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 dysconnectivity with resting state functional magnetic resonance imaging in a population-based cohort of 188 youths aged 8-22 years with psychosis-spectrum (PS) symptoms and 204 typically developing (TD) comparators. We found evidence for multi-focal dysconnectivity in PS youths, implicating the bilateral anterior cingulate, frontal pole, medial temporal lobe, opercular cortex and right orbitofrontal cortex. Follow-up seed-based and network-level analyses demonstrated that these results were driven by hyper-connectivity among DM regions and diminished connectivity among CO regions, as well as diminished coupling between frontal and DM regions. Collectively, these results provide novel evidence for functional dysconnectivity in PS youths, which show marked correspondence to abnormalities reported in adults with established psychotic disorders.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Satterthwaite TD,Vandekar SN,Wolf DH,Bassett DS,Ruparel K,Shehzad Z,Craddock RC,Shinohara RT,Moore TM,Gennatas ED,Jackson C,Roalf DR,Milham MP,Calkins ME,Hakonarson H,Gur RC,Gur REdoi
10.1038/mp.2015.66subject
Has Abstractpub_date
2015-12-01 00:00:00pages
1508-15issue
12eissn
1359-4184issn
1476-5578pii
mp201566journal_volume
20pub_type
杂志文章abstract::Myo-inositol exerts behavioral effects in animal models of psychiatric disorders and is effective in clinical trials in psychiatric patients. Interestingly, epi-inositol exerts behavioral effects similar to myo-inositol, even though epi-inositol is not a substrate for synthesis of phosphatidylinositol. We postulated t...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000965
更新日期:2002-01-01 00:00:00
abstract::Neurobiological disorders have diverse manifestations and symptomology. Neurodegenerative disorders, such as Alzheimer's disease, manifest late in life and are characterized by, among other symptoms, progressive loss of synaptic markers. Developmental disorders, such as autism spectrum, appear in childhood. Neuropsych...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2009.82
更新日期:2009-11-01 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::Suicide is a major public health concern and a leading cause of death in most societies. Suicidal behaviour is complex and heterogeneous, likely resulting from several causes. It associates with multiple factors, including psychopathology, personality traits, early-life adversity and stressful life events, among other...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2017.141
更新日期:2017-10-01 00:00:00
abstract::A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, iloperidone, administered to treat patients with schizophrenia. Genotypes of 407 patients were analyzed for 334,563 single nucleotide polymorphisms (SNPs). SNPs associated with iloperidone efficacy w...
journal_title:Molecular psychiatry
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/mp.2008.56
更新日期:2009-08-01 00:00:00
abstract::Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact....
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.61
更新日期:2017-04-01 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
abstract::Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs in activating latent infection in HIV strains derived from the central nervous system (C...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.111
更新日期:2016-04-01 00:00:00
abstract::Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations hav...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0355-y
更新日期:2020-04-01 00:00:00
abstract::The 12/15-lipoxygenase (12/15LO) enzyme is widely distributed within the central nervous system. Previous work showed that this protein is upregulated in Alzheimer's disease (AD), and plays an active role in the development of brain amyloidosis in amyloid beta (Aβ)-precursor protein transgenic mice (Tg2576). In the pr...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2014.170
更新日期:2015-11-01 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::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::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::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::Serotonergic (5HT) neurons exert diverse and widespread functions in the brain. Dysfunction of the serotonergic system gives rise to a variety of mental illnesses including depression, anxiety, obsessive compulsive disorder, autism and eating disorders. Here we show that human primary fibroblasts were directly convert...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.101
更新日期:2016-01-01 00:00:00
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 ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.2
更新日期:2013-01-01 00:00:00
abstract::Normal development of cortical circuits, including experience-dependent cortical maturation and plasticity, requires precise temporal regulation of gene expression and molecular signaling. Such regulation, and the concomitant impact on plasticity and critical periods, is hypothesized to be disrupted in neurodevelopmen...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0635-6
更新日期:2020-01-03 00:00:00
abstract::Episodic memory, a fundamental component of human cognition, is significantly impaired in autism. We believe we report the first evidence for this problem in the Fmr1-knockout (KO) mouse model of Fragile X syndrome and describe potentially treatable underlying causes. The hippocampus is critical for the formation and ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.221
更新日期:2018-08-01 00:00:00
abstract::The amygdala is a key brain region that is critically involved in the processing and expression of anxiety and fear-related signals. In parallel, a growing number of preclinical and human studies have implicated the microbiome-gut-brain in regulating anxiety and stress-related responses. However, the role of the micro...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.100
更新日期:2018-05-01 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::The Wistar-Kyoto (WKY) rat strain demonstrates endogenous hormonal and behavioral abnormalities that emulate many of those found in symptom-presenting depressive patients. Evidence suggests that the WKY strain may harbor heterogeneity not found in other inbred strains, including greater behavioral and genetic variabil...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001345
更新日期:2003-11-01 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::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::The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been repeatedly associated with antidepressant response in mood disorder patients, but findings are not consistent across studies. A meta-analysis was performed on 15 studies including data of 1435 subjects. We tested three phenotypes: remission rate,...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析
doi:10.1038/sj.mp.4001926
更新日期:2007-03-01 00:00:00
abstract::The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adul...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001978
更新日期:2007-06-01 00:00:00
abstract::Low hippocampal volume is a consistent finding in schizophrenia and across the psychosis spectrum. However, there is a lack of studies investigating longitudinal hippocampal development and its relationship with psychotic symptoms. The 22q11.2 deletion syndrome (22q11DS) has proven to be a remarkable model for the pro...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0443-z
更新日期:2020-11-01 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
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::We previously found that ovarian steroids promote neuroprotection in serotonin neurons by decreasing the expression of pro-apoptotic genes and proteins in the dorsal raphe nucleus of rhesus macaques, even in the absence of overt injury. In this study, we questioned whether these actions would lead to a reduction in DN...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2009.97
更新日期:2010-06-01 00:00:00
abstract::The long alleles (> or =6 repeats) of the dopamine D4 dopamine receptor exon III polymorphism have been linked in some, but not all, studies to Novelty Seeking (NS), one of four personality traits defined by Cloninger's tridimensional personality questionnarie (TPQ). In order to further examine the robustness of our o...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000333
更新日期:1997-10-01 00:00:00