TSPO expression and brain structure in the psychosis spectrum

Hafizi, Sina; Guma, Elisa; Koppel, Alex; Silva, Tânia Maria Sarmento; Kiang, Michael; Houle, Sylvain; Wilson, Alan A.; Rusjan, Pablo; Chakravarty, M. Mallar; Mizrahi, Romina

doi:10.1016/j.bbi.2018.06.009

Cited by 18 publications

(16 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Operating under the hypothesis that microglial pruning may be causative in grey matter loss, the same group then attempted to correlate changes in TSPO with grey matter volume reductions in CHR subjects. They found a positive correlation between increased TSPO signal and grey matter volume loss in FEP, but not in CHR subjects ( 90 ). Selvaraj et al used the [ 11 C]PBR28 ligand to investigate the same relationship and also failed to observe an association between cortical grey matter volumes and TSPO signal in CHR subjects ( 91 ).…”

Section: Inflammatory Phenotypesmentioning

confidence: 99%

Selective Review of Neuroimaging Findings in Youth at Clinical High Risk for Psychosis: On the Path to Biomarkers for Conversion

2020

View full text Add to dashboard Cite

First episode psychosis (FEP), and subsequent diagnosis of schizophrenia or schizoaffective disorder, predominantly occurs during late adolescence, is accompanied by a significant decline in function and represents a traumatic experience for patients and families alike. Prior to first episode psychosis, most patients experience a prodromal period of 1–2 years, during which symptoms first appear and then progress. During that time period, subjects are referred to as being at Clinical High Risk (CHR), as a prodromal period can only be designated in hindsight in those who convert. The clinical high-risk period represents a critical window during which interventions may be targeted to slow or prevent conversion to psychosis. However, only one third of subjects at clinical high risk will convert to psychosis and receive a formal diagnosis of a primary psychotic disorder. Therefore, in order for targeted interventions to be developed and applied, predicting who among this population will convert is of critical importance. To date, a variety of neuroimaging modalities have identified numerous differences between CHR subjects and healthy controls. However, complicating attempts at predicting conversion are increasingly recognized co-morbidities, such as major depressive disorder, in a significant number of CHR subjects. The result of this is that phenotypes discovered between CHR subjects and healthy controls are likely non-specific to psychosis and generalized for major mental illness. In this paper, we selectively review evidence for neuroimaging phenotypes in CHR subjects who later converted to psychosis. We then evaluate the recent landscape of machine learning as it relates to neuroimaging phenotypes in predicting conversion to psychosis.

show abstract

Section: Inflammatory Phenotypesmentioning

confidence: 99%

Selective Review of Neuroimaging Findings in Youth at Clinical High Risk for Psychosis: On the Path to Biomarkers for Conversion

2020

View full text Add to dashboard Cite

show abstract

“…Moreover, these cytokine changes are comparably present in these disorders, again suggesting a common underlying pathway for immune dysfunction [15]. Interestingly, proinflammatory activity has been associated with structural brain changes [16] as well as with the cognitive and motor dysfunctions [17,18] seen in each of these disorders. It should be noted that although peripheral and central immune alterations are present, these may be unrelated [19] and may even be inversely related [20,21], which could point towards compensatory reverse mechanisms in the brain following systemic proinflammatory immune activity [20,21].…”

mentioning

confidence: 96%

Do Immune Dysregulations and Oxidative Damage Drive Mood and Psychotic Disorders?

Morrens¹,

Coppens²,

Walther³

2019

Neuropsychobiology

View full text Add to dashboard Cite

“…Eleven MA users and 26 healthy controls provided written informed consent and completed a [F‐18]FEPPA PET scan and one magnetic resonance imaging (MRI) scan as part of a study approved by the Centre for Addiction and Mental Health Research Ethics Board. PET/[F‐18]FEPPA data have been previously reported for some of the healthy controls 9,19–20 . All subjects underwent a comprehensive medical and psychiatric screening (Semi‐structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders [DSM‐IV]) 21 .…”

Section: Methodsmentioning

confidence: 99%

“…PET/ [F-18]FEPPA data have been previously reported for some of the healthy controls. 9,19,20 All subjects underwent a comprehensive medical and psychiatric screening (Semi-structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders [DSM-IV]). 21 Drug history of MA use and other drugs of abuse was verified using scalp hair toxicology (USDTL, Illinois, USA) in MA users and urinalysis in all subjects at screening (LC-MS and EMIT immunoassay; Rapid Response BTNX Inc., Markham, Canada).…”

Section: Study Participantsmentioning

confidence: 99%

Microglia imaging in methamphetamine use disorder: a positron emission tomography study with the 18 kDa translocator protein radioligand [F‐18]FEPPA

et al. 2020

Self Cite

View full text Add to dashboard Cite

Activation of brain microglial cells, microgliosis, has been linked to methamphetamine (MA)-seeking behavior, suggesting that microglia could be a new therapeutic target for MA use disorder. Animal data show marked brain microglial activation following acute high-dose MA, but microglial status in human MA users is uncertain, with one positron emission tomography (PET) investigation reporting massively and globally increased translocator protein 18 kDa (TSPO; [C-11](R)-PK11195) binding, a biomarker for microgliosis, in MA users. Our aim was to measure binding of a secondgeneration TSPO radioligand, [F-18]FEPPA, in brain of human chronic MA users. Regional total volume of distribution (V T) of [F-18]FEPPA was estimated with a twotissue compartment model with arterial plasma input function for 10 regions of interest in 11 actively using MA users and 26 controls. A RM-ANOVA corrected for TSPO rs6971 polymorphism was employed to test significance. There was no main effect of group on [F-18]FEPPA V T (P = .81). No significant correlations between [F-18] FEPPA V T and MA use duration, weekly dosage, blood MA concentrations, regional brain volumes, and self-reported craving were observed. Our preliminary findings, consistent with our earlier postmortem data, do not suggest substantial brain microgliosis in MA use disorder but do not rule out microglia as a therapeutic target in MA addiction. Absence of increased [F-18]FEPPA TSPO binding might be related to insufficient MA dose or blunting of microglial response following repeated MA exposure, as suggested by some animal data.

show abstract

TSPO expression and brain structure in the psychosis spectrum

Cited by 18 publications

References 74 publications

Selective Review of Neuroimaging Findings in Youth at Clinical High Risk for Psychosis: On the Path to Biomarkers for Conversion

Selective Review of Neuroimaging Findings in Youth at Clinical High Risk for Psychosis: On the Path to Biomarkers for Conversion

Do Immune Dysregulations and Oxidative Damage Drive Mood and Psychotic Disorders?

Microglia imaging in methamphetamine use disorder: a positron emission tomography study with the 18 kDa translocator protein radioligand [F‐18]FEPPA

Contact Info

Product

Resources

About