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  • 1
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    Brain region binding of the D 2/3 agonist [ 11 C]‐(+)‐PHNO and the D 2/3 antagonist [ 11 C]raclopride in healthy humans
    Wiley ; 2008
    In:  Human Brain Mapping Vol. 29, No. 4 ( 2008-04), p. 400-410
    Details
    In: Human Brain Mapping, Wiley, Vol. 29, No. 4 ( 2008-04), p. 400-410
    Abstract: The D 2 receptors exist in either the high‐ or low‐affinity state with respect to agonists, and while agonists bind preferentially to the high‐affinity state, antagonists do not distinguish between the two states. [ 11 C]‐(+)‐PHNO is a PET D 2 agonist radioligand and therefore provides a preferential measure of the D 2 high receptors. In contrast, [ 11 C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D 2 high‐ and low‐affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [ 11 C]‐(+)‐PHNO and [ 11 C]raclopride in volunteers using a within‐subject design. Both radioligands accumulated in brain areas rich in D 2 /D 3 ‐receptors. However, [ 11 C]‐(+)‐PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [ 11 C]raclopride showed preferential uptake in the dorsal striatum. Mean binding potentials were higher in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [ 11 C]raclopride, equal in the ventral‐striatum (3.4 vs. 3.3), and higher in the globus pallidus for [ 11 C]‐(+)‐PHNO (1.8 vs. 3.3). Moreover [ 11 C]‐(+)‐PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [ 11 C]‐(+)‐PHNO in the globus pallidus and ventral‐striatum could be the presence of a greater proportion of high‐ vs. low‐affinity receptors in these areas. Alternatively, the observed distribution could also be explained by a preferential binding of D 3 ‐over‐D 2 with [ 11 C]‐(+)‐PHNO. This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
    Type of Medium: Online Resource
    ISSN: 1065-9471 , 1097-0193
    URL: Issue
    URL: Article
    DOI: 10.1002/hbm.v29:4
    DOI: 10.1002/hbm.20392
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 1492703-2
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  • 2
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    Quantitative imaging of neuroinflammation in human white matter: A positron emission tomography study with translocator protein 18 kDa radioligand, [ 18 F]‐FEPPA
    Wiley ; 2014
    In:  Synapse Vol. 68, No. 11 ( 2014-11), p. 536-547
    Details
    In: Synapse, Wiley, Vol. 68, No. 11 ( 2014-11), p. 536-547
    Abstract: The ability to quantify translocator protein 18 kDa (TSPO) in white matter (WM) is important to understand the role of neuroinflammation in neurological disorders with WM involvement. This article aims to extend the utility of TSPO imaging in WM using a second‐generation radioligand, [ 18 F]‐FEPPA, and high‐ resolution research tomograph (HRRT) positron emission tomography (PET) camera system. Four WM regions of interests (WM‐ROI), relevant to the study of aging and neuroinflammatory diseases, were examined. The corpus callosum, cingulum bundle, superior longitudinal fasciculus, and posterior limb of internal capsule were delineated automatically onto subject's T 1 ‐weighted magnetic resonance image using a diffusion tensor imaging‐based WM template. The TSPO polymorphism (rs6971) stratified individuals to three genetic groups: high‐affinity binders (HAB), mixed‐affinity binders (MAB), and low‐affinity binders. [ 18 F]‐FEPPA PET scans were acquired on 32 healthy subjects and analyzed using a full kinetic compartment analysis. The two‐tissue compartment model showed moderate identifiability (coefficient of variation 15–19%) for [ 18 F]‐FEPPA total volume distribution ( V T ) in WM‐ROIs. Noise affects V T variability, although its effect on bias was small (6%). In a worst‐case scenario, ≤6% of simulated data did not fit reliably. A simulation of increased TSPO density exposed minimal effect on variability and identifiability of [ 18 F]‐FEPPA V T in WM‐ROIs. We found no association between age and [ 18 F]‐FEPPA V T in WM‐ROIs. The V T values were 15% higher in HAB than in MAB, although the difference was not statistically significant. This study provides evidence for the utility and limitations of [ 18 F]‐FEPPA PET to measure TSPO expression in WM. Synapse 68:536–547, 2014 . © 2014 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0887-4476 , 1098-2396
    URL: Issue
    URL: Article
    DOI: 10.1002/syn.v68.11
    DOI: 10.1002/syn.21765
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 1474927-0
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  • 3
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    N400 event‐related brain potential as an index of real‐world and neurocognitive function in patients at clinical high risk for schizophrenia
    Wiley ; 2021
    In:  Early Intervention in Psychiatry Vol. 15, No. 1 ( 2021-02), p. 68-75
    Details
    In: Early Intervention in Psychiatry, Wiley, Vol. 15, No. 1 ( 2021-02), p. 68-75
    Abstract: The N400 event‐related potential is a neurophysiological index of cognitive processing of real‐world knowledge. In healthy populations, N400 amplitude is smaller in response to stimuli that are more related to preceding context. This ‘N400 semantic priming effect’ is thought to reflect activation of contextually related information in semantic memory (SM). N400 semantic priming deficits have been found in schizophrenia, and in patients at clinical high risk (CHR) for this disorder. Because this abnormality in processing relationships between meaningful stimuli could affect ability to navigate everyday situations, we hypothesized it would be associated with real‐world functional impairment in CHR patients. Second, we hypothesized it would correlate with global neurocognitive impairment in this group. Methods We measured N400 semantic priming in 35 CHR patients who viewed prime words each followed by a related or unrelated target word, at stimulus‐onset asynchrony (SOA) of 300 or 750 ms. We measured academic/occupational and social function with the global function (GF): Role and Social scales, and cognitive function with the MATRICS Consensus Cognitive Battery (MCCB). Results Decreased N400 semantic priming at the 300‐ms SOA correlated with lower GF:Role scores. Decreased N400 semantic priming at the 750‐ms SOA correlated with lower MCCB composite scores. Conclusions Deficits in activating contextually related concepts in SM over short time intervals may contribute to functional impairment in CHR patients. Furthermore, N400 priming deficits over longer intervals may be a biomarker of global cognitive dysfunction in this population. Longitudinal studies are needed to determine whether these deficits are associated with schizophrenia risk within this population.
    Type of Medium: Online Resource
    ISSN: 1751-7885 , 1751-7893
    URL: Issue
    URL: Article
    DOI: 10.1111/eip.v15.1
    DOI: 10.1111/eip.12911
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2272425-4
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  • 4
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    Microglia imaging in methamphetamine use disorder: a positron emission tomography study with the 18 kDa translocator protein radioligand [F‐18]FEPPA
    Wiley ; 2021
    In:  Addiction Biology Vol. 26, No. 1 ( 2021-01)
    Details
    In: Addiction Biology, Wiley, Vol. 26, No. 1 ( 2021-01)
    Abstract: 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 second‐generation 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 two‐tissue 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]FEP PA TSPO binding might be related to insufficient MA dose or blunting of microglial response following repeated MA exposure, as suggested by some animal data.
    Type of Medium: Online Resource
    ISSN: 1355-6215 , 1369-1600
    URL: Issue
    URL: Article
    DOI: 10.1111/adb.v26.1
    DOI: 10.1111/adb.12876
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1495537-4
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  • 5
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    N400 event‐related brain potential and functional outcome in persons at clinical high risk for psychosis: A longitudinal study
    Wiley ; 2022
    In:  Psychiatry and Clinical Neurosciences Vol. 76, No. 4 ( 2022-04), p. 114-121
    Details
    In: Psychiatry and Clinical Neurosciences, Wiley, Vol. 76, No. 4 ( 2022-04), p. 114-121
    Abstract: The N400 event‐related brain potential (ERP) semantic priming effect is thought to reflect activation by meaningful stimuli of related concepts in semantic memory and has been found to be deficient in schizophrenia. We tested the hypothesis that, among individuals at clinical high risk (CHR) for psychosis, N400 semantic priming deficits predict worse symptomatic and functional outcomes after one year. Methods We measured N400 semantic priming at baseline in CHR patients ( n  = 47) and healthy control participants ( n  = 25) who viewed prime words each followed by a related or unrelated target word, at stimulus‐onset asynchronies (SOAs) of 300 or 750 ms. We measured patients' psychosis‐like symptoms with the Scale of Prodromal Symptoms (SOPS) Positive subscale, and academic/occupational and social functioning with the Global Functioning (GF):Role and Social scales, respectively, at baseline and one‐year follow‐up ( n  = 29). Results CHR patients exhibited less N400 semantic priming than controls across SOAs; planned contrasts indicated this difference was significant at the 750‐ms but not the 300‐ms SOA. In patients, reduced N400 semantic priming at the 750‐ms SOA was associated with lower GF:Social scores at follow‐up, and greater GF:Social decrements from baseline to follow‐up. Patients' N400 semantic priming was not associated with SOPS Positive or GF:Role scores at follow‐up, or change in these from baseline to follow‐up. Conclusions In CHR patients, reduced N400 semantic priming at baseline predicted worse social functioning after one year, and greater decline in social functioning over this period. Thus, the N400 may be a useful prognostic biomarker of real‐world functional outcome in CHR patients.
    Type of Medium: Online Resource
    ISSN: 1323-1316 , 1440-1819
    URL: Issue
    URL: Article
    DOI: 10.1111/pcn.v76.4
    DOI: 10.1111/pcn.13330
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2010264-1
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  • 6
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    Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long‐term cannabis users: A secondary analysis of a case–control study
    Wiley ; 2022
    In:  Lipids Vol. 57, No. 2 ( 2022-03), p. 125-140
    Details
    In: Lipids, Wiley, Vol. 57, No. 2 ( 2022-03), p. 125-140
    Abstract: Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users ( n  = 21) and non‐cannabis users ( n  = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon‐specific isotope analysis, which allows for the determination of fatty acid 13 C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched 13 C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2‐arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti‐inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.
    Type of Medium: Online Resource
    ISSN: 0024-4201 , 1558-9307
    URL: Issue
    URL: Article
    DOI: 10.1002/lipd.v57.2
    DOI: 10.1002/lipd.12336
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2030265-4
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  • 7
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    Fatty acid amide hydrolase is lower in young cannabis users
    Wiley ; 2021
    In:  Addiction Biology Vol. 26, No. 1 ( 2021-01)
    Details
    In: Addiction Biology, Wiley, Vol. 26, No. 1 ( 2021-01)
    Abstract: We have recently shown that levels of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide, are lower in the brains of adult cannabis users (CUs) (34 ± 11 years of age), tested during early abstinence. Here, we examine replication of the lower FAAH levels in a separate, younger cohort (23 ± 5 years of age). Eighteen healthy volunteers (HVs) and fourteen CUs underwent a positron emission tomography scan using the FAAH radioligand [ 11 C]CURB. Regional [ 11 C]CURB binding was calculated using an irreversible two‐tissue compartment model with a metabolite‐corrected arterial plasma input function. The FAAH C385A genetic polymorphism (rs324420) was included as a covariate. All CUs underwent a urine screen to confirm recent cannabis use and had serum cannabinoids measured. One CU screened negative for cannabinoids via serum and was removed from analysis. All HVs reported less than five lifetime cannabis exposures more than a month prior to study initiation. There was a significant effect of group ( F 1,26 = 4.31; P = .048) when two A/A (rs324420) HVs were removed from analysis to match the genotype of the CU group (n = 16 HVs, n = 13 CUs). Overall, [ 11 C]CURB λk 3 was 12% lower in CU compared with HV. Exploratory correlations showed that lower brain [ 11 C]CURB binding was related to greater use of cannabis throughout the past year. We confirmed our previous report and extended these findings by detecting lower [ 11 C]CURB binding in a younger cohort with less cumulative cannabis exposure.
    Type of Medium: Online Resource
    ISSN: 1355-6215 , 1369-1600
    URL: Issue
    URL: Article
    DOI: 10.1111/adb.v26.1
    DOI: 10.1111/adb.12872
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 8
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    Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography
    Wiley ; 2006
    In:  Journal of Neurochemistry Vol. 97, No. 4 ( 2006-05), p. 1089-1103
    Details
    In: Journal of Neurochemistry, Wiley, Vol. 97, No. 4 ( 2006-05), p. 1089-1103
    Type of Medium: Online Resource
    ISSN: 0022-3042 , 1471-4159
    URL: Issue
    URL: Article
    DOI: 10.1111/jnc.2006.97.issue-4
    DOI: 10.1111/j.1471-4159.2006.03840.x
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2020528-4
    SSG: 12
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  • 9
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    Negative symptoms in the clinical high‐risk state for psychosis: Connection with cognition and primacy in impacting functioning
    Wiley ; 2020
    In:  Early Intervention in Psychiatry Vol. 14, No. 2 ( 2020-04), p. 188-195
    Details
    In: Early Intervention in Psychiatry, Wiley, Vol. 14, No. 2 ( 2020-04), p. 188-195
    Abstract: In the clinical high‐risk (CHR) state for psychosis, both negative symptoms and lower cognitive function have been associated with poorer daily functioning. Recent evidence suggests that negative symptoms share overlapping variability with cognition and may partially mediate the relationship between cognition and functioning. However, the nature of this overlap is unknown, and the reverse mediation model remains untested leaving the precise nature of these associations unclear. Methods In order to clarify these relationships, a sample of community‐dwelling youth meeting CHR criteria was collected from a specialty CHR clinic (n = 91, mean age = 21, 63% male). Bootstrapping methods were then applied in a mediation analysis to test both negative symptoms and cognition as independent variables and mediating variables predicting social and role functioning in CHR individuals. Canonical correlation analysis was used to characterize the overlapping variability between negative symptoms and cognition. Results Support for a primary role of negative symptoms in predicting functioning and cognition was observed. Canonical correlation revealed a single dimension of overlap between the two symptom types ( r = .62), represented by a strong correlation between negative symptoms in general and tasks involving verbal working memory, vigilance and social cognition specifically. A single cognitive factor composed primarily of these tasks was found to predict role functioning (adjusted R 2 = .04). Conclusions The results highlight the importance of considering specific cognitive mechanisms overlapping with negative symptoms in research and rehabilitative practice in CHR populations, as well as the primary importance of targeting negative symptoms.
    Type of Medium: Online Resource
    ISSN: 1751-7885 , 1751-7893
    URL: Issue
    URL: Article
    DOI: 10.1111/eip.v14.2
    DOI: 10.1111/eip.12843
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 10
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    Amyloid deposition in semantic dementia: a positron emission tomography study
    Wiley ; 2016
    In:  International Journal of Geriatric Psychiatry Vol. 31, No. 9 ( 2016-09), p. 1064-1074
    Details
    In: International Journal of Geriatric Psychiatry, Wiley, Vol. 31, No. 9 ( 2016-09), p. 1064-1074
    Abstract: Pittsburgh compound B ([11C]‐PIB) identifies amyloid‐β (Aβ) deposition in vivo . Asymptomatic Aβ deposition has been reported consistently in some healthy older subjects. Of patients with frontotemporal dementia, those who have later onset have a higher potential for Aβ deposition. Objective Comparison of Aβ deposition in Alzheimer's disease (AD), healthy older controls, and patients with early‐ and late‐onset semantic dementia (SD), a subtype of frontotemporal dementia. Methods Subjects were recruited from tertiary academic care centers specializing in assessment and management of patients with neurodegenerative disease. We used the radiotracer [11C]‐PIB in a high‐resolution positron emission tomography scanner to evaluate 11 participants with SD (six with onset before age 65 and five with later onset), 9 with probable AD, and 10 controls over age 60. The main outcome measures were frontal, temporal, parietal, and total [11C] ‐PIB standardized uptake value ratios to establish PIB‐positive (PIB+) cutoff. Results The five patients with late‐onset SD were PIB‐negative. Two of six with early‐onset SD, seven of nine with AD, and 1 of 10 controls were PIB+. The SD participants who were PIB+ did not have memory or visuospatial deficits that are typical in AD. Conclusions Aβ deposition does not seem to be associated with late‐onset SD. Future larger studies might confirm whether a significant minority of early‐onset SD patients exhibit Aβ deposition. Copyright © 2016 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 0885-6230 , 1099-1166
    URL: Issue
    URL: Article
    DOI: 10.1002/gps.v31.9
    DOI: 10.1002/gps.4423
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 1500455-7
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