Abstract:
:The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids have a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well being in the social environment.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Hsu DT,Sanford BJ,Meyers KK,Love TM,Hazlett KE,Wang H,Ni L,Walker SJ,Mickey BJ,Korycinski ST,Koeppe RA,Crocker JK,Langenecker SA,Zubieta JKdoi
10.1038/mp.2013.96subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1211-7issue
11eissn
1359-4184issn
1476-5578pii
mp201396journal_volume
18pub_type
杂志文章abstract::Corticotropin-releasing hormone (CRH) is the principal regulator of the hypothalamic-pituitary-adrenal (HPA) axis and an activator of the sympathoadrenal (SA) and systemic sympathetic (SS) systems. Mental disorders, including major depression and, more recently, Alzheimer's disease have been associated with dysregulat...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000720
更新日期:2000-03-01 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::The term 'mood stabilizer' has been applied to a number of medications for the treatment of patients with bipolar disorder. The operational definition of the properties of a mood-stabilizing medication has varied according to the properties of specific medications and the clinical characteristics of the illness. Rando...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4001013
更新日期:2002-01-01 00:00:00
abstract::To quantify aging- and disease-associated alterations in the integrative and interactive components of a pulsatile neuroendocrine axis, novel biomathematical strategies are required. Here, I illustrate as an investigative paradigm otherwise subtle aging-dependent disturbances of the gonadotropin-releasing-hormone (GnR...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4000232
更新日期:1997-01-01 00:00:00
abstract::Research on avoidance conditioning began in the late 1930s as a way to use laboratory experiments to better understand uncontrollable fear and anxiety. Avoidance was initially conceived of as a two-factor learning process in which fear is first acquired through Pavlovian aversive conditioning (so-called fear condition...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2016.166
更新日期:2017-01-01 00:00:00
abstract::The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic var...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000744
更新日期:2000-07-01 00:00:00
abstract::Cariprazine (CAR) is a strong inhibitor of the Dhcr7 enzyme, the last enzyme in the cholesterol biosynthesis pathway. We assessed the effects of CAR on maternally exposed Dhcr7+/- and wild-type mouse offspring, and tested the biochemical effects of CAR in human serum samples. Dhcr7+/- and wild-type time-pregnant mice ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0801-x
更新日期:2020-11-01 00:00:00
abstract::The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.192
更新日期:2016-11-01 00:00:00
abstract::How do joint measures of premorbid cognitive ability and familial cognitive aptitude (FCA) reflect risk for a diversity of psychiatric and substance use disorders? To address this question, we examined, using Cox models, the predictive effects of school achievement (SA) measured at age 16 and FCA-assessed from SA in s...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.78
更新日期:2018-04-01 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::Bipolar affective disorder is one of the most common mental illnesses with a population prevalence of approximately 1%. The disorder is genetically complex, with an increasing number of loci being implicated through genetic linkage studies. However, the specific genetic variations and molecules involved in bipolar sus...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001113
更新日期:2002-01-01 00:00:00
abstract::Linkage disequilibrium (LD) mapping was used to follow up reports of linkage between reading disability (RD) and an 18 cM region of chromosome 6p21.3-22. Using a two-stage approach, we tested for association between RD and 22 microsatellite markers in two independent samples of 101 (Stage 1) and 77 (Stage 2) parent/pr...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001216
更新日期:2003-02-01 00:00:00
abstract::The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcripti...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2014.147
更新日期:2015-07-01 00:00:00
abstract::Biological characterization of genetic variants identified in genome-wide association studies (GWAS) remains a substantial challenge. Here we used human-induced pluripotent stem cells (iPSC) and their neural derivatives to characterize common variants on chromosome 3p22 that have been associated by GWAS with major men...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0207-1
更新日期:2019-04-01 00:00:00
abstract::The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compar...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.236
更新日期:2018-03-01 00:00:00
abstract::Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and other members of the neurotrophin family, are central mediators of the activity-dependent plasticity through which environmental experiences, such as sensory information are translated into the structure and function of neuronal networks. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.61
更新日期:2017-08-01 00:00:00
abstract::Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.148
更新日期:2013-02-01 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::Anorexia nervosa (AN) and other eating disorders continue to constitute significant challenges for individual and public health. AN is thought to develop as a result of complex interactions between environmental triggers, psychological risk factors, sociocultural influences, and genetic vulnerability. Recent research ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/s41380-019-0366-8
更新日期:2019-10-01 00:00:00
abstract::We previously reported that expression level of LIM (ENH, PDLIM5) was significantly and commonly increased in the brains of patients with bipolar disorder, schizophrenia, and major depression. Expression of LIM was decreased in the lymphoblastoid cells derived from patients with bipolar disorders and schizophrenia. LI...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001719
更新日期:2005-11-01 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::Serum antibodies against amyloid-β peptide (Aβ) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against t...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.70
更新日期:2013-03-01 00:00:00
abstract::Calcium, the most versatile second messenger, regulates essential biology including crucial cellular events in embryogenesis. We investigated impacts of calcium channels and purinoceptors on neuronal differentiation of normal mouse embryonic stem cells (ESCs), with outcomes being compared to those of in vitro models o...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0717-5
更新日期:2020-04-29 00:00:00
abstract::Although schizophrenia is considered a brain disorder, the role of brain organization for symptomatic improvement remains inadequately defined. We investigated the relationship between baseline brain morphology, resting-state network connectivity and clinical response after 24-weeks of antipsychotic treatment in patie...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0269-0
更新日期:2020-04-01 00:00:00
abstract::Converging advances in the fields of molecular biology, molecular genetics, cellular biology and embryology have given researchers the tools for the targeted delivery and stable germline transmission of foreign genes (transgenes) in the mouse. In the realm of neuropsychiatry, this so-named transgenic technology has be...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:
更新日期:1996-05-01 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::The dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2008.7
更新日期:2009-06-01 00:00:00
abstract::The core nature of nicotine dependence is evident in wide variations in how individuals become and remain smokers. Individuals with pre-existing behavioral traits are more likely to develop nicotine dependence and experience difficulty when attempting to quit. Many molecular factors likely contribute to individual var...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2009.16
更新日期:2009-07-01 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::Schizophrenia is a chronic, severe and highly complex mental illness. Current treatments manage the positive symptoms, yet have minimal effects on the negative and cognitive symptoms, two prominent features of the disease with critical impact on the long-term morbidity. In addition, antipsychotic treatments trigger se...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.57
更新日期:2013-05-01 00:00:00