, DNA damage were significantly enriched striatal neurons individuals markers also elevated opioid-exposed rhesus macaques. Sex-specific molecular differences glial subtypes associated chronic stress found particularly female individuals. Together, describe different types identify type-specific alterations

Язык: Английский

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Reward Deficiency Syndrome (RDS) Surprisingly Is Evolutionary and Found Everywhere: Is It “Blowin’ in the Wind”?

Journal of Personalized Medicine, Год журнала: 2022, Номер 12(2), С. 321 - 321

Опубликована: Фев. 21, 2022

Reward Deficiency Syndrome (RDS) encompasses many mental health disorders, including a wide range of addictions and compulsive impulsive behaviors. Described as an octopus behavioral dysfunction, RDS refers to abnormal behavior caused by breakdown the cascade reward in neurotransmission due genetic epigenetic influences. The resultant deficiencies interfere with pleasure derived from satisfying powerful human physiological drives. Epigenetic repair may be possible precision gene-guided therapy using formulations KB220, nutraceutical that has demonstrated pro-dopamine regulatory function animal neuroimaging clinical trials. Recently, large GWAS studies have revealed significant dopaminergic gene risk polymorphic allele overlap between depressed schizophrenic cohorts. A volume literature also identified ADHD, PTSD, spectrum disorders having known neurogenetic psychological underpinnings RDS. hypothesis is true phenotype RDS, are endophenotypes. Is it logical wonder if exists everywhere? Although complex, "the answer blowin' wind," rather than intangible, foundational species evolution survival, array neurotransmitters loci influencing functionality.

Язык: Английский

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The Genetically Informed Neurobiology of Addiction (GINA) model

Nature reviews. Neuroscience, Год журнала: 2022, Номер 24(1), С. 40 - 57

Опубликована: Ноя. 29, 2022

Язык: Английский

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Cannabis Pharmacogenomics: A Path to Personalized Medicine

Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(4), С. 3479 - 3514

Опубликована: Апрель 17, 2023

Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids incidence side are still difficult to determine. Pharmacogenomics may provide answers questions concerns regarding cannabis/cannabinoid treatment help us understand variability responses associated risks. has made meaningful progress identifying genetic variations that play critical role interpatient response cannabis. This review classifies current knowledge pharmacogenomics with medical marijuana can assist improving outcomes cannabinoid minimize adverse cannabis use. Specific examples informing pharmacotherapy path personalized medicine discussed.

Язык: Английский

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Genetic and non-genetic predictors of risk for opioid dependence

Psychological Medicine, Год журнала: 2024, Номер 54(8), С. 1779 - 1786

Опубликована: Фев. 6, 2024

Abstract Background Elucidation of the interaction biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding etiology OD. We examined role in moderating polygenic for use disorder (OUD). Methods Data from 1958 European ancestry adults who participated Yale-Penn 3 study were analyzed. Polygenic scores (PRS) based a large-scale multi-trait analysis genome-wide association studies (MTAG) OUD. Results A total 420 (21.1%) individuals had lifetime diagnosis OUD PRS positively associated with OD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.21–1.66). Household income education strongest correlates Among higher PRS, those level lower odds (OR 0.92, CI 0.85–0.98); posttraumatic stress (PTSD) more likely to have relative without PTSD 1.56, 1.04–2.35). Conclusions suggest an interplay between genetics psychosocial environment contributing risk. While alone do not yet useful clinical predictive utility, may help enhance prediction. These findings could targeted policy interventions address this public health crisis.

Язык: Английский

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Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Янв. 12, 2022

Genetic liability to substance use disorders can be parsed into loci conferring general and substance-specific addiction risk. We report a multivariate genome-wide association study that disaggregates for problematic alcohol use, tobacco cannabis opioid in sample of 1,025,550 individuals European 92,630 African descent. Nineteen were significant the risk factor (addiction-rf), which showed high polygenicity. Across ancestries PDE4B was (among others), suggesting dopamine regulation as cross-trait vulnerability. The addiction-rf polygenic score associated with disorders, psychopathologies, somatic conditions, environments onset addictions. Substance-specific (9 alcohol, 32 tobacco, 5 cannabis, 1 opioids) included metabolic receptor genes. These findings provide insight genetic architecture disorder may leveraged treatment targets.

Язык: Английский

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The collaborative study on the genetics of alcoholism: Genetics

Genes Brain & Behavior, Год журнала: 2023, Номер 22(5)

Опубликована: Июнь 30, 2023

Abstract This review describes the genetic approaches and results from family‐based Collaborative Study on Genetics of Alcoholism (COGA). COGA was designed during linkage era to identify genes affecting risk for alcohol use disorder (AUD) related problems, among first AUD‐focused studies subsequently adopt a genome‐wide association (GWAS) approach. COGA's structure, multimodal assessment with gold‐standard clinical neurophysiological data, availability prospective longitudinal phenotyping continues provide insights into etiology AUD disorders. These include investigations trajectories substance disorders, phenome‐wide loci interest, pleiotropy, social genomics, nurture, within‐family comparisons. is one few genetics projects that includes substantial number participants African ancestry. The sharing data biospecimens has been cornerstone project, key contributor large‐scale GWAS consortia. wealth publicly available extensive unique adaptable resource our understanding traits.

Язык: Английский

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