Abstract:
:Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Dean KR,Hammamieh R,Mellon SH,Abu-Amara D,Flory JD,Guffanti G,Wang K,Daigle BJ Jr,Gautam A,Lee I,Yang R,Almli LM,Bersani FS,Chakraborty N,Donohue D,Kerley K,Kim TK,Laska E,Young Lee M,Lindqvist D,Lori A,Lu L,Mdoi
10.1038/s41380-019-0496-zsubject
Has Abstractpub_date
2020-12-01 00:00:00pages
3337-3349issue
12eissn
1359-4184issn
1476-5578pii
10.1038/s41380-019-0496-zjournal_volume
25pub_type
杂志文章abstract::Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN-/-) mice developed Alzheimer's like pathologies, cerebral insulin resistance, and cogniti...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0701-0
更新日期:2020-03-04 00:00:00
abstract::Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.156
更新日期:2018-11-01 00:00:00
abstract::Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0281-4
更新日期:2020-05-01 00:00:00
abstract::Major depressive disorder (MDD) is associated with reduced concentrations of γ-aminobutyric acid (GABA) that are normalized by antidepressant therapies. Moreover, depressive-like phenotypes of GABAA receptor mutant mice can be reversed by treatment with conventional antidepressants drugs, as well as by subanesthetic d...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.188
更新日期:2017-06-01 00:00:00
abstract::Contemporary models of psychosis suggest that a continuum of severity of psychotic symptoms exists, with subthreshold psychotic experiences (PEs) potentially reflecting some genetic and environmental risk factors shared with clinical psychosis. Thus, identifying abnormalities in brain activity that manifest across thi...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00983-1
更新日期:2021-01-18 00:00:00
abstract::Between 1997 and 2002, 48 data sets from the hippocampus were produced on samples from the Stanley Neuropathology Consortium. From these data sets, 224 total measures were available from the various subdivisions of the hippocampus. An integrative analysis of these measures was performed using a multivariate, nonparame...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001471
更新日期:2004-06-01 00:00:00
abstract::This corrects the article DOI: 10.1038/mp.2016.107. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,已发布勘误
doi:10.1038/mp.2017.203
更新日期:2018-01-01 00:00:00
abstract::Mol Psychiatry 2000; 5: 77-84 ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000752
更新日期:2000-07-01 00:00:00
abstract::Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions i...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.54
更新日期:2011-08-01 00:00:00
abstract::Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted onl...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.172
更新日期:2018-05-01 00:00:00
abstract::Previous work has demonstrated associations between lower cognitive ability and childhood and adult non-psychotic psychopathology. As both cognitive ability (CA) and child psychopathology (CP) are influenced by genetic factors, one explanation for the association is that they are the pleiotropic manifestations of the ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000971
更新日期:2002-01-01 00:00:00
abstract::Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizo...
journal_title:Molecular psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1038/mp.2017.41
更新日期:2018-02-01 00:00:00
abstract::Signalling by retinoid compounds is vital for embryonic development, with particular importance for neurogenesis in the human brain. Retinoids, metabolites of vitamin A, exert influence over the expression of thousands of transcripts genome wide, and thus, act as master regulators of many important biological processe...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/s41380-019-0566-2
更新日期:2020-04-01 00:00:00
abstract::Depression often accompanies the perimenopausal transition and it often precedes overt symptomology in common neurodegenerative diseases (NDDs, such as Alzheimer's, Parkinson's, Huntington, amyotrophic lateral sclerosis). Serotonin dysfunction is frequently found in the different etiologies of depression. We have show...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2014.178
更新日期:2015-12-01 00:00:00
abstract::Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood....
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.80
更新日期:2018-05-01 00:00:00
abstract::We conducted a 10 centimorgan (cM) linkage genome scan in a set of American extended pedigrees ascertained through probands with panic disorder. Several anxiety disorders segregate in these families. In this article, we describe results for simple phobia from 14 of these families (including 129 subjects of whom 57 are...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001224
更新日期:2003-01-01 00:00:00
abstract::Endogenous opioid and non-opioid mechanisms (for example, dopamine (DA), endocannabinoids (eCB)) have been implicated in the formation of placebo analgesic effects, with initial reports dating back three decades. Besides the perspective that placebo effects confound randomized clinical trials, the information so far a...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2014.164
更新日期:2015-04-01 00:00:00
abstract::Perturbation of Disrupted-In-Schizophrenia-1 (DISC1) and D-serine/NMDA receptor hypofunction have both been implicated in the pathophysiology of schizophrenia and other psychiatric disorders. In the present study, we demonstrate that these two pathways intersect with behavioral consequences. DISC1 binds to and stabili...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.97
更新日期:2013-05-01 00:00:00
abstract::Polymorphic variants of the dopamine D(4) receptor have been consistently associated with attention-deficit hyperactivity disorder (ADHD). However, the functional significance of the risk polymorphism (variable number of tandem repeats in exon 3) is still unclear. Here, we show that whereas the most frequent 4-repeat ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.93
更新日期:2012-06-01 00:00:00
abstract::Association between attention-deficit hyperactivity disorder (ADHD) and the 10-repeat allele of the dopamine transporter gene (DAT1) has been reported in independent clinical samples using a categorical clinical definition of ADHD. The present study adopts a quantitative trait loci (QTL) approach to examine the associ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001641
更新日期:2005-07-01 00:00:00
abstract::Many antidepressants stimulate adult hippocampal neurogenesis, but the mechanisms by which they increase neurogenesis and modulate behavior are incompletely understood. Here we show that hippocampal bone morphogenetic protein (BMP) signaling is modulated by antidepressant treatment, and that the changes in BMP signali...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.160
更新日期:2017-06-01 00:00:00
abstract::Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0432-2
更新日期:2020-05-01 00:00:00
abstract::There are well-replicated, independent lines of evidence supporting a role for corticotropin-releasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CR...
journal_title:Molecular psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/sj.mp.4001587
更新日期:2004-12-01 00:00:00
abstract::We earlier reported a genome-wide significant linkage to schizophrenia at chromosome 17 that was identified in a single pedigree (C702) consisting of six affected, male siblings with DSM-IV schizophrenia and prominent mood symptoms. In this study, we adopted several approaches in an attempt to map the putative disease...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2009.96
更新日期:2010-11-01 00:00:00
abstract::In our genome scan for schizophrenia genes in 265 Irish pedigrees, marker D5S818 in 5q22 produced the second best result of the first 223 markers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizophrenia in region 5q22-31. This region ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000258
更新日期:1997-03-01 00:00:00
abstract::The actions of CRF in the brain and in the periphery are mediated through multiple binding sites. There are three receptors, CRF1, CRF2 alpha and CRF2 beta, which encode 411, 415 and 431 amino acid proteins and transduce signals via the stimulation of intracellular cAMP production. The recent identification of high-af...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:
更新日期:1996-09-01 00:00:00
abstract::Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depres...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2013.129
更新日期:2014-02-01 00:00:00
abstract::Cannabis is one of the most commonly and widely used psychoactive drugs. The rates of cannabis misuse have been increasing. Therefore, understanding the effects of cannabis use on the brain is important. Adolescent and adult rodents exposed to repeated administration of cannabinoids show persistent microstructural cha...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00891-4
更新日期:2020-09-24 00:00:00
abstract::APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 ac...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001755
更新日期:2006-01-01 00:00:00
abstract::Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4002047
更新日期:2008-07-01 00:00:00