Structural dysconnectivity of key cognitive and emotional hubs in young people at high genetic risk for bipolar disorder.

Abstract:

:Emerging evidence suggests that psychiatric disorders are associated with disturbances in structural brain networks. Little is known, however, about brain networks in those at high risk (HR) of bipolar disorder (BD), with such disturbances carrying substantial predictive and etiological value. Whole-brain tractography was performed on diffusion-weighted images acquired from 84 unaffected HR individuals with at least one first-degree relative with BD, 38 young patients with BD and 96 matched controls (CNs) with no family history of mental illness. We studied structural connectivity differences between these groups, with a focus on highly connected hubs and networks involving emotional centres. HR participants showed lower structural connectivity in two lateralised sub-networks centred on bilateral inferior frontal gyri and left insular cortex, as well as increased connectivity in a right lateralised limbic sub-network compared with CN subjects. BD was associated with weaker connectivity in a small right-sided sub-network involving connections between fronto-temporal and temporal areas. Although these sub-networks preferentially involved structural hubs, the integrity of the highly connected structural backbone was preserved in both groups. Weaker structural brain networks involving key emotional centres occur in young people at genetic risk of BD and those with established BD. In contrast to other psychiatric disorders such as schizophrenia, the structural core of the brain remains intact, despite the local involvement of network hubs. These results add to our understanding of the neurobiological correlates of BD and provide predictions for outcomes in young people at high genetic risk for BD.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Roberts G,Perry A,Lord A,Frankland A,Leung V,Holmes-Preston E,Levy F,Lenroot RK,Mitchell PB,Breakspear M

doi

10.1038/mp.2016.216

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

413-421

issue

2

eissn

1359-4184

issn

1476-5578

pii

mp2016216

journal_volume

23

pub_type

杂志文章
  • Genome-wide interaction study of brain beta-amyloid burden and cognitive impairment in Alzheimer's disease.

    abstract::The lack of strong association between brain beta-amyloid deposition and cognitive impairment has been a challenge for the Alzheimer's disease (AD) field. Although beta-amyloid is necessary for the pathologic diagnosis of AD, it is not sufficient to make the pathologic diagnosis or cause dementia. We sought to identif...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2016.35

    authors: Roostaei T,Nazeri A,Felsky D,De Jager PL,Schneider JA,Pollock BG,Bennett DA,Voineskos AN,Alzheimer’s Disease Neuroimaging Initiative (ADNI).

    更新日期:2017-02-01 00:00:00

  • RNA editing of the 5-HT(2C) receptor is reduced in schizophrenia.

    abstract::5-HT(2C) receptor (5HT(2C)R, serotonin-2C) RNA undergoes editing to produce several receptor variants, some with pharmacological differences. This investigation comprised two parts: the characterisation of 5-HT(2C)R RNA editing in a larger human control sample than previously examined, and a comparative study in subje...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4000920

    authors: Sodhi MS,Burnet PW,Makoff AJ,Kerwin RW,Harrison PJ

    更新日期:2001-07-01 00:00:00

  • CK2 regulates 5-HT4 receptor signaling and modulates depressive-like behavior.

    abstract::The serotonergic neurotransmitter system has been widely implicated in the pathophysiology of mood-related disorders such as anxiety and major depressive disorder (MDD). The onset of therapeutic efficacy of traditional antidepressants is delayed by several weeks. The 5-HT4 receptor has emerged as a new therapeutic tar...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2017.240

    authors: Castello J,LeFrancois B,Flajolet M,Greengard P,Friedman E,Rebholz H

    更新日期:2018-04-01 00:00:00

  • Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor-dependent manner.

    abstract::Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in hum...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2017.165

    authors: Garcia-Garcia AL,Canetta S,Stujenske JM,Burghardt NS,Ansorge MS,Dranovsky A,Leonardo ED

    更新日期:2018-10-01 00:00:00

  • Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?

    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

    authors: Chandy KG,Fantino E,Wittekindt O,Kalman K,Tong LL,Ho TH,Gutman GA,Crocq MA,Ganguli R,Nimgaonkar V,Morris-Rosendahl DJ,Gargus JJ

    更新日期:1998-01-01 00:00:00

  • Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow.

    abstract::The catechol-O-methyl transferase (COMT) gene is considered a leading schizophrenia candidate gene. Although its role in increasing schizophrenia susceptibility has been conflicting, recent studies suggest the valine allele may contribute to poor cognitive function in schizophrenia. V(158)M COMT genotype was obtained ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4001616

    authors: Ho BC,Wassink TH,O'Leary DS,Sheffield VC,Andreasen NC

    更新日期:2005-03-01 00:00:00

  • Corticostriatal dysfunction and social interaction deficits in mice lacking the cystine/glutamate antiporter.

    abstract::The astrocytic cystine/glutamate antiporter system xc- represents an important source of extracellular glutamate in the central nervous system, with potential impact on excitatory neurotransmission. Yet, its function and importance in brain physiology remain incompletely understood. Employing slice electrophysiology a...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-020-0751-3

    authors: Bentea E,Villers A,Moore C,Funk AJ,O'Donovan SM,Verbruggen L,Lara O,Janssen P,De Pauw L,Declerck NB,DePasquale EAK,Churchill MJ,Sato H,Hermans E,Arckens L,Meshul CK,Ris L,McCullumsmith RE,Massie A

    更新日期:2020-05-04 00:00:00

  • Altered temporal, but intact spatial, features of transient network dynamics in psychosis.

    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

    authors: Wang D,Peng X,Pelletier-Baldelli A,Orlov N,Farabaugh A,Nasr S,Eryilmaz H,Fava M,Holmes AJ,Roffman JL,Liu H,Holt DJ

    更新日期:2021-01-18 00:00:00

  • Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide.

    abstract::Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autoph...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-018-0090-9

    authors: Gulbins A,Schumacher F,Becker KA,Wilker B,Soddemann M,Boldrin F,Müller CP,Edwards MJ,Goodman M,Caldwell CC,Kleuser B,Kornhuber J,Szabo I,Gulbins E

    更新日期:2018-12-01 00:00:00

  • Preliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder.

    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

    authors: D'Souza DC,Radhakrishnan R,Naganawa M,Ganesh S,Nabulsi N,Najafzadeh S,Ropchan J,Ranganathan M,Cortes-Briones J,Huang Y,Carson RE,Skosnik P

    更新日期:2020-09-24 00:00:00

  • Genome-wide association study of Alzheimer's disease with psychotic symptoms.

    abstract::Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysi...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,meta分析,多中心研究

    doi:10.1038/mp.2011.125

    authors: Hollingworth P,Sweet R,Sims R,Harold D,Russo G,Abraham R,Stretton A,Jones N,Gerrish A,Chapman J,Ivanov D,Moskvina V,Lovestone S,Priotsi P,Lupton M,Brayne C,Gill M,Lawlor B,Lynch A,Craig D,McGuinness B,Johnston J

    更新日期:2012-12-01 00:00:00

  • Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children.

    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

    authors: Tahir E,Yazgan Y,Cirakoglu B,Ozbay F,Waldman I,Asherson PJ

    更新日期:2000-07-01 00:00:00

  • Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.

    abstract::Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cyto...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2015.29

    authors: Hornig M,Gottschalk G,Peterson DL,Knox KK,Schultz AF,Eddy ML,Che X,Lipkin WI

    更新日期:2016-02-01 00:00:00

  • Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer's disease mouse model.

    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

    authors: Ng RC,Jian M,Ma OK,Bunting M,Kwan JS,Zhou GJ,Senthilkumar K,Iyaswamy A,Chan PK,Li M,Leung KM,Kumar Durairajan SS,Lam KS,Chu LW,Festenstein R,Chung SK,Chan KH

    更新日期:2020-03-04 00:00:00

  • Nitric oxide in health and disease of the nervous system.

    abstract::Nitric oxide (NO) is a widespread and multifunctional biological messenger molecule. It mediates vasodilation of blood vessels, host defence against infectious agents and tumors, and neurotransmission of the central and peripheral nervous systems. In the nervous system, NO is generated by three nitric oxide synthase (...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审

    doi:10.1038/sj.mp.4000272

    authors: Yun HY,Dawson VL,Dawson TM

    更新日期:1997-07-01 00:00:00

  • Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia.

    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

    authors: Greene C,Kealy J,Humphries MM,Gong Y,Hou J,Hudson N,Cassidy LM,Martiniano R,Shashi V,Hooper SR,Grant GA,Kenna PF,Norris K,Callaghan CK,Islam MD,O'Mara SM,Najda Z,Campbell SG,Pachter JS,Thomas J,Williams NM,Humph

    更新日期:2018-11-01 00:00:00

  • Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol.

    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

    authors: O'Hara R,Schröder CM,Mahadevan R,Schatzberg AF,Lindley S,Fox S,Weiner M,Kraemer HC,Noda A,Lin X,Gray HL,Hallmayer JF

    更新日期:2007-06-01 00:00:00

  • White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals.

    abstract::Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophr...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-019-0553-7

    authors: Koshiyama D,Fukunaga M,Okada N,Morita K,Nemoto K,Usui K,Yamamori H,Yasuda Y,Fujimoto M,Kudo N,Azechi H,Watanabe Y,Hashimoto N,Narita H,Kusumi I,Ohi K,Shimada T,Kataoka Y,Yamamoto M,Ozaki N,Okada G,Okamoto Y,Ha

    更新日期:2020-04-01 00:00:00

  • Ovarian steroids regulate gene expression related to DNA repair and neurodegenerative diseases in serotonin neurons of macaques.

    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

    authors: Bethea CL,Reddy AP

    更新日期:2015-12-01 00:00:00

  • Connectome imaging for mapping human brain pathways.

    abstract::With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2017.92

    authors: Shi Y,Toga AW

    更新日期:2017-09-01 00:00:00

  • Maternal cariprazine exposure inhibits embryonic and postnatal brain cholesterol biosynthesis.

    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

    authors: Genaro-Mattos TC,Anderson A,Allen LB,Tallman KA,Porter NA,Korade Z,Mirnics K

    更新日期:2020-11-01 00:00:00

  • Environmental enrichment or selective activation of parvalbumin-expressing interneurons ameliorates synaptic and behavioral deficits in animal models with schizophrenia-like behaviors during adolescence.

    abstract::Synaptic deficit-induced excitation and inhibition (E/I) imbalance have been implicated in the pathogenesis of schizophrenia. Using in vivo two-photon microscopy, we examined the dynamic plasticity of dendritic spines of pyramidal neurons (PNs) and "en passant" axonal bouton of parvalbumin-expressing interneurons (PVI...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-020-01005-w

    authors: Huang Y,Jiang H,Zheng Q,Fok AHK,Li X,Lau CG,Lai CSW

    更新日期:2021-01-20 00:00:00

  • Dopa decarboxylase genotypes may influence age at onset of schizophrenia.

    abstract::Several lines of evidence implicate dopa decarboxylase (DDC) with schizophrenia. By analysis of two putative functional DDC variants in 173 schizophrenic patients and 204 controls we tested the hypotheses that DDC is involved in: (1) predisposition to schizophrenia; and (2) modulation of age at disease onset. No assoc...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4000902

    authors: Børglum AD,Hampson M,Kjeldsen TE,Muir W,Murray V,Ewald H,Mors O,Blackwood D,Kruse TA

    更新日期:2001-11-01 00:00:00

  • Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank.

    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

    authors: Warland A,Kendall KM,Rees E,Kirov G,Caseras X

    更新日期:2020-04-01 00:00:00

  • PS1 FAD mutants decrease ephrinB2-regulated angiogenic functions, ischemia-induced brain neovascularization and neuronal survival.

    abstract::Microvascular pathology and ischemic lesions contribute substantially to neuronal dysfunction and loss that lead to Alzheimer disease (AD). To facilitate recovery, the brain stimulates neovascularization of damaged tissue via sprouting angiogenesis, a process regulated by endothelial cell (EC) sprouting and the EphB4/...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-020-0812-7

    authors: Yoon Y,Voloudakis G,Doran N,Zhang E,Dimovasili C,Chen L,Shao Z,Darmanis S,Tang C,Tang J,Wang VX,Hof PR,Robakis NK,Georgakopoulos A

    更新日期:2020-06-15 00:00:00

  • Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium.

    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

    authors: Knable MB,Barci BM,Webster MJ,Meador-Woodruff J,Torrey EF,Stanley Neuropathology Consortium.

    更新日期:2004-06-01 00:00:00

  • Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer's disease therapy.

    abstract::Here, we report a novel target of the drug memantine, ATP-sensitive K+ (KATP) channels, potentially relevant to memory improvement. We confirmed that memantine antagonizes memory impairment in Alzheimer's model APP23 mice. Memantine increased CaMKII activity in the APP23 mouse hippocampus, and memantine-induced enhanc...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2016.187

    authors: Moriguchi S,Ishizuka T,Yabuki Y,Shioda N,Sasaki Y,Tagashira H,Yawo H,Yeh JZ,Sakagami H,Narahashi T,Fukunaga K

    更新日期:2018-02-01 00:00:00

  • Preventing intrusive memories after trauma via a brief intervention involving Tetris computer game play in the emergency department: a proof-of-concept randomized controlled trial.

    abstract::After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,随机对照试验

    doi:10.1038/mp.2017.23

    authors: Iyadurai L,Blackwell SE,Meiser-Stedman R,Watson PC,Bonsall MB,Geddes JR,Nobre AC,Holmes EA

    更新日期:2018-03-01 00:00:00

  • Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response.

    abstract::High-affinity transporters for norepinephrine (NE) and serotonin (5-HT), which ensure neurotransmitter clearance at the synapse, are the principal targets of widely used antidepressant drugs. Antidepressants targeting these high-affinity transporters, however, do not provide positive treatment outcomes for all patient...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2011.87

    authors: Bacq A,Balasse L,Biala G,Guiard B,Gardier AM,Schinkel A,Louis F,Vialou V,Martres MP,Chevarin C,Hamon M,Giros B,Gautron S

    更新日期:2012-09-01 00:00:00

  • Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids.

    abstract::Stress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, a...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2011.126

    authors: Rodrigues AJ,Leão P,Pêgo JM,Cardona D,Carvalho MM,Oliveira M,Costa BM,Carvalho AF,Morgado P,Araújo D,Palha JA,Almeida OF,Sousa N

    更新日期:2012-12-01 00:00:00