Peripheral benzodiazepine receptors in patients with chronic schizophrenia: a PET study with [11C]DAA1106

Takano, Akihiro; Arakawa, Ryosuke; Ito, Hiroshi; Tateno, Amane; Takahashi, Hidehiko; Matsumoto, Ryohei; Okubo, Yoshiro; Suhara, Tetsuya

doi:10.1017/s1461145710000313

Cited by 169 publications

(141 citation statements)

References 36 publications

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“…In vivo positron emission tomography (PET) imaging studies have also identified microgliosis in schizophrenia. A study of people with recent-onset schizophrenia and another study of individuals who were recovering from a psychotic episode both found increases in a marker indicative of microgliosis (binding of [ 11 C]PK11195 to the mitochondrial 18kDa translocator protein (TSPO)) in grey matter (Doorduin et al, 2009;Van Berckel et al, 2008); whereas another study of chronic patients with schizophrenia failed to find a change using another microglial marker (Takano et al, 2010) (binding of [ 11 C] DAA1106, an agonist with greater affinity for TSPO than PK11195). The latter study did find a positive correlation between microglial marker binding and positive symptoms, and thus the three in vivo PET studies are consistent with increased microgliosis being especially prominent in those with recent psychotic exacerbation.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Catts

Wong

Fillman

et al. 2014

Aust N Z J Psychiatry

130

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Objective: While schizophrenia may have a progressive component, the evidence for neurodegenerative processes as indicated by reactive astrocytes is inconclusive. We recently identified a subgroup of individuals with schizophrenia with increased expression of inflammatory markers in prefrontal cortex, and hypothesized that this subgroup would also have reactive astrocytes. Method:We measured glial fibrillary acidic protein (GFAP) mRNA by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels by immunoblotting in grey matter homogenate from 37 individuals with schizophrenia and 37 unaffected controls. We examined the morphology of GFAP-positive astrocytes in immunostained sections of middle frontal gyrus. We tested if GFAP expression or astrocyte morphology were altered in people with schizophrenia with increased expression of inflammatory markers. We used RNA-Seq data on a subset of patients and controls (n=20/group) to ascertain whether mRNA transcripts associated with astrogliosis were elevated in the individuals with active neuroinflammation.Results: GFAP (mRNA and protein) levels and astrocyte morphology were not significantly different between people with schizophrenia and controls overall. However, individuals with schizophrenia with neuroinflammation had increased expression of GFAP mRNA (t(33)=2.978, p=0.005), hypertrophic astrocyte morphology (χ 2 (2)=6.281, p=0.043), and statistically significant elevated expression of three mRNA transcripts previously associated with astrogliosis. Conclusions:We found clear evidence of astrogliosis in a subset of people with schizophrenia. We suggest that the lack of astrogliosis reported in previous studies may be due to cohort differences in aetiopathology, illness stage, treatment exposure, or a failure to examine subsets of people with schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Catts

Wong

Fillman

et al. 2014

Aust N Z J Psychiatry

130

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“…Although [ 11 C]-(R)-PK11195 is widely used for imaging of microglia, its considerable high plasma protein binding, high levels of nonspecific binding, relatively poor blood-brain barrier permeability and short half-life, limits its use in brain imaging (Chauveau et al, 2008). Recently, alternative PET radioligands for TSPO including the phenoxyarylacetamide derivative [ 11 C]-DAA1106 and its analogues (Gulyas et al, 2009;Takano et al, 2010;Venneti et al, 2008), the imidazopyridines (PBR111) and its analogues (Boutin et al, 2007a;Fookes et al, 2008) (Boutin et al, 2007b;James et al, 2008) have been investigated.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Neuroinflammation in Transferred EAE Via a Translocator Protein Ligand

Mattner¹,

Staykova²,

Callaghan³

et al. 2012

Experimental Autoimmune Encephalomyelitis - Models, Disease Biology and Experimental Therapy

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“…Another PET study on a novel positron emission tomography (PET) ligand, [ 11 C]DAA1106, instead indicated that there were no significant microglial alterations in any of the brain regions between patients with chronic schizophrenia and control subjects. There was no significant difference between [ 11 C]DAA1106 binding of the cortical regions of normal controls and patients with schizophrenia, whereas the patients had a positive correlation between cortical [11C]DAA1106 binding and positive symptom scores [52].…”

Section: Microglial Activation In Psychiatric Disorders Based On Imagmentioning

confidence: 77%

Microglial Gene Expression Alterations in the Brains of Patients with Psychiatric Disorders

Sakai

Takahashi

et al. 2016

NIB

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Abstract.As recent studies have shown that microglia play a key role in inflammation and immunological challenges as well as have broader roles in synaptic modulation in the brain, studies on psychiatric disorders have increasingly focused on microglia. Microglial abnormalities have consistently been observed in psychiatric postmortem brain studies, including altered microglial activation and changes in the protein and mRNA expression levels of microglial marker molecules, such as major histocompatibility complex, class II, DR (HLA-DR), complement receptor type 3 (CD11b), ionized calcium binding adaptor molecule 1 (IBA-1), macrosialin (CD68) and glucose transporter type 5 (GLUT5). Microglial abnormalities have also been observed in positron emission tomography (PET) studies. Recent advances in omics-based microglial gene expression profiling of psychiatric brains may elucidate microglial involvement in the pathogeneses of psychiatric disorders. In the present paper, we review the current status of research on expression profiling of microglia-relevant molecules in psychiatric postmortem and imaging studies and we discuss future research directions.

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Peripheral benzodiazepine receptors in patients with chronic schizophrenia: a PET study with [11C]DAA1106

Cited by 169 publications

References 36 publications

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Assessment of Neuroinflammation in Transferred EAE Via a Translocator Protein Ligand

Microglial Gene Expression Alterations in the Brains of Patients with Psychiatric Disorders

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