Abstract:
:Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Raison CL,Miller AHdoi
10.1038/mp.2012.2subject
Has Abstractpub_date
2013-01-01 00:00:00pages
15-37issue
1eissn
1359-4184issn
1476-5578pii
mp20122journal_volume
18pub_type
杂志文章abstract::The effect of endogenous dopamine (DA) on neostriatal DA D(1) and D(2) receptor binding potentials (D(1)RBP and D(2)RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [(11)C]SCH23390 and [(11)C]raclopride, respectively, by comparing the D(1)RBP and D(2)RBP before and ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001062
更新日期:2002-01-01 00:00:00
abstract::Among the most consistent results of studies of post-mortem brain tissue from schizophrenia patients (SZP) is the finding that in this disease, several genes expressed by GABAergic neurons are downregulated. This downregulation may be caused by hypermethylation of the relevant promoters in affected neurons. Indeed, in...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001954
更新日期:2007-04-01 00:00:00
abstract::Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system (CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underp...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.183
更新日期:2014-02-01 00:00:00
abstract::Depression is a common mental illness, affecting more than 300 million people worldwide. Decades of investigation have yielded symptomatic therapies for this disabling condition but have not led to a consensus about its pathogenesis. There are data to support several different theories of causation, including the mono...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/s41380-020-00930-0
更新日期:2021-01-01 00:00:00
abstract::Exposure to severe stressors increases the risk for psychiatric disorders in vulnerable individuals, but can lead to positive outcomes for others. However, it remains unknown how severe stress affects neural functioning in humans and what factors mediate individual differences in the neural sequelae of stress. The amy...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.132
更新日期:2011-06-01 00:00:00
abstract::Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down synd...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0200-8
更新日期:2020-11-01 00:00:00
abstract::Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase IIalpha (PIP5K2A), in...
journal_title:Molecular psychiatry
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.mp.4001864
更新日期:2006-09-01 00:00:00
abstract::Familial and twin studies have suggested that anorexia nervosa (AN) is a multifactorial disorder with a substantial genetic contribution. The hSKCa3 potassium channel gene, which contains polymorphic CAG repeats in the coding region and is involved in the regulation of neuronal activity, may be a candidate gene for AN...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000931
更新日期:2002-01-01 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 Article was originally published under Nature Research's License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the Article have been modified accordingly. ...
journal_title:Molecular psychiatry
pub_type: 已发布勘误
doi:10.1038/s41380-018-0327-7
更新日期:2019-09-01 00:00:00
abstract::Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that co...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000353
更新日期:1998-01-01 00:00:00
abstract::Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) rev...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析
doi:10.1038/mp.2016.231
更新日期:2018-02-01 00:00:00
abstract::Depression is a heritable disorder that is often precipitated by stress. Abnormalities of the stress-reactive hypothalamic-pituitary-adrenal (HPA) axis are also common in depressed patients. In animal models, the forced swim test (FST) is the most frequently used test of depressive-like behavior. We have used a propos...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001255
更新日期:2003-04-01 00:00:00
abstract::We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001463
更新日期:2004-04-01 00:00:00
abstract::The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.164
更新日期:2018-02-01 00:00:00
abstract::Genomic risk profile scores (GRPSs) have been shown to predict case-control status of schizophrenia (SCZ), albeit with varying sensitivity and specificity. The extent to which this variability in prediction accuracy is related to differences in sampling strategies is unknown. Danish population-based registers and Neon...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.130
更新日期:2016-07-01 00:00:00
abstract::Adults with psychotic disorders have dysconnectivity in critical brain networks, including the default mode (DM) and the cingulo-opercular (CO) networks. However, it is unknown whether such deficits are present in youth with less severe symptoms. We conducted a multivariate connectome-wide association study examining ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.66
更新日期:2015-12-01 00:00:00
abstract::Schizophrenia and bipolar disorder have both been linked to structural abnormalities of the hippocampus, which is consistent with a neurodevelopmental anomaly. One isoform of the neural cell adhesion molecule (N-CAM) protein, cytosolic N-CAM 105-115 kDa, was previously shown to be increased in schizophrenia in the hip...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000547
更新日期:1999-09-01 00:00:00
abstract::It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripher...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00908-y
更新日期:2020-10-16 00:00:00
abstract::We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析,评审
doi:10.1038/sj.mp.4002136
更新日期:2009-04-01 00:00:00
abstract::Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with th...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4001909
更新日期:2007-01-01 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::Cigarette smoking is more prevalent in subjects with schizophrenia compared to those with other psychiatric disorders or the general population and could therefore affect molecular pathways that impact the pathophysiology of this disorder. As smoking is also known to suppress immune responses, we investigated the effe...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2008.120
更新日期:2010-04-01 00:00:00
abstract::Attention-deficit hyperactivity disorder (ADHD) is typically characterized as a disorder of inattention and hyperactivity/impulsivity but there is increasing evidence of deficits in motivation. Using positron emission tomography (PET), we showed decreased function in the brain dopamine reward pathway in adults with AD...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.97
更新日期:2011-11-01 00:00:00
abstract::Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we ex...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.60
更新日期:2012-02-01 00:00:00
abstract::We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of p...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0345-5
更新日期:2019-04-01 00:00:00
abstract::Circular RNAs (circRNAs), highly expressed in the central nervous system, are involved in various regulatory processes and implicated in some pathophysiology. However, the potential role of circRNAs in psychiatric diseases, particularly major depressive disorder (MDD), remains largely unknown. Here, we demonstrated th...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0285-0
更新日期:2020-06-01 00:00:00
abstract::Identifying biomarkers in schizophrenia during the first episode without the confounding effects of treatment has been challenging. Leveraging these biomarkers to establish diagnosis and make individualized predictions of future treatment responses to antipsychotics would be of great value, but there has been limited ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0106-5
更新日期:2020-04-01 00:00:00
abstract::Abnormalities in the gamma-aminobutyric acid (GABA) neurotransmitter system have been noted in subjects with mood and anxiety disorders. Glutamic acid decarboxylase (GAD) enzymes synthesize GABA from glutamate, and, thus, are reasonable candidate susceptibility genes for these conditions. In this study, we examined th...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001845
更新日期:2006-08-01 00:00:00
abstract::Obscure work on the inheritance of two peculiar genetic traits in yeast has recently collided with work on infectious, neurodegenerative diseases in mammals. The impact illuminates both fields. The yeast work reveals a new mechanism of genetic variation that is based on differences in protein conformation rather than ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:
更新日期:1996-11-01 00:00:00