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PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

ABSTRACT: We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [¹¹C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (¹¹C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BP_ND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BP_ND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BP_ND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BP_ND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BP_ND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of ¹¹C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by ¹¹C-(R)-PK11195 BP_ND.

SUBMITTER: Di Biase MA

PROVIDER: S-EPMC5611755 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

Di Biase M A MA Zalesky A A O'keefe G G Laskaris L L Baune B T BT Weickert C S CS Olver J J McGorry P D PD Amminger G P GP Nelson B B Scott A M AM Hickie I I Banati R R Turkheimer F F Yaqub M M Everall I P IP Pantelis C C Cropley V V

Translational psychiatry 20170829 8

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [<sup>11</sup>C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (<sup>11</sup>C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy co ...[more]

PMID: 28850113

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Project description:ObjectiveThis study seeks to quantify the treatment goals of people recently diagnosed with schizophrenia and explore their impact on treatment plan.MethodsPeople aged 18-35 years with a confirmed diagnosis of schizophrenia within the past 5 years were surveyed in the UK, Germany, and Italy. Treatment goals were assessed via a validated best-worst scaling instrument, where participants evaluated subsets of 13 possible treatment goals identified using a balanced incomplete block design. Participants identified the most and least important goals within each task. Data were also collected on current treatment and preference for daily oral versus long-acting injectable (LAI) treatment. Hierarchical Bayes was used to identify preference weights for the goals, and latent class analysis was used to identify segments of people with similar goals. The segments were compared with the current treatment and preference for oral versus LAI treatment.ResultsAcross 100 participants, the average age was 26 years, 75% were male and 50% were diagnosed within 2 years ago. Overall, preferences were most favorable for reduced disease symptoms, think clearly, reduced hospitalizations, reduced anxiety, and take care of self. A total of 61% preferred oral medication and 39% LAI. Two groups were identified with different treatment goals; 50% of participants emphasized clinical goals, including reduced disease symptoms (preference weight =19.7%), reduced hospitalizations (15.5%), and reduced anxiety (10.5%). The other 50% emphasized functional goals, including improved relationships with family/friends (11.4%), increased interest in work (10.6%), experiencing a fuller range of emotions (8.4%), and ability to socialize (7.5%). Those emphasizing functional goals were more likely to be on LAI (44% versus 26%; p=0.059) and preferred LAI (46% versus 32%; p=0.151).ConclusionsPeople with recent-onset schizophrenia may focus more on clinical goals or functional goals, a discussion of which may help facilitate patient engagement.

Project description:BackgroundA post hoc analysis from a multiphase trial with open-label transition and maintenance phases, a double-blind relapse prevention phase, and an optional open-label extension examined the long-term tolerability with continuous once-monthly injectable paliperidone palmitate 39, 78, 117, or 156 mg (25, 50, 75, or 100 mg equivalents [mg eq] of paliperidone) in subjects with recently diagnosed (≤5 years; n = 216) versus chronic illness (>5 years; n = 429) schizophrenia.MethodsAdverse events reported at a ≥2% margin between subgroups were identified. Relative risks (in the recently diagnosed compared with the chronically ill) and 95% confidence intervals (CI) were determined, and CI not including 1 were considered potentially significant.ResultsIn both subgroups, the mean monthly dose was 109 mg (69.9 mg eq). Continuous mean exposures were 333.9 ± 271.9 and 308.7 ± 278.3 days in the recently diagnosed and chronic illness subgroups, respectively. Using the criteria outlined in the methods, nasopharyngitis was a potentially significant event reported in more chronically ill than recently diagnosed subjects at months 6, 9, 12, and endpoint (7.2% versus 2.8%; relative risk 0.384; 95% CI 0.163-0.907). Influenza (2.8% versus 0.7%; relative risk 3.9; 95% CI 1.003-15.730) and amenorrhea (3.2% versus 0.9%; relative risk 3.476; 95% CI 1.029-11.744) at endpoint were potentially significant events in more recently diagnosed than chronically ill subjects. Mean weight changes, sedation/somnolence, any extrapyramidal symptom-related or glucose-related events were generally similar between the groups. The mean prolactin level increased in both sexes in both subgroups (changes from baseline of +41.8 ng/mL and +26.5 ng/mL in recently diagnosed and chronic illness females and +12.3 ng/mL and +15.1 ng/mL in recently diagnosed and chronic illness males, respectively), and were higher in females with recently diagnosed illness than in females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related events were reported by 7.9% of recently diagnosed subjects with schizophrenia and 3.5% of those who were chronically ill.ConclusionThe long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.

Dataset Information

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

Publications

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

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