title: In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [(11)C]DPA-713 PET and analysis of CSF and plasma.
abstract: Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [(11)C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [(11)C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Coughlin
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Ambinder
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Ward
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: I
authors.initials: I
authors.lastname: Minn
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vranesic
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Kim
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: C N
authors.initials: CN
authors.lastname: Ford
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Higgs
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: L N
authors.initials: LN
authors.lastname: Hayes
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Schretlen
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
authors.affiliation: School of Chemistry and Faculty of Health Sciences, The University of Sydney, Sydney, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000081:Acetamides; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles; D011743:Pyrimidines; D012559:Schizophrenia / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D055815:Young Adult
chemical_list: D000081:Acetamides; D015415:Biomarkers; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines